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Int. J. Mol. Sci., Volume 16, Issue 2 (February 2015) , Pages 2269-4361

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Open AccessArticle Metastatic Melanoma Cells Evade Immune Detection by Silencing STAT1
Int. J. Mol. Sci. 2015, 16(2), 4343-4361; https://doi.org/10.3390/ijms16024343
Received: 25 November 2014 / Accepted: 11 February 2015 / Published: 17 February 2015
Cited by 8 | Viewed by 2613 | PDF Full-text (2686 KB) | HTML Full-text | XML Full-text
Abstract
Transcriptional activation of major histocompatibility complex (MHC) I and II molecules by the cytokine, interferon γ (IFN-γ), is a key step in cell-mediated immunity against pathogens and tumors. Recent evidence suggests that suppression of MHC I and II expression on multiple tumor types
[...] Read more.
Transcriptional activation of major histocompatibility complex (MHC) I and II molecules by the cytokine, interferon γ (IFN-γ), is a key step in cell-mediated immunity against pathogens and tumors. Recent evidence suggests that suppression of MHC I and II expression on multiple tumor types plays important roles in tumor immunoevasion. One such tumor is malignant melanoma, a leading cause of skin cancer-related deaths. Despite growing awareness of MHC expression defects, the molecular mechanisms by which melanoma cells suppress MHC and escape from immune-mediated elimination remain unknown. Here, we analyze the dysregulation of the Janus kinase (JAK)/STAT pathway and its role in the suppression of MHC II in melanoma cell lines at the radial growth phase (RGP), the vertical growth phase (VGP) and the metastatic phase (MET). While RGP and VGP cells both express MHC II, MET cells lack not only MHC II, but also the critical transcription factors, interferon response factor (IRF) 1 and its upstream activator, signal transducer and activator of transcription 1 (STAT1). Suppression of STAT1 in vitro was also observed in patient tumor samples, suggesting STAT1 silencing as a global mechanism of MHC II suppression and immunoevasion. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Introducing a Semi-Coated Model to Investigate Antibacterial Effects of Biocompatible Polymers on Titanium Surfaces
Int. J. Mol. Sci. 2015, 16(2), 4327-4342; https://doi.org/10.3390/ijms16024327
Received: 18 November 2014 / Accepted: 12 February 2015 / Published: 17 February 2015
Cited by 10 | Viewed by 2868 | PDF Full-text (4735 KB) | HTML Full-text | XML Full-text
Abstract
Peri-implant infections from bacterial biofilms on artificial surfaces are a common threat to all medical implants. They are a handicap for the patient and can lead to implant failure or even life-threatening complications. New implant surfaces have to be developed to reduce biofilm
[...] Read more.
Peri-implant infections from bacterial biofilms on artificial surfaces are a common threat to all medical implants. They are a handicap for the patient and can lead to implant failure or even life-threatening complications. New implant surfaces have to be developed to reduce biofilm formation and to improve the long-term prognosis of medical implants. The aim of this study was (1) to develop a new method to test the antibacterial efficacy of implant surfaces by direct surface contact and (2) to elucidate whether an innovative antimicrobial copolymer coating of 4-vinyl-N-hexylpyridinium bromide and dimethyl(2-methacryloyloxyethyl) phosphonate (VP:DMMEP 30:70) on titanium is able to reduce the attachment of bacteria prevalent in peri-implant infections. With a new in vitro model with semi-coated titanium discs, we were able to show a dramatic reduction in the adhesion of various pathogenic bacteria (Streptococcus sanguinis, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis), completely independently of effects caused by soluble materials. In contrast, soft tissue cells (human gingival or dermis fibroblasts) were less affected by the same coating, despite a moderate reduction in initial adhesion of gingival fibroblasts. These data confirm the hypothesis that VP:DMMEP 30:70 is a promising antibacterial copolymer that may be of use in several clinical applications. Full article
(This article belongs to the Special Issue Antimicrobial Polymers)
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Open AccessArticle Comprehensive Analysis Suggests Overlapping Expression of Rice ONAC Transcription Factors in Abiotic and Biotic Stress Responses
Int. J. Mol. Sci. 2015, 16(2), 4306-4326; https://doi.org/10.3390/ijms16024306
Received: 29 December 2014 / Accepted: 11 February 2015 / Published: 17 February 2015
Cited by 16 | Viewed by 2683 | PDF Full-text (5104 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
NAC (NAM/ATAF/CUC) transcription factors comprise a large plant-specific gene family that contains more than 149 members in rice. Extensive studies have revealed that NAC transcription factors not only play important roles in plant growth and development, but also have functions in regulation of
[...] Read more.
NAC (NAM/ATAF/CUC) transcription factors comprise a large plant-specific gene family that contains more than 149 members in rice. Extensive studies have revealed that NAC transcription factors not only play important roles in plant growth and development, but also have functions in regulation of responses to biotic and abiotic stresses. However, biological functions for most of the members in the NAC family remain unknown. In this study, microarray data analyses revealed that a total of 63 ONAC genes exhibited overlapping expression patterns in rice under various abiotic (salt, drought, and cold) and biotic (infection by fungal, bacterial, viral pathogens, and parasitic plants) stresses. Thirty-eight ONAC genes exhibited overlapping expression in response to any two abiotic stresses, among which 16 of 30 selected ONAC genes were upregulated in response to exogenous ABA. Sixty-five ONAC genes showed overlapping expression patterns in response to any two biotic stresses. Results from the present study suggested that members of the ONAC genes with overlapping expression pattern may have pleiotropic biological functions in regulation of defense response against different abiotic and biotic stresses, which provide clues for further functional analysis of the ONAC genes in stress tolerance and pathogen resistance. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessReview Personalization of the Immunosuppressive Treatment in Renal Transplant Recipients: The Great Challenge in “Omics” Medicine
Int. J. Mol. Sci. 2015, 16(2), 4281-4305; https://doi.org/10.3390/ijms16024281
Received: 22 December 2014 / Revised: 4 February 2015 / Accepted: 9 February 2015 / Published: 17 February 2015
Cited by 13 | Viewed by 3188 | PDF Full-text (1621 KB) | HTML Full-text | XML Full-text
Abstract
Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over
[...] Read more.
Renal transplantation represents the most favorable treatment for patients with advanced renal failure and it is followed, in most cases, by a significant enhancement in patients’ quality of life. Significant improvements in one-year renal allograft and patients’ survival rates have been achieved over the last 10 years primarily as a result of newer immunosuppressive regimens. Despite these notable achievements in the short-term outcome, long-term graft function and survival rates remain less than optimal. Death with a functioning graft and chronic allograft dysfunction result in an annual rate of 3%–5%. In this context, drug toxicity and long-term chronic adverse effects of immunosuppressive medications have a pivotal role. Unfortunately, at the moment, except for the evaluation of trough drug levels, no clinically useful tools are available to correctly manage immunosuppressive therapy. The proper use of these drugs could potentiate therapeutic effects minimizing adverse drug reactions. For this purpose, in the future, “omics” techniques could represent powerful tools that may be employed in clinical practice to routinely aid the personalization of drug treatment according to each patient’s genetic makeup. However, it is unquestionable that additional studies and technological advances are needed to standardize and simplify these methodologies. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
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Open AccessArticle β-Hydroxybutyric Sodium Salt Inhibition of Growth Hormone and Prolactin Secretion via the cAMP/PKA/CREB and AMPK Signaling Pathways in Dairy Cow Anterior Pituitary Cells
Int. J. Mol. Sci. 2015, 16(2), 4265-4280; https://doi.org/10.3390/ijms16024265
Received: 17 November 2014 / Revised: 16 January 2015 / Accepted: 9 February 2015 / Published: 16 February 2015
Cited by 4 | Viewed by 4232 | PDF Full-text (2267 KB) | HTML Full-text | XML Full-text
Abstract
β-hydroxybutyric acid (BHBA) regulates the synthesis and secretion of growth hormone (GH) and prolactin (PRL), but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL
[...] Read more.
β-hydroxybutyric acid (BHBA) regulates the synthesis and secretion of growth hormone (GH) and prolactin (PRL), but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL gene transcription, and GH and PRL secretion in dairy cow anterior pituitary cells (DCAPCs). The results showed that BHBA decreased intracellular cAMP levels and a subsequent reduction in protein kinase A (PKA) activity. Inhibition of PKA activity reduced cAMP response element-binding protein (CREB) phosphorylation, thereby inhibiting GH and PRL transcription and secretion. The effects of BHBA were attenuated by a specific Gαi inhibitor, pertussis toxin (PTX). In addition, intracellular BHBA uptake mediated by monocarboxylate transporter 1 (MCT1) could trigger AMPK signaling and result in the decrease in GH and PRL mRNA translation in DCAPCs cultured under low-glucose and non-glucose condition when compared with the high-glucose group. This study identifies a biochemical mechanism for the regulatory action of BHBA on GH and PRL gene transcription, translation, and secretion in DCAPCs, which may be one of the factors that regulate pituitary function during the transition period in dairy cows. Full article
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
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Open AccessArticle Cultivation of Chlorella vulgaris and Arthrospira platensis with Recovered Phosphorus from Wastewater by Means of Zeolite Sorption
Int. J. Mol. Sci. 2015, 16(2), 4250-4264; https://doi.org/10.3390/ijms16024250
Received: 21 December 2014 / Revised: 3 February 2015 / Accepted: 10 February 2015 / Published: 16 February 2015
Cited by 13 | Viewed by 2368 | PDF Full-text (791 KB) | HTML Full-text | XML Full-text
Abstract
In this study, zeolite was employed for the separation and recovery of P from synthetic wastewater and its use as phosphorus (P) source for the cultivation of the green microalga Chlorella vulgaris and the cyanobacterium Arthrospira (Spirulina) platensis. At P-loaded zeolite concentration
[...] Read more.
In this study, zeolite was employed for the separation and recovery of P from synthetic wastewater and its use as phosphorus (P) source for the cultivation of the green microalga Chlorella vulgaris and the cyanobacterium Arthrospira (Spirulina) platensis. At P-loaded zeolite concentration of 0.15–1 g/L, in which P was limited, the two species displayed quite different behavior regarding their growth and biomass composition. C. vulgaris preferred to increase the intracellular P and did not synthesize biomass, while A. platensis synthesized biomass keeping the intracellular P as low as possible. In addition under P limitation, C. vulgaris did display some little alteration of the biomass composition, while A. platensis did it significantly, accumulating carbohydrates around 70% from about 15%–20% (control). Both species could desorb P from zeolite biologically. A. platensis could recover over 65% and C. vulgaris 25% of the P bounded onto zeolite. When P-loaded zeolite concentration increased to 5 g/L, P was adequate to support growth for both species. Especially in the case of C. vulgaris, growth was stimulated from the presence of P-loaded zeolite and produced more biomass compared to the control. Full article
(This article belongs to the Special Issue Green Chemistry and the Biorefinery)
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Open AccessReview Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure
Int. J. Mol. Sci. 2015, 16(2), 4226-4249; https://doi.org/10.3390/ijms16024226
Received: 5 January 2014 / Revised: 5 February 2015 / Accepted: 9 February 2015 / Published: 16 February 2015
Cited by 11 | Viewed by 3080 | PDF Full-text (1532 KB) | HTML Full-text | XML Full-text
Abstract
Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including
[...] Read more.
Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-α), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water. Full article
(This article belongs to the Special Issue Pathogenesis of Cardiac Arrhythmias and Heart Failure)
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Open AccessArticle Phosphoproteomic Analysis of the Highly-Metastatic Hepatocellular Carcinoma Cell Line, MHCC97-H
Int. J. Mol. Sci. 2015, 16(2), 4209-4225; https://doi.org/10.3390/ijms16024209
Received: 2 December 2014 / Revised: 3 February 2015 / Accepted: 3 February 2015 / Published: 16 February 2015
Cited by 8 | Viewed by 2887 | PDF Full-text (2983 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Invasion and metastasis of hepatocellular carcinoma (HCC) is a major cause for lethal liver cancer. Signaling pathways associated with cancer progression are frequently reconfigured by aberrant phosphorylation of key proteins. To capture the key phosphorylation events in HCC metastasis, we established a methodology
[...] Read more.
Invasion and metastasis of hepatocellular carcinoma (HCC) is a major cause for lethal liver cancer. Signaling pathways associated with cancer progression are frequently reconfigured by aberrant phosphorylation of key proteins. To capture the key phosphorylation events in HCC metastasis, we established a methodology by an off-line high-pH HPLC separation strategy combined with multi-step IMAC and LC–MS/MS to study the phosphoproteome of a metastatic HCC cell line, MHCC97-H (high metastasis). In total, 6593 phosphopeptides with 6420 phosphorylation sites (p-sites) of 2930 phosphoproteins were identified. Statistical analysis of gene ontology (GO) categories for the identified phosphoproteins showed that several of the biological processes, such as transcriptional regulation, mRNA processing and RNA splicing, were over-represented. Further analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations demonstrated that phosphoproteins in multiple pathways, such as spliceosome, the insulin signaling pathway and the cell cycle, were significantly enriched. In particular, we compared our dataset with a previously published phosphoproteome in a normal liver sample, and the results revealed that a number of proteins in the spliceosome pathway, such as U2 small nuclear RNA Auxiliary Factor 2 (U2AF2), Eukaryotic Initiation Factor 4A-III (EIF4A3), Cell Division Cycle 5-Like (CDC5L) and Survival Motor Neuron Domain Containing 1 (SMNDC1), were exclusively identified as phosphoproteins only in the MHCC97-H cell line. These results indicated that the phosphorylation of spliceosome proteins may participate in the metastasis of HCC by regulating mRNA processing and RNA splicing. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Open AccessReview The Role of BH3-Mimetic Drugs in the Treatment of Pediatric Hepatoblastoma
Int. J. Mol. Sci. 2015, 16(2), 4190-4208; https://doi.org/10.3390/ijms16024190
Received: 29 November 2014 / Revised: 1 February 2015 / Accepted: 9 February 2015 / Published: 16 February 2015
Cited by 7 | Viewed by 2416 | PDF Full-text (1310 KB) | HTML Full-text | XML Full-text
Abstract
Pediatric hepatoblastoma (HB) is commonly treated by neoadjuvant chemotherapy and surgical tumor resection according to international multicenter trial protocols. Complete tumor resection is essential and survival rates up to 95% have now been achieved in those tumors classified as standard-risk HB. Drug resistance
[...] Read more.
Pediatric hepatoblastoma (HB) is commonly treated by neoadjuvant chemotherapy and surgical tumor resection according to international multicenter trial protocols. Complete tumor resection is essential and survival rates up to 95% have now been achieved in those tumors classified as standard-risk HB. Drug resistance and occurrence of metastases remain the major challenges in the treatment of HB, especially in high-risk tumors. These conditions urgently require the development of alternative therapeutic strategies. One of those alternatives is the modulation of apoptosis in HB cells. HBs regularly overexpress anti-apoptotic proteins of the Bcl-family in comparison to healthy liver tissue. This fact may contribute to the development of chemoresistance of HB cells. Synthetic small inhibitory molecules with BH3-mimetic effects, such as ABT-737 and obatoclax, enhance the susceptibility of tumor cells to different cytotoxic drugs and thereby affect initiator proteins of the apoptosis cascade via the intrinsic pathway. Besides additive effects on HB cell viability when used in combination with cytotoxic drugs, BH3-mimetics also play a role in preventing metastasation by reducing adhesion and inhibiting cell migration abilities. Presumably, including additive BH3-mimetic drugs into existing therapeutic regimens in HB patients might allow dose reduction of established cytotoxic drugs and thereby associated immanent side effects, while maintaining the antitumor activity. Furthermore, reduction of tumor growth and inhibition of tumor cell dissemination may facilitate complete surgical tumor resection, which is mandatory in this tumor type resulting in improved survival rates in high-risk HB. Currently, there are phase I and phase II clinical trials in several cancer entities using this potential target. This paper reviews the available literature regarding the use of BH3-mimetic drugs as single agents or in combination with chemotherapy in various malignancies and focuses on results in HB cells. Full article
(This article belongs to the collection Molecular Mechanisms of Human Liver Diseases)
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Open AccessArticle Genetic Variant in Interleukin-18 Is Associated with Idiopathic Recurrent Miscarriage in Chinese Han Population
Int. J. Mol. Sci. 2015, 16(2), 4180-4189; https://doi.org/10.3390/ijms16024180
Received: 19 December 2014 / Revised: 23 January 2015 / Accepted: 10 February 2015 / Published: 16 February 2015
Cited by 6 | Viewed by 2081 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text
Abstract
Levels of IL-18 were significantly lower in women with recurrent miscarriage (RM) than those without idiopathic RM. IL-18 promoter single nucleotide polymorphisms were previously identified to have an impact on IL18 gene transcription activity and influence the level of IL-18 protein production. The
[...] Read more.
Levels of IL-18 were significantly lower in women with recurrent miscarriage (RM) than those without idiopathic RM. IL-18 promoter single nucleotide polymorphisms were previously identified to have an impact on IL18 gene transcription activity and influence the level of IL-18 protein production. The aim of this study was to evaluate whether IL-18 gene polymorphisms are risk factors for idiopathic RM in Chinese Han population. Study subjects comprised of 484 idiopathic RM patients and 468 controls. Three polymorphisms (rs360717, rs187238, rs1946518) in IL-18 gene and serum IL-18 concentrations were assessed. rs187238 variant exhibits significant association with RM in additive and recessive genetic model (additive model p = 1.05 × 10−4, dominant model p = 0.025, recessive model p = 2.43 × 10−5). In contrast, rs360717 and rs1946518 are not significantly associated with RM. Serum IL-18 levels are significantly lower in RM cases than in control (111.98 ± 93.13 versus 148.74 ± 130.51 pg/mL, p = 7.42 × 10−7). There are lower levels of serum IL-18 in rs187238 homozygous mutant (CC) than homozygous wild-type (GG) in this study population, including cases and control groups (98.31 ± 86.46 versus 131.87 ± 115.02 pg/mL, p = 0.015). These results suggest that reduced IL-18 levels and rs187238 variant may contribute to pathogenesis of idiopathic RM in Chinese Han population. Full article
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Open AccessReview Biological Functions of Thyroid Hormone in Placenta
Int. J. Mol. Sci. 2015, 16(2), 4161-4179; https://doi.org/10.3390/ijms16024161
Received: 3 November 2014 / Revised: 3 February 2015 / Accepted: 4 February 2015 / Published: 16 February 2015
Cited by 7 | Viewed by 2401 | PDF Full-text (1360 KB) | HTML Full-text | XML Full-text
Abstract
The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development
[...] Read more.
The thyroid hormone, 3,3,5-triiodo-l-thyronine (T3), modulates several physiological processes, including cellular growth, differentiation, metabolism, inflammation and proliferation, via interactions with thyroid hormone response elements (TREs) in the regulatory regions of target genes. Infection and inflammation are critical processes in placental development and pregnancy-related diseases. In particular, infection is the leading cause of neonatal mortality and morbidity worldwide. However, to date, no successful approach has been developed for the effective diagnosis of infection in preterm infants. Pre-eclampsia (PE) is a serious disorder that adversely affects ~5% of human pregnancies. Recent studies identified a multiprotein complex, the inflammasome, including the Nod-like receptor (NLR) family of cytosolic pattern recognition receptors, the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1, which plays a vital role in the placenta. The thyroid hormone modulates inflammation processes and is additionally implicated in placental development and disease. Therefore, elucidation of thyroid hormone receptor-regulated inflammation-related molecules, and their underlying mechanisms in placenta, should facilitate the identification of novel predictive and therapeutic targets for placental disorders. This review provides a detailed summary of current knowledge with respect to identification of useful biomarkers and their physiological significance in placenta. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Major Peptides from Amaranth (Amaranthus cruentus) Protein Inhibit HMG-CoA Reductase Activity
Int. J. Mol. Sci. 2015, 16(2), 4150-4160; https://doi.org/10.3390/ijms16024150
Received: 24 June 2014 / Revised: 2 December 2014 / Accepted: 18 December 2014 / Published: 16 February 2015
Cited by 18 | Viewed by 2284 | PDF Full-text (820 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to identify the major peptides generated by the in vitro hydrolysis of Amaranthus cruentus protein and to verify the effect of these peptides on the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a key enzyme in cholesterol biosynthesis.
[...] Read more.
The objective of this study was to identify the major peptides generated by the in vitro hydrolysis of Amaranthus cruentus protein and to verify the effect of these peptides on the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), a key enzyme in cholesterol biosynthesis. A protein isolate was prepared, and an enzymatic hydrolysis that simulated the in vivo digestion of the protein was performed. After hydrolysis, the peptide mixture was filtered through a 3 kDa membrane. The peptide profile of this mixture was determined by reversed phase high performance chromatography (RP-HPLC), and the peptide identification was performed by LC-ESI MS/MS. Three major peptides under 3 kDa were detected, corresponding to more than 90% of the peptides of similar size produced by enzymatic hydrolysis. The sequences identified were GGV, IVG or LVG and VGVI or VGVL. These peptides had not yet been described for amaranth protein nor are they present in known sequences of amaranth grain protein, except LVG, which can be found in amaranth α‑amylase. Their ability to inhibit the activity of HMG-CoA reductase was determined, and we found that the sequences GGV, IVG, and VGVL, significantly inhibited this enzyme, suggesting a possible hypocholesterolemic effect. Full article
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
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Open AccessArticle Isolation and Molecular Characterization of 1-Aminocyclopropane-1-carboxylic Acid Synthase Genes in Hevea brasiliensis
Int. J. Mol. Sci. 2015, 16(2), 4136-4149; https://doi.org/10.3390/ijms16024136
Received: 31 October 2014 / Accepted: 6 February 2015 / Published: 16 February 2015
Cited by 3 | Viewed by 2101 | PDF Full-text (2083 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Ethylene is an important factor that stimulates Hevea brasiliensis to produce natural rubber. 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is a rate-limiting enzyme in ethylene biosynthesis. However, knowledge of the ACS gene family of H. brasiliensis is limited. In this study, nine ACS-like genes
[...] Read more.
Ethylene is an important factor that stimulates Hevea brasiliensis to produce natural rubber. 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is a rate-limiting enzyme in ethylene biosynthesis. However, knowledge of the ACS gene family of H. brasiliensis is limited. In this study, nine ACS-like genes were identified in H. brasiliensis. Sequence and phylogenetic analysis results confirmed that seven isozymes (HbACS1–7) of these nine ACS-like genes were similar to ACS isozymes with ACS activity in other plants. Expression analysis results showed that seven ACS genes were differentially expressed in roots, barks, flowers, and leaves of H. brasiliensis. However, no or low ACS gene expression was detected in the latex of H. brasiliensis. Moreover, seven genes were differentially up-regulated by ethylene treatment. These results provided relevant information to help determine the functions of the ACS gene in H. brasiliensis, particularly the functions in regulating ethylene stimulation of latex production. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Genetic Polymorphisms in Estrogen-Related Genes and the Risk of Breast Cancer among Han Chinese Women
Int. J. Mol. Sci. 2015, 16(2), 4121-4135; https://doi.org/10.3390/ijms16024121
Received: 3 November 2014 / Revised: 21 January 2015 / Accepted: 4 February 2015 / Published: 13 February 2015
Cited by 7 | Viewed by 2161 | PDF Full-text (704 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women.
[...] Read more.
Exposure to high levels of estrogen is considered an important risk factor for susceptibility to breast cancer. Common polymorphisms in genes that affect estrogen levels may be associated with breast cancer risk, but no comprehensive study has been performed among Han Chinese women. In the present study, 32 single-nucleotide polymorphisms (SNPs) in estrogen-related genes were genotyped using the MassARRAY IPLEX platform in 1076 Han Chinese women. Genotypic and allelic frequencies were compared between case and control groups. Unconditional logistic regression was used to assess the effects of SNPs on breast cancer risk. Associations were also evaluated for breast cancer subtypes stratified by estrogen receptor (ER) and progesterone receptor (PR) status. Case-control analysis showed a significant relation between heterozygous genotypes of rs700519 and rs2069522 and breast cancer risk (OR = 0.723, 95% CI = 0.541–0.965, p = 0.028 and OR = 1.500, 95% CI = 1.078–2.087, p = 0.016, respectively). Subgroup comparisons revealed that rs2446405 and rs17268974 were related to ER status, and rs130021 was associated with PR status. Our findings suggest that rs700519 and rs2069522 are associated with susceptibility to breast cancer among the Han Chinese population and have a cumulative effect with three other identified SNPs. Further genetic and functional studies are needed to identify additional SNPs, and to elucidate the underlying molecular mechanisms. Full article
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
Open AccessReview The Actin Depolymerizing Factor (ADF)/Cofilin Signaling Pathway and DNA Damage Responses in Cancer
Int. J. Mol. Sci. 2015, 16(2), 4095-4120; https://doi.org/10.3390/ijms16024095
Received: 22 December 2014 / Revised: 26 January 2015 / Accepted: 9 February 2015 / Published: 13 February 2015
Cited by 19 | Viewed by 3916 | PDF Full-text (1768 KB) | HTML Full-text | XML Full-text
Abstract
The actin depolymerizing factor (ADF)/cofilin protein family is essential for actin dynamics, cell division, chemotaxis and tumor metastasis. Cofilin-1 (CFL-1) is a primary non-muscle isoform of the ADF/cofilin protein family accelerating the actin filamental turnover in vitro and in vivo. In response
[...] Read more.
The actin depolymerizing factor (ADF)/cofilin protein family is essential for actin dynamics, cell division, chemotaxis and tumor metastasis. Cofilin-1 (CFL-1) is a primary non-muscle isoform of the ADF/cofilin protein family accelerating the actin filamental turnover in vitro and in vivo. In response to environmental stimulation, CFL-1 enters the nucleus to regulate the actin dynamics. Although the purpose of this cytoplasm-nucleus transition remains unclear, it is speculated that the interaction between CFL-1 and DNA may influence various biological responses, including DNA damage repair. In this review, we will discuss the possible involvement of CFL-1 in DNA damage responses (DDR) induced by ionizing radiation (IR), and the implications for cancer radiotherapy. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2014)
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Open AccessReview Autophagy as a Regulatory Component of Erythropoiesis
Int. J. Mol. Sci. 2015, 16(2), 4083-4094; https://doi.org/10.3390/ijms16024083
Received: 8 January 2015 / Revised: 5 February 2015 / Accepted: 9 February 2015 / Published: 13 February 2015
Cited by 17 | Viewed by 3151 | PDF Full-text (793 KB) | HTML Full-text | XML Full-text
Abstract
Autophagy is a process that leads to the degradation of unnecessary or dysfunctional cellular components and long-lived protein aggregates. Erythropoiesis is a branch of hematopoietic differentiation by which mature red blood cells (RBCs) are generated from multi-potential hematopoietic stem cells (HSCs). Autophagy plays
[...] Read more.
Autophagy is a process that leads to the degradation of unnecessary or dysfunctional cellular components and long-lived protein aggregates. Erythropoiesis is a branch of hematopoietic differentiation by which mature red blood cells (RBCs) are generated from multi-potential hematopoietic stem cells (HSCs). Autophagy plays a critical role in the elimination of mitochondria, ribosomes and other organelles during erythroid terminal differentiation. Here, the modulators of autophagy that regulate erythroid differentiation were summarized, including autophagy-related (Atg) genes, the B-cell lymphoma 2 (Bcl-2) family member Bcl-2/adenovirus E1B 19 kDa interacting protein 3-like (Nix/Binp3L), transcription factors globin transcription factor 1 (GATA1) and forkhead box O3 (FoxO3), intermediary factor KRAB-associated protein1 (KAP1), and other modulators, such as focal adhesion kinase family-interacting protein of 200-kDa (FIP200), Ca2+ and 15-lipoxygenase. Understanding the modulators of autophagy in erythropoiesis will benefit the autophagy research field and facilitate the prevention and treatment of autophagy-related red blood cell disorders. Full article
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Open AccessReview The 15q11.2 BP1–BP2 Microdeletion Syndrome: A Review
Int. J. Mol. Sci. 2015, 16(2), 4068-4082; https://doi.org/10.3390/ijms16024068
Received: 5 January 2015 / Revised: 3 February 2015 / Accepted: 10 February 2015 / Published: 13 February 2015
Cited by 46 | Viewed by 6986 | PDF Full-text (1062 KB) | HTML Full-text | XML Full-text
Abstract
Patients with the 15q11.2 BP1–BP2 microdeletion can present with developmental and language delay, neurobehavioral disturbances and psychiatric problems. Autism, seizures, schizophrenia and mild dysmorphic features are less commonly seen. The 15q11.2 BP1–BP2 microdeletion involving four genes (i.e., TUBGCP5, CYFIP1,
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Patients with the 15q11.2 BP1–BP2 microdeletion can present with developmental and language delay, neurobehavioral disturbances and psychiatric problems. Autism, seizures, schizophrenia and mild dysmorphic features are less commonly seen. The 15q11.2 BP1–BP2 microdeletion involving four genes (i.e., TUBGCP5, CYFIP1, NIPA1, NIPA2) is emerging as a recognized syndrome with a prevalence ranging from 0.57%–1.27% of patients presenting for microarray analysis which is a two to four fold increase compared with controls. Review of clinical features from about 200 individuals were grouped into five categories and included developmental (73%) and speech (67%) delays; dysmorphic ears (46%) and palatal anomalies (46%); writing (60%) and reading (57%) difficulties, memory problems (60%) and verbal IQ scores ≤75 (50%); general behavioral problems, unspecified (55%) and abnormal brain imaging (43%). Other clinical features noted but not considered as common were seizures/epilepsy (26%), autism spectrum disorder (27%), attention deficit disorder (ADD)/attention deficit hyperactivity disorder (ADHD) (35%), schizophrenia/paranoid psychosis (20%) and motor delay (42%). Not all individuals with the deletion are clinically affected, yet the collection of findings appear to share biological pathways and presumed genetic mechanisms. Neuropsychiatric and behavior disturbances and mild dysmorphic features are associated with genomic imbalances of the 15q11.2 BP1–BP2 region, including microdeletions, but with an apparent incomplete penetrance and variable expressivity. Full article
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Open AccessReview Induced Pluripotent Stem Cells and Their Use in Cardiac and Neural Regenerative Medicine
Int. J. Mol. Sci. 2015, 16(2), 4043-4067; https://doi.org/10.3390/ijms16024043
Received: 29 December 2014 / Revised: 27 January 2015 / Accepted: 2 February 2015 / Published: 13 February 2015
Cited by 9 | Viewed by 4038 | PDF Full-text (764 KB) | HTML Full-text | XML Full-text
Abstract
Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by Yamanaka and colleagues to induce pluripotency in somatic cells has reshaped the field of stem cell research.
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Stem cells are unique pools of cells that are crucial for embryonic development and maintenance of adult tissue homeostasis. The landmark Nobel Prize winning research by Yamanaka and colleagues to induce pluripotency in somatic cells has reshaped the field of stem cell research. The complications related to the usage of pluripotent embryonic stem cells (ESCs) in human medicine, particularly ESC isolation and histoincompatibility were bypassed with induced pluripotent stem cell (iPSC) technology. The human iPSCs can be used for studying embryogenesis, disease modeling, drug testing and regenerative medicine. iPSCs can be diverted to different cell lineages using small molecules and growth factors. In this review we have focused on iPSC differentiation towards cardiac and neuronal lineages. Moreover, we deal with the use of iPSCs in regenerative medicine and modeling diseases like myocardial infarction, Timothy syndrome, dilated cardiomyopathy, Parkinson’s, Alzheimer’s and Huntington’s disease. Despite the promising potential of iPSCs, genome contamination and low efficacy of cell reprogramming remain significant challenges. Full article
(This article belongs to the Special Issue Molecular and Cellular Basis of Regeneration and Tissue Repair)
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Open AccessArticle Functional Properties of the Catalytic Domain of Mouse Acidic Mammalian Chitinase Expressed in Escherichia coli
Int. J. Mol. Sci. 2015, 16(2), 4028-4042; https://doi.org/10.3390/ijms16024028
Received: 26 December 2014 / Accepted: 3 February 2015 / Published: 13 February 2015
Cited by 14 | Viewed by 2499 | PDF Full-text (2436 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mouse acidic mammalian chitinase (AMCase) plays important physiological roles in defense and nutrition. AMCase is composed of an N-terminal catalytic domain (CatD) and a C-terminal chitin-binding domain (CBD). We expressed CatD of mouse AMCase as a recombinant fusion protein with Protein
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Mouse acidic mammalian chitinase (AMCase) plays important physiological roles in defense and nutrition. AMCase is composed of an N-terminal catalytic domain (CatD) and a C-terminal chitin-binding domain (CBD). We expressed CatD of mouse AMCase as a recombinant fusion protein with Protein A and V5-His in Escherichia coli (Protein A-CatD-V5-His), evaluated its functional properties and compared them to the full-length AMCase (Protein A-AMCase-V5-His). Under our experimental conditions, the chitinolytic activity of both proteins against 4-nitrophenyl N,N'-diacetyl-β-d-chitobioside was equivalent with regard to their specific enzymatic activities, optimal pH and temperature as well as to the pH and temperature stability. CatD bound to chitin beads and cleaved the N-acetylglucosamine hexamer, colloidal and crystalline chitin as well as the shrimp shell, and released primarily N,N'-diacetylchitobiose fragments at pH 2.0. These results indicate that the primary structure of CatD is sufficient to form a proper tertiary structure required for chitinolytic activity, recognize chitin substrates and degrade them in the absence of a CBD. Our recombinant proteins can be used for further studies evaluating pathophysiological roles of AMCase in different diseases. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle Multiscale Experimental and Theoretical Investigations of Spin Crossover FeII Complexes: Examples of [Fe(phen)2(NCS)2] and [Fe(PM-BiA)2(NCS)2]
Int. J. Mol. Sci. 2015, 16(2), 4007-4027; https://doi.org/10.3390/ijms16024007
Received: 24 December 2014 / Revised: 14 January 2015 / Accepted: 30 January 2015 / Published: 12 February 2015
Cited by 10 | Viewed by 2359 | PDF Full-text (2410 KB) | HTML Full-text | XML Full-text
Abstract
For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron
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For spin crossover (SCO) complexes, computation results are reported and confirmed with experiments at multiscale levels of the isolated molecule and extended solid on the one hand and theory on the other hand. The SCO phenomenon which characterizes organometallics based on divalent iron in an octahedral FeN6-like environment with high spin (HS) and low spin (LS) states involves the LS/HS switching at the cost of small energies provided by temperature, pressure or light, the latter connected with Light-Induced Excited Spin-State Trapping (LIESST) process. Characteristic infra red (IR) and Raman vibration frequencies are computed within density functional theory (DFT) framework. In [Fe(phen)2(NCS)2] a connection of selected frequencies is established with an ultra-fast light-induced LS → HS photoswitching mechanism. In the extended solid, density of state DOS and electron localization function (ELF) are established for both LS and HS forms, leading to characterizion of the compound as an insulator in both spin states with larger gaps for LS configuration, while keeping molecular features in the solid. In [Fe(PM-BiA)2(NCS)2], by combining DFT and classical molecular dynamics, the properties and the domains of existence of the different phases are obtained by expressing the potential energy surfaces in a short range potential for Fe–N interactions. Applying such Fe–N potentials inserted in a classical force field and carrying out molecular dynamics (MD) in so-called “semi-classical MD” calculations, lead to the relative energies of HS/LS configurations of the crystal and to the assessment of the experimental (P, T) phase diagram. Full article
(This article belongs to the Special Issue Chemical Bond and Bonding 2015)
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Open AccessArticle Effect of Porcine Akirin2 on Skeletal Myosin Heavy Chain Isoform Expression
Int. J. Mol. Sci. 2015, 16(2), 3996-4006; https://doi.org/10.3390/ijms16023996
Received: 7 December 2014 / Revised: 4 February 2015 / Accepted: 9 February 2015 / Published: 12 February 2015
Cited by 5 | Viewed by 1825 | PDF Full-text (2019 KB) | HTML Full-text | XML Full-text
Abstract
Akirin2 plays an important role in skeletal myogenesis. In this study, we found that porcine Akirin2 (pAkirin2) mRNA level was significantly higher in fast extensor digitorum longus (EDL) and longissimus lumborum (LL) muscles than in slow soleus (SOL) muscle of pigs.
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Akirin2 plays an important role in skeletal myogenesis. In this study, we found that porcine Akirin2 (pAkirin2) mRNA level was significantly higher in fast extensor digitorum longus (EDL) and longissimus lumborum (LL) muscles than in slow soleus (SOL) muscle of pigs. Overexpression of pAkirin2 increased the number of myosin heavy chain (MHC)-positive cells, indicating that pAkirin2 promoted myoblast differentiation. We also found that overexpression of pAkirin2 increased the mRNA expressions of MHCI and MHCIIa and decreased the mRNA expression of MHCIIb. Myocyte enhancer factor 2 (MEF2) and nuclear factor of activated T cells (NFAT) are the major downstream effectors of calcineurin. Here we also observed that the mRNA expressions of MEF2C and NFATc1 were notably elevated by pAkirin2 overexpression. Together, our data indicate that the role of pAkirin2 in modulating MHCI and MHCIIa expressions may be achieved through calcineurin/NFATc1 signaling pathway. Full article
(This article belongs to the Section Biochemistry)
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Open AccessCommunication Development of Biodegradable Nanocarriers Loaded with a Monoclonal Antibody
Int. J. Mol. Sci. 2015, 16(2), 3990-3995; https://doi.org/10.3390/ijms16023990
Received: 23 December 2014 / Revised: 21 January 2015 / Accepted: 28 January 2015 / Published: 12 February 2015
Cited by 12 | Viewed by 2421 | PDF Full-text (983 KB) | HTML Full-text | XML Full-text
Abstract
Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles
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Treatments utilizing monoclonal antibody therapeutics against intracellular protein-protein interactions in cancer cells have been hampered by several factors, including poor intracellular uptake and rapid lysosomal degradation. Our current work examines the feasibility of encapsulating monoclonal antibodies within poly(lactic-co-glycolic acid) (PLGA) nanoparticles using a water/oil/water double emulsion solvent evaporation technique. This method can be used to prepare protective polymeric nanoparticles for transporting functional antibodies to the cytoplasmic compartment of cancer cells. Nanoparticles were formulated and then characterized using a number of physical and biological parameters. The average nanoparticle size ranged from 221 to 252 nm with a low polydispersity index. Encapsulation efficiency of 16%–22% and antibody loading of 0.3%–1.12% were observed. The antibody molecules were released from the nanoparticles in a sustained manner and upon release maintained functionality. Our studies achieved successful formulation of antibody loaded polymeric nanoparticles, thus indicating that a PLGA-based antibody nanoformulation is a promising intracellular delivery vehicle for a large number of new intracellular antibody targets in cancer cells. Full article
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
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Open AccessArticle Isolation and Cytotoxicity Evaluation of the Chemical Constituents from Cephalantheropsis gracilis
Int. J. Mol. Sci. 2015, 16(2), 3980-3989; https://doi.org/10.3390/ijms16023980
Received: 15 January 2015 / Revised: 2 February 2015 / Accepted: 2 February 2015 / Published: 12 February 2015
Cited by 16 | Viewed by 1990 | PDF Full-text (709 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Cephalantheropsis gracilis afforded five new compounds: cephalanthrin-A (1), cephalanthrin-B (2), cephathrene-A (3), cephathrene-B (4), methyl 2-(aminocarbonyl) phenylcarbamate (5), and 52 known compounds. The structures of the new compounds were determined by spectroscopic analysis.
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Cephalantheropsis gracilis afforded five new compounds: cephalanthrin-A (1), cephalanthrin-B (2), cephathrene-A (3), cephathrene-B (4), methyl 2-(aminocarbonyl) phenylcarbamate (5), and 52 known compounds. The structures of the new compounds were determined by spectroscopic analysis. Among the compounds isolated, tryptanthrin (6), phaitanthrin A (7), cephalinone D (19), and flavanthrin (30) showed significant cytotoxicity against MCF-7, NCI-H460, and SF-268 cell lines. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview Regulation of Translation Factor EEF1D Gene Function by Alternative Splicing
Int. J. Mol. Sci. 2015, 16(2), 3970-3979; https://doi.org/10.3390/ijms16023970
Received: 19 December 2014 / Accepted: 4 February 2015 / Published: 12 February 2015
Cited by 5 | Viewed by 1947 | PDF Full-text (930 KB) | HTML Full-text | XML Full-text
Abstract
Alternative splicing is an exquisite mechanism that allows one coding gene to have multiple functions. The alternative splicing machinery is necessary for proper development, differentiation and stress responses in a variety of organisms, and disruption of this machinery is often implicated in human
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Alternative splicing is an exquisite mechanism that allows one coding gene to have multiple functions. The alternative splicing machinery is necessary for proper development, differentiation and stress responses in a variety of organisms, and disruption of this machinery is often implicated in human diseases. Previously, we discovered a long form of eukaryotic elongation factor 1Bδ (eEF1Bδ; this long-form eEF1Bδ results from alternative splicing of EEF1D transcripts and regulates the cellular stress response by transcriptional activation, not translational enhancement, of heat-shock responsive genes. In this review, we discuss the molecular function of EEF1D alternative splicing products and the estimated implication of human diseases. Full article
(This article belongs to the Special Issue Pre-mRNA Splicing)
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Open AccessArticle Multifunctional Composites of Chiral Valine Derivative Schiff Base Cu(II) Complexes and TiO2
Int. J. Mol. Sci. 2015, 16(2), 3955-3969; https://doi.org/10.3390/ijms16023955
Received: 15 January 2015 / Revised: 27 January 2015 / Accepted: 5 February 2015 / Published: 12 February 2015
Cited by 3 | Viewed by 2191 | PDF Full-text (1118 KB) | HTML Full-text | XML Full-text
Abstract
We have prepared four new Cu(II) complexes containing valine moieties with imidazole ligands at the fourth coordination sites and examined their photo-induced reactions with TiO2 in order of understanding the reaction mechanisms. Under a nitrogen atmosphere, the intermolecular electron transfer reactions (essentially
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We have prepared four new Cu(II) complexes containing valine moieties with imidazole ligands at the fourth coordination sites and examined their photo-induced reactions with TiO2 in order of understanding the reaction mechanisms. Under a nitrogen atmosphere, the intermolecular electron transfer reactions (essentially supramolecular interactions) of these systems, which resulted in the reduction of Cu(II) species to Cu(I) ones, occurred after UV light irradiation. In this study, we have investigated the conditions of the redox reactions in view of substituent effects of aldehyde moieties. The results of cyclic voltammetry (CV) on an rotating ring-disk electrode (RRDE) suggested that the substitution effects and redox potentials were correlated. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were also performed to simulate the UV–Vis and circular dichroism (CD) spectra; the results revealed a reasonably good correlation between the substituent effects and the highest occupied molecular orbitals and the lowest unoccupied molecular orbitals (HOMO-LUMO) gaps associated with the most intense transition bands. In addition, we summarized the substitution effects of Cu(II) complexes for their corresponding UV light-induced reactions. Full article
(This article belongs to the Special Issue Supramolecular Interactions)
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Open AccessReview Tumor Immunotargeting Using Innovative Radionuclides
Int. J. Mol. Sci. 2015, 16(2), 3932-3954; https://doi.org/10.3390/ijms16023932
Received: 5 January 2015 / Accepted: 29 January 2015 / Published: 11 February 2015
Cited by 18 | Viewed by 2700 | PDF Full-text (829 KB) | HTML Full-text | XML Full-text
Abstract
This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical
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This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality. Full article
(This article belongs to the Special Issue Frontiers of Radioimmunotherapy)
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Open AccessArticle Valproic Acid as a Potential Inhibitor of Plasmodium falciparum Histone Deacetylase 1 (PfHDAC1): An in Silico Approach
Int. J. Mol. Sci. 2015, 16(2), 3915-3931; https://doi.org/10.3390/ijms16023915
Received: 3 December 2014 / Accepted: 30 January 2015 / Published: 11 February 2015
Cited by 4 | Viewed by 3654 | PDF Full-text (2774 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A new Plasmodium falciparum histone deacetylase1 (PfHDAC1) homology model was built based on the highest sequence identity available template human histone deacetylase 2 structure. The generated model was carefully evaluated for stereochemical accuracy, folding correctness and overall structure quality. All evaluations
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A new Plasmodium falciparum histone deacetylase1 (PfHDAC1) homology model was built based on the highest sequence identity available template human histone deacetylase 2 structure. The generated model was carefully evaluated for stereochemical accuracy, folding correctness and overall structure quality. All evaluations were acceptable and consistent. Docking a group of hydroxamic acid histone deacetylase inhibitors and valproic acid has shown binding poses that agree well with inhibitor-bound histone deacetylase-solved structural interactions. Docking affinity dG scores were in agreement with available experimental binding affinities. Further, enzyme-ligand complex stability and reliability were investigated by running 5-nanosecond molecular dynamics simulations. Thorough analysis of the simulation trajectories has shown that enzyme-ligand complexes were stable during the simulation period. Interestingly, the calculated theoretical binding energies of the docked hydroxamic acid inhibitors have shown that the model can discriminate between strong and weaker inhibitors and agrees well with the experimental affinities reported in the literature. The model and the docking methodology can be used in screening virtual libraries for PfHDAC1 inhibitors, since the docking scores have ranked ligands in accordance with experimental binding affinities. Valproic acid calculated theoretical binding energy suggests that it may inhibit PfHDAC1. Full article
(This article belongs to the Section Molecular Recognition)
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Open AccessReview Nutritionally Enhanced Food Crops; Progress and Perspectives
Int. J. Mol. Sci. 2015, 16(2), 3895-3914; https://doi.org/10.3390/ijms16023895
Received: 22 December 2014 / Accepted: 4 February 2015 / Published: 11 February 2015
Cited by 46 | Viewed by 6258 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world’s poor are under development as
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Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world’s poor are under development as well as new varieties of crops which have the ability to combat chronic disease. This review discusses the improvement of the nutritional status of crops to make a positive impact on global human health. Several examples of nutritionally enhanced crops which have been developed using biotechnological approaches will be discussed. These range from biofortified crops to crops with novel abilities to fight disease. The review concludes with a discussion of hurdles faced with respect to public perception, as well as directions of future research and development for nutritionally enhanced food crops. Full article
(This article belongs to the Special Issue Pharmaceuticals and Nutraceuticals by Molecular Farming)
Open AccessArticle A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study
Int. J. Mol. Sci. 2015, 16(2), 3885-3894; https://doi.org/10.3390/ijms16023885
Received: 14 December 2014 / Accepted: 6 February 2015 / Published: 11 February 2015
Cited by 4 | Viewed by 2371 | PDF Full-text (708 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Objective: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, but there is limited information about the genetic contribution to atherosclerosis in this population. Therefore, we examined the association between selected genetic polymorphisms and coronary atherosclerosis in patients with RA. Methods: Genotypes for single-nucleotide
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Objective: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, but there is limited information about the genetic contribution to atherosclerosis in this population. Therefore, we examined the association between selected genetic polymorphisms and coronary atherosclerosis in patients with RA. Methods: Genotypes for single-nucleotide polymorphisms (SNPs) in 152 candidate genes linked with autoimmune or cardiovascular risk were measured in 140 patients with RA. The association between the presence of coronary artery calcium (CAC) and SNP allele frequency was assessed by logistic regression with adjustment for age, sex, and race. To adjust for multiple comparisons, a false discovery rate (FDR) threshold was set at 20%. Results: Patients with RA were 54 ± 11 years old and predominantly Caucasian (89%) and female (69%). CAC was present in 70 patients (50%). A variant in rs2073618 that encodes an Asn3Lys missense substitution in the osteoprotegerin gene (OPG, TNFRSF11B) was significantly associated with the presence of CAC (OR = 4.09, p < 0.00026) and withstands FDR correction. Conclusion: Our results suggest that a polymorphism of the TNFRSF11B gene, which encodes osteoprotegerin, is associated with the presence of coronary atherosclerosis in patients with RA. Replication of this finding in independent validation cohorts will be of interest. Full article
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging) Printed Edition available
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Open AccessArticle Autism and Intellectual Disability Associated with Mitochondrial Disease and Hyperlactacidemia
Int. J. Mol. Sci. 2015, 16(2), 3870-3884; https://doi.org/10.3390/ijms16023870
Received: 26 November 2014 / Accepted: 4 February 2015 / Published: 11 February 2015
Cited by 10 | Viewed by 3006 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
Autism spectrum disorder (ASD) with intellectual disability (ID) is a life-long debilitating condition, which is characterized by cognitive function impairment and other neurological signs. Children with ASD-ID typically attain motor skills with a significant delay. A sub-group of ASD-IDs has been linked to
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Autism spectrum disorder (ASD) with intellectual disability (ID) is a life-long debilitating condition, which is characterized by cognitive function impairment and other neurological signs. Children with ASD-ID typically attain motor skills with a significant delay. A sub-group of ASD-IDs has been linked to hyperlactacidemia and alterations in mitochondrial respiratory chain activity. The objective of this report is to describe the clinical features of patients with these comorbidities in order to shed light on difficult diagnostic and therapeutic approaches in such patients. We reported the different clinical features of children with ID associated with hyperlactacidemia and deficiencies in mitochondrial respiratory chain complex II–IV activity whose clinical presentations are commonly associated with the classic spectrum of mitochondrial diseases. We concluded that patients with ASD and ID presenting with persistent hyperlactacidemia should be evaluated for mitochondrial disorders. Administration of carnitine, coenzyme Q10, and folic acid is partially beneficial, although more studies are needed to assess the efficacy of this vitamin/cofactor treatment combination. Full article
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