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Int. J. Mol. Sci., Volume 13, Issue 1 (January 2012) , Pages 1-1268

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Open AccessArticle
Prunella vulgaris Suppresses HG-Induced Vascular Inflammation via Nrf2/HO-1/eNOS Activation
Int. J. Mol. Sci. 2012, 13(1), 1258-1268; https://doi.org/10.3390/ijms13011258
Received: 9 October 2011 / Revised: 11 January 2012 / Accepted: 11 January 2012 / Published: 23 January 2012
Cited by 21 | Viewed by 4049 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV [...] Read more.
Vascular inflammation is an important factor which can promote diabetic complications. In this study, the inhibitory effects of aqueous extract from Prunella vulgaris (APV) on high glucose (HG)-induced expression of cell adhesion molecules in human umbilical vein endothelial cells (HUVEC) are reported. APV decreased HG-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. APV also dose-dependently inhibited HG-induced adhesion of HL-60 monocytic cells. APV suppressed p65 NF-κB activation in HG-treated cells. APV significantly inhibited the formation of intracellular reactive oxygen species (ROS). HG-stimulated HUVEC secreted gelatinases, however, APV inhibited it. APV induced Akt phosphorylation as well as activation of heme oxygenase-1 (HO-1), eNOS, and nuclear factor E2-related factor 2 (Nrf2), which may protect vascular inflammation caused by HG. In conclusion, APV exerts anti-inflammatory effect via inhibition of ROS/NF-κB pathway by inducing HO-1 and eNOS expression mediated by Nrf2, thereby suggesting that Prunella vulgaris may be a possible therapeutic approach to the inhibition of diabetic vascular diseases. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle
The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes
Int. J. Mol. Sci. 2012, 13(1), 1239-1257; https://doi.org/10.3390/ijms13011239
Received: 13 December 2011 / Revised: 12 January 2012 / Accepted: 13 January 2012 / Published: 23 January 2012
Cited by 50 | Viewed by 4441 | PDF Full-text (507 KB) | HTML Full-text | XML Full-text
Abstract
The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM [...] Read more.
The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC—in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)—has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration. Full article
Open AccessReview
Disruption of Axonal Transport in Motor Neuron Diseases
Int. J. Mol. Sci. 2012, 13(1), 1225-1238; https://doi.org/10.3390/ijms13011225
Received: 2 November 2011 / Revised: 11 January 2012 / Accepted: 16 January 2012 / Published: 23 January 2012
Cited by 31 | Viewed by 3820 | PDF Full-text (310 KB) | HTML Full-text | XML Full-text
Abstract
Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, [...] Read more.
Motor neurons typically have very long axons, and fine-tuning axonal transport is crucial for their survival. The obstruction of axonal transport is gaining attention as a cause of neuronal dysfunction in a variety of neurodegenerative motor neuron diseases. Depletions in dynein and dynactin-1, motor molecules regulating axonal trafficking, disrupt axonal transport in flies, and mutations in their genes cause motor neuron degeneration in humans and rodents. Axonal transport defects are among the early molecular events leading to neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS). Gene expression profiles indicate that dynactin-1 mRNA is downregulated in degenerating spinal motor neurons of autopsied patients with sporadic ALS. Dynactin-1 mRNA is also reduced in the affected neurons of a mouse model of spinal and bulbar muscular atrophy, a motor neuron disease caused by triplet CAG repeat expansion in the gene encoding the androgen receptor. Pathogenic androgen receptor proteins also inhibit kinesin-1 microtubule-binding activity and disrupt anterograde axonal transport by activating c-Jun N-terminal kinase. Disruption of axonal transport also underlies the pathogenesis of spinal muscular atrophy and hereditary spastic paraplegias. These observations suggest that the impairment of axonal transport is a key event in the pathological processes of motor neuron degeneration and an important target of therapy development for motor neuron diseases. Full article
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Graphical abstract

Open AccessArticle
Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death
Int. J. Mol. Sci. 2012, 13(1), 1209-1224; https://doi.org/10.3390/ijms13011209
Received: 12 December 2011 / Revised: 10 January 2012 / Accepted: 12 January 2012 / Published: 20 January 2012
Cited by 27 | Viewed by 3661 | PDF Full-text (778 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet [...] Read more.
Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle
Inhibition of AKT2 Enhances Sensitivity to Gemcitabine via Regulating PUMA and NF-κB Signaling Pathway in Human Pancreatic Ductal Adenocarcinoma
Int. J. Mol. Sci. 2012, 13(1), 1186-1208; https://doi.org/10.3390/ijms13011186
Received: 1 October 2011 / Revised: 8 December 2011 / Accepted: 21 December 2011 / Published: 20 January 2012
Cited by 27 | Viewed by 3438 | PDF Full-text (1182 KB) | HTML Full-text | XML Full-text
Abstract
Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles to successful treatment of pancreatic cancer, and a better understanding of the molecular basis of this malignancy may lead to improved therapeutics. In the present study, we investigated whether AKT2 silencing sensitized [...] Read more.
Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles to successful treatment of pancreatic cancer, and a better understanding of the molecular basis of this malignancy may lead to improved therapeutics. In the present study, we investigated whether AKT2 silencing sensitized pancreatic cancer L3.6pl, BxPC-3, PANC-1 and MIAPaCa-2 cells to gemcitabine via regulating PUMA (p53-upregulated modulator of apoptosis) and nuclear factor (NF)-κB signaling pathway. MTT, TUNEL, EMSA and NF-κB reporter assays were used to detect tumor cell proliferation, apoptosis and NF-κB activity. Western blotting was used to detect different protein levels. Xenograft of established tumors was used to evaluate primary tumor growth and apoptosis after treatment with gemcitabine alone or in combination with AKT2 siRNA. Gemcitabine activated AKT2 and NF-κB in MIAPaCa-2 and L3.6pl cells in vitro or in vivo, and in PANC-1 cells only in vivo. Gemcitabine only activated NF-κB in BxPC-3 cells in vitro. The presence of PUMA was necessary for gemcitabine-induced apoptosis only in BxPC-3 cells in vitro. AKT2 inhibition sensitized gemcitabine-induced apoptosis via PUMA upregulation in MIAPaCa-2 cells in vitro, and via NF-κB activity inhibition in L3.6pl cells in vitro. In PANC-1 and MIAPaCa-2 cells in vivo, AKT2 inhibition sensitized gemcitabine-induced apoptosis and growth inhibition via both PUMA upregulation and NF-κB inhibition. We suggest that AKT2 inhibition abrogates gemcitabine-induced activation of AKT2 and NF-κB, and promotes gemcitabine-induced PUMA upregulation, resulting in chemosensitization of pancreatic tumors to gemcitabine, which is probably an important strategy for the treatment of pancreatic cancer. Full article
(This article belongs to the Section Molecular Toxicology)
Open AccessArticle
microRNA Response to Listeria monocytogenes Infection in Epithelial Cells
Int. J. Mol. Sci. 2012, 13(1), 1173-1185; https://doi.org/10.3390/ijms13011173
Received: 2 December 2011 / Revised: 5 January 2012 / Accepted: 13 January 2012 / Published: 20 January 2012
Cited by 31 | Viewed by 4073 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following [...] Read more.
microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (∆inlAB or ∆hly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR-146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following ∆inlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessArticle
High-Dimensional Descriptor Selection and Computational QSAR Modeling for Antitumor Activity of ARC-111 Analogues Based on Support Vector Regression (SVR)
Int. J. Mol. Sci. 2012, 13(1), 1161-1172; https://doi.org/10.3390/ijms13011161
Received: 3 November 2011 / Revised: 9 January 2012 / Accepted: 17 January 2012 / Published: 20 January 2012
Cited by 12 | Viewed by 3451 | PDF Full-text (183 KB) | HTML Full-text | XML Full-text
Abstract
To design ARC-111 analogues with improved efficiency, we constructed the QSAR of 22 ARC-111 analogues with RPMI8402 tumor cells. First, the optimized support vector regression (SVR) model based on the literature descriptors and the worst descriptor elimination multi-roundly (WDEM) method had similar generalization [...] Read more.
To design ARC-111 analogues with improved efficiency, we constructed the QSAR of 22 ARC-111 analogues with RPMI8402 tumor cells. First, the optimized support vector regression (SVR) model based on the literature descriptors and the worst descriptor elimination multi-roundly (WDEM) method had similar generalization as the artificial neural network (ANN) model for the test set. Secondly, seven and 11 more effective descriptors out of 2,923 features were selected by the high-dimensional descriptor selection nonlinearly (HDSN) and WDEM method, and the SVR models (SVR3 and SVR4) with these selected descriptors resulted in better evaluation measures and a more precise predictive power for the test set. The interpretability system of better SVR models was further established. Our analysis offers some useful parameters for designing ARC-111 analogues with enhanced antitumor activity. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle
Isolation and Characterization of New 24 Microsatellite DNA Markers for Golden Cuttlefish (Sepia esculenta)
Int. J. Mol. Sci. 2012, 13(1), 1154-1160; https://doi.org/10.3390/ijms13011154
Received: 23 December 2011 / Revised: 12 January 2012 / Accepted: 13 January 2012 / Published: 20 January 2012
Cited by 1 | Viewed by 2798 | PDF Full-text (88 KB) | HTML Full-text | XML Full-text
Abstract
Twenty-four microsatellite DNA markers were isolated and characterized for golden cuttlefish (Sepia esculenta) from a (GT)13—enriched genomic library. Loci were tested in 48 individuals from Jiaozhou bay of China. The numbers of alleles per locus ranged from two [...] Read more.
Twenty-four microsatellite DNA markers were isolated and characterized for golden cuttlefish (Sepia esculenta) from a (GT)13—enriched genomic library. Loci were tested in 48 individuals from Jiaozhou bay of China. The numbers of alleles per locus ranged from two to 25 with an average of 10.3. The observed and expected heterozygosities ranged from 0.063 to 0.896 and from 0.137 to 0.953, with averages of 0.519 and 0.633, respectively. Six loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni’s correction and no significant linkage disequilibrium between loci pairs was detected. These microsatellite markers would be useful for analyzing the population genetic structure to make conservation and management decisions for S. esculenta. Full article
Open AccessReview
Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors
Int. J. Mol. Sci. 2012, 13(1), 1126-1153; https://doi.org/10.3390/ijms13011126
Received: 7 December 2011 / Revised: 1 January 2012 / Accepted: 16 January 2012 / Published: 20 January 2012
Cited by 11 | Viewed by 3345 | PDF Full-text (189 KB) | HTML Full-text | XML Full-text
Abstract
Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the [...] Read more.
Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle
The Effect of Temozolomide/Poly(lactide-co-glycolide) (PLGA)/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior
Int. J. Mol. Sci. 2012, 13(1), 1109-1125; https://doi.org/10.3390/ijms13011109
Received: 7 November 2011 / Revised: 20 December 2011 / Accepted: 11 January 2012 / Published: 19 January 2012
Cited by 29 | Viewed by 4288 | PDF Full-text (1891 KB) | HTML Full-text | XML Full-text
Abstract
In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning [...] Read more.
In this study, we investigated the effects of temozolomide (TMZ)/Poly (lactide-co-glycolide)(PLGA)/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma. Full article
(This article belongs to the Section Materials Science)
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Graphical abstract

Open AccessArticle
Local Mechanical Stimulation of Mardin-Darby Canine Kidney Cell Sheets on Temperature-Responsive Hydrogel
Int. J. Mol. Sci. 2012, 13(1), 1095-1108; https://doi.org/10.3390/ijms13011095
Received: 13 September 2011 / Revised: 25 December 2011 / Accepted: 13 January 2012 / Published: 19 January 2012
Cited by 4 | Viewed by 3885 | PDF Full-text (4759 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Collective motion of cell sheets plays a role not only in development and repair, but also in devastating diseases such as cancer. However, unlike single-cell motility, collective motion of cell sheets involves complex cell-cell communication during migration; therefore, its mechanism is largely unknown. [...] Read more.
Collective motion of cell sheets plays a role not only in development and repair, but also in devastating diseases such as cancer. However, unlike single-cell motility, collective motion of cell sheets involves complex cell-cell communication during migration; therefore, its mechanism is largely unknown. To elucidate propagation of signaling transduced by cell-cell interaction, we designed a hydrogel substrate that can cause local mechanical stretching of cell sheets. Poly (N-isopropyl acrylamide) (PNIPAAm) hydrogel is a temperature-responsive polymer gel whose volume changes isotropically in response to temperature changes below 37 °C. We designed a combined hydrogel substrate consisting of collagen-immobilized PNIPAAm as the local stimulation side and polyacrylamide (PAAm) as the non-stimulation side to assess propagation of mechanical transduction. Mardin-Darby canine kidney (MDCK) cells adhered to the collagen-immobilized PNIPAAm gel increased it area and were flattened as the gel swelled with temperature decrease. E-cadherin in these cells became undetectable in some domains, and actin stress fibers were more clearly observed at the cell base. In contrast, E-cadherin in cells adhered to the collagen-immobilized PAAm side was equally stained as that in cells adhered to the collagen-immobilized PAAm side even after temperature decrease. ERK1/2 MAPK activation of cells on the non-stimulated substrate occurred after partial stretching of the cell sheet suggesting the propagation of signaling. These results indicate that a change in the balance of mechanical tension induced by partial stretching of cell sheets leads to activation and propagation of the cell signaling. Full article
(This article belongs to the Special Issue Programmable Materials for Mechanobiology)
Open AccessArticle
On the Several Molecules and Nanostructures of Water
Int. J. Mol. Sci. 2012, 13(1), 1066-1094; https://doi.org/10.3390/ijms13011066
Received: 30 September 2011 / Revised: 4 January 2012 / Accepted: 5 January 2012 / Published: 19 January 2012
Cited by 2 | Viewed by 2890 | PDF Full-text (353 KB) | HTML Full-text | XML Full-text
Abstract
This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting [...] Read more.
This paper investigates the water molecule from a variety of viewpoints. Water can involve different isotopes of Hydrogen and Oxygen, it can form differently shaped isomer molecules, and, when frozen, it occupies space differently than most other substances do. The tool for conducting the investigation of all this is called ‘Algebraic Chemistry’. This tool is a quantitative model for predicting the energy budget for all sorts of changes between different ionization states of atoms that are involved in chemical reactions and in changes of physical state. The model is based on consistent patterns seen in empirical data about ionization potentials, together with rational scaling laws that can interpolate and extrapolate for situations where no data are available. The results of the investigation of the water molecule include comments, both positive and negative, about technologies involving heavy water, poly water, Brown’s gas, and cold fusion. Full article
(This article belongs to the Special Issue Atoms in Molecules and in Nanostructures)
Open AccessArticle
Studies on Bioflocculant Production by Arthrobacter sp. Raats, a Freshwater Bacteria Isolated from Tyume River, South Africa
Int. J. Mol. Sci. 2012, 13(1), 1054-1065; https://doi.org/10.3390/ijms13011054
Received: 24 November 2011 / Revised: 6 January 2012 / Accepted: 17 January 2012 / Published: 19 January 2012
Cited by 29 | Viewed by 3619 | PDF Full-text (259 KB) | HTML Full-text | XML Full-text
Abstract
A bioflocculant-producing bacteria was isolated from Tyume River in the Eastern Cape Province, South Africa and identified by 16S rRNA gene nucleotide sequence to have 91% similarity to Arthrobacter sp. 5J12A, and the nucleotide sequence was deposited in GenBank as Arthrobacter sp. Raats [...] Read more.
A bioflocculant-producing bacteria was isolated from Tyume River in the Eastern Cape Province, South Africa and identified by 16S rRNA gene nucleotide sequence to have 91% similarity to Arthrobacter sp. 5J12A, and the nucleotide sequence was deposited in GenBank as Arthrobacter sp. Raats (accession number HQ875723). The bacteria produced an extracellular bioflocculant when grown aerobically in a production medium containing glucose as sole carbon source and had an initial pH of 7.0. Influences of carbon, nitrogen and metal ions sources, as well as initial pH on flocculating activity were investigated. The bacteria optimally produced the bioflocullant when lactose and urea were used as sole sources of carbon and nitrogen respectively with flocculating activities of 75.4% and 83.4% respectively. Also, the bacteria produced the bioflocculant optimally when initial pH of the medium was 7.0 (flocculating activity 84%), and when Mg2+ was used as cation (flocculating activity 77%). Composition analyses indicated the bioflocculant to be principally a glycoprotein made up of about 56% protein and 25% total carbohydrate. Full article
Open AccessArticle
Cloning and Expression Analysis of a PISTILLATA Homologous Gene from Pineapple (Ananas comosus L. Merr)
Int. J. Mol. Sci. 2012, 13(1), 1039-1053; https://doi.org/10.3390/ijms13011039
Received: 6 December 2011 / Revised: 27 December 2011 / Accepted: 11 January 2012 / Published: 19 January 2012
Cited by 9 | Viewed by 3769 | PDF Full-text (1505 KB) | HTML Full-text | XML Full-text
Abstract
PISTILLATA (PI)-like genes are crucial regulators of flowering in angiosperms. A homologue of PI, designated as AcPI (Genbank accession number HQ717796), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid [...] Read more.
PISTILLATA (PI)-like genes are crucial regulators of flowering in angiosperms. A homologue of PI, designated as AcPI (Genbank accession number HQ717796), was isolated from pineapple cultivar Comte de Paris by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The cDNA sequence of AcPI is 907 bp in length and contains an open reading frame of 594 bp, which encodes a protein of 197 amino acids. The molecular weight was 2.29 kDa and the isoelectric point was 9.28. The alignment showed that AcPI had a high identity with CsPIC2 (78.6%), AoPI (77.4%), OrcPI (75.7%) and HPI2 (72.4%). Quantitative real-time polymerase chain reaction (qRT-PCR) analyses in different tissues showed that the expression pattern of AcPI was different from the B-class genes in eudicots. AcPI was expressed in all the tissues investigated. The expression level was very low in fruit stems, bracts, leaves and sepals, high in petals and carpels, and moderate in apical meristems, flesh and stamens. The qRT-PCR analyses in different stages indicated that the expression of AcPI reached the highest level at 40 days after flower inducement, when the multiple fruit and floral organs were forming. It proved the important role of AcPI in floral organs and fruit development. The 35S::AcPI transgenic Arabidopsis plants flowered earlier and had more inflorescences or branches than wild type plants. Full article
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Graphical abstract

Open AccessArticle
Structural Elucidation and Bioactivity of Biflavonoids from the Stems of Wikstroemia taiwanensis
Int. J. Mol. Sci. 2012, 13(1), 1029-1038; https://doi.org/10.3390/ijms13011029
Received: 6 December 2011 / Revised: 1 January 2012 / Accepted: 10 January 2012 / Published: 18 January 2012
Cited by 8 | Viewed by 3262 | PDF Full-text (153 KB) | HTML Full-text | XML Full-text
Abstract
Three new biflavonoids, wikstaiwanones A–C (13), along with four known compounds (47) were isolated from the stems of Wikstroemia taiwanensis (Thymelaeaceae). Their structures were elucidated by spectroscopic analysis. Compounds 4 and 5 showed antitubercular activity [...] Read more.
Three new biflavonoids, wikstaiwanones A–C (13), along with four known compounds (47) were isolated from the stems of Wikstroemia taiwanensis (Thymelaeaceae). Their structures were elucidated by spectroscopic analysis. Compounds 4 and 5 showed antitubercular activity against Mycobacterium tuberculosis with MIC values of 15 μg/mL, respectively. Full article
Open AccessArticle
Plasmonic Molecular Nanohybrids—Spectral Dependence of Fluorescence Quenching
Int. J. Mol. Sci. 2012, 13(1), 1018-1028; https://doi.org/10.3390/ijms13011018
Received: 21 December 2011 / Revised: 11 January 2012 / Accepted: 13 January 2012 / Published: 18 January 2012
Cited by 13 | Viewed by 3869 | PDF Full-text (343 KB) | HTML Full-text | XML Full-text
Abstract
We demonstrate strong spectral dependence of the efficiency of fluorescence quenching in molecular systems composed of organic dyes and gold nanoparticles. In order to probe the coupling with metallic nanoparticles we use dyes with varied spectral overlap between the plasmon resonance and their [...] Read more.
We demonstrate strong spectral dependence of the efficiency of fluorescence quenching in molecular systems composed of organic dyes and gold nanoparticles. In order to probe the coupling with metallic nanoparticles we use dyes with varied spectral overlap between the plasmon resonance and their absorption. Hybrid molecular structures were obtained via conjugation of metallic nanoparticles with the dyes using biotin-streptavidin linkage. For dyes featuring absorption above the plasmon excitation in gold nanoparticles, laser excitation induces minute changes in the fluorescence intensity and its lifetime for both conjugated and non-conjugated mixtures, which are the reference. In contrast, when the absorption of the dye overlaps with the plasmon resonance, the effect is quite dramatic, reaching 85% and 95% fluorescence quenching for non-conjugated and conjugated mixtures, respectively. The degree of fluorescence quenching strongly depends upon the concentration of metallic nanoparticles. Importantly, the origin of the fluorescence quenching is different in the case of the conjugated mixture, as evidenced by time-resolved fluorescence. For conjugated mixtures of dyes resonant with plasmon, excitation features two-exponential decay. This is in contrast to the single exponential decay measured for the off-resonant configuration. The results provide valuable insight into spectral dependence of the fluorescence quenching in molecular assemblies involving organic dyes and metallic nanoparticles. Full article
(This article belongs to the Special Issue From Molecules to Nanomaterials)
Open AccessArticle
Photostability of Isovaline and its Precursor 5-Ethyl-5-methylhydantoin Exposed to Simulated Space Radiations
Int. J. Mol. Sci. 2012, 13(1), 1006-1017; https://doi.org/10.3390/ijms13011006
Received: 9 November 2011 / Revised: 4 January 2012 / Accepted: 9 January 2012 / Published: 17 January 2012
Cited by 4 | Viewed by 3193 | PDF Full-text (477 KB) | HTML Full-text | XML Full-text
Abstract
Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and γ-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. [...] Read more.
Aqueous solutions of isovaline and its precursor molecule, 5-ethyl-5-methylhydantoin, were irradiated with ultraviolet and γ-ray photons, to evaluate their structural stability against space radiation. The degree of photolysis was measured and irradiation products were identified using chiral, reversed-phase and ion-exchange high-performance liquid chromatography. The experimental results show that the degree of photolysis of 5-ethyl-5-methylhydantoin is more significant than that of isovaline under ultraviolet light irradiation, while the results under γ-ray irradiation are the opposite. As the products of isovaline photolysis, aspartic acid, serine, glutamic acid and alanine were dominantly detected. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle
Boesenbergia pandurata Attenuates Diet-Induced Obesity by Activating AMP-Activated Protein Kinase and Regulating Lipid Metabolism
Int. J. Mol. Sci. 2012, 13(1), 994-1005; https://doi.org/10.3390/ijms13010994
Received: 20 December 2011 / Revised: 22 December 2011 / Accepted: 11 January 2012 / Published: 17 January 2012
Cited by 18 | Viewed by 4612 | PDF Full-text (583 KB) | HTML Full-text | XML Full-text
Abstract
Obesity, a chronic metabolic disorder, is characterized by enlarged fat mass and dysregulation of lipid metabolism. The medicinal plant, Boesenbergia pandurata (Roxb.) Schltr., has been reported to possess anti-oxidative and anti-inflammatory properties; however, its anti-obesity activity is unexplored. The present study was conducted [...] Read more.
Obesity, a chronic metabolic disorder, is characterized by enlarged fat mass and dysregulation of lipid metabolism. The medicinal plant, Boesenbergia pandurata (Roxb.) Schltr., has been reported to possess anti-oxidative and anti-inflammatory properties; however, its anti-obesity activity is unexplored. The present study was conducted to determine whether B. pandurata extract (BPE), prepared from its rhizome parts, attenuated high-fat diet (HFD)-induced obesity in C57BL/6J mice. The molecular mechanism was investigated in 3T3-L1 adipocytes and HepG2 human hepatoma cells. BPE treatment decreased triglyceride accumulation in both 3T3-L1 adipocytes and HepG2 hepatocytes by activating AMP-activated protein kinase (AMPK) signaling and regulating the expression of lipid metabolism-related proteins. In the animal model, oral administration of BPE (200 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were suppressed by BPE administration. Fat pad masses were reduced in BPE-treated mice, as evidenced by reduced adipocyte size. Furthermore, BPE protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. BPE also activated AMPK signaling and altered the expression of lipid metabolism-related proteins in white adipose tissue and liver. Taken together, these findings indicate that BPE attenuates HFD-induced obesity by activating AMPK and regulating lipid metabolism, suggesting a potent anti-obesity agent. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle
Isoflurane Protects Against Human Endothelial Cell Apoptosis by Inducing Sphingosine Kinase-1 via ERK MAPK
Int. J. Mol. Sci. 2012, 13(1), 977-993; https://doi.org/10.3390/ijms13010977
Received: 19 December 2011 / Revised: 11 January 2012 / Accepted: 12 January 2012 / Published: 17 January 2012
Cited by 15 | Viewed by 3642 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Endothelial dysfunction is a major clinical problem affecting virtually every patient requiring critical care. Volatile anesthetics are frequently used during the perioperative period and protect the heart and kidney against ischemia and reperfusion injury. We aimed to determine whether isoflurane, the most commonly [...] Read more.
Endothelial dysfunction is a major clinical problem affecting virtually every patient requiring critical care. Volatile anesthetics are frequently used during the perioperative period and protect the heart and kidney against ischemia and reperfusion injury. We aimed to determine whether isoflurane, the most commonly used volatile anesthetic in the USA, protects against endothelial apoptosis and necrosis and the mechanisms involved in this protection. Human endothelial EA.hy926 cells were pretreated with isoflurane or carrier gas (95% room air + 5% CO2) then subjected to apoptosis with tumor necrosis factor-α or to necrosis with hydrogen peroxide. DNA laddering and in situ Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick-End Labeling (TUNEL) staining determined EA.hy926 cell apoptosis and percent LDH released determined necrosis. We also determined whether isoflurane modulates the expression and activity of sphingosine kinase-1 (SK1) and induces the phosphorylation of extracellular signal regulated kinase (ERK MAPK) as both enzymes are known to protect against cell death. Isoflurane pretreatment significantly decreased apoptosis in EA.hy926 cells as evidenced by reduced TUNEL staining and DNA laddering without affecting necrosis. Mechanistically, isoflurane induces the phosphorylation of ERK MAPK and increased SK1 expression and activity in EA.hy926 cells. Finally, selective blockade of SK1 (with SKI-II) or S1P1 receptor (with W146) abolished the anti-apoptotic effects of isoflurane. Taken together, we demonstrate that isoflurane, in addition to its potent analgesic and anesthetic properties, protects against endothelial apoptosis most likely via SK1 and ERK MAPK activation. Our findings have significant clinical implication for protection of endothelial cells during the perioperative period and patients requiring critical care. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle
Freshwater Plants Synthesize Sulfated Polysaccharides: Heterogalactans from Water Hyacinth (Eicchornia crassipes)
Int. J. Mol. Sci. 2012, 13(1), 961-976; https://doi.org/10.3390/ijms13010961
Received: 28 November 2011 / Revised: 30 December 2011 / Accepted: 6 January 2012 / Published: 17 January 2012
Cited by 21 | Viewed by 4486 | PDF Full-text (966 KB) | HTML Full-text | XML Full-text
Abstract
Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the [...] Read more.
Sulfated polysaccharides (SP) are found mainly in seaweeds and animals. To date, they have only been found in six plants and all inhabit saline environments. Furthermore, there are no reports of SP in freshwater or terrestrial plants. As such, this study investigated the presence of SP in freshwaters Eichhornia crassipes, Egeria densa, Egeria naja, Cabomba caroliniana, Hydrocotyle bonariensis and Nymphaea ampla. Chemical analysis identified sulfate in N. ampla, H. bonariensis and, more specifically, E. crassipes. In addition, chemical analysis, FT-IR spectroscopy, histological analysis, scanning electron microscopy (SEM) and energy-dispersive X-ray analysis (EDXA), as well as agarose gel electrophoresis detected SP in all parts of E. crassipes, primarily in the root (epidermis and vascular bundle). Galactose, glucose and arabinose are the main monosaccharides found in the sulfated polysaccharides from E. crassipes. In activated partial thromboplastin time (APTT) test, to evaluate the intrinsic coagulation pathway, SP from the root and rhizome prolonged the coagulation time to double the baseline value, with 0.1 mg/mL and 0.15 mg/mL, respectively. However, SP from the leaf and petiole showed no anticoagulant activity. Eichornia SP demonstrated promising anticoagulant potential and have been selected for further studies on bioguided fractionation; isolation and characterization of pure polysaccharides from this species. Additionally in vivo experiments are needed and are already underway. Full article
Open AccessArticle
Improvement of Thermal Stability via Outer-Loop Ion Pair Interaction of Mutated T1 Lipase from Geobacillus zalihae Strain T1
Int. J. Mol. Sci. 2012, 13(1), 943-960; https://doi.org/10.3390/ijms13010943
Received: 8 October 2011 / Revised: 25 November 2011 / Accepted: 28 November 2011 / Published: 17 January 2012
Cited by 15 | Viewed by 4093 | PDF Full-text (1631 KB) | HTML Full-text | XML Full-text
Abstract
Mutant D311E and K344R were constructed using site-directed mutagenesis to introduce an additional ion pair at the inter-loop and the intra-loop, respectively, to determine the effect of ion pairs on the stability of T1 lipase isolated from Geobacillus zalihae. A series of [...] Read more.
Mutant D311E and K344R were constructed using site-directed mutagenesis to introduce an additional ion pair at the inter-loop and the intra-loop, respectively, to determine the effect of ion pairs on the stability of T1 lipase isolated from Geobacillus zalihae. A series of purification steps was applied, and the pure lipases of T1, D311E and K344R were obtained. The wild-type and mutant lipases were analyzed using circular dichroism. The Tm for T1 lipase, D311E lipase and K344R lipase were approximately 68.52 °C, 70.59 °C and 68.54 °C, respectively. Mutation at D311 increases the stability of T1 lipase and exhibited higher Tm as compared to the wild-type and K344R. Based on the above, D311E lipase was chosen for further study. D311E lipase was successfully crystallized using the sitting drop vapor diffusion method. The crystal was diffracted at 2.1 Å using an in-house X-ray beam and belonged to the monoclinic space group C2 with the unit cell parameters a = 117.32 Å, b = 81.16 Å and c = 100.14 Å. Structural analysis showed the existence of an additional ion pair around E311 in the structure of D311E. The additional ion pair in D311E may regulate the stability of this mutant lipase at high temperatures as predicted in silico and spectroscopically. Full article
(This article belongs to the Special Issue Protein Crystallography in Molecular Biology)
Open AccessArticle
Effect of Enzymatic Treatment of Different Starch Sources on the in Vitro Rate and Extent of Starch Digestion
Int. J. Mol. Sci. 2012, 13(1), 929-942; https://doi.org/10.3390/ijms13010929
Received: 16 December 2011 / Revised: 5 January 2012 / Accepted: 5 January 2012 / Published: 17 January 2012
Cited by 12 | Viewed by 3649 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text | Correction | Supplementary Files
Abstract
Gelatinized wheat, potato and waxy maize starches were treated enzymatically in order to increase the degree of branching of the amylopectin fraction and thereby change the starch degradation profile towards a higher proportion of slowly digestible starch (SDS). The materials were characterized by [...] Read more.
Gelatinized wheat, potato and waxy maize starches were treated enzymatically in order to increase the degree of branching of the amylopectin fraction and thereby change the starch degradation profile towards a higher proportion of slowly digestible starch (SDS). The materials were characterized by single-pulse 1H HR-MAS NMR spectroscopy and in vitro digestion profile according to the Englyst procedure. Using various concentrations and incubation times with branching enzyme (EC 2.4.1.18) without or with additional treatment with the hydrolytic enzymes; β-amylase (EC 3.2.1.2), α-glucosidase (EC 3.2.1.20), or amyloglucosidase (EC 3.2.1.3) the proportion of α-(1-6) linkages was increased by up to a factor of 4.1, 5 and 5.8 in waxy maize, wheat and potato starches, respectively. The proportion of SDS was significantly increased when using hydrolytic enzymes after treatment with branching enzyme but it was only for waxy maize that the proportion of α-(1-6) bonds and the in vitro digestion profile was significantly correlated. Full article
Open AccessArticle
Characterization of Electrosynthesized Conjugated Polymer-Carbon Nanotube Composite: Optical Nonlinearity and Electrical Property
Int. J. Mol. Sci. 2012, 13(1), 918-928; https://doi.org/10.3390/ijms13010918
Received: 23 October 2011 / Accepted: 19 December 2011 / Published: 16 January 2012
Cited by 17 | Viewed by 3332 | PDF Full-text (1002 KB) | HTML Full-text | XML Full-text
Abstract
The effects of multi-walled carbon nanotube (MWNT) concentration on the structural, optical and electrical properties of conjugated polymer-carbon nanotube composite are discussed. Multi-walled carbon nanotube-polypyrrole nanocomposites were synthesized by electrochemical polymerization of monomers in the presence of different amounts of MWNTs using sodium [...] Read more.
The effects of multi-walled carbon nanotube (MWNT) concentration on the structural, optical and electrical properties of conjugated polymer-carbon nanotube composite are discussed. Multi-walled carbon nanotube-polypyrrole nanocomposites were synthesized by electrochemical polymerization of monomers in the presence of different amounts of MWNTs using sodium dodecylbenzensulfonate (SDBS) as surfactant at room temperature and normal pressure. Field emission scanning electron microscopy (FESEM) indicates that the polymer is wrapped around the nanotubes. Measurement of the nonlinear refractive indices (n2) and the nonlinear absorption (β) of the samples with different MWNT concentrations measurements were performed by a single Z-scan method using continuous wave (CW) laser beam excitation wavelength of λ = 532 nm. The results show that both nonlinear optical parameters increased with increasing the concentration of MWNTs. The third order nonlinear susceptibilities were also calculated and found to follow the same trend as n2 and β. In addition, the conductivity of the composite film was found to increase rapidly with the increase in the MWNT concentration. Full article
(This article belongs to the Section Materials Science)
Open AccessArticle
Structural Modeling and Biochemical Characterization of Recombinant KPN_02809, a Zinc-Dependent Metalloprotease from Klebsiella pneumoniae MGH 78578
Int. J. Mol. Sci. 2012, 13(1), 901-917; https://doi.org/10.3390/ijms13010901
Received: 27 October 2011 / Revised: 29 December 2011 / Accepted: 9 January 2012 / Published: 16 January 2012
Cited by 7 | Viewed by 4047 | PDF Full-text (3917 KB) | HTML Full-text | XML Full-text
Abstract
Klebsiella pneumoniae is a Gram-negative, cylindrical rod shaped opportunistic pathogen that is found in the environment as well as existing as a normal flora in mammalian mucosal surfaces such as the mouth, skin, and intestines. Clinically it is the most important member of [...] Read more.
Klebsiella pneumoniae is a Gram-negative, cylindrical rod shaped opportunistic pathogen that is found in the environment as well as existing as a normal flora in mammalian mucosal surfaces such as the mouth, skin, and intestines. Clinically it is the most important member of the family of Enterobacteriaceae that causes neonatal sepsis and nosocomial infections. In this work, a combination of protein sequence analysis, structural modeling and molecular docking simulation approaches were employed to provide an understanding of the possible functions and characteristics of a hypothetical protein (KPN_02809) from K. pneumoniae MGH 78578. The computational analyses showed that this protein was a metalloprotease with zinc binding motif, HEXXH. To verify this result, a ypfJ gene which encodes for this hypothetical protein was cloned from K. pneumoniae MGH 78578 and the protein was overexpressed in Escherichia coli BL21 (DE3). The purified protein was about 32 kDa and showed maximum protease activity at 30 °C and pH 8.0. The enzyme activity was inhibited by metalloprotease inhibitors such as EDTA, 1,10-phenanthroline and reducing agent, 1,4-dithiothreitol (DTT). Each molecule of KPN_02809 protein was also shown to bind one zinc ion. Hence, for the first time, we experimentally confirmed that KPN_02809 is an active enzyme with zinc metalloprotease activity. Full article
(This article belongs to the Special Issue Hypothetical Proteins)
Open AccessArticle
Molecular Cloning, Characterization and Predicted Structure of a Putative Copper-Zinc SOD from the Camel, Camelus dromedarius
Int. J. Mol. Sci. 2012, 13(1), 879-900; https://doi.org/10.3390/ijms13010879
Received: 13 December 2011 / Revised: 25 December 2011 / Accepted: 28 December 2011 / Published: 16 January 2012
Cited by 7 | Viewed by 3838 | PDF Full-text (1090 KB) | HTML Full-text | XML Full-text
Abstract
Superoxide dismutase (SOD) is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and [...] Read more.
Superoxide dismutase (SOD) is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and expression of SOD gene in an animal naturally exposed most of its life to the direct sunlight as a cause of oxidative stress. Arabian camel (one humped camel, Camelus dromedarius) is adapted to the widely varying desert climatic conditions that extremely changes during daily life in the Arabian Gulf. Studying the cSOD1 in C. dromedarius could help understand the impact of exposure to direct sunlight and desert life on the health status of such mammal. The full coding region of a putative CuZnSOD gene of C. dromedarius (cSOD1) was amplified by reverse transcription PCR and cloned for the first time (gene bank accession number for nucleotides and amino acids are JF758876 and AEF32527, respectively). The cDNA sequencing revealed an open reading frame of 459 nucleotides encoding a protein of 153 amino acids which is equal to the coding region of SOD1 gene and protein from many organisms. The calculated molecular weight and isoelectric point of cSOD1 was 15.7 kDa and 6.2, respectively. The level of expression of cSOD1 in different camel tissues (liver, kidney, spleen, lung and testis) was examined using Real Time-PCR. The highest level of cSOD1 transcript was found in the camel liver (represented as 100%) followed by testis (45%), kidney (13%), lung (11%) and spleen (10%), using 18S ribosomal subunit as endogenous control. The deduced amino acid sequence exhibited high similarity with Cebus apella (90%), Sus scrofa (88%), Cavia porcellus (88%), Mus musculus (88%), Macaca mulatta (87%), Pan troglodytes (87%), Homo sapiens (87%), Canis familiaris (86%), Bos taurus (86%), Pongo abelii (85%) and Equus caballus (82%). Phylogenetic analysis revealed that cSOD1 is grouped together with S. scrofa. The predicted 3D structure of cSOD1 showed high similarity with the human and bovine CuZnSOD homologues. The Root-mean-square deviation (rmsd) between cSOD1/hSOD1 and cSOD1/bSOD1 superimposed structure pairs were 0.557 and 0.425 A. The Q-score of cSOD1-hSOD1 and cSOD1-bSOD1 were 0.948 and 0.961, respectively. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle
Icariin Ameliorates Streptozotocin-Induced Diabetic Retinopathy in Vitro and in Vivo
Int. J. Mol. Sci. 2012, 13(1), 866-878; https://doi.org/10.3390/ijms13010866
Received: 8 November 2011 / Revised: 22 December 2011 / Accepted: 28 December 2011 / Published: 16 January 2012
Cited by 20 | Viewed by 3500 | PDF Full-text (567 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two [...] Read more.
This study investigated the effect of Icariin (ICA) supplementation on diabetic retinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague Dawley rats were randomly distributed into a control group and a streptozotocin-induced diabetes group. Diabetic rats were randomly divided into two groups; one group received ICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a placebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV), vascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a expression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at various concentrations (0, 101, 102, 103 nmol/mL) on neurite growth were investigated also in retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous pathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as decreased Collagen IV and Müller cell content) were noted in the retinal vessels of diabetic rats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced neurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations are indicated. Full article
Open AccessArticle
MiRNAs and LincRNAs: Could They Be Considered as Biomarkers in Colorectal Cancer?
Int. J. Mol. Sci. 2012, 13(1), 840-865; https://doi.org/10.3390/ijms13010840
Received: 2 November 2011 / Revised: 15 December 2011 / Accepted: 28 December 2011 / Published: 16 January 2012
Cited by 18 | Viewed by 4401 | PDF Full-text (345 KB) | HTML Full-text | XML Full-text
Abstract
Recent advances in the field of RNA research have provided compelling evidence implicating microRNA (miRNA) and long non-coding RNA molecules in many diverse and substantial biological processes, including transcriptional and post-transcriptional regulation of gene expression, genomic imprinting, and modulation of protein activity. Thus, [...] Read more.
Recent advances in the field of RNA research have provided compelling evidence implicating microRNA (miRNA) and long non-coding RNA molecules in many diverse and substantial biological processes, including transcriptional and post-transcriptional regulation of gene expression, genomic imprinting, and modulation of protein activity. Thus, studies of non-coding RNA (ncRNA) may contribute to the discovery of possible biomarkers in human cancers. Considering that the response to chemotherapy can differ amongst individuals, researchers have begun to isolate and identify the genes responsible. Identification of targets of this ncRNA associated with cancer can suggest that networks of these linked to oncogenes or tumor suppressors play pivotal roles in cancer development. Moreover, these ncRNA are attractive drug targets since they may be differentially expressed in malignant versus normal cells and regulate expression of critical proteins in the cell. This review focuses on ncRNAs that are differently expressed in malignant tissue, and discusses some of challenges derived from their use as potential biomarkers of tumor properties. Full article
Open AccessArticle
Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways
Int. J. Mol. Sci. 2012, 13(1), 828-839; https://doi.org/10.3390/ijms13010828
Received: 16 December 2011 / Revised: 28 December 2011 / Accepted: 4 January 2012 / Published: 16 January 2012
Cited by 24 | Viewed by 3021 | PDF Full-text (504 KB) | HTML Full-text | XML Full-text
Abstract
Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. Methods: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time [...] Read more.
Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. Methods: mRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot. Results: Lewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level. There were no differences in proteins and the mRNA levels of CDK2, CDK4 and CDK6 before and after gene transfection. Anti-Lewis y antibody, ERK and PI3K pathway inhibitors PD98059 and LY294002 reduced the difference in cyclin and CKI expression caused by Lewis y overexpression. Conclusion: Lewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation. Full article
Open AccessArticle
Evaluation of a Centrifuged Double Y-Shape Microfluidic Platform for Simple Continuous Cell Environment Exchange
Int. J. Mol. Sci. 2012, 13(1), 819-827; https://doi.org/10.3390/ijms13010819
Received: 7 December 2011 / Revised: 6 January 2012 / Accepted: 9 January 2012 / Published: 13 January 2012
Cited by 2 | Viewed by 3039 | PDF Full-text (796 KB) | HTML Full-text | XML Full-text
Abstract
We have demonstrated the efficacy of a microfluidic medium exchange method for single cells using passive centrifugal force of a rotating microfluidic-chip based platform. At the boundary of two laminar flows at the gathering area of two microfluidic pathways in a Y-shape, the [...] Read more.
We have demonstrated the efficacy of a microfluidic medium exchange method for single cells using passive centrifugal force of a rotating microfluidic-chip based platform. At the boundary of two laminar flows at the gathering area of two microfluidic pathways in a Y-shape, the cells were successfully transported from one laminar flow to the other, without mixing the two microfluidic mediums of the two laminar flows during cell transportation, within 5 s with 1 g (150 rpm) to 36.3 g (900 rpm) acceleration, with 93.5% efficiency. The results indicate that this is one of the most simple and precise tools for exchanging medium in the shortest amount of time. Full article
(This article belongs to the Special Issue Microfluidics)
Open AccessArticle
Procyanidins from Wild Grape (Vitis amurensis) Seeds Regulate ARE-Mediated Enzyme Expression via Nrf2 Coupled with p38 and PI3K/Akt Pathway in HepG2 Cells
Int. J. Mol. Sci. 2012, 13(1), 801-818; https://doi.org/10.3390/ijms13010801
Received: 19 December 2011 / Revised: 30 December 2011 / Accepted: 5 January 2012 / Published: 13 January 2012
Cited by 36 | Viewed by 4151 | PDF Full-text (339 KB) | HTML Full-text | XML Full-text
Abstract
Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles [...] Read more.
Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1–F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway. Full article
(This article belongs to the Special Issue Advances in Nutraceutical Research)
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