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Int. J. Mol. Sci., Volume 14, Issue 10 (October 2013), Pages 19361-21201

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Open AccessArticle Inhibition of Oxidative Stress by Low-Molecular-Weight Polysaccharides with Various Functional Groups in Skin Fibroblasts
Int. J. Mol. Sci. 2013, 14(10), 19399-19415; doi:10.3390/ijms141019399
Received: 9 July 2013 / Revised: 28 August 2013 / Accepted: 4 September 2013 / Published: 25 September 2013
Cited by 5 | PDF Full-text (457 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., [...] Read more.
The aim of this study was to evaluate the in cellulo inhibition of hydrogen-peroxide-induced oxidative stress in skin fibroblasts using different low-molecular-weight polysaccharides (LMPS) prepared from agar (LMAG), chitosan (LMCH) and starch (LMST), which contain various different functional groups (i.e., sulfate, amine, and hydroxyl groups). The following parameters were evaluated: cell viability, intracellular oxidant production, lipid peroxidation, and DNA damage. Trolox was used as a positive control in order to allow comparison of the antioxidant efficacies of the various LMPS. The experimentally determined attenuation of oxidative stress by LMPS in skin fibroblasts was: LMCH > LMAG > LMST. The different protection levels of these LMPS may be due to the physic-chemical properties of the LMPS’ functional groups, including electron transfer ability, metal ion chelating capacities, radical stabilizing capacity, and the hydrophobicity of the constituent sugars. The results suggest that LMCH might constitute a novel and potential dermal therapeutic and sun-protective agent. Full article
(This article belongs to the Special Issue Oxidative Stress and Ageing)
Open AccessArticle Systematic Exploration of Natural and Synthetic Flavonoids for the Inhibition of Staphylococcus aureus Biofilms
Int. J. Mol. Sci. 2013, 14(10), 19434-19451; doi:10.3390/ijms141019434
Received: 14 August 2013 / Revised: 3 September 2013 / Accepted: 10 September 2013 / Published: 25 September 2013
Cited by 14 | PDF Full-text (478 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
When single-cell (or suspended) bacteria switch into the biofilm lifestyle, they become less susceptible to antimicrobials, imposing the need for anti-biofilms research. Flavonoids are among the most extensively studied natural compounds with an unprecedented amount of bioactivity claims. Most studies focus on [...] Read more.
When single-cell (or suspended) bacteria switch into the biofilm lifestyle, they become less susceptible to antimicrobials, imposing the need for anti-biofilms research. Flavonoids are among the most extensively studied natural compounds with an unprecedented amount of bioactivity claims. Most studies focus on the antibacterial effects against suspended cells; fewer reports have researched their anti-biofilm properties. Here, a high throughput phenotypic platform was utilized to screen for the inhibitory activity of 500 flavonoids, including natural and synthetic derivatives, against Staphylococcus aureus biofilms. Since discrepancies among results from earlier antibacterial studies on flavonoids had been noted, the current study aimed to minimize sources of variations. After the first screen, flavonoids were classified as inactive (443), moderately active (47) or highly active (10). Further, exclusion criteria combining bioactivity and selectivity identified two synthetic flavans as the most promising. The body of data reported here serves three main purposes. First, it offers an improved methodological workflow for anti-biofilm screens of chemical libraries taking into account the (many times ignored) connections between anti-biofilm and antibacterial properties. This is particularly relevant for the study of flavonoids and other natural products. Second, it provides a large and freely available anti-biofilm bioactivity dataset that expands the knowledge on flavonoids and paves the way for future structure-activity relationship studies and structural optimizations. Finally, it identifies two new flavans that can successfully act on biofilms, as well as on suspended bacteria and represent more feasible antibacterial candidates. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria) Print Edition available
Open AccessArticle Mixtures of l-Amino Acids as Reaction Medium for Formation of Iron Nanoparticles: The Order of Addition into a Ferrous Salt Solution Matters
Int. J. Mol. Sci. 2013, 14(10), 19452-19473; doi:10.3390/ijms141019452
Received: 17 May 2013 / Revised: 24 June 2013 / Accepted: 30 August 2013 / Published: 25 September 2013
Cited by 3 | PDF Full-text (5028 KB) | HTML Full-text | XML Full-text
Abstract
Owing to Mössbauer spectroscopy, an advanced characterization technique for iron-containing materials, the present study reveals previously unknown possibilities using l-amino acids for the generation of magnetic particles. Based on our results, a simple choice of the order of l-amino acids addition into [...] Read more.
Owing to Mössbauer spectroscopy, an advanced characterization technique for iron-containing materials, the present study reveals previously unknown possibilities using l-amino acids for the generation of magnetic particles. Based on our results, a simple choice of the order of l-amino acids addition into a reaction mixture containing ferrous ions leads to either superparamagnetic ferric oxide/oxyhydroxide particles, or magnetically strong Fe0-Fe2O3/FeOOH core-shell particles after chemical reduction. Conversely, when ferric salts are employed with the addition of selected l-amino acids, only Fe0-Fe2O3/FeOOH core-shell particles are observed, regardless of the addition order. We explain this phenomenon by a specific transient/intermediate complex formation between Fe2+ and l-glutamic acid. This type of complexation prevents ferrous ions from spontaneous oxidation in solutions with full air access. Moreover, due to surface-enhanced Raman scattering spectroscopy we show that the functional groups of l-amino acids are not destroyed during the borohydride-induced reduction. These functionalities can be further exploited for (i) attachment of l-amino acids to the as-prepared magnetic particles, and (ii) for targeted bio- and/or environmental applications where the surface chemistry needs to be tailored and directed toward biocompatible species. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
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Open AccessArticle Parts Per Trillion Detection of 7-Aminonitrazepam by Nano-Enhanced ELISA
Int. J. Mol. Sci. 2013, 14(10), 19474-19483; doi:10.3390/ijms141019474
Received: 10 July 2013 / Revised: 6 September 2013 / Accepted: 12 September 2013 / Published: 25 September 2013
Cited by 5 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
It is challenging to detect 7-aminonitrazepam (7-ANZP) residue in animal tissues simply and sensitively by the enzyme-linked sorbent immunoassay (ELISA) method. This paper demonstrates that utilizing a bioconjugate of gold nanoparticles and enzyme-labeled antibody as a signal probe increases the sensitivity of [...] Read more.
It is challenging to detect 7-aminonitrazepam (7-ANZP) residue in animal tissues simply and sensitively by the enzyme-linked sorbent immunoassay (ELISA) method. This paper demonstrates that utilizing a bioconjugate of gold nanoparticles and enzyme-labeled antibody as a signal probe increases the sensitivity of a traditional ELISA for 7-ANZP by nearly 20 times. The sensitivity of this ELISA for 7-ANZP was 5.6 pg/mL in buffer, and the limit of detection (LOD) of 0.18 µg/kg for 7-ANZP in urine could be achieved after the urine samples were simply hydrolyzed and diluted by buffer. This simple and sensitive method has potential application for improving the sensitivity of ELISA methods against various small molecules. Full article
(This article belongs to the Section Molecular Diagnostics)
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Open AccessArticle Semisynthesis and Antifeedant Activity of New Derivatives of a Dihydro-β-Agarofuran from Parnassia wightiana
Int. J. Mol. Sci. 2013, 14(10), 19484-19493; doi:10.3390/ijms141019484
Received: 1 July 2013 / Revised: 22 August 2013 / Accepted: 10 September 2013 / Published: 26 September 2013
Cited by 12 | PDF Full-text (467 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Five new derivatives (26) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 26 [...] Read more.
Five new derivatives (26) were semi-synthesized using compound 1, a dihydro-β-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 26 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (16) were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Synthesis and Activity of Novel Acylthiourea with Hydantoin
Int. J. Mol. Sci. 2013, 14(10), 19526-19539; doi:10.3390/ijms141019526
Received: 23 July 2013 / Revised: 29 August 2013 / Accepted: 18 September 2013 / Published: 26 September 2013
Cited by 7 | PDF Full-text (283 KB) | HTML Full-text | XML Full-text
Abstract
The 41 novel acylthiourea derivatives with hydantoin were synthesized in moderate to excellent yields by using 5-(4-aminophenyl)- and 5-(4-aminobenzyl)-hydantoin or 5-(4-aminobenzyl)-thiohydantoin as raw materials and characterized by IR, 1H NMR spectra and elementary analysis. The preliminary bioassay showed that these compounds [...] Read more.
The 41 novel acylthiourea derivatives with hydantoin were synthesized in moderate to excellent yields by using 5-(4-aminophenyl)- and 5-(4-aminobenzyl)-hydantoin or 5-(4-aminobenzyl)-thiohydantoin as raw materials and characterized by IR, 1H NMR spectra and elementary analysis. The preliminary bioassay showed that these compounds exhibit certain selectively herbicidal activities with the 91%, 94% and 87% inhibition rates of 7l, 8o and 8p against B. campestris, 100%, 100% and 95% efficacy against B. campestris in a greenhouse test, respectively. 7a, 7b, 7c and 7d exhibited 74%, 79%, 79% and 71% inhibition rates against F. oxysporum, respectively. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation
Int. J. Mol. Sci. 2013, 14(10), 19540-19555; doi:10.3390/ijms141019540
Received: 5 July 2013 / Revised: 3 September 2013 / Accepted: 10 September 2013 / Published: 26 September 2013
Cited by 4 | PDF Full-text (3513 KB) | HTML Full-text | XML Full-text
Abstract
In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from [...] Read more.
In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2–4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Investigations of the Binding of [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II) to DNA via Various Cross-Linking Modes
Int. J. Mol. Sci. 2013, 14(10), 19556-19586; doi:10.3390/ijms141019556
Received: 11 July 2013 / Revised: 14 August 2013 / Accepted: 10 September 2013 / Published: 26 September 2013
Cited by 2 | PDF Full-text (5891 KB) | HTML Full-text | XML Full-text
Abstract
We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and [...] Read more.
We have constructed models for a series of platinum-DNA adducts that represent the binding of two agents, [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II), to DNA via inter- and intra-strand cross-linking, and carried out molecular dynamics simulations and DNA conformational dynamics calculations. The effects of trans- and cis-configurations of the centers of these di-nuclear platinum agents, and of different bridging linkers, have been investigated on the conformational distortions of platinum-DNA adducts formed via inter- and intra-strand cross-links. The results demonstrate that the DNA conformational distortions for the various platinum-DNA adducts with differing cross-linking modes are greatly influenced by the difference between the platinum-platinum distance for the platinum agent and the platinum-bound N7–N7 distance for the DNA molecule, and by the flexibility of the bridging linkers in the platinum agent. However, the effects of trans/cis-configurations of the platinum-centers on the DNA conformational distortions in the platinum-DNA adducts depend on the inter- and intra-strand cross-linking modes. In addition, we discuss the relevance of DNA base motions, including opening, shift and roll, to the changes in the parameters of the DNA major and minor grooves caused by binding of the platinum agent. Full article
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
Open AccessArticle Regulation of MIR Genes in Response to Abiotic Stress in Hevea brasiliensis
Int. J. Mol. Sci. 2013, 14(10), 19587-19604; doi:10.3390/ijms141019587
Received: 31 May 2013 / Revised: 6 September 2013 / Accepted: 16 September 2013 / Published: 27 September 2013
Cited by 6 | PDF Full-text (824 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Increasing demand for natural rubber (NR) calls for an increase in latex yield and also an extension of rubber plantations in marginal zones. Both harvesting and abiotic stresses lead to tapping panel dryness through the production of reactive oxygen species. Many microRNAs [...] Read more.
Increasing demand for natural rubber (NR) calls for an increase in latex yield and also an extension of rubber plantations in marginal zones. Both harvesting and abiotic stresses lead to tapping panel dryness through the production of reactive oxygen species. Many microRNAs regulated during abiotic stress modulate growth and development. The objective of this paper was to study the regulation of microRNAs in response to different types of abiotic stress and hormone treatments in Hevea. Regulation of MIR genes differs depending on the tissue and abiotic stress applied. A negative co-regulation between HbMIR398b with its chloroplastic HbCuZnSOD target messenger is observed in response to salinity. The involvement of MIR gene regulation during latex harvesting and tapping panel dryness (TPD) occurrence is further discussed. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
Open AccessArticle Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts
Int. J. Mol. Sci. 2013, 14(10), 19605-19617; doi:10.3390/ijms141019605
Received: 8 July 2013 / Revised: 27 August 2013 / Accepted: 11 September 2013 / Published: 27 September 2013
Cited by 10 | PDF Full-text (664 KB) | HTML Full-text | XML Full-text
Abstract
Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide hydroxamic [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic inflammation and excessive collagen accumulation in the lung. Myofibroblasts are the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide hydroxamic acid (SAHA), are US FDA approved for cancer treatment. In this study, we investigated SAHA’s effects on the expression of collagen III alpha 1 (COL3A1) in primary human IPF fibroblasts and in a murine model of pulmonary fibrosis. We observed that increased COL3A1 expression in IPF fibroblasts can be substantially reduced by SAHA treatment at the level of transcription as detected by RT-PCR; collagen III protein level was also reduced, as detected by Western blots and immunofluorescence. The deacetylation inhibitor effect of SAHA was verified by observing higher acetylation levels of both histone H3 and H4 in treated IPF cells. Chromatin immunoprecipitation (ChIP) experiments demonstrated that the reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. In our murine model of bleomycin-induced pulmonary fibrosis, the SAHA treated group demonstrated significantly less collagen III, as detected by immunohistochemistry. Our data indicate that the HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle A Combination of Pre- and Post-Exposure Ascorbic Acid Rescues Mice from Radiation-Induced Lethal Gastrointestinal Damage
Int. J. Mol. Sci. 2013, 14(10), 19618-19635; doi:10.3390/ijms141019618
Received: 26 June 2013 / Revised: 9 September 2013 / Accepted: 13 September 2013 / Published: 27 September 2013
Cited by 7 | PDF Full-text (2141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage [...] Read more.
The development of an effective therapy for radiation-induced gastrointestinal damage is important, because it is currently a major complication of treatment and there are few effective therapies available. Although we have recently demonstrated that pretreatment with ascorbic acid attenuates lethal gastrointestinal damage in irradiated mice, more than half of mice eventually died, thus indicating that better approach was needed. We then investigated a more effective therapy for radiation-induced gastrointestinal damage. Mice receiving abdominal radiation at 13 Gy were orally administered ascorbic acid (250 mg/kg/day) for three days before radiation (pretreatment), one shot of engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent for seven days after radiation (post-treatment). None of the control mice survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage (without bone marrow damage). Neither pretreatment with ascorbic acid (20% survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated mice. However, combination therapy using ascorbic acid, including pretreatment, engulfment and post-treatment, rescued all of the mice from lethal abdominal radiation, and was accompanied by remarkable improvements in the gastrointestinal damage (100% survival). Omitting post-treatment from the combination therapy with ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the importance of post-treatment with ascorbic acid. Combination therapy with ascorbic acid may be a potent therapeutic tool for radiation-induced gastrointestinal damage. Full article
(This article belongs to the collection Radiation Toxicity in Cells)
Open AccessArticle Chitosan-Coated Magnetic Nanoparticles Prepared in One Step by Reverse Microemulsion Precipitation
Int. J. Mol. Sci. 2013, 14(10), 19636-19650; doi:10.3390/ijms141019636
Received: 31 May 2013 / Revised: 5 September 2013 / Accepted: 12 September 2013 / Published: 27 September 2013
Cited by 4 | PDF Full-text (535 KB) | HTML Full-text | XML Full-text
Abstract
Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 °C and 80 °C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures [...] Read more.
Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70 °C and 80 °C in a one-step method, which comprises precipitation in reverse microemulsion in the presence of low chitosan concentration in the aqueous phase. X-ray diffractometry showed that CMNP obtained at both temperatures contain a mixture of magnetite and maghemite nanoparticles with ≈4.5 nm in average diameter, determined by electron microscopy, which suggests that precipitation temperature does not affect the particle size. The chitosan coating on nanoparticles was inferred from Fourier transform infrared spectrometry measurements; furthermore, the carbon concentration in the nanoparticles allowed an estimation of chitosan content in CMNP of 6%–7%. CMNP exhibit a superparamagnetic behavior with relatively high final magnetization values (≈49–53 emu/g) at 20 kOe and room temperature, probably due to a higher magnetite content in the mixture of magnetic nanoparticles. In addition, a slight direct effect of precipitation temperature on magnetization was identified, which was ascribed to a possible higher degree of nanoparticles crystallinity as temperature at which they are obtained increases. Tested for Pb2+ removal from a Pb(NO3)2 aqueous solution, CMNP showed a recovery efficacy of 100%, which makes them attractive for using in heavy metals ion removal from waste water. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles 2013)
Open AccessArticle BTG1 Expression Correlates with the Pathogenesis and Progression of Ovarian Carcinomas
Int. J. Mol. Sci. 2013, 14(10), 19670-19680; doi:10.3390/ijms141019670
Received: 13 May 2013 / Revised: 5 September 2013 / Accepted: 6 September 2013 / Published: 27 September 2013
Cited by 8 | PDF Full-text (1265 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was [...] Read more.
BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and angiogenesis and regulate cell cycle progression and differentiation in a variety of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and progression. A BTG1-expressing plasmid was transfected into ovarian carcinoma cells and their phenotypes and related proteins were examined. BTG1 mRNA expression was detected in ovarian normal tissue (n = 17), ovarian benign tumors (n = 12), and ovarian carcinoma (n = 64) using real-time RT-PCR. Ectopic BTG1 expression resulted in lower growth rate, high cisplatin sensitivity, G1 arrest, apoptosis, and decreased migration and invasion. Phosphoinositide 3-kinase, protein kinase B, Bcl-xL, survivin, vascular endothelial growth factor, and matrix metalloproteinase-2 mRNA and protein expression was reduced in transfectants as compared to control cells. There was higher expression of BTG1 mRNA in normal tissue than in carcinoma tissue (p = 0.001) and in benign tumors than in carcinoma tissue (p = 0.027). BTG1 mRNA expression in International Federation of Gynecology and Obstetrics (FIGO) stage I/II ovarian carcinomas was higher than that in FIGO stage III/IV ovarian carcinomas (p = 0.038). Altered BTG1 expression might play a role in the pathogenesis and progression of ovarian carcinoma by modulating proliferation, migration, invasion, the cell cycle, and apoptosis. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessArticle The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes
Int. J. Mol. Sci. 2013, 14(10), 19705-19715; doi:10.3390/ijms141019705
Received: 31 July 2013 / Revised: 6 September 2013 / Accepted: 10 September 2013 / Published: 30 September 2013
Cited by 5 | PDF Full-text (589 KB) | HTML Full-text | XML Full-text
Abstract
Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used [...] Read more.
Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl conductance. The TNFα-evoked Cl current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
Open AccessArticle Preparation and Characterization of Nanoliposomes Entrapping Medium-Chain Fatty Acids and Vitamin C by Lyophilization
Int. J. Mol. Sci. 2013, 14(10), 19763-19773; doi:10.3390/ijms141019763
Received: 15 July 2013 / Revised: 12 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013
Cited by 4 | PDF Full-text (136 KB) | HTML Full-text | XML Full-text
Abstract
The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 [...] Read more.
The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under −86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2013)
Open AccessCommunication Generation of an ICF Syndrome Model by Efficient Genome Editing of Human Induced Pluripotent Stem Cells Using the CRISPR System
Int. J. Mol. Sci. 2013, 14(10), 19774-19781; doi:10.3390/ijms141019774
Received: 28 August 2013 / Revised: 11 September 2013 / Accepted: 17 September 2013 / Published: 30 September 2013
Cited by 28 | PDF Full-text (519 KB) | HTML Full-text | XML Full-text
Abstract
Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome [...] Read more.
Genome manipulation of human induced pluripotent stem (iPS) cells is essential to achieve their full potential as tools for regenerative medicine. To date, however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be extremely difficult. Recently, an efficient genome manipulation technology using the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic repeats (CRISPR) system, has been developed. Here we report the efficient generation of an iPS cell model for immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is highly efficient and useful for genome engineering of human iPS cells. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Relationship between Serum Osteocalcin Levels and Non-Alcoholic Fatty Liver Disease in Adult Males, South China
Int. J. Mol. Sci. 2013, 14(10), 19782-19791; doi:10.3390/ijms141019782
Received: 31 July 2013 / Revised: 20 September 2013 / Accepted: 22 September 2013 / Published: 30 September 2013
Cited by 7 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
AIM: To determine serum osteocalcin levels in South Chinese males with non-alcoholic fatty liver disease (NAFLD) and to examine the relation between serum osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the Fangchenggang Area Male Healthy and Examination Survey [...] Read more.
AIM: To determine serum osteocalcin levels in South Chinese males with non-alcoholic fatty liver disease (NAFLD) and to examine the relation between serum osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the Fangchenggang Area Male Healthy and Examination Survey (FAMHES) from September 2009 to December 2009. Serum osteocalcin was measured with electrochemiluminescence immunoassay. An abdominal ultrasonographic examination for all individuals was performed by two experienced ultrasonographers. The associations of serum osteocalcin with NAFLD were evaluated. RESULTS: The levels of serum osteocalcin were lower in 364 NAFLD participants than in 1319 non-NAFLD participants (24.51 ± 1.38 ng/mL vs. 20.81 ± 1.33 ng/mL, p < 0.001). Serum osteocalin level was associated with the scale of NAFLD (r = −0.150, p < 0.01). Serum osteocalin level tended to decrease with the scale of NAFLD. Binary logistic regression analysis showed that decreased ORs for NAFLD were observed from the first to the fourth osteocalcin quartiles. CONCLUSIONS: Our findings suggest that a lower serum osteocalcin level is associated with the presence of NAFLD. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
Open AccessArticle Achyranthes bidentata Polypeptides Reduces Oxidative Stress and Exerts Protective Effects against Myocardial Ischemic/Reperfusion Injury in Rats
Int. J. Mol. Sci. 2013, 14(10), 19792-19804; doi:10.3390/ijms141019792
Received: 19 August 2013 / Revised: 16 September 2013 / Accepted: 17 September 2013 / Published: 30 September 2013
Cited by 9 | PDF Full-text (768 KB) | HTML Full-text | XML Full-text
Abstract
Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test [...] Read more.
Achyranthes bidentata, a Chinese medicinal herb, is reported to be neuroprotective. However, its role in cardioprotection remains largely unknown. Our present study aimed to investigate the effects of Achyranthes bidentata polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R) injury and to test the possible mechanisms. Rats were treated with ABPP (10 mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP preconditioning for one week significantly improved cardiac function following MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide generation, gp91phox expression, malonaldialdehyde formation and enhanced superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart. PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated anti-oxidant effect and cardioprotection. Our study demonstrated for the first time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R injury in rats. Inhibition of PTEN and activation of Akt may contribute to the anti-oxidant capacity and cardioprotection of ABPP. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessArticle Cytokines, Chaperones and Neuroinflammatory Responses in Heroin-Related Death: What Can We Learn from Different Patterns of Cellular Expression?
Int. J. Mol. Sci. 2013, 14(10), 19831-19845; doi:10.3390/ijms141019831
Received: 26 August 2013 / Revised: 22 September 2013 / Accepted: 26 September 2013 / Published: 30 September 2013
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Abstract
Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation [...] Read more.
Heroin (3,6-diacetylmorphine) has various effects on the central nervous system with several neuropathological alterations including hypoxic-ischemic brain damage from respiratory depressing effects and neuroinflammatory response. Both of these mechanisms induce the release of cytokines, chemokines and other inflammatory mediators by the activation of many cell types such as leucocytes and endothelial and glial cells, especially microglia, the predominant immunocompetent cell type within the central nervous system. The aim of this study is to clarify the correlation between intravenous heroin administration in heroin related death and the neuroinflammatory response. We selected 45 cases among autopsies executed for heroin-related death (358 total cases); immunohistochemical studies and Western blotting analyses were used to investigate the expression of brain markers such as tumor necrosis factor-α, oxygen-regulated protein 150, (interleukins) IL-1β, IL-6, IL-8, IL-10, IL-15, cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387). Findings demonstrated that morphine induces inflammatory response and cytokine release. In particular, oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and IL-15 cytokines were over-expressed with different patterns of cellular expression. Full article
(This article belongs to the collection Molecular Research in Neurotoxicology)
Open AccessArticle Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions
Int. J. Mol. Sci. 2013, 14(10), 19911-19922; doi:10.3390/ijms141019911
Received: 15 July 2013 / Revised: 9 September 2013 / Accepted: 23 September 2013 / Published: 1 October 2013
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Abstract
Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma [...] Read more.
Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637) cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Using Next-Generation Sequencing and Cross-Species Amplification in the Genus Pseudopungtungia
Int. J. Mol. Sci. 2013, 14(10), 19923-19931; doi:10.3390/ijms141019923
Received: 1 June 2013 / Revised: 10 July 2013 / Accepted: 18 September 2013 / Published: 1 October 2013
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Abstract
Nuclear microsatellite markers for Pungtungia herzi were developed using a combination of next-generation sequencing and Sanger sequencing. One hundred primer sets in the flanking region of dinucleotide and trinucleotide repeat motifs were designed and tested for efficiency in polymerase chain reaction amplification. [...] Read more.
Nuclear microsatellite markers for Pungtungia herzi were developed using a combination of next-generation sequencing and Sanger sequencing. One hundred primer sets in the flanking region of dinucleotide and trinucleotide repeat motifs were designed and tested for efficiency in polymerase chain reaction amplification. Of these primer sets, 16 new markers (16%) were successfully amplified with unambiguous polymorphic alleles in 16 individuals of Pungtungia herzi. Cross-species amplification with these markers was then examined in two related species, Pseudopungtungia nigra and Pseudopungtungia tenuicorpa. Fifteen and 11 primer pairs resulted in successful amplification in Pseudopungtungia nigra and Pseudopungtungia tenuicorpa, respectively, with various polymorphisms, ranging from one allele (monomorphic) to 11 alleles per marker. These results indicated that developing microsatellite markers for cross-amplification from a species that is abundant and phylogenetically close to the species of interest is a good alternative when tissue samples of an endangered species are insufficient to develop microsatellites. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle CD8+ T Cell-Induced Expression of Tissue Inhibitor of Metalloproteinses-1 Exacerbated Osteoarthritis
Int. J. Mol. Sci. 2013, 14(10), 19951-19970; doi:10.3390/ijms141019951
Received: 27 July 2013 / Revised: 11 September 2013 / Accepted: 22 September 2013 / Published: 8 October 2013
Cited by 5 | PDF Full-text (1181 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue [...] Read more.
Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle N,N’-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers
Int. J. Mol. Sci. 2013, 14(10), 19976-19986; doi:10.3390/ijms141019976
Received: 31 May 2013 / Revised: 16 September 2013 / Accepted: 17 September 2013 / Published: 8 October 2013
Cited by 3 | PDF Full-text (336 KB) | HTML Full-text | XML Full-text
Abstract
Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). [...] Read more.
Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N’-bisalkylated imidazolium salts were identified as QSIs; they were active at the µM range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
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Open AccessArticle Transcriptional Regulation of a Chitinase Gene by 20-Hydroxyecdysone and Starvation in the Oriental Fruit Fly, Bactrocera dorsalis
Int. J. Mol. Sci. 2013, 14(10), 20048-20063; doi:10.3390/ijms141020048
Received: 2 August 2013 / Revised: 24 September 2013 / Accepted: 25 September 2013 / Published: 9 October 2013
Cited by 3 | PDF Full-text (841 KB) | HTML Full-text | XML Full-text
Abstract
Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The [...] Read more.
Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The cDNA contains an open reading frame (ORF) of 1449 bp that encodes 483 amino acid residues and 126- and 296-bp non-coding regions at the 5'- and 3'-ends, respectively. The BdCht2 genome has four exons and three introns. The predicted molecular mass of the deduced BdCht2 is approximately 54.3 kDa, with an isoelectric point of 5.97. The 977 bp 5' flanking region was identified and the transcription factor binding sites were predicted. Bioinformatic analyses showed that the deduced amino acid sequence of BdCht2 had 34%–66% identity to that of chitinases identified in other insect species. Quantitative real-time PCR (qPCR) analyses indicated that BdCht2 was mainly expressed during the larval-pupal and pupal-adult transitions. The tissue-specific expression showed that the highest expression was in the integument, followed by the fat body and other tissues. Moreover, the expression of BdCht2 was upregulated significantly upon 20-hydroxyecdysone (20E) at different dose injections after 8 h compared to that of the control. Starvation also increased the expression of BdCht2 in the third-instar larvae and was suppressed again by re-feeding the insects. These results suggest that BdCht2 plays an important role in the molting process of B. dorsalis larvae and can be regulated by 20E. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Characterization of Apoptosis Induced by Emodin and Related Regulatory Mechanisms in Human Neuroblastoma Cells
Int. J. Mol. Sci. 2013, 14(10), 20139-20156; doi:10.3390/ijms141020139
Received: 1 July 2013 / Revised: 26 September 2013 / Accepted: 26 September 2013 / Published: 9 October 2013
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Abstract
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Recent studies have shown that emodin can induce or prevent cell apoptosis, although the precise molecular mechanisms underlying these effects are unknown. Experiments from the current study revealed [...] Read more.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Recent studies have shown that emodin can induce or prevent cell apoptosis, although the precise molecular mechanisms underlying these effects are unknown. Experiments from the current study revealed that emodin (10–20 μM) induces apoptotic processes in the human neuroblastoma cell line, IMR-32, but exerts no injury effects at treatment doses below 10 μM. Treatment with emodin at concentrations of 10–20 μM led to a direct increase in the reactive oxygen species (ROS) content in IMR-32 cells, along with significant elevation of cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with nitric oxide (NO) scavengers suppressed the apoptotic biochemical changes induced by 20 μM emodin, and attenuated emodin-induced p53 and p21 expression involved in apoptotic signaling. Our results collectively indicate that emodin at concentrations of 10–20 μM triggers apoptosis of IMR-32 cells via a mechanism involving both ROS and NO. Based on the collective results, we propose a model for an emodin-triggered apoptotic signaling cascade that sequentially involves ROS, Ca2+, NO, p53, caspase-9 and caspase-3. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
Open AccessArticle Microscale Diffusion Measurements and Simulation of a Scaffold with a Permeable Strut
Int. J. Mol. Sci. 2013, 14(10), 20157-20170; doi:10.3390/ijms141020157
Received: 16 July 2013 / Revised: 6 September 2013 / Accepted: 10 September 2013 / Published: 10 October 2013
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Abstract
Electrospun nanofibrous structures provide good performance to scaffolds in tissue engineering. We measured the local diffusion coefficients of 3-kDa FITC-dextran in line patterns of electrospun nanofibrous structures fabricated by the direct-write electrospinning (DWES) technique using the fluorescence recovery after photobleaching (FRAP) method. [...] Read more.
Electrospun nanofibrous structures provide good performance to scaffolds in tissue engineering. We measured the local diffusion coefficients of 3-kDa FITC-dextran in line patterns of electrospun nanofibrous structures fabricated by the direct-write electrospinning (DWES) technique using the fluorescence recovery after photobleaching (FRAP) method. No significant differences were detected between DWES line patterns fabricated with polymer supplied at flow rates of 0.1 and 0.5 mL/h. The oxygen diffusion coefficients of samples were estimated to be ~92%–94% of the oxygen diffusion coefficient in water based on the measured diffusion coefficient of 3-kDa FITC-dextran. We also simulated cell growth and distribution within spatially patterned scaffolds with struts consisting of either oxygen-permeable or non-permeable material. The permeable strut scaffolds exhibited enhanced cell growth. Saturated depths at which cells could grow to confluence were 15% deeper for the permeable strut scaffolds than for the non-permeable strut scaffold. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
Open AccessArticle Understanding the Electronic Structures and Absorption Properties of Porphyrin Sensitizers YD2 and YD2-o-C8 for Dye-Sensitized Solar Cells
Int. J. Mol. Sci. 2013, 14(10), 20171-20188; doi:10.3390/ijms141020171
Received: 19 August 2013 / Revised: 20 September 2013 / Accepted: 23 September 2013 / Published: 10 October 2013
Cited by 16 | PDF Full-text (1236 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The electronic structures and excitation properties of dye sensitizers determine the photon-to-current conversion efficiency of dye sensitized solar cells (DSSCs). In order to understand the different performance of porphyrin dye sensitizers YD2 and YD2-o-C8 in DSSC, their geometries and electronic structures have [...] Read more.
The electronic structures and excitation properties of dye sensitizers determine the photon-to-current conversion efficiency of dye sensitized solar cells (DSSCs). In order to understand the different performance of porphyrin dye sensitizers YD2 and YD2-o-C8 in DSSC, their geometries and electronic structures have been studied using density functional theory (DFT), and the electronic absorption properties have been investigated via time-dependent DFT (TDDFT) with polarizable continuum model for solvent effects. The geometrical parameters indicate that YD2 and YD2-o-C8 have similar conjugate length and charge transfer (CT) distance. According to the experimental spectra, the HSE06 functional in TDDFT is the most suitable functional for describing the Q and B absorption bands of porphyrins. The transition configurations and molecular orbital analysis suggest that the diarylamino groups are major chromophores for effective CT excitations (ECTE), and therefore act as electron donor in photon-induced electron injection in DSSCs. The analysis of excited states properties and the free energy changes for electron injection support that the better performance of YD2-o-C8 in DSSCs result from the more excited states with ECTE character and the larger absolute value of free energy change for electron injection. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle Effect of Chain-Extenders on the Properties and Hydrolytic Degradation Behavior of the Poly(lactide)/ Poly(butylene adipate-co-terephthalate) Blends
Int. J. Mol. Sci. 2013, 14(10), 20189-20203; doi:10.3390/ijms141020189
Received: 2 September 2013 / Revised: 15 September 2013 / Accepted: 23 September 2013 / Published: 10 October 2013
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Abstract
Biodegradable poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) blends were prepared by reactive blending in the presence of chain-extenders. Two chain-extenders with multi-epoxy groups were studied. The effect of chain-extenders on the morphology, mechanical properties, thermal behavior, and hydrolytic degradation of the blends was [...] Read more.
Biodegradable poly(lactide)/poly(butylene adipate-co-terephthalate) (PLA/PBAT) blends were prepared by reactive blending in the presence of chain-extenders. Two chain-extenders with multi-epoxy groups were studied. The effect of chain-extenders on the morphology, mechanical properties, thermal behavior, and hydrolytic degradation of the blends was investigated. The compatibility between the PLA and PBAT was significantly improved by in situ formation of PLA-co-PBAT copolymers in the presence of the chain-extenders, results in an enhanced ductility of the blends, e.g., the elongation at break was increased to 500% without any decrease in the tensile strength. The differential scanning calorimeter (DSC) results reveal that cold crystallization of PLA was enhanced due to heterogeneous nucleation effect of the in situ compatibilized PBAT domains. As known before, PLA is sensitive to hydrolysis and in the presence of PBAT and the chain-extenders, the hydrolytic degradation of the blend was evident. A three-stage hydrolysis mechanism for the system is proposed based on a study of weight loss and molecular weight reduction of the samples and the pH variation of the degradation medium. Full article
(This article belongs to the Section Material Sciences and Nanotechnology)
Open AccessArticle OsPOP5, A Prolyl Oligopeptidase Family Gene from Rice Confers Abiotic Stress Tolerance in Escherichia coli
Int. J. Mol. Sci. 2013, 14(10), 20204-20219; doi:10.3390/ijms141020204
Received: 23 July 2013 / Revised: 16 September 2013 / Accepted: 27 September 2013 / Published: 10 October 2013
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Abstract
The prolyl oligopeptidase family, which is a group of serine peptidases, can hydrolyze peptides smaller than 30 residues. The prolyl oligopeptidase family in plants includes four members, which are prolyl oligopeptidase (POP, EC3.4.21.26), dipeptidyl peptidase IV (DPPIV, EC3.4.14.5), oligopeptidase B (OPB, EC3.4.21.83), [...] Read more.
The prolyl oligopeptidase family, which is a group of serine peptidases, can hydrolyze peptides smaller than 30 residues. The prolyl oligopeptidase family in plants includes four members, which are prolyl oligopeptidase (POP, EC3.4.21.26), dipeptidyl peptidase IV (DPPIV, EC3.4.14.5), oligopeptidase B (OPB, EC3.4.21.83), and acylaminoacyl peptidase (ACPH, EC3.4.19.1). POP is found in human and rat, and plays important roles in multiple biological processes, such as protein secretion, maturation and degradation of peptide hormones, and neuropathies, signal transduction and memory and learning. However, the function of POP is unclear in plants. In order to study POP function in plants, we cloned the cDNA of the OsPOP5 gene from rice by nested-PCR. Sequence analysis showed that the cDNA encodes a protein of 596 amino acid residues with Mw ≈ 67.29 kD. In order to analyze the protein function under different abiotic stresses, OsPOP5 was expressed in Escherichia coli. OsPOP5 protein enhanced the tolerance of E. coli to high salinity, high temperature and simulated drought. The results indicate that OsPOP5 is a stress-related gene in rice and it may play an important role in plant tolerance to abiotic stress. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Proteomic Analysis Identifies an NADPH Oxidase 1 (Nox1)-Mediated Role for Actin-Related Protein 2/3 Complex Subunit 2 (ARPC2) in Promoting Smooth Muscle Cell Migration
Int. J. Mol. Sci. 2013, 14(10), 20220-20235; doi:10.3390/ijms141020220
Received: 8 August 2013 / Revised: 28 August 2013 / Accepted: 16 September 2013 / Published: 11 October 2013
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Abstract
A variety of vascular pathologies, including hypertension, restenosis and atherosclerosis, are characterized by vascular smooth muscle cell (VSMC) hypertrophy and migration. NADPH oxidase 1 (Nox1) plays a pivotal role in these phenotypes via distinct downstream signaling. However, the mediators differentiating these distinct [...] Read more.
A variety of vascular pathologies, including hypertension, restenosis and atherosclerosis, are characterized by vascular smooth muscle cell (VSMC) hypertrophy and migration. NADPH oxidase 1 (Nox1) plays a pivotal role in these phenotypes via distinct downstream signaling. However, the mediators differentiating these distinct phenotypes and their precise role in vascular disease are still not clear. The present study was designed to identify novel targets of VSMC Nox1 signaling using 2D Differential In-Gel Electrophoresis and Mass Spectrometry (2D-DIGE/MS). VSMC treatment with scrambled (Scrmb) or Nox1 siRNA and incubation with the oxidant hydrogen peroxide (H2O2; 50 µM, 3 h) followed by 2D-DIGE/MS on cell lysates identified 10 target proteins. Among these proteins, actin-related protein 2/3 complex subunit 2 (ARPC2) with no previous link to Nox isozymes, H2O2, or other reactive oxygen species (ROS), was identified and postulated to play an intermediary role in VSMC migration. Western blot confirmed that Nox1 mediates H2O2-induced ARPC2 expression in VSMC. Treatment with a p38 MAPK inhibitor (SB203580) resulted in reduced ARPC2 expression in H2O2-treated VSMC. Additionally, wound-healing “scratch” assay confirmed that H2O2 stimulates VSMC migration via Nox1. Importantly, gene silencing of ARPC2 suppressed H2O2-stimulated VSMC migration. These results demonstrate for the first time that Nox1-mediated VSMC migration involves ARPC2 as a downstream signaling target. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessArticle Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8
Int. J. Mol. Sci. 2013, 14(10), 20236-20255; doi:10.3390/ijms141020236
Received: 16 August 2013 / Revised: 15 September 2013 / Accepted: 16 September 2013 / Published: 11 October 2013
Cited by 9 | PDF Full-text (1585 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. [...] Read more.
Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65) is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs). Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression. Full article
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
Open AccessArticle HuR-Regulated mRNAs Associated with Nuclear hnRNP A1-RNP Complexes
Int. J. Mol. Sci. 2013, 14(10), 20256-20281; doi:10.3390/ijms141020256
Received: 29 July 2013 / Revised: 6 September 2013 / Accepted: 16 September 2013 / Published: 11 October 2013
Cited by 1 | PDF Full-text (562 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components [...] Read more.
Post-transcriptional regulatory networks are dependent on the interplay of many RNA-binding proteins having a major role in mRNA processing events in mammals. We have been interested in the concerted action of the two RNA-binding proteins hnRNP A1 and HuR, both stable components of immunoselected hnRNP complexes and having a major nuclear localization. Specifically, we present here the application of the RNA-immunoprecipitation (RIP)-Chip technology to identify a population of nuclear transcripts associated with hnRNP A1-RNPs as isolated from the nuclear extract of either HuR WT or HuR-depleted (KO) mouse embryonic fibroblast (MEF) cells. The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes. Real time PCR analysis was applied to validate a selected number of nuclear mRNA transcripts, as well as to identify pre-spliced transcripts (in addition to their mature mRNA counterpart) within the isolated nuclear hnRNP A1-RNPs. The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism. Full article
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Open AccessArticle Targeting of Rho Kinase Ameliorates Impairment of Diabetic Endothelial Function in Intrarenal Artery
Int. J. Mol. Sci. 2013, 14(10), 20282-20298; doi:10.3390/ijms141020282
Received: 19 June 2013 / Revised: 11 July 2013 / Accepted: 9 September 2013 / Published: 14 October 2013
Cited by 2 | PDF Full-text (1209 KB) | HTML Full-text | XML Full-text
Abstract
Endothelial dysfunction in kidney vasculature is the initial and key element for nephropathy in diabetes mellitus. Accumulating evidence suggests the protective role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS activity and NO production. However, the role of Rho kinase [...] Read more.
Endothelial dysfunction in kidney vasculature is the initial and key element for nephropathy in diabetes mellitus. Accumulating evidence suggests the protective role of Rho kinase inhibitors in endothelial dysfunction via modulating eNOS activity and NO production. However, the role of Rho kinase in diabetes-related endothelial dysfunction in kidney vasculature and the relevant mechanisms remain unknown. We assessed whether pharmacological inhibition of Rho kinase attenuates endothelial dysfunction in intrarenal arteries from type 1 diabetic rats. Fasudil, a Rho kinase inhibitor effectively decreased the phosphorylated level of MYPT1 without affecting the expression of ROCKs in the kidney. Fasudil treatment showed no improvement in diabetes-related abnormality in metabolic indices, but it significantly ameliorated endothelial dysfunction in intrarenal arteries and lessened the mesangial matrix expansion in the kidney cortex. Mechanistically, superoxide production in the intrarenal artery and NOX4 member of NADPH oxidase in the renal cortex that contribute to diabetic nephropathy were also prevented by the Rho kinase inhibitor. In conclusion, the present results indicate that Rho kinase is involved in endothelial dysfunction in type 1 diabetes via enhancement of oxidative stress and provides new evidence for Rho kinase inhibitors as potential therapeutic agents for the treatment of diabetic nephropathy. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Physiological and Proteomic Responses of Diploid and Tetraploid Black Locust (Robinia pseudoacacia L.) Subjected to Salt Stress
Int. J. Mol. Sci. 2013, 14(10), 20299-20325; doi:10.3390/ijms141020299
Received: 17 June 2013 / Revised: 31 August 2013 / Accepted: 9 September 2013 / Published: 14 October 2013
Cited by 19 | PDF Full-text (2063 KB) | HTML Full-text | XML Full-text
Abstract
Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress. Here, we compared morphological, physiological, ultrastructural, and proteomic traits of leaves in tetraploid black locust and its diploid relatives under salt stress. The results showed that diploid (2×) plants suffered [...] Read more.
Tetraploid black locust (Robinia pseudoacacia L.) is adaptable to salt stress. Here, we compared morphological, physiological, ultrastructural, and proteomic traits of leaves in tetraploid black locust and its diploid relatives under salt stress. The results showed that diploid (2×) plants suffered from greater negative effects than those of tetraploid (4×) plants. After salt treatment, plant growth was inhibited, photosynthesis was reduced, reactive oxygen species, malondialdehyde content, and relative electrolyte leakage increased, and defense-related enzyme activities decreased in 2× compared to those in 4×. In addition, salt stress resulted in distorted chloroplasts, swollen thylakoid membranes, accumulation of plastoglobules, and increased starch grains in 2× compared to those in 4×. However, 4× developed diverse responses under salt stress. A comparative proteomic analysis revealed that 41 and 37 proteins were differentially expressed in 2× and 4×, respectively. These proteins were mainly involved in photosynthesis, stress and defense, energy, metabolism, transcription/translation, and transportation. Distinct patterns of protein changes between 2× and 4× were analyzed. Collectively, our results suggest that the plants showed significantly different responses to salt stress based on ploidy level of the plant. The 4× possessed a better salt protection mechanism than that of 2×, suggesting salt tolerance in the polyploid plant. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle MicroRNA Expression Profiling of the Porcine Developing Hypothalamus and Pituitary Tissue
Int. J. Mol. Sci. 2013, 14(10), 20326-20339; doi:10.3390/ijms141020326
Received: 19 August 2013 / Revised: 17 September 2013 / Accepted: 23 September 2013 / Published: 14 October 2013
Cited by 5 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding [...] Read more.
MicroRNAs (miRNAs), a class of small non-coding RNA molecules, play important roles in gene expressions at transcriptional and post-transcriptional stages in mammalian brain. So far, a growing number of porcine miRNAs and their function have been identified, but little is known regarding the porcine developing hypothalamus and pituitary. In the present study, Solexa sequencing analysis showed 14,129,397 yielded reads, 6,680,678 of which were related to 674 unique miRNAs. After a microarray assay, we detected 175 unique miRNAs in the hypothalamus, including 136 previously known miRNAs and 39 novel candidates, while a total of 140 miRNAs, including 104 known and 36 new candidate miRNAs, were discovered in pituitary. More importantly, 37 and 30 differentially expressed miRNAs from several developmental stages of hypothalamus and pituitary were revealed, respectively. The 37 differentially expressed miRNAs in hypothalamus represented 6 different expression patterns, while the 30 differentially expressed miRNAs in pituitary represented 7 different expression patterns. To clarify potential target genes and specific functions of these differentially expressed miRNAs in hypothalamus and pituitary, TargetScan and Gorilla prediction tools were then applied. The current functional analysis showed that the differentially expressed miRNAs in hypothalamus and pituitary shared many biological processes, with the main differences being found in tissue-specific processes including: CDP-diacylglycerol biosynthetic/metabolic process; phosphatidic acid biosynthetic/metabolic process; energy reserve metabolic process for hypothalamus; adult behavior; sterol transport/homeostasis; and cholesterol/reverse cholesterol transport for pituitary. Overall, this study identified miRNA profiles and differentially expressed miRNAs among various developmental stages in hypothalamus and pituitary and indicated miRNA profiles change with age and brain location, enhancing our knowledge about spatial and temporal expressions of miRNAs in the porcine developing brain. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Strengths and Weaknesses of Recently Engineered Red Fluorescent Proteins Evaluated in Live Cells Using Fluorescence Correlation Spectroscopy
Int. J. Mol. Sci. 2013, 14(10), 20340-20358; doi:10.3390/ijms141020340
Received: 15 July 2013 / Revised: 13 September 2013 / Accepted: 23 September 2013 / Published: 14 October 2013
Cited by 6 | PDF Full-text (834 KB) | HTML Full-text | XML Full-text
Abstract
The scientific community is still looking for a bright, stable red fluorescent protein (FP) as functional as the current best derivatives of green fluorescent protein (GFP). The red FPs exploit the reduced background of cells imaged in the red region of the [...] Read more.
The scientific community is still looking for a bright, stable red fluorescent protein (FP) as functional as the current best derivatives of green fluorescent protein (GFP). The red FPs exploit the reduced background of cells imaged in the red region of the visible spectrum, but photophysical short comings have limited their use for some spectroscopic approaches. Introduced nearly a decade ago, mCherry remains the most often used red FP for fluorescence correlation spectroscopy (FCS) and other single molecule techniques, despite the advent of many newer red FPs. All red FPs suffer from complex photophysics involving reversible conversions to a dark state (flickering), a property that results in fairly low red FP quantum yields and potential interference with spectroscopic analyses including FCS. The current report describes assays developed to determine the best working conditions for, and to uncover the shortcoming of, four recently engineered red FPs for use in FCS and other diffusion and spectroscopic studies. All five red FPs assayed had potential shortcomings leading to the conclusion that the current best red FP for FCS is still mCherry. The assays developed here aim to enable the rapid evaluation of new red FPs and their smooth adaptation to live cell spectroscopic microscopy and nanoscopy. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
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Open AccessArticle Molecular Study of a Hoxa2 Gain-of-Function in Chondrogenesis: A Model of Idiopathic Proportionate Short Stature
Int. J. Mol. Sci. 2013, 14(10), 20386-20398; doi:10.3390/ijms141020386
Received: 13 June 2013 / Revised: 16 September 2013 / Accepted: 16 September 2013 / Published: 14 October 2013
Cited by 1 | PDF Full-text (2239 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first [...] Read more.
In a previous study using transgenic mice ectopically expressing Hoxa2 during chondrogenesis, we associated the animal phenotype to human idiopathic proportionate short stature. Our analysis showed that this overall size reduction was correlated with a negative influence of Hoxa2 at the first step of endochondral ossification. However, the molecular pathways leading to such phenotype are still unknown. Using protein immunodetection and histological techniques comparing transgenic mice to controls, we show here that the persistent expression of Hoxa2 in chondrogenic territories provokes a general down-regulation of the main factors controlling the differentiation cascade, such as Bapx1, Bmp7, Bmpr1a, Ihh, Msx1, Pax9, Sox6, Sox9 and Wnt5a. These data confirm the impairment of chondrogenic differentiation by Hoxa2 overexpression. They also show a selective effect of Hoxa2 on endochondral ossification processes since Gdf5 and Gdf10, and Bmp4 or PthrP were up-regulated and unmodified, respectively. Since Hoxa2 deregulation in mice induces a proportionate short stature phenotype mimicking human idiopathic conditions, our results give an insight into understanding proportionate short stature pathogenesis by highlighting molecular factors whose combined deregulation may be involved in such a disease. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
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Open AccessArticle Genetic Diversity and Population Differentiation of Calanthe tsoongiana, a Rare and Endemic Orchid in China
Int. J. Mol. Sci. 2013, 14(10), 20399-20413; doi:10.3390/ijms141020399
Received: 20 August 2013 / Revised: 24 September 2013 / Accepted: 25 September 2013 / Published: 14 October 2013
Cited by 7 | PDF Full-text (337 KB) | HTML Full-text | XML Full-text
Abstract
Calanthe tsoongiana is a rare terrestrial orchid endemic to China, and this species has experienced severe habitat loss and fragmentation. Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity and differentiation of six populations of C. tsoongiana. Based [...] Read more.
Calanthe tsoongiana is a rare terrestrial orchid endemic to China, and this species has experienced severe habitat loss and fragmentation. Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity and differentiation of six populations of C. tsoongiana. Based on 124 discernible fragments yielded by eleven selected primers, high genetic diversity was revealed at the species level; however, genetic diversity at the population level was relatively low. High-level genetic differentiation among populations was detected based on analysis of molecular variance (AMOVA), indicating potential limited gene flow. No significant relationship was observed between genetic and geographic distances among the sampled populations. These results suggested that restricted gene flow might be due to habitat fragmentation and reduced population size as a result of human activities. Based on the findings, several conservation strategies were proposed for the preservation of this threatened species. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Characterization of 42 Microsatellite Markers from Poison Ivy, Toxicodendron radicans (Anacardiaceae)
Int. J. Mol. Sci. 2013, 14(10), 20414-20426; doi:10.3390/ijms141020414
Received: 21 August 2013 / Revised: 22 September 2013 / Accepted: 23 September 2013 / Published: 14 October 2013
Cited by 7 | PDF Full-text (622 KB) | HTML Full-text | XML Full-text
Abstract
Poison ivy, Toxicodendron radicans, and poison oaks, T. diversilobum and T. pubescens, are perennial woody species of the Anacardiaceae and are poisonous, containing strong allergens named urushiols that cause allergic contact dermatitis. Poison ivy is a species distributed [...] Read more.
Poison ivy, Toxicodendron radicans, and poison oaks, T. diversilobum and T. pubescens, are perennial woody species of the Anacardiaceae and are poisonous, containing strong allergens named urushiols that cause allergic contact dermatitis. Poison ivy is a species distributed from North America to East Asia, while T. diversilobum and T. pubescens are distributed in western and eastern North America, respectively. Phylogreography and population structure of these species remain unclear. Here, we developed microsatellite markers, via constructing a magnetic enriched microsatellite library, from poison ivy. We designed 51 primer pairs, 42 of which successfully yielded products that were subsequently tested for polymorphism in poison oak, and three subspecies of poison ivy. Among the 42 loci, 38 are polymorphic, while 4 are monomorphic. The number of alleles and the expected heterozygosity ranged from 1 to 12 and from 0.10 to 0.87, respectively, in poison ivy, while varied from 2 to 8 and, from 0.26 to 0.83, respectively in poison oak. Genetic analysis revealed distinct differentiation between poison ivy and poison oak, whereas slight genetic differentiation was detected among three subspecies of poison ivy. These highly polymorphic microsatellite fingerprints enable biologists to explore the population genetics, phylogeography, and speciation in Toxicodendron. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells
Int. J. Mol. Sci. 2013, 14(10), 20443-20458; doi:10.3390/ijms141020443
Received: 10 May 2013 / Revised: 19 September 2013 / Accepted: 25 September 2013 / Published: 14 October 2013
Cited by 25 | PDF Full-text (760 KB) | HTML Full-text | XML Full-text
Abstract
Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis [...] Read more.
Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions. Full article
Open AccessArticle Twist and miR-34a Are Involved in the Generation of Tumor-Educated Myeloid-Derived Suppressor Cells
Int. J. Mol. Sci. 2013, 14(10), 20459-20477; doi:10.3390/ijms141020459
Received: 7 July 2013 / Revised: 19 September 2013 / Accepted: 23 September 2013 / Published: 14 October 2013
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Abstract
Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells in the tumor microenvironment, contributing to tumor immunological escapes. Many studies have demonstrated that multiple factors could induce myeloid precursor cells into myeloid-derived suppressor cells, not dendritic [...] Read more.
Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells in the tumor microenvironment, contributing to tumor immunological escapes. Many studies have demonstrated that multiple factors could induce myeloid precursor cells into myeloid-derived suppressor cells, not dendritic cells. In our study, we found that tumor supernatants could induce the generation of myeloid-derived suppressor cells by disturbing the development of dendritic cells. Twist and miR-34a may regulate the effect of tumor cells inducing myeloid-derived suppressor cells via TGF-β and/or IL-10. Full article
Open AccessArticle Transcriptome Comparative Profiling of Barley eibi1 Mutant Reveals Pleiotropic Effects of HvABCG31 Gene on Cuticle Biogenesis and Stress Responsive Pathways
Int. J. Mol. Sci. 2013, 14(10), 20478-20491; doi:10.3390/ijms141020478
Received: 2 September 2013 / Revised: 26 September 2013 / Accepted: 26 September 2013 / Published: 14 October 2013
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Abstract
Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. [...] Read more.
Wild barley eibi1 mutant with HvABCG31 gene mutation has low capacity to retain leaf water, a phenotype associated with reduced cutin deposition and a thin cuticle. To better understand how such a mutant plant survives, we performed a genome-wide gene expression analysis. The leaf transcriptomes between the near-isogenic lines eibi1 and the wild type were compared using the 22-k Barley1 Affymetrix microarray. We found that the pleiotropic effect of the single gene HvABCG31 mutation was linked to the co-regulation of metabolic processes and stress-related system. The cuticle development involved cytochrome P450 family members and fatty acid metabolism pathways were significantly up-regulated by the HvABCG31 mutation, which might be anticipated to reduce the levels of cutin monomers or wax and display conspicuous cuticle defects. The candidate genes for responses to stress were induced by eibi1 mutant through activating the jasmonate pathway. The down-regulation of co-expressed enzyme genes responsible for DNA methylation and histone deacetylation also suggested that HvABCG31 mutation may affect the epigenetic regulation for barley development. Comparison of transcriptomic profiling of barley under biotic and abiotic stresses revealed that the functions of HvABCG31 gene to high-water loss rate might be different from other osmotic stresses of gene mutations in barley. The transcriptional profiling of the HvABCG31 mutation provided candidate genes for further investigation of the physiological and developmental changes caused by the mutant. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Significant Overexpression of DVL1 in Taiwanese Colorectal Cancer Patients with Liver Metastasis
Int. J. Mol. Sci. 2013, 14(10), 20492-20507; doi:10.3390/ijms141020492
Received: 1 August 2013 / Revised: 24 September 2013 / Accepted: 29 September 2013 / Published: 14 October 2013
Cited by 2 | PDF Full-text (870 KB) | HTML Full-text | XML Full-text
Abstract
Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and [...] Read more.
Undetected micrometastasis plays a key role in the metastasis of cancer in colorectal cancer (CRC) patients. The aim of this study is to identify a biomarker of CRC patients with liver metastasis through the detection of circulating tumor cells (CTCs). Microarray and bioinformatics analysis of 10 CRC cancer tissue specimens compared with normal adjacent tissues revealed that 31 genes were up-regulated (gene expression ratio of cancer tissue to paired normal tissue > 2) in the cancer patients. We used a weighted enzymatic chip array (WEnCA) including 31 prognosis-related genes to investigate CTCs in 214 postoperative stage I–III CRC patients and to analyze the correlation between gene expression and clinico-pathological parameters. We employed the immunohistochemistry (IHC) method with polyclonal mouse antibody against DVL1 to detect DVL1 expression in 60 CRC patients. CRC liver metastasis occurred in 19.16% (41/214) of the patients. Using univariate analysis and multivariate proportional hazards regression analysis, we found that DVL1 mRNA overexpression had a significant, independent predictive value for liver metastasis in CRC patients (OR: 5.764; 95% CI: 2.588–12.837; p < 0.0001 on univariate analysis; OR: 3.768; 95% CI: 1.469–9.665; p = 0.006 on multivariate analysis). IHC staining of the immunoreactivity of DVL1 showed that DVL1 was localized in the cytoplasm of CRC cells. High expression of DVL1 was observed in 55% (33/60) of CRC tumor specimens and was associated significantly with tumor depth, perineural invasion and liver metastasis status (all p < 0.05). Our experimental results demonstrated that DVL1 is significantly overexpressed in CRC patients with liver metastasis, leading us to conclude that DVL1 could be a potential prognostic and predictive marker for CRC patients. Full article
(This article belongs to the Special Issue Pathogenesis and Prevention of Colorectal Cancer)
Open AccessArticle Combined Taurine, Epigallocatechin Gallate and Genistein Therapy Reduces HSC-T6 Cell Proliferation and Modulates the Expression of Fibrogenic Factors
Int. J. Mol. Sci. 2013, 14(10), 20543-20554; doi:10.3390/ijms141020543
Received: 12 August 2013 / Revised: 20 September 2013 / Accepted: 22 September 2013 / Published: 14 October 2013
Cited by 7 | PDF Full-text (348 KB) | HTML Full-text | XML Full-text
Abstract
Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the [...] Read more.
Hepatic fibrogenesis involves the activation of hepatic stellate cells (HSCs), which synthesize excess extracellular matrix and contribute to the development of liver fibrosis. In a prior study we tested the effect of combined treatment with taurine, epigallocatechin gallate and genistein on the development of alcohol-induced liver fibrosis in vitro. In this study, the biological activity of the combination of these molecules was assessed by measuring its effect on cell proliferation, fibrosis-related gene expression, and proteomic expression profiling in the activated HSC cell line, HSC-T6. HSC-T6 cells were incubated with different concentrations of the drug combination taurine, epigallocatechin gallate and genistein. Cell proliferation was evaluated by MTT assay. Transforming growth factor β1 (TGF-β1), collagen type I (Col-I), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) mRNA were analyzed by semi-quantitative reverse-transcription PCR. Proteomic profiling of HSC-T6 cells was also performed by SELDI-TOF-MS. Combined drug treatment significantly inhibited cell proliferation and TGF-β1, Col-I, TIMP-1 and TIMP-2 mRNA expression in activated HSC-T6 cells, while the expression of MMP-2 mRNA increased. A total of 176 protein m/z peaks were identified. The intensities of 10 protein peaks were downregulated and two protein peaks were upregulated in HSC-T6 cells after combined drug treatment. In conclusion, combined drug treatment with taurine, epigallocatechin gallate and genistein can inhibit HSC proliferation, and impact fibrosis-related gene and protein expression. The antifibrotic effects of this drug combination may be due to its effects on the expression of fibrogenic genes. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
Open AccessArticle The Key Enzyme of the Sialic Acid Metabolism Is Involved in Embryoid Body Formation and Expression of Marker Genes of Germ Layer Formation
Int. J. Mol. Sci. 2013, 14(10), 20555-20563; doi:10.3390/ijms141020555
Received: 28 August 2013 / Revised: 24 September 2013 / Accepted: 27 September 2013 / Published: 14 October 2013
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Abstract
The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they [...] Read more.
The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice. Here, we report that GNE-deficient embryonic stem cells express less differentiation markers compared to wild-type embryonic stem cells. As a result, GNE-deficient embryonic stem cells fail to form proper embryoid bodies (EB) within the first day of culture. However, when culturing these cells in the presence of sialic acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient embryonic stem cells proliferate faster and form larger EBs without any change in the expression of markers of the germ layers. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
Open AccessArticle Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling
Int. J. Mol. Sci. 2013, 14(10), 20564-20577; doi:10.3390/ijms141020564
Received: 9 September 2013 / Revised: 25 September 2013 / Accepted: 30 September 2013 / Published: 15 October 2013
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Abstract
Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated [...] Read more.
Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling. Full article
Open AccessArticle Structural Insights into a Novel Interkingdom Signaling Circuit by Cartography of the Ligand-Binding Sites of the Homologous Quorum Sensing LuxR-Family
Int. J. Mol. Sci. 2013, 14(10), 20578-20596; doi:10.3390/ijms141020578
Received: 1 August 2013 / Revised: 13 September 2013 / Accepted: 1 October 2013 / Published: 15 October 2013
Cited by 7 | PDF Full-text (2311 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have identified a novel interkingdom signaling circuit, via plant signaling molecules, and a bacterial sub-family of LuxR proteins, bridging eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators that, [...] Read more.
Recent studies have identified a novel interkingdom signaling circuit, via plant signaling molecules, and a bacterial sub-family of LuxR proteins, bridging eukaryotes and prokaryotes. Indeed pivotal plant-bacteria interactions are regulated by the so called Plant Associated Bacteria (PAB) LuxR solo regulators that, although closely related to the quorum sensing (QS) LuxR family, do not bind or respond to canonical quorum sensing N-acyl homoserine lactones (AHLs), but only to specific host plant signal molecules. The large body of structural data available for several members of the QS LuxR family complexed with different classes of ligands (AHLs and other compounds), has been exploited to dissect the cartography of their regulatory domains through structure-based multiple sequence alignments, structural superimposition and a comparative analysis of the contact residues involved in ligand binding. In the absence of experimentally determined structures of members of the PAB LuxR solos subfamily, an homology model of its prototype OryR is presented, aiming to elucidate the architecture of its ligand-binding site. The obtained model, in combination with the cartography of the regulatory domains of the homologous QS LuxRs, provides novel insights into the 3D structure of its ligand-binding site and unveils the probable molecular determinants responsible for differences in selectivity towards specific host plant signal molecules, rather than to canonical QS compounds. Full article
(This article belongs to the Special Issue Quorum Sensing Research in Microbial Systems)
Open AccessArticle A Comparative Proteomic Analysis of Pinellia ternata Leaves Exposed to Heat Stress
Int. J. Mol. Sci. 2013, 14(10), 20614-20634; doi:10.3390/ijms141020614
Received: 20 July 2013 / Revised: 22 September 2013 / Accepted: 29 September 2013 / Published: 15 October 2013
Cited by 4 | PDF Full-text (1193 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Pinellia ternata is an important traditional Chinese medicinal plant. The growth of P. ternata is sensitive to high temperatures. To gain a better understanding of heat stress responses in P. ternata, we performed a comparative proteomic analysis. P. ternata seedlings were [...] Read more.
Pinellia ternata is an important traditional Chinese medicinal plant. The growth of P. ternata is sensitive to high temperatures. To gain a better understanding of heat stress responses in P. ternata, we performed a comparative proteomic analysis. P. ternata seedlings were subjected to a temperature of 38 °C and samples were collected 24 h after treatment. Increased relative ion leakage and lipid peroxidation suggested that oxidative stress was frequently generated in rice leaves exposed to high temperature. Two-dimensional electrophoresis (2-DE) was used to analyze heat-responsive proteins. More than 600 protein spots were reproducibly detected on each gel; of these spots, 20 were up-regulated, and 7 were down-regulated. A total of 24 proteins and protein species were successfully identified by MALDI-TOF/TOF MS. These proteins and protein species were found to be primarily small heat shock proteins (58%) as well as proteins involved in RNA processing (17%), photosynthesis (13%), chlorophyll biosynthetic processes (4%), protein degradation (4%) and defense (4%). Using 2-DE Western blot analysis, we confirmed the identities of the cytosolic class II small heat shock protein (sHSPs-CII) identified by MS. The expression levels of four different proteins [cytosolic class I small heat shock protein (sHSPs-CI), sHSPs-CII, mitochondrial small heat shock protein (sHSPs-MIT), glycine-rich RNA-binding protein (GRP)] were analyzed at the transcriptional level by quantitative real-time PCR. The mRNA levels of three sHSPs correlated with the corresponding protein levels. However, GRP was down-regulated at the beginning of heat stress but then increased substantially to reach a peak after 24 h of heat stress. Our study provides valuable new insight into the responses of P. ternata to heat stress. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Absolute Quantification of Selected Proteins in the Human Osteoarthritic Secretome
Int. J. Mol. Sci. 2013, 14(10), 20658-20681; doi:10.3390/ijms141020658
Received: 21 June 2013 / Revised: 19 August 2013 / Accepted: 23 September 2013 / Published: 15 October 2013
Cited by 18 | PDF Full-text (493 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome enables the global study of secreted proteins. These are an important class of molecules with roles in numerous pathological [...] Read more.
Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome enables the global study of secreted proteins. These are an important class of molecules with roles in numerous pathological mechanisms. Although cartilage studies have identified profiles of secreted proteins, quantitative proteomics techniques have been implemented that would enable further biological questions to be addressed. To overcome this limitation, we used the secretome from human OA cartilage explants stimulated with IL-1β and compared proteins released into the media using a label-free LC-MS/MS-based strategy. We employed QconCAT technology to quantify specific proteins using selected reaction monitoring. A total of 252 proteins were identified, nine were differentially expressed by IL-1 β stimulation. Selected protein candidates were quantified in absolute amounts using QconCAT. These findings confirmed a significant reduction in TIMP-1 in the secretome following IL-1β stimulation. Label-free and QconCAT analysis produced equivocal results indicating no effect of cytokine stimulation on aggrecan, cartilage oligomeric matrix protein, fibromodulin, matrix metalloproteinases 1 and 3 or plasminogen release. This study enabled comparative protein profiling and absolute quantification of proteins involved in molecular pathways pertinent to understanding the pathogenesis of OA. Full article
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Open AccessArticle Thermal Properties and Crystallite Morphology of Nylon 66 Modified with a Novel Biphenyl Aromatic Liquid Crystalline Epoxy Resin
Int. J. Mol. Sci. 2013, 14(10), 20682-20691; doi:10.3390/ijms141020682
Received: 19 August 2013 / Revised: 23 September 2013 / Accepted: 30 September 2013 / Published: 15 October 2013
Cited by 2 | PDF Full-text (435 KB) | HTML Full-text | XML Full-text
Abstract
In order to improve the thermal properties of important engineering plastics, a novel kind of liquid crystalline epoxy resin (LCER), 3,3',5,5' -Tetramethylbiphenyl-4,4' -diyl bis(4-(oxiran-2-ylmethoxy)benzoate) (M1) was introduced to blend with nylon 66 (M2) at high temperature. The effects of [...] Read more.
In order to improve the thermal properties of important engineering plastics, a novel kind of liquid crystalline epoxy resin (LCER), 3,3',5,5' -Tetramethylbiphenyl-4,4' -diyl bis(4-(oxiran-2-ylmethoxy)benzoate) (M1) was introduced to blend with nylon 66 (M2) at high temperature. The effects of M1 on chemical modification and crystallite morphology of M2 were investigated by rheometry, thermo gravimetric analysis (TGA), dynamic differential scanning calorimetry (DSC) and polarized optical microscopy (POM). TGA results showed that the initial decomposition temperature of M2 increased by about 8 °C by adding 7% wt M1, indicating the improvement of thermal stability. DSC results illustrated that the melting point of composites decreased by 12 °C compared to M2 as the content of M1 increased, showing the improvement of processing property. POM measurements confirmed that dimension of nylon-66 spherulites and crystallization region decreased because of the addition of liquid crystalline epoxy M1. Full article
Open AccessArticle Molecular Cloning and Characterization of the Calcineurin Subunit A from Plutella xylostella
Int. J. Mol. Sci. 2013, 14(10), 20692-20703; doi:10.3390/ijms141020692
Received: 20 August 2013 / Revised: 25 September 2013 / Accepted: 27 September 2013 / Published: 15 October 2013
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Abstract
Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This [...] Read more.
Calcineurin (or PP2B) has been reported to be involved in an array of physiological process in insects, and the calcineurin subunit A (CNA) plays a central role in calcineurin activity. We cloned the CNA gene from Plutella xylostella (PxCNA). This gene contains an ORF of 1488 bp that encodes a 495 amino acid protein, showing 98%, and 80% identities to the CNA of Bombyx mori, and humans respectively. The full-length of PxCNA and its catalytic domain (CNA1–341, defined as PxCNα) were both expressed in Escherichia coli. Purified recombinant PxCNA displayed no phosphatase activity, whereas recombinant PxCNα showed high phosphatase activity with a Km of 4.6 mM and a kcat of 0.66 S−1 against pNPP. It could be activated at different degrees by Mn2+, Ni2+, Mg2+, and Ca2+. The optimum reaction pH was about 7.5 and the optimum reaction temperature was around 45 °C. An in vitro inhibition assay showed that okadaic acid (OA) and cantharidin (CTD) competitively inhibited recombinant PxCNα activity with the IC50 values of 8.95 μM and 77.64 μM, respectively. However, unlike previous reports, pyrethroid insecticides were unable to inhibit recombinant PxCNα, indicating that the P. xylostella calcineurin appears not to be sensitive to class II pyrethroid insecticides. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Supramolecular Interactions of Terpyridine-Derived Cores of Metallomesogen Precursors
Int. J. Mol. Sci. 2013, 14(10), 20729-20743; doi:10.3390/ijms141020729
Received: 13 August 2013 / Revised: 22 September 2013 / Accepted: 22 September 2013 / Published: 15 October 2013
Cited by 2 | PDF Full-text (557 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Use of Hirshfeld surfaces calculated from crystal structure determinations on various transition metal ion complexes of three terpyridine ligands carrying trimethoxyphenyl substituents has enabled an assessment of the contribution made by the ligand components to the interactions determining the lattice structures, interactions [...] Read more.
Use of Hirshfeld surfaces calculated from crystal structure determinations on various transition metal ion complexes of three terpyridine ligands carrying trimethoxyphenyl substituents has enabled an assessment of the contribution made by the ligand components to the interactions determining the lattice structures, interactions expected also to be present in metallomesogens derived from similar ligands. The form of the link joining the trimethoxyphenyl substituent to the 4' position of 2,2';6',2''-terpyridine is of some importance. In the case of the Co(II) complexes of two of the ligands, their spin-crossover characteristics can be rationalised in terms of the different interactions seen in their lattices. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Application of Supramolecular Systems)
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Open AccessArticle Molecular Cloning, Sequence Characterization and Expression Analysis of a CD63 Homologue from the Coleopteran Beetle, Tenebrio molitor
Int. J. Mol. Sci. 2013, 14(10), 20744-20767; doi:10.3390/ijms141020744
Received: 6 September 2013 / Revised: 27 September 2013 / Accepted: 3 October 2013 / Published: 15 October 2013
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Abstract
CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from larvae of a coleopteran beetle, Tenebrio molitor. [...] Read more.
CD63, a member of the tetraspanin membrane protein family, plays a pivotal role in cell growth, motility, signal transduction, host-pathogen interactions and cancer. In this work, the cDNA encoding CD63 homologue (TmCD63) was cloned from larvae of a coleopteran beetle, Tenebrio molitor. The cDNA is comprised of an open reading frame of 705 bp, encoding putative protein of 235 amino acid residues. In silico analysis shows that the protein has four putative transmembrane domains and one large extracellular loop. The characteristic “Cys-Cys-Gly” motif and “Cys188” residues are highly conserved in the large extracellular loop. Phylogenetic analysis of TmCD63 revealed that they belong to the insect cluster with 50%–56% identity. Analysis of spatial expression patterns demonstrated that TmCD63 mRNA is mainly expressed in gut and Malphigian tubules of larvae and the testis of the adult. Developmental expression patterns of CD63 mRNA showed that TmCD63 transcripts are detected in late larval, pupal and adult stages. Interestingly, TmCD63 transcripts are upregulated to the maximum level of 4.5 fold, in response to DAP-type peptidoglycan during the first 6 h, although other immune elicitors also caused significant increase to the transcript level at later time-points. These results suggest that CD63 might contribute to T. molitor immune response against various microbial pathogens. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Crosstalk between Beta-Catenin and Snail in the Induction of Epithelial to Mesenchymal Transition in Hepatocarcinoma: Role of the ERK1/2 Pathway
Int. J. Mol. Sci. 2013, 14(10), 20768-20792; doi:10.3390/ijms141020768
Received: 9 July 2013 / Revised: 23 September 2013 / Accepted: 3 October 2013 / Published: 16 October 2013
Cited by 17 | PDF Full-text (1241 KB) | HTML Full-text | XML Full-text
Abstract
Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. [...] Read more.
Epithelial to mesenchymal transition (EMT) is an integral process in the progression of many epithelial tumors. It involves a coordinated series of events, leading to the loss of epithelial features and the acquisition of a mesenchymal phenotype, resulting in invasion and metastasis. The EMT of hepatocellular carcinoma (HCC) cells is thought to be a key event in intrahepatic dissemination and distal metastasis. In this study, we used 12-O-tet-radecanoylphorbol-13-acetate (TPA) to dissect the signaling pathways involved in the EMT of HepG2 hepatocarcinoma cells. The spectacular change in phenotype induced by TPA, leading to a pronounced spindle-shaped fibroblast-like cell morphology, required ERK1/2 activation. This ERK1/2-dependent EMT process was characterized by a loss of E-cadherin function, modification of the cytoskeleton, the acquisition of mesenchymal markers and profound changes to extracellular matrix composition and mobility. Snail was essential for E-cadherin repression, but was not sufficient for full commitment of the TPA-triggered EMT. We found that TPA triggered the formation of a complex between Snail and β-catenin that activated the Wnt pathway. This study thus provides the first evidence for the existence of a complex network governed by the ERK1/2 signaling pathway, converging on the coregulation of Snail and the Wnt/β-catenin pathway and responsible for the onset and the progression of EMT in hepatocellular carcinoma cells. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
Open AccessArticle Ultrastructural Analysis of Nanogold-Labeled Cell Surface Microvilli in Liquid by Atmospheric Scanning Electron Microscopy and Their Relevance in Cell Adhesion
Int. J. Mol. Sci. 2013, 14(10), 20809-20819; doi:10.3390/ijms141020809
Received: 6 September 2013 / Revised: 6 October 2013 / Accepted: 7 October 2013 / Published: 16 October 2013
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Abstract
The adhesion of leukocytes circulating in the blood to vascular endothelium is critical for their trafficking in the vasculature, and CD44 is an important cell surface receptor for rolling adhesion. In this study, we demonstrate the correlative observation of CD44 distribution at [...] Read more.
The adhesion of leukocytes circulating in the blood to vascular endothelium is critical for their trafficking in the vasculature, and CD44 is an important cell surface receptor for rolling adhesion. In this study, we demonstrate the correlative observation of CD44 distribution at the lymphocyte cell surface in liquid by fluorescence optical microscopy and immuno-electron microscopy using an atmospheric scanning electron microscope (ASEM). The ultrastructure of the cell surface was clearly imaged by ASEM using positively charged Nanogold particles. ASEM analysis demonstrated microvilli projections around the cell surface and the localization of CD44 on the microvilli. Treatment of cells with cytochalasin D resulted in a loss of the microvilli projections and concomitantly abrogated CD44-mediated adhesion to its ligand hyaluronan. These results suggest the functional relevance of microvilli in CD44-mediated rolling adhesion under shear flow. Full article
(This article belongs to the Special Issue Frontiers of Micro-Spectroscopy in Biological Applications)
Open AccessArticle Identification of Novel MicroRNAs in Primates by Using the Synteny Information and Small RNA Deep Sequencing Data
Int. J. Mol. Sci. 2013, 14(10), 20820-20832; doi:10.3390/ijms141020820
Received: 16 July 2013 / Revised: 22 September 2013 / Accepted: 9 October 2013 / Published: 16 October 2013
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Abstract
Current technologies that are used for genome-wide microRNA (miRNA) prediction are mainly based on BLAST tool. They often produce a large number of false positives. Here, we describe an effective approach for identifying orthologous pre-miRNAs in several primates based on syntenic information. [...] Read more.
Current technologies that are used for genome-wide microRNA (miRNA) prediction are mainly based on BLAST tool. They often produce a large number of false positives. Here, we describe an effective approach for identifying orthologous pre-miRNAs in several primates based on syntenic information. Some of them have been validated by small RNA high throughput sequencing data. This approach uses the synteny information and experimentally validated miRNAs of human, and incorporates currently available algorithms and tools to identify the pre-miRNAs in five other primates. First, we identified 929 potential pre-miRNAs in the marmoset in which miRNAs have not yet been reported. Then, we predicted the miRNAs in other primates, and we successfully re-identified most of the published miRNAs and found 721, 979, 650 and 639 new potential pre-miRNAs in chimpanzee, gorilla, orangutan and rhesus macaque, respectively. Furthermore, the miRNA transcriptome in the four primates have been re-analyzed and some novel predicted miRNAs have been supported by the small RNA sequencing data. Finally, we analyzed the potential functions of those validated miRNAs and explored the regulatory elements and transcription factors of some validated miRNA genes of interest. The results show that our approach can effectively identify novel miRNAs and some miRNAs that supported by small RNA sequencing data maybe play roles in the nervous system. Full article
(This article belongs to the Section Molecular Diagnostics)
Open AccessArticle Lentivirus-Mediated ERK2 siRNA Reduces Joint Capsule Fibrosis in a Rat Model of Post-Traumatic Joint Contracture
Int. J. Mol. Sci. 2013, 14(10), 20833-20844; doi:10.3390/ijms141020833
Received: 28 May 2013 / Revised: 25 September 2013 / Accepted: 30 September 2013 / Published: 17 October 2013
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Abstract
Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after [...] Read more.
Extracellular signal-regulated kinase (ERK)-2 is presumed to play an important role in the development of post-traumatic joint contractures. Using a rat injury model, we investigated whether treatment with ERK2 small interfering RNA (siRNA) could reduce the extent of joint capsule fibrosis after an induced injury. Rats were separated into three groups (n = 32 each): non-operated control group, operated contracture group and contracture-treatment group. Stable post-traumatic joint contracture was created through surgical intra-articular joint injury followed by eight weeks of immobilization. In the contracture-treatment group, the rats were treated with lentivirus (LV)-mediated ERK2 siRNA at days 3 and 7 post-surgery. The posterior joint capsule was assessed by western blotting, immunohistochemistry and biochemical analysis for changes in ERK2, phosphorylated (p)-ERK2, myofibroblast, total collagen and relative collagen Type III expression level. Biomechanical testing was used to assess the development of flexion contractures. Statistical analysis was performed using an analysis of variance. In the operated contracture group, rats that developed flexion contractures also showed elevated phosphorylated p-ERK2 expression. In the contracture-treatment group, ERK2 siRNA significantly reduced p-ERK2 expression levels, as well as the severity of flexion contracture development (p < 0.01). Myofibroblast numbers and measurements of total collagen content were also significantly reduced following ERK2 siRNA (p < 0.01). Relative collagen type III expression as a proportion of total of Types I and III collagen, however, was significantly increased in response to ERK2 siRNA (p < 0.01). Our findings demonstrate a role for ERK2 in the induction of joint capsule fibrosis after injury. Furthermore, we show that development of flexion contractures and the resultant increase of joint capsule fibrosis can be reduced by LV-mediated ERK2 siRNA treatment. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Serial Changes of Serum Growth Factor Levels and Liver Regeneration after Partial Hepatectomy in Healthy Humans
Int. J. Mol. Sci. 2013, 14(10), 20877-20889; doi:10.3390/ijms141020877
Received: 28 August 2013 / Revised: 8 October 2013 / Accepted: 14 October 2013 / Published: 17 October 2013
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Abstract
This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various [...] Read more.
This study aimed to investigate the associations of the serial changes of serum levels of various growth factors with liver regeneration after hepatectomy in healthy liver donors. Sixteen healthy liver donors who underwent conventional liver resection were included. Serum levels of various growth factors before hepatectomy and on postoperative day (POD) 1, 3, 5 and 7 were measured. Liver volume data calculated by multi-detector computed tomography using workstation. The ratio of remnant liver volume on POD 0 to liver volume before the operation was 51% ± 20%. The ratio of liver volume on POD 14 to liver volume on POD 0 were inversely correlated with remnant liver volume on POD 0 (r = −0.91). The ratio of liver volume on POD 14 to liver volume on POD 0 were significantly correlated with serum hepatocyte growth factor (HGF) levels on POD 1 (r = 0.54), serum leptin levels on POD 1 (r = 0.54), and serum macrophage colony-stimulating factor (M-CSF) levels on POD 5 (r = 0.76) and POD 7 (r = 0.80). These results suggest that early-phase elevation of serum levels of HGF, leptin and M-CSF may be associated with the acceleration of liver regeneration after hepatectomy in humans. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
Open AccessArticle Overexpression of Ferredoxin, PETF, Enhances Tolerance to Heat Stress in Chlamydomonas reinhardtii
Int. J. Mol. Sci. 2013, 14(10), 20913-20929; doi:10.3390/ijms141020913
Received: 31 August 2013 / Revised: 10 October 2013 / Accepted: 11 October 2013 / Published: 17 October 2013
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Abstract
Reactive oxygen species (ROS) produced by plants in adverse environments can cause damage to organelles and trigger cell death. Removal of excess ROS can be achieved through the ascorbate scavenger pathway to prevent plant cell death. The amount of this scavenger can [...] Read more.
Reactive oxygen species (ROS) produced by plants in adverse environments can cause damage to organelles and trigger cell death. Removal of excess ROS can be achieved through the ascorbate scavenger pathway to prevent plant cell death. The amount of this scavenger can be regulated by ferredoxin (FDX). Chloroplastic FDXs are electron transfer proteins that perform in distributing photosynthetic reducing power. In this study, we demonstrate that overexpression of the endogenous photosynthetic FDX gene, PETF, in Chlamydomonas reinhardtii could raise the level of reduced ascorbate and diminish H2O2 levels under normal growth conditions. Furthermore, the overexpressing PETF transgenic Chlamydomonas lines produced low levels of H2O2 and exhibited protective effects that were observed through decreased chlorophyll degradation and increased cell survival under heat-stress conditions. The findings of this study suggest that overexpression of PETF can increase the efficiency of ROS scavenging in chloroplasts to confer heat tolerance. The roles of PETF in the downregulation of the ROS level offer a method for potentially improving the tolerance of crops against heat stress. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Pesticide Removal from Aqueous Solutions by Adding Salting Out Agents
Int. J. Mol. Sci. 2013, 14(10), 20954-20965; doi:10.3390/ijms141020954
Received: 16 September 2013 / Revised: 12 October 2013 / Accepted: 12 October 2013 / Published: 18 October 2013
Cited by 5 | PDF Full-text (432 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Phase segregation in aqueous biphasic systems (ABS) composed of four hydrophilic ionic liquids (ILs): 1-butyl-3-methylimidazolium methylsulfate and 1-ethyl-3-methylimidazolium methylsulfate (CnC1im C1SO4, n = 2 and 4), tributylmethyl phosphonium methylsulfate (P4441 C1SO [...] Read more.
Phase segregation in aqueous biphasic systems (ABS) composed of four hydrophilic ionic liquids (ILs): 1-butyl-3-methylimidazolium methylsulfate and 1-ethyl-3-methylimidazolium methylsulfate (CnC1im C1SO4, n = 2 and 4), tributylmethyl phosphonium methylsulfate (P4441 C1SO4) and methylpyridinium methylsulfate (C1Py C1SO4) and two high charge density potassium inorganic salts (K2CO3 and K2HPO4) were determined by the cloud point method at 298.15 K. The influence of the addition of the selected inorganic salts to aqueous mixtures of ILs was discussed in the light of the Hofmeister series and in terms of molar Gibbs free energy of hydration. The effect of the alkyl chain length of the cation on the methylsulfate-based ILs has been investigated. All the solubility data were satisfactorily correlated to several empirical equations. A pesticide (pentachlorophenol, PCP) extraction process based on the inorganic salt providing a greater salting out effect was tackled. The viability of the proposed process was analyzed in terms of partition coefficients and extraction efficiencies. Full article
(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)
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Open AccessArticle DNA Damage Induced MutS Homologue hMSH4 Acetylation
Int. J. Mol. Sci. 2013, 14(10), 20966-20982; doi:10.3390/ijms141020966
Received: 21 August 2013 / Revised: 16 September 2013 / Accepted: 8 October 2013 / Published: 18 October 2013
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Abstract
Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by [...] Read more.
Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing radiation (IR). To determine which acetyltransferases are responsible for hMSH4 acetylation in response to DNA damage, potential interactions of hMSH4 with hTip60, hGCN5, and hMof were analyzed. The results of these experiments indicate that only hMof interacts with hMSH4 in a DNA damage-dependent manner. Intriguingly, the interplay between hMSH4 and hMof manipulates the outcomes of nonhomologous end joining (NHEJ)-mediated DNA double strand break (DSB) repair and thereby controls cell survival in response to IR. This study also shows that hMSH4 interacts with HDAC3, by which HDAC3 negatively regulates the levels of hMSH4 acetylation. Interestingly, elevated levels of HDAC3 correlate with increased NHEJ-mediated DSB repair, suggesting that hMSH4 acetylation per se may not directly affect the role of hMSH4 in DSB repair. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Differences in the Structure of the Gut Bacteria Communities in Development Stages of the Chinese White Pine Beetle (Dendroctonus armandi)
Int. J. Mol. Sci. 2013, 14(10), 21006-21020; doi:10.3390/ijms141021006
Received: 10 September 2013 / Revised: 12 October 2013 / Accepted: 14 October 2013 / Published: 18 October 2013
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Abstract
The Chinese white pine beetle Dendroctonus armandi Tsai and Li, is arguably the most destructive forest insect in the Qinling Mountains in Northern China. Little is known about the structure of the bacterial communities associated with D. armandi even though this [...] Read more.
The Chinese white pine beetle Dendroctonus armandi Tsai and Li, is arguably the most destructive forest insect in the Qinling Mountains in Northern China. Little is known about the structure of the bacterial communities associated with D. armandi even though this wood-boring insect plays important roles in ecosystem and biological invasion processes that result in huge economic losses in pine forests. The aim of this study was to investigate the composition of the bacterial communities present in the guts of D. armandi at different developmental stages using a culture-independent method involving PCR-denaturing gradient gel electrophoresis (DGGE). Analysis of PCR-amplified 16S rRNA gene fragments of bacteria from the guts of larvae, pupae, and male and female adults revealed bacterial communities of low complexity that differed according to the developmental stage. Citrobacter spp. and Pantoea spp. predominated in larvae and adults, whereas Methylobacterium was the dominant genus at the pupal stage. The main difference between the guts of male and female adults was the greater dominance of Citrobacter in females. Previous studies suggest that the bacterial community associated with D. armandi guts may influence insect development. The data obtained in this study regarding the phylogenetic relationships and the community structure of intestinal bacteria at different developmental stages of the D. armandi life cycle contribute to our understanding of D. armandi and could aid the development of new pest control strategies. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle The Influence of Silica Nanoparticles on Ionic Liquid Behavior: A Clear Difference between Adsorption and Confinement
Int. J. Mol. Sci. 2013, 14(10), 21045-21052; doi:10.3390/ijms141021045
Received: 12 August 2013 / Revised: 26 September 2013 / Accepted: 29 September 2013 / Published: 18 October 2013
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Abstract
The phase behaviors of ionic liquids (ILs) confined in nanospace and adsorbed on outer surface of nanoparticles are expected to be different from those of the bulk. Anomalous phase behaviors of room temperature ionic liquid tributylhexadecylphosphonium bromide (P44416Br) confined in [...] Read more.
The phase behaviors of ionic liquids (ILs) confined in nanospace and adsorbed on outer surface of nanoparticles are expected to be different from those of the bulk. Anomalous phase behaviors of room temperature ionic liquid tributylhexadecylphosphonium bromide (P44416Br) confined in ordered mesoporous silica nanoparticles with average pore size 3.7 nm and adsorbed on outer surface of the same silica nanoparticles were reported. It was revealed that the melting points (Tm) of confined and adsorbed ILs depressed significantly in comparison with the bulk one. The Tm depressions for confined and adsorbed ILs are 8 °C and 14 °C, respectively. For comparison with the phase behavior of confined P44416Br, 1-butyl-3-methylimidazolium bromide (BmimBr) was entrapped within silica nanopores, we observed an enhancement of 50 °C in Tm under otherwise similar conditions. The XRD analysis indicates the formation of crystalline-like phase under confinement, in contrast to the amorphous phase in adsorbed IL. It was confirmed that the behavior of IL has clear difference. Moreover, the complex π-π stacking and H-bonding do not exist in the newly proposed phosphonium-based IL in comparison with the widely studied imidazolium-based IL. The opposite change in melting point of P44416Br@SiO2 and BmimBr@SiO2 indicates that the cationic species plays an important role in the variation of melting point. Full article
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Open AccessArticle A Genome-Wide Expression Profile of Salt-Responsive Genes in the Apple Rootstock Malus zumi
Int. J. Mol. Sci. 2013, 14(10), 21053-21070; doi:10.3390/ijms141021053
Received: 10 July 2013 / Revised: 9 August 2013 / Accepted: 23 September 2013 / Published: 18 October 2013
Cited by 8 | PDF Full-text (950 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In some areas of cultivation, a lack of salt tolerance severely affects plant productivity. Apple, Malus x domestica Borkh., is sensitive to salt, and, as a perennial woody plant the mechanism of salt stress adaption will be different from that of annual [...] Read more.
In some areas of cultivation, a lack of salt tolerance severely affects plant productivity. Apple, Malus x domestica Borkh., is sensitive to salt, and, as a perennial woody plant the mechanism of salt stress adaption will be different from that of annual herbal model plants, such as Arabidopsis. Malus zumi is a salt tolerant apple rootstock, which survives high salinity (up to 0.6% NaCl). To examine the mechanism underlying this tolerance, a genome-wide expression analysis was performed, using a cDNA library constructed from salt-treated seedlings of Malus zumi. A total of 15,000 cDNA clones were selected for microarray analysis. In total a group of 576 cDNAs, of which expression changed more than four-fold, were sequenced and 18 genes were selected to verify their expression pattern under salt stress by semi-quantitative RT-PCR. Our genome-wide expression analysis resulted in the isolation of 50 novel Malus genes and the elucidation of a new apple-specific mechanism of salt tolerance, including the stabilization of photosynthesis under stress, involvement of phenolic compounds, and sorbitol in ROS scavenging and osmoprotection. The promoter regions of 111 genes were analyzed by PlantCARE, suggesting an intensive cross-talking of abiotic stress in Malus zumi. An interaction network of salt responsive genes was constructed and molecular regulatory pathways of apple were deduced. Our research will contribute to gene function analysis and further the understanding of salt-tolerance mechanisms in fruit trees. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessArticle Crosstalk between Delta Opioid Receptor and Nerve Growth Factor Signaling Modulates Neuroprotection and Differentiation in Rodent Cell Models
Int. J. Mol. Sci. 2013, 14(10), 21114-21139; doi:10.3390/ijms141021114
Received: 15 August 2013 / Revised: 16 September 2013 / Accepted: 26 September 2013 / Published: 21 October 2013
Cited by 4 | PDF Full-text (1185 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve [...] Read more.
Both opioid signaling and neurotrophic factor signaling have played an important role in neuroprotection and differentiation in the nervous system. Little is known about whether the crosstalk between these two signaling pathways will affect neuroprotection and differentiation. Previously, we found that nerve growth factor (NGF) could induce expression of the delta opioid receptor gene (Oprd1, dor), mainly through PI3K/Akt/NF-κB signaling in PC12h cells. In this study, using two NGF-responsive rodent cell model systems, PC12h cells and F11 cells, we found the delta opioid neuropeptide [D-Ala2, D-Leu5] enkephalin (DADLE)-mediated neuroprotective effect could be blocked by pharmacological reagents: the delta opioid antagonist naltrindole, PI3K inhibitor LY294002, MAPK inhibitor PD98059, and Trk inhibitor K252a, respectively. Western blot analysis revealed that DADLE activated both the PI3K/Akt and MAPK pathways in the two cell lines. siRNA Oprd1 gene knockdown experiment showed that the upregulation of NGF mRNA level was inhibited with concomitant inhibition of the survival effects of DADLE in the both cell models. siRNA Oprd1 gene knockdown also attenuated the DADLE-mediated neurite outgrowth in PC12h cells as well as phosphorylation of MAPK and Akt in PC12h and F11 cells, respectively. These data together strongly suggest that delta opioid peptide DADLE acts through the NGF-induced functional G protein-coupled Oprd1 to provide its neuroprotective and differentiating effects at least in part by regulating survival and differentiating MAPK and PI3K/Akt signaling pathways in NGF-responsive rodent neuronal cells. Full article
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
Open AccessArticle The Effect on Proliferation and Differentiation of Cementoblast by Using Sclerostin as Inhibitor
Int. J. Mol. Sci. 2013, 14(10), 21140-21152; doi:10.3390/ijms141021140
Received: 13 September 2013 / Revised: 15 October 2013 / Accepted: 15 October 2013 / Published: 21 October 2013
Cited by 4 | PDF Full-text (2255 KB) | HTML Full-text | XML Full-text
Abstract
Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. [...] Read more.
Cementogenesis is of great importance for normal teeth root development and is involved in the repair process of root resorption caused by orthodontic treatment. As highly differentiated mesenchymal cells, cementoblasts are responsible for this process under the regulation of many endogenous agents. Among these molecules, sclerostin has been much investigated recently for its distinct antagonism effect on bone metabolism. Encoded by the sost gene, sclerostin is expressed in osteocytes and cementocytes of cellular cementum. it is still unclear. In the current study, we investigated the effects of sclerostin on the processes of proliferation and differentiation; a series of experiments including MTT, apoptosis examination, alkaline phosphatase (ALP) activity, gene analysis, and alizarin red staining were carried out to evaluate the proliferation and differentiation of cementoblasts. Protein expression including osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were also checked to analyze changes in osteoclastogenesis. Results show that sclerostin inhibits cementoblasts proliferation and differentiation, and promotes osteoclastogenesis. Interestingly, the monoclonal antibody for sclerostin has shown positive effects on osteoporosis, indicating that it may facilitate cementogenesis and benefit the treatment of cementum related diseases. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Open AccessArticle Identification of Combined Genetic Determinants of Liver Stiffness within the SREBP1c-PNPLA3 Pathway
Int. J. Mol. Sci. 2013, 14(10), 21153-21166; doi:10.3390/ijms141021153
Received: 27 August 2013 / Revised: 15 October 2013 / Accepted: 16 October 2013 / Published: 22 October 2013
Cited by 8 | PDF Full-text (286 KB) | HTML Full-text | XML Full-text
Abstract
The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association [...] Read more.
The common PNPLA3 (adiponutrin) variant, p.I148M, was identified as a genetic determinant of liver fibrosis. Since the expression of PNPLA3 is induced by sterol regulatory element binding protein 1c (SREBP1c), we investigate two common SREBP1c variants (rs2297508 and rs11868035) for their association with liver stiffness. In 899 individuals (aged 17–83 years, 547 males) with chronic liver diseases, hepatic fibrosis was non-invasively phenotyped by transient elastography (TE). The SREBP1c single nucleotide polymorphisms (SNPs) were genotyped using PCR-based assays with 5'-nuclease and fluorescence detection. The SREBP1c rs11868035 variant affected liver fibrosis significantly (p = 0.029): median TE levels were 7.2, 6.6 and 6.0 kPa in carriers of (TT) (n = 421), (CT) (n = 384) and (CC) (n = 87) genotypes, respectively. Overall, the SREBP1c SNP was associated with low TE levels (5.0–8.0 kPa). Carriers of both PNPLA3 and SREBP1c risk genotypes displayed significantly (p = 0.005) higher median liver stiffness, as compared to patients carrying none of these variants. The common SREBP1c variant may affect early stages of liver fibrosis. Our study supports a role of the SREBP1c-PNPLA3 pathway as a “disease module” that promotes hepatic fibrogenesis. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
Open AccessArticle Multivalent Protein Assembly Using Monovalent Self-Assembling Building Blocks
Int. J. Mol. Sci. 2013, 14(10), 21189-21201; doi:10.3390/ijms141021189
Received: 15 August 2013 / Revised: 13 September 2013 / Accepted: 8 October 2013 / Published: 22 October 2013
Cited by 1 | PDF Full-text (1608 KB) | HTML Full-text | XML Full-text
Abstract
Discotic molecules, which self-assemble in water into columnar supramolecular polymers, emerged as an alternative platform for the organization of proteins. Here, a monovalent discotic decorated with one single biotin was synthesized to study the self-assembling multivalency of this system in regard to [...] Read more.
Discotic molecules, which self-assemble in water into columnar supramolecular polymers, emerged as an alternative platform for the organization of proteins. Here, a monovalent discotic decorated with one single biotin was synthesized to study the self-assembling multivalency of this system in regard to streptavidin. Next to tetravalent streptavidin, monovalent streptavidin was used to study the protein assembly along the supramolecular polymer in detail without the interference of cross-linking. Upon self-assembly of the monovalent biotinylated discotics, multivalent proteins can be assembled along the supramolecular polymer. The concentration of discotics, which influences the length of the final polymers at the same time dictates the amount of assembled proteins. Full article
(This article belongs to the Special Issue Synthesis, Characterization and Application of Supramolecular Systems)

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Open AccessReview EGFR-Ras-Raf Signaling in Epidermal Stem Cells: Roles in Hair Follicle Development, Regeneration, Tissue Remodeling and Epidermal Cancers
Int. J. Mol. Sci. 2013, 14(10), 19361-19384; doi:10.3390/ijms141019361
Received: 11 July 2013 / Revised: 12 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
Cited by 7 | PDF Full-text (532 KB) | HTML Full-text | XML Full-text
Abstract
The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While [...] Read more.
The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review, we briefly discuss the properties of the epidermal stem cells and review the role of EGFR-Ras-Raf signaling in keratinocyte stem cells during homeostatic and pathological conditions. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessReview Keratin K15 as a Biomarker of Epidermal Stem Cells
Int. J. Mol. Sci. 2013, 14(10), 19385-19398; doi:10.3390/ijms141019385
Received: 21 June 2013 / Revised: 5 September 2013 / Accepted: 10 September 2013 / Published: 25 September 2013
Cited by 11 | PDF Full-text (445 KB) | HTML Full-text | XML Full-text
Abstract
Keratin 15 (K15) is type I keratin protein co-expressed with the K5/K14 pair present in the basal keratinocytes of all stratified epithelia. Although it is a minor component of the cytoskeleton with a variable expression pattern, nonetheless its expression has been reported [...] Read more.
Keratin 15 (K15) is type I keratin protein co-expressed with the K5/K14 pair present in the basal keratinocytes of all stratified epithelia. Although it is a minor component of the cytoskeleton with a variable expression pattern, nonetheless its expression has been reported as a stem cell marker in the bulge of hair follicles. Conversely, suprabasal expression of K15 has also been reported in both normal and diseased tissues, which is inconsistent with its role as a stem cell marker. Our recently published work has given evidence of the molecular pathways that seem to control the expression of K15 in undifferentiated and differentiated cells. In this article, we have critically reviewed the published work to establish the reliability of K15 as an epidermal stem cell marker. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessReview Mechanisms of Chemical Carcinogenesis in the Kidneys
Int. J. Mol. Sci. 2013, 14(10), 19416-19433; doi:10.3390/ijms141019416
Received: 2 May 2013 / Revised: 5 September 2013 / Accepted: 9 September 2013 / Published: 25 September 2013
Cited by 4 | PDF Full-text (465 KB) | HTML Full-text | XML Full-text
Abstract
Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the [...] Read more.
Chemical carcinogens are substances which induce malignant tumours, increase their incidence or decrease the time taken for tumour formation. Often, exposure to chemical carcinogens results in tissue specific patterns of tumorigenicity. The very same anatomical, biochemical and physiological specialisations which permit the kidney to perform its vital roles in maintaining tissue homeostasis may in fact increase the risk of carcinogen exposure and contribute to the organ specific carcinogenicity observed with numerous kidney carcinogens. This review will address the numerous mechanisms which play a role in the concentration, bioactivation, and uptake of substances from both the urine and blood which significantly increase the risk of cancer in the kidney. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Organ-Specific Toxicity)
Open AccessReview Molecular Research in Penile Cancer—Lessons Learned from the Past and Bright Horizons of the Future?
Int. J. Mol. Sci. 2013, 14(10), 19494-19505; doi:10.3390/ijms141019494
Received: 19 July 2013 / Revised: 11 September 2013 / Accepted: 12 September 2013 / Published: 26 September 2013
Cited by 2 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
Penile cancer is a rare tumor. There is a limited understanding of the biological mediators of prognostic and therapeutic importance in penile cancer. However, there exists some fundamental understanding of the major pathways involved in the development of penile pre-neoplastic lesions and [...] Read more.
Penile cancer is a rare tumor. There is a limited understanding of the biological mediators of prognostic and therapeutic importance in penile cancer. However, there exists some fundamental understanding of the major pathways involved in the development of penile pre-neoplastic lesions and neoplasms. The aim of the present review is to highlight our current state of molecular knowledge in penile cancer to foster the necessary tools for researchers to pave major advancements in our current treatment paradigms and cancer specific outcomes. Full article
(This article belongs to the Special Issue Molecular Research in Urology)
Open AccessReview Single Molecule Studies on Dynamics in Liquid Crystals
Int. J. Mol. Sci. 2013, 14(10), 19506-19525; doi:10.3390/ijms141019506
Received: 15 August 2013 / Revised: 11 September 2013 / Accepted: 12 September 2013 / Published: 26 September 2013
Cited by 5 | PDF Full-text (2724 KB) | HTML Full-text | XML Full-text
Abstract
Single molecule (SM) methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC). Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion [...] Read more.
Single molecule (SM) methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC). Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion caused by the guest molecules. The anisotropic structure of LC materials is used to retrieve specific conformation related properties of larger guest molecules like conjugated polymers. This in particular sheds light on organization mechanisms within biological cells, where large molecules are found in nematic LC surroundings. This review gives a short overview related to the application of highly sensitive SM detection schemes in LC. Full article
Open AccessReview Advanced Knowledge of Three Important Classes of Grape Phenolics: Anthocyanins, Stilbenes and Flavonols
Int. J. Mol. Sci. 2013, 14(10), 19651-19669; doi:10.3390/ijms141019651
Received: 17 July 2013 / Revised: 11 September 2013 / Accepted: 12 September 2013 / Published: 27 September 2013
Cited by 44 | PDF Full-text (319 KB) | HTML Full-text | XML Full-text
Abstract
Grape is qualitatively and quantitatively very rich in polyphenols. In particular, anthocyanins, flavonols and stilbene derivatives play very important roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins are responsible for the color of red grapes and wines and confer organoleptic [...] Read more.
Grape is qualitatively and quantitatively very rich in polyphenols. In particular, anthocyanins, flavonols and stilbene derivatives play very important roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins are responsible for the color of red grapes and wines and confer organoleptic characteristics on the wine. They are used for chemotaxonomic studies and to evaluate the polyphenolic ripening stage of grape. They are natural colorants, have antioxidant, antimicrobial and anticarcinogenic activity, exert protective effects on the human cardiovascular system, and are used in the food and pharmaceutical industries. Stilbenes are vine phytoalexins present in grape berries and associated with the beneficial effects of drinking wine. The principal stilbene, resveratrol, is characterized by anticancer, antioxidant, anti-inflammatory and cardioprotective activity. Resveratrol dimers and oligomers also occur in grape, and are synthetized by the vine as active defenses against exogenous attack, or produced by extracellular enzymes released from pathogens in an attempt to eliminate undesirable toxic compounds. Flavonols are a ubiquitous class of flavonoids with photo-protection and copigmentation (together with anthocyanins) functions. The lack of expression of the enzyme flavonoid 3',5'-hydroxylase in white grapes restricts the presence of these compounds to quercetin, kaempferol and isorhamnetin derivatives, whereas red grapes usually also contain myricetin, laricitrin and syringetin derivatives. In the last ten years, the technological development of analytical instrumentation, particularly mass spectrometry, has led to great improvements and further knowledge of the chemistry of these compounds. In this review, the biosynthesis and biological role of these grape polyphenols are briefly introduced, together with the latest knowledge of their chemistry. Full article
(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism)
Open AccessReview Non-Coding RNAs in Muscle Dystrophies
Int. J. Mol. Sci. 2013, 14(10), 19681-19704; doi:10.3390/ijms141019681
Received: 5 August 2013 / Revised: 5 September 2013 / Accepted: 9 September 2013 / Published: 30 September 2013
Cited by 10 | PDF Full-text (287 KB) | HTML Full-text | XML Full-text
Abstract
ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and [...] Read more.
ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
Open AccessReview Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions
Int. J. Mol. Sci. 2013, 14(10), 19731-19762; doi:10.3390/ijms141019731
Received: 31 July 2013 / Revised: 4 September 2013 / Accepted: 10 September 2013 / Published: 30 September 2013
Cited by 16 | PDF Full-text (565 KB) | HTML Full-text | XML Full-text
Abstract
Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer [...] Read more.
Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
Open AccessReview Interplay between Cartilage and Subchondral Bone Contributing to Pathogenesis of Osteoarthritis
Int. J. Mol. Sci. 2013, 14(10), 19805-19830; doi:10.3390/ijms141019805
Received: 30 August 2013 / Revised: 17 September 2013 / Accepted: 23 September 2013 / Published: 30 September 2013
Cited by 25 | PDF Full-text (492 KB) | HTML Full-text | XML Full-text
Abstract
Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt [...] Read more.
Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
Open AccessReview Development of Nonalcoholic Hepatopathy: Contributions of Oxidative Stress and Advanced Glycation End Products
Int. J. Mol. Sci. 2013, 14(10), 19846-19866; doi:10.3390/ijms141019846
Received: 24 July 2013 / Revised: 7 September 2013 / Accepted: 10 September 2013 / Published: 1 October 2013
Cited by 13 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text
Abstract
Advanced glycation end products (AGEs) are generated spontaneously in cells; however, under conditions of hyperglycemia and lipid peroxidation, their levels are higher than usual, which contribute to the development of diseases such as the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated [...] Read more.
Advanced glycation end products (AGEs) are generated spontaneously in cells; however, under conditions of hyperglycemia and lipid peroxidation, their levels are higher than usual, which contribute to the development of diseases such as the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with oxidative stress (OS), which is linked to the transition of steatosis to steatohepatitis due to lipid peroxidation. The AGE-receptor interaction in hepatic stellate cells leads to an increase in reactive oxygen species and enhances the proliferation and activation of these cells, worsening liver fibrosis and disease progression. In this vicious cycle, there is production of (carboxymethyl)lysine, a biomarker for products of advanced glycation and lipid peroxidation, being a shared component between the two pathways. In this review, we aim to compile evidence to support the basic molecular mechanisms of AGEs and OS generation and their influence, independently or combined, on the evolution of NAFLD. The deeper understanding of the interrelations of AGEs + OS may help to elucidate the pathogenic pathways of NAFLD and to devise rational therapeutic interventions for this disease, with an expected positive impact on quality of life of patients. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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Open AccessReview Immunological Mechanisms in the Pathophysiology of Non-Alcoholic Steatohepatitis
Int. J. Mol. Sci. 2013, 14(10), 19867-19890; doi:10.3390/ijms141019867
Received: 26 August 2013 / Revised: 11 September 2013 / Accepted: 22 September 2013 / Published: 1 October 2013
Cited by 20 | PDF Full-text (569 KB) | HTML Full-text | XML Full-text
Abstract
Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. [...] Read more.
Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose tissue. Obesity is considered a chronic low-grade inflammatory state and the liver has been recognized as being an “immunological organ”. The complex role of the immune system in the pathogenesis of NASH is currently raising great interest, also in view of the possible therapeutic potential of immunotherapy in NASH. This review focuses on the disturbances of the cells constituting the innate and adaptive immune system in the liver and in adipose tissue. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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Open AccessReview Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond
Int. J. Mol. Sci. 2013, 14(10), 19891-19910; doi:10.3390/ijms141019891
Received: 8 August 2013 / Revised: 5 September 2013 / Accepted: 5 September 2013 / Published: 1 October 2013
Cited by 51 | PDF Full-text (457 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal [...] Read more.
Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE) mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessReview Nematicons and Their Electro-Optic Control: Light Localization and Signal Readdressing via Reorientation in Liquid Crystals
Int. J. Mol. Sci. 2013, 14(10), 19932-19950; doi:10.3390/ijms141019932
Received: 30 August 2013 / Revised: 16 September 2013 / Accepted: 22 September 2013 / Published: 8 October 2013
Cited by 1 | PDF Full-text (4099 KB) | HTML Full-text | XML Full-text
Abstract
Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely [...] Read more.
Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely “nematicons”. Nematicons can guide other light signals and interact with inhomogeneities and other beams. Moreover, they can be effectively deviated by using the electro-optic response of the medium, leading to several strategies for voltage-controlled reconfiguration of light-induced guided-wave circuits and signal readdressing. Hereby, we outline the main features of nematicons and review the outstanding progress achieved in the last twelve years on beam self-trapping and electro-optic readdressing. Full article
Open AccessReview Non-Coding RNAs: The “Dark Matter” of Cardiovascular Pathophysiology
Int. J. Mol. Sci. 2013, 14(10), 19987-20018; doi:10.3390/ijms141019987
Received: 4 July 2013 / Revised: 12 September 2013 / Accepted: 16 September 2013 / Published: 9 October 2013
Cited by 20 | PDF Full-text (1299 KB) | HTML Full-text | XML Full-text
Abstract
Large-scale analyses of mammalian transcriptomes have identified a significant number of different RNA molecules that are not translated into protein. In fact, the use of new sequencing technologies has identified that most of the genome is transcribed, producing a heterogeneous population of [...] Read more.
Large-scale analyses of mammalian transcriptomes have identified a significant number of different RNA molecules that are not translated into protein. In fact, the use of new sequencing technologies has identified that most of the genome is transcribed, producing a heterogeneous population of RNAs which do not encode for proteins (ncRNAs). Emerging data suggest that these transcripts influence the development of cardiovascular disease. The best characterized non-coding RNA family is represented by short highly conserved RNA molecules, termed microRNAs (miRNAs), which mediate a process of mRNA silencing through transcript degradation or translational repression. These microRNAs (miRNAs) are expressed in cardiovascular tissues and play key roles in many cardiovascular pathologies, such as coronary artery disease (CAD) and heart failure (HF). Potential links between other ncRNAs, like long non-coding RNA, and cardiovascular disease are intriguing but the functions of these transcripts are largely unknown. Thus, the functional characterization of ncRNAs is essential to improve the overall understanding of cellular processes involved in cardiovascular diseases in order to define new therapeutic strategies. This review outlines the current knowledge of the different ncRNA classes and summarizes their role in cardiovascular development and disease. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
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Open AccessReview Genetic Correction of Stem Cells in the Treatment of Inherited Diseases and Focus on Xeroderma Pigmentosum
Int. J. Mol. Sci. 2013, 14(10), 20019-20036; doi:10.3390/ijms141020019
Received: 29 July 2013 / Revised: 11 September 2013 / Accepted: 17 September 2013 / Published: 9 October 2013
Cited by 2 | PDF Full-text (513 KB) | HTML Full-text | XML Full-text
Abstract
Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo [...] Read more.
Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID)) have demonstrated the efficacy of ex vivo gene therapy. Similarly, adult epidermal stem cells have the capacity to renew epidermis, the fully differentiated, protective envelope of our body. Stable skin replacement of severely burned patients have proven life saving. Xeroderma pigmentosum (XP) is a devastating disease due to severe defects in the repair of mutagenic DNA lesions introduced upon exposure to solar radiations. Most patients die from the consequences of budding hundreds of skin cancers in the absence of photoprotection. We have developed a safe procedure of genetic correction of epidermal stem cells isolated from XP patients. Preclinical and safety assessments indicate successful correction of XP epidermal stem cells in the long term and their capacity to regenerate a normal skin with full capacities of DNA repair. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells)
Open AccessReview New Insights in the Pathogenesis of Multiple Sclerosis—Role of Acrolein in Neuronal and Myelin Damage
Int. J. Mol. Sci. 2013, 14(10), 20037-20047; doi:10.3390/ijms141020037
Received: 13 August 2013 / Revised: 17 September 2013 / Accepted: 18 September 2013 / Published: 9 October 2013
Cited by 10 | PDF Full-text (156 KB) | HTML Full-text | XML Full-text
Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury [...] Read more.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by an inappropriate inflammatory reaction resulting in widespread myelin injury along white matter tracts. Neurological impairment as a result of the disease can be attributed to immune-mediated injury to myelin, axons and mitochondria, but the molecular mechanisms underlying the neuropathy remain incompletely understood. Incomplete mechanistic knowledge hinders the development of therapies capable of alleviating symptoms and slowing disease progression in the long-term. Recently, oxidative stress has been implicated as a key component of neural tissue damage prompting investigation of reactive oxygen species (ROS) scavengers as a potential therapeutic option. Despite the establishment of oxidative stress as a crucial process in MS development and progression, ROS scavengers have had limited success in animal studies which has prompted pursuit of an alternative target capable of curtailing oxidative stress. Acrolein, a toxic β-unsaturated aldehyde capable of initiating and perpetuating oxidative stress, has been suggested as a viable point of intervention to guide the development of new treatments. Sequestering acrolein using an FDA-approved compound, hydralazine, offers neuroprotection resulting in dampened symptom severity and slowed disease progression in experimental autoimmune encephalomyelitis (EAE) mice. These results provide promise for therapeutic development, indicating the possible utility of neutralizing acrolein to preserve and improve neurological function in MS patients. Full article
(This article belongs to the Special Issue Pathology and Treatment of Central Nervous System Diseases)
Open AccessReview Marine Polysaccharide Networks and Diatoms at the Nanometric Scale
Int. J. Mol. Sci. 2013, 14(10), 20064-20078; doi:10.3390/ijms141020064
Received: 2 August 2013 / Revised: 14 September 2013 / Accepted: 18 September 2013 / Published: 9 October 2013
Cited by 8 | PDF Full-text (3656 KB) | HTML Full-text | XML Full-text
Abstract
Despite many advances in research on photosynthetic carbon fixation in marine diatoms, the biophysical and biochemical mechanisms of extracellular polysaccharide production remain significant challenges to be resolved at the molecular scale in order to proceed toward an understanding of their functions at [...] Read more.
Despite many advances in research on photosynthetic carbon fixation in marine diatoms, the biophysical and biochemical mechanisms of extracellular polysaccharide production remain significant challenges to be resolved at the molecular scale in order to proceed toward an understanding of their functions at the cellular level, as well as their interactions and fate in the ocean. This review covers studies of diatom extracellular polysaccharides using atomic force microscopy (AFM) imaging and the quantification of physical forces. Following a brief summary of the basic principle of the AFM experiment and the first AFM studies of diatom extracellular polymeric substance (EPS), we focus on the detection of supramolecular structures in polysaccharide systems produced by marine diatoms. Extracellular polysaccharide fibrils, attached to the diatom cell wall or released into the surrounding seawater, form distinct supramolecular assemblies best described as gel networks. AFM makes characterization of the diatom polysaccharide networks at the micro and nanometric scales and a clear distinction between the self-assembly and self-organization of these complex systems in marine environments possible. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria) Print Edition available
Open AccessReview Disease Animal Models of TDP-43 Proteinopathy and Their Pre-Clinical Applications
Int. J. Mol. Sci. 2013, 14(10), 20079-20111; doi:10.3390/ijms141020079
Received: 5 July 2013 / Revised: 13 September 2013 / Accepted: 18 September 2013 / Published: 9 October 2013
Cited by 7 | PDF Full-text (792 KB) | HTML Full-text | XML Full-text
Abstract
Frontotemperal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are two common neurodegenerative diseases. TDP-43 is considered to be a major disease protein in FTLD/ALS, but it’s exact role in the pathogenesis and the effective treatments remains unknown. To address this question [...] Read more.
Frontotemperal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are two common neurodegenerative diseases. TDP-43 is considered to be a major disease protein in FTLD/ALS, but it’s exact role in the pathogenesis and the effective treatments remains unknown. To address this question and to determine a potential treatment for FTLD/ALS, the disease animal models of TDP-43 proteinopathy have been established. TDP-43 proteinopathy is the histologic feature of FTLD/ALS and is associated with disease progression. Studies on the disease animal models with TDP-43 proteinopathy and their pre-clinical applications are reviewed and summarized. Through these disease animal models, parts of TDP-43 functions in physiological and pathological conditions will be better understood and possible treatments for FTLD/ALS with TDP-43 proteinopathy may be identified for possible clinical applications in the future. Full article
Open AccessReview Role of Hepatic Progenitor Cells in Nonalcoholic Fatty Liver Disease Development: Cellular Cross-Talks and Molecular Networks
Int. J. Mol. Sci. 2013, 14(10), 20112-20130; doi:10.3390/ijms141020112
Received: 6 August 2013 / Revised: 18 September 2013 / Accepted: 18 September 2013 / Published: 9 October 2013
Cited by 14 | PDF Full-text (1007 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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Open AccessReview HKT Transporters—State of the Art
Int. J. Mol. Sci. 2013, 14(10), 20359-20385; doi:10.3390/ijms141020359
Received: 15 July 2013 / Revised: 15 August 2013 / Accepted: 18 September 2013 / Published: 14 October 2013
Cited by 14 | PDF Full-text (1335 KB) | HTML Full-text | XML Full-text
Abstract
The increase in soil salinity poses a serious threat to agricultural yields. Under salinity stress, several Na+ transporters play an essential role in Na+ tolerance in plants. Amongst all Na+ transporters, HKT has been shown to have a crucial [...] Read more.
The increase in soil salinity poses a serious threat to agricultural yields. Under salinity stress, several Na+ transporters play an essential role in Na+ tolerance in plants. Amongst all Na+ transporters, HKT has been shown to have a crucial role in both mono and dicotyledonous plants in the tolerance to salinity stress. Here we present an overview of the physiological role of HKT transporters in plant Na+ homeostasis. HKT regulation and amino acids important to the correct function of HKT transporters are reviewed. The functions of the most recently characterized HKT members from both HKT1 and HKT2 subfamilies are also discussed. Topics that still need to be studied in future research (e.g., HKT regulation) as well as research suggestions (e.g., generation of HKT mutants) are addressed. Full article
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
Open AccessReview An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders
Int. J. Mol. Sci. 2013, 14(10), 20427-20442; doi:10.3390/ijms141020427
Received: 14 June 2013 / Revised: 18 September 2013 / Accepted: 25 September 2013 / Published: 14 October 2013
Cited by 11 | PDF Full-text (284 KB) | HTML Full-text | XML Full-text
Abstract
A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological [...] Read more.
A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered. Full article
(This article belongs to the Special Issue Regulation by non-coding RNAs 2013)
Open AccessReview Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives
Int. J. Mol. Sci. 2013, 14(10), 20508-20542; doi:10.3390/ijms141020508
Received: 6 August 2013 / Revised: 3 September 2013 / Accepted: 13 September 2013 / Published: 14 October 2013
Cited by 17 | PDF Full-text (301 KB) | HTML Full-text | XML Full-text
Abstract
Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals [...] Read more.
Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin)
Open AccessReview The Epidermal Growth Factor Receptor and Its Ligands in Cardiovascular Disease
Int. J. Mol. Sci. 2013, 14(10), 20597-20613; doi:10.3390/ijms141020597
Received: 24 July 2013 / Revised: 20 September 2013 / Accepted: 8 October 2013 / Published: 15 October 2013
Cited by 20 | PDF Full-text (635 KB) | HTML Full-text | XML Full-text
Abstract
The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role [...] Read more.
The epidermal growth factor receptor (EGFR) family and its ligands serve as a switchboard for the regulation of multiple cellular processes. While it is clear that EGFR activity is essential for normal cardiac development, its function in the vasculature and its role in cardiovascular disease are only beginning to be elucidated. In the blood vessel, endothelial cells and smooth muscle cells are both a source and a target of EGF-like ligands. Activation of EGFR has been implicated in blood pressure regulation, endothelial dysfunction, neointimal hyperplasia, atherogenesis, and cardiac remodeling. Furthermore, increased circulating EGF-like ligands may mediate accelerated vascular disease associated with chronic inflammation. Although EGFR inhibitors are currently being used clinically for the treatment of cancer, additional studies are necessary to determine whether abrogation of EGFR signaling is a potential strategy for the treatment of cardiovascular disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
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Open AccessReview Mass Spectrometry Coupled Experiments and Protein Structure Modeling Methods
Int. J. Mol. Sci. 2013, 14(10), 20635-20657; doi:10.3390/ijms141020635
Received: 30 July 2013 / Revised: 17 September 2013 / Accepted: 19 September 2013 / Published: 15 October 2013
Cited by 2 | PDF Full-text (545 KB) | HTML Full-text | XML Full-text
Abstract
With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its [...] Read more.
With the accumulation of next generation sequencing data, there is increasing interest in the study of intra-species difference in molecular biology, especially in relation to disease analysis. Furthermore, the dynamics of the protein is being identified as a critical factor in its function. Although accuracy of protein structure prediction methods is high, provided there are structural templates, most methods are still insensitive to amino-acid differences at critical points that may change the overall structure. Also, predicted structures are inherently static and do not provide information about structural change over time. It is challenging to address the sensitivity and the dynamics by computational structure predictions alone. However, with the fast development of diverse mass spectrometry coupled experiments, low-resolution but fast and sensitive structural information can be obtained. This information can then be integrated into the structure prediction process to further improve the sensitivity and address the dynamics of the protein structures. For this purpose, this article focuses on reviewing two aspects: the types of mass spectrometry coupled experiments and structural data that are obtainable through those experiments; and the structure prediction methods that can utilize these data as constraints. Also, short review of current efforts in integrating experimental data in the structural modeling is provided. Full article
(This article belongs to the collection Protein Folding)
Open AccessReview Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)
Int. J. Mol. Sci. 2013, 14(10), 20704-20728; doi:10.3390/ijms141020704
Received: 30 August 2013 / Revised: 18 September 2013 / Accepted: 29 September 2013 / Published: 15 October 2013
Cited by 38 | PDF Full-text (590 KB) | HTML Full-text | XML Full-text
Abstract
Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, [...] Read more.
Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease. Full article
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
Open AccessReview Lipid Transport and Metabolism in Healthy and Osteoarthritic Cartilage
Int. J. Mol. Sci. 2013, 14(10), 20793-20808; doi:10.3390/ijms141020793
Received: 23 August 2013 / Revised: 8 October 2013 / Accepted: 8 October 2013 / Published: 16 October 2013
Cited by 12 | PDF Full-text (822 KB) | HTML Full-text | XML Full-text
Abstract
Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules [...] Read more.
Cartilage is an avascular tissue and cartilage metabolism depends on molecule diffusion from synovial fluid and subchondral bone. Thus, nutrient availability is limited by matrix permeability according to the size and charge of the molecules. Matrix composition limits the access of molecules to chondrocytes, determining cell metabolism and cartilage maintenance. Lipids are important nutrients in chondrocyte metabolism and are available for these cells through de novo synthesis but also through diffusion from surrounding tissues. Cartilage status and osteoarthritis development depend on lipid availability. This paper reviews lipid transport and metabolism in cartilage. We also analyze signalling pathways directly mediated by lipids and those that involve mTOR pathways, both in normal and osteoarthritic cartilage. Full article
(This article belongs to the Special Issue The Chondrocyte Phenotype in Cartilage Biology)
Open AccessReview Protein Glutathionylation in Cardiovascular Diseases
Int. J. Mol. Sci. 2013, 14(10), 20845-20876; doi:10.3390/ijms141020845
Received: 29 August 2013 / Revised: 2 October 2013 / Accepted: 8 October 2013 / Published: 17 October 2013
Cited by 17 | PDF Full-text (586 KB) | HTML Full-text | XML Full-text
Abstract
The perturbation of thiol-disulfide homeostasis is an important consequence of many diseases, with redox signals implicated in several physio-pathological processes. A prevalent form of cysteine modification is the reversible formation of protein mixed disulfides with glutathione (S-glutathionylation). The abundance of [...] Read more.
The perturbation of thiol-disulfide homeostasis is an important consequence of many diseases, with redox signals implicated in several physio-pathological processes. A prevalent form of cysteine modification is the reversible formation of protein mixed disulfides with glutathione (S-glutathionylation). The abundance of glutathione in cells and the ready conversion of sulfenic acids to S-glutathione mixed disulfides supports the reversible protein S-glutathionylation as a common feature of redox signal transduction, able to regulate the activities of several redox sensitive proteins. In particular, protein S-glutathionylation is emerging as a critical signaling mechanism in cardiovascular diseases, because it regulates numerous physiological processes involved in cardiovascular homeostasis, including myocyte contraction, oxidative phosphorylation, protein synthesis, vasodilation, glycolytic metabolism and response to insulin. Thus, perturbations in protein glutathionylation status may contribute to the etiology of many cardiovascular diseases, such as myocardial infarction, cardiac hypertrophy and atherosclerosis. Various reports show the importance of oxidative cysteine modifications in modulating cardiovascular function. In this review, we illustrate tools and strategies to monitor protein S-glutathionylation and describe the proteins so far identified as glutathionylated in myocardial contraction, hypertrophy and inflammation. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease)
Open AccessReview Boronic Acid-Based Approach for Separation and Immobilization of Glycoproteins and Its Application in Sensing
Int. J. Mol. Sci. 2013, 14(10), 20890-20912; doi:10.3390/ijms141020890
Received: 29 August 2013 / Revised: 20 September 2013 / Accepted: 8 October 2013 / Published: 17 October 2013
Cited by 18 | PDF Full-text (948 KB) | HTML Full-text | XML Full-text
Abstract
Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis [...] Read more.
Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols in the oligosaccharide chains of glycoproteins to form five- or six-membered cyclic esters. Based on this interaction, boronic acid-based ligands and materials have attracted much attention in both chemistry and biology as the recognition motif for enrichment and chemo/biosensing of glycoproteins in recent years. In this work, we reviewed the progress in the separation, immobilization and detection of glycoproteins with boronic acid-functionalized materials and addressed its application in sensing. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
Open AccessReview MicroRNA-Regulated Pathways in Hematological Malignancies: How to Avoid Cells Playing Out of Tune
Int. J. Mol. Sci. 2013, 14(10), 20930-20953; doi:10.3390/ijms141020930
Received: 31 July 2013 / Revised: 3 October 2013 / Accepted: 10 October 2013 / Published: 18 October 2013
Cited by 9 | PDF Full-text (402 KB) | HTML Full-text | XML Full-text
Abstract
The coordinated expression and interplay among lineage specific transcription factors and microRNAs contribute to the regulation of gene expression and determination of cell specificity. In hematopoietic stem cells (HSCs), unique combinations of transcription factors largely control growth and maturation of different blood [...] Read more.
The coordinated expression and interplay among lineage specific transcription factors and microRNAs contribute to the regulation of gene expression and determination of cell specificity. In hematopoietic stem cells (HSCs), unique combinations of transcription factors largely control growth and maturation of different blood cell lineages through cooperative regulation of specific target genes. MicroRNAs provide an additional level of control beyond transcription factors. By acting as regulators of crucial lineage-specific genetic programs, microRNAs direct early multipotential progenitor cells to adopt a certain cell fate program. Thus, alteration of specific microRNA levels may affect proliferation, differentiation and genetic stability of HSCs, contributing to the onset of myeloproliferative disorders and leukemia. The major aim of this review is to highlight the critical role of microRNA-regulated pathways during the establishment and progression of hematological malignancies, with a particular attention to leukemia, lymphomas and myelodysplastic syndromes. This will give us the opportunity to discuss the potential use of microRNA-based therapeutic approaches in these diseases. MicroRNAs are indeed emerging as relevant tools to improve the efficacy of currently used therapeutic protocols. Full article
(This article belongs to the Special Issue Molecular Bases of Cancer Research)
Open AccessReview Biofilm Matrix and Its Regulation in Pseudomonas aeruginosa
Int. J. Mol. Sci. 2013, 14(10), 20983-21005; doi:10.3390/ijms141020983
Received: 21 August 2013 / Revised: 29 September 2013 / Accepted: 9 October 2013 / Published: 18 October 2013
Cited by 32 | PDF Full-text (683 KB) | HTML Full-text | XML Full-text
Abstract
Biofilms are communities of microorganisms embedded in extracellular polymeric substances (EPS) matrix. Bacteria in biofilms demonstrate distinct features from their free-living planktonic counterparts, such as different physiology and high resistance to immune system and antibiotics that render biofilm a source of chronic [...] Read more.
Biofilms are communities of microorganisms embedded in extracellular polymeric substances (EPS) matrix. Bacteria in biofilms demonstrate distinct features from their free-living planktonic counterparts, such as different physiology and high resistance to immune system and antibiotics that render biofilm a source of chronic and persistent infections. A deeper understanding of biofilms will ultimately provide insights into the development of alternative treatment for biofilm infections. The opportunistic pathogen Pseudomonas aeruginosa, a model bacterium for biofilm research, is notorious for its ability to cause chronic infections by its high level of drug resistance involving the formation of biofilms. In this review, we summarize recent advances in biofilm formation, focusing on the biofilm matrix and its regulation in P. aeruginosa, aiming to provide resources for the understanding and control of bacterial biofilms. Full article
(This article belongs to the Special Issue Biofilms: Extracellular Bastions of Bacteria) Print Edition available
Open AccessReview Impaired Glutathione Synthesis in Neurodegeneration
Int. J. Mol. Sci. 2013, 14(10), 21021-21044; doi:10.3390/ijms141021021
Received: 23 August 2013 / Revised: 30 September 2013 / Accepted: 1 October 2013 / Published: 18 October 2013
Cited by 32 | PDF Full-text (665 KB) | HTML Full-text | XML Full-text
Abstract
Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its [...] Read more.
Glutathione (GSH) was discovered in yeast cells in 1888. Studies of GSH in mammalian cells before the 1980s focused exclusively on its function for the detoxication of xenobiotics or for drug metabolism in the liver, in which GSH is present at its highest concentration in the body. Increasing evidence has demonstrated other important roles of GSH in the brain, not only for the detoxication of xenobiotics but also for antioxidant defense and the regulation of intracellular redox homeostasis. GSH also regulates cell signaling, protein function, gene expression, and cell differentiation/proliferation in the brain. Clinically, inborn errors in GSH-related enzymes are very rare, but disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain. GSH depletion would precipitate oxidative damage in the brain, leading to neurodegenerative diseases. This review focuses on the significance of GSH function, the synthesis of GSH and its metabolism, and clinical disorders of GSH metabolism. A potential approach to increase brain GSH levels against neurodegeneration is also discussed. Full article
(This article belongs to the collection Molecular Research in Neurotoxicology)
Open AccessReview Angiotensin-Converting Enzymes Play a Dominant Role in Fertility
Int. J. Mol. Sci. 2013, 14(10), 21071-21086; doi:10.3390/ijms141021071
Received: 10 August 2013 / Revised: 14 October 2013 / Accepted: 14 October 2013 / Published: 21 October 2013
Cited by 1 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%–20% incidence worldwide. An accumulating body of evidence has shown that the renin–angiotensin system is involved in the fertility problems observed in some populations. [...] Read more.
According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%–20% incidence worldwide. An accumulating body of evidence has shown that the renin–angiotensin system is involved in the fertility problems observed in some populations. Moreover, alterations in the expression of angiotensin-converting enzyme-1, angiotensin-converting enzyme-2, and angiotensin-converting enzyme-3 might be one of the most important mechanisms underlying both female and male infertility. However, as a pseudogene in humans, further studies are needed to explore whether the abnormal angiotensin-converting enzyme-3 gene could result in the problems of human reproduction. In this review, the relationship between angiotensin-converting enzymes and fertile ability is summarized, and a new procedure for the treatment of infertility is discussed. Full article
Open AccessReview Cancer Development, Progression, and Therapy: An Epigenetic Overview
Int. J. Mol. Sci. 2013, 14(10), 21087-21113; doi:10.3390/ijms141021087
Received: 30 August 2013 / Revised: 27 September 2013 / Accepted: 4 October 2013 / Published: 21 October 2013
Cited by 38 | PDF Full-text (692 KB) | HTML Full-text | XML Full-text
Abstract
Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, [...] Read more.
Carcinogenesis involves uncontrolled cell growth, which follows the activation of oncogenes and/or the deactivation of tumor suppression genes. Metastasis requires down-regulation of cell adhesion receptors necessary for tissue-specific, cell–cell attachment, as well as up-regulation of receptors that enhance cell motility. Epigenetic changes, including histone modifications, DNA methylation, and DNA hydroxymethylation, can modify these characteristics. Targets for these epigenetic changes include signaling pathways that regulate apoptosis and autophagy, as well as microRNA. We propose that predisposed normal cells convert to cancer progenitor cells that, after growing, undergo an epithelial-mesenchymal transition. This process, which is partially under epigenetic control, can create a metastatic form of both progenitor and full-fledged cancer cells, after which metastasis to a distant location may occur. Identification of epigenetic regulatory mechanisms has provided potential therapeutic avenues. In particular, epigenetic drugs appear to potentiate the action of traditional therapeutics, often by demethylating and re-expressing tumor suppressor genes to inhibit tumorigenesis. Epigenetic drugs may inhibit both the formation and growth of cancer progenitor cells, thus reducing the recurrence of cancer. Adopting epigenetic alteration as a new hallmark of cancer is a logical and necessary step that will further encourage the development of novel epigenetic biomarkers and therapeutics. Full article
(This article belongs to the Special Issue Molecular Research of Carcinogenesis)
Open AccessReview Dietary Polyunsaturated Fatty Acids and Inflammation: The Role of Phospholipid Biosynthesis
Int. J. Mol. Sci. 2013, 14(10), 21167-21188; doi:10.3390/ijms141021167
Received: 31 July 2013 / Revised: 11 October 2013 / Accepted: 14 October 2013 / Published: 22 October 2013
Cited by 21 | PDF Full-text (935 KB) | HTML Full-text | XML Full-text
Abstract
The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid [...] Read more.
The composition of fatty acids in the diets of both human and domestic animal species can regulate inflammation through the biosynthesis of potent lipid mediators. The substrates for lipid mediator biosynthesis are derived primarily from membrane phospholipids and reflect dietary fatty acid intake. Inflammation can be exacerbated with intake of certain dietary fatty acids, such as some ω-6 polyunsaturated fatty acids (PUFA), and subsequent incorporation into membrane phospholipids. Inflammation, however, can be resolved with ingestion of other fatty acids, such as ω-3 PUFA. The influence of dietary PUFA on phospholipid composition is influenced by factors that control phospholipid biosynthesis within cellular membranes, such as preferential incorporation of some fatty acids, competition between newly ingested PUFA and fatty acids released from stores such as adipose, and the impacts of carbohydrate metabolism and physiological state. The objective of this review is to explain these factors as potential obstacles to manipulating PUFA composition of tissue phospholipids by specific dietary fatty acids. A better understanding of the factors that influence how dietary fatty acids can be incorporated into phospholipids may lead to nutritional intervention strategies that optimize health. Full article
(This article belongs to the Special Issue Phospholipids: Molecular Sciences 2012)

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Open AccessTechnical Note A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen
Int. J. Mol. Sci. 2013, 14(10), 19716-19730; doi:10.3390/ijms141019716
Received: 22 July 2013 / Revised: 4 September 2013 / Accepted: 9 September 2013 / Published: 30 September 2013
Cited by 2 | PDF Full-text (2106 KB) | HTML Full-text | XML Full-text
Abstract
The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope [...] Read more.
The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS). We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery. Full article
(This article belongs to the Special Issue Xenobiotic Metabolism)
Open AccessShort Note Eleven Novel Polymorphic Microsatellite Loci for Oval Squid Sepioteuthis Lessoniana (Shiro-Ika Type)
Int. J. Mol. Sci. 2013, 14(10), 19971-19975; doi:10.3390/ijms141019971
Received: 9 August 2013 / Revised: 5 September 2013 / Accepted: 25 September 2013 / Published: 8 October 2013
Cited by 3 | PDF Full-text (169 KB) | HTML Full-text | XML Full-text
Abstract
The oval squid Sepioteuthis lessoniana is one of the most economically important squid species in Japan; however, its population structure is poorly understood due to the lack of hypervariable markers. Such information is critical for managing sustainable fisheries, as well as for [...] Read more.
The oval squid Sepioteuthis lessoniana is one of the most economically important squid species in Japan; however, its population structure is poorly understood due to the lack of hypervariable markers. Such information is critical for managing sustainable fisheries, as well as for ensuring the existence of wild S. lessoniana stocks. Eleven candidate microsatellite loci were isolated from a small insert genomic DNA library. Polymorphisms in these 11 loci were screened in 24 wild individuals. The number of alleles per locus was found to range from 5 to 19 alleles, and the observed heterozygosity ranged from 0.292 to 0.958. No evidence for linkage disequilibrium was detected among all the loci. The genotypic proportions conformed to Hardy-Weinberg equilibrium, except at one locus. In conclusion, these polymorphic microsatellite loci may be used to develop a genetic framework to manage S. lessoniana in the future. Full article
Open AccessTechnical Note Determination of Homoarginine, Arginine, NMMA, ADMA, and SDMA in Biological Samples by HPLC-ESI-Mass Spectrometry
Int. J. Mol. Sci. 2013, 14(10), 20131-20138; doi:10.3390/ijms141020131
Received: 29 July 2013 / Revised: 28 August 2013 / Accepted: 18 September 2013 / Published: 9 October 2013
Cited by 5 | PDF Full-text (208 KB) | HTML Full-text | XML Full-text
Abstract
NG,NG-dimethyl-L-arginine (ADMA) and NG-methyl-L-arginine (NMMA) are endogenous inhibitors of nitric oxide synthase (NOS). In contrast, NG,N'G-dimethyl-L-arginine (SDMA) possesses only a weak inhibitory potency towards neuronal NOS and it is [...] Read more.
NG,NG-dimethyl-L-arginine (ADMA) and NG-methyl-L-arginine (NMMA) are endogenous inhibitors of nitric oxide synthase (NOS). In contrast, NG,N'G-dimethyl-L-arginine (SDMA) possesses only a weak inhibitory potency towards neuronal NOS and it is known to limit nitric oxide (NO) production by competing with L-arginine for cellular uptake. The inhibition of NOS is associated with endothelial dysfunction in cardiovascular diseases as well in chronic renal failure. L-Homoarginine (HArg), a structural analog of L-arginine (Arg), is an alternative but less efficient substrate for NOS. Besides, it inhibits arginase, leading to an increased availability of L-arginine for NOS to produce NO. However, its relation with cardiovascular disease remains unclear. To date, several analytical methods for the quantitative determination of Arg, HArg, NMMA, AMDA, and SDMA in biological samples have been described. Here, we present a simple, fast, and accurate HPLC-ESI-MS/MS method which allows both the simultaneous determination and quantification of these compounds without needing derivatization, and the possibility to easily modulate the chromatographic separation between HArg and NMMA (or between SDMA and ADMA). Data on biological samples revealed the feasibility of the method, the minimal sample preparation, and the fast run time which make this method very suitable and accurate for analysis in the basic and clinical settings. Full article
(This article belongs to the Special Issue ADMA and Nitrergic System)

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