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Int. J. Mol. Sci., Volume 15, Issue 5 (May 2014), Pages 7049-9172

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Open AccessArticle The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice
Int. J. Mol. Sci. 2014, 15(5), 9160-9172; https://doi.org/10.3390/ijms15059160
Received: 6 March 2014 / Revised: 7 May 2014 / Accepted: 12 May 2014 / Published: 22 May 2014
Cited by 6 | Viewed by 2515 | PDF Full-text (2622 KB) | HTML Full-text | XML Full-text
Abstract
Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura
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Activation of peroxisome proliferator-activated receptor (PPAR) α disrupts growth-related activities in a variety of human cancers. This study was designed to determine whether fenofibrate, a PPARα agonist, can suppress 4-nitroquinoline 1-oxide (4-NQO)-induced proliferative lesions in the lung of obese hyperlipidemic mice. Male Tsumura Suzuki Obese Diabetic mice were subcutaneously injected with 4-NQO to induce lung proliferative lesions, including adenocarcinomas. They were then fed a diet containing 0.01% or 0.05% fenofibrate for 29 weeks, starting 1 week after 4-NQO administration. At week 30, the incidence and multiplicity (number of lesions/mouse) of pulmonary proliferative lesions were lower in mice treated with 4-NQO and both doses of fenofibrate compared with those in mice treated with 4-NQO alone. The incidence and multiplicity of lesions were significantly lower in mice treated with 4-NQO and 0.05% fenofibrate compared with those in mice treated with 4-NQO alone (p < 0.05). Both doses of fenofibrate significantly reduced the proliferative activity of the lesions in 4-NQO-treated mice (p < 0.05). Fenofibrate also significantly reduced the serum insulin and insulin-like growth factor (IGF)-1 levels, and decreased the immunohistochemical expression of IGF-1 receptor (IGF-1R), phosphorylated Akt, and phosphorylated Erk1/2 in lung adenocarcinomas. Our results indicate that fenofibrate can prevent the development of 4-NQO-induced proliferative lesions in the lung by modulating the insulin-IGF axis. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Functional Polymorphisms of the ABCG2 Gene Are Associated with Gout Disease in the Chinese Han Male Population
Int. J. Mol. Sci. 2014, 15(5), 9149-9159; https://doi.org/10.3390/ijms15059149
Received: 30 January 2014 / Revised: 23 April 2014 / Accepted: 12 May 2014 / Published: 22 May 2014
Cited by 17 | Viewed by 2264 | PDF Full-text (335 KB) | HTML Full-text | XML Full-text
Abstract
Background: Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further
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Background: Gout is a common type of arthritis that is characterized by hyperuricemia, tophi and joint inflammation. Genetic variations in the ABCG2 gene have been reported to influence serum uric acid levels and to participate in the pathogenesis of gout, but no further data have been reported in the Han Chinese population. Methods: Peripheral blood DNA was isolated from 352 male patients with gout and 350 gout-free normal male controls. High-resolution melting analysis and Sanger sequencing were performed to identify the genetic polymorphisms V12M, Q141K and Q126X in the ABCG2 gene. Genotype and haplotype analyses were utilized to determine the disease odds ratios (ORs). A prediction model for gout risk using ABCG2 protein function was established based on the genotype combination of Q126X and Q141K. Results: For Q141K, the A allele frequency was 49.6% in the gout patients and 30.9% in the controls (OR 2.20, 95% confidence interval (CI): 1.77–2.74, p = 8.99 × 10−13). Regarding Q126X, the T allele frequency was 4.7% in the gout patients and 1.7% in the controls (OR 2.91, 95% CI: 1.49–5.68, p = 1.57 × 10−3). The A allele frequency for V12M was lower (18.3%) in the gout patients than in the controls (29%) (OR 0.55, 95% CI 0.43–0.71, p = 2.55 × 10−6). In the order of V12M, Q126X and Q141K, the GCA and GTC haplotypes indicated increased disease risk (OR = 2.30 and 2.71, respectively). Patients with mild to severe ABCG2 dysfunction accounted for 78.4% of gout cases. Conclusion: The ABCG2 126X and 141K alleles are associated with an increased risk of gout, whereas 12M has a protective effect on gout susceptibility in the Han Chinese population. ABCG2 dysfunction can be used to evaluate gout risk. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle Aerobic Degradation of Trichloroethylene by Co-Metabolism Using Phenol and Gasoline as Growth Substrates
Int. J. Mol. Sci. 2014, 15(5), 9134-9148; https://doi.org/10.3390/ijms15059134
Received: 29 January 2014 / Revised: 24 April 2014 / Accepted: 4 May 2014 / Published: 22 May 2014
Cited by 10 | Viewed by 2590 | PDF Full-text (366 KB) | HTML Full-text | XML Full-text
Abstract
Trichloroethylene (TCE) is a common groundwater contaminant of toxic and carcinogenic concern. Aerobic co-metabolic processes are the predominant pathways for TCE complete degradation. In this study, Pseudomonas fluorescens was studied as the active microorganism to degrade TCE under aerobic condition by co-metabolic degradation
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Trichloroethylene (TCE) is a common groundwater contaminant of toxic and carcinogenic concern. Aerobic co-metabolic processes are the predominant pathways for TCE complete degradation. In this study, Pseudomonas fluorescens was studied as the active microorganism to degrade TCE under aerobic condition by co-metabolic degradation using phenol and gasoline as growth substrates. Operating conditions influencing TCE degradation efficiency were optimized. TCE co-metabolic degradation rate reached the maximum of 80% under the optimized conditions of degradation time of 3 days, initial OD600 of microorganism culture of 0.14 (1.26 × 107 cell/mL), initial phenol concentration of 100 mg/L, initial TCE concentration of 0.1 mg/L, pH of 6.0, and salinity of 0.1%. The modified transformation capacity and transformation yield were 20 μg (TCE)/mg (biomass) and 5.1 μg (TCE)/mg (phenol), respectively. Addition of nutrient broth promoted TCE degradation with phenol as growth substrate. It was revealed that catechol 1,2-dioxygenase played an important role in TCE co-metabolism. The dechlorination of TCE was complete, and less chlorinated products were not detected at the end of the experiment. TCE could also be co-metabolized in the presence of gasoline; however, the degradation rate was not high (28%). When phenol was introduced into the system of TCE and gasoline, TCE and gasoline could be removed at substantial rates (up to 59% and 69%, respectively). This study provides a promising approach for the removal of combined pollution of TCE and gasoline. Full article
(This article belongs to the Special Issue Biodegradability of Materials)
Open AccessReview Brain Metastasis-Initiating Cells: Survival of the Fittest
Int. J. Mol. Sci. 2014, 15(5), 9117-9133; https://doi.org/10.3390/ijms15059117
Received: 15 April 2014 / Revised: 12 May 2014 / Accepted: 13 May 2014 / Published: 22 May 2014
Cited by 12 | Viewed by 3826 | PDF Full-text (548 KB) | HTML Full-text | XML Full-text
Abstract
Brain metastases (BMs) are the most common brain tumor in adults, developing in about 10% of adult cancer patients. It is not the incidence of BM that is alarming, but the poor patient prognosis. Even with aggressive treatments, median patient survival is only
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Brain metastases (BMs) are the most common brain tumor in adults, developing in about 10% of adult cancer patients. It is not the incidence of BM that is alarming, but the poor patient prognosis. Even with aggressive treatments, median patient survival is only months. Despite the high rate of BM-associated mortality, very little research is conducted in this area. Lack of research and staggeringly low patient survival is indicative that a novel approach to BMs and their treatment is needed. The ability of a small subset of primary tumor cells to produce macrometastases is reminiscent of brain tumor-initiating cells (BTICs) or cancer stem cells (CSCs) hypothesized to form primary brain tumors. BTICs are considered stem cell-like due to their self-renewal and differentiation properties. Similar to the subset of cells forming metastases, BTICs are most often a rare subpopulation. Based on the functional definition of a TIC, cells capable of forming a BM could be considered to be brain metastasis-initiating cells (BMICs). These putative BMICs would not only have the ability to initiate tumor growth in a secondary niche, but also the machinery to escape the primary tumor, migrate through the circulation, and invade the neural niche. Full article
(This article belongs to the Special Issue Brain Metastasis 2014)
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Open AccessArticle Chemical Characterization and Antitumor Activities of Polysaccharide Extracted from Ganoderma lucidum
Int. J. Mol. Sci. 2014, 15(5), 9103-9116; https://doi.org/10.3390/ijms15059103
Received: 19 March 2014 / Revised: 1 May 2014 / Accepted: 4 May 2014 / Published: 22 May 2014
Cited by 23 | Viewed by 3078 | PDF Full-text (2188 KB) | HTML Full-text | XML Full-text
Abstract
Ganoderma lucidum polysaccharide (GLP) is a biologically active substance reported to possess anti-tumor ability. Nonetheless, the mechanisms of GLP-stimulated apoptosis are still unclear. This study aims to determine the inhibitory and apoptosis-inducing effects of GLP on HCT-116 cells. We found that GLP reduced
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Ganoderma lucidum polysaccharide (GLP) is a biologically active substance reported to possess anti-tumor ability. Nonetheless, the mechanisms of GLP-stimulated apoptosis are still unclear. This study aims to determine the inhibitory and apoptosis-inducing effects of GLP on HCT-116 cells. We found that GLP reduced cell viability on HCT-116 cells in a time- and dose-dependent manner, which in turn, induced cell apoptosis. The observed apoptosis was characterized by morphological changes, DNA fragmentation, mitochondrial membrane potential decrease, S phase population increase, and caspase-3 and -9 activation. Furthermore, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 led to a dramatic decrease of the GLP-induced apoptosis. Western blot analysis unveiled that GLP up-regulated the expression of Bax/Bcl-2, caspase-3 and poly (ADP-ribose) polymerase (PARP). These results demonstrate that apoptosis stimulated by GLP in human colorectal cancer cells is associated with activation of mitochondrial and mitogen-activated protein kinase (MAPK) pathways. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Green Conversion of Agroindustrial Wastes into Chitin and Chitosan by Rhizopus arrhizus and Cunninghamella elegans Strains
Int. J. Mol. Sci. 2014, 15(5), 9082-9102; https://doi.org/10.3390/ijms15059082
Received: 12 January 2014 / Revised: 31 March 2014 / Accepted: 25 April 2014 / Published: 21 May 2014
Cited by 11 | Viewed by 2534 | PDF Full-text (1067 KB) | HTML Full-text | XML Full-text
Abstract
This article sets out a method for producing chitin and chitosan by Cunninghamella elegans and Rhizopus arrhizus strains using a green metabolic conversion of agroindustrial wastes (corn steep liquor and molasses). The physicochemical characteristics of the biopolymers and antimicrobial activity are described. Chitin
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This article sets out a method for producing chitin and chitosan by Cunninghamella elegans and Rhizopus arrhizus strains using a green metabolic conversion of agroindustrial wastes (corn steep liquor and molasses). The physicochemical characteristics of the biopolymers and antimicrobial activity are described. Chitin and chitosan were extracted by alkali-acid treatment, and characterized by infrared spectroscopy, viscosity and X-ray diffraction. The effectiveness of chitosan from C. elegans and R. arrhizus in inhibiting the growth of Listeria monocytogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli and Yersinia enterocolitica were evaluated by determining the minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC). The highest production of biomass (24.60 g/L), chitin (83.20 mg/g) and chitosan (49.31 mg/g) was obtained by R. arrhizus. Chitin and chitosan from both fungi showed a similar degree of deacetylation, respectively of 25% and 82%, crystallinity indices of 33.80% and 32.80% for chitin, and 20.30% and 17.80% for chitosan. Both chitin and chitosan presented similar viscosimetry of 3.79–3.40 cP and low molecular weight of 5.08 × 103 and 4.68 × 103 g/mol. They both showed identical MIC and MBC for all bacteria assayed. These results suggest that: agricultural wastes can be produced in an environmentally friendly way; chitin and chitosan can be produced economically; and that chitosan has antimicrobial potential against pathogenic bacteria. Full article
(This article belongs to the Section Green Chemistry)
Open AccessArticle A pH and Redox Dual Responsive 4-Arm Poly(ethylene glycol)-block-poly(disulfide histamine) Copolymer for Non-Viral Gene Transfection in Vitro and in Vivo
Int. J. Mol. Sci. 2014, 15(5), 9067-9081; https://doi.org/10.3390/ijms15059067
Received: 28 January 2014 / Revised: 6 May 2014 / Accepted: 12 May 2014 / Published: 21 May 2014
Cited by 13 | Viewed by 3326 | PDF Full-text (2224 KB) | HTML Full-text | XML Full-text
Abstract
A novel 4-arm poly(ethylene glycol)-b-poly(disulfide histamine) copolymer was synthesized by Michael addition reaction of poly(ethylene glycol) (PEG) vinyl sulfone and amine-capped poly(disulfide histamine) oligomer, being denoted as 4-arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes (<200 nm in average
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A novel 4-arm poly(ethylene glycol)-b-poly(disulfide histamine) copolymer was synthesized by Michael addition reaction of poly(ethylene glycol) (PEG) vinyl sulfone and amine-capped poly(disulfide histamine) oligomer, being denoted as 4-arm PEG-SSPHIS. This copolymer was able to condense DNA into nanoscale polyplexes (<200 nm in average diameter) with almost neutral surface charge (+(5–10) mV). Besides, these polyplexes were colloidal stable within 4 h in HEPES buffer saline at pH 7.4 (physiological environment), but rapidly dissociated to liberate DNA in the presence of 10 mM glutathione (intracellular reducing environment). The polyplexes also revealed pH-responsive surface charges which markedly increased with reducing pH values from 7.4–6.3 (tumor microenvironment). In vitro transfection experiments showed that polyplexes of 4-arm PEG-SSPHIS were capable of exerting enhanced transfection efficacy in MCF-7 and HepG2 cancer cells under acidic conditions (pH 6.3–7.0). Moreover, intravenous administration of the polyplexes to nude mice bearing HepG2-tumor yielded high transgene expression largely in tumor rather other normal organs. Importantly, this copolymer and its polyplexes had low cytotoxicity against the cells in vitro and caused no death of the mice. The results of this study indicate that 4-arm PEG-SSPHIS has high potential as a dual responsive gene delivery vector for cancer gene therapy. Full article
(This article belongs to the Special Issue Biodegradable Materials)
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Open AccessArticle Detection of a Specific Biomarker for Epstein-Barr Virus Using a Polymer-Based Genosensor
Int. J. Mol. Sci. 2014, 15(5), 9051-9066; https://doi.org/10.3390/ijms15059051
Received: 31 July 2013 / Revised: 4 May 2014 / Accepted: 7 May 2014 / Published: 21 May 2014
Cited by 9 | Viewed by 2075 | PDF Full-text (868 KB) | HTML Full-text | XML Full-text
Abstract
This paper describes methodology for direct and indirect detections of a specific oligonucleotide for Epstein-Barr virus (EBV) using electrochemical techniques. The sequence of oligonucleotide probe (EBV1) revealed a high sequence identity (100%) with the EBV genome. For the development of the genosensor, EBV1
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This paper describes methodology for direct and indirect detections of a specific oligonucleotide for Epstein-Barr virus (EBV) using electrochemical techniques. The sequence of oligonucleotide probe (EBV1) revealed a high sequence identity (100%) with the EBV genome. For the development of the genosensor, EBV1 was grafted to the platform sensitized with poly(4-aminothiophenol). After that, the hybridization reaction was carried out with the complementary target (EBV2) on the modified electrode surface using ethidium bromide as DNA intercalator. The oxidation peak currents of ethidium bromide increased linearly with the values of the concentration of the complementary sequences in the range from 3.78 to 756 µmol·L−1. In nonstringent experimental conditions, this genosensor can detect 17.32 nmol·L−1 (three independent experiments) of oligonucleotide target, discriminating between complementary and non-complementary oligonucleotides, as well as differentiating one-base mismatch, as required for detection of genetic diseases caused by point mutations. The biosensor also displayed high specificity to the EBV target with elimination of interference from mix (alanine, glucose, uric acid, ascorbic acid, bovine serum albumin (BSA), glutamate and glycine) and good stability (120 days). In addition, it was possible to observe differences between hybridized and non-hybridized surfaces through atomic force microscopy. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Open AccessArticle Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction
Int. J. Mol. Sci. 2014, 15(5), 9036-9050; https://doi.org/10.3390/ijms15059036
Received: 17 April 2014 / Revised: 12 May 2014 / Accepted: 14 May 2014 / Published: 21 May 2014
Cited by 6 | Viewed by 2332 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger
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Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators
Int. J. Mol. Sci. 2014, 15(5), 9016-9035; https://doi.org/10.3390/ijms15059016
Received: 16 January 2014 / Revised: 21 April 2014 / Accepted: 24 April 2014 / Published: 20 May 2014
Cited by 15 | Viewed by 2836 | PDF Full-text (3835 KB) | HTML Full-text | XML Full-text
Abstract
Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells
[...] Read more.
Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of mangiferin-induced β-cell proliferation. For this purpose, adult C57BL/6J mice after 7–14 days post-PPx, or a sham operation were subjected to mangiferin (30 and 90 mg/kg body weight) or control solvent injection. Mangiferin-treated mice exhibited an improved glycemia and glucose tolerance, increased serum insulin levels, enhanced β-cell hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis. Further dissection at the molecular level showed several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent kinase 4 (Cdk4) were significantly up-regulated in mangiferin-treated mice. In addition, critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (Ngn3), glucose transporter 2 (GLUT-2), Forkhead box protein O1 (Foxo-1), and glucokinase (GCK), were found to be promoted by mangiferin at both the mRNA and protein expression level. Thus, mangiferin administration markedly facilitates β-cell proliferation and islet regeneration, likely by regulating essential genes in the cell cycle and the process of islet regeneration. These effects therefore suggest that mangiferin bears a therapeutic potential in preventing and/or treating the diabetes. Full article
(This article belongs to the Special Issue Nutritional Control of Metabolism)
Open AccessArticle Effect of a Novel Quaternary Ammonium Methacrylate Polymer (QAMP) on Adhesion and Antibacterial Properties of Dental Adhesives
Int. J. Mol. Sci. 2014, 15(5), 8998-9015; https://doi.org/10.3390/ijms15058998
Received: 3 March 2014 / Revised: 14 April 2014 / Accepted: 16 April 2014 / Published: 20 May 2014
Cited by 9 | Viewed by 3213 | PDF Full-text (988 KB) | HTML Full-text | XML Full-text
Abstract
This study investigated the resin–dentin bond strength (μTBS), degree of conversion (DC), and antibacterial potential of an innovative adhesive system containing a quaternary ammonium methacrylate polymer (QAMP) using in situ and in vitro assays. Forty-two human third molars were flattened until the dentin
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This study investigated the resin–dentin bond strength (μTBS), degree of conversion (DC), and antibacterial potential of an innovative adhesive system containing a quaternary ammonium methacrylate polymer (QAMP) using in situ and in vitro assays. Forty-two human third molars were flattened until the dentin was exposed and were randomly distributed into three groups of self-etching adhesive systems: Clearfil™ SE Bond containing 5% QAMP (experimental group), Clearfil™ Protect Bond (positive control) and Clearfil™ SE Bond (negative control). After light curing, three 1 mm-increments of composite resin were bonded to each dentin surface. A total of thirty of these bonded teeth (10 teeth per group) was sectioned to obtain stick-shaped specimens and tested under tensile stress immediately, and after 6 and 12 months of storage in distilled water. Twelve bonded teeth (4 teeth per group) were longitudinally sectioned in a mesio-to-distal direction to obtain resin-bonded dentin slabs. In situ DC was evaluated by micro-Raman spectroscopy. In vitro DC of thin films of each adhesive system was measured using Fourier transform infrared spectroscopy. In vitro susceptibility tests of these three adhesive systems were performed by the minimum inhibitory/minimum bactericidal concentration (MIC/MBC) assays against Streptococcus mutans, Lactobacillus casei, and Actinomyces naeslundii. No statistically significant difference in μTBS was observed between Clearfil™ SE Bond containing 5% QAMP and Clearfil™ SE Bond (p > 0.05) immediately, and after 6 and 12 months of water storage. However Clearfil™ Protect Bond showed a significant reduction of μTBS after 12 months of storage (p = 0.039). In addition, QAMP provided no significant change in DC after incorporating into Clearfil™ SE Bond (p > 0.05). Clearfil™ SE Bond containing 5% QAMP demonstrated MIC/MBC values similar to the positive control against L. casei and A. naeslundii and higher than the negative control for all evaluated bacterial strains. The use of QAMP in an adhesive system demonstrated effective bond strength, a suitable degree of conversion, and adequate antibacterial effects against oral bacteria, and may be useful as a new approach to provide long-lasting results for dental adhesives. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
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Open AccessArticle Transition from Cyclosporine-Induced Renal Dysfunction to Nephrotoxicity in an in Vivo Rat Model
Int. J. Mol. Sci. 2014, 15(5), 8979-8997; https://doi.org/10.3390/ijms15058979
Received: 7 April 2014 / Revised: 5 May 2014 / Accepted: 13 May 2014 / Published: 20 May 2014
Cited by 11 | Viewed by 3053 | PDF Full-text (2146 KB) | HTML Full-text | XML Full-text
Abstract
Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical
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Cyclosporin A (CsA), a calcineurin inhibitor, remain the cornerstone of immunosuppressive regimens, regardless of nephrotoxicity, which depends on the duration of drug exposure. The mechanisms and biomarkers underlying the transition from CsA-induced renal dysfunction to nephrotoxicity deserve better elucidation, and would help clinical decisions. This study aimed to clarify these issues, using a rat model of short- and long-term CsA (5 mg/kg bw/day) treatments (3 and 9 weeks, respectively). Renal function was assessed on serum and urine; kidney tissue was used for histopathological characterization and gene and/or protein expression of markers of proliferation, fibrosis and inflammation. In the short-term, creatinine and blood urea nitrogen (BUN) levels increased and clearances decreased, accompanied by glomerular filtration rate (GFR) reduction, but without kidney lesions; at that stage, CsA exposure induced proliferating cell nuclear antigen (PCNA), transforming growth factor beta 1 (TGF-β1), factor nuclear kappa B (NF-κβ) and Tumor Protein P53 (TP53) kidney mRNA up-regulation. In the long-term treatment, renal dysfunction data was accompanied by glomerular and tubulointerstitial lesions, with remarkable kidney mRNA up-regulation of the mammalian target of rapamycin (mTOR) and the antigen identified by monoclonal antibody Ki-67 (Mki67), accompanied by mTOR protein overexpression. Transition from CsA-induced renal dysfunction to nephrotoxicity is accompanied by modification of molecular mechanisms and biomarkers, being mTOR one of the key players for kidney lesion evolution, thus suggesting, by mean of molecular evidences, that early CsA replacement by mTOR inhibitors is indeed the better therapeutic choice to prevent chronic allograft nephropathy. Full article
(This article belongs to the Special Issue Renal Toxicology—Epidemiology and Mechanisms)
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Open AccessArticle Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells
Int. J. Mol. Sci. 2014, 15(5), 8959-8978; https://doi.org/10.3390/ijms15058959
Received: 13 February 2014 / Revised: 5 May 2014 / Accepted: 13 May 2014 / Published: 20 May 2014
Cited by 11 | Viewed by 2457 | PDF Full-text (2549 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF), we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM) induced
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Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF), we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM) induced cell death concomitant with decreases in mitochondrial membrane potential, chromatin condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up-regulated and 548 down-regulated genes, that were differentially expressed by >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4 groups by K-means clustering. Ingenuity® pathway analysis revealed several gene networks from gene clusters. The gene networks Up-I and Up-II included many up-regulated genes that were mainly associated with the biological function of induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos (for Up-I) and Atf4 and Hspa5 (for Up-II). Interestingly, knockdown of Ddit3 and Hspa5 significantly increased and decreased the number of viable cells, respectively. Moreover, several endoplasmic reticulum (ER) stress-related genes including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These findings will provide further insight into the molecular mechanisms of NaF-induced cell death accompanying ER stress in oral epithelial cells. Full article
(This article belongs to the Section Molecular Toxicology)
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Open AccessArticle Synthesis and Bioactivity of 5-Substituted-2-furoyl Diacylhydazide Derivatives with Aliphatic Chain
Int. J. Mol. Sci. 2014, 15(5), 8941-8958; https://doi.org/10.3390/ijms15058941
Received: 24 March 2014 / Revised: 2 May 2014 / Accepted: 5 May 2014 / Published: 20 May 2014
Cited by 7 | Viewed by 1809 | PDF Full-text (384 KB) | HTML Full-text | XML Full-text
Abstract
A series of 5-substituted-2-furoyl diacylhydazide derivatives with aliphatic chain were designed and synthesized. Their structures were characterized by IR, 1H NMR, elemental analysis, and X-ray single crystal diffraction. The anti-tumor bioassay revealed that some title compounds exhibited promising activity against the selected
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A series of 5-substituted-2-furoyl diacylhydazide derivatives with aliphatic chain were designed and synthesized. Their structures were characterized by IR, 1H NMR, elemental analysis, and X-ray single crystal diffraction. The anti-tumor bioassay revealed that some title compounds exhibited promising activity against the selected cancer cell lines, especially against the human promyelocytic leukemic cells (HL-60). Their fungicidal tests indicated that most of the title compounds showed significant anti-fungal activity. The preliminary structure-activity relationship showed that the aliphatic chain length and differences in the R2 group had obvious effects on the anti-tumor and anti-fungal activities. The bioassay results demonstrated that the title compounds hold great promise as novel lead compounds for further drug discovery. Full article
(This article belongs to the Section Materials Science)
Open AccessArticle Tagging SNPs in the MTHFR Gene and Risk of Ischemic Stroke in a Chinese Population
Int. J. Mol. Sci. 2014, 15(5), 8931-8940; https://doi.org/10.3390/ijms15058931
Received: 10 March 2014 / Revised: 7 May 2014 / Accepted: 8 May 2014 / Published: 20 May 2014
Cited by 19 | Viewed by 2356 | PDF Full-text (219 KB) | HTML Full-text | XML Full-text
Abstract
Stroke is currently the leading cause of functional impairments worldwide. Folate supplementation is inversely associated with risk of ischemic stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism. The aim of this study is to examine whether genetic variants in
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Stroke is currently the leading cause of functional impairments worldwide. Folate supplementation is inversely associated with risk of ischemic stroke. Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism. The aim of this study is to examine whether genetic variants in MTHFR gene are associated with the risk of ischemic stroke and fasting total serum homocysteine (tHcy) level. We genotyped nine tag SNPs in the MTHFR gene in a case-control study, including 543 ischemic stroke cases and 655 healthy controls in China. We found that subjects with the rs1801133 TT genotype and rs1801131 CC genotype had significant increased risks of ischemic stroke (adjusted odds ratio (OR) = 1.82, 95% confidence interval (CI): 1.27–2.61, p = 0.004; adjusted OR = 1.99, 95% CI: 1.12–3.56, p = 0.01) compared with subjects with the major alleles. Haplotype analysis also found that carriers of the MTHFR CTTCGA haplotype (rs12121543-rs13306553-rs9651118-rs1801133-rs2274976-rs1801131) had a significant reduced risk of ischemic stroke (adjusted OR = 0.53, 95% CI: 0.35–0.82) compared with those with the CTTTGA haplotype. Besides, the MTHFR rs1801133 and rs9651118 were significantly associated with serum levels of tHcy in healthy controls (p < 0.0001 and p = 0.02). These findings suggest that variants in the MTHFR gene may influence the risk of ischemic stroke and serum tHcy. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessHypothesis Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?
Int. J. Mol. Sci. 2014, 15(5), 8893-8930; https://doi.org/10.3390/ijms15058893
Received: 23 March 2014 / Revised: 28 April 2014 / Accepted: 12 May 2014 / Published: 19 May 2014
Cited by 25 | Viewed by 8589 | PDF Full-text (596 KB) | HTML Full-text | XML Full-text
Abstract
Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms
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Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined. Full article
(This article belongs to the Special Issue Advances in the Research of Melatonin 2014)
Open AccessReview Marine Microbial Metagenomics: From Individual to the Environment
Int. J. Mol. Sci. 2014, 15(5), 8878-8892; https://doi.org/10.3390/ijms15058878
Received: 31 March 2014 / Revised: 29 April 2014 / Accepted: 8 May 2014 / Published: 19 May 2014
Cited by 19 | Viewed by 3023 | PDF Full-text (222 KB) | HTML Full-text | XML Full-text
Abstract
Microbes are the most abundant biological entities on earth, therefore, studying them is important for understanding their roles in global ecology. The science of metagenomics is a relatively young field of research that has enjoyed significant effort since its inception in 1998. Studies
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Microbes are the most abundant biological entities on earth, therefore, studying them is important for understanding their roles in global ecology. The science of metagenomics is a relatively young field of research that has enjoyed significant effort since its inception in 1998. Studies using next-generation sequencing techniques on single genomes and collections of genomes have not only led to novel insights into microbial genomics, but also revealed a close association between environmental niches and genome evolution. Herein, we review studies investigating microbial genomics (largely in the marine ecosystem) at the individual and community levels to summarize our current understanding of microbial ecology in the environment. Full article
(This article belongs to the Special Issue Metagenomics: a Powerful Lens Viewing the Microbial World)
Open AccessArticle The Cytoprotective Effect of Sulfuretin against tert-Butyl Hydroperoxide-Induced Hepatotoxicity through Nrf2/ARE and JNK/ERK MAPK-Mediated Heme Oxygenase-1 Expression
Int. J. Mol. Sci. 2014, 15(5), 8863-8877; https://doi.org/10.3390/ijms15058863
Received: 26 March 2014 / Revised: 12 May 2014 / Accepted: 13 May 2014 / Published: 19 May 2014
Cited by 30 | Viewed by 2988 | PDF Full-text (355 KB) | HTML Full-text | XML Full-text
Abstract
Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t
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Sulfuretin is one of the major flavonoid components in Rhus verniciflua Stokes (Anacardiaceae) isolates. In this study, we investigated the protective effects of sulfuretin against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury. The results indicated that the addition of sulfuretin before t-BHP treatment significantly inhibited cytotoxicity and reactive oxygen species (ROS) production in human liver-derived HepG2 cells. Sulfuretin up-regulated the activity of the antioxidant enzyme heme oxygenase (HO)-1 via nuclear factor E2-related factor 2 (Nrf2) translocation into the nucleus and increased the promoter activity of the antioxidant response element (ARE). Moreover, sulfuretin exposure enhanced the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2), which are members of the mitogen-activated protein kinase (MAPK) family. Furthermore, cell treatment with a JNK inhibitor (SP600125) and ERK inhibitor (PD98059) reduced sulfuretin-induced HO-1 expression and decreased its protective effects. Taken together, these results suggest that the protective effect of sulfuretin against t-BHP-induced oxidative damage in human liver-derived HepG2 cells is attributable to its ability to scavenge ROS and up-regulate the activity of HO-1 through the Nrf2/ARE and JNK/ERK signaling pathways. Therefore, sulfuretin could be advantageous as a bioactive source for the prevention of oxidative injury. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle Selection of Suitable Endogenous Reference Genes for Relative Copy Number Detection in Sugarcane
Int. J. Mol. Sci. 2014, 15(5), 8846-8862; https://doi.org/10.3390/ijms15058846
Received: 19 February 2014 / Revised: 20 April 2014 / Accepted: 7 May 2014 / Published: 19 May 2014
Cited by 12 | Viewed by 3263 | PDF Full-text (298 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM) crops by quantitative real-time PCR (qPCR) or
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Transgene copy number has a great impact on the expression level and stability of exogenous gene in transgenic plants. Proper selection of endogenous reference genes is necessary for detection of genetic components in genetically modification (GM) crops by quantitative real-time PCR (qPCR) or by qualitative PCR approach, especially in sugarcane with polyploid and aneuploid genomic structure. qPCR technique has been widely accepted as an accurate, time-saving method on determination of copy numbers in transgenic plants and on detection of genetically modified plants to meet the regulatory and legislative requirement. In this study, to find a suitable endogenous reference gene and its real-time PCR assay for sugarcane (Saccharum spp. hybrids) DNA content quantification, we evaluated a set of potential “single copy” genes including P4H, APRT, ENOL, CYC, TST and PRR, through qualitative PCR and absolute quantitative PCR. Based on copy number comparisons among different sugarcane genotypes, including five S. officinarum, one S. spontaneum and two S. spp. hybrids, these endogenous genes fell into three groups: ENOL-3—high copy number group, TST-1 and PRR-1—medium copy number group, P4H-1, APRT-2 and CYC-2—low copy number group. Among these tested genes, P4H, APRT and CYC were the most stable, while ENOL and TST were the least stable across different sugarcane genotypes. Therefore, three primer pairs of P4H-3, APRT-2 and CYC-2 were then selected as the suitable reference gene primer pairs for sugarcane. The test of multi-target reference genes revealed that the APRT gene was a specific amplicon, suggesting this gene is the most suitable to be used as an endogenous reference target for sugarcane DNA content quantification. These results should be helpful for establishing accurate and reliable qualitative and quantitative PCR analysis of GM sugarcane. Full article
(This article belongs to the Section Biochemistry)
Open AccessArticle Molecular Characterization of α- and β-Thalassaemia among Malay Patients
Int. J. Mol. Sci. 2014, 15(5), 8835-8845; https://doi.org/10.3390/ijms15058835
Received: 11 February 2014 / Revised: 6 March 2014 / Accepted: 13 March 2014 / Published: 19 May 2014
Cited by 6 | Viewed by 2318 | PDF Full-text (1470 KB) | HTML Full-text | XML Full-text
Abstract
Both α- and β-thalassaemia syndromes are public health problems in the multi-ethnic population of Malaysia. To molecularly characterise the α- and β-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and multiplexed amplification refractory mutation systems were used to study 13 α-thalassaemia determinants
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Both α- and β-thalassaemia syndromes are public health problems in the multi-ethnic population of Malaysia. To molecularly characterise the α- and β-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and multiplexed amplification refractory mutation systems were used to study 13 α-thalassaemia determinants and 20 β-thalassaemia mutations in 28 and 40 unrelated Malays, respectively. Four α-thalassaemia deletions and mutations were demonstrated. −−SEA deletion and αCSα accounted for more than 70% of the α-thalassaemia alleles. Out of the 20 β-thalassaemia alleles studied, nine different β-thalassaemia mutations were identified of which βE accounted for more than 40%. We concluded that the highest prevalence of (α- and β-thalassaemia alleles in the Malays from Penang are −−SEA deletion and βE mutation, respectively. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
Open AccessArticle Antibody-Conjugated Paramagnetic Nanobeads: Kinetics of Bead-Cell Binding
Int. J. Mol. Sci. 2014, 15(5), 8821-8834; https://doi.org/10.3390/ijms15058821
Received: 3 February 2014 / Revised: 23 April 2014 / Accepted: 24 April 2014 / Published: 19 May 2014
Cited by 7 | Viewed by 2201 | PDF Full-text (621 KB) | HTML Full-text | XML Full-text
Abstract
Specific labelling of target cell surfaces using antibody-conjugated paramagnetic nanobeads is essential for efficient magnetic cell separation. However, studies examining parameters determining the kinetics of bead-cell binding are scarce. The present study determines the binding rates for specific and unspecific binding of 150
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Specific labelling of target cell surfaces using antibody-conjugated paramagnetic nanobeads is essential for efficient magnetic cell separation. However, studies examining parameters determining the kinetics of bead-cell binding are scarce. The present study determines the binding rates for specific and unspecific binding of 150 nm paramagnetic nanobeads to highly purified target and non-target cells. Beads bound to cells were enumerated spectrophotometrically. Results show that the initial bead-cell binding rate and saturation levels depend on initial bead concentration and fit curves of the form A(1 − exp(−kt)). Unspecific binding within conventional experimental time-spans (up to 60 min) was not detectable photometrically. For CD3-positive cells, the probability of specific binding was found to be around 80 times larger than that of unspecific binding. Full article
(This article belongs to the Section Materials Science)
Open AccessCommunication Synthesis, Preliminary Bioevaluation and Computational Analysis of Caffeic Acid Analogues
Int. J. Mol. Sci. 2014, 15(5), 8808-8820; https://doi.org/10.3390/ijms15058808
Received: 1 March 2014 / Revised: 31 March 2014 / Accepted: 17 April 2014 / Published: 16 May 2014
Cited by 1 | Viewed by 2571 | PDF Full-text (750 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO) generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for
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A series of caffeic acid amides were designed, synthesized and evaluated for anti-inflammatory activity. Most of them exhibited promising anti-inflammatory activity against nitric oxide (NO) generation in murine macrophage RAW264.7 cells. A 3D pharmacophore model was created based on the biological results for further structural optimization. Moreover, predication of the potential targets was also carried out by the PharmMapper server. These amide analogues represent a promising class of anti-inflammatory scaffold for further exploration and target identification. Full article
Open AccessArticle Biological Evaluation and 3D-QSAR Studies of Curcumin Analogues as Aldehyde Dehydrogenase 1 Inhibitors
Int. J. Mol. Sci. 2014, 15(5), 8795-8807; https://doi.org/10.3390/ijms15058795
Received: 4 January 2014 / Revised: 13 March 2014 / Accepted: 24 March 2014 / Published: 16 May 2014
Cited by 3 | Viewed by 2616 | PDF Full-text (1093 KB) | HTML Full-text | XML Full-text
Abstract
Aldehyde dehydrogenase 1 (ALDH1) is reported as a biomarker for identifying some cancer stem cells, and down-regulation or inhibition of the enzyme can be effective in anti-drug resistance and a potent therapeutic for some tumours. In this paper, the inhibitory activity, mechanism mode,
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Aldehyde dehydrogenase 1 (ALDH1) is reported as a biomarker for identifying some cancer stem cells, and down-regulation or inhibition of the enzyme can be effective in anti-drug resistance and a potent therapeutic for some tumours. In this paper, the inhibitory activity, mechanism mode, molecular docking and 3D-QSAR (three-dimensional quantitative structure activity relationship) of curcumin analogues (CAs) against ALDH1 were studied. Results demonstrated that curcumin and CAs possessed potent inhibitory activity against ALDH1, and the CAs compound with ortho di-hydroxyl groups showed the most potent inhibitory activity. This study indicates that CAs may represent a new class of ALDH1 inhibitor. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
Open AccessArticle In Vitro Treatment of Melanoma Brain Metastasis by Simultaneously Targeting the MAPK and PI3K Signaling Pathways
Int. J. Mol. Sci. 2014, 15(5), 8773-8794; https://doi.org/10.3390/ijms15058773
Received: 24 March 2014 / Revised: 4 May 2014 / Accepted: 6 May 2014 / Published: 16 May 2014
Cited by 11 | Viewed by 4621 | PDF Full-text (2405 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK) pathway [1]. In addition, increased PI3K (phosphoinositide
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Malignant melanoma is the most lethal form of skin cancer, with a high propensity to metastasize to the brain. More than 60% of melanomas have the BRAFV600E mutation, which activates the mitogen-activated protein kinase (MAPK) pathway [1]. In addition, increased PI3K (phosphoinositide 3-kinase) pathway activity has been demonstrated, through the loss of activity of the tumor suppressor gene, PTEN [2]. Here, we treated two melanoma brain metastasis cell lines, H1_DL2, harboring a BRAFV600E mutation and PTEN loss, and H3, harboring WT (wild-type) BRAF and PTEN loss, with the MAPK (BRAF) inhibitor vemurafenib and the PI3K pathway associated mTOR inhibitor temsirolimus. Combined use of the drugs inhibited tumor cell growth and proliferation in vitro in H1_DL2 cells, compared to single drug treatment. Treatment was less effective in the H3 cells. Furthermore, a strong inhibitory effect on the viability of H1_DL2 cells, when grown as 3D multicellular spheroids, was seen. The treatment inhibited the expression of pERK1/2 and reduced the expression of pAKT and p-mTOR in H1_DL2 cells, confirming that the MAPK and PI3K pathways were inhibited after drug treatment. Microarray experiments followed by principal component analysis (PCA) mapping showed distinct gene clustering after treatment, and cell cycle checkpoint regulators were affected. Global gene analysis indicated that functions related to cell survival and invasion were influenced by combined treatment. In conclusion, we demonstrate for the first time that combined therapy with vemurafenib and temsirolimus is effective on melanoma brain metastasis cells in vitro. The presented results highlight the potential of combined treatment to overcome treatment resistance that may develop after vemurafenib treatment of melanomas. Full article
(This article belongs to the Special Issue Brain Metastasis 2014)
Open AccessReview Colonization and Infection of the Skin by S. aureus: Immune System Evasion and the Response to Cationic Antimicrobial Peptides
Int. J. Mol. Sci. 2014, 15(5), 8753-8772; https://doi.org/10.3390/ijms15058753
Received: 18 April 2014 / Revised: 2 May 2014 / Accepted: 7 May 2014 / Published: 16 May 2014
Cited by 37 | Viewed by 5391 | PDF Full-text (976 KB) | HTML Full-text | XML Full-text
Abstract
Staphylococcus aureus (S. aureus) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by S. aureus reflects in part the competition between host cutaneous immune defenses and S. aureus
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Staphylococcus aureus (S. aureus) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by S. aureus reflects in part the competition between host cutaneous immune defenses and S. aureus virulence factors. As part of the innate immune system in the skin, cationic antimicrobial peptides (CAMPs) such as the β-defensins and cathelicidin contribute to host cutaneous defense, which prevents harmful microorganisms, like S. aureus, from crossing epithelial barriers. Conversely, S. aureus utilizes evasive mechanisms against host defenses to promote its colonization and infection of the skin. In this review, we focus on host-pathogen interactions during colonization and infection of the skin by S. aureus and methicillin-resistant Staphylococcus aureus (MRSA). We will discuss the peptides (defensins, cathelicidins, RNase7, dermcidin) and other mediators (toll-like receptor, IL-1 and IL-17) that comprise the host defense against S. aureus skin infection, as well as the various mechanisms by which S. aureus evades host defenses. It is anticipated that greater understanding of these mechanisms will enable development of more sustainable antimicrobial compounds and new therapeutic approaches to the treatment of S. aureus skin infection and colonization. Full article
Open AccessArticle Molecular Recognition of Agonist and Antagonist for Peroxisome Proliferator-Activated Receptor-α Studied by Molecular Dynamics Simulations
Int. J. Mol. Sci. 2014, 15(5), 8743-8752; https://doi.org/10.3390/ijms15058743
Received: 19 January 2014 / Revised: 3 May 2014 / Accepted: 5 May 2014 / Published: 15 May 2014
Cited by 1 | Viewed by 2106 | PDF Full-text (600 KB) | HTML Full-text | XML Full-text
Abstract
Peroxisome proliferator activated receptor-α (PPAR-α) is a ligand-activated transcription factor which plays important roles in lipid and glucose metabolism. The aim of this work is to find residues which selectively recognize PPAR-α agonists and antagonists. To achieve this aim, PPAR-α/13M and PPAR-α/471 complexes
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Peroxisome proliferator activated receptor-α (PPAR-α) is a ligand-activated transcription factor which plays important roles in lipid and glucose metabolism. The aim of this work is to find residues which selectively recognize PPAR-α agonists and antagonists. To achieve this aim, PPAR-α/13M and PPAR-α/471 complexes were subjected to perform molecular dynamics simulations. This research suggests that several key residues only participate in agonist recognition, while some other key residues only contribute to antagonist recognition. It is hoped that such work is useful for medicinal chemists to design novel PPAR-α agonists and antagonists. Full article
(This article belongs to the Section Physical Chemistry, Theoretical and Computational Chemistry)
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Open AccessReview Role of Mitochondria in Nonalcoholic Fatty Liver Disease
Int. J. Mol. Sci. 2014, 15(5), 8713-8742; https://doi.org/10.3390/ijms15058713
Received: 4 March 2014 / Revised: 4 May 2014 / Accepted: 7 May 2014 / Published: 15 May 2014
Cited by 66 | Viewed by 4975 | PDF Full-text (384 KB) | HTML Full-text | XML Full-text
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis
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Nonalcoholic fatty liver disease (NAFLD) affects about 30% of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis of NALFD; however the key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated. Accumulating and emerging evidence indicate that hepatic mitochondria play a critical role in the development and pathogenesis of steatosis and NAFLD. Here, we review studies that document a link between the pathogenesis of NAFLD and hepatic mitochondrial dysfunction with particular focus on new insights into the role of impaired fatty acid oxidation, the transcription factor peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuins in development and progression of NAFLD. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
Open AccessArticle Expression and Effects of High-Mobility Group Box 1 in Cervical Cancer
Int. J. Mol. Sci. 2014, 15(5), 8699-8712; https://doi.org/10.3390/ijms15058699
Received: 28 January 2014 / Revised: 4 May 2014 / Accepted: 5 May 2014 / Published: 15 May 2014
Cited by 21 | Viewed by 2709 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text
Abstract
We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial
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We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag) was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05). In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05). HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05). HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05). Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment. Full article
Open AccessReview Signaling Pathways in Cartilage Repair
Int. J. Mol. Sci. 2014, 15(5), 8667-8698; https://doi.org/10.3390/ijms15058667
Received: 25 February 2014 / Revised: 28 April 2014 / Accepted: 4 May 2014 / Published: 15 May 2014
Cited by 45 | Viewed by 3656 | PDF Full-text (367 KB) | HTML Full-text | XML Full-text
Abstract
In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since
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In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. Full article
(This article belongs to the Special Issue Signal Transduction of Tissue Repair)
Open AccessArticle Geminal Brønsted Acid Ionic Liquids as Catalysts for the Mannich Reaction in Water
Int. J. Mol. Sci. 2014, 15(5), 8656-8666; https://doi.org/10.3390/ijms15058656
Received: 21 March 2014 / Revised: 30 April 2014 / Accepted: 6 May 2014 / Published: 15 May 2014
Cited by 13 | Viewed by 2743 | PDF Full-text (360 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Quaternary ammonium geminal Brønsted acid ionic liquids (GBAILs) based on zwitterionic 1,2-bis[N-methyl-N-(3-sulfopropyl)-alkylammonium]ethane (where the carbon number of the alkyl chain is 4, 8, 10, 12, 14, 16, or 18) and p-toluenesulfonic acid monohydrate were synthesized. The catalytic ionic
[...] Read more.
Quaternary ammonium geminal Brønsted acid ionic liquids (GBAILs) based on zwitterionic 1,2-bis[N-methyl-N-(3-sulfopropyl)-alkylammonium]ethane (where the carbon number of the alkyl chain is 4, 8, 10, 12, 14, 16, or 18) and p-toluenesulfonic acid monohydrate were synthesized. The catalytic ionic liquids were applied in three-component Mannich reactions with an aldehyde, ketone, and amine at 25 °C in water. The effects of the type and amount of catalyst and reaction time as well as the scope of the reaction were investigated. Results showed that GBAIL-C14 has excellent catalytic activity and fair reusability. The catalytic procedure was simple, and the catalyst could be recycled seven times via a simple separation process without noticeable decreases in catalytic activity. Full article
(This article belongs to the Special Issue Ionic Liquids 2014 & Selected Papers from ILMAT 2013)
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