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Int. J. Mol. Sci., Volume 14, Issue 1 (January 2013), Pages 1-2229

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Open AccessArticle Cantharidin and Its Anhydride-Modified Derivatives: Relation of Structure to Insecticidal Activity
Int. J. Mol. Sci. 2013, 14(1), 1-16; doi:10.3390/ijms14010001
Received: 21 September 2012 / Revised: 12 November 2012 / Accepted: 26 November 2012 / Published: 20 December 2012
Cited by 10 | PDF Full-text (741 KB) | HTML Full-text | XML Full-text
Abstract
Cantharidin is a natural compound of novel structure with ideal insecticidal activity. However, the relationship of structure to insecticidal activity of cantharidin and its derivatives has not been ever clarified. To explore what determines the insecticidal activity structurally of cantharidin-related compounds, two series
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Cantharidin is a natural compound of novel structure with ideal insecticidal activity. However, the relationship of structure to insecticidal activity of cantharidin and its derivatives has not been ever clarified. To explore what determines the insecticidal activity structurally of cantharidin-related compounds, two series target compounds 6 and 7 were synthesized by replacing the anhydride ring of norcantharidin with an aromatic amine or fatty amine with different electron density, respectively. The structures of these compounds were characterized by 1H NMR, 13C NMR and HRMS-ESI. A bioassay showed that compounds 6 (am) lacked any larvicidal activity against Plutella xylostella; whereas their ring-opened partners 7 (am) provided a variety of larvicidal activities against P. xylostella, and compound 7f indicated the highest larvicidal activity with LC50 value of 0.43 mM. The present work demonstrated that the form of the compound (cyclic or ring-opened) or their ability to hydrolyze facilely was the key to determine whether it exhibits larvicidal activity. Moreover, it revealed that the improvement of insecticidal activity required a reasonable combination of both aliphatic amide and aromatic amide moieties, and the type of substituent Y on the aniline ring was critical. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Characterization of a Polyamine Microsphere and Its Adsorption for Protein
Int. J. Mol. Sci. 2013, 14(1), 17-29; doi:10.3390/ijms14010017
Received: 31 August 2012 / Revised: 28 November 2012 / Accepted: 10 December 2012 / Published: 20 December 2012
Cited by 18 | PDF Full-text (474 KB) | HTML Full-text | XML Full-text
Abstract
A novel polyamine microsphere, prepared from the water-in-oil emulsion of polyethylenimine, was characterized. The investigation of scanning electron microscopy showed that the polyamine microsphere is a regular ball with a smooth surface. The diameter distribution of the microsphere is 0.37–4.29 μm. The isoelectric
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A novel polyamine microsphere, prepared from the water-in-oil emulsion of polyethylenimine, was characterized. The investigation of scanning electron microscopy showed that the polyamine microsphere is a regular ball with a smooth surface. The diameter distribution of the microsphere is 0.37–4.29 μm. The isoelectric point of the microsphere is 10.6. The microsphere can adsorb proteins through the co-effect of electrostatic and hydrophobic interactions. Among the proteins tested, the highest value of adsorption of microsphere, 127.8 mg·g−1 microsphere, was obtained with lipase. In comparison with other proteins, the hydrophobic force is more important in promoting the adsorption of lipase. The microsphere can preferentially adsorb lipase from an even mixture of proteins. The optimum temperature and pH for the selective adsorption of lipase by the microsphere was 35 °C and pH 7.0. Full article
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
Open AccessArticle Immunological Effects of Oenothein B, an Ellagitannin Dimer, on Dendritic Cells
Int. J. Mol. Sci. 2013, 14(1), 46-56; doi:10.3390/ijms14010046
Received: 11 October 2012 / Revised: 11 December 2012 / Accepted: 12 December 2012 / Published: 20 December 2012
Cited by 7 | PDF Full-text (330 KB) | HTML Full-text | XML Full-text
Abstract
Oenothein B is a unique macrocyclic ellagitannin dimer that has been found in various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae, with diverse biological activities. The immunological effects of tannins in terms of cytokine-release from macrophages and monocytes have been discussed, while
[...] Read more.
Oenothein B is a unique macrocyclic ellagitannin dimer that has been found in various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae, with diverse biological activities. The immunological effects of tannins in terms of cytokine-release from macrophages and monocytes have been discussed, while the effects on other immunocompetent cells have been the subject of minimal investigation. We evaluated the immunomodulatory effects induced by tannin treatment in human dendritic cells (DCs), which play a critical role in the initial immune response, by measuring the changes in cytokine production, cell differentiation, and cell viability. Oenothein B showed significant down-regulation of the expression of cell surface molecules, CD1a and CD83, suggesting the inhibition of DC differentiation and/or maturation. The suppressive effect on DCs was associated with the induction of apoptosis without the activation of caspase-3/7, 8, and 9, and this was supported by the morphological features indicating significant nuclear condensation. Oenothein B also markedly suppressed the production of inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. These data may, in part, be able to explain the traditional use of tannin-containing medicinal plants for the treatment of a variety of inflammatory diseases, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Chromosome-Specific DNA Repeats: Rapid Identification in Silico and Validation Using Fluorescence in Situ Hybridization
Int. J. Mol. Sci. 2013, 14(1), 57-71; doi:10.3390/ijms14010057
Received: 2 December 2012 / Revised: 9 December 2012 / Accepted: 10 December 2012 / Published: 20 December 2012
Cited by 1 | PDF Full-text (1327 KB) | HTML Full-text | XML Full-text
Abstract
Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present
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Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present bottlenecks in the procedure are a limited number of commercial, non-isotopically labeled probes that can be combined in multiplex FISH assays and the relatively high price and effort to develop additional probes. We describe a streamlined approach for rapid probe definition, synthesis and validation, which is based on the analysis of publicly available DNA sequence information, also known as “database mining”. Examples of probe preparation for the human gonosomes and chromosome 16 as a selected autosome outline the probe selection strategy, define a timeline for expedited probe production and compare this novel selection strategy to more conventional probe cloning protocols. Full article
(This article belongs to the Section Molecular Diagnostics)
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Open AccessArticle Modulation of P1 and EGF Expression by Baicalin
Int. J. Mol. Sci. 2013, 14(1), 146-157; doi:10.3390/ijms14010146
Received: 14 September 2012 / Revised: 7 December 2012 / Accepted: 10 December 2012 / Published: 20 December 2012
Cited by 2 | PDF Full-text (568 KB) | HTML Full-text | XML Full-text
Abstract
Mycoplasma pneumoniae (M. pneumoniae) is increasingly recognized as a major cause of acute respiratory tract infections. Today, macrolides are used in the primary treatment of M. pneumoniae infection. However, with the increasing prevalence of strains resistant to macrolides, as well as
[...] Read more.
Mycoplasma pneumoniae (M. pneumoniae) is increasingly recognized as a major cause of acute respiratory tract infections. Today, macrolides are used in the primary treatment of M. pneumoniae infection. However, with the increasing prevalence of strains resistant to macrolides, as well as reports of toxicity and adverse side effects, it is necessary to develop an alternative therapeutic agent. A compound recipe — Qinbaiqingfei pellets (Qinbai) — have already been approved in China as the first effective traditional Chinese medicine to be used against M. pneumoniae. Herein, we characterize the mechanism by which Qinbai interacts with M. pneumoniae and lung epithelial cells. The fact that Baicalin is the key component of Qingbai leads us to believe its study is important to elucidating the mechanism of the action of Qinbai. In this study, we describe the complex impact of Baicalin on the adhesin protein P1 of M. pneumoniae and on the expression of epidermal growth factor (EGF) in BALB/c mice and A549 cells infected with M. pneumonia. We draw the conclusion that Baicalin not only cured M. pneumoniae infection by inhibiting P1 expression, but also enhanced the repair of lung epithelial cells by upregulating EGF. Finally, we demonstrate that Baicalin plays a role in Qinbai treatment. Full article
Open AccessArticle A Potential Daidzein Derivative Enhances Cytotoxicity of Epirubicin on Human Colon Adenocarcinoma Caco-2 Cells
Int. J. Mol. Sci. 2013, 14(1), 158-176; doi:10.3390/ijms14010158
Received: 9 November 2012 / Revised: 12 December 2012 / Accepted: 17 December 2012 / Published: 21 December 2012
Cited by 9 | PDF Full-text (659 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we evaluated the effects of 8-hydroxydaidzein (8HD), an isoflavone isolated from fermented soy germ koji, and epirubicin (Epi), an antineoplastic agent, on the production of reactive oxygen species (ROS). We subsequently correlated the ROS levels to the anticancer mechanisms of
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In this study, we evaluated the effects of 8-hydroxydaidzein (8HD), an isoflavone isolated from fermented soy germ koji, and epirubicin (Epi), an antineoplastic agent, on the production of reactive oxygen species (ROS). We subsequently correlated the ROS levels to the anticancer mechanisms of Epi and 8HD in human colon adenocarcinoma Caco-2 cells. 8HD enhanced cytotoxicity of Epi and generated a synergistic effect. Epi and/or 8HD treatments increased the hydrogen peroxide and superoxide levels. Combined treatment markedly decreased mRNA expression levels of multidrug resistance protein 1 (MDR1), MDR-associated protein (MRP) 1, and MRP2. 8HD significantly intensified Epi intracellular accumulation in Caco-2 cells. 8HD and/or Epi-induced apoptosis, as indicated by the reduced mitochondrial membrane potential and increased sub-G1 phase in cell cycle. Moreover, 8HD and Epi significantly enhanced the mRNA expressions of Bax, p53, caspases-3, -8, and -9. To our best knowledge, this study verifies for the first time that 8HD effectively circumvents MDR in Caco-2 cells through the ROS-dependent inhibition of efflux transporters and p53-mediated activation of both death receptor and mitochondrial pathways of apoptosis. Our findings of 8HD shed light on the future search for potential biotransformed isoflavones to intensify the cytotoxicity of anticancer drugs through simultaneous reversal of pump and nonpump resistance. Full article
(This article belongs to the Section Molecular Toxicology)
Open AccessArticle Expression and Functional Studies on the Noncoding RNA, PRINS
Int. J. Mol. Sci. 2013, 14(1), 205-225; doi:10.3390/ijms14010205
Received: 5 November 2012 / Revised: 30 November 2012 / Accepted: 10 December 2012 / Published: 21 December 2012
Cited by 5 | PDF Full-text (6531 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and
[...] Read more.
PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and a consistent staining pattern in epidermal keratinocytes and in vitro cultured keratinocytes. To identify the cellular function(s) of PRINS, we searched for a direct interacting partner(s) of this stress-induced molecule. In HaCaT and NHEK cell lysates, the protein proved to be nucleophosmin (NPM) protein as a potential physical interactor with PRINS. Immunohistochemical experiments revealed an elevated expression of NPM in the dividing cells of the basal layers of psoriatic involved skin samples as compared with healthy and psoriatic uninvolved samples. Others have previously shown that NPM is a ubiquitously expressed nucleolar phosphoprotein which shuttles to the nucleoplasm after UV-B irradiation in fibroblasts and cancer cells. We detected a similar translocation of NPM in UV-B-irradiated cultured keratinocytes. The gene-specific silencing of PRINS resulted in the retention of NPM in the nucleolus of UV-B-irradiated keratinocytes; suggesting that PRINS may play a role in the NPM-mediated cellular stress response in the skin. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessArticle Nano Size Effects of TiO2 Nanotube Array on the Glioma Cells Behavior
Int. J. Mol. Sci. 2013, 14(1), 244-254; doi:10.3390/ijms14010244
Received: 4 September 2012 / Revised: 26 November 2012 / Accepted: 11 December 2012 / Published: 21 December 2012
Cited by 3 | PDF Full-text (559 KB) | HTML Full-text | XML Full-text
Abstract
In order to investigate the interplay between the cells and TiO2 nanotube array, and to explore the ability of cells to sense the size change in nano-environment, we reported on the behavior of glioma C6 cells on nanotube array coatings in terms
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In order to investigate the interplay between the cells and TiO2 nanotube array, and to explore the ability of cells to sense the size change in nano-environment, we reported on the behavior of glioma C6 cells on nanotube array coatings in terms of proliferation and apoptosis. The behavior of glioma C6 cells was obviously size-dependent on the coatings; the caliber with 15 nm diameter provided effective spacing to improve the cells proliferation and enhanced the cellular activities. C6 cells’ biological behaviors showed many similar tendencies to many phorocytes; the matching degree of geometry between nanotube and integrin defined that a spacing of 15 nm was optimal for inducing signals to nucleus, which results in achieving maximum activity of glioma cells. In addition, the immune behavior of cells was studied, a variety of inflammatory mediator’s gene expression levels were controlled by the nanoscale dimension, the expressions of IL-6 and IL-10 were higher on 30 nm than on 15 nm nanotube. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Role of Carnitine Acetyl Transferase in Regulation of Nitric Oxide Signaling in Pulmonary Arterial Endothelial Cells
Int. J. Mol. Sci. 2013, 14(1), 255-272; doi:10.3390/ijms14010255
Received: 16 October 2012 / Revised: 26 November 2012 / Accepted: 30 November 2012 / Published: 21 December 2012
Cited by 4 | PDF Full-text (933 KB) | HTML Full-text | XML Full-text
Abstract
Congenital heart defects with increased pulmonary blood flow (PBF) result in pulmonary endothelial dysfunction that is dependent, at least in part, on decreases in nitric oxide (NO) signaling. Utilizing a lamb model with left-to-right shunting of blood and increased PBF that mimics the
[...] Read more.
Congenital heart defects with increased pulmonary blood flow (PBF) result in pulmonary endothelial dysfunction that is dependent, at least in part, on decreases in nitric oxide (NO) signaling. Utilizing a lamb model with left-to-right shunting of blood and increased PBF that mimics the human disease, we have recently shown that a disruption in carnitine homeostasis, due to a decreased carnitine acetyl transferase (CrAT) activity, correlates with decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that the CrAT enzyme plays a major role in regulating NO signaling through its effect on mitochondrial function. We utilized the siRNA gene knockdown approach to mimic the effect of decreased CrAT activity in pulmonary arterial endothelial cells (PAEC). Our data indicate that silencing the CrAT gene disrupted cellular carnitine homeostasis, reduced the expression of mitochondrial superoxide dismutase-and resulted in an increase in oxidative stress within the mitochondrion. CrAT gene silencing also disrupted mitochondrial bioenergetics resulting in reduced ATP generation and decreased NO signaling secondary to a reduction in eNOS/Hsp90 interactions. Thus, this study links the disruption of carnitine homeostasis to the loss of NO signaling observed in children with CHD. Preserving carnitine homeostasis may have important clinical implications that warrant further investigation. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessArticle Antitumor Effects of Rapamycin in Pancreatic Cancer Cells by Inducing Apoptosis and Autophagy
Int. J. Mol. Sci. 2013, 14(1), 273-285; doi:10.3390/ijms14010273
Received: 7 November 2012 / Revised: 2 December 2012 / Accepted: 12 December 2012 / Published: 21 December 2012
Cited by 19 | PDF Full-text (843 KB) | HTML Full-text | XML Full-text
Abstract
Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism
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Rapamycin (Rapa), an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. This study aims to investigate the effects of Rapa suppressing proliferation of pancreatic carcinoma PC-2 cells in vitro and its molecular mechanism involved in antitumor activities. MTT assays showed that the inhibition of proliferation of PC-2 cells in vitro was in a time- and dose-dependent manner. By using transmission electron microscopy, apoptosis bodies and formation of abundant autophagic vacuoles were observed in PC-2 cells after Rapa treatment. Flow cytometry assays also showed Rapa had a positive effect on apoptosis. MDC staining showed that the fluorescent density was higher and the number of MDC-labeled particles in PC-2 cells was greater in the Rapa treatment group than in the control group. RT-PCR revealed that the expression levels of p53, Bax and Beclin 1 were up-regulated in a dose-dependent manner, indicating that Beclin 1 was involved in Rapa induced autophagy and Rapa induced apoptosis as well as p53 up-regulation in PC-2 cells. The results demonstrated that Rapa could effectively inhibit proliferation and induce apoptosis and autophagy in PC-2 cells. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Quantitative Profiling of DNA Damage and Apoptotic Pathways in UV Damaged Cells Using PTMScan Direct
Int. J. Mol. Sci. 2013, 14(1), 286-307; doi:10.3390/ijms14010286
Received: 31 October 2012 / Revised: 4 December 2012 / Accepted: 10 December 2012 / Published: 21 December 2012
Cited by 5 | PDF Full-text (5068 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Traditional methods for analysis of peptides using liquid chromatography and tandem mass spectrometry (LC-MS/MS) lack the specificity to comprehensively monitor specific biological processes due to the inherent duty cycle limitations of the MS instrument and the stochastic nature of the analytical platform. PTMScan
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Traditional methods for analysis of peptides using liquid chromatography and tandem mass spectrometry (LC-MS/MS) lack the specificity to comprehensively monitor specific biological processes due to the inherent duty cycle limitations of the MS instrument and the stochastic nature of the analytical platform. PTMScan Direct is a novel, antibody-based method that allows quantitative LC-MS/MS profiling of specific peptides from proteins that reside in the same signaling pathway. New PTMScan Direct reagents have been produced that target peptides from proteins involved in DNA Damage/Cell Cycle and Apoptosis/Autophagy pathways. Together, the reagents provide access to 438 sites on 237 proteins in these signaling cascades. These reagents have been used to profile the response to UV damage of DNA in human cell lines. UV damage was shown to activate canonical DNA damage response pathways through ATM/ATR-dependent signaling, stress response pathways and induce the initiation of apoptosis, as assessed by an increase in the abundance of peptides corresponding to cleaved, activated caspases. These data demonstrate the utility of PTMScan Direct as a multiplexed assay for profiling specific cellular responses to various stimuli, such as UV damage of DNA. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessArticle Purification and Properties of an Insecticidal Metalloprotease Produced by Photorhabdus luminescens Strain 0805-P5G, the Entomopathogenic Nematode Symbiont
Int. J. Mol. Sci. 2013, 14(1), 308-321; doi:10.3390/ijms14010308
Received: 29 October 2012 / Revised: 3 December 2012 / Accepted: 4 December 2012 / Published: 21 December 2012
Cited by 1 | PDF Full-text (675 KB) | HTML Full-text | XML Full-text
Abstract
A total of 13 Photorhabdus luminescens strains were screened for proteolytic activity. The P. luminescens strain 0805-P5G had the highest activity on both skim milk and gelatin plates. The protease was purified to electrophoretical homogeneity by using a two-step column chromatographic procedure. It
[...] Read more.
A total of 13 Photorhabdus luminescens strains were screened for proteolytic activity. The P. luminescens strain 0805-P5G had the highest activity on both skim milk and gelatin plates. The protease was purified to electrophoretical homogeneity by using a two-step column chromatographic procedure. It had a molecular weight of 51.8 kDa, as determined by MALDI-TOF mass spectrometry. The optimum pH, temperature, as well as pH and thermal stabilities were 8, 60 °C, 5–10, and 14–60 °C, respectively. It was completely inhibited by EDTA and 1,10-phenanthroline. Bioassay of the purified protease against Galleria mellonella by injection showed high insecticidal activity. The protease also showed high oral toxicity to the diamondback moth (Plutella xylostella) of a Taiwan field-collected strain, but low toxicity to an American strain. To our knowledge, this is the first report to demonstrate that the purified protease of P. luminescens has direct toxicity to P. xylostella and biopesticide potentiality. Full article
(This article belongs to the Special Issue Green Biocides)
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Open AccessArticle Synthesis and Self-Organization of Fluorene-Conjugated Bisimidazolylporphyrin and Its Optical Properties
Int. J. Mol. Sci. 2013, 14(1), 322-331; doi:10.3390/ijms14010322
Received: 26 November 2012 / Revised: 14 December 2012 / Accepted: 17 December 2012 / Published: 21 December 2012
PDF Full-text (284 KB) | HTML Full-text | XML Full-text
Abstract
A conjugated-bisimidazolylporphyrin bridged by bis(ethynylfluorene) was synthesized and organized into linear polymer through self-coordination having mean molecular weights, Mw and Mn, of ~2.1 × 105 Da and ~1.6 × 105 Da, respectively. A large two-photon absorption cross section
[...] Read more.
A conjugated-bisimidazolylporphyrin bridged by bis(ethynylfluorene) was synthesized and organized into linear polymer through self-coordination having mean molecular weights, Mw and Mn, of ~2.1 × 105 Da and ~1.6 × 105 Da, respectively. A large two-photon absorption cross section value of 3.4 × 105 GM (per dimer unit) was observed. This value was comparable to that of the previously reported self-assembled linear polymer consisting of butadiyne-bridged imidazolylporphyrins. The two-photon absorption properties could be controlled by tuning the wavelength and absorption intensity of the one-photon absorption. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessArticle The Dynamics of Embolism Refilling in Abscisic Acid (ABA)-Deficient Tomato Plants
Int. J. Mol. Sci. 2013, 14(1), 359-377; doi:10.3390/ijms14010359
Received: 16 November 2012 / Revised: 18 December 2012 / Accepted: 19 December 2012 / Published: 24 December 2012
Cited by 11 | PDF Full-text (4147 KB) | HTML Full-text | XML Full-text
Abstract
Plants are in danger of embolism formation in xylem vessels when the balance between water transport capacity and transpirational demand is compromised. To maintain this delicate balance, plants must regulate the rate of transpiration and, if necessary, restore water transport in embolized vessels.
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Plants are in danger of embolism formation in xylem vessels when the balance between water transport capacity and transpirational demand is compromised. To maintain this delicate balance, plants must regulate the rate of transpiration and, if necessary, restore water transport in embolized vessels. Abscisic acid (ABA) is the dominant long-distance signal responsible for plant response to stress, and it is possible that it plays a role in the embolism/refilling cycle. To test this idea, a temporal analysis of embolism and refilling dynamics, transpiration rate and starch content was performed on ABA-deficient mutant tomato plants. ABA-deficient mutants were more vulnerable to embolism formation than wild-type plants, and application of exogenous ABA had no effect on vulnerability. However, mutant plants treated with exogenous ABA had lower stomatal conductance and reduced starch content in the xylem parenchyma cells. The lower starch content could have an indirect effect on the plant’s refilling activity. The results confirm that plants with high starch content (moderately stressed mutant plants) were more likely to recover from loss of water transport capacity than plants with low starch content (mutant plants with application of exogenous ABA) or plants experiencing severe water stress. This study demonstrates that ABA most likely does not play any direct role in embolism refilling, but through the modulation of carbohydrate content, it could influence the plant’s capacity for refilling. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Exploration of the Role of the Non-Coding RNA SbrE in L. monocytogenes Stress Response
Int. J. Mol. Sci. 2013, 14(1), 378-393; doi:10.3390/ijms14010378
Received: 5 November 2012 / Revised: 11 December 2012 / Accepted: 14 December 2012 / Published: 24 December 2012
Cited by 7 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
SbrE is a ncRNA in Listeria monocytogenes, reported to be up-regulated by the alternative sigma factor σB. Initial quantitative RT-PCR (qRT-PCR) experiments on parent strains and isogenic ΔsigB strains demonstrated σB-dependent expression of SbrE across the four L.
[...] Read more.
SbrE is a ncRNA in Listeria monocytogenes, reported to be up-regulated by the alternative sigma factor σB. Initial quantitative RT-PCR (qRT-PCR) experiments on parent strains and isogenic ΔsigB strains demonstrated σB-dependent expression of SbrE across the four L. monocytogenes lineages and in L. innocua. Microarray and proteomics (MDLC/MS/MS with iTRAQ labeling) experiments with the L. monocytogenes parent strain and an isogenic ΔsbrE strain identified a single gene (lmo0636) and two proteins (Lmo0637 and Lmo2094) that showed lower expression levels in the ΔsbrE strain. qRT-PCR demonstrated an increase in SbrE transcript levels in stationary phase L. monocytogenes and in bacteria exposed to oxidative stress (mean log2 transcript levels 7.68 ± 0.57 and 1.70 ± 0.71 greater than in mid-log phase cells, respectively). However, no significant differences in growth or survival between the parent strain and ΔsbrE strain were confirmed under a variety of environmental stress conditions tested. Our data suggest that σB-dependent transcription of SbrE represents a conserved mechanism that contributes, across Listeria species, to fine-tuning of gene expression under specific environmental conditions that remain to be defined. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessArticle Nitric Oxide Synthesis Is Increased in Cybrid Cells with m.3243A>G Mutation
Int. J. Mol. Sci. 2013, 14(1), 394-410; doi:10.3390/ijms14010394
Received: 7 October 2012 / Revised: 10 December 2012 / Accepted: 14 December 2012 / Published: 24 December 2012
Cited by 5 | PDF Full-text (1040 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of L-arginine to citrulline. Supplementation of L-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke
[...] Read more.
Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of L-arginine to citrulline. Supplementation of L-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome), a mitochondrial disease caused by the m.3243A>G mutation. Low levels of serum arginine and endothelium dysfunction have been reported in MELAS and this treatment may increase NO in endothelial cells and promote vasodilation, decreasing cerebral ischemia and strokes. Although clinical benefits have been reported, little is known about NO synthesis in MELAS. In this study we found that osteosarcoma derived cybrid cells with high levels of m.3243A>G had increased nitrite, an NO metabolite, and increased intracellular NO, demonstrated by an NO fluorescent probe (DAF-FM). Muscle vessels from patients with the same mutation had increased staining in NADPH diaphorase, suggestive of increased NOS. These results indicate increased production of NO in cells harboring the m.3243A>G, however no nitrated protein was detected by Western blotting. Further studies are necessary to clarify the exact mechanisms of L-arginine effect to determine the appropriate clinical use of this drug therapy. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessArticle TNF-α Gene Knockout in Triple Negative Breast Cancer Cell Line Induces Apoptosis
Int. J. Mol. Sci. 2013, 14(1), 411-420; doi:10.3390/ijms14010411
Received: 9 October 2012 / Revised: 30 November 2012 / Accepted: 6 December 2012 / Published: 24 December 2012
Cited by 9 | PDF Full-text (1062 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the promotion and progression of cancer, including triple negative breast cancer cells. Thus, there is significant interest in understanding the molecular signaling pathways that connect TNF-α with the survival of tumor cells.
[...] Read more.
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the promotion and progression of cancer, including triple negative breast cancer cells. Thus, there is significant interest in understanding the molecular signaling pathways that connect TNF-α with the survival of tumor cells. In our experiments, we used as an in vitro model for triple negative breast cancer the cell line Hs578T. The purpose of this study is to determine the gene expression profiling of apoptotic signaling networks after blocking TNF-α formation by using specially designed siRNA molecules to target TNF-α messenger RNA. Knockdown of TNF-α gene was associated with cell proliferation inhibition and apoptosis, as observed by monitoring the cell index using the xCELLigence RTCA System and flow cytometry. PCR array technology was used to examine the transcript levels of 84 genes involved in apoptosis. 15 genes were found to be relevant after comparing the treated group with the untreated one of which 3 were down-regulated and 12 up-regulated. The down-regulated genes are all involved in cell survival, whereas the up-regulated ones are involved in and interact with pro-apoptotic pathways. The results described here indicate that the direct target of TNF-α in the Hs578T breast cancer cell line increases the level of certain pro-apoptotic factors that modulate different cellular networks that direct the cells towards death. Full article
(This article belongs to the Section Molecular Toxicology)
Open AccessArticle Effects of Organoboron Antifoulants on Oyster and Sea Urchin Embryo Development
Int. J. Mol. Sci. 2013, 14(1), 421-433; doi:10.3390/ijms14010421
Received: 9 October 2012 / Revised: 22 November 2012 / Accepted: 8 December 2012 / Published: 24 December 2012
Cited by 4 | PDF Full-text (5961 KB) | HTML Full-text | XML Full-text
Abstract
Prohibition of Ot (organotin) compounds was introduced in Japan in 1997 and worldwide from September 2008. This meant that the production of paints containing TBT compounds was stopped and alternatives to the available Ot antifoulants had to be developed. It has been claimed
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Prohibition of Ot (organotin) compounds was introduced in Japan in 1997 and worldwide from September 2008. This meant that the production of paints containing TBT compounds was stopped and alternatives to the available Ot antifoulants had to be developed. It has been claimed that the degradation by-products of these alternative antifoulants were less toxic than those of Ot compounds. Since the introduction of the alternative antifoulants, the accumulation of these compounds has been reported in many countries. However, the toxicity of these compounds was still largely unreported. In this research, the toxicity of the alternative Ot antifoulants TPBP (triphenylborane pyridine) and TPBOA (triphenylborane octadecylamine) and their degradation products on Crassostea gigas and Hemicentrotus pulcherrimus were tested. The results showed that toxic effects in Crassostea gigas was higher for each antifouling biocide than that in Hemicentrotus pulcherrimus. Also, while the toxicity of the Organoboron antifoulants and the Ots were the same, the former’s degradation products were much less harmful. Full article
Open AccessArticle The Effect of Long-Term Storage on the Physiochemical and Bactericidal Properties of Electrochemically Activated Solutions
Int. J. Mol. Sci. 2013, 14(1), 457-469; doi:10.3390/ijms14010457
Received: 6 October 2012 / Revised: 11 December 2012 / Accepted: 12 December 2012 / Published: 24 December 2012
Cited by 8 | PDF Full-text (256 KB) | HTML Full-text | XML Full-text
Abstract
Electrochemically activated solutions (ECAS) are generated by electrolysis of NaCl solutions, and demonstrate broad spectrum antimicrobial activity and high environmental compatibility. The biocidal efficacy of ECAS at the point of production is widely reported in the literature, as are its credentials as a
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Electrochemically activated solutions (ECAS) are generated by electrolysis of NaCl solutions, and demonstrate broad spectrum antimicrobial activity and high environmental compatibility. The biocidal efficacy of ECAS at the point of production is widely reported in the literature, as are its credentials as a “green biocide.” Acidic ECAS are considered most effective as biocides at the point of production and ill suited for extended storage. Acidic ECAS samples were stored at 4 °C and 20 °C in glass and polystyrene containers for 398 days, and tested for free chlorine, pH, ORP and bactericidal activity throughout. ORP and free chlorine (mg/L) in stored ECAS declined over time, declining at the fastest rate when stored at 20 °C in polystyrene and at the slowest rate when stored at 4 °C in glass. Bactericidal efficacy was also affected by storage and ECAS failed to produce a 5 log10 reduction on five occasions when stored at 20 °C. pH remained stable throughout the storage period. This study represents the longest storage evaluation of the physiochemical parameters and bactericidal efficacy of acidic ECAS within the published literature and reveals that acidic ECAS retain useful bactericidal activity for in excess of 12 months, widening potential applications. Full article
(This article belongs to the Special Issue Green Biocides)
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Open AccessArticle Isolation and Characterisation of 11 Polymorphic Microsatellite Markers in Papaver rhoeas L. (Corn Poppy), a Major Annual Plant Species from Cultivated Areas
Int. J. Mol. Sci. 2013, 14(1), 470-479; doi:10.3390/ijms14010470
Received: 16 November 2012 / Revised: 7 December 2012 / Accepted: 10 December 2012 / Published: 24 December 2012
Cited by 4 | PDF Full-text (192 KB) | HTML Full-text | XML Full-text
Abstract
Papaver rhoeas, an annual plant species in the Papaveraceae family, is part of the biodiversity of agricultural ecosystems and also a noxious agronomic weed. We developed microsatellite markers to study the genetic diversity of P. rhoeas, using an enriched microsatellite library
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Papaver rhoeas, an annual plant species in the Papaveraceae family, is part of the biodiversity of agricultural ecosystems and also a noxious agronomic weed. We developed microsatellite markers to study the genetic diversity of P. rhoeas, using an enriched microsatellite library coupled with 454 next-generation sequencing. A total of 13,825 sequences were obtained that yielded 1795 microsatellite loci. After discarding loci with less than six repeats of the microsatellite motif, automated primer design was successful for 598 loci. We tested 74 of these loci for amplification with a total of 97 primer pairs. Thirty loci passed our tests and were subsequently tested for polymorphism using 384 P. rhoeas plants originating from 12 populations from France. Of the 30 loci, 11 showed reliable polymorphism not affected by the presence of null alleles. The number of alleles and the expected heterozygosity ranged from 3 to 7.4 and from 0.27 to 0.73, respectively. A low but significant genetic differentiation among populations was observed (FST = 0.04; p < 0.001). The 11 validated polymorphic microsatellite markers developed in this work will be useful in studies of genetic diversity and population structure of P. rhoeas, assisting in designing management strategies for the control or the conservation of this species. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Chemical Constituents from Andrographis echioides and Their Anti-Inflammatory Activity
Int. J. Mol. Sci. 2013, 14(1), 496-514; doi:10.3390/ijms14010496
Received: 12 November 2012 / Revised: 11 December 2012 / Accepted: 17 December 2012 / Published: 27 December 2012
Cited by 4 | PDF Full-text (341 KB) | HTML Full-text | XML Full-text
Abstract
Phytochemical investigation of the whole plants of Andrographis echioides afforded two new 2'-oxygenated flavonoids (1) and (2), two new phenyl glycosides (3) and (4), along with 37 known structures. The structures of new compounds were elucidated
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Phytochemical investigation of the whole plants of Andrographis echioides afforded two new 2'-oxygenated flavonoids (1) and (2), two new phenyl glycosides (3) and (4), along with 37 known structures. The structures of new compounds were elucidated by spectral analysis and chemical transformation studies. Among the isolated compounds, (12) and (619) were subjected into the examination for their iNOS inhibitory bioactivity. The structure-activity relationships of the flavonoids for their inhibition of NO production were also discussed. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain
Int. J. Mol. Sci. 2013, 14(1), 515-526; doi:10.3390/ijms14010515
Received: 30 November 2012 / Revised: 13 December 2012 / Accepted: 14 December 2012 / Published: 27 December 2012
Cited by 2 | PDF Full-text (1368 KB) | HTML Full-text | XML Full-text
Abstract
In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes
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In the animal model of brain metastasis using human lung squamous cell carcinoma-derived cells (HARA-B) inoculated into the left ventricle of the heart of nude mice, metastasized tumor cells and brain resident cells interact with each other. Among them, tumor cells and astrocytes have been reported to stimulate each other, releasing soluble factors from both sides, subsequently promoting tumor growth significantly. Among the receptors for soluble factors released from astrocytes, only IL-6 receptor (IL-6R) on tumor cells was up-regulated during the activation with astrocytes. Application of monoclonal antibody against human IL-6R (tocilizumab) to the activated HARA-B cells, the growth of HARA-B cells stimulated by the conditioned medium of HARA-B/astrocytes was significantly inhibited. Injecting tocilizumab to animal models of brain metastasis starting at three weeks of inoculation of HARA-B cells, two times a week for three weeks, significantly inhibited the size of the metastasized tumor foci. The up-regulated expression of IL-6R on metastasized lung tumor cells was also observed in the tissue from postmortem patients. These results suggest that IL-6R on metastasized lung tumor cells would be a therapeutic target to inhibit the growth of the metastasized lung tumor cells in the brain. Full article
(This article belongs to the Special Issue Brain Metastasis)
Open AccessArticle Sorption, Solubility, Bond Strength and Hardness of Denture Soft Lining Incorporated with Silver Nanoparticles
Int. J. Mol. Sci. 2013, 14(1), 563-574; doi:10.3390/ijms14010563
Received: 7 November 2012 / Revised: 12 December 2012 / Accepted: 17 December 2012 / Published: 27 December 2012
Cited by 15 | PDF Full-text (374 KB) | HTML Full-text | XML Full-text
Abstract
The colonization of denture soft lining material by oral fungi can result in infections and stomatitis of oral tissues. In this study, 0 ppm to 200 ppm of silver nanoparticles was incorporated as an antimicrobial agent into composites to reduce the microbial colonization
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The colonization of denture soft lining material by oral fungi can result in infections and stomatitis of oral tissues. In this study, 0 ppm to 200 ppm of silver nanoparticles was incorporated as an antimicrobial agent into composites to reduce the microbial colonization of lining materials. The effect of silver nanoparticle incorporation into a soft lining material on the sorption, solubility, hardness (on the Shore A scale) and tensile bond strength of the composites was investigated. The data were statistically analyzed using two-way ANOVA and Newman-Keuls post hoc tests or the chi-square Pearson test at the p < 0.05 level. An increase in the nanosilver concentration resulted in a decrease in hardness, an increase in sorption and solubility, a decrease in bond strength and a change in the failure type of the samples. The best combination of bond strength, sorption, solubility and hardness with antifungal efficacy was achieved for silver nanoparticle concentrations ranging from 20 ppm to 40 ppm. These composites did not show properties worse than those of the material without silver nanoparticles and exhibited enhanced in vitro antifungal efficiency. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle Isolation and Molecular Characterization of Thirteen R2R3-MYB Transcription Factors from Epimedium sagittatum
Int. J. Mol. Sci. 2013, 14(1), 594-610; doi:10.3390/ijms14010594
Received: 16 November 2012 / Revised: 11 December 2012 / Accepted: 11 December 2012 / Published: 27 December 2012
Cited by 8 | PDF Full-text (1343 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Epimedium sagittatum (Sieb. et Zucc.) Maxim, a popular traditional Chinese medicinal plant, has been widely used for treating sexual dysfunction and osteoporosis in China. The main bioactive components in herba epimedii are prenylated flavonol glycosides, which are end products of a branch of
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Epimedium sagittatum (Sieb. et Zucc.) Maxim, a popular traditional Chinese medicinal plant, has been widely used for treating sexual dysfunction and osteoporosis in China. The main bioactive components in herba epimedii are prenylated flavonol glycosides, which are end products of a branch of the flavonoid biosynthetic pathway. The MYB transcription factors (TF) act as activators or repressors to regulate the flavonoid pathway. In this study, 13 full-length cDNA clones of R2R3-MYB TFs from E. sagittatum (designated as EsMYB1 to EsMYB13) were isolated and characterized. Sequence similarity and phylogenetic analysis placed nine R2R3-MYB members of epimedii into five subgroups of the Arabidopsis R2R3-MYB family, while four members were not clustered into a defined subgroup. The number and length of introns from epimedii R2R3-MYB genes varied significantly, but intron positions and phases were well conserved. Expression patterns of epimedii R2R3-MYB genes in various tissues showed diverse. Finally, it is suggested that five epimedii R2R3-MYB genes may be involved in regulating the flavonoid pathway and could be used as valuable candidate genes for metabolic engineering studies in future. Sequence information of 13 R2R3-MYB genes discovered here will also provide an entry point into the overview of whole R2R3-MYB family in epimedii. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Disruption of the Expression of a Non-Coding RNA Significantly Impairs Cellular Differentiation in Toxoplasma gondii
Int. J. Mol. Sci. 2013, 14(1), 611-624; doi:10.3390/ijms14010611
Received: 2 November 2012 / Revised: 14 December 2012 / Accepted: 18 December 2012 / Published: 28 December 2012
Cited by 3 | PDF Full-text (362 KB) | HTML Full-text | XML Full-text
Abstract
The protozoan parasite Toxoplasma gondii is an important human and veterinary pathogen. Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing “tachyzoites” and latent “bradyzoite” tissue cysts. Tachyzoites are responsible for acute illness and congenital
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The protozoan parasite Toxoplasma gondii is an important human and veterinary pathogen. Asexual replication of T. gondii in humans and intermediate hosts is characterized by two forms: rapidly growing “tachyzoites” and latent “bradyzoite” tissue cysts. Tachyzoites are responsible for acute illness and congenital neurological birth defects, while the more slowly dividing bradyzoite form can remain latent within the tissues for many years, representing a threat to immunocompromised patients. We have developed a genetic screen to identify regulatory genes that control parasite differentiation and have isolated mutants that fail to convert to bradyzoites. One of these mutants has an insertion disrupting a locus that encodes a developmentally regulated non-coding RNA transcript, named Tg-ncRNA-1. Microarray hybridizations suggest that Tg-ncRNA-1 is involved in the early steps of bradyzoite differentiation. Since Tg-ncRNA-1 does not contain an open reading frame, we used the algorithm Coding Potential Calculator (CPC) that evaluates the protein-coding potential of a transcript, to classify Tg-ncRNA-1. The CPC results strongly indicate that Tg-ncRNA-1 is a non-coding RNA (ncRNA). Interestingly, a previously generated mutant also contains an insertion in Tg-ncRNA-1. We show that both mutants have a decreased ability to form bradyzoites, and complementation of both mutants with wild-type Tg-ncRNA-1 restores the ability of the parasites to differentiate. It has been shown that an important part of bradyzoite differentiation is transcriptionally controlled, but this is the first time that a non-coding RNA is implicated in this process. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessArticle Nuclear Factor-κB (NF-κB) Regulates the Expression of Human Testis-Enriched Leucine-Rich Repeats and WD Repeat Domain Containing 1 (LRWD1) Gene
Int. J. Mol. Sci. 2013, 14(1), 625-639; doi:10.3390/ijms14010625
Received: 26 October 2012 / Revised: 11 December 2012 / Accepted: 12 December 2012 / Published: 28 December 2012
Cited by 7 | PDF Full-text (1874 KB) | HTML Full-text | XML Full-text
Abstract
The human Leucine-rich Repeats and WD repeat Domain containing 1 (LRWD1) gene was originally identified by cDNA microarray as one of the genes down-regulated in the testicular tissues of patients with severe spermatogenic defects. Human LRWD1 is a testicular-enriched protein that
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The human Leucine-rich Repeats and WD repeat Domain containing 1 (LRWD1) gene was originally identified by cDNA microarray as one of the genes down-regulated in the testicular tissues of patients with severe spermatogenic defects. Human LRWD1 is a testicular-enriched protein that is present predominantly in the cytoplasm of spermatocytes and spermatids and colocalizes with the centrosome at the base of sperm tail. Reporter assay, Chromatin immunoprecipitation (ChIP) analysis, and gel electrophoretic mobility shift assay (EMSA) were used to identify the core promoter region of LRWD1. A 198 bp segment upstream of the LRWD1 transcription initiation site exhibited promoter activity. The LRWD1 core promoter lacked a TATA box but contained a NF-κB binding site. Chromatin immunoprecipitation (ChIP) analysis and gel electrophoretic mobility shift assay (EMSA) showed basal binding of the NF-κB subunit to the LRWD1 promoter. LRWD1 promoter activity was positively regulated by NF-κB, and this regulation was dependent on the presence of the conserved κB site in the LRWD1 promoter region. Our data suggest that NF-κB is an important regulator for the expression of LRWD1. This is the first study showing that the expression of the testis-enriched LRWD1 gene is regulated by NF-κB. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle A Molecular-Modeling Toolbox Aimed at Bridging the Gap between Medicinal Chemistry and Computational Sciences
Int. J. Mol. Sci. 2013, 14(1), 684-700; doi:10.3390/ijms14010684
Received: 12 December 2012 / Revised: 21 December 2012 / Accepted: 26 December 2012 / Published: 4 January 2013
Cited by 4 | PDF Full-text (2989 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the current era of high-throughput drug discovery and development, molecular modeling has become an indispensable tool for identifying, optimizing and prioritizing small-molecule drug candidates. The required background in computational chemistry and the knowledge of how to handle the complex underlying protocols, however,
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In the current era of high-throughput drug discovery and development, molecular modeling has become an indispensable tool for identifying, optimizing and prioritizing small-molecule drug candidates. The required background in computational chemistry and the knowledge of how to handle the complex underlying protocols, however, might keep medicinal chemists from routinely using in silico technologies. Our objective is to encourage those researchers to exploit existing modeling technologies more frequently through easy-to-use graphical user interfaces. In this account, we present two innovative tools (which we are prepared to share with academic institutions) facilitating computational tasks commonly utilized in drug discovery and development: (1) the VirtualDesignLab estimates the binding affinity of small molecules by simulating and quantifying their binding to the three-dimensional structure of a target protein; and (2) the MD Client launches molecular dynamics simulations aimed at exploring the time-dependent stability of ligand–protein complexes and provides residue-based interaction energies. This allows medicinal chemists to identify sites of potential improvement in their candidate molecule. As a case study, we present the application of our tools towards the design of novel antagonists for the FimH adhesin. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle The Voltage-Dependent Anion Channel 1 (AtVDAC1) Negatively Regulates Plant Cold Responses during Germination and Seedling Development in Arabidopsis and Interacts with Calcium Sensor CBL1
Int. J. Mol. Sci. 2013, 14(1), 701-713; doi:10.3390/ijms14010701
Received: 26 October 2012 / Revised: 12 December 2012 / Accepted: 12 December 2012 / Published: 4 January 2013
Cited by 7 | PDF Full-text (676 KB) | HTML Full-text | XML Full-text
Abstract
The voltage-dependent anion channel (VDAC), a highly conserved major mitochondrial outer membrane protein, plays crucial roles in energy metabolism and metabolite transport. However, knowledge about the roles of the VDAC family in plants is limited. In this study, we investigated the expression pattern
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The voltage-dependent anion channel (VDAC), a highly conserved major mitochondrial outer membrane protein, plays crucial roles in energy metabolism and metabolite transport. However, knowledge about the roles of the VDAC family in plants is limited. In this study, we investigated the expression pattern of VDAC1 in Arabidopsis and found that cold stress promoted the accumulation of VDAC1 transcripts in imbibed seeds and mature plants. Overexpression of VDAC1 reduced tolerance to cold stress in Arabidopsis. Phenotype analysis of VDAC1 T-DNA insertion mutant plants indicated that a vdac1 mutant line had faster germination kinetics under cold treatment and showed enhanced tolerance to freezing. The yeast two-hybrid system revealed that VDAC1 interacts with CBL1, a calcium sensor in plants. Like the vdac1, a cbl1 mutant also exhibited a higher seed germination rate. We conclude that both VDAC1 and CBL1 regulate cold stress responses during seed germination and plant development. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Molecular Eigensolution Symmetry Analysis and Fine Structure
Int. J. Mol. Sci. 2013, 14(1), 714-806; doi:10.3390/ijms14010714
Received: 3 September 2012 / Revised: 26 November 2012 / Accepted: 27 November 2012 / Published: 4 January 2013
Cited by 3 | PDF Full-text (17475 KB) | HTML Full-text | XML Full-text
Abstract
Spectra of high-symmetry molecules contain fine and superfine level cluster structure related to J-tunneling between hills and valleys on rovibronic energy surfaces (RES). Such graphic visualizations help disentangle multi-level dynamics, selection rules, and state mixing effects including widespread violation of nuclear spin
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Spectra of high-symmetry molecules contain fine and superfine level cluster structure related to J-tunneling between hills and valleys on rovibronic energy surfaces (RES). Such graphic visualizations help disentangle multi-level dynamics, selection rules, and state mixing effects including widespread violation of nuclear spin symmetry species. A review of RES analysis compares it to that of potential energy surfaces (PES) used in Born-Oppenheimer approximations. Both take advantage of adiabatic coupling in order to visualize Hamiltonian eigensolutions. RES of symmetric and D2 asymmetric top rank-2-tensor Hamiltonians are compared with Oh spherical top rank-4-tensor fine-structure clusters of 6-fold and 8-fold tunneling multiplets. Then extreme 12-fold and 24-fold multiplets are analyzed by RES plots of higher rank tensor Hamiltonians. Such extreme clustering is rare in fundamental bands but prevalent in hot bands, and analysis of its superfine structure requires more efficient labeling and a more powerful group theory. This is introduced using elementary examples involving two groups of order-6 (C6 and D3~C3v), then applied to families of Oh clusters in SF6 spectra and to extreme clusters. Full article
(This article belongs to the Special Issue Molecular Symmetry)
Open AccessArticle A Model of Interaction between Nicotinamide Adenine Dinucleotide Phosphate (NADPH) Oxidase and Apocynin Analogues by Docking Method
Int. J. Mol. Sci. 2013, 14(1), 807-817; doi:10.3390/ijms14010807
Received: 14 November 2012 / Revised: 11 December 2012 / Accepted: 24 December 2012 / Published: 4 January 2013
Cited by 2 | PDF Full-text (309 KB) | HTML Full-text | XML Full-text
Abstract
Some apocynin analogues have exhibited outstanding inhibition to NADPH oxidase. In this study, the key interactions between apocynin analogues and NADPH oxidase were analyzed by the docking method. The potential active site was first identified by the SiteID program combining with the key
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Some apocynin analogues have exhibited outstanding inhibition to NADPH oxidase. In this study, the key interactions between apocynin analogues and NADPH oxidase were analyzed by the docking method. The potential active site was first identified by the SiteID program combining with the key residue CYS378. Afterwards, the compounds in the training set were docked into NADPH oxidase (1K4U) under specific docking constraints to discuss the key interactions between ligands and the receptor. These key interactions were then validated by the consistence between the docking result and the experimental result of the test set. The result reveals that the Pi interaction between apocynin analogues and NADPH oxidase has a direct contribution to inhibition activities, except for H-bond formation and docking score. The key interactions might be valuable to discover and screen apocynin analogues as potent inhibitors of NADPH oxidase. Full article
(This article belongs to the Section Molecular Recognition)
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Open AccessArticle Ameliorating Effects of Exogenously Applied Proline on Seed Composition, Seed Oil Quality and Oil Antioxidant Activity of Maize (Zea mays L.) under Drought Stress
Int. J. Mol. Sci. 2013, 14(1), 818-835; doi:10.3390/ijms14010818
Received: 20 September 2012 / Revised: 10 November 2012 / Accepted: 19 December 2012 / Published: 4 January 2013
Cited by 11 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
This study was carried out to appraise whether or not the exogenous application of a potential osmoprotectant, proline, could ameliorate the adverse effects of drought stress on maize seed and seed oil composition, as well as oil antioxidant activity. Water stress reduced the
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This study was carried out to appraise whether or not the exogenous application of a potential osmoprotectant, proline, could ameliorate the adverse effects of drought stress on maize seed and seed oil composition, as well as oil antioxidant activity. Water stress reduced the kernel sugar, oil, protein and moisture contents and most of the seed macro- and micro-elements analyzed in both maize cultivars but it increased the contents of seed fiber and ash. Water stress increased the oil oleic acid content with a subsequent decrease in the amount of linoleic acid, resulting in an increased oil oleic/linoleic ratio for both maize cultivars. However, no variation was observed in oil stearic and palmitic acids content due to water stress. A considerable drought induced an increase in seed oil α-, γ-, δ- and total tocopherols and flavonoids were observed in both maize cultivars. However, oil phenolic and carotenoid content as well as 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activity decreased. Foliar-applied proline significantly increased the content of seed sugar, oil, protein, moisture, fiber and ash in both maize cultivars under well irrigated and water deficit conditions. Furthermore, exogenous application of proline increased the oil oleic and linoleic acid contents. The concentrations of antioxidant compounds namely phenolics, carotenoids, flavonoids and tocopherols estimated in the seed oil increased due to foliar-applied proline under water deficit conditions that was positively correlated with the enhanced oil DPPH free radical scavenging activity. Moreover, the increase in the contents of these antioxidant compounds and oil antioxidant activity due to the foliar application of proline was noted to be more pronounced under water deficit conditions. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Pharmacokinetics of Dibutyl Phthalate (DBP) in the Rat Determined by UPLC-MS/MS
Int. J. Mol. Sci. 2013, 14(1), 836-849; doi:10.3390/ijms14010836
Received: 10 September 2012 / Revised: 12 December 2012 / Accepted: 18 December 2012 / Published: 4 January 2013
Cited by 1 | PDF Full-text (478 KB) | HTML Full-text | XML Full-text
Abstract
Dibutyl phthalate (DBP) is commonly used to increase the flexibility of plastics in industrial products. However, several plasticizers have been illegally used as clouding agents to increase dispersion of aqueous matrix in beverages. This study thus develops a rapid and validated analytical method
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Dibutyl phthalate (DBP) is commonly used to increase the flexibility of plastics in industrial products. However, several plasticizers have been illegally used as clouding agents to increase dispersion of aqueous matrix in beverages. This study thus develops a rapid and validated analytical method by ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) for the evaluation of pharmacokinetics of DBP in free moving rats. The UPLC-MS/MS system equipped with positive electrospray ionization (ESI) source in multiple reaction monitoring (MRM) mode was used to monitor m/z 279.25→148.93 transitions for DBP. The limit of quantification for DBP in rat plasma and feces was 0.05 µg/mL and 0.125 µg/g, respectively. The pharmacokinetic results demonstrate that DBP appeared to have a two-compartment model in the rats; the area under concentration versus time (AUC) was 57.8 ± 5.93 min μg/mL and the distribution and elimination half-life (t1/2,α and t1/2,β) were 5.77 ± 1.14 and 217 ± 131 min, respectively, after DBP administration (30 mg/kg, i.v.). About 0.18% of the administered dose was recovered from the feces within 48 h. The pharmacokinetic behavior demonstrated that DBP was quickly degraded within 2 h, suggesting a rapid metabolism low fecal cumulative excretion in the rat. Full article
Open AccessArticle Apoptosis is Induced in Cancer Cells via the Mitochondrial Pathway by the Novel Xylocydine-Derived Compound JRS-15
Int. J. Mol. Sci. 2013, 14(1), 850-870; doi:10.3390/ijms14010850
Received: 24 October 2012 / Revised: 17 December 2012 / Accepted: 21 December 2012 / Published: 4 January 2013
Cited by 11 | PDF Full-text (4047 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The novel compound JRS-15 was obtained through the chemical modification of xylocydine. JRS-15 exhibited much stronger cytotoxic and pro-apoptotic activity than its parent compound in various cancer cell lines, with IC50 values in HeLa, HepG2, SK-HEP-1, PC-3M and A549 cells ranging from
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The novel compound JRS-15 was obtained through the chemical modification of xylocydine. JRS-15 exhibited much stronger cytotoxic and pro-apoptotic activity than its parent compound in various cancer cell lines, with IC50 values in HeLa, HepG2, SK-HEP-1, PC-3M and A549 cells ranging from 12.42 to 28.25 µM. In addition, it is more potent for killing cancer than non-cancerous cells. Mechanistic studies showed that JRS-15 treatment arrested cell cycle at the G1/S phase, which further triggered the translocation of Bax and Bak to the mitochondria, resulting in mitochondrial membrane potential (MMP) depolarization and the subsequent release of cytochrome c and the second mitochondria-derived activator of caspase (Smac). The sequential activation of caspase-9 and caspase-3/7 and the cleavage of poly (ADP-ribose) polymerase (PARP) were observed following these mitochondrial events. Caspase-8, an initiator caspase that is required to activate the membrane receptor-mediated extrinsic apoptosis pathway was not activated in JRS-15-treated cells. Further analysis showed that the levels of the anti-apoptotic proteins Bcl-xL and XIAP were significantly reduced upon JRS-15 treatment. Furthermore, the caspase-9 inhibitor z-LEHD-fmk, the pan-caspase inhibitor z-VAD-fmk, and Bcl-xL or XIAP overexpression all effectively prevented JRS-15-induced apoptosis. Taken together, these results indicate that JRS-15 induces cancer cell apoptosis by regulating multiple apoptosis-related proteins, and this compound may therefore be a good candidate reagent for anticancer therapy. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Cloning, Expression and Characterization of Mitochondrial Manganese Superoxide Dismutase from the Whitefly, Bemisia tabaci
Int. J. Mol. Sci. 2013, 14(1), 871-887; doi:10.3390/ijms14010871
Received: 7 October 2012 / Revised: 21 November 2012 / Accepted: 24 December 2012 / Published: 7 January 2013
Cited by 10 | PDF Full-text (4382 KB) | HTML Full-text | XML Full-text
Abstract
A mitochondrial manganese superoxide dismutase from an invasive species of the whitefly Bemisia tabaci complex (Bt-mMnSOD) was cloned and analyzed. The full length cDNA of Bt-mMnSOD is 1210 bp with a 675 bp open reading frame, corresponding to 224 amino acids, which include
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A mitochondrial manganese superoxide dismutase from an invasive species of the whitefly Bemisia tabaci complex (Bt-mMnSOD) was cloned and analyzed. The full length cDNA of Bt-mMnSOD is 1210 bp with a 675 bp open reading frame, corresponding to 224 amino acids, which include 25 residues of the mitochondrial targeting sequence. Compared with various vertebrate and invertebrate animals, the MnSOD signature (DVWEHAYY) and four conserved amino acids for manganese binding (H54, H102, D186 and H190) were observed in Bt-mMnSOD. Recombinant Bt-mMnSOD was overexpressed in Escherichia coli, and the enzymatic activity of purified mMnSOD was assayed under various temperatures. Quantitative real-time PCR analysis with whiteflies of different development stages showed that the mRNA levels of Bt-mMnSOD were significantly higher in the 4th instar than in other stages. In addition, the in vivo activities of MnSOD in the whitefly were measured under various conditions, including exposure to low (4 °C) and high (40 °C) temperatures, transfer from a favorable to an unfavorable host plant (from cotton to tobacco) and treatment with pesticides. Our results indicate that the whitefly MnSOD plays an important role in cellular stress responses and anti-oxidative processes and that it might contribute to the successful worldwide distribution of the invasive whitefly. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Proteome and Peptidome of Human Acquired Enamel Pellicle on Deciduous Teeth
Int. J. Mol. Sci. 2013, 14(1), 920-934; doi:10.3390/ijms14010920
Received: 13 October 2012 / Revised: 18 December 2012 / Accepted: 4 January 2013 / Published: 7 January 2013
Cited by 17 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Understanding the composition and structure of the acquired enamel pellicle (AEP) has been a major goal in oral biology. Our lab has conducted studies on the composition of AEP formed on permanent enamel. The exhaustive exploration has provided a comprehensive identification of more
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Understanding the composition and structure of the acquired enamel pellicle (AEP) has been a major goal in oral biology. Our lab has conducted studies on the composition of AEP formed on permanent enamel. The exhaustive exploration has provided a comprehensive identification of more than 100 proteins from AEP formed on permanent enamel. The AEP formed on deciduous enamel has not been subjected to the same biochemical characterization scrutiny as that of permanent enamel, despite the fact that deciduous enamel is structurally different from permanent enamel. We hypothesized that the AEP proteome and peptidome formed on deciduous enamel may also be composed of unique proteins, some of which may not be common with AEP of permanent enamel explored previously. Pellicle material was collected from 10 children (aged 18–54 months) and subjected to mass spectrometry analysis. A total of 76 pellicle proteins were identified from the deciduous pellicle proteome. In addition, 38 natural occurring AEP peptides were identified from 10 proteins, suggesting that primary AEP proteome/peptidome presents a unique proteome composition. This is the first study to provide a comprehensive investigation of in vivo AEP formed on deciduous enamel. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessArticle Ochratoxin A Inhibits Mouse Embryonic Development by Activating a Mitochondrion-Dependent Apoptotic Signaling Pathway
Int. J. Mol. Sci. 2013, 14(1), 935-953; doi:10.3390/ijms14010935
Received: 22 October 2012 / Revised: 10 December 2012 / Accepted: 24 December 2012 / Published: 7 January 2013
Cited by 14 | PDF Full-text (611 KB) | HTML Full-text | XML Full-text
Abstract
Ochratoxin A (OTA), a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, both in vitro and in vivo. In the present study, we explored the cytotoxic effects exerted by OTA on the blastocyst stage of mouse embryos, on subsequent
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Ochratoxin A (OTA), a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, both in vitro and in vivo. In the present study, we explored the cytotoxic effects exerted by OTA on the blastocyst stage of mouse embryos, on subsequent embryonic attachment, on outgrowth in vitro, and following in vivo implantation via embryo transfer. Mouse blastocysts were incubated with or without OTA (1, 5, or 10 μM) for 24 h. Cell proliferation and growth were investigated using dual differential staining; apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay; and embryo implantation and post-implantation development were assessed by examination of in vitro growth and the outcome of in vivo embryo transfer, respectively. Blastocysts treated with 10 μM OTA displayed a significantly increased level of apoptosis and a reduction in total cell number. Interestingly, we observed no marked difference in implantation success rate between OTA-pretreated and control blastocysts either during in vitro embryonic development (following implantation in a fibronectin-coated culture dish) or after in vivo embryo transfer. However, in vitro treatment with 10 μM OTA was associated with increased resorption of post-implantation embryos by the mouse uterus, and decreased fetal weight upon embryo transfer. Our results collectively indicate that in vitro exposure to OTA triggers apoptosis and retards early post-implantation development after transfer of embryos to host mice. In addition, OTA induces apoptosis-mediated injury of mouse blastocysts, via reactive oxygen species (ROS) generation, and promotes mitochondrion-dependent apoptotic signaling processes that impair subsequent embryonic development. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessArticle Population Subdivision of Japanese Flounder Paralichthys olivaceus in the Pacific Coast of Tohoku Japan Detected by Means of Mitochondrial Phylogenetic Information
Int. J. Mol. Sci. 2013, 14(1), 954-963; doi:10.3390/ijms14010954
Received: 9 September 2012 / Revised: 6 December 2012 / Accepted: 19 December 2012 / Published: 7 January 2013
PDF Full-text (639 KB) | HTML Full-text | XML Full-text
Abstract
This study deals with mitochondrial phylogenetic information of Japanese flounder in the Pacific coast of Tohoku Japan to estimate the genetic population subdivision that was undetectable by conventional population statistics. We determined complete sequences of mitochondrial NADH dehydrogenase subunit-2 (ND2) and subunit-5 (ND5)
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This study deals with mitochondrial phylogenetic information of Japanese flounder in the Pacific coast of Tohoku Japan to estimate the genetic population subdivision that was undetectable by conventional population statistics. We determined complete sequences of mitochondrial NADH dehydrogenase subunit-2 (ND2) and subunit-5 (ND5) genes for 151 individuals from northern (Aomori and Iwate prefectures, 40–41°N) and southern (Miyagi and Fukushima prefectures, 37–38°N) waters. Samples from both waters showed high genetic diversity, including 126 haplotypes. These haplotypes were located at mixed and nested positions on an inferred phylogenetic tree, and traditional F-statistics indicated no significant population divergence (φST = −0.00335, p > 0.05), corroborating our previous study. Three variable sites, however, showed significant base composition heterogeneity between samples from the northern and southern waters (Fisher’s exact-test, p < 0.01). Nucleotide substitutions at the three sites converged on an apical clade, which consisted of the five southern individuals, whereas its sister clade consisted only of the three northern individuals. This phylogenetic information corroborates previous ecological studies indicating the presence of separate stocks in the northern and southern waters. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Enhancement of Palmarumycins C12 and C13 Production in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12 after Treatments with Metal Ions
Int. J. Mol. Sci. 2013, 14(1), 979-998; doi:10.3390/ijms14010979
Received: 12 November 2012 / Revised: 15 December 2012 / Accepted: 25 December 2012 / Published: 7 January 2013
Cited by 11 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C12 and C
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The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C12 and C13 production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 were investigated. Three metal ions, Ca2+, Cu2+ and Al3+ were exhibited as the most effective to enhance mycelia growth and palmarumycin production. When calcium ion (Ca2+) was applied to the medium at 10.0 mmol/L on day 3, copper ion (Cu2+) to the medium at 1.0 mmol/L on day 3, aluminum ion (Al3+) to the medium at 2.0 mmol/L on day 6, the maximal yields of palmarumycins C12 plus C13 were obtained as 137.57 mg/L, 146.28 mg/L and 156.77 mg/L, which were 3.94-fold, 4.19-fold and 4.49-fold in comparison with that (34.91 mg/L) of the control, respectively. Al3+ favored palmarumycin C12 production when its concentration was higher than 4 mmol/L. Ca2+ had an improving effect on mycelia growth of Berkleasmium sp. Dzf12. The combination effects of Ca2+, Cu2+ and Al3+ on palmarumycin C13 production were further studied by employing a statistical method based on the central composite design (CCD) and response surface methodology (RSM). By solving the quadratic regression equation between palmarumycin C13 and three metal ions, the optimal concentrations of Ca2+, Cu2+ and Al3+ in medium for palmarumycin C13 production were determined as 7.58, 1.36 and 2.05 mmol/L, respectively. Under the optimum conditions, the predicted maximum palmarumycin C13 yield reached 208.49 mg/L. By optimizing the combination of Ca2+, Cu2+ and Al3+ in medium, palmarumycin C13 yield was increased to 203.85 mg/L, which was 6.00-fold in comparison with that (33.98 mg/L) in the original basal medium. The results indicate that appropriate metal ions (i.e., Ca2+, Cu2+ and Al3+) could enhance palmarumycin production. Application of the metal ions should be an effective strategy for palmarumycin production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Photophysical Property and Photocatalytic Activity of New Gd2InSbO7 and Gd2FeSbO7 Compounds under Visible Light Irradiation
Int. J. Mol. Sci. 2013, 14(1), 999-1021; doi:10.3390/ijms14010999
Received: 3 December 2012 / Revised: 21 December 2012 / Accepted: 24 December 2012 / Published: 7 January 2013
Cited by 3 | PDF Full-text (762 KB) | HTML Full-text | XML Full-text
Abstract
Gd2InSbO7 and Gd2FeSbO7 were synthesized first, and their structural and photocatalytic properties were studied. The lattice parameters and the band gaps for Gd2InSbO7 and Gd2FeSbO7 were 10.449546 Å, 10.276026 Å, 2.897
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Gd2InSbO7 and Gd2FeSbO7 were synthesized first, and their structural and photocatalytic properties were studied. The lattice parameters and the band gaps for Gd2InSbO7 and Gd2FeSbO7 were 10.449546 Å, 10.276026 Å, 2.897 eV and 2.151 eV. The photocatalytic degradation of rhodamine B was performed with Gd2InSbO7 and Gd2FeSbO7 under visible light irradiation. Gd2InSbO7 and Gd2FeSbO7 had higher catalytic activity compared with Bi2InTaO7. Gd2FeSbO7 exhibited higher catalytic activity than Gd2InSbO7. The photocatalytic degradation of rhodamine B followed with the first-order reaction kinetics, and the first-order rate constant k was 0.01606, 0.02220 or 0.00329 min−1 with Gd2InSbO7, Gd2FeSbO7 or Bi2InTaO7 as photocatalyst. Complete removal of rhodamine B was observed after visible light irradiation for 225 min or 260 min with Gd2FeSbO7 or Gd2InSbO7 as photocatalyst. The evolution of CO2 was realized, and it indicated continuous mineralization of rhodamine B during the photocatalytic process. The possible photocatalytic degradation pathway of rhodamine B was proposed. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessArticle The Effect of Remelting on the Physical Properties of Borotellurite Glass Doped with Manganese
Int. J. Mol. Sci. 2013, 14(1), 1022-1030; doi:10.3390/ijms14011022
Received: 7 October 2012 / Revised: 26 December 2012 / Accepted: 29 December 2012 / Published: 7 January 2013
Cited by 11 | PDF Full-text (325 KB) | HTML Full-text | XML Full-text
Abstract
A systematic set of borotellurite glasses doped with manganese (1–x) [(B2O3)0.3(TeO2)0.7]-xMnO, with x = 0.1, 0.2, 0.3 and 0.4 mol%, were successfully synthesized by using a conventional melt and
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A systematic set of borotellurite glasses doped with manganese (1–x) [(B2O3)0.3(TeO2)0.7]-xMnO, with x = 0.1, 0.2, 0.3 and 0.4 mol%, were successfully synthesized by using a conventional melt and quench-casting technique. In this study, the remelting effect of the glass samples on their microstructure was investigated through density measurement and FT-IR spectra and evaluated by XRD techniques. Initial experimental results from XRD evaluation show that there are two distinct phases of glassy and crystallite microstructure due to the existence of peaks in the sample. The different physical behaviors of the studied glasses were closely related to the concentration of manganese in each phase. FTIR spectra revealed that the addition of manganese oxide contributes the transformation of TeO4 trigonal bipyramids with bridging oxygen (BO) to TeO3 trigonal pyramids with non-bridging oxygen (NBO). Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Mitochondrial Cytochrome c Oxidase and F1Fo-ATPase Dysfunction in Peppers (Capsicum annuum L.) with Cytoplasmic Male Sterility and Its Association with orf507 and Ψatp6-2 Genes
Int. J. Mol. Sci. 2013, 14(1), 1050-1068; doi:10.3390/ijms14011050
Received: 23 November 2012 / Revised: 13 December 2012 / Accepted: 28 December 2012 / Published: 7 January 2013
Cited by 13 | PDF Full-text (3189 KB) | HTML Full-text | XML Full-text
Abstract
Cytoplasmic male sterility (CMS) in pepper (Capsicum annuum L.) has been associated with novel genes in the mitochondria, such as orf507 and Ψatp6-2. Plant sterility has been proved to result from the rearrangement of the mitochondrial genome. Previous studies have demonstrated
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Cytoplasmic male sterility (CMS) in pepper (Capsicum annuum L.) has been associated with novel genes in the mitochondria, such as orf507 and Ψatp6-2. Plant sterility has been proved to result from the rearrangement of the mitochondrial genome. Previous studies have demonstrated that orf507 is co-transcribed with the cox II gene, and Ψatp6-2 is truncated at the 3' region of the atp6-2 that is found in the maintainer line. Until this time, little has been known about the relationship between the novel gene and the function of its corresponding enzyme in mitochondria from the CMS pepper line. Moreover, the aberrant function of the mitochondrial enzymes is seldom reported in pepper. In this study, we observed that anther abortion occurred after the tetrad stage in the CMS line (HW203A), which was accompanied by premature programmed cell death (PCD) in the tapetum. The spatiotemporal expression patterns of orf507 and Ψatp6-2 were analyzed together with the corresponding enzyme activities to investigate the interactions of the genes and mitochondrial enzymes. The two genes were both highly expressed in the anther. The orf507 was down-regulated in HW203A (CMS line), with nearly no expression in HW203B (the maintainer line). In contrast, the cytochrome c oxidase activity in HW203A showed the opposite trend, reaching its highest peak at the tetrad stage when compared with HW203B at the same stage. The Ψatp6-2 in the CMS line was also down-regulated, but it was up-regulated in the maintainer line. The corresponding F1Fo-ATPase activity in the CMS line was gradually decreased along with the development of the anther, which showed the same trend for Ψatp6-2 gene expression. On the contrary, with up-regulated gene expression of atp6-2 in the maintainer line, the F1Fo-ATPase activity sharply decreased after the initial development stage, but gradually increased following the tetrad stage, which was contrary to what happened in the CMS line. Taken together, all these results may provide evidence for the involvement of aberrant mitochondrial cytochrome c oxidase and F1Fo-ATPase in CMS pepper anther abortion. Moreover, the novel orf507 and Ψatp6-2 genes in the mitochondria may be involved in the dysfunction of the cytochrome c oxidase and F1Fo-ATPase, respectively, which are responsible for the abortion of anthers in the CMS line. Full article
(This article belongs to the Special Issue Abiotic and Biotic Stress Tolerance Mechanisms in Plants)
Open AccessArticle Organic Nitrates Favor Regression of Left Ventricular Hypertrophy in Hypertensive Patients on Chronic Peritoneal Dialysis
Int. J. Mol. Sci. 2013, 14(1), 1069-1079; doi:10.3390/ijms14011069
Received: 10 September 2012 / Revised: 4 December 2012 / Accepted: 28 December 2012 / Published: 7 January 2013
Cited by 5 | PDF Full-text (190 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH) in hypertensive patients on chronic peritoneal dialysis (PD). Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two
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The aim of the study was to evaluate the effect of nitrates on left ventricular hypertrophy (LVH) in hypertensive patients on chronic peritoneal dialysis (PD). Sixty-four PD patients with hypertension were enrolled in this study. All patients accepted antihypertensive drugs at baseline. Thirty-two patients (nitrate group) took isosorbide mononitrate for 24 weeks. The remaining 32 patients (non-nitrate group) took other antihypertensive drugs. Blood pressure (BP), left ventricular mass index (LVMI) and plasma asymmetric dimethylarginine (ADMA) were monitored. Subjects with normal renal function were included as the control group (n = 30). At baseline, plasma ADMA levels in PD patients were significantly higher than the control group, but there was no significant difference in plasma ADMA levels between the two groups. At the end of the 24-week period, BP, LVMI, LVH prevalence and plasma ADMA levels in the nitrate group were significantly lower than those in the non-nitrate group. BP did not show a significant difference between 12 and 24 weeks in the nitrate group with a reduced need for other medication. Logistic regression analysis showed that nitrate supplementation and SBP reduction were independent risk factors of LVMI change in PD patients after adjusting for age, gender, diabetes history and CCB supplementation. It was concluded that organic nitrates favor regression of LVH in hypertensive patients on chronic peritoneal dialysis, and nitrates may be considered for use before employing the five other antihypertensive agents other than nitrates. Full article
Open AccessArticle In Vitro Cytotoxicity of Fluorescent Silica Nanoparticles Hybridized with Aggregation-Induced Emission Luminogens for Living Cell Imaging
Int. J. Mol. Sci. 2013, 14(1), 1080-1092; doi:10.3390/ijms14011080
Received: 21 November 2012 / Revised: 28 December 2012 / Accepted: 28 December 2012 / Published: 7 January 2013
Cited by 5 | PDF Full-text (1917 KB) | HTML Full-text | XML Full-text
Abstract
Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and
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Fluorescent silica nanoparticles (FSNPs) can provide high-intensity and photostable fluorescent signals as a probe for biomedical analysis. In this study, FSNPs hybridized with aggregation-induced emission (AIE) luminogens (namely FSNP-SD) were successfully fabricated by a surfactant-free sol-gel method. The FSNP-SD were spherical, monodisperse and uniform in size, with an average diameter of approximately 100 nm, and emitted strong fluorescence at the peak of 490 nm. The FSNP-SD selectively stained the cytoplasmic regions and were distributed in the cytoplasm. Moreover, they can stay inside cells, enabling the tacking of cells over a long period of time. The intracellular vesicles and multinucleated cells were increase gradually with the rise of FSNP-SD concentration. Both cell viability and survival only lost less than 20% when the cells were exposed to the high concentration of 100 μg/mL FSNP-SD. Additionally, the cell apoptosis and intracellular ROS assay indicated that FSNP-SD had no significant toxic effects at the maximum working concentration of 80 μg/mL. This study demonstrated that the FSNP-SD are promising biocompatible fluorescent probes for living cell imaging. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessArticle Detection of Tumor Cell-Specific mRNA in the Peripheral Blood of Patients with Breast Cancer — Evaluation of Several Markers with Real-Time Reverse Transcription-PCR
Int. J. Mol. Sci. 2013, 14(1), 1093-1104; doi:10.3390/ijms14011093
Received: 12 November 2012 / Revised: 3 December 2012 / Accepted: 31 December 2012 / Published: 8 January 2013
Cited by 10 | PDF Full-text (716 KB) | HTML Full-text | XML Full-text
Abstract
It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be
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It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy. Full article
(This article belongs to the Special Issue Advances in Molecular Diagnostics)
Open AccessArticle Identification of Recurrence Related microRNAs in Hepatocellular Carcinoma after Surgical Resection
Int. J. Mol. Sci. 2013, 14(1), 1105-1118; doi:10.3390/ijms14011105
Received: 31 October 2012 / Revised: 11 December 2012 / Accepted: 24 December 2012 / Published: 8 January 2013
Cited by 12 | PDF Full-text (769 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers with a high frequency of post-surgical recurrence. It is very critical to diagnose HCC recurrence at an early stage for a better therapeutic treatment. In this study, we examined the microRNA (miRNA)
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Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers with a high frequency of post-surgical recurrence. It is very critical to diagnose HCC recurrence at an early stage for a better therapeutic treatment. In this study, we examined the microRNA (miRNA) expression profiling in tumor tissues obtained from early and late recurrent HCC patients post-resection, using a microarray assay. A total of 32 miRNAs were identified to be differentially expressed during the progression of recurrence. Among these, 16 miRNAs were upregulated and 16 were downregulated. In addition, this miRNA expression signature was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, functional annotation of predicted target genes of these recurrent HCC-related miRNAs indicates that multiple biological pathways (i.e., focal adhesion pathway, cancer-related pathways and mitogen-activated protein kinase (MAPK) signaling) that are all critical for cancer development and progression, may participate in the recurrence of HCC. Our data suggest potential molecular mechanisms underpinning miRNA-controlled HCC recurrence, and support the notion that miRNA expression signature and miRNA-based therapy can be useful tools for a better diagnosis and treatment stratification of this disease. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
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Open AccessArticle Characterization of a Crabs Claw Gene in Basal Eudicot Species Epimedium sagittatum (Berberidaceae)
Int. J. Mol. Sci. 2013, 14(1), 1119-1131; doi:10.3390/ijms14011119
Received: 28 September 2012 / Revised: 13 December 2012 / Accepted: 28 December 2012 / Published: 8 January 2013
Cited by 2 | PDF Full-text (698 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Crabs Claw (CRC) YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots,
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The Crabs Claw (CRC) YABBY gene is required for regulating carpel development in angiosperms and has played an important role in nectary evolution during core eudicot speciation. The function or expression of CRC-like genes has been explored in two basal eudicots, Eschscholzia californica and Aquilegia formosa. To further investigate the function of CRC orthologous genes related to evolution of carpel and nectary development in basal eudicots, a CRC ortholog, EsCRC, was isolated and characterized from Epimedium sagittatum (Sieb. and Zucc.) Maxim. A phylogenetic analysis of EsCRC and previously identified CRC-like genes placed EsCRC within the basal eudicot lineage. Gene expression results suggest that EsCRC is involved in the development of sepals and carpels, but not nectaries. Phenotypic complementation of the Arabidopsis mutant crc-1 was achieved by constitutive expression of EsCRC. In addition, over-expression of EsCRC in Arabidopsis and tobacco gave rise to abaxially curled leaves. Transgenic results together with the gene expression analysis suggest that EsCRC may maintain a conserved function in carpel development and also play a novel role related to sepal formation. Absence of EsCRC and ElCRC expression in nectaries further indicates that nectary development in non-core eudicots is unrelated to expression of CRC-like genes. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Structural and Phylogenetic Analysis of Rhodobacter capsulatus NifF: Uncovering General Features of Nitrogen-fixation (nif)-Flavodoxins
Int. J. Mol. Sci. 2013, 14(1), 1152-1163; doi:10.3390/ijms14011152
Received: 1 November 2012 / Revised: 14 November 2012 / Accepted: 20 November 2012 / Published: 9 January 2013
Cited by 4 | PDF Full-text (446 KB) | HTML Full-text | XML Full-text
Abstract
Analysis of the crystal structure of NifF from Rhodobacter capsulatus and its homologues reported so far reflects the existence of unique structural features in nif flavodoxins: a leucine at the re face of the isoalloxazine, an eight-residue insertion at the C-terminus of
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Analysis of the crystal structure of NifF from Rhodobacter capsulatus and its homologues reported so far reflects the existence of unique structural features in nif flavodoxins: a leucine at the re face of the isoalloxazine, an eight-residue insertion at the C-terminus of the 50’s loop and a remarkable difference in the electrostatic potential surface with respect to non-nif flavodoxins. A phylogenetic study on 64 sequences from 52 bacterial species revealed four clusters, including different functional prototypes, correlating the previously defined as “short-chain” with the firmicutes flavodoxins and the “long-chain” with gram-negative species. The comparison of Rhodobacter NifF structure with other bacterial flavodoxin prototypes discloses the concurrence of specific features of these functional electron donors to nitrogenase. Full article
(This article belongs to the Special Issue Flavins)
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Open AccessArticle Interaction of Proteins Identified in Human Thyroid Cells
Int. J. Mol. Sci. 2013, 14(1), 1164-1178; doi:10.3390/ijms14011164
Received: 8 November 2012 / Revised: 21 December 2012 / Accepted: 6 January 2013 / Published: 9 January 2013
Cited by 20 | PDF Full-text (903 KB) | HTML Full-text | XML Full-text
Abstract
Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated
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Influence of gravity forces on the regulation of protein expression by healthy and malignant thyroid cells was studied with the aim to identify protein interactions. Western blot analyses of a limited number of proteins suggested a time-dependent regulation of protein expression by simulated microgravity. After applying free flow isoelectric focusing and mass spectrometry to search for differently expressed proteins by thyroid cells exposed to simulated microgravity for three days, a considerable number of candidates for gravi-sensitive proteins were detected. In order to show how proteins sensitive to microgravity could directly influence other proteins, we investigated all polypeptide chains identified with Mascot scores above 100, looking for groups of interacting proteins. Hence, UniProtKB entry numbers of all detected proteins were entered into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and processed. The program indicated that we had detected various groups of interacting proteins in each of the three cell lines studied. The major groups of interacting proteins play a role in pathways of carbohydrate and protein metabolism, regulation of cell growth and cell membrane structuring. Analyzing these groups, networks of interaction could be established which show how a punctual influence of simulated microgravity may propagate via various members of interaction chains. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessArticle Coumarins from the Herb Cnidium monnieri and Chemically Modified Derivatives as Antifoulants against Balanus albicostatus and Bugula neritina Larvae
Int. J. Mol. Sci. 2013, 14(1), 1197-1206; doi:10.3390/ijms14011197
Received: 11 October 2012 / Revised: 24 November 2012 / Accepted: 11 December 2012 / Published: 9 January 2013
Cited by 7 | PDF Full-text (252 KB) | HTML Full-text | XML Full-text
Abstract
In the search for new environmental friendly antifouling (AF) agents, four coumarins were isolated from the herbal plant Cnidium monnieri, known as osthole (1), imperatorin (2), isopimpinellin (3) and auraptenol (4). Furthermore, five coumarin
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In the search for new environmental friendly antifouling (AF) agents, four coumarins were isolated from the herbal plant Cnidium monnieri, known as osthole (1), imperatorin (2), isopimpinellin (3) and auraptenol (4). Furthermore, five coumarin derivatives, namely 8-epoxypentylcoumarin (5), meranzin hydrate (6), 2'-deoxymetranzin hydrate (7), 8-methylbutenalcoumarin (8), and micromarin-F (9) were synthesized from osthole. Compounds 1, 2, 4, 7 showed high inhibitory activities against larval settlement of Balanus albicostatus with EC50 values of 4.64, 3.39, 3.38, 4.67 μg mL−1. Compound 8 could significantly inhibit larval settlement of Bugula neritina with an EC50 value of 3.87 μg mL−1. The impact of functional groups on anti-larval settlement activities suggested that the groups on C-5' and C-2'/C-3' of isoamylene chian could affect the AF activities. Full article
(This article belongs to the Special Issue Green Biocides)
Open AccessArticle Consequences of Morphology on Molecularly Imprinted Polymer-Ligand Recognition
Int. J. Mol. Sci. 2013, 14(1), 1207-1217; doi:10.3390/ijms14011207
Received: 20 November 2012 / Revised: 24 December 2012 / Accepted: 1 January 2013 / Published: 9 January 2013
Cited by 9 | PDF Full-text (362 KB) | HTML Full-text | XML Full-text
Abstract
The relationship between molecularly imprinted polymer (MIP) morphology and template-rebinding over a series of warfarin-imprinted methacrylic acid co(ethylene dimethacrylate) polymers has been explored. Detailed investigations of the nature of template recognition revealed that an optimal template binding was obtained with polymers possessing
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The relationship between molecularly imprinted polymer (MIP) morphology and template-rebinding over a series of warfarin-imprinted methacrylic acid co(ethylene dimethacrylate) polymers has been explored. Detailed investigations of the nature of template recognition revealed that an optimal template binding was obtained with polymers possessing a narrow population of pores (~3–4 nm) in the mesopore size range. Importantly, the warfarin-polymer rebinding analyses suggest strategies for regulating ligand binding capacity and specificity through variation of the degree of cross-linking, where polymers prepared with a lower degree of cross-linking afford higher capacity though non-specific in character. In contrast, the co-existence of specific and non-specific binding was found in conjunction with higher degrees of cross-linking and resultant meso- and macropore size distributions. Full article
(This article belongs to the Special Issue Molecular Imprinting Science and Technology)
Open AccessArticle Catalytic Mechanism of Short Ethoxy Chain Nonylphenol Dehydrogenase Belonging to a Polyethylene Glycol Dehydrogenase Group in the GMC Oxidoreductase Family
Int. J. Mol. Sci. 2013, 14(1), 1218-1231; doi:10.3390/ijms14011218
Received: 10 October 2012 / Revised: 21 December 2012 / Accepted: 2 January 2013 / Published: 10 January 2013
Cited by 5 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol
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Ethoxy (EO) chain nonylphenol dehydrogenase (NPEO-DH) from Ensifer sp. AS08 and EO chain octylphenol dehydrogenase from Pseudomonas putida share common molecular characteristics with polyethylene glycol (PEG) dehydrogenases (PEG-DH) and comprise a PEG-DH subgroup in the family of glucose-methanol-choline (GMC) oxidoreductases that includes glucose/alcohol oxidase and glucose/choline dehydrogenase. Three-dimensional (3D) molecular modeling suggested that differences in the size, secondary structure and hydropathy in the active site caused differences in their substrate specificities toward EO chain alkylphenols and free PEGs. Based on 3D molecular modeling, site-directed mutagenesis was utilized to introduce mutations into potential catalytic residues of NPEO-DH. From steady state and rapid kinetic characterization of wild type and mutant NPEO-DHs, we can conclude that His465 and Asn507 are directly involved in the catalysis. Asn507 mediates the transfer of proton from a substrate to FAD and His465 transfers the same proton from the reduced flavin to an electron acceptor. Full article
(This article belongs to the Special Issue Flavins)
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Open AccessArticle Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity
Int. J. Mol. Sci. 2013, 14(1), 1293-1309; doi:10.3390/ijms14011293
Received: 14 November 2012 / Revised: 2 December 2012 / Accepted: 5 December 2012 / Published: 10 January 2013
Cited by 10 | PDF Full-text (286 KB) | HTML Full-text | XML Full-text
Abstract
The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus
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The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect
Int. J. Mol. Sci. 2013, 14(1), 1323-1334; doi:10.3390/ijms14011323
Received: 20 December 2012 / Revised: 1 January 2013 / Accepted: 5 January 2013 / Published: 10 January 2013
Cited by 11 | PDF Full-text (752 KB) | HTML Full-text | XML Full-text
Abstract
Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent
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Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si). Alminoprofen is a non-steroid anti-inflammatory drug (NSAID) used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme) was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessArticle Anticancer Effects of Bufalin on Human Hepatocellular Carcinoma HepG2 Cells: Roles of Apoptosis and Autophagy
Int. J. Mol. Sci. 2013, 14(1), 1370-1382; doi:10.3390/ijms14011370
Received: 6 November 2012 / Revised: 25 December 2012 / Accepted: 25 December 2012 / Published: 11 January 2013
Cited by 18 | PDF Full-text (1888 KB) | HTML Full-text | XML Full-text
Abstract
The traditional Chinese medicine bufalin, extracted from toad’s skin, has been demonstrated to exert anticancer activities in various kinds of human cancers. The mechanisms of action lie in its capacity to induce apoptosis, or termed type I programmed cell death (PCD). However, type
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The traditional Chinese medicine bufalin, extracted from toad’s skin, has been demonstrated to exert anticancer activities in various kinds of human cancers. The mechanisms of action lie in its capacity to induce apoptosis, or termed type I programmed cell death (PCD). However, type II PCD, or autophagy, participates in cancer proliferation, progression, and relapse, as well. Recent studies on autophagy seem to be controversial because of the dual roles of autophagy in cancer survival and death. In good agreement with previous studies, we found that 100 nM bufalin induced extensive HepG2 cell apoptosis. However, we also noticed bufalin triggered autophagy and enhanced Beclin-1 expression, LC3-I to LC3-II conversion, as well as decreased p62 expression and mTOR signaling activation in HepG2 cells. Blockage of autophagy by selective inhibitor 3-MA decreased apoptotic ratio in bufalin-treated HepG2 cells, suggesting a proapoptotic role of bufalin-induced autophagy. Furthermore, we investigated the underlying mechanisms of bufalin-induced autophagy. Bufalin treatment dose-dependently promoted AMPK phosphorylation while AMPK inhibition by compound C significantly attenuated bufalin-induced autophagy. Taken together, we report for the first time that bufalin induces HepG2 cells PCD, especially for autophagy, and the mechanism of action is, at least in part, AMPK-mTOR dependent. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessArticle Shear Stress Inhibits Apoptosis of Ischemic Brain Microvascular Endothelial Cells
Int. J. Mol. Sci. 2013, 14(1), 1412-1427; doi:10.3390/ijms14011412
Received: 8 August 2012 / Revised: 22 November 2012 / Accepted: 20 December 2012 / Published: 11 January 2013
Cited by 4 | PDF Full-text (2931 KB) | HTML Full-text | XML Full-text
Abstract
As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF) is the most fundamental option. Laminar shear stress (LS), as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs). In order to study
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As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF) is the most fundamental option. Laminar shear stress (LS), as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs). In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs) through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Buckwheat (Fagopyrum esculentum M.) Sprout Treated with Methyl Jasmonate (MeJA) Improved Anti-Adipogenic Activity Associated with the Oxidative Stress System in 3T3-L1 Adipocytes
Int. J. Mol. Sci. 2013, 14(1), 1428-1442; doi:10.3390/ijms14011428
Received: 9 November 2012 / Revised: 25 December 2012 / Accepted: 3 January 2013 / Published: 11 January 2013
Cited by 10 | PDF Full-text (938 KB) | HTML Full-text | XML Full-text
Abstract
Buckwheat sprouts contain various bioactive compounds including rutin which have a number of biological activities. We have previously shown that buckwheat sprouts (TBWE) treated with methyl jasmonate (MeJA) significantly increased the amount of phenolics and the antioxidant activity. The aim of this study
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Buckwheat sprouts contain various bioactive compounds including rutin which have a number of biological activities. We have previously shown that buckwheat sprouts (TBWE) treated with methyl jasmonate (MeJA) significantly increased the amount of phenolics and the antioxidant activity. The aim of this study was to demonstrate the effect of TBWE on anti-adipogenesis and pro-oxidant enzyme in 3T3-L1 adipocytes. We also evaluated the anti-oxidative activity of TBWE in adipocytes by using the nitroblue tetrazolium assay. Our data showed that TBWE markedly inhibited adipocyte differentiation and ROS production in 3T3-L1 cells compared with control groups. Moreover, TBWE has strongly shown the inhibition of adipogenic transcription factor as well as pro-oxidant enzymes. Together, we demonstrate that the MeJA treatment significantly increased the amount of phenolic compound, resulting in the suppression of adipogenesis and ROS production in the 3T3-L1 cells. These findings indicate that TBWE has the potential for anti-adipogenesis activity with anti-oxidative properties. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Quantitative Structure-Activity Relationships Predicting the Antioxidant Potency of 17β-Estradiol-Related Polycyclic Phenols to Inhibit Lipid Peroxidation
Int. J. Mol. Sci. 2013, 14(1), 1443-1454; doi:10.3390/ijms14011443
Received: 13 December 2012 / Revised: 3 January 2013 / Accepted: 5 January 2013 / Published: 11 January 2013
Cited by 3 | PDF Full-text (323 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order
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The antioxidant potency of 17β-estradiol and related polycyclic phenols has been well established. This property is an important component of the complex events by which these types of agents are capable to protect neurons against the detrimental consequences of oxidative stress. In order to relate their molecular structure and properties with their capacity to inhibit lipid peroxidation, a marker of oxidative stress, quantitative structure-activity relationship (QSAR) studies were conducted. The inhibition of Fe3+-induced lipid peroxidation in rat brain homogenate, measured through an assay detecting thiobarbituric acid reactive substances for about seventy compounds were correlated with various molecular descriptors. We found that lipophilicity (modeled by the logarithm of the n-octanol/water partition coefficient, logP) was the property that influenced most profoundly the potency of these compounds to inhibit lipid peroxidation in the biological medium studied. Additionally, the important contribution of the bond dissociation enthalpy of the phenolic O-H group, a shape index, the solvent-accessible surface area and the energy required to remove an electron from the highest occupied molecular orbital were also confirmed. Several QSAR equations were validated as potentially useful exploratory tools for identifying or designing novel phenolic antioxidants incorporating the structural backbone of 17β-estradiol to assist therapy development against oxidative stress-associated neurodegeneration. Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2012)
Open AccessArticle Folate-Equipped Nanolipoplexes Mediated Efficient Gene Transfer into Human Epithelial Cells
Int. J. Mol. Sci. 2013, 14(1), 1477-1501; doi:10.3390/ijms14011477
Received: 10 December 2012 / Revised: 31 December 2012 / Accepted: 6 January 2013 / Published: 14 January 2013
Cited by 9 | PDF Full-text (1914 KB) | HTML Full-text | XML Full-text
Abstract
Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the
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Since recombinant viral vectors have been associated with serious side effects, such as immunogenicity and oncogenicity, synthetic delivery systems represent a realistic alternative for achieving efficacy in gene therapy. A major challenge for non-viral nanocarriers is the optimization of transgene expression in the targeted cells. This goal can be achieved by fine-tuning the chemical carriers and the adding specific motifs to promote cellular penetration. Our study focuses on the development of novel folate-based complexes that contain varying quantities of folate motifs. After controlling for their physical properties, neutral folate-modified lipid formulations were compared in vitro to lipoplexes leading to comparable expression levels. In addition, no cytotoxicity was detected, unlike what was observed in the cationic controls. Mechanistically, the delivery of the transgene appeared to be, in part, due to endocytosis mediated by folate receptor targeting. This mechanism was further validated by the observation that adding free folate into the medium decreased luciferase expression by 50%. In vivo transfection with the folate-modified MM18 lipid, containing the highest amount of FA-PEG570-diether co-lipid (w:w; 90:10), at a neutral charge ratio, gave luciferase transgene expression. These studies indicate that modification of lipids with folate residues could enhance non-toxic, cell-specific gene delivery. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessArticle Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways
Int. J. Mol. Sci. 2013, 14(1), 1502-1515; doi:10.3390/ijms14011502
Received: 12 December 2012 / Revised: 1 January 2013 / Accepted: 7 January 2013 / Published: 14 January 2013
Cited by 11 | PDF Full-text (535 KB) | HTML Full-text | XML Full-text
Abstract
Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins
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Anthocyanins are naturally occurring polyphenols that impart bright color to fruits, vegetables and plants and have a variety of protective properties, which have generally been attributed to their antioxidant capacity. However, little is known about the molecular mechanisms underlying anti-inflammatory effects of anthocyanins related to neurodegenerative diseases. Therefore, we determined whether anthocyanins isolated from black soybean seed coats would inhibit pro-inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells. Our results showed that anthocyanins significantly inhibited LPS-induced pro-inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2, and pro-inflammatory cytokines including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, without significant cytotoxicity. Anthocyanins also downregulated excessive expression of inducible NO synthase, cyclooxygenase-2, TNF-α, and IL-1β in LPS-stimulated BV2 cells. Moreover, anthocyanins inhibited nuclear translocation of nuclear factor-kappa B (NF-κB) by reducing inhibitor of NF-κB alpha degradation as well as phosphorylating extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and Akt. These findings suggest that anthocyanins may offer substantial therapeutic potential for treating inflammatory and neurodegenerative diseases accompanied by microglial activation. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Depigmentation Effect of Kadsuralignan F on Melan-A Murine Melanocytes and Human Skin Equivalents
Int. J. Mol. Sci. 2013, 14(1), 1655-1666; doi:10.3390/ijms14011655
Received: 17 December 2012 / Revised: 7 January 2013 / Accepted: 10 January 2013 / Published: 15 January 2013
Cited by 7 | PDF Full-text (513 KB) | HTML Full-text | XML Full-text
Abstract
The development of melanogenic inhibitors is important for the prevention of hyperpigmentation, and, recently, consideration has been given to natural materials or traditionally used ingredients such as Chinese medicine. The aim of this study is the evaluation of a new anti-melanogenic candidate, kadsuralignan
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The development of melanogenic inhibitors is important for the prevention of hyperpigmentation, and, recently, consideration has been given to natural materials or traditionally used ingredients such as Chinese medicine. The aim of this study is the evaluation of a new anti-melanogenic candidate, kadsuralignan F, from the natural plant Kadsura coccinea, as well as the determination of mechanisms of melanogenesis inhibition at a molecular level. Kadsuralignan F significantly reduced melanin synthesis in a dose-dependent manner in a murine melanocyte cell line and human skin equivalents. There was no direct inhibition on mushroom tyrosinase or cell-extract tyrosinase activity, and mRNA expression of tyrosinase and other melanogenic genes such as tyrosinase-related protein-1 (trp-1) or trp-2 were not affected by kadsuralignan F. Interestingly, the protein level of tyrosinase was dramatically downregulated with kadsuralignan F treatment. We found that a decrease of tyrosinase protein by kadsuralignan F was fully recovered by MG132, a proteasome inhibitor, but not by chloroquine, a lysosome inhibitor. In this study, we found that kadsuralignan F, a lignan from an extract of Kadsura coccinea, has an inhibitory activity on melanin synthesis through tyrosinase degradation. These findings suggest that kadsuralignan F can be used as an active ingredient for hyperpigmentation treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Crystal Structure of Dimeric Flavodoxin from Desulfovibrio gigas Suggests a Potential Binding Region for the Electron-Transferring Partner
Int. J. Mol. Sci. 2013, 14(1), 1667-1683; doi:10.3390/ijms14011667
Received: 24 October 2012 / Revised: 3 December 2012 / Accepted: 25 December 2012 / Published: 15 January 2013
Cited by 4 | PDF Full-text (1104 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Flavodoxins, which exist widely in microorganisms, have been found in various pathways with multiple physiological functions. The flavodoxin (Fld) containing the cofactor flavin mononucleotide (FMN) from sulfur-reducing bacteria Desulfovibrio gigas (D. gigas) is a short-chain enzyme that comprises 146 residues with
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Flavodoxins, which exist widely in microorganisms, have been found in various pathways with multiple physiological functions. The flavodoxin (Fld) containing the cofactor flavin mononucleotide (FMN) from sulfur-reducing bacteria Desulfovibrio gigas (D. gigas) is a short-chain enzyme that comprises 146 residues with a molecular mass of 15 kDa and plays important roles in the electron-transfer chain. To investigate its structure, we purified this Fld directly from anaerobically grown D. gigas cells. The crystal structure of Fld, determined at resolution 1.3 Å, is a dimer with two FMN packing in an orientation head to head at a distance of 17 Å, which generates a long and connected negatively charged region. Two loops, Thr59–Asp63 and Asp95–Tyr100, are located in the negatively charged region and between two FMN, and are structurally dynamic. An analysis of each monomer shows that the structure of Fld is in a semiquinone state; the positions of FMN and the surrounding residues in the active site deviate. The crystal structure of Fld from D. gigas agrees with a dimeric form in the solution state. The dimerization area, dynamic characteristics and structure variations between monomers enable us to identify a possible binding area for its functional partners. Full article
(This article belongs to the Special Issue Flavins)
Open AccessArticle Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma
Int. J. Mol. Sci. 2013, 14(1), 1684-1697; doi:10.3390/ijms14011684
Received: 23 November 2012 / Revised: 4 January 2013 / Accepted: 6 January 2013 / Published: 15 January 2013
Cited by 8 | PDF Full-text (1781 KB) | HTML Full-text | XML Full-text
Abstract
Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study,
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Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle Biofunctional Constituents from Liriodendron tulipifera with Antioxidants and Anti-Melanogenic Properties
Int. J. Mol. Sci. 2013, 14(1), 1698-1712; doi:10.3390/ijms14011698
Received: 25 October 2012 / Revised: 16 December 2012 / Accepted: 4 January 2013 / Published: 15 January 2013
Cited by 10 | PDF Full-text (1261 KB) | HTML Full-text | XML Full-text
Abstract
From the stems of Liriodendron tulipifera, seventeen known compounds have been extracted, isolated and purified. By using spectroscopic analysis, the structures of these pure constituents were determined as three lignans, four steroids and ten benzenoids. Identified compounds were screened for antioxidant abilities
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From the stems of Liriodendron tulipifera, seventeen known compounds have been extracted, isolated and purified. By using spectroscopic analysis, the structures of these pure constituents were determined as three lignans, four steroids and ten benzenoids. Identified compounds were screened for antioxidant abilities using: 1,1-diphenyl-2-picrylhydrazul (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging free radical activity assays; metal chelating power test; and ferric reducing/antioxidant power (FRAP) examination. The result revealed that seventeen compounds had potential anti-oxidative capabilities. In addition, the anti-tyrosinase effect was determined by calculating the hydroxylation of L-tyrosine to L-dopa and the oxidization of L-dopa to dopaquinone, according to in vitro mushroom tyrosinase evaluation platform. Furthermore, based on assays on B16F10 cell line, our data suggest that five compounds isolated from L. tulipifera would be able to inhibit tyrosinase activity and reduce the melanin content in animal cells. Therefore, some of the examined compounds could be potentially used in the cosmetic skin whitening business, therapeutic applications or the food industry. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Gamma-Aminobutyric Acid Production Using Immobilized Glutamate Decarboxylase Followed by Downstream Processing with Cation Exchange Chromatography
Int. J. Mol. Sci. 2013, 14(1), 1728-1739; doi:10.3390/ijms14011728
Received: 17 November 2012 / Revised: 1 January 2013 / Accepted: 2 January 2013 / Published: 15 January 2013
Cited by 10 | PDF Full-text (571 KB) | HTML Full-text | XML Full-text
Abstract
We have developed a gamma-aminobutyric acid (GABA) production technique using his-tag mediated immobilization of Escherichia coli-derived glutamate decarboxylase (GAD), an enzyme that catalyzes the conversion of glutamate to GABA. The GAD was obtained at 1.43 g/L from GAD-overexpressed E. coli fermentation and
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We have developed a gamma-aminobutyric acid (GABA) production technique using his-tag mediated immobilization of Escherichia coli-derived glutamate decarboxylase (GAD), an enzyme that catalyzes the conversion of glutamate to GABA. The GAD was obtained at 1.43 g/L from GAD-overexpressed E. coli fermentation and consisted of 59.7% monomer, 29.2% dimer and 2.3% tetramer with a 97.6% soluble form of the total GAD. The harvested GAD was immobilized to metal affinity gel with an immobilization yield of 92%. Based on an investigation of specific enzyme activity and reaction characteristics, glutamic acid (GA) was chosen over monosodium glutamate (MSG) as a substrate for immobilized GAD, resulting in conversion of 2.17 M GABA in a 1 L reactor within 100 min. The immobilized enzymes retained 58.1% of their initial activities after ten consecutive uses. By using cation exchange chromatography followed by enzymatic conversion, GABA was separated from the residual substrate and leached GAD. As a consequence, the glutamic acid was mostly removed with no detectable GAD, while 91.2% of GABA was yielded in the purification step. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Comparative Proteomic Analysis of Puccinellia tenuiflora Leaves under Na2CO3 Stress
Int. J. Mol. Sci. 2013, 14(1), 1740-1762; doi:10.3390/ijms14011740
Received: 17 October 2012 / Revised: 31 December 2012 / Accepted: 6 January 2013 / Published: 15 January 2013
Cited by 14 | PDF Full-text (675 KB) | HTML Full-text | XML Full-text
Abstract
Soil salt-alkalinization is a widespread environmental stress that limits crop growth and agricultural productivity. The influence of soil alkalization caused by Na2CO3 on plants is more severe than that of soil salinization. Plants have evolved some unique mechanisms to cope
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Soil salt-alkalinization is a widespread environmental stress that limits crop growth and agricultural productivity. The influence of soil alkalization caused by Na2CO3 on plants is more severe than that of soil salinization. Plants have evolved some unique mechanisms to cope with alkali stress; however, the plant alkaline-responsive signaling and molecular pathways are still unknown. In the present study, Na2CO3 responsive characteristics in leaves from 50-day-old seedlings of halophyte Puccinellia tenuiflora were investigated using physiological and proteomic approaches. Comparative proteomics revealed 43 differentially expressed proteins in P. tenuiflora leaves in response to Na2CO3 treatment for seven days. These proteins were mainly involved in photosynthesis, stress and defense, carbohydrate/energy metabolism, protein metabolism, signaling, membrane and transport. By integrating the changes of photosynthesis, ion contents, and stress-related enzyme activities, some unique Na2CO3 responsive mechanisms have been discovered in P. tenuiflora. This study provides new molecular information toward improving the alkali tolerance of cereals. Full article
(This article belongs to the collection Advances in Proteomic Research)
Open AccessArticle Study of the UTMD-Based Delivery System to Induce Cervical Cancer Cell Apoptosis and Inhibit Proliferation with shRNA targeting Survivin
Int. J. Mol. Sci. 2013, 14(1), 1763-1777; doi:10.3390/ijms14011763
Received: 3 November 2012 / Revised: 4 January 2013 / Accepted: 6 January 2013 / Published: 16 January 2013
Cited by 5 | PDF Full-text (1469 KB) | HTML Full-text | XML Full-text
Abstract
Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo
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Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo transfected by the UTMD-based shRNA delivery system. Nude mice with transplanted tumors of cervical cancer were randomly arranged into three groups: control group, plasmid injection and ultrasound (P + US), P + UTMD group. Expressions of Survivin and proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, Caspase-3, Ki-67, nucleostemin (NS) were investigated by immunohistochemistry. Furthermore, microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by TUNEL. As compared with those in the control and P + US groups, protein expressions of PCNA, Ki-67, Bcl-2, Survivin and NS in P + UTMD groups were down-regulated markedly, while those of Bax, Caspase-3 were up-regulated significantly (p < 0.05). MVD decreased significantly, whereas AI increased remarkably (p < 0.05). We suggested that UTMD-based shRNA delivery system could induce apoptosis and inhibit proliferation significantly, without causing any apparently adverse effect, representing a new, promising technology that would be used in the future gene therapy and research. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Stable Isolation of Phycocyanin from Spirulina platensis Associated with High-Pressure Extraction Process
Int. J. Mol. Sci. 2013, 14(1), 1778-1787; doi:10.3390/ijms14011778
Received: 18 October 2012 / Revised: 17 December 2012 / Accepted: 7 January 2013 / Published: 16 January 2013
Cited by 6 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
A method for stably purifying a functional dye, phycocyanin from Spirulina platensis was developed by a hexane extraction process combined with high pressure. This was necessary because this dye is known to be very unstable during normal extraction processes. The purification yield of
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A method for stably purifying a functional dye, phycocyanin from Spirulina platensis was developed by a hexane extraction process combined with high pressure. This was necessary because this dye is known to be very unstable during normal extraction processes. The purification yield of this method was estimated as 10.2%, whose value is 3%–5% higher than is the case from another conventional separation method using phosphate buffer. The isolated phycocyanin from this process also showed the highest purity of 0.909 based on absorbance of 2.104 at 280 nm and 1.912 at 620 nm. Two subunits of phycocyanin namely α-phycocyanin (18.4 kDa) and β-phycocyanin (21.3 kDa) were found to remain from the original mixtures after being extracted, based on SDS-PAGE analysis, clearly demonstrating that this process can stably extract phycocyanin and is not affected by extraction solvent, temperature, etc. The stability of the extracted phycocyanin was also confirmed by comparing its DPPH (α,α-diphenyl-β-picrylhydrazyl) scavenging activity, showing 83% removal of oxygen free radicals. This activity was about 15% higher than that of commercially available standard phycocyanin, which implies that the combined extraction method can yield relatively intact chromoprotein through absence of degradation. The results were achieved because the low temperature and high pressure extraction effectively disrupted the cell membrane of Spirulina platensis and degraded less the polypeptide subunits of phycocyanin (which is a temperature/pH-sensitive chromoprotein) as well as increasing the extraction yield. Full article
Open AccessArticle Modeling of Anopheles minimus Mosquito NADPH-Cytochrome P450 Oxidoreductase (CYPOR) and Mutagenesis Analysis
Int. J. Mol. Sci. 2013, 14(1), 1788-1801; doi:10.3390/ijms14011788
Received: 25 September 2012 / Revised: 19 November 2012 / Accepted: 5 January 2013 / Published: 16 January 2013
Cited by 4 | PDF Full-text (979 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Malaria is one of the most dangerous mosquito-borne diseases in many tropical countries, including Thailand. Studies in a deltamethrin resistant strain of Anopheles minimus mosquito, suggest cytochrome P450 enzymes contribute to the detoxification of pyrethroid insecticides. Purified A. minimus CYPOR enzyme (AnCYPOR), which
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Malaria is one of the most dangerous mosquito-borne diseases in many tropical countries, including Thailand. Studies in a deltamethrin resistant strain of Anopheles minimus mosquito, suggest cytochrome P450 enzymes contribute to the detoxification of pyrethroid insecticides. Purified A. minimus CYPOR enzyme (AnCYPOR), which is the redox partner of cytochrome P450s, loses flavin-adenosine di-nucleotide (FAD) and FLAVIN mono-nucleotide (FMN) cofactors that affect its enzyme activity. Replacement of leucine residues at positions 86 and 219 with phenylalanines in FMN binding domain increases FMN binding, enzyme stability, and cytochrome c reduction activity. Membrane-Bound L86F/L219F-AnCYPOR increases A. minimus P450-mediated pyrethroid metabolism in vitro. In this study, we constructed a comparative model structure of AnCYPOR using a rat CYPOR structure as a template. Overall model structure is similar to rat CYPOR, with some prominent differences. Based on primary sequence and structural analysis of rat and A. minimus CYPOR, C427R, W678A, and W678H mutations were generated together with L86F/L219F resulting in three soluble Δ55 triple mutants. The C427R triple AnCYPOR mutant retained a higher amount of FAD binding and increased cytochrome c reduction activity compared to wild-type and L86F/L219F-Δ55AnCYPOR double mutant. However W678A and W678H mutations did not increase FAD and NAD(P)H bindings. The L86F/L219F double and C427R triple membrane-bound AnCYPOR mutants supported benzyloxyresorufin O-deakylation (BROD) mediated by mosquito CYP6AA3 with a two- to three-fold increase in efficiency over wild-type AnCYPOR. The use of rat CYPOR in place of AnCYPOR most efficiently supported CYP6AA3-mediated BROD compared to all AnCYPORs. Full article
(This article belongs to the Special Issue Flavins)
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Open AccessArticle The Combination of Catechin and Epicatechin Gallate from Fructus Crataegi Potentiates β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus (MRSA) in Vitro and in Vivo
Int. J. Mol. Sci. 2013, 14(1), 1802-1821; doi:10.3390/ijms14011802
Received: 8 October 2012 / Revised: 29 November 2012 / Accepted: 8 January 2013 / Published: 16 January 2013
Cited by 14 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fructus crataegi (hawthorn) is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of
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Fructus crataegi (hawthorn) is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+)-catechin (C), (−)-epicatechin gallate (ECg) and (−)-epigallocatechin (EGC) were isolated from the hawthorn under the guide of antibacterial sensitization activity. The bioactivity of the composite fraction in enhancing the antibacterial effect of oxacillin against methicillin-resistant Staphylococcus aureus (MRSA) was greater than that of the individual monomer of the hawthorn extract in vitro. Two-fold dilution and checkerboard methods were used to analyze antibacterial activity and screen for the combination and proportion of monomers with the best bioactivity. The result showed that C (128 mg/L) combined with ECg (16 mg/L) had the greatest effect and the combination also reduced the bacterial load in blood of septic mice challenged with a sublethal dose of MRSA, increased daunomycin accumulation within MRSA and down-regulated the mRNA expression of norA, norC and abcA, three important efflux pumps of MRSA. In summary, C and ECg enhanced the antibacterial effect of β-lactam antibiotics against MRSA in vitro and in vivo, which might be related to the increased accumulation of antibiotics within MRSA via suppression of important efflux pumps’ gene expression. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessArticle Synthesis of Bisindolylmethanes and Their Cytotoxicity Properties
Int. J. Mol. Sci. 2013, 14(1), 1843-1853; doi:10.3390/ijms14011843
Received: 19 November 2012 / Revised: 10 December 2012 / Accepted: 24 December 2012 / Published: 16 January 2013
Cited by 12 | PDF Full-text (221 KB) | HTML Full-text | XML Full-text
Abstract
Polymer supported dichlorophosphate (PEG-OPOCl2) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and
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Polymer supported dichlorophosphate (PEG-OPOCl2) is an efficient green catalyst for the electrophilic substitution reaction of indole with aromatic aldehydes, in neat condition, to afford an excellent yield of bis(indolyl) methanes with short reaction time, at room temperature. The synthesized compounds and their anti-cancer activity are evaluated. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Quaternized Chitosan as an Antimicrobial Agent: Antimicrobial Activity, Mechanism of Action and Biomedical Applications in Orthopedics
Int. J. Mol. Sci. 2013, 14(1), 1854-1869; doi:10.3390/ijms14011854
Received: 3 December 2012 / Revised: 8 January 2013 / Accepted: 9 January 2013 / Published: 16 January 2013
Cited by 55 | PDF Full-text (275 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan (CS) is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral
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Chitosan (CS) is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral or high pH substantially limits its use. Quaternary ammonium CS, which was prepared by introducing a quaternary ammonium group on a dissociative hydroxyl group or amino group of the CS, exhibited improved water solubility and stronger antibacterial activity relative to CS over an entire range of pH values; thus, this quaternary modification increases the potential biomedical applications of CS in the field of anti-infection. This review discusses the current findings on the antimicrobial properties of quaternized CS synthesized using different methods and the mechanisms of its antimicrobial actions. The potential antimicrobial applications in the orthopedic field and perspectives regarding future studies in this field are also considered. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
Open AccessArticle Sericin Enhances the Bioperformance of Collagen-Based Matrices Preseeded with Human-Adipose Derived Stem Cells (hADSCs)
Int. J. Mol. Sci. 2013, 14(1), 1870-1889; doi:10.3390/ijms14011870
Received: 22 October 2012 / Revised: 23 December 2012 / Accepted: 25 December 2012 / Published: 16 January 2013
Cited by 13 | PDF Full-text (3223 KB) | HTML Full-text | XML Full-text
Abstract
Current clinical strategies for adipose tissue engineering (ATE), including autologous fat implants or the use of synthetic surrogates, not only are failing in the long term, but also can’t face the latest requirements regarding the aesthetic restoration of the resulted imperfections. In this
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Current clinical strategies for adipose tissue engineering (ATE), including autologous fat implants or the use of synthetic surrogates, not only are failing in the long term, but also can’t face the latest requirements regarding the aesthetic restoration of the resulted imperfections. In this context, modern strategies in current ATE applications are based on the implantation of 3D cell-scaffold bioconstructs, designed for prospective achievement of in situ functional de novo tissue. Thus, in this paper, we reported for the first time the evaluation of a spongious 60% collagen and 40% sericin scaffold preseeded with human adipose-derived stem cells (hADSCs) in terms of biocompatibility and adipogenic potential in vitro. We showed that the addition of the sticky protein sericin in the composition of a classical collagen sponge enhanced the adhesion and also the proliferation rate of the seeded cells, thus improving the biocompatibility of the novel scaffold. In addition, sericin stimulated PPARγ2 overexpression, triggering a subsequent upregulated expression profile of FAS, aP2 and perilipin adipogenic markers. These features, together with the already known sericin stimulatory potential on cellular collagen production, promote collagen-sericin biomatrix as a good candidate for soft tissue reconstruction and wound healing applications. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Neuroprotective Effects of Ultra-Low-Molecular-Weight Heparin on Cerebral Ischemia/Reperfusion Injury in Rats: Involvement of Apoptosis, Inflammatory Reaction and Energy Metabolism
Int. J. Mol. Sci. 2013, 14(1), 1932-1939; doi:10.3390/ijms14011932
Received: 16 October 2012 / Revised: 21 December 2012 / Accepted: 26 December 2012 / Published: 17 January 2013
Cited by 8 | PDF Full-text (262 KB) | HTML Full-text | XML Full-text
Abstract
Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal
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Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Resveratrol Down-Regulates Myosin Light Chain Kinase, Induces Apoptosis and Inhibits Diethylnitrosamine-Induced Liver Tumorigenesis in Rats
Int. J. Mol. Sci. 2013, 14(1), 1940-1951; doi:10.3390/ijms14011940
Received: 7 November 2012 / Revised: 27 December 2012 / Accepted: 31 December 2012 / Published: 17 January 2013
Cited by 3 | PDF Full-text (534 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. However, our understanding of the mechanism of liver tumorigenesis remains incomplete. We report the expression of myosin light chain kinase (MLCK) in the livers of
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Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. However, our understanding of the mechanism of liver tumorigenesis remains incomplete. We report the expression of myosin light chain kinase (MLCK) in the livers of rats with diethylnitrosamine (DENA)-induced HCC and investigated the correlation between MLCK and liver tumorigenesis by observing the expression of MLCK in a rat model of HCC. HCC was induced in rats by an intraperitoneal injection of DENA, and resveratrol-treated rats were orally administered resveratrol with 50 mg/kg body weight/day. The livers of rats were excised after 20 weeks and immersed in 10% formaldehyde prior to immunohistochemical and Western blot analyses for determining the level of MLCK expression. These analyses indicated that the MLCK expression was higher in the livers of HCC rats than in normal and resveratrol-treated rats. High level of MLCK expression was responsible for proliferation and anti-apoptotic effects. However, resveratrol down-regulated the expression of MLCK, which induced cell apoptosis and inhibited liver tumorigenesis in rats with DENA-induced HCC. Our results suggest that the over expression of MLCK may be related to the development of liver tumorigenesis. Full article
Open AccessArticle pH Dependence of the Fluorescence Lifetime of FAD in Solution and in Cells
Int. J. Mol. Sci. 2013, 14(1), 1952-1963; doi:10.3390/ijms14011952
Received: 21 November 2012 / Revised: 27 December 2012 / Accepted: 9 January 2013 / Published: 18 January 2013
Cited by 26 | PDF Full-text (1030 KB) | HTML Full-text | XML Full-text
Abstract
We have studied physiological parameters in a living cell using fluorescence lifetime imaging of endogenous chromophores. In this study, pH dependence of the fluorescence lifetime of flavin adenine dinucleotide (FAD), that is a significant cofactor exhibiting autofluorescence, has been investigated in buffer solution
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We have studied physiological parameters in a living cell using fluorescence lifetime imaging of endogenous chromophores. In this study, pH dependence of the fluorescence lifetime of flavin adenine dinucleotide (FAD), that is a significant cofactor exhibiting autofluorescence, has been investigated in buffer solution and in cells. The fluorescence lifetime of FAD remained unchanged with pH 5 to 9 in solution. However, the fluorescence lifetime in HeLa cells was found to decrease with increasing intracellular pH, suggesting that pH in a single cell can be estimated from the fluorescence lifetime imaging of FAD without adding exogenous fluorescent probes. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Quantitative and Chemical Fingerprint Analysis for the Quality Evaluation of Receptaculum Nelumbinis by RP-HPLC Coupled with Hierarchical Clustering Analysis
Int. J. Mol. Sci. 2013, 14(1), 1999-2010; doi:10.3390/ijms14011999
Received: 28 September 2012 / Revised: 10 January 2013 / Accepted: 11 January 2013 / Published: 21 January 2013
Cited by 9 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text
Abstract
A simple and reliable method of high-performance liquid chromatography with photodiode array detection (HPLC-DAD) was developed to evaluate the quality of Receptaculum Nelumbinis (dried receptacle of Nelumbo nucifera) through establishing chromatographic fingerprint and simultaneous determination of five flavonol glycosides, including hyperoside, isoquercitrin,
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A simple and reliable method of high-performance liquid chromatography with photodiode array detection (HPLC-DAD) was developed to evaluate the quality of Receptaculum Nelumbinis (dried receptacle of Nelumbo nucifera) through establishing chromatographic fingerprint and simultaneous determination of five flavonol glycosides, including hyperoside, isoquercitrin, quercetin-3-O-β-d-glucuronide, isorhamnetin-3-O-β-d-galactoside and syringetin-3-O-β-d-glucoside. In quantitative analysis, the five components showed good regression (R > 0.9998) within linear ranges, and their recoveries were in the range of 98.31%–100.32%. In the chromatographic fingerprint, twelve peaks were selected as the characteristic peaks to assess the similarities of different samples collected from different origins in China according to the State Food and Drug Administration (SFDA) requirements. Furthermore, hierarchical cluster analysis (HCA) was also applied to evaluate the variation of chemical components among different sources of Receptaculum Nelumbinis in China. This study indicated that the combination of quantitative and chromatographic fingerprint analysis can be readily utilized as a quality control method for Receptaculum Nelumbinis and its related traditional Chinese medicinal preparations. Full article
Open AccessArticle Catalysis of Transesterification Reactions by a Self-Assembled Nanosystem
Int. J. Mol. Sci. 2013, 14(1), 2011-2021; doi:10.3390/ijms14012011
Received: 30 November 2012 / Accepted: 14 January 2013 / Published: 21 January 2013
Cited by 2 | PDF Full-text (461 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Histidine-containing peptides self-assemble on the surface of monolayer protected gold nanoparticles to form a catalytic system for transesterification reactions. Self-assembly is a prerequisite for catalysis, since the isolated peptides do not display catalytic activity by themselves. A series of catalytic peptides and substrates
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Histidine-containing peptides self-assemble on the surface of monolayer protected gold nanoparticles to form a catalytic system for transesterification reactions. Self-assembly is a prerequisite for catalysis, since the isolated peptides do not display catalytic activity by themselves. A series of catalytic peptides and substrates are studied in order to understand the structural parameters that are of relevance to the catalytic efficiency of the system. It is shown that the distance between the His-residue and the anionic tail does not affect the catalytic activity. On the other hand, the catalytic His-residue is sensitive to the chemical nature of the flanking amino acid residues. In particular, the presence of polar Ser-residues causes a significant increase in activity. Finally, kinetic studies of a series of substrates reveal that substrates with a hydrophobic component are very suitable for this catalytic system. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessArticle Self-Assembly of Discrete Metal Complexes in Aqueous Solution via Block Copolypeptide Amphiphiles
Int. J. Mol. Sci. 2013, 14(1), 2022-2035; doi:10.3390/ijms14012022
Received: 11 December 2012 / Revised: 9 January 2013 / Accepted: 17 January 2013 / Published: 21 January 2013
Cited by 8 | PDF Full-text (2075 KB) | HTML Full-text | XML Full-text
Abstract
The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets
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The integration of discrete metal complexes has been attracting significant interest due to the potential of these materials for soft metal-metal interactions and supramolecular assembly. Additionally, block copolypeptide amphiphiles have been investigated concerning their capacity for self-assembly into structures such as nanoparticles, nanosheets and nanofibers. In this study, we combined these two concepts by investigating the self-assembly of discrete metal complexes in aqueous solution using block copolypeptides. Normally, discrete metal complexes such as [Au(CN)2], when molecularly dispersed in water, cannot interact with one another. Our results demonstrated, however, that the addition of block copolypeptide amphiphiles such as K183L19 to [Au(CN)2] solutions induced one-dimensional integration of the discrete metal complex, resulting in photoluminescence originating from multinuclear complexes with metal-metal interactions. Transmission electron microscopy (TEM) showed a fibrous nanostructure with lengths and widths of approximately 100 and 20 nm, respectively, which grew to form advanced nanoarchitectures, including those resembling the weave patterns of Waraji (traditional Japanese straw sandals). This concept of combining block copolypeptide amphiphiles with discrete coordination compounds allows the design of flexible and functional supramolecular coordination systems in water. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessArticle Corneal Stromal Cell Growth on Gelatin/Chondroitin Sulfate Scaffolds Modified at Different NHS/EDC Molar Ratios
Int. J. Mol. Sci. 2013, 14(1), 2036-2055; doi:10.3390/ijms14012036
Received: 5 November 2012 / Revised: 13 December 2012 / Accepted: 5 January 2013 / Published: 21 January 2013
Cited by 13 | PDF Full-text (674 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A nanoscale modification strategy that can incorporate chondroitin sulfate (CS) into the cross-linked porous gelatin materials has previously been proposed to give superior performance for designed corneal keratocyte scaffolds. The purpose of this work was to further investigate the influence of carbodiimide chemistry
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A nanoscale modification strategy that can incorporate chondroitin sulfate (CS) into the cross-linked porous gelatin materials has previously been proposed to give superior performance for designed corneal keratocyte scaffolds. The purpose of this work was to further investigate the influence of carbodiimide chemistry on the characteristics and biofunctionalities of gelatin/CS scaffolds treated with varying N-hydroxysuccinimide (NHS)/1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) molar ratios (0-1) at a constant EDC concentration of 10 mM. Results of Fourier transform infrared spectroscopy and dimethylmethylene blue assays consistently indicated that when the NHS to EDC molar ratio exceeds a critical level (i.e., 0.5), the efficiency of carbodiimide-mediated biomaterial modification is significantly reduced. With the optimum NHS/EDC molar ratio of 0.5, chemical treatment could achieve relatively high CS content in the gelatin scaffolds, thereby enhancing the water content, glucose permeation, and fibronectin adsorption. Live/Dead assays and interleukin-6 mRNA expression analyses demonstrated that all the test samples have good cytocompatibility without causing toxicity and inflammation. In the molar ratio range of NHS to EDC from 0 to 0.5, the cell adhesion ratio and proliferation activity on the chemically modified samples significantly increased, which is attributed to the increasing CS content. Additionally, the materials with highest CS content (0.143 ± 0.007 nmol/10 mg scaffold) showed the greatest stimulatory effect on the biosynthetic activity of cultivated keratocytes. These findings suggest that a positive correlation is noticed between the NHS to EDC molar ratio and the CS content in the biopolymer matrices, thereby greatly affecting the corneal stromal cell growth. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Development of Collagen/Demineralized Bone Powder Scaffolds and Periosteum-Derived Cells for Bone Tissue Engineering Application
Int. J. Mol. Sci. 2013, 14(1), 2056-2071; doi:10.3390/ijms14012056
Received: 24 October 2012 / Revised: 11 January 2013 / Accepted: 14 January 2013 / Published: 21 January 2013
Cited by 9 | PDF Full-text (2113 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to investigate physical and biological properties of collagen (COL) and demineralized bone powder (DBP) scaffolds for bone tissue engineering. DBP was prepared and divided into three groups, based on various particle sizes: 75–125 µm, 125–250 µm, and
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The aim of this study was to investigate physical and biological properties of collagen (COL) and demineralized bone powder (DBP) scaffolds for bone tissue engineering. DBP was prepared and divided into three groups, based on various particle sizes: 75–125 µm, 125–250 µm, and 250–500 µm. DBP was homogeneously mixed with type I collagen and three-dimensional scaffolds were constructed, applying chemical crosslinking and lyophilization. Upon culture with human periosteum-derived cells (PD cells), osteogenic differentiation of PD cells was investigated using alkaline phosphatase (ALP) activity and calcium assay kits. The physical properties of the COL/DBP scaffolds were obviously different from COL scaffolds, irrespective of the size of DBP. In addition, PD cells cultured with COL scaffolds showed significantly higher cell adhesion and proliferation than those with COL/DBP scaffolds. In contrast, COL/DBP scaffolds exhibited greater osteoinductive potential than COL scaffolds. The PD cells with COL/DBP scaffolds possessed higher ALP activity than those with COL scaffolds. PD cells cultured with COL/DBP scaffolds with 250–500 mm particle size yielded the maximum calcium deposition. In conclusion, PD cells cultured on the scaffolds could exhibit osteoinductive potential. The composite scaffold of COL/DBP with 250–500 mm particle size could be considered a potential bone tissue engineering implant. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Blood microRNAs in Low or No Risk Ischemic Stroke Patients
Int. J. Mol. Sci. 2013, 14(1), 2072-2084; doi:10.3390/ijms14012072
Received: 6 November 2012 / Revised: 11 December 2012 / Accepted: 17 January 2013 / Published: 22 January 2013
Cited by 16 | PDF Full-text (492 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ischemic stroke is a multi-factorial disease where some patients present themselves with little or no risk factors. Blood microRNA expression profiles are becoming useful in the diagnosis and prognosis of human diseases. We therefore investigated the blood microRNA profiles in young stroke patients
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Ischemic stroke is a multi-factorial disease where some patients present themselves with little or no risk factors. Blood microRNA expression profiles are becoming useful in the diagnosis and prognosis of human diseases. We therefore investigated the blood microRNA profiles in young stroke patients who presented with minimal or absence of risk factors for stroke such as type 2 diabetes, dyslipidemia and hypertension. Blood microRNA profiles from these patients varied with stroke subtypes as well as different functional outcomes (based on modified Rankin Score). These microRNAs have been shown to target genes that are involved in stroke pathogenesis. The findings from our study suggest that molecular mechanisms in stroke pathogenesis involving low or no risk ischemic stroke patients could differ substantially from those with pre-existing risk factors. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessArticle Pre-Treatment of Platinum Resistant Ovarian Cancer Cells with an MMP-9/MMP-2 Inhibitor Prior to Cisplatin Enhances Cytotoxicity as Determined by High Content Screening
Int. J. Mol. Sci. 2013, 14(1), 2085-2103; doi:10.3390/ijms14012085
Received: 7 November 2012 / Revised: 5 January 2013 / Accepted: 6 January 2013 / Published: 22 January 2013
Cited by 6 | PDF Full-text (535 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2
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Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
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Open AccessArticle Metabolic Profiles of Brain Metastases
Int. J. Mol. Sci. 2013, 14(1), 2104-2118; doi:10.3390/ijms14012104
Received: 26 October 2012 / Accepted: 9 January 2013 / Published: 22 January 2013
Cited by 10 | PDF Full-text (2255 KB) | HTML Full-text | XML Full-text
Abstract
Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile
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Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49) were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01), irrespective of their primary origin. The principal component analysis (PCA) showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01), indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors. Full article
(This article belongs to the Special Issue Brain Metastasis)
Open AccessArticle Low Oxygen Tension Maintains Multipotency, Whereas Normoxia Increases Differentiation of Mouse Bone Marrow Stromal Cells
Int. J. Mol. Sci. 2013, 14(1), 2119-2134; doi:10.3390/ijms14012119
Received: 21 November 2012 / Revised: 4 January 2013 / Accepted: 5 January 2013 / Published: 22 January 2013
Cited by 20 | PDF Full-text (857 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very
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Optimization of mesenchymal stem cells (MSC) culture conditions is of great importance for their more successful application in regenerative medicine. O2 regulates various aspects of cellular biology and, in vivo, MSC are exposed to different O2 concentrations spanning from very low tension in the bone marrow niche, to higher amounts in wounds. In our present work, we isolated mouse bone marrow stromal cells (BMSC) and showed that they contained a population meeting requirements for MSC definition. In order to establish the effect of low O2 on cellular properties, we examined BSMC cultured under hypoxic (3% O2) conditions. Our results demonstrate that 3% O2 augmented proliferation of BMSC, as well as the formation of colonies in the colony-forming unit assay (CFU-A), the percentage of quiescent cells, and the expression of stemness markers Rex-1 and Oct-4, thereby suggesting an increase in the stemness of culture when exposed to hypoxia. In contrast, intrinsic differentiation processes were inhibited by 3% O2. Overall yield of differentiation was dependent on the adjustment of O2 tension to the specific stage of BMSC culture. Thus, we established a strategy for efficient BMSC in vitro differentiation using an initial phase of cell propagation at 3% O2, followed by differentiation stage at 21% O2. We also demonstrated that 3% O2 affected BMSC differentiation in p53 and reactive oxygen species (ROS) independent pathways. Our findings can significantly contribute to the obtaining of high-quality MSC for effective cell therapy. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessArticle Induction of Heat Shock Protein 70 Ameliorates Ultraviolet-Induced Photokeratitis in Mice
Int. J. Mol. Sci. 2013, 14(1), 2175-2189; doi:10.3390/ijms14012175
Received: 7 November 2012 / Revised: 9 January 2013 / Accepted: 18 January 2013 / Published: 22 January 2013
Cited by 7 | PDF Full-text (3228 KB) | HTML Full-text | XML Full-text
Abstract
Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP)70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined
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Acute ultraviolet (UV) B exposure causes photokeratitis and induces apoptosis in corneal cells. Geranylgeranylacetone (GGA) is an acyclic polyisoprenoid that induces expression of heat shock protein (HSP)70, a soluble intracellular chaperone protein expressed in various tissues, protecting cells against stress conditions. We examined whether induction of HSP70 has therapeutic effects on UV-photokeratitis in mice. C57 BL/6 mice were divided into four groups, GGA-treated (500 mg/kg/mouse) and UVB-exposed (400 mJ/cm2), GGA-untreated UVB-exposed (400 mJ/cm2), GGA-treated (500 mg/kg/mouse) but not exposed and naive controls. Eyeballs were collected 24 h after irradiation, and corneas were stained with hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). HSP70, reactive oxygen species (ROS) production, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and protein kinase B (Akt) expression were also evaluated. Irradiated corneal epithelium was significantly thicker in the eyes of mice treated with GGA compared with those given the vehicle alone (p < 0.01). Significantly fewer TUNEL-positive cells were observed in the eyes of GGA-treated mice than controls after irradiation (p < 0.01). Corneal HSP70 levels were significantly elevated in corneas of mice treated with GGA (p < 0.05). ROS signal was not affected by GGA. NF-κB activation was reduced but phospho-(Ser/Ther) Akt substrate expression was increased in corneas after irradiation when treated with GGA. GGA-treatment induced HSP70 expression and ameliorated UV-induced corneal damage through the reduced NF-κB activation and possibly increased Akt phosphorilation. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessArticle Effect of Repetitive Lysine-Tryptophan Motifs on the Eukaryotic Membrane
Int. J. Mol. Sci. 2013, 14(1), 2190-2202; doi:10.3390/ijms14012190
Received: 27 November 2012 / Revised: 14 January 2013 / Accepted: 15 January 2013 / Published: 22 January 2013
Cited by 7 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
In a previous study, we synthesized a series of peptides containing simple sequence repeats, (KW)nNH2 (n = 2,3,4 and 5) and determined their antimicrobial and hemolytic activities, as well as their mechanism of antimicrobial action. However, (KW)5
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In a previous study, we synthesized a series of peptides containing simple sequence repeats, (KW)nNH2 (n = 2,3,4 and 5) and determined their antimicrobial and hemolytic activities, as well as their mechanism of antimicrobial action. However, (KW)5 showed undesirable cytotoxicity against RBC cells. In order to identify the mechanisms behind the hemolytic and cytotoxic activities of (KW)5, we measured the ability of these peptides to induce aggregation of liposomes. In addition, their binding and permeation activities were assessed by Trp fluorescence, calcein leakage and circular dichrorism using artificial phospholipids that mimic eukaryotic liposomes, including phosphatidylcholine (PC), PC/sphingomyelin (SM) (2:1, w/w) and PC/cholesterol (CH) (2:1, w/w). Experiments confirmed that only (KW)5 induced aggregation of all liposomes; it formed much larger aggregates with PC:CH (2:1, w/w) than with PC or PC:SM (2:1, w/w). Longer peptide (KW)5, but not (KW)3 or (KW)4, strongly bound and partially inserted into PC:CH compared to PC or PC:SM (2:1, w/w). Calcein release experiments showed that (KW)5 induced calcein leakage from the eukaryotic membrane. Greater calcein leakage was induced by (KW)5 from PC:CH than from PC:SM (2:1, w/w) or PC, whereas (KW)4 did not induce calcein leakage from any of the liposomes. Circular dichroism measurements indicated that (KW)5 showed higher conformational transition compared to (KW)4 due to peptide-liposome interactions. Taken together, our results suggest that (KW)5 reasonably mediates the aggregation and permeabilization of eukaryotic membranes, which could in turn explain why (KW)5 displays efficient hemolytic activity. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
Open AccessArticle Adhesion-Induced Phase Behavior of Two-Component Membranes and Vesicles
Int. J. Mol. Sci. 2013, 14(1), 2203-2229; doi:10.3390/ijms14012203
Received: 20 December 2012 / Revised: 17 January 2013 / Accepted: 18 January 2013 / Published: 22 January 2013
Cited by 5 | PDF Full-text (931 KB) | HTML Full-text | XML Full-text
Abstract
The interplay of adhesion and phase separation is studied theoretically for two-component membranes that can phase separate into two fluid phases such as liquid-ordered and liquid-disordered phases. Many adhesion geometries provide two different environments for these membranes and then partition the membranes into
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The interplay of adhesion and phase separation is studied theoretically for two-component membranes that can phase separate into two fluid phases such as liquid-ordered and liquid-disordered phases. Many adhesion geometries provide two different environments for these membranes and then partition the membranes into two segments that differ in their composition. Examples are provided by adhering vesicles, by hole- or pore-spanning membranes, and by membranes supported by chemically patterned surfaces. Generalizing a lattice model for binary mixtures to these adhesion geometries, we show that the phase behavior of the adhering membranes depends, apart from composition and temperature, on two additional parameters, the area fraction of one membrane segment and the affinity contrast between the two segments. For the generic case of non-vanishing affinity contrast, the adhering membranes undergo two distinct phase transitions and the phase diagrams in the composition/temperature plane have a generic topology that consists of two two-phase coexistence regions separated by an intermediate one-phase region. As a consequence, phase separation and domain formation is predicted to occur separately in each of the two membrane segments but not in both segments simultaneously. Furthermore, adhesion is also predicted to suppress the phase separation process for certain regions of the phase diagrams. These generic features of the adhesion-induced phase behavior are accessible to experiment. Full article
(This article belongs to the Special Issue Self-Assembled Soft Matter Nanostructures at Interfaces)

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Open AccessReview Novel Molecular Targets for the Treatment of Gastroenteropancreatic Endocrine Tumors: Answers and Unsolved Problems
Int. J. Mol. Sci. 2013, 14(1), 30-45; doi:10.3390/ijms14010030
Received: 11 October 2012 / Revised: 1 December 2012 / Accepted: 3 December 2012 / Published: 20 December 2012
Cited by 2 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
As more knowledge on molecular alterations favoring carcinogenesis and spreading of gastroenteropancreatic endocrine tumors has become available, a number of targeted agents interfering with key growth and angiogenic pathways have been explored in preclinical and clinical studies. The mTOR inhibitor Everolimus, and the
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As more knowledge on molecular alterations favoring carcinogenesis and spreading of gastroenteropancreatic endocrine tumors has become available, a number of targeted agents interfering with key growth and angiogenic pathways have been explored in preclinical and clinical studies. The mTOR inhibitor Everolimus, and the multi-target antiangiogenetic agent Sunitinib, have been shown to be effective and thus have been approved by the FDA for treatment of pancreatic endocrine tumors. However, there is little data on the primary resistance to targeted agents on these tumors. The goals of the present review are to elucidate the possible advantage of combined treatments in overcoming induced resistances, and to identify biomarkers able to predict clinical efficacy. Moreover, the role of interesting targets for which a strong biological rationale exists, and specific inhibitors are available, such as the Src Family Kinases and the Hedgehog Pathway, are discussed. There is now need for more preclinical studies on cell lines and animal models to provide a stronger preclinical background in this field, as well as clinical trials specifically comparing one targeted therapy with another or combining different targeted agents. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessReview Spatial Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis
Int. J. Mol. Sci. 2013, 14(1), 72-87; doi:10.3390/ijms14010072
Received: 20 November 2012 / Revised: 10 December 2012 / Accepted: 12 December 2012 / Published: 20 December 2012
Cited by 7 | PDF Full-text (156 KB) | HTML Full-text | XML Full-text
Abstract
Signaling by cell surface receptors appears to be relatively straight-forward: ligand binds to the extracellular domain of the receptor and biochemical changes are communicated into the cell. However, this process is more complex than it first seems due to the various mechanisms that
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Signaling by cell surface receptors appears to be relatively straight-forward: ligand binds to the extracellular domain of the receptor and biochemical changes are communicated into the cell. However, this process is more complex than it first seems due to the various mechanisms that regulate signaling. In order to effectively target these receptors for pharmacological purposes, a more complete understanding of how their signaling is regulated is needed. Here, how the endocytic pathway regulates receptor signaling is discussed, using the epidermal growth factor receptor (EGFR) as a model. In particular, the spatial regulation of signaling is examined. Areas of discussion include: how endocytic trafficking affects biology/pathology, varying approaches for studying the relationship between receptor endocytosis and signaling, and developments in how the endocytic pathway controls EGFR:effector communication and EGFR-mediated cell biology. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
Open AccessReview The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy
Int. J. Mol. Sci. 2013, 14(1), 88-107; doi:10.3390/ijms14010088
Received: 26 July 2012 / Revised: 30 November 2012 / Accepted: 14 December 2012 / Published: 20 December 2012
Cited by 23 | PDF Full-text (710 KB) | HTML Full-text | XML Full-text
Abstract
Vascular endothelial growth factor C (VEGF-C) has been identified as a multifaceted factor participating in the regulation of tumor angiogenesis and lymphangiogenesis. VEGF-C is not only expressed in endothelial cells, but also in tumor cells. VEGF-C signaling is important for progression of various
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Vascular endothelial growth factor C (VEGF-C) has been identified as a multifaceted factor participating in the regulation of tumor angiogenesis and lymphangiogenesis. VEGF-C is not only expressed in endothelial cells, but also in tumor cells. VEGF-C signaling is important for progression of various cancer types through both VEGF receptor-2 (VEGFR-2) and VEGF receptor-3 (VEGFR-3). Likewise, both receptors are expressed mainly on endothelial cells, but also expressed in tumor cells. The dimeric VEGF-C undergoes a series of proteolytic cleavage steps that increase the protein binding affinity to VEGFR-3; however, only complete processing, removing both the N- and C-terminal propeptides, yields mature VEGF-C that can bind to VEGFR-2. The processed VEGF-C can bind and activate VEGFR-3 homodimers and VEGFR-2/VEGFR-3 heterodimers to elicit biological responses. High levels of VEGF-C expression and VEGF-C/VEGFRs signaling correlate significantly with poorer prognosis in a variety of malignancies. Therefore, the development of new drugs that selectively target the VEGF-C/VEGFRs axis seems to be an effective means to potentiate anti-tumor therapies in the future. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance
Int. J. Mol. Sci. 2013, 14(1), 108-145; doi:10.3390/ijms14010108
Received: 15 October 2012 / Revised: 10 December 2012 / Accepted: 12 December 2012 / Published: 20 December 2012
Cited by 62 | PDF Full-text (973 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy,
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Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessReview Changes in Translational Control after Pro-Apoptotic Stress
Int. J. Mol. Sci. 2013, 14(1), 177-190; doi:10.3390/ijms14010177
Received: 30 July 2012 / Revised: 6 November 2012 / Accepted: 10 December 2012 / Published: 21 December 2012
PDF Full-text (273 KB) | HTML Full-text | XML Full-text
Abstract
In stressed cells, a general decrease in the rate of protein synthesis occurs due to modifications in the activity of translation initiation factors. Compelling data now indicate that these changes also permit a selective post-transcriptional expression of proteins necessary for either cell survival
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In stressed cells, a general decrease in the rate of protein synthesis occurs due to modifications in the activity of translation initiation factors. Compelling data now indicate that these changes also permit a selective post-transcriptional expression of proteins necessary for either cell survival or completion of apoptosis when cells are exposed to severe or prolonged stress. In this review, we summarize the modifications that inhibit the activity of the main canonical translation initiation factors, and the data explaining how certain mRNAs encoding proteins involved in either cell survival or apoptosis can be selectively translated. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessReview The Role of Photolabile Dermal Nitric Oxide Derivates in Ultraviolet Radiation (UVR)-Induced Cell Death
Int. J. Mol. Sci. 2013, 14(1), 191-204; doi:10.3390/ijms14010191
Received: 26 October 2012 / Revised: 11 December 2012 / Accepted: 12 December 2012 / Published: 21 December 2012
Cited by 2 | PDF Full-text (324 KB) | HTML Full-text | XML Full-text
Abstract
Human skin is exposed to solar ultraviolet radiation comprising UVB (280–315 nm) and UVA (315–400 nm) on a daily basis. Within the last two decades, the molecular and cellular response to UVA/UVB and the possible effects on human health have been investigated extensively.
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Human skin is exposed to solar ultraviolet radiation comprising UVB (280–315 nm) and UVA (315–400 nm) on a daily basis. Within the last two decades, the molecular and cellular response to UVA/UVB and the possible effects on human health have been investigated extensively. It is generally accepted that the mutagenic and carcinogenic properties of UVB is due to the direct interaction with DNA. On the other hand, by interaction with non-DNA chromophores as endogenous photosensitizers, UVA induces formation of reactive oxygen species (ROS), which play a pivotal role as mediators of UVA-induced injuries in human skin. This review gives a short overview about relevant findings concerning the molecular mechanisms underlying UVA/UVB-induced cell death. Furthermore, we will highlight the potential role of cutaneous antioxidants and photolabile nitric oxide derivates (NODs) in skin physiology. UVA-induced decomposition of the NODs, like nitrite, leads not only to non-enzymatic formation of nitric oxide (NO), but also to toxic reactive nitrogen species (RNS), like peroxynitrite. Whereas under antioxidative conditions the generation of protective amounts of NO is favored, under oxidative conditions, less injurious reactive nitrogen species are generated, which may enhance UVA-induced cell death. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessReview The Controversial Role of Retinoic Acid in Fibrotic Diseases: Analysis of Involved Signaling Pathways
Int. J. Mol. Sci. 2013, 14(1), 226-243; doi:10.3390/ijms14010226
Received: 1 August 2012 / Revised: 3 September 2012 / Accepted: 10 December 2012 / Published: 21 December 2012
Cited by 18 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text
Abstract
Fibrotic diseases, such as liver, pulmonary and renal fibrosis, are common end-stage conditions and represent a major global health problem. Furthermore, effective therapeutic measures are presently unavailable. Extracellular matrix accumulation is the most prominent characteristic in the pathogenesis of fibrotic disease. Retinoic acid,
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Fibrotic diseases, such as liver, pulmonary and renal fibrosis, are common end-stage conditions and represent a major global health problem. Furthermore, effective therapeutic measures are presently unavailable. Extracellular matrix accumulation is the most prominent characteristic in the pathogenesis of fibrotic disease. Retinoic acid, including all-trans retinoic acid, 9-cis and 13-cis retinoic acid, play important roles in various physiological processes, such as in embryonic development, reproduction, vision, cell growth, differentiation, apoptosis and inflammation. Present studies report that retinoic acid treatment may affect various processes involved in the onset and progression of fibrotic disease. However, the therapeutic effects of retinoic acid in such diseases remain controversial. Several reports indicate that retinoic acid positively affects the progression of fibrosis and alleviates the accumulation of the extracellular matrix, whereas other studies report the opposite; that retinoic acid exacerbates fibrosis and induces extracellular matrix accumulation. Signaling pathways might be an important influencing factor and differences in signaling events might be responsible for the contradictory role of retinoic acid in fibrotic diseases. Since there was no review available that investigated the role of retinoic acid and the signaling pathways involved, we retrospectively studied the literature and provide a comprehensive analysis of retinoic acid’s role in fibrotic diseases, and provide an overview of the signal transduction pathways involved in its pathogenesis. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview Spontaneous Crystallization in Athermal Polymer Packings
Int. J. Mol. Sci. 2013, 14(1), 332-358; doi:10.3390/ijms14010332
Received: 28 November 2012 / Accepted: 14 December 2012 / Published: 24 December 2012
Cited by 12 | PDF Full-text (2276 KB) | HTML Full-text | XML Full-text
Abstract
We review recent results from extensive simulations of the crystallization of athermal polymer packings. It is shown that above a certain packing density, and for sufficiently long simulations, all random assemblies of freely-jointed chains of tangent hard spheres of uniform size show a
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We review recent results from extensive simulations of the crystallization of athermal polymer packings. It is shown that above a certain packing density, and for sufficiently long simulations, all random assemblies of freely-jointed chains of tangent hard spheres of uniform size show a spontaneous transition into a crystalline phase. These polymer crystals adopt predominantly random hexagonal close packed morphologies. An analysis of the local environment around monomers based on the shape and size of the Voronoi polyhedra clearly shows that Voronoi cells become more spherical and more symmetric as the system transits to the ordered state. The change in the local environment leads to an increase in the monomer translational contribution to the entropy of the system, which acts as the driving force for the phase transition. A comparison of the crystallization of hard-sphere polymers and monomers highlights similarities and differences resulting from the constraints imposed by chain connectivity. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessReview An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases
Int. J. Mol. Sci. 2013, 14(1), 434-456; doi:10.3390/ijms14010434
Received: 26 October 2012 / Revised: 1 December 2012 / Accepted: 13 December 2012 / Published: 24 December 2012
Cited by 76 | PDF Full-text (579 KB) | HTML Full-text | XML Full-text
Abstract
The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also
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The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also intra-ER Ca2+ cause the production of ER stress-induced reactive oxygen species (ROS). Protein disulfide isomerases, endoplasmic reticulum oxidoreductin-1, reduced glutathione and mitochondrial electron transport chain proteins also play crucial roles in ER stress-induced production of ROS. In this article, we discuss ER stress-associated ROS and related diseases, and the current understanding of the signaling transduction involved in ER stress. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessReview Recent Insights and Novel Bioinformatics Tools to Understand the Role of MicroRNAs Binding to 5' Untranslated Region
Int. J. Mol. Sci. 2013, 14(1), 480-495; doi:10.3390/ijms14010480
Received: 12 November 2012 / Revised: 6 December 2012 / Accepted: 6 December 2012 / Published: 27 December 2012
Cited by 26 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through the binding of the 3' untranslated region (3'UTR) of specific mRNAs. MiRNAs are post-transcriptional regulators and determine the repression of translation processes or the degradation of mRNA targets. Recently, another kind of
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MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through the binding of the 3' untranslated region (3'UTR) of specific mRNAs. MiRNAs are post-transcriptional regulators and determine the repression of translation processes or the degradation of mRNA targets. Recently, another kind of miRNA-mediated regulation of translation (repression or activation) involving the binding of miRNA to the 5'UTR of target gene has been reported. The possible interactions and the mechanism of action have been reported in many works that we reviewed here. Moreover, we discussed also the available bioinformatics tools for predicting the miRNA binding sites in the 5'UTR and public databases collecting this information. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Ultraviolet B (UVB) Irradiation-Induced Apoptosis in Various Cell Lineages in Vitro
Int. J. Mol. Sci. 2013, 14(1), 532-546; doi:10.3390/ijms14010532
Received: 31 October 2012 / Revised: 19 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012
Cited by 18 | PDF Full-text (762 KB) | HTML Full-text | XML Full-text
Abstract
Ultraviolet B (UVB) radiation acts as a strong apoptotic trigger in many cell types, in tumor and normal cells. Several studies have demonstrated that UVB-induced cell death occurs through the generation of reactive oxygen species. The consequent oxidative stress includes the impairment of
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Ultraviolet B (UVB) radiation acts as a strong apoptotic trigger in many cell types, in tumor and normal cells. Several studies have demonstrated that UVB-induced cell death occurs through the generation of reactive oxygen species. The consequent oxidative stress includes the impairment of cellular antioxidants, the induction of DNA damage and the occurrence of apoptosis. In this review, we investigated UVB apoptotic action in various cell models by using ultrastructural, molecular and cytofluorimetric techniques. Myeloid leukemia HL-60, T-lymphoblastoid Molt-4 and myelomonocytic U937 human cells, generally affected by apoptotic stimuli, were studied. Human chondrocytes and C2C12 skeletal muscle cells, known to be more resistant to damage, were also considered. All of them, when exposed to UVB radiation, revealed a number of characteristic apoptotic markers. Membrane blebbing, cytoplasm shrinkage and chromatin condensation were detected by means of electron microscopy. DNA cleavage, investigated by using agarose gel electrophoresis and TUNEL reaction, was observed in suspended cells. Differently, in chondrocytes and in skeletal muscle cells, oligonucleosomic DNA fragmentation did not appear, even if a certain TUNEL positivity was detected. These findings demonstrate that UVB radiation appears to be an ideal tool to study the apoptotic behavior. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessReview Dendritic Cells and Multiple Sclerosis: Disease, Tolerance and Therapy
Int. J. Mol. Sci. 2013, 14(1), 547-562; doi:10.3390/ijms14010547
Received: 25 September 2012 / Revised: 6 December 2012 / Accepted: 20 December 2012 / Published: 27 December 2012
Cited by 12 | PDF Full-text (321 KB) | HTML Full-text | XML Full-text
Abstract
Multiple sclerosis (MS) is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact. The majority of therapies for this disease were developed in, or are beneficial in experimental autoimmune encephalomyelitis (EAE), the animal model of MS.
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Multiple sclerosis (MS) is a devastating neurological disease that predominantly affects young adults resulting in severe personal and economic impact. The majority of therapies for this disease were developed in, or are beneficial in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. While known to target adaptive anti-CNS immune responses, they also target, the innate immune arm. This mini-review focuses on the role of dendritic cells (DCs), the professional antigen presenting cells of the innate immune system. The evidence for a role for DCs in the appropriate regulation of anti-CNS autoimmune responses and their role in MS disease susceptibility and possible therapeutic utility are discussed. Additionally, the current controversy regarding the evidence for the presence of functional DCs in the normal CNS is reviewed. Furthermore, the role of CNS DCs and potential routes of their intercourse between the CNS and cervical lymph nodes are considered. Finally, the future role that this nexus between the CNS and the cervical lymph nodes might play in site directed molecular and cellular therapy for MS is outlined. Full article
Open AccessReview Why Flavins Are not Competitors of Chlorophyll in the Evolution of Biological Converters of Solar Energy
Int. J. Mol. Sci. 2013, 14(1), 575-593; doi:10.3390/ijms14010575
Received: 9 October 2012 / Revised: 10 December 2012 / Accepted: 13 December 2012 / Published: 27 December 2012
Cited by 3 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
Excited flavin molecules can photocatalyze reactions, leading to the accumulation of free energy in the products, and the data accumulated through biochemical experiments and by modeling prebiological processes suggest that flavins were available in the earliest stages of evolution. Furthermore, model experiments have
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Excited flavin molecules can photocatalyze reactions, leading to the accumulation of free energy in the products, and the data accumulated through biochemical experiments and by modeling prebiological processes suggest that flavins were available in the earliest stages of evolution. Furthermore, model experiments have shown that abiogenic flavin conjugated with a polyamino acid matrix, a pigment that photocatalyzes the phosphorylation of ADP to form ATP, could have been present in the prebiotic environment. Indeed, excited flavin molecules play key roles in many photoenzymes and regulatory photoreceptors, and the substantial structural differences between photoreceptor families indicate that evolution has repeatedly used flavins as chromophores for photoreceptor proteins. Some of these photoreceptors are equipped with a light-harvesting antenna, which transfers excitation energy to chemically reactive flavins in the reaction center. The sum of the available data suggests that evolution could have led to the formation of a flavin-based biological converter to convert light energy into energy in the form of ATP. Full article
(This article belongs to the Special Issue Flavins)
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Open AccessReview Ovarian Cancer: In Search of Better Marker Systems Based on DNA Repair Defects
Int. J. Mol. Sci. 2013, 14(1), 640-673; doi:10.3390/ijms14010640
Received: 27 August 2012 / Revised: 14 December 2012 / Accepted: 24 December 2012 / Published: 4 January 2013
Cited by 10 | PDF Full-text (798 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer is the fifth most common female cancer in the Western world, and the deadliest gynecological malignancy. The overall poor prognosis for ovarian cancer patients is a consequence of aggressive biological behavior and a lack of adequate diagnostic tools for early detection.
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Ovarian cancer is the fifth most common female cancer in the Western world, and the deadliest gynecological malignancy. The overall poor prognosis for ovarian cancer patients is a consequence of aggressive biological behavior and a lack of adequate diagnostic tools for early detection. In fact, approximately 70% of all patients with epithelial ovarian cancer are diagnosed at advanced tumor stages. These facts highlight a significant clinical need for reliable and accurate detection methods for ovarian cancer, especially for patients at high risk. Because CA125 has not achieved satisfactory sensitivity and specificity in detecting ovarian cancer, numerous efforts, including those based on single and combined molecule detection and “omics” approaches, have been made to identify new biomarkers. Intriguingly, more than 10% of all ovarian cancer cases are of familial origin. BRCA1 and BRCA2 germline mutations are the most common genetic defects underlying hereditary ovarian cancer, which is why ovarian cancer risk assessment in developed countries, aside from pedigree analysis, relies on genetic testing of BRCA1 and BRCA2. Because not only BRCA1 and BRCA2 but also other susceptibility genes are tightly linked with ovarian cancer-specific DNA repair defects, another possible approach for defining susceptibility might be patient cell-based functional testing, a concept for which support came from a recent case-control study. This principle would be applicable to risk assessment and the prediction of responsiveness to conventional regimens involving platinum-based drugs and targeted therapies involving poly (ADP-ribose) polymerase (PARP) inhibitors. Full article
(This article belongs to the Special Issue Cancer Molecules in Ovarian Cancer 2012)
Open AccessReview HGF–MET Cascade, a Key Target for Inhibiting Cancer Metastasis: The Impact of NK4 Discovery on Cancer Biology and Therapeutics
Int. J. Mol. Sci. 2013, 14(1), 888-919; doi:10.3390/ijms14010888
Received: 15 October 2012 / Revised: 6 December 2012 / Accepted: 10 December 2012 / Published: 7 January 2013
Cited by 15 | PDF Full-text (572 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocyte growth factor (HGF) was discovered in 1984 as a mitogen of rat hepatocytes in a primary culture system. In the mid-1980s, MET was identified as an oncogenic mutant protein that induces malignant phenotypes in a human cell line. In the early 1990s,
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Hepatocyte growth factor (HGF) was discovered in 1984 as a mitogen of rat hepatocytes in a primary culture system. In the mid-1980s, MET was identified as an oncogenic mutant protein that induces malignant phenotypes in a human cell line. In the early 1990s, wild-type MET was shown to be a functional receptor of HGF. Indeed, HGF exerts multiple functions, such as proliferation, morphogenesis and anti-apoptosis, in various cells via MET tyrosine kinase phosphorylation. During the past 20 years, we have accumulated evidence that HGF is an essential conductor for embryogenesis and tissue regeneration in various types of organs. Furthermore, we found in the mid-1990s that stroma-derived HGF is a major contributor to cancer invasion at least in vitro. Based on this background, we prepared NK4 as an antagonist of HGF: NK4 inhibits HGF-mediated MET tyrosine phosphorylation by competing with HGF for binding to MET. In vivo, NK4 treatments produced the anti-tumor outcomes in mice bearing distinct types of malignant cancers, associated with the loss in MET activation. There are now numerous reports showing that HGF-antagonists and MET-inhibitors are logical for inhibiting tumor growth and metastasis. Additionally, NK4 exerts anti-angiogenic effects, partly through perlecan-dependent cascades. This paper focuses on the chronology and significance of HGF-antagonisms in anti-tumor researches, with an interest in NK4 discovery. Tumor HGF–MET axis is now critical for drug resistance and cancer stem cell maintenance. Thus, oncologists cannot ignore this cascade for the future success of anti-metastatic therapy. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
Open AccessReview VCD Studies on Chiral Characters of Metal Complex Oligomers
Int. J. Mol. Sci. 2013, 14(1), 964-978; doi:10.3390/ijms14010964
Received: 11 December 2012 / Revised: 27 December 2012 / Accepted: 31 December 2012 / Published: 7 January 2013
Cited by 17 | PDF Full-text (722 KB) | HTML Full-text | XML Full-text
Abstract
The present article reviews the results on the application of vibrational circular dichroism (VCD) spectroscopy to the study of stereochemical properties of chiral metal complexes in solution. The chiral characters reflecting on the vibrational properties of metal complexes are revealed by measurements of
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The present article reviews the results on the application of vibrational circular dichroism (VCD) spectroscopy to the study of stereochemical properties of chiral metal complexes in solution. The chiral characters reflecting on the vibrational properties of metal complexes are revealed by measurements of a series of β-diketonato complexes with the help of theoretical calculation. Attention is paid to the effects of electronic properties of a central metal ion on vibrational energy levels or low-lying electronic states. The investigation is further extended to the oligomers of β-diketonato complex units. The induction of chiral structures is confirmed by the VCD spectra when chiral inert moieties are connected with labile metal ions. These results have demonstrated how VCD spectroscopy is efficient in revealing the static and dynamic properties of mononuclear and multinuclear chiral metal complexes, which are difficult to clarify by means of other spectroscopes. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
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Open AccessReview Signalling Pathways that Inhibit the Capacity of Precursor Cells for Myelin Repair
Int. J. Mol. Sci. 2013, 14(1), 1031-1049; doi:10.3390/ijms14011031
Received: 27 November 2012 / Revised: 21 December 2012 / Accepted: 31 December 2012 / Published: 7 January 2013
Cited by 6 | PDF Full-text (126 KB) | HTML Full-text | XML Full-text
Abstract
In demyelinating disorders such as Multiple Sclerosis (MS), targets of injury are myelin and oligodendrocytes, leading to severe neurological dysfunction. Regenerative therapies aimed at promoting oligodendrocyte maturation and remyelination are promising strategies for treatment in demyelinating disorders. Endogenous precursor cells or exogenous transplanted
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In demyelinating disorders such as Multiple Sclerosis (MS), targets of injury are myelin and oligodendrocytes, leading to severe neurological dysfunction. Regenerative therapies aimed at promoting oligodendrocyte maturation and remyelination are promising strategies for treatment in demyelinating disorders. Endogenous precursor cells or exogenous transplanted cells are potential sources for remyelinating oligodendrocytes in the central nervous system (CNS). Several signalling pathways have been implicated in regulating the capacity of these cell populations for myelin repair. Here, we review neural precursor cells and oligodendrocyte progenitor cells as potential sources for remyelinating oligodendrocytes and evidence for the functional role of key signalling pathways in inhibiting regeneration from these precursor cell populations. Full article
(This article belongs to the Special Issue Recent Advances in the Research of Multiple Sclerosis)
Open AccessReview The Role of Altered Nucleotide Excision Repair and UVB-Induced DNA Damage in Melanomagenesis
Int. J. Mol. Sci. 2013, 14(1), 1132-1151; doi:10.3390/ijms14011132
Received: 31 October 2012 / Revised: 29 November 2012 / Accepted: 26 December 2012 / Published: 9 January 2013
Cited by 28 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left
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UVB radiation is the most mutagenic component of the UV spectrum that reaches the earth’s surface and causes the development of DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts. UV radiation usually results in cellular death, but if left unchecked, it can affect DNA integrity, cell and tissue homeostasis and cause mutations in oncogenes and tumour-suppressor genes. These mutations, if unrepaired, can lead to abnormal cell growth, increasing the risk of cancer development. Epidemiological data strongly associates UV exposure as a major factor in melanoma development, but the exact biological mechanisms involved in this process are yet to be fully elucidated. The nucleotide excision repair (NER) pathway is responsible for the repair of UV-induced lesions. Patients with the genetic disorder Xeroderma Pigmentosum have a mutation in one of eight NER genes associated with the XP complementation groups XP-A to XP-G and XP variant (XP-V). XP is characterized by diminished repair capacity, as well as a 1000-fold increase in the incidence of skin cancers, including melanoma. This has suggested a significant role for NER in melanoma development as a result of UVB exposure. This review discusses the current research surrounding UVB radiation and NER capacity and how further investigation of NER could elucidate the role of NER in avoiding UV-induced cellular death resulting in melanomagenesis. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessReview Hedgehog Signaling Pathway in Ovarian Cancer
Int. J. Mol. Sci. 2013, 14(1), 1179-1196; doi:10.3390/ijms14011179
Received: 17 December 2012 / Revised: 30 December 2012 / Accepted: 5 January 2013 / Published: 9 January 2013
Cited by 10 | PDF Full-text (187 KB) | HTML Full-text | XML Full-text
Abstract
Despite advances in surgical and chemotherapeutic treatment options, less than 50% of patients with advanced-stage ovarian cancer survive five years after initial diagnosis. In this regard, novel treatment approaches are warranted utilizing molecularly targeted therapies directed against particular components of specific signaling pathways
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Despite advances in surgical and chemotherapeutic treatment options, less than 50% of patients with advanced-stage ovarian cancer survive five years after initial diagnosis. In this regard, novel treatment approaches are warranted utilizing molecularly targeted therapies directed against particular components of specific signaling pathways which are required for tumor development and progression. One molecular pathway of interest is the hedgehog (Hh) signaling pathway. Activation of the Hh pathway has been observed in several cancer types, including ovarian cancer. This review highlights the crucial role of Hh signaling in the development and progression of ovarian cancer and might lead to a better understanding of the Hh signaling in ovarian tumorigenesis, thus encouraging the investigation of novel targeted therapies. Full article
(This article belongs to the Special Issue Genes and Pathways in the Pathogenesis of Ovarian Cancer)
Open AccessReview From Protein Engineering to Immobilization: Promising Strategies for the Upgrade of Industrial Enzymes
Int. J. Mol. Sci. 2013, 14(1), 1232-1277; doi:10.3390/ijms14011232
Received: 3 September 2012 / Revised: 14 November 2012 / Accepted: 24 December 2012 / Published: 10 January 2013
Cited by 86 | PDF Full-text (1151 KB) | HTML Full-text | XML Full-text
Abstract
Enzymes found in nature have been exploited in industry due to their inherent catalytic properties in complex chemical processes under mild experimental and environmental conditions. The desired industrial goal is often difficult to achieve using the native form of the enzyme. Recent developments
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Enzymes found in nature have been exploited in industry due to their inherent catalytic properties in complex chemical processes under mild experimental and environmental conditions. The desired industrial goal is often difficult to achieve using the native form of the enzyme. Recent developments in protein engineering have revolutionized the development of commercially available enzymes into better industrial catalysts. Protein engineering aims at modifying the sequence of a protein, and hence its structure, to create enzymes with improved functional properties such as stability, specific activity, inhibition by reaction products, and selectivity towards non-natural substrates. Soluble enzymes are often immobilized onto solid insoluble supports to be reused in continuous processes and to facilitate the economical recovery of the enzyme after the reaction without any significant loss to its biochemical properties. Immobilization confers considerable stability towards temperature variations and organic solvents. Multipoint and multisubunit covalent attachments of enzymes on appropriately functionalized supports via linkers provide rigidity to the immobilized enzyme structure, ultimately resulting in improved enzyme stability. Protein engineering and immobilization techniques are sequential and compatible approaches for the improvement of enzyme properties. The present review highlights and summarizes various studies that have aimed to improve the biochemical properties of industrially significant enzymes. Full article
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
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Open AccessReview ANRIL: Molecular Mechanisms and Implications in Human Health
Int. J. Mol. Sci. 2013, 14(1), 1278-1292; doi:10.3390/ijms14011278
Received: 6 November 2012 / Revised: 28 December 2012 / Accepted: 4 January 2013 / Published: 10 January 2013
Cited by 48 | PDF Full-text (448 KB) | HTML Full-text | XML Full-text
Abstract
ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other conditions.
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ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other conditions. ANRIL has been shown to regulate its neighbor tumor suppressors CDKN2A/B by epigenetic mechanisms and thereby regulate cell proliferation and senescence. However, the clear role of ANRIL in the pathogenesis of these conditions is yet to be understood. Here, we review the recent findings on ANRIL molecular characterization and function, with a particular focus on its implications in human disease. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessReview Phospholipids and Alzheimer’s Disease: Alterations, Mechanisms and Potential Biomarkers
Int. J. Mol. Sci. 2013, 14(1), 1310-1322; doi:10.3390/ijms14011310
Received: 27 November 2012 / Revised: 20 December 2012 / Accepted: 24 December 2012 / Published: 10 January 2013
Cited by 30 | PDF Full-text (190 KB) | HTML Full-text | XML Full-text
Abstract
Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to
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Brain is one of the richest organs in lipid content. Phospholipids (glycerophospholipids and sphingolipids) are important building blocks of cell membranes, which provide an optimal environment for protein interactions, trafficking and function. Because of that, alterations in their cellular levels could lead to different pathogenic processes in the brain, such as in Alzheimer’s disease (AD), the most common type of dementia among older populations. There is increasing evidence that phospholipid changes occur during pathogenic processes in AD. It is known that lipids are tightly connected with metabolism of the Amyloid Precursor Protein (APP), which produces Amyloid-beta peptide (Aβ), the main component of senile plaques, which represent the main pathological hallmark of AD. However, the mechanism(s) of the lipid-effect on Aβ metabolism and AD pathogenesis is still not completely understood. This review summarizes the current knowledge on phospholipid changes occurring during normal aging and discusses phospholipid changes in the human brain associated with different stages of AD, as well changes in the cerebrospinal fluid and blood/plasma, which are interesting potential biomarkers for AD diagnosis and disease monitoring. At the end, we have discussed future perspectives of phospholipid changes as potential biomarkers and as targets for development of novel treatment strategies against AD. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
Open AccessReview Potential Applications of Carbohydrases Immobilization in the Food Industry
Int. J. Mol. Sci. 2013, 14(1), 1335-1369; doi:10.3390/ijms14011335
Received: 30 October 2012 / Revised: 17 December 2012 / Accepted: 18 December 2012 / Published: 11 January 2013
Cited by 14 | PDF Full-text (328 KB) | HTML Full-text | XML Full-text
Abstract
Carbohydrases find a wide application in industrial processes and products, mainly in the food industry. With these enzymes, it is possible to obtain different types of sugar syrups (viz. glucose, fructose and inverted sugar syrups), prebiotics (viz. galactooligossacharides and fructooligossacharides) and
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Carbohydrases find a wide application in industrial processes and products, mainly in the food industry. With these enzymes, it is possible to obtain different types of sugar syrups (viz. glucose, fructose and inverted sugar syrups), prebiotics (viz. galactooligossacharides and fructooligossacharides) and isomaltulose, which is an interesting sweetener substitute for sucrose to improve the sensory properties of juices and wines and to reduce lactose in milk. The most important carbohydrases to accomplish these goals are of microbial origin and include amylases (α-amylases and glucoamylases), invertases, inulinases, galactosidases, glucosidases, fructosyltransferases, pectinases and glucosyltransferases. Yet, for all these processes to be cost-effective for industrial application, a very efficient, simple and cheap immobilization technique is required. Immobilization techniques can involve adsorption, entrapment or covalent bonding of the enzyme into an insoluble support, or carrier-free methods, usually based on the formation of cross-linked enzyme aggregates (CLEAs). They include a broad variety of supports, such as magnetic materials, gums, gels, synthetic polymers and ionic resins. All these techniques present advantages and disadvantages and several parameters must be considered. In this work, the most recent and important studies on the immobilization of carbohydrases with potential application in the food industry are reviewed. Full article
(This article belongs to the Special Issue Enzyme Optimization and Immobilization)
Open AccessReview Role of the Blood-Brain Barrier in the Formation of Brain Metastases
Int. J. Mol. Sci. 2013, 14(1), 1383-1411; doi:10.3390/ijms14011383
Received: 17 October 2012 / Revised: 12 December 2012 / Accepted: 14 December 2012 / Published: 11 January 2013
Cited by 32 | PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier
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The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation. Full article
(This article belongs to the Special Issue Brain Metastasis)
Open AccessReview Role of Oxidative Stress in Refractory Epilepsy: Evidence in Patients and Experimental Models
Int. J. Mol. Sci. 2013, 14(1), 1455-1476; doi:10.3390/ijms14011455
Received: 9 October 2012 / Revised: 6 November 2012 / Accepted: 18 December 2012 / Published: 14 January 2013
Cited by 28 | PDF Full-text (279 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress, a state of imbalance in the production of reactive oxygen species and nitrogen, is induced by a wide variety of factors. This biochemical state is associated with systemic diseases, and diseases affecting the central nervous system. Epilepsy is a chronic neurological
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Oxidative stress, a state of imbalance in the production of reactive oxygen species and nitrogen, is induced by a wide variety of factors. This biochemical state is associated with systemic diseases, and diseases affecting the central nervous system. Epilepsy is a chronic neurological disorder with refractoriness to drug therapy at about 30%. Currently, experimental evidence supports the involvement of oxidative stress in seizures, in the process of their generation, and in the mechanisms associated with refractoriness to drug therapy. Hence, the aim of this review is to present information in order to facilitate the handling of this evidence and determine the therapeutic impact of the biochemical status for this pathology. Full article
(This article belongs to the Special Issue Advances in Free Radicals in Biology and Medicine)
Open AccessReview Role of RNA Interference (RNAi) in the Moss Physcomitrella patens
Int. J. Mol. Sci. 2013, 14(1), 1516-1540; doi:10.3390/ijms14011516
Received: 21 November 2012 / Revised: 9 December 2012 / Accepted: 10 December 2012 / Published: 14 January 2013
Cited by 7 | PDF Full-text (956 KB) | HTML Full-text | XML Full-text
Abstract
RNA interference (RNAi) is a mechanism that regulates genes by either transcriptional (TGS) or posttranscriptional gene silencing (PTGS), required for genome maintenance and proper development of an organism. Small non-coding RNAs are the key players in RNAi and have been intensively studied in
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RNA interference (RNAi) is a mechanism that regulates genes by either transcriptional (TGS) or posttranscriptional gene silencing (PTGS), required for genome maintenance and proper development of an organism. Small non-coding RNAs are the key players in RNAi and have been intensively studied in eukaryotes. In plants, several classes of small RNAs with specific sizes and dedicated functions have evolved. The major classes of small RNAs include microRNAs (miRNAs) and small interfering RNAs (siRNAs), which differ in their biogenesis. miRNAs are synthesized from a short hairpin structure while siRNAs are derived from long double-stranded RNAs (dsRNA). Both miRNA and siRNAs control the expression of cognate target RNAs by binding to reverse complementary sequences mediating cleavage or translational inhibition of the target RNA. They also act on the DNA and cause epigenetic changes such as DNA methylation and histone modifications. In the last years, the analysis of plant RNAi pathways was extended to the bryophyte Physcomitrella patens, a non-flowering, non-vascular ancient land plant that diverged from the lineage of seed plants approximately 450 million years ago. Based on a number of characteristic features and its phylogenetic key position in land plant evolution P. patens emerged as a plant model species to address basic as well as applied topics in plant biology. Here we summarize the current knowledge on the role of RNAi in P. patens that shows functional overlap with RNAi pathways from seed plants, and also unique features specific to this species. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Aqueous Self-Sorting in Extended Supramolecular Aggregates
Int. J. Mol. Sci. 2013, 14(1), 1541-1565; doi:10.3390/ijms14011541
Received: 6 December 2012 / Revised: 27 December 2012 / Accepted: 4 January 2013 / Published: 14 January 2013
Cited by 19 | PDF Full-text (1610 KB) | HTML Full-text | XML Full-text
Abstract
Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet. Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes
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Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet. Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade. Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or—to a lesser extent—in water have been investigated. In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules. We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species. The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter. Full article
(This article belongs to the Special Issue Molecular Self-Assembly 2012)
Open AccessReview RUNX1: A MicroRNA Hub in Normal and Malignant Hematopoiesis
Int. J. Mol. Sci. 2013, 14(1), 1566-1588; doi:10.3390/ijms14011566
Received: 12 December 2012 / Revised: 31 December 2012 / Accepted: 4 January 2013 / Published: 14 January 2013
Cited by 15 | PDF Full-text (550 KB) | HTML Full-text | XML Full-text
Abstract
Hematopoietic development is orchestrated by gene regulatory networks that progressively induce lineage-specific transcriptional programs. To guarantee the appropriate level of complexity, flexibility, and robustness, these networks rely on transcriptional and post-transcriptional circuits involving both transcription factors (TFs) and microRNAs (miRNAs). The focus of
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Hematopoietic development is orchestrated by gene regulatory networks that progressively induce lineage-specific transcriptional programs. To guarantee the appropriate level of complexity, flexibility, and robustness, these networks rely on transcriptional and post-transcriptional circuits involving both transcription factors (TFs) and microRNAs (miRNAs). The focus of this review is on RUNX1 (AML1), a master hematopoietic transcription factor which is at the center of miRNA circuits necessary for both embryonic and post-natal hematopoiesis. Interference with components of these circuits can perturb RUNX1-controlled coding and non-coding transcriptional programs in leukemia. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities
Int. J. Mol. Sci. 2013, 14(1), 1589-1607; doi:10.3390/ijms14011589
Received: 20 December 2012 / Revised: 9 January 2013 / Accepted: 10 January 2013 / Published: 14 January 2013
Cited by 25 | PDF Full-text (639 KB) | HTML Full-text | XML Full-text
Abstract
The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the
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The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane — monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)
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Open AccessReview UV-Induced Cell Death in Plants
Int. J. Mol. Sci. 2013, 14(1), 1608-1628; doi:10.3390/ijms14011608
Received: 1 November 2012 / Revised: 5 December 2012 / Accepted: 4 January 2013 / Published: 14 January 2013
Cited by 42 | PDF Full-text (1642 KB) | HTML Full-text | XML Full-text
Abstract
Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm),
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Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD). Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessReview Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering
Int. J. Mol. Sci. 2013, 14(1), 1629-1654; doi:10.3390/ijms14011629
Received: 24 September 2012 / Revised: 27 November 2012 / Accepted: 7 January 2013 / Published: 14 January 2013
Cited by 105 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text
Abstract
There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including
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There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessReview CXCR4/CXCL12 in Non-Small-Cell Lung Cancer Metastasis to the Brain
Int. J. Mol. Sci. 2013, 14(1), 1713-1727; doi:10.3390/ijms14011713
Received: 12 November 2012 / Revised: 4 January 2013 / Accepted: 7 January 2013 / Published: 15 January 2013
Cited by 8 | PDF Full-text (721 KB) | HTML Full-text | XML Full-text
Abstract
Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before
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Lung cancer represents the leading cause of cancer-related mortality throughout the world. Patients die of local progression, disseminated disease, or both. At least one third of the people with lung cancer develop brain metastases at some point during their disease, even often before the diagnosis of lung cancer is made. The high rate of brain metastasis makes lung cancer the most common type of tumor to spread to the brain. It is critical to understand the biologic basis of brain metastases to develop novel diagnostic and therapeutic approaches. This review will focus on the emerging data supporting the involvement of the chemokine CXCL12 and its receptor CXCR4 in the brain metastatic evolution of non-small-cell lung cancer (NSCLC) and the pharmacological tools that may be used to interfere with this signaling axis. Full article
(This article belongs to the Special Issue Brain Metastasis)
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Open AccessReview Modulation of Cancer Traits by Tumor Suppressor microRNAs
Int. J. Mol. Sci. 2013, 14(1), 1822-1842; doi:10.3390/ijms14011822
Received: 20 November 2012 / Revised: 28 December 2012 / Accepted: 10 January 2013 / Published: 16 January 2013
Cited by 12 | PDF Full-text (687 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. In mammalian cells, miRNAs typically suppress mRNA stability and/or translation through partial complementarity with target mRNAs. Each miRNA can regulate a wide range of mRNAs, and a single mRNA can be regulated by multiple
[...] Read more.
MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. In mammalian cells, miRNAs typically suppress mRNA stability and/or translation through partial complementarity with target mRNAs. Each miRNA can regulate a wide range of mRNAs, and a single mRNA can be regulated by multiple miRNAs. Through these complex regulatory interactions, miRNAs participate in many cellular processes, including carcinogenesis. By altering gene expression patterns, cancer cells can develop specific phenotypes that allow them to proliferate, survive, secure oxygen and nutrients, evade immune recognition, invade other tissues and metastasize. At the same time, cancer cells acquire miRNA signature patterns distinct from those of normal cells; the differentially expressed miRNAs contribute to enabling the cancer traits. Over the past decade, several miRNAs have been identified, which functioned as oncogenic miRNAs (oncomiRs) or tumor-suppressive miRNAs (TS-miRNAs). In this review, we focus specifically on TS-miRNAs and their effects on well-established cancer traits. We also discuss the rising interest in TS-miRNAs in cancer therapy. Full article
(This article belongs to the Special Issue Non-Coding RNAs 2012)
Open AccessReview Neuroprotection for Ischemic Stroke: Moving Past Shortcomings and Identifying Promising Directions
Int. J. Mol. Sci. 2013, 14(1), 1890-1917; doi:10.3390/ijms14011890
Received: 9 November 2012 / Revised: 4 January 2013 / Accepted: 10 January 2013 / Published: 17 January 2013
Cited by 14 | PDF Full-text (408 KB) | HTML Full-text | XML Full-text
Abstract
The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke,
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The translation of neuroprotective agents for ischemic stroke from bench-to-bedside has largely failed to produce improved treatments since the development of tissue plasminogen activator (tPA). One possible reason for lack of translation is the failure to acknowledge the greatest risk factor for stroke, age, and other common comorbidities such as hypertension, obesity, and diabetes that are associated with stroke. In this review, we highlight both mechanisms of studying these factors and results of those that have been addressed. We also discuss the potential role of other lifestyle factors associated with an increased stroke risk such as sleep fragmentation and/or deprivation. Furthermore, many proposed therapeutic agents have targeted molecular mechanisms occurring soon after the onset of ischemia despite data indicating delayed patient presentation following ischemic stroke. Modulating inflammation has been identified as a promising therapeutic avenue consistent with preliminary success of ongoing clinical trials for anti-inflammatory compounds such as minocycline. We review the role of inflammation in stroke and in particular, the role of inflammatory cell recruitment and macrophage phenotype in the inflammatory process. Emerging evidence indicates an increasing role of neuro-immune crosstalk, which has led to increased interest in identification of peripheral biomarkers indicative of neural injury. It is our hope that identification and investigation of factors influencing stroke pathophysiology may lead to improved therapeutics. Full article
Open AccessReview Nanostructured Surfaces of Dental Implants
Int. J. Mol. Sci. 2013, 14(1), 1918-1931; doi:10.3390/ijms14011918
Received: 9 October 2012 / Revised: 21 December 2012 / Accepted: 4 January 2013 / Published: 17 January 2013
Cited by 17 | PDF Full-text (473 KB) | HTML Full-text | XML Full-text
Abstract
The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been
[...] Read more.
The structural and functional fusion of the surface of the dental implant with the surrounding bone (osseointegration) is crucial for the short and long term outcome of the device. In recent years, the enhancement of bone formation at the bone-implant interface has been achieved through the modulation of osteoblasts adhesion and spreading, induced by structural modifications of the implant surface, particularly at the nanoscale level. In this context, traditional chemical and physical processes find new applications to achieve the best dental implant technology. This review provides an overview of the most common manufacture techniques and the related cells-surface interactions and modulation. A Medline and a hand search were conducted to identify studies concerning nanostructuration of implant surface and their related biological interaction. In this paper, we stressed the importance of the modifications on dental implant surfaces at the nanometric level. Nowadays, there is still little evidence of the long-term benefits of nanofeatures, as the promising results achieved in vitro and in animals have still to be confirmed in humans. However, the increasing interest in nanotechnology is undoubted and more research is going to be published in the coming years. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
Open AccessReview Vitamin D and Death by Sunshine
Int. J. Mol. Sci. 2013, 14(1), 1964-1977; doi:10.3390/ijms14011964
Received: 6 December 2012 / Revised: 4 January 2013 / Accepted: 10 January 2013 / Published: 18 January 2013
Cited by 8 | PDF Full-text (425 KB) | HTML Full-text | XML Full-text
Abstract
Exposure to sunlight is the major cause of skin cancer. Ultraviolet radiation (UV) from the sun causes damage to DNA by direct absorption and can cause skin cell death. UV also causes production of reactive oxygen species that may interact with DNA to
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Exposure to sunlight is the major cause of skin cancer. Ultraviolet radiation (UV) from the sun causes damage to DNA by direct absorption and can cause skin cell death. UV also causes production of reactive oxygen species that may interact with DNA to indirectly cause oxidative DNA damage. UV increases accumulation of p53 in skin cells, which upregulates repair genes but promotes death of irreparably damaged cells. A benefit of sunlight is vitamin D, which is formed following exposure of 7-dehydrocholesterol in skin cells to UV. The relatively inert vitamin D is metabolized to various biologically active compounds, including 1,25-dihydroxyvitamin D3. Therapeutic use of vitamin D compounds has proven beneficial in several cancer types, but more recently these compounds have been shown to prevent UV-induced cell death and DNA damage in human skin cells. Here, we discuss the effects of vitamin D compounds in skin cells that have been exposed to UV. Specifically, we examine the various signaling pathways involved in the vitamin D-induced protection of skin cells from UV. Full article
(This article belongs to the Special Issue UV-Induced Cell Death 2012)
Open AccessReview The Twenty-Year Story of a Plant-Based Vaccine Against Hepatitis B: Stagnation or Promising Prospects?
Int. J. Mol. Sci. 2013, 14(1), 1978-1998; doi:10.3390/ijms14011978
Received: 17 December 2012 / Revised: 7 January 2013 / Accepted: 14 January 2013 / Published: 21 January 2013
Cited by 14 | PDF Full-text (591 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization
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Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization trials, based on ingestion of raw plant tissue and conjugated with injection or exclusively oral administration of lyophilized tissue, were either impractical or insufficient due to oral tolerance acquisition. Plant-produced purified HBV antigens were highly immunogenic when injected, but their yields were initially insufficient for practical purposes. However, knowledge and technology have progressed, hence new plant-derived anti-HBV vaccines can be proposed today. All HBV antigens can be efficiently produced in stable or transient expression systems. Processing of injection vaccines has been developed and needs only to be successfully completed. Purified antigens can be used for injection in an equivalent manner to the present commercial vaccines. Although oral vaccines require improvement, plant tissue, lyophilized or extracted and converted into tablets, etc., may serve as a boosting vaccine. Preliminary data indicate also that both vaccines can be combined in an effective parenteral-oral immunization procedure. A partial substitution of injection vaccines with oral formulations still offers good prospects for economically viable and efficacious anti-HBV plant-based vaccines. Full article
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
Open AccessReview Innovative Therapeutic Strategies in the Treatment of Brain Metastases
Int. J. Mol. Sci. 2013, 14(1), 2135-2174; doi:10.3390/ijms14012135
Received: 9 December 2012 / Revised: 8 January 2013 / Accepted: 9 January 2013 / Published: 22 January 2013
Cited by 18 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
Brain metastases (BM) are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the
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Brain metastases (BM) are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases are associated with a poor prognosis and a poor performance status. Metastasis development involves the migration of a cancer cell from the bulk tumor into the surrounding tissue, extravasation from the blood into tissue elsewhere in the body, and formation of a secondary tumor. In the recent past, important results have been obtained in the management of patients affected by BM, using surgery, radiation therapy, or both. Conventional chemotherapies have generally produced disappointing results, possibly due to their limited ability to penetrate the blood–brain barrier. The advent of new technologies has led to the discovery of novel molecules and pathways that have better depicted the metastatic process. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review, we will report current data on targeted therapies. A brief review about brain metastatic process will be also presented. Full article
(This article belongs to the Special Issue Brain Metastasis)

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Open AccessShort Note Isolation and Characterization of Nine Microsatellite Loci for a Parasitoid Wasp, Encarsia smithi (Silvestri) (Hymenoptera: Aphelinidae)
Int. J. Mol. Sci. 2013, 14(1), 527-531; doi:10.3390/ijms14010527
Received: 11 October 2012 / Revised: 18 November 2012 / Accepted: 8 December 2012 / Published: 27 December 2012
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Abstract
The parasitoid wasp Encarsia smithi is an important agent in the classical biological control of two species of invasive spiny whiteflies, Aleurocanthus spiniferus and Aleurocanthus camelliae. To evaluate the performance of parasitism indexed by genetic diversity, a highly polymorphic genetic marker is
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The parasitoid wasp Encarsia smithi is an important agent in the classical biological control of two species of invasive spiny whiteflies, Aleurocanthus spiniferus and Aleurocanthus camelliae. To evaluate the performance of parasitism indexed by genetic diversity, a highly polymorphic genetic marker is required. In this report, nine microsatellite loci are described for E. smithi. The microsatellite loci were obtained through the construction of an enriched library and exhibited polymorphisms (2–6 alleles per locus) and high levels of expected heterozygosities (0.203–0.780, average 0.537). Linkage disequilibrium and null alleles were not detected in these microsatellite loci. The isolated microsatellite markers may be useful to estimate the genetic diversity of E. smithi. Full article
Open AccessConcept Paper Overlapping ATP2C1 and ASTE1 Genes in Human Genome: Implications for SPCA1 Expression?
Int. J. Mol. Sci. 2013, 14(1), 674-683; doi:10.3390/ijms14010674
Received: 20 November 2012 / Revised: 5 December 2012 / Accepted: 7 December 2012 / Published: 4 January 2013
Cited by 3 | PDF Full-text (344 KB) | HTML Full-text | XML Full-text
Abstract
The ATP2C1 gene encodes for the secretory pathway calcium (Ca2+)-ATPase pump (SPCA1), which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic
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The ATP2C1 gene encodes for the secretory pathway calcium (Ca2+)-ATPase pump (SPCA1), which localizes along the secretory pathway, mainly in the trans-Golgi. The loss of one ATP2C1 allele causes Hailey-Hailey disease in humans but not mice. Examining differences in genomic organization between mouse and human we speculate that the overlap between ATP2C1 and ASTE1 genes only in humans could explain this different response to ATP2C1 dysregulation. We propose that ASTE1, overlapping with ATP2C1 in humans, affects alternative splicing, and potentially protein expression of the latter. If dysregulated, the composition of the SPCA1 isoform pool could diverge from the physiological status, affecting cytosolic Ca2+-signaling, and in turn perturbing cell division, leading to cell death or to neoplastic transformation. Full article
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)

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