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Int. J. Mol. Sci., Volume 17, Issue 5 (May 2016)

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Cover Story (view full-size image) Ionic liquid crystals combine the properties of ionic liquids and liquid crystals. They are often [...] Read more.
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Open AccessReview
Prodrug Strategies for Paclitaxel
Int. J. Mol. Sci. 2016, 17(5), 796; https://doi.org/10.3390/ijms17050796
Received: 23 March 2016 / Revised: 4 May 2016 / Accepted: 11 May 2016 / Published: 23 May 2016
Cited by 11 | Viewed by 2394 | PDF Full-text (3543 KB) | HTML Full-text | XML Full-text
Abstract
Paclitaxel is an anti-tumor agent with remarkable anti-tumor activity and wide clinical uses. However, it is also faced with various challenges especially for its poor water solubility and low selectivity for the target. To overcome these disadvantages of paclitaxel, approaches using small molecule [...] Read more.
Paclitaxel is an anti-tumor agent with remarkable anti-tumor activity and wide clinical uses. However, it is also faced with various challenges especially for its poor water solubility and low selectivity for the target. To overcome these disadvantages of paclitaxel, approaches using small molecule modifications and macromolecule modifications have been developed by many research groups from all over the world. In this review, we discuss the different strategies especially prodrug strategies that are currently used to make paclitaxel more effective. Full article
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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Open AccessArticle
Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice
Int. J. Mol. Sci. 2016, 17(5), 795; https://doi.org/10.3390/ijms17050795
Received: 15 April 2016 / Revised: 12 May 2016 / Accepted: 18 May 2016 / Published: 23 May 2016
Cited by 11 | Viewed by 2296 | PDF Full-text (3831 KB) | HTML Full-text | XML Full-text
Abstract
Cold exposure or β3-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or [...] Read more.
Cold exposure or β3-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β3-adrenoceptor agonist (CL316,243)-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1–5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT) and epididymal WAT (eWAT) were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessReview
Gibberellic Acid: A Key Phytohormone for Spikelet Fertility in Rice Grain Production
Int. J. Mol. Sci. 2016, 17(5), 794; https://doi.org/10.3390/ijms17050794
Received: 8 April 2016 / Revised: 14 May 2016 / Accepted: 19 May 2016 / Published: 23 May 2016
Cited by 6 | Viewed by 2203 | PDF Full-text (1007 KB) | HTML Full-text | XML Full-text
Abstract
The phytohormone gibberellic acid (GA) has essential signaling functions in multiple processes during plant development. In the “Green Revolution”, breeders developed high-yield rice cultivars that exhibited both semi-dwarfism and altered GA responses, thus improving grain production. Most studies of GA have concentrated on [...] Read more.
The phytohormone gibberellic acid (GA) has essential signaling functions in multiple processes during plant development. In the “Green Revolution”, breeders developed high-yield rice cultivars that exhibited both semi-dwarfism and altered GA responses, thus improving grain production. Most studies of GA have concentrated on germination and cell elongation, but GA also has a pivotal role in floral organ development, particularly in stamen/anther formation. In rice, GA signaling plays an important role in spikelet fertility; however, the molecular genetic and biochemical mechanisms of GA in male fertility remain largely unknown. Here, we review recent progress in understanding the network of GA signaling and its connection with spikelet fertility, which is tightly associated with grain productivity in cereal crops. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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Open AccessReview
The Role of Proanthocyanidins Complex in Structure and Nutrition Interaction in Alfalfa Forage
Int. J. Mol. Sci. 2016, 17(5), 793; https://doi.org/10.3390/ijms17050793
Received: 22 April 2016 / Revised: 11 May 2016 / Accepted: 17 May 2016 / Published: 23 May 2016
Cited by 10 | Viewed by 1549 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Alfalfa (Medicago sativa L.) is one of the main forages grown in the world. Alfalfa is a winter hardy, drought tolerant, N-fixing legume with a good longevity, high yield, high nutrient levels, high digestibility, unique structural to non-structural components ratio, high dry [...] Read more.
Alfalfa (Medicago sativa L.) is one of the main forages grown in the world. Alfalfa is a winter hardy, drought tolerant, N-fixing legume with a good longevity, high yield, high nutrient levels, high digestibility, unique structural to non-structural components ratio, high dry matter intake, and high animal productivity per hectare. However, its main limitation is its excessively rapid initial rate of protein degradation in the rumen, which results in pasture bloat and inefficient use of protein with consequent excessive excretions of nitrogen into the environment. Proanthocyanidins are secondary plant metabolites that can bind with protein and thereby reduce the rate and extent of ruminal protein degradation. However, these secondary metabolites do not accumulate in alfalfa. This review aims to firstly describe the events involved in the rapid release of protein from alfalfa and its effect on ruminant nutrition, environmental pollution, and pasture bloat; secondly, to describe occurrence, structure, functions and benefits of moderate amounts of proanthocyanidin; and finally, to describe the development of alfalfa which accumulates moderate amounts of proanthocyanidins. The emphasis of this review focuses on the role of proanthocyanidins compounds in structure and nutrition interaction in ruminant livestock systems. Full article
(This article belongs to the Section Molecular Plant Sciences)
Open AccessCommunication
A Novel Technique to Detect EGFR Mutations in Lung Cancer
Int. J. Mol. Sci. 2016, 17(5), 792; https://doi.org/10.3390/ijms17050792
Received: 30 March 2016 / Revised: 17 May 2016 / Accepted: 18 May 2016 / Published: 23 May 2016
Cited by 5 | Viewed by 2625 | PDF Full-text (5870 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Epidermal growth factor receptor (EGFR) gene mutations occur in multiple human cancers; therefore, the detection of EGFR mutations could lead to early cancer diagnosis. This study describes a novel EGFR mutation detection technique. Compared to direct DNA sequencing detection methods, this [...] Read more.
Epidermal growth factor receptor (EGFR) gene mutations occur in multiple human cancers; therefore, the detection of EGFR mutations could lead to early cancer diagnosis. This study describes a novel EGFR mutation detection technique. Compared to direct DNA sequencing detection methods, this method is based on allele-specific amplification (ASA), recombinase polymerase amplification (RPA), peptide nucleic acid (PNA), and SYBR Green I (SYBR), referred to as the AS-RPA-PNA-SYBR (ARPS) system. The principle of this technique is based on three continuous steps: ASA or ASA combined with PNA to prevent non-target sequence amplification (even single nucleotide polymorphisms, SNPs), the rapid amplification advantage of RPA, and appropriate SYBR Green I detection (the samples harboring EGFR mutations show a green signal). Using this method, the EGFR 19Del(2) mutation was detected in 5 min, while the EGFR L858R mutation was detected in 10 min. In this study, the detection of EGFR mutations in clinical samples using the ARPS system was compatible with that determined by polymerase chain reaction (PCR) and DNA sequencing methods. Thus, this newly developed methodology that uses the ARPS system with appropriate primer sets is a rapid, reliable, and practical way to assess EGFR mutations in clinical samples. Full article
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Open AccessReview
Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers
Int. J. Mol. Sci. 2016, 17(5), 791; https://doi.org/10.3390/ijms17050791
Received: 31 March 2016 / Revised: 29 April 2016 / Accepted: 10 May 2016 / Published: 23 May 2016
Cited by 11 | Viewed by 2386 | PDF Full-text (776 KB) | HTML Full-text | XML Full-text
Abstract
Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) [...] Read more.
Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20–22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs. Full article
(This article belongs to the Special Issue MicroRNA in Various Disease States as Biomarkers)
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Open AccessArticle
Analysis of 2-(2-Phenylethyl)chromones by UPLC-ESI-QTOF-MS and Multivariate Statistical Methods in Wild and Cultivated Agarwood
Int. J. Mol. Sci. 2016, 17(5), 771; https://doi.org/10.3390/ijms17050771
Received: 8 April 2016 / Revised: 11 May 2016 / Accepted: 13 May 2016 / Published: 23 May 2016
Cited by 12 | Viewed by 2235 | PDF Full-text (1439 KB) | HTML Full-text | XML Full-text
Abstract
Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in [...] Read more.
Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in the Convention on the International Trade in Endangered Species (CITES). We characterized the 2-(2-phenylethyl)chromones in agarwood by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC–ESI-QTOF-MS) and differentiated wild from cultivated agarwood by metabolomic analysis. A total of 141 chromones including 50 potentially new compounds were evaluated as belonging to four structural classes (unoxidized 2-(2-phenylethyl)chromones, 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones, bi-2-(2-phenylethyl)chromones, and tri-2-(2-phenylethyl)chromones). The metabolic difference between wild and cultivated agarwood was analyzed by component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen markers of metabolisms in wild and cultivated agarwood were constructed (e.g., 6,7-dimethoxy-2-(2-phenylethyl)chromone, 6,8-dihydroxy-2-(2-phenylethyl)chromone, 6-methoxy-2-(2-phenylethyl)chromone, etc.). These results indicated that UPLC–ESI-QTOF-MS-based metabonomics analysis in agarwood may be useful for distinguishing wild agarwood from cultivated agarwood. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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Open AccessArticle
Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types
Int. J. Mol. Sci. 2016, 17(5), 790; https://doi.org/10.3390/ijms17050790
Received: 12 April 2016 / Revised: 12 May 2016 / Accepted: 16 May 2016 / Published: 21 May 2016
Cited by 18 | Viewed by 2258 | PDF Full-text (3355 KB) | HTML Full-text | XML Full-text
Abstract
In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to [...] Read more.
In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. Full article
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Open AccessReview
Functions of miRNAs during Mammalian Heart Development
Int. J. Mol. Sci. 2016, 17(5), 789; https://doi.org/10.3390/ijms17050789
Received: 30 March 2016 / Revised: 26 April 2016 / Accepted: 13 May 2016 / Published: 21 May 2016
Cited by 16 | Viewed by 1624 | PDF Full-text (198 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest [...] Read more.
MicroRNAs (miRNAs) play essential roles during mammalian heart development and have emerged as attractive therapeutic targets for cardiovascular diseases. The mammalian embryonic heart is mainly derived from four major cell types during development. These include cardiomyocytes, endocardial cells, epicardial cells, and neural crest cells. Recent data have identified various miRNAs as critical regulators of the proper differentiation, proliferation, and survival of these cell types. In this review, we briefly introduce the contemporary understanding of mammalian cardiac development. We also focus on recent developments in the field of cardiac miRNAs and their functions during the development of different cell types. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
Open AccessArticle
Extraction Optimization, Preliminary Characterization and Bioactivities in Vitro of Ligularia hodgsonii Polysaccharides
Int. J. Mol. Sci. 2016, 17(5), 788; https://doi.org/10.3390/ijms17050788
Received: 29 March 2016 / Revised: 6 May 2016 / Accepted: 10 May 2016 / Published: 21 May 2016
Cited by 7 | Viewed by 1548 | PDF Full-text (1358 KB) | HTML Full-text | XML Full-text
Abstract
The optimization extraction, preliminary characterization and bioactivities of Ligularia hodgsonii polysaccharides were investigated. Based on single-factor experiments and orthogonal array test, the optimum extraction conditions were obtained as follows: extraction time 3 h, temperature 85 °C, water/raw material ratio 36. Further Sevag deproteinization [...] Read more.
The optimization extraction, preliminary characterization and bioactivities of Ligularia hodgsonii polysaccharides were investigated. Based on single-factor experiments and orthogonal array test, the optimum extraction conditions were obtained as follows: extraction time 3 h, temperature 85 °C, water/raw material ratio 36. Further Sevag deproteinization and dialysis yielded the dialyzed Ligularia hodgsonii polysaccharides (DLHP, 19.2 ± 1.4 mg/g crude herb). Compositional analysis, size-exclusion chromatography connected with multi-angle laser light-scattering and refractive index (SEC-MALLS-RI), Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (NMR) spectroscopy were employed for characterization of the polysaccharides. DLHP was found to have a major component with a weight-average molecular weight of 1.17 × 105 Da, mainly comprising of glucose, galactose, arabinose, mannose, rhamnose, glucuronic acid and galacturonic acid. By in vitro antioxidant activity assays, DLHP presented remarkable scavenging capacities towards 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl radicals, and ferrous ions chelating ability. Moreover, it exhibited appreciable anti-hyperglycemic activity as demonstrated by differential inhibition of α-glucosidase and α-amylase. The results indicated that DLHP could potentially be a resource for antioxidant and hypoglycemic agents. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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Open AccessArticle
Functional and Biochemical Characterization of Three Recombinant Human Glucose-6-Phosphate Dehydrogenase Mutants: Zacatecas, Vanua-Lava and Viangchan
Int. J. Mol. Sci. 2016, 17(5), 787; https://doi.org/10.3390/ijms17050787
Received: 21 April 2016 / Revised: 21 April 2016 / Accepted: 16 May 2016 / Published: 21 May 2016
Cited by 7 | Viewed by 2699 | PDF Full-text (12457 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation [...] Read more.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency in humans causes severe disease, varying from mostly asymptomatic individuals to patients showing neonatal jaundice, acute hemolysis episodes or chronic nonspherocytic hemolytic anemia. In order to understand the effect of the mutations in G6PD gene function and its relation with G6PD deficiency severity, we report the construction, cloning and expression as well as the detailed kinetic and stability characterization of three purified clinical variants of G6PD that present in the Mexican population: G6PD Zacatecas (Class I), Vanua-Lava (Class II) and Viangchan (Class II). For all the G6PD mutants, we obtained low purification yield and altered kinetic parameters compared with Wild Type (WT). Our results show that the mutations, regardless of the distance from the active site where they are located, affect the catalytic properties and structural parameters and that these changes could be associated with the clinical presentation of the deficiency. Specifically, the structural characterization of the G6PD Zacatecas mutant suggests that the R257L mutation have a strong effect on the global stability of G6PD favoring an unstable active site. Using computational analysis, we offer a molecular explanation of the effects of these mutations on the active site. Full article
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Open AccessReview
Marine Antimicrobial Peptides: Nature Provides Templates for the Design of Novel Compounds against Pathogenic Bacteria
Int. J. Mol. Sci. 2016, 17(5), 785; https://doi.org/10.3390/ijms17050785
Received: 22 April 2016 / Revised: 11 May 2016 / Accepted: 18 May 2016 / Published: 21 May 2016
Cited by 26 | Viewed by 2553 | PDF Full-text (1840 KB) | HTML Full-text | XML Full-text
Abstract
The discovery of antibiotics for the treatment of bacterial infections brought the idea that bacteria would no longer endanger human health. However, bacterial diseases still represent a worldwide treat. The ability of microorganisms to develop resistance, together with the indiscriminate use of antibiotics, [...] Read more.
The discovery of antibiotics for the treatment of bacterial infections brought the idea that bacteria would no longer endanger human health. However, bacterial diseases still represent a worldwide treat. The ability of microorganisms to develop resistance, together with the indiscriminate use of antibiotics, is mainly responsible for this situation; thus, resistance has compelled the scientific community to search for novel therapeutics. In this scenario, antimicrobial peptides (AMPs) provide a promising strategy against a wide array of pathogenic microorganisms, being able to act directly as antimicrobial agents but also being important regulators of the innate immune system. This review is an attempt to explore marine AMPs as a rich source of molecules with antimicrobial activity. In fact, the sea is poorly explored in terms of AMPs, but it represents a resource with plentiful antibacterial agents performing their role in a harsh environment. For the application of AMPs in the medical field limitations correlated to their peptide nature, their inactivation by environmental pH, presence of salts, proteases, or other components have to be solved. Thus, these peptides may act as templates for the design of more potent and less toxic compounds. Full article
(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)
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Open AccessArticle
Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies
Int. J. Mol. Sci. 2016, 17(5), 781; https://doi.org/10.3390/ijms17050781
Received: 31 March 2016 / Revised: 2 May 2016 / Accepted: 6 May 2016 / Published: 21 May 2016
Cited by 4 | Viewed by 1790 | PDF Full-text (1736 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (ZnII) thiosemicarbazone complexes [Zn(atc-Et)2] (1) and [Zn(atc-Ph)2] (2 [...] Read more.
Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (ZnII) thiosemicarbazone complexes [Zn(atc-Et)2] (1) and [Zn(atc-Ph)2] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (1H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research. Full article
(This article belongs to the Special Issue Recent Advances in Metal Based Drugs)
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Open AccessArticle
An Eco-Friendly Ultrasound-Assisted Synthesis of Novel Fluorinated Pyridinium Salts-Based Hydrazones and Antimicrobial and Antitumor Screening
Int. J. Mol. Sci. 2016, 17(5), 766; https://doi.org/10.3390/ijms17050766
Received: 10 April 2016 / Revised: 28 April 2016 / Accepted: 9 May 2016 / Published: 21 May 2016
Cited by 7 | Viewed by 1989 | PDF Full-text (1145 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde [...] Read more.
The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde (2) followed by the nucleophilic alkylation of the resulting N-(4-fluorobenzylidene)isonicotinohydrazide (3) with a different alkyl iodide. The iodide counteranion of 510 was subjected to an anion exchange metathesis reaction in the presence of an excess of the appropriate metal salts to afford a new series of fluorinated pyridinium salts tethering a hydrazone linkage 1140. Ultrasound irradiation led to higher yields in considerably less time than the conventional methods. The newly synthesized ILs were well-characterized with FT-IR, 1H NMR, 13C NMR, 11B, 19F, 31P and mass spectral analyses. The ILs were also screened for their antimicrobial and antitumor activities. Within the series, the salts tethering fluorinated counter anions 1113, 2123, 3133 and 3638 were found to be more potent against all bacterial and fungal strains at MIC 4–8 µg/mL. The in vitro antiproliferative activity was also investigated against four tumor cell lines (human ductal breast epithelial tumor T47D, human breast adenocarcinoma MCF-7, human epithelial carcinoma HeLa and human epithelial colorectal adenocarcinoma Caco-2) using the MTT assay, which revealed that promising antitumor activity was exhibited by compounds 5, 12 and 14. Full article
(This article belongs to the Special Issue Ionic Liquids 2016 and Selected Papers from ILMAT III)
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Open AccessArticle
Expression Patterns and Functional Novelty of Ribonuclease 1 in Herbivorous Megalobrama amblycephala
Int. J. Mol. Sci. 2016, 17(5), 786; https://doi.org/10.3390/ijms17050786
Received: 4 March 2016 / Revised: 22 April 2016 / Accepted: 13 May 2016 / Published: 20 May 2016
Cited by 3 | Viewed by 1708 | PDF Full-text (11601 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ribonuclease 1 (RNase1) is an important digestive enzyme that has been used to study the molecular evolutionary and plant-feeding adaptation of mammals. However, the expression patterns and potential biological function of RNase1 in herbivorous fish is not known. Here, we identified RNase1 from [...] Read more.
Ribonuclease 1 (RNase1) is an important digestive enzyme that has been used to study the molecular evolutionary and plant-feeding adaptation of mammals. However, the expression patterns and potential biological function of RNase1 in herbivorous fish is not known. Here, we identified RNase1 from five fish species and illuminated the functional diversification and expression of RNase1 in herbivorous Megalobrama amblycephala. The five identified fish RNase1 genes all have the signature motifs of the RNase A superfamily. No expression of Ma-RNase1 was detected in early developmental stages but a weak expression was detected at 120 and 144 hours post-fertilization (hpf). Ma-RNase1 was only expressed in the liver and heart of one-year-old fish but strongly expressed in the liver, spleen, gut, kidney and testis of two-year-old fish. Moreover, the immunostaining localized RNase1 production to multiple tissues of two-year-old fish. A biological functional analysis of the recombinant protein demonstrated that M. amblycephala RNase1 had a relatively strong ribonuclease activity at its optimal pH 6.1, which is consistent with the pH of its intestinal microenvironment. Collectively, these results clearly show that Ma-RNase1 protein has ribonuclease activity and the expression patterns of Ma-RNase1 are dramatically different in one year and two-year-old fish, suggesting the functional differentiation during fish growing. Full article
(This article belongs to the Special Issue Fish Molecular Biology)
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Open AccessArticle
Impact of Faba Bean-Seed Rhizobial Inoculation on Microbial Activity in the Rhizosphere Soil during Growing Season
Int. J. Mol. Sci. 2016, 17(5), 784; https://doi.org/10.3390/ijms17050784
Received: 22 March 2016 / Revised: 5 May 2016 / Accepted: 12 May 2016 / Published: 20 May 2016
Cited by 6 | Viewed by 1762 | PDF Full-text (966 KB) | HTML Full-text | XML Full-text
Abstract
Inoculation of legume seeds with Rhizobium affects soil microbial community and processes, especially in the rhizosphere. This study aimed at assessing the effect of Rhizobium inoculation on microbial activity in the faba bean rhizosphere during the growing season in a field experiment on [...] Read more.
Inoculation of legume seeds with Rhizobium affects soil microbial community and processes, especially in the rhizosphere. This study aimed at assessing the effect of Rhizobium inoculation on microbial activity in the faba bean rhizosphere during the growing season in a field experiment on a Haplic Luvisol derived from loess. Faba bean (Vicia faba L.) seeds were non-inoculated (NI) or inoculated (I) with Rhizobium leguminosarum bv. viciae and sown. The rhizosphere soil was analyzed for the enzymatic activities of dehydrogenases, urease, protease and acid phosphomonoesterase, and functional diversity (catabolic potential) using the Average Well Color Development, Shannon-Weaver, and Richness indices following the community level physiological profiling from Biolog EcoPlate™. The analyses were done on three occasions corresponding to the growth stages of: 5–6 leaf, flowering, and pod formation. The enzymatic activities were higher in I than NI (p < 0.05) throughout the growing season. However, none of the functional diversity indices differed significantly under both treatments, regardless of the growth stage. This work showed that the functional diversity of the microbial communities was a less sensitive tool than enzyme activities in assessment of rhizobial inoculation effects on rhizosphere microbial activity. Full article
(This article belongs to the Special Issue Molecular Signals in Nodulation Control)
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Open AccessArticle
Quantitative Metabolomic Analysis of Urinary Citrulline and Calcitroic Acid in Mice after Exposure to Various Types of Ionizing Radiation
Int. J. Mol. Sci. 2016, 17(5), 782; https://doi.org/10.3390/ijms17050782
Received: 12 January 2016 / Revised: 23 March 2016 / Accepted: 10 May 2016 / Published: 20 May 2016
Cited by 6 | Viewed by 1888 | PDF Full-text (4005 KB) | HTML Full-text | XML Full-text
Abstract
With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids [...] Read more.
With the safety of existing nuclear power plants being brought into question after the Fukushima disaster and the increased level of concern over terrorism-sponsored use of improvised nuclear devices, it is more crucial to develop well-defined radiation injury markers in easily accessible biofluids to help emergency-responders with injury assessment during patient triage. Here, we focused on utilizing ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to identify and quantitate the unique changes in the urinary excretion of two metabolite markers, calcitroic acid and citrulline, in mice induced by different forms of irradiation; X-ray irradiation at a low dose rate (LDR) of 3.0 mGy/min and a high dose rate (HDR) of 1.1 Gy/min, and internal exposure to Cesium-137 (137Cs) and Strontium-90 (90Sr). The multiple reaction monitoring analysis showed that, while exposure to 137Cs and 90Sr induced a statistically significant and persistent decrease, similar doses of X-ray beam at the HDR had the opposite effect, and the LDR had no effect on the urinary levels of these two metabolites. This suggests that the source of exposure and the dose rate strongly modulate the in vivo metabolomic injury responses, which may have utility in clinical biodosimetry assays for the assessment of exposure in an affected population. This study complements our previous investigations into the metabolomic profile of urine from mice internally exposed to 90Sr and 137Cs and to X-ray beam radiation. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle
Angiotensin II Stimulation of DPP4 Activity Regulates Megalin in the Proximal Tubules
Int. J. Mol. Sci. 2016, 17(5), 780; https://doi.org/10.3390/ijms17050780
Received: 3 April 2016 / Revised: 12 May 2016 / Accepted: 13 May 2016 / Published: 20 May 2016
Cited by 10 | Viewed by 1920 | PDF Full-text (1836 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is [...] Read more.
Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT1R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4. We used Ang II (200 ng/kg/min) infusion in mice and Ang II (10−8 M) treatment of T35OK-AT1R proximal tubule cells to test our hypothesis. Ang II-infused mouse kidneys displayed increases in DPP4 activity and decreases in megalin. In proximal tubule cells, Ang II stimulated DPP4 activity concurrent with suppression of megalin. MK0626, a DPP4 inhibitor, partially restored megalin expression similar to U0126, a mitogen activated protein kinase (MAPK)/extracellular regulated kinase (ERK) kinase kinase (MEK) 1/2 inhibitor and AG1478, an epidermal growth factor receptor (EGFR) inhibitor. Similarly, Ang II-induced ERK phosphorylation was suppressed with MK0626 and Ang II-induced DPP4 activity was suppressed by U0126. Therefore, our study reveals a cross talk between AT1R signaling and DPP4 activation in the regulation of megalin and underscores the significance of targeting DPP4 in the prevention of obesity related kidney injury progression. Full article
(This article belongs to the Special Issue Advances in Chronic Kidney Disease)
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Open AccessEditorial
International Journal of Molecular Sciences 2016 Best Paper Award
Int. J. Mol. Sci. 2016, 17(5), 777; https://doi.org/10.3390/ijms17050777
Received: 18 May 2016 / Revised: 18 May 2016 / Accepted: 18 May 2016 / Published: 20 May 2016
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Abstract
The Editors of the International Journal of Molecular Sciences have established the Best Paper Award to recognize the most outstanding articles published in the areas of molecular biology, molecular physics and chemistry that have been published in the International Journal of Molecular Sciences.[...] [...] Read more.
The Editors of the International Journal of Molecular Sciences have established the Best Paper Award to recognize the most outstanding articles published in the areas of molecular biology, molecular physics and chemistry that have been published in the International Journal of Molecular Sciences.[...] Full article
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Open AccessArticle
Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models
Int. J. Mol. Sci. 2016, 17(5), 776; https://doi.org/10.3390/ijms17050776
Received: 5 April 2016 / Revised: 10 May 2016 / Accepted: 16 May 2016 / Published: 20 May 2016
Cited by 3 | Viewed by 2273 | PDF Full-text (1096 KB) | HTML Full-text | XML Full-text
Abstract
Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and [...] Read more.
Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and integrated analysis were employed on an eight microarray series. We explored the functions and pathways of target genes in gene ontology (GO) enrichment analysis and constructed a protein-protein interaction network. Meta-analysis identified 360 differentially expressed genes (DEGs) for Mus musculus and 255 for Rattus norvegicus. Differential expression analysis identified 44 DEGs for Mus musculus and 21 for Rattus norvegicus. Timp1 and Lcn2 were overexpressed in both species. The cytokine-cytokine receptor interaction and chemokine signaling pathway were highly enriched for the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. We have exhibited a global view of the potential molecular differences between middle cerebral artery occlusion (MCAO) animal model and sham for Mus musculus or Rattus norvegicus, including the biological process and enriched pathways in DEGs. This research helps contribute to a clearer understanding of the inflammation process and accurate identification of ischemic infarction stages, which might be transformed into a therapeutic approach. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessReview
The Natural Course of Non-Alcoholic Fatty Liver Disease
Int. J. Mol. Sci. 2016, 17(5), 774; https://doi.org/10.3390/ijms17050774
Received: 29 April 2016 / Revised: 12 May 2016 / Accepted: 12 May 2016 / Published: 20 May 2016
Cited by 117 | Viewed by 5908 | PDF Full-text (574 KB) | HTML Full-text | XML Full-text
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from “bland steatosis” to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death. Full article
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Open AccessArticle
Polymeric Nanoparticle-Based Photodynamic Therapy for Chronic Periodontitis in Vivo
Int. J. Mol. Sci. 2016, 17(5), 769; https://doi.org/10.3390/ijms17050769
Received: 14 March 2016 / Revised: 25 April 2016 / Accepted: 4 May 2016 / Published: 20 May 2016
Cited by 19 | Viewed by 2610 | PDF Full-text (1593 KB) | HTML Full-text | XML Full-text
Abstract
Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light [...] Read more.
Antimicrobial photodynamic therapy (aPDT) is increasingly being explored for treatment of periodontitis. Here, we investigated the effect of aPDT on human dental plaque bacteria in suspensions and biofilms in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles (MB-NP) and red light at 660 nm. The effect of MB-NP-based aPDT was also evaluated in a clinical pilot study with 10 adult human subjects with chronic periodontitis. Dental plaque samples from human subjects were exposed to aPDT—in planktonic and biofilm phases—with MB or MB-NP (25 µg/mL) at 20 J/cm2 in vitro. Patients were treated either with ultrasonic scaling and scaling and root planing (US + SRP) or ultrasonic scaling + SRP + aPDT with MB-NP (25 µg/mL and 20 J/cm2) in a split-mouth design. In biofilms, MB-NP eliminated approximately 25% more bacteria than free MB. The clinical study demonstrated the safety of aPDT. Both groups showed similar improvements of clinical parameters one month following treatments. However, at three months ultrasonic SRP + aPDT showed a greater effect (28.82%) on gingival bleeding index (GBI) compared to ultrasonic SRP. The utilization of PLGA nanoparticles encapsulated with MB may be a promising adjunct in antimicrobial periodontal treatment. Full article
(This article belongs to the Special Issue Drug Delivery and Antimicrobial Agents)
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Open AccessRetraction
Retraction: Zihan Xu, et al. Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers. Int. J. Mol. Sci. 2014, 15, 18117–18130
Int. J. Mol. Sci. 2016, 17(5), 768; https://doi.org/10.3390/ijms17050768
Received: 17 May 2016 / Revised: 17 May 2016 / Accepted: 17 May 2016 / Published: 20 May 2016
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Abstract
We have been made aware that text, figures and experimental data reported in the title paper [1] are duplicated in another publication by Zihan Xu et al. [2].[...] Full article
Open AccessArticle
Development of Therapeutic Chimeric Uricase by Exon Replacement/Restoration and Site-Directed Mutagenesis
Int. J. Mol. Sci. 2016, 17(5), 764; https://doi.org/10.3390/ijms17050764
Received: 30 March 2016 / Revised: 1 May 2016 / Accepted: 6 May 2016 / Published: 20 May 2016
Cited by 1 | Viewed by 1695 | PDF Full-text (5198 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The activity of urate oxidase was lost during hominoid evolution, resulting in high susceptibility to hyperuricemia and gout in humans. In order to develop a more “human-like” uricase for therapeutic use, exon replacement/restoration and site-directed mutagenesis were performed to obtain porcine–human uricase with [...] Read more.
The activity of urate oxidase was lost during hominoid evolution, resulting in high susceptibility to hyperuricemia and gout in humans. In order to develop a more “human-like” uricase for therapeutic use, exon replacement/restoration and site-directed mutagenesis were performed to obtain porcine–human uricase with higher homology to deduced human uricase (dHU) and increased uricolytic activity. In an exon replacement study, substitution of exon 6 in wild porcine uricase (wPU) gene with corresponding exon in dhu totally abolished its activity. Substitutions of exon 5, 3, and 1–2 led to 85%, 60%, and 45% loss of activity, respectively. However, replacement of exon 4 and 7–8 did not significantly change the enzyme activity. When exon 5, 6, and 3 in dhu were replaced by their counterparts in wpu, the resulting chimera H1-2P3H4P5-6H7-8 was active, but only about 28% of wPU. Multiple sequence alignment and homology modeling predicted that mutations of E24D and E83G in H1-2P3H4P5-6H7-8 were favorable for further increase of its activity. After site-directed mutagenesis, H1-2P3H4P5-6H7-8 (E24D & E83G) with increased homology (91.45%) with dHU and higher activity and catalytic efficiency than the FDA-approved porcine–baboon chimera (PBC) was obtained. It showed optimum activity at pH 8.5 and 35 °C and was stable in a pH range of 6.5–11.0 and temperature range of 20–40 °C. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Degree of Conversion and BisGMA, TEGDMA, UDMA Elution from Flowable Bulk Fill Composites
Int. J. Mol. Sci. 2016, 17(5), 732; https://doi.org/10.3390/ijms17050732
Received: 20 March 2016 / Revised: 4 May 2016 / Accepted: 9 May 2016 / Published: 20 May 2016
Cited by 13 | Viewed by 2443 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text
Abstract
The degree of conversion (DC) and the released bisphenol A diglycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers of bulk-fill composites compared to that of conventional flowable ones were assessed using micro-Raman spectroscopy and high performance liquid chromatography [...] Read more.
The degree of conversion (DC) and the released bisphenol A diglycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers of bulk-fill composites compared to that of conventional flowable ones were assessed using micro-Raman spectroscopy and high performance liquid chromatography (HPLC). Four millimeter-thick samples were prepared from SureFil SDR Flow (SDR), X-tra Base (XB), Filtek Bulk Fill (FBF) and two and four millimeter samples from Filtek Ultimate Flow (FUF). They were measured with micro-Raman spectroscopy to determine the DC% of the top and the bottom surfaces. The amount of released monomers in 75% ethanol extraction media was measured with HPLC. The differences between the top and bottom DC% were significant for each material. The mean DC values were in the following order for the bottom surfaces: SDR_4mm_20s > FUF_2mm_20s > XB_4mm_20s > FBF_4mm_20s > XB_4mm_10s > FBF_4mm_10s > FUF_4mm_20s. The highest rate in the amount of released BisGMA and TEGDMA was found from the 4 mm-thick conventional flowable FUF. Among bulk-fills, FBF showed a twenty times higher amount of eluted UDMA and twice more BisGMA; meanwhile, SDR released a significantly higher amount of TEGDMA. SDR bulk-fill showed significantly higher DC%; meanwhile XB, FBF did not reach the same level DC, as that of the 2 mm-thick conventional composite at the bottom surface. Conventional flowable composites showed a higher rate of monomer elution compared to the bulk-fills, except FBF, which showed a high amount of UDMA release. Full article
(This article belongs to the Special Issue Molecular Research on Dental Materials and Biomaterials)
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Open AccessArticle
Ruthenium Complexes Induce HepG2 Human Hepatocellular Carcinoma Cell Apoptosis and Inhibit Cell Migration and Invasion through Regulation of the Nrf2 Pathway
Int. J. Mol. Sci. 2016, 17(5), 775; https://doi.org/10.3390/ijms17050775
Received: 29 February 2016 / Revised: 28 April 2016 / Accepted: 5 May 2016 / Published: 19 May 2016
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Abstract
Ruthenium (Ru) complexes are currently the focus of substantial interest because of their potential application as chemotherapeutic agents with broad anticancer activities. This study investigated the in vitro and in vivo anticancer activities and mechanisms of two Ru complexes—2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine Ru(II) carbonyl (Ru1) and [...] Read more.
Ruthenium (Ru) complexes are currently the focus of substantial interest because of their potential application as chemotherapeutic agents with broad anticancer activities. This study investigated the in vitro and in vivo anticancer activities and mechanisms of two Ru complexes—2,3,7,8,12,13,17,18-Octaethyl-21H,23H-porphine Ru(II) carbonyl (Ru1) and 5,10,15,20-Tetraphenyl-21H,23H-porphine Ru(II) carbonyl (Ru2)—against human hepatocellular carcinoma (HCC) cells. These Ru complexes effectively inhibited the cellular growth of three human hepatocellular carcinoma (HCC) cells, with IC50 values ranging from 2.7–7.3 μM. In contrast, the complexes exhibited lower toxicity towards L02 human liver normal cells with IC50 values of 20.4 and 24.8 μM, respectively. Moreover, Ru2 significantly inhibited HepG2 cell migration and invasion, and these effects were dose-dependent. The mechanistic studies demonstrated that Ru2 induced HCC cell apoptosis, as evidenced by DNA fragmentation and nuclear condensation, which was predominately triggered via caspase family member activation. Furthermore, HCC cell treatment significantly decreased the expression levels of Nrf2 and its downstream effectors, NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1). Ru2 also exhibited potent in vivo anticancer efficacy in a tumor-bearing nude mouse model, as demonstrated by a time- and dose-dependent inhibition on tumor growth. The results demonstrate the therapeutic potential of Ru complexes against HCC via Nrf2 pathway regulation. Full article
(This article belongs to the Special Issue Recent Advances in Metal Based Drugs)
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Open AccessArticle
Predicting MicroRNA Biomarkers for Cancer Using Phylogenetic Tree and Microarray Analysis
Int. J. Mol. Sci. 2016, 17(5), 773; https://doi.org/10.3390/ijms17050773
Received: 23 March 2016 / Revised: 13 May 2016 / Accepted: 16 May 2016 / Published: 19 May 2016
Cited by 8 | Viewed by 2159 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are shown to be involved in the initiation and progression of cancers in the literature, and the expression of miRNAs is used as an important cancer prognostic tool. The aim of this study is to predict high-confidence miRNA biomarkers for cancer. [...] Read more.
MicroRNAs (miRNAs) are shown to be involved in the initiation and progression of cancers in the literature, and the expression of miRNAs is used as an important cancer prognostic tool. The aim of this study is to predict high-confidence miRNA biomarkers for cancer. We adopt a method that combines miRNA phylogenetic structure and miRNA microarray data analysis to discover high-confidence miRNA biomarkers for colon, prostate, pancreatic, lung, breast, bladder and kidney cancers. There are 53 miRNAs selected through this method that either have potential to involve a single cancer’s development or to involve several cancers’ development. These miRNAs can be used as high-confidence miRNA biomarkers of these seven investigated cancers for further experiment validation. miR-17, miR-20, miR-106a, miR-106b, miR-92, miR-25, miR-16, miR-195 and miR-143 are selected to involve a single cancer’s development in these seven cancers. They have the potential to be useful miRNA biomarkers when the result can be confirmed by experiments. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessArticle
A Study of Single Nucleotide Polymorphisms of the SLC19A1/RFC1 Gene in Subjects with Autism Spectrum Disorder
Int. J. Mol. Sci. 2016, 17(5), 772; https://doi.org/10.3390/ijms17050772
Received: 19 February 2016 / Revised: 24 April 2016 / Accepted: 2 May 2016 / Published: 19 May 2016
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Abstract
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with complex genetic etiology. Recent studies have indicated that children with ASD may have altered folate or methionine metabolism, suggesting that the folate–methionine cycle may play a key role in the etiology of [...] Read more.
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with complex genetic etiology. Recent studies have indicated that children with ASD may have altered folate or methionine metabolism, suggesting that the folate–methionine cycle may play a key role in the etiology of ASD. SLC19A1, also referred to as reduced folate carrier 1 (RFC1), is a member of the solute carrier group of transporters and is one of the key enzymes in the folate metabolism pathway. Findings from multiple genomic screens suggest the presence of an autism susceptibility locus on chromosome 21q22.3, which includes SLC19A1. Therefore, we performed a case-control study in a Japanese population. In this study, DNA samples obtained from 147 ASD patients at the Kanazawa University Hospital in Japan and 150 unrelated healthy Japanese volunteers were examined by the sequence-specific primer-polymerase chain reaction method pooled with fluorescence correlation spectroscopy. p < 0.05 was considered to represent a statistically significant outcome. Of 13 single nucleotide polymorphisms (SNPs) examined, a significant p-value was obtained for AA genotype of one SNP (rs1023159, OR = 0.39, 95% CI = 0.16–0.91, p = 0.0394; Fisher’s exact test). Despite some conflicting results, our findings supported a role for the polymorphism rs1023159 of the SLC19A1 gene, alone or in combination, as a risk factor for ASD. However, the findings were not consistent after multiple testing corrections. In conclusion, although our results supported a role of the SLC19A1 gene in the etiology of ASD, it was not a significant risk factor for the ASD samples analyzed in this study. Full article
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Open AccessArticle
Downregulation of Runx2 by 1,25-Dihydroxyvitamin D3 Induces the Transdifferentiation of Osteoblasts to Adipocytes
Int. J. Mol. Sci. 2016, 17(5), 770; https://doi.org/10.3390/ijms17050770
Received: 7 March 2016 / Revised: 27 April 2016 / Accepted: 16 May 2016 / Published: 19 May 2016
Cited by 5 | Viewed by 1669 | PDF Full-text (14984 KB) | HTML Full-text | XML Full-text
Abstract
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) indirectly stimulates bone formation, but little is known about its direct effect on bone formation. In this study, we observed that 1,25(OH)2D3 enhances adipocyte differentiation, but inhibits osteoblast differentiation during osteogenesis. The [...] Read more.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) indirectly stimulates bone formation, but little is known about its direct effect on bone formation. In this study, we observed that 1,25(OH)2D3 enhances adipocyte differentiation, but inhibits osteoblast differentiation during osteogenesis. The positive role of 1,25(OH)2D3 in adipocyte differentiation was confirmed when murine osteoblasts were cultured in adipogenic medium. Additionally, 1,25(OH)2D3 enhanced the expression of adipocyte marker genes, but inhibited the expression of osteoblast marker genes in osteoblasts. The inhibition of osteoblast differentiation and promotion of adipocyte differentiation mediated by 1,25(OH)2D3 were compensated by Runx2 overexpression. Our results suggest that 1,25(OH)2D3 induces the transdifferentiation of osteoblasts to adipocytes via Runx2 downregulation in osteoblasts. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
How Diet Intervention via Modulation of DNA Damage Response through MicroRNAs May Have an Effect on Cancer Prevention and Aging, an in Silico Study
Int. J. Mol. Sci. 2016, 17(5), 752; https://doi.org/10.3390/ijms17050752
Received: 1 March 2016 / Revised: 29 April 2016 / Accepted: 9 May 2016 / Published: 19 May 2016
Cited by 6 | Viewed by 2102 | PDF Full-text (2702 KB) | HTML Full-text | XML Full-text
Abstract
The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play [...] Read more.
The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as “fatty acids biosynthesis/metabolism”, “extracellular matrix-receptor interaction” and “signaling regulating the pluripotency of stem cells”, appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2016)
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