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Int. J. Mol. Sci., Volume 16, Issue 12 (December 2015)

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Cover Story Blood vessels are ubiquitous and one of the most important organs of all vertebrate animals, since [...] Read more.
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Open AccessReview
Epigenetics of Aging and Alzheimer’s Disease: Implications for Pharmacogenomics and Drug Response
Int. J. Mol. Sci. 2015, 16(12), 30483-30543; https://doi.org/10.3390/ijms161226236
Received: 30 September 2015 / Revised: 16 November 2015 / Accepted: 8 December 2015 / Published: 21 December 2015
Cited by 34 | Viewed by 3024 | PDF Full-text (4039 KB) | HTML Full-text | XML Full-text
Abstract
Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes [...] Read more.
Epigenetic variability (DNA methylation/demethylation, histone modifications, microRNA regulation) is common in physiological and pathological conditions. Epigenetic alterations are present in different tissues along the aging process and in neurodegenerative disorders, such as Alzheimer’s disease (AD). Epigenetics affect life span and longevity. AD-related genes exhibit epigenetic changes, indicating that epigenetics might exert a pathogenic role in dementia. Epigenetic modifications are reversible and can potentially be targeted by pharmacological intervention. Epigenetic drugs may be useful for the treatment of major problems of health (e.g., cancer, cardiovascular disorders, brain disorders). The efficacy and safety of these and other medications depend upon the efficiency of the pharmacogenetic process in which different clusters of genes (pathogenic, mechanistic, metabolic, transporter, pleiotropic) are involved. Most of these genes are also under the influence of the epigenetic machinery. The information available on the pharmacoepigenomics of most drugs is very limited; however, growing evidence indicates that epigenetic changes are determinant in the pathogenesis of many medical conditions and in drug response and drug resistance. Consequently, pharmacoepigenetic studies should be incorporated in drug development and personalized treatments. Full article
(This article belongs to the Special Issue Pharmacogenetics and Personalized Medicine)
Open AccessCase Report
Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report
Int. J. Mol. Sci. 2015, 16(12), 30470-30482; https://doi.org/10.3390/ijms161226244
Received: 28 November 2015 / Revised: 12 December 2015 / Accepted: 16 December 2015 / Published: 21 December 2015
Cited by 16 | Viewed by 2609 | PDF Full-text (2011 KB) | HTML Full-text | XML Full-text
Abstract
The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. Methods: Fifteen months after the accident, the patient [...] Read more.
The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. Methods: Fifteen months after the accident, the patient was treated with GH, 1 mg/day, at three-month intervals, followed by one-month resting, together with daily neurorehabilitation. Blood analysis at admission showed that no pituitary deficits existed. At admission, the patient presented: spastic tetraplegia, dysarthria, dysphagia, very severe cognitive deficits and joint deformities. Computerized tomography scanners (CT-Scans) revealed the practical loss of the right brain hemisphere and important injuries in the left one. Clinical and blood analysis assessments were performed every three months for three years. Feet surgery was needed because of irreducible equinovarus. Results: Clinical and kinesitherapy assessments revealed a prompt improvement in cognitive functions, dysarthria and dysphagia disappeared and three years later the patient was able to live a practically normal life, walking alone and coming back to his studies. No adverse effects were observed during and after GH administration. Conclusions: These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in TBI patients, once the acute phase is resolved, regardless of whether or not they have GH-deficiency (GHD). Full article
(This article belongs to the Special Issue Neuroprotective Strategies 2015)
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Open AccessReview
Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications
Int. J. Mol. Sci. 2015, 16(12), 30458-30469; https://doi.org/10.3390/ijms161226207
Received: 1 October 2015 / Revised: 1 December 2015 / Accepted: 7 December 2015 / Published: 21 December 2015
Cited by 10 | Viewed by 2972 | PDF Full-text (861 KB) | HTML Full-text | XML Full-text
Abstract
Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte [...] Read more.
Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs. Full article
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2015)
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Open AccessArticle
Cloning of the Lycopene β-cyclase Gene in Nicotiana tabacum and Its Overexpression Confers Salt and Drought Tolerance
Int. J. Mol. Sci. 2015, 16(12), 30438-30457; https://doi.org/10.3390/ijms161226243
Received: 20 October 2015 / Revised: 11 December 2015 / Accepted: 15 December 2015 / Published: 21 December 2015
Cited by 8 | Viewed by 2275 | PDF Full-text (7359 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Carotenoids are important pigments in plants that play crucial roles in plant growth and in plant responses to environmental stress. Lycopene β cyclase (β-LCY) functions at the branch point of the carotenoid biosynthesis pathway, catalyzing the cyclization of lycopene. Here, a β-LCY gene [...] Read more.
Carotenoids are important pigments in plants that play crucial roles in plant growth and in plant responses to environmental stress. Lycopene β cyclase (β-LCY) functions at the branch point of the carotenoid biosynthesis pathway, catalyzing the cyclization of lycopene. Here, a β-LCY gene from Nicotiana tabacum, designated as Ntβ-LCY1, was cloned and functionally characterized. Robust expression of Ntβ-LCY1 was found in leaves, and Ntβ-LCY1 expression was obviously induced by salt, drought, and exogenous abscisic acid treatments. Strong accumulation of carotenoids and expression of carotenoid biosynthesis genes resulted from Ntβ-LCY1 overexpression. Additionally, compared to wild-type plants, transgenic plants with overexpression showed enhanced tolerance to salt and drought stress with higher abscisic acid levels and lower levels of malondialdehyde and reactive oxygen species. Conversely, transgenic RNA interference plants had a clear albino phenotype in leaves, and some plants did not survive beyond the early developmental stages. The suppression of Ntβ-LCY1 expression led to lower expression levels of genes in the carotenoid biosynthesis pathway and to reduced accumulation of carotenoids, chlorophyll, and abscisic acid. These results indicate that Ntβ-LCY1 is not only a likely cyclization enzyme involved in carotenoid accumulation but also confers salt and drought stress tolerance in Nicotiana tabacum. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle
Effects of Ethanol on the Expression Level of Various BDNF mRNA Isoforms and Their Encoded Protein in the Hippocampus of Adult and Embryonic Rats
Int. J. Mol. Sci. 2015, 16(12), 30422-30437; https://doi.org/10.3390/ijms161226242
Received: 11 October 2015 / Revised: 29 November 2015 / Accepted: 14 December 2015 / Published: 21 December 2015
Cited by 6 | Viewed by 2010 | PDF Full-text (1413 KB) | HTML Full-text | XML Full-text
Abstract
We aimed to compare the effects of oral ethanol (Eth) alone or combined with the phytoestrogen resveratrol (Rsv) on the expression of various brain-derived neurotrophic factor (BDNF) transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low [...] Read more.
We aimed to compare the effects of oral ethanol (Eth) alone or combined with the phytoestrogen resveratrol (Rsv) on the expression of various brain-derived neurotrophic factor (BDNF) transcripts and the encoded protein pro-BDNF in the hippocampus of pregnant and embryonic rats. A low (0.25 g/kg body weight (BW)/day) dose of Eth produced an increase in the expression of BDNF exons I, III and IV and a decrease in that of the exon IX in embryos, but failed to affect BDNF transcript and pro-BDNF protein expression in adults. However, co-administration of Eth 0.25 g/kg·BW/day and Rsv led to increased expression of BDNF exons I, III and IV and to a small but significant increase in the level of pro-BDNF protein in maternal rats. A high (2.5 g/kg·BW/day) dose of Eth increased the expression of BDNF exons III and IV in embryos, but it decreased the expression of exon IX containing BDNF mRNAs in the maternal rats. While the high dose of Eth alone reduced the level of pro-BDNF in adults, it failed to change the levels of pro-BDNF in embryos. Eth differentially affects the expression pattern of BDNF transcripts and levels of pro-BDNF in the hippocampus of both adult and embryonic rats. Full article
(This article belongs to the Special Issue Mechanisms of Neurodegeneration)
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Open AccessArticle
Combination Treatment with Sublethal Ionizing Radiation and the Proteasome Inhibitor, Bortezomib, Enhances Death-Receptor Mediated Apoptosis and Anti-Tumor Immune Attack
Int. J. Mol. Sci. 2015, 16(12), 30405-30421; https://doi.org/10.3390/ijms161226238
Received: 13 November 2015 / Revised: 8 December 2015 / Accepted: 11 December 2015 / Published: 21 December 2015
Cited by 11 | Viewed by 2063 | PDF Full-text (2943 KB) | HTML Full-text | XML Full-text
Abstract
Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce [...] Read more.
Sub-lethal doses of radiation can modulate gene expression, making tumor cells more susceptible to T-cell-mediated immune attack. Proteasome inhibitors demonstrate broad anti-tumor activity in clinical and pre-clinical cancer models. Here, we use a combination treatment of proteasome inhibition and irradiation to further induce immunomodulation of tumor cells that could enhance tumor-specific immune responses. We investigate the effects of the 26S proteasome inhibitor, bortezomib, alone or in combination with radiotherapy, on the expression of immunogenic genes in normal colon and colorectal cancer cell lines. We examined cells for changes in the expression of several death receptors (DR4, DR5 and Fas) commonly used by T cells for killing of target cells. Our results indicate that the combination treatment resulted in increased cell surface expression of death receptors by increasing their transcript levels. The combination treatment further increases the sensitivity of carcinoma cells to apoptosis through FAS and TRAIL receptors but does not change the sensitivity of normal non-malignant epithelial cells. Furthermore, the combination treatment significantly enhances tumor cell killing by tumor specific CD8+ T cells. This study suggests that combining radiotherapy and proteasome inhibition may simultaneously enhance tumor immunogenicity and the induction of antitumor immunity by enhancing tumor-specific T-cell activity. Full article
(This article belongs to the collection Radiation Toxicity in Cells)
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Open AccessArticle
Effects of Heat Stress on Metabolite Accumulation and Composition, and Nutritional Properties of Durum Wheat Grain
Int. J. Mol. Sci. 2015, 16(12), 30382-30404; https://doi.org/10.3390/ijms161226241
Received: 18 November 2015 / Revised: 9 December 2015 / Accepted: 14 December 2015 / Published: 19 December 2015
Cited by 12 | Viewed by 2355 | PDF Full-text (1858 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Durum wheat (Triticum turgidum (L.) subsp. turgidum (L.) convar. durum (Desf.)) is momentous for human nutrition, and environmental stresses can strongly limit the expression of yield potential and affect the qualitative characteristics of the grain. The aim of this study was to [...] Read more.
Durum wheat (Triticum turgidum (L.) subsp. turgidum (L.) convar. durum (Desf.)) is momentous for human nutrition, and environmental stresses can strongly limit the expression of yield potential and affect the qualitative characteristics of the grain. The aim of this study was to determine how heat stress (five days at 37 °C) applied five days after flowering affects the nutritional composition, antioxidant capacity and metabolic profile of the grain of two durum wheat genotypes: “Primadur”, an elite cultivar with high yellow index, and “T1303”, an anthocyanin-rich purple cultivar. Qualitative traits and metabolite evaluation (by gas chromatography linked to mass spectrometry) were carried out on immature (14 days after flowering) and mature seeds. The effects of heat stress were genotype-dependent. Although some metabolites (e.g., sucrose, glycerol) increased in response to heat stress in both genotypes, clear differences were observed. Following the heat stress, there was a general increase in most of the analyzed metabolites in “Primadur”, with a general decrease in “T1303”. Heat shock applied early during seed development produced changes that were observed in immature seeds and also long-term effects that changed the qualitative and quantitative parameters of the mature grain. Therefore, short heat-stress treatments can affect the nutritional value of grain of different genotypes of durum wheat in different ways. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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Open AccessReview
Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells
Int. J. Mol. Sci. 2015, 16(12), 30362-30381; https://doi.org/10.3390/ijms161226240
Received: 4 November 2015 / Revised: 7 December 2015 / Accepted: 9 December 2015 / Published: 19 December 2015
Cited by 13 | Viewed by 2927 | PDF Full-text (2502 KB) | HTML Full-text | XML Full-text
Abstract
The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could [...] Read more.
The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could originate in (human) cancers and could contribute to the progression of the disease is still missing, suggesting that the cell fusion hypothesis is rather fiction than fact. However, is the lack of this ultimate proof a valid argument against this hypothesis, particularly if one has to consider that appropriate markers do not (yet) exist, thus making it virtually impossible to identify a human tumor cell clearly as a tumor hybrid cell. In the present review, we will summarize the evidence supporting the cell fusion in cancer concept. Moreover, we will refine the cell fusion hypothesis by providing evidence that cell fusion is a potent inducer of aneuploidy, genomic instability and, most likely, even chromothripsis, suggesting that cell fusion, like mutations and aneuploidy, might be an inducer of a mutator phenotype. Finally, we will show that “accidental” tissue repair processes during cancer therapy could lead to the origin of therapy resistant cancer hybrid stem cells. Full article
(This article belongs to the Special Issue Stem Cell Activation in Adult Organism)
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Open AccessArticle
Protein Sub-Nuclear Localization Based on Effective Fusion Representations and Dimension Reduction Algorithm LDA
Int. J. Mol. Sci. 2015, 16(12), 30343-30361; https://doi.org/10.3390/ijms161226237
Received: 9 October 2015 / Revised: 7 December 2015 / Accepted: 11 December 2015 / Published: 19 December 2015
Cited by 21 | Viewed by 1723 | PDF Full-text (2841 KB) | HTML Full-text | XML Full-text
Abstract
An effective representation of a protein sequence plays a crucial role in protein sub-nuclear localization. The existing representations, such as dipeptide composition (DipC), pseudo-amino acid composition (PseAAC) and position specific scoring matrix (PSSM), are insufficient to represent protein sequence due to their single [...] Read more.
An effective representation of a protein sequence plays a crucial role in protein sub-nuclear localization. The existing representations, such as dipeptide composition (DipC), pseudo-amino acid composition (PseAAC) and position specific scoring matrix (PSSM), are insufficient to represent protein sequence due to their single perspectives. Thus, this paper proposes two fusion feature representations of DipPSSM and PseAAPSSM to integrate PSSM with DipC and PseAAC, respectively. When constructing each fusion representation, we introduce the balance factors to value the importance of its components. The optimal values of the balance factors are sought by genetic algorithm. Due to the high dimensionality of the proposed representations, linear discriminant analysis (LDA) is used to find its important low dimensional structure, which is essential for classification and location prediction. The numerical experiments on two public datasets with KNN classifier and cross-validation tests showed that in terms of the common indexes of sensitivity, specificity, accuracy and MCC, the proposed fusing representations outperform the traditional representations in protein sub-nuclear localization, and the representation treated by LDA outperforms the untreated one. Full article
(This article belongs to the Section Biochemistry)
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Open AccessRetraction
Retraction: X. Ma et al. Hybrid Endovascular Repair in Aortic Arch Pathologies: A Retrospective Study. Int. J. Mol. Sci. 2010, 11, 4687–4696
Int. J. Mol. Sci. 2015, 16(12), 30342; https://doi.org/10.3390/ijms161226233
Received: 17 December 2015 / Accepted: 17 December 2015 / Published: 18 December 2015
Viewed by 1505 | PDF Full-text (143 KB) | HTML Full-text | XML Full-text
Abstract
We have been made aware that the figures and experimental data reported in the title paper [1] are duplicated in another publication by P. Bergeron [2]. [...] Full article
Open AccessReview
FLIP the Switch: Regulation of Apoptosis and Necroptosis by cFLIP
Int. J. Mol. Sci. 2015, 16(12), 30321-30341; https://doi.org/10.3390/ijms161226232
Received: 10 November 2015 / Revised: 9 December 2015 / Accepted: 11 December 2015 / Published: 18 December 2015
Cited by 33 | Viewed by 3835 | PDF Full-text (1713 KB) | HTML Full-text | XML Full-text
Abstract
cFLIP (cellular FLICE-like inhibitory protein) is structurally related to caspase-8 but lacks proteolytic activity due to multiple amino acid substitutions of catalytically important residues. cFLIP protein is evolutionarily conserved and expressed as three functionally different isoforms in humans (cFLIPL, cFLIPS [...] Read more.
cFLIP (cellular FLICE-like inhibitory protein) is structurally related to caspase-8 but lacks proteolytic activity due to multiple amino acid substitutions of catalytically important residues. cFLIP protein is evolutionarily conserved and expressed as three functionally different isoforms in humans (cFLIPL, cFLIPS, and cFLIPR). cFLIP controls not only the classical death receptor-mediated extrinsic apoptosis pathway, but also the non-conventional pattern recognition receptor-dependent apoptotic pathway. In addition, cFLIP regulates the formation of the death receptor-independent apoptotic platform named the ripoptosome. Moreover, recent studies have revealed that cFLIP is also involved in a non-apoptotic cell death pathway known as programmed necrosis or necroptosis. These functions of cFLIP are strictly controlled in an isoform-, concentration- and tissue-specific manner, and the ubiquitin-proteasome system plays an important role in regulating the stability of cFLIP. In this review, we summarize the current scientific findings from biochemical analyses, cell biological studies, mathematical modeling, and gene-manipulated mice models to illustrate the critical role of cFLIP as a switch to determine the destiny of cells among survival, apoptosis, and necroptosis. Full article
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Open AccessReview
Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy
Int. J. Mol. Sci. 2015, 16(12), 30309-30320; https://doi.org/10.3390/ijms161226234
Received: 31 October 2015 / Revised: 28 November 2015 / Accepted: 11 December 2015 / Published: 18 December 2015
Cited by 3 | Viewed by 2276 | PDF Full-text (1395 KB) | HTML Full-text | XML Full-text
Abstract
Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ [...] Read more.
Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies. Full article
(This article belongs to the collection Radiation Toxicity in Cells)
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Open AccessReview
Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine
Int. J. Mol. Sci. 2015, 16(12), 30269-30308; https://doi.org/10.3390/ijms161226225
Received: 10 October 2015 / Revised: 2 December 2015 / Accepted: 4 December 2015 / Published: 18 December 2015
Cited by 61 | Viewed by 4259 | PDF Full-text (2540 KB) | HTML Full-text | XML Full-text
Abstract
Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized [...] Read more.
Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized by increased OS or decreased glutathione (GSH) level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59) of the cases evaluated (n = 69, 100%). Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription. Full article
(This article belongs to the Special Issue Antioxidant 2.0——Redox Modulation by Food and Drugs)
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Open AccessArticle
Short- and Long-Term Effects of Prenatal Exposure to Iron Oxide Nanoparticles: Influence of Surface Charge and Dose on Developmental and Reproductive Toxicity
Int. J. Mol. Sci. 2015, 16(12), 30251-30268; https://doi.org/10.3390/ijms161226231
Received: 31 July 2015 / Revised: 27 October 2015 / Accepted: 10 December 2015 / Published: 18 December 2015
Cited by 15 | Viewed by 2293 | PDF Full-text (6164 KB) | HTML Full-text | XML Full-text
Abstract
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. [...] Read more.
Iron oxide nanoparticles (NPs) are commonly utilized for biomedical, industrial, and commercial applications due to their unique properties and potential biocompatibility. However, little is known about how exposure to iron oxide NPs may affect susceptible populations such as pregnant women and developing fetuses. To examine the influence of NP surface-charge and dose on the developmental toxicity of iron oxide NPs, Crl:CD1(ICR) (CD-1) mice were exposed to a single, low (10 mg/kg) or high (100 mg/kg) dose of positively-charged polyethyleneimine-Fe2O3-NPs (PEI-NPs), or negatively-charged poly(acrylic acid)-Fe2O3-NPs (PAA-NPs) during critical windows of organogenesis (gestation day (GD) 8, 9, or 10). A low dose of NPs, regardless of charge, did not induce toxicity. However, a high exposure led to charge-dependent fetal loss as well as morphological alterations of the uteri (both charges) and testes (positive only) of surviving offspring. Positively-charged PEI-NPs given later in organogenesis resulted in a combination of short-term fetal loss (42%) and long-term alterations in reproduction, including increased fetal loss for second generation matings (mice exposed in utero). Alternatively, negatively-charged PAA-NPs induced fetal loss (22%) earlier in organogenesis to a lesser degree than PEI-NPs with only mild alterations in offspring uterine histology observed in the long-term. Full article
(This article belongs to the Special Issue Developmental and Reproductive Toxicity of Iron Oxide Nanoparticles)
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Open AccessReview
Applications of Micro-Fourier Transform Infrared Spectroscopy (FTIR) in the Geological Sciences—A Review
Int. J. Mol. Sci. 2015, 16(12), 30223-30250; https://doi.org/10.3390/ijms161226227
Received: 29 May 2015 / Revised: 18 November 2015 / Accepted: 23 November 2015 / Published: 18 December 2015
Cited by 43 | Viewed by 5000 | PDF Full-text (6948 KB) | HTML Full-text | XML Full-text
Abstract
Fourier transform infrared spectroscopy (FTIR) can provide crucial information on the molecular structure of organic and inorganic components and has been used extensively for chemical characterization of geological samples in the past few decades. In this paper, recent applications of FTIR in the [...] Read more.
Fourier transform infrared spectroscopy (FTIR) can provide crucial information on the molecular structure of organic and inorganic components and has been used extensively for chemical characterization of geological samples in the past few decades. In this paper, recent applications of FTIR in the geological sciences are reviewed. Particularly, its use in the characterization of geochemistry and thermal maturation of organic matter in coal and shale is addressed. These investigations demonstrate that the employment of high-resolution micro-FTIR imaging enables visualization and mapping of the distributions of organic matter and minerals on a micrometer scale in geological samples, and promotes an advanced understanding of heterogeneity of organic rich coal and shale. Additionally, micro-FTIR is particularly suitable for in situ, non-destructive characterization of minute microfossils, small fluid and melt inclusions within crystals, and volatiles in glasses and minerals. This technique can also assist in the chemotaxonomic classification of macrofossils such as plant fossils. These features, barely accessible with other analytical techniques, may provide fundamental information on paleoclimate, depositional environment, and the evolution of geological (e.g., volcanic and magmatic) systems. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma
Int. J. Mol. Sci. 2015, 16(12), 30204-30222; https://doi.org/10.3390/ijms161226230
Received: 12 November 2015 / Revised: 8 December 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Cited by 6 | Viewed by 3394 | PDF Full-text (4753 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and [...] Read more.
MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method “miRlastic”, which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic. Full article
(This article belongs to the collection Regulation by Non-Coding RNAs)
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Open AccessArticle
Comparative Transcriptome Analysis of Genes Involved in GA-GID1-DELLA Regulatory Module in Symbiotic and Asymbiotic Seed Germination of Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae)
Int. J. Mol. Sci. 2015, 16(12), 30190-30203; https://doi.org/10.3390/ijms161226224
Received: 25 November 2015 / Revised: 9 December 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Cited by 17 | Viewed by 2133 | PDF Full-text (1691 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae) is an endangered medicinal plant in China, also called “King Medicine”. Due to lacking of sufficient nutrients in dust-like seeds, orchid species depend on mycorrhizal fungi for seed germination in the wild. As part of a conservation plan [...] Read more.
Anoectochilus roxburghii (Wall.) Lindl. (Orchidaceae) is an endangered medicinal plant in China, also called “King Medicine”. Due to lacking of sufficient nutrients in dust-like seeds, orchid species depend on mycorrhizal fungi for seed germination in the wild. As part of a conservation plan for the species, research on seed germination is necessary. However, the molecular mechanism of seed germination and underlying orchid-fungus interactions during symbiotic germination are poorly understood. In this study, Illumina HiSeq 4000 transcriptome sequencing was performed to generate a substantial sequence dataset of germinating A. roxburghii seed. A mean of 44,214,845 clean reads were obtained from each sample. 173,781 unigenes with a mean length of 653 nt were obtained. A total of 51,514 (29.64%) sequences were annotated, among these, 49 unigenes encoding proteins involved in GA-GID1-DELLA regulatory module, including 31 unigenes involved in GA metabolism pathway, 5 unigenes encoding GID1, 11 unigenes for DELLA and 2 unigenes for GID2. A total of 11,881 genes showed significant differential expression in the symbiotic germinating seed sample compared with the asymbiotic germinating seed sample, of which six were involved in the GA-GID1-DELLA regulatory module, and suggested that they might be induced or suppressed by fungi. These results will help us understand better the molecular mechanism of orchid seed germination and orchid-fungus symbiosis. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle
Randomized Controlled Trial of Darbepoetin α Versus Continuous Erythropoietin Receptor Activator Injected Subcutaneously Once Every Four Weeks in Patients with Chronic Kidney Disease at the Pre-Dialysis Stage
Int. J. Mol. Sci. 2015, 16(12), 30181-30189; https://doi.org/10.3390/ijms161226229
Received: 7 October 2015 / Revised: 2 December 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Cited by 3 | Viewed by 2592 | PDF Full-text (971 KB) | HTML Full-text | XML Full-text
Abstract
Continuous erythropoietin receptor activator (CERA) seems to maintain a stable hemoglobin (Hb) level because its half-life is longer than darbepoetin α (DA). Twenty chronic kidney disease (CKD) patients at the pre-dialysis stage who had been administered DA for over 24 weeks were randomly [...] Read more.
Continuous erythropoietin receptor activator (CERA) seems to maintain a stable hemoglobin (Hb) level because its half-life is longer than darbepoetin α (DA). Twenty chronic kidney disease (CKD) patients at the pre-dialysis stage who had been administered DA for over 24 weeks were randomly assigned to receive subcutaneous CERA or DA once every four weeks during 48 weeks. In both groups, the rate of achievement of target Hb level changed from 70% to 100% in weeks 0 to 48, with no significant difference between the groups. Compared with week 0, the Hb level was significantly increased from week 24 in the DA group and from week 8 in the CERA group. In addition, the reticulocyte count was significantly increased from week 4 in the CERA group compared with the DA group. There was no significant difference in the levels of estimated glomerular filtration rate and iron status between both groups. Because of the small number of patients in this study, only limited conclusions can be drawn. However, the results suggest that subcutaneous administration of DA or CERA once every four weeks to predialysis patients has similar effects on achievement of target Hb levels. Full article
(This article belongs to the Special Issue Advances in Chronic Kidney Disease)
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Open AccessReview
Plant Adaptation to Multiple Stresses during Submergence and Following Desubmergence
Int. J. Mol. Sci. 2015, 16(12), 30164-30180; https://doi.org/10.3390/ijms161226226
Received: 1 November 2015 / Revised: 3 December 2015 / Accepted: 10 December 2015 / Published: 17 December 2015
Cited by 23 | Viewed by 3168 | PDF Full-text (1106 KB) | HTML Full-text | XML Full-text
Abstract
Plants require water for growth and development, but excessive water negatively affects their productivity and viability. Flash floods occasionally result in complete submergence of plants in agricultural and natural ecosystems. When immersed in water, plants encounter multiple stresses including low oxygen, low light, [...] Read more.
Plants require water for growth and development, but excessive water negatively affects their productivity and viability. Flash floods occasionally result in complete submergence of plants in agricultural and natural ecosystems. When immersed in water, plants encounter multiple stresses including low oxygen, low light, nutrient deficiency, and high risk of infection. As floodwaters subside, submerged plants are abruptly exposed to higher oxygen concentration and greater light intensity, which can induce post-submergence injury caused by oxidative stress, high light, and dehydration. Recent studies have emphasized the significance of multiple stress tolerance in the survival of submergence and prompt recovery following desubmergence. A mechanistic understanding of acclimation responses to submergence at molecular and physiological levels can contribute to the deciphering of the regulatory networks governing tolerance to other environmental stresses that occur simultaneously or sequentially in the natural progress of a flood event. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessReview
Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia
Int. J. Mol. Sci. 2015, 16(12), 30144-30163; https://doi.org/10.3390/ijms161226228
Received: 14 October 2015 / Revised: 1 December 2015 / Accepted: 8 December 2015 / Published: 17 December 2015
Cited by 17 | Viewed by 3040 | PDF Full-text (7250 KB) | HTML Full-text | XML Full-text
Abstract
Although the dopamine D2 receptor (DRD2) has been a main target of antipsychotic pharmacotherapy for the treatment of schizophrenia, the standard treatment does not offer sufficient relief of symptoms to 20%–30% of patients suffering from this disorder. Moreover, over 80% of patients experience [...] Read more.
Although the dopamine D2 receptor (DRD2) has been a main target of antipsychotic pharmacotherapy for the treatment of schizophrenia, the standard treatment does not offer sufficient relief of symptoms to 20%–30% of patients suffering from this disorder. Moreover, over 80% of patients experience relapsed psychotic episodes within five years following treatment initiation. These data strongly suggest that the continuous blockade of DRD2 by antipsychotic(s) could eventually fail to control the psychosis in some point during long-term treatment, even if such treatment has successfully provided symptomatic improvement for the first-episode psychosis, or stability for the subsequent chronic stage. Dopamine supersensitivity psychosis (DSP) is historically known as a by-product of antipsychotic treatment in the manner of tardive dyskinesia or transient rebound psychosis. Numerous data in psychopharmacological studies suggest that the up-regulation of DRD2, caused by antipsychotic(s), is likely the mechanism underlying the development of the dopamine supersensitivity state. However, regardless of evolving notions of dopamine signaling, particularly dopamine release, signal transduction, and receptor recycling, most of this research has been conducted and discussed from the standpoint of disease etiology or action mechanism of the antipsychotic, not of DSP. Hence, the mechanism of the DRD2 up-regulation or mechanism evoking clinical DSP, both of which are caused by pharmacotherapy, remains unknown. Once patients experience a DSP episode, they become increasingly difficult to treat. Light was recently shed on a new aspect of DSP as a treatment-resistant factor. Clarification of the detailed mechanism of DSP is therefore crucial, and a preventive treatment strategy for DSP or treatment-resistant schizophrenia is urgently needed. Full article
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Open AccessArticle
Selective Analysis of Sulfur-Containing Species in a Heavy Crude Oil by Deuterium Labeling Reactions and Ultrahigh Resolution Mass Spectrometry
Int. J. Mol. Sci. 2015, 16(12), 30133-30143; https://doi.org/10.3390/ijms161226205
Received: 3 November 2015 / Revised: 4 December 2015 / Accepted: 9 December 2015 / Published: 17 December 2015
Cited by 10 | Viewed by 2355 | PDF Full-text (3738 KB) | HTML Full-text | XML Full-text
Abstract
A heavy crude oil has been treated with deuterated alkylating reagents (CD3I and C2D5I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron [...] Read more.
A heavy crude oil has been treated with deuterated alkylating reagents (CD3I and C2D5I) and directly analyzed without any prior fractionation and chromatographic separation by high-field Orbitrap Fourier Transform Mass Spectrometry (FTMS) and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) using electrospray ionization (ESI). The reaction of a polycyclic aromatic sulfur heterocycles (PASHs) dibenzothiophene (DBT), in the presence of silver tetrafluoroborate (AgBF4) with ethyl iodide (C2H5I) in anhydrous dichloroethane (DCE) was optimized as a sample reaction to study heavy crude oil mixtures, and the reaction yield was monitored and determined by proton nuclear magnetic resonance spectroscopy (1H-NMR). The obtained conditions were then applied to a mixture of standard aromatic CH-, N-, O- and S-containing compounds and then a heavy crude oil, and only sulfur-containing compounds were selectively alkylated. The deuterium labeled alkylating reagents, iodomethane-d3 (CD3I) and iodoethane-d5 (C2D5I), were employed to the alkylation of heavy crude oil to selectively differentiate the tagged sulfur species from the original crude oil. Full article
(This article belongs to the Special Issue Fourier Transform Mass Spectrometry in Molecular Sciences)
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Open AccessArticle
Exogenous Spermidine Alleviates Low Temperature Injury in Mung Bean (Vigna radiata L.) Seedlings by Modulating Ascorbate-Glutathione and Glyoxalase Pathway
Int. J. Mol. Sci. 2015, 16(12), 30117-30132; https://doi.org/10.3390/ijms161226220
Received: 2 October 2015 / Revised: 6 December 2015 / Accepted: 8 December 2015 / Published: 17 December 2015
Cited by 27 | Viewed by 2415 | PDF Full-text (3126 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The role of exogenous spermidine (Spd) in alleviating low temperature (LT) stress in mung bean (Vigna radiata L. cv. BARI Mung-3) seedlings has been investigated. Low temperature stress modulated the non-enzymatic and enzymatic components of ascorbate-glutathione (AsA-GSH) cycle, increased H2O [...] Read more.
The role of exogenous spermidine (Spd) in alleviating low temperature (LT) stress in mung bean (Vigna radiata L. cv. BARI Mung-3) seedlings has been investigated. Low temperature stress modulated the non-enzymatic and enzymatic components of ascorbate-glutathione (AsA-GSH) cycle, increased H2O2 content and lipid peroxidation, which indicate oxidative damage of seedlings. Low temperature reduced the leaf relative water content (RWC) and destroyed leaf chlorophyll, which inhibited seedlings growth. Exogenous pretreatment of Spd in LT-affected seedlings significantly increased the contents of non-enzymatic antioxidants of AsA-GSH cycle, which include AsA and GSH. Exogenous Spd decreased dehydroascorbate (DHA), increased AsA/DHA ratio, decreased glutathione disulfide (GSSG) and increased GSH/GSSG ratio under LT stress. Activities of AsA-GSH cycle enzymes such as ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) increased after Spd pretreatment in LT affected seedlings. Thus, the oxidative stress was reduced. Protective effects of Spd are also reflected from reduction of methylglyoxal (MG) toxicity by improving glyoxalase cycle components, and by maintaining osmoregulation, water status and improved seedlings growth. The present study reveals the vital roles of AsA-GSH and glyoxalase cycle in alleviating LT injury. Full article
(This article belongs to the Special Issue Plant Molecular Biology)
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Open AccessArticle
MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features
Int. J. Mol. Sci. 2015, 16(12), 30105-30116; https://doi.org/10.3390/ijms161226223
Received: 7 December 2015 / Revised: 12 December 2015 / Accepted: 15 December 2015 / Published: 17 December 2015
Cited by 22 | Viewed by 3137 | PDF Full-text (864 KB) | HTML Full-text | XML Full-text
Abstract
Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure [...] Read more.
Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. Full article
(This article belongs to the Special Issue MicroRNA Regulation)
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Open AccessCorrection
Correction: Xiong, Z., et al. Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development. Int. J. Mol. Sci. 2015, 16, 21153–21176
Int. J. Mol. Sci. 2015, 16(12), 30103-30104; https://doi.org/10.3390/ijms161226222
Received: 9 November 2015 / Revised: 9 November 2015 / Accepted: 23 November 2015 / Published: 17 December 2015
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Abstract
The authors wish to replace Figure 4A on Page 21161 of their paper published in IJMS [1]. [...] Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
The Complete Mitochondrial Genome of Mindarus keteleerifoliae (Insecta: Hemiptera: Aphididae) and Comparison with Other Aphididae Insects
Int. J. Mol. Sci. 2015, 16(12), 30091-30102; https://doi.org/10.3390/ijms161226219
Received: 8 October 2015 / Revised: 8 December 2015 / Accepted: 8 December 2015 / Published: 17 December 2015
Cited by 4 | Viewed by 2269 | PDF Full-text (3742 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The mitogenome of Mindarus keteleerifoliae Zhang (Hemiptera: Aphididae) is a 15,199 bp circular molecule. The gene order and orientation of M. keteleerifoliae is similarly arranged to that of the ancestral insect of other aphid mitogenomes, and, a tRNA isomerism event maybe identified in [...] Read more.
The mitogenome of Mindarus keteleerifoliae Zhang (Hemiptera: Aphididae) is a 15,199 bp circular molecule. The gene order and orientation of M. keteleerifoliae is similarly arranged to that of the ancestral insect of other aphid mitogenomes, and, a tRNA isomerism event maybe identified in the mitogenome of M. keteleerifoliae. The tRNA-Trp gene is coded in the J-strand and the same sequence in the N-strand codes for the tRNA-Ser gene. A similar phenomenon was also found in the mitogenome of Eriosoma lanigerum. However, whether tRNA isomers in aphids exist requires further study. Phylogenetic analyses, using all available protein-coding genes, support Mindarinae as the basal position of Aphididae. Two tribes of Aphidinae were recovered with high statistical significance. Characteristics of the M. keteleerifoliae mitogenome revealed distinct mitogenome structures and provided abundant phylogenetic signals, thus advancing our understanding of insect mitogenomic architecture and evolution. But, because only eight complete aphid mitogenomes, including M. keteleerifoliae, were published, future studies with larger taxon sampling sizes are necessary. Full article
(This article belongs to the Section Biochemistry)
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Open AccessReview
Date (Phoenix dactylifera) Polyphenolics and Other Bioactive Compounds: A Traditional Islamic Remedy’s Potential in Prevention of Cell Damage, Cancer Therapeutics and Beyond
Int. J. Mol. Sci. 2015, 16(12), 30075-30090; https://doi.org/10.3390/ijms161226210
Received: 13 November 2015 / Revised: 8 December 2015 / Accepted: 9 December 2015 / Published: 17 December 2015
Cited by 13 | Viewed by 3349 | PDF Full-text (2015 KB) | HTML Full-text | XML Full-text
Abstract
This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by [...] Read more.
This review analyzes current studies of the therapeutic effects of Phoenix dactylifera, or date palm fruit, on the physiologic system. Specifically, we sought to summarize the effects of its application in preventing cell damage, improving cancer therapeutics and reducing damage caused by conventional chemotherapy. Phoenix dactylifera exhibits potent anti-oxidative properties both in vitro and in vivo. This allows the fruit to prevent depletion of intrinsic protection from oxidative cell damage and assist these defense systems in reducing cell damage. Macroscopically, this mechanism may be relevant to the prevention of various adverse drug events common to chemotherapy including hepatotoxicity, nephrotoxicity, gastrotoxicity, and peripheral neuropathy. While such effects have only been studied in small animal systems, research suggests a potential application to more complex mammalian systems and perhaps a solution to some problems of chemotherapy in hepato-compromised and nephro-compromised patients. Full article
(This article belongs to the Special Issue Advances in Molecular Research of Functional and Nutraceutical Food)
Open AccessArticle
Biochemical Characterization of An Arginine-Specific Alkaline Trypsin from Bacillus licheniformis
Int. J. Mol. Sci. 2015, 16(12), 30061-30074; https://doi.org/10.3390/ijms161226200
Received: 8 November 2015 / Revised: 8 December 2015 / Accepted: 9 December 2015 / Published: 17 December 2015
Cited by 1 | Viewed by 2934 | PDF Full-text (2231 KB) | HTML Full-text | XML Full-text
Abstract
In the present study, we isolated a trypsin-producing strain DMN6 from the leather waste and identified it as Bacillus licheniformis through a two-step screening strategy. The trypsin activity was increased up to 140 from 20 U/mL through culture optimization. The enzyme was purified [...] Read more.
In the present study, we isolated a trypsin-producing strain DMN6 from the leather waste and identified it as Bacillus licheniformis through a two-step screening strategy. The trypsin activity was increased up to 140 from 20 U/mL through culture optimization. The enzyme was purified to electrophoretic homogeneity with a molecular mass of 44 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the specific activity of purified enzyme is 350 U/mg with Nα-Benzoyl-l-arginine ethylester as the substrate. The optimum temperature and pH for the trypsin are 65 °C and pH 9.0, respectively. Also, the enzyme can be significantly activated by Ba2+. This enzyme is relatively stable in alkaline environment and displays excellent activity at low temperatures. It could retain over 95% of enzyme activity after 180 min of incubation at 45 °C. The distinguished activity under low temperature and prominent stability enhance its catalytic potential. In the current work, the open reading frame was obtained with a length of 1371 nucleotides that encoded a protein of 456 amino acids. These data would warrant the B. licheniformis trypsin as a promising candidate for catalytic application in collagen preparation and leather bating through further protein engineering. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Biosynthesis of Essential Polyunsaturated Fatty Acids in Wheat Triggered by Expression of Artificial Gene
Int. J. Mol. Sci. 2015, 16(12), 30046-30060; https://doi.org/10.3390/ijms161226137
Received: 22 October 2015 / Revised: 16 November 2015 / Accepted: 19 November 2015 / Published: 16 December 2015
Cited by 5 | Viewed by 2305 | PDF Full-text (3455 KB) | HTML Full-text | XML Full-text
Abstract
The artificial gene D6D encoding the enzyme ∆6desaturase was designed and synthesized using the sequence of the same gene from the fungus Thamnidium elegans. The original start codon was replaced by the signal sequence derived from the wheat gene for [...] Read more.
The artificial gene D6D encoding the enzyme ∆6desaturase was designed and synthesized using the sequence of the same gene from the fungus Thamnidium elegans. The original start codon was replaced by the signal sequence derived from the wheat gene for high-molecular-weight glutenin subunit and the codon usage was completely changed for optimal expression in wheat. Synthesized artificial D6D gene was delivered into plants of the spring wheat line CY-45 and the gene itself, as well as transcribed D6D mRNA were confirmed in plants of T0 and T1 generations. The desired product of the wheat genetic modification by artificial D6D gene was the γ-linolenic acid. Its presence was confirmed in mature grains of transgenic wheat plants in the amount 0.04%–0.32% (v/v) of the total amount of fatty acids. Both newly synthesized γ-linolenic acid and stearidonic acid have been detected also in leaves, stems, roots, awns, paleas, rachillas, and immature grains of the T1 generation as well as in immature and mature grains of the T2 generation. Contents of γ-linolenic acid and stearidonic acid varied in range 0%–1.40% (v/v) and 0%–1.53% (v/v) from the total amount of fatty acids, respectively. This approach has opened the pathway of desaturation of fatty acids and production of essential polyunsaturated fatty acids in wheat. Full article
(This article belongs to the Special Issue Metabolomics in the Plant Sciences)
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Open AccessArticle
A Combined Metabolomic and Proteomic Analysis of Gestational Diabetes Mellitus
Int. J. Mol. Sci. 2015, 16(12), 30034-30045; https://doi.org/10.3390/ijms161226133
Received: 3 July 2015 / Revised: 28 October 2015 / Accepted: 20 November 2015 / Published: 16 December 2015
Cited by 11 | Viewed by 3188 | PDF Full-text (1469 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18) and [...] Read more.
The aim of this pilot study was to apply a novel combined metabolomic and proteomic approach in analysis of gestational diabetes mellitus. The investigation was performed with plasma samples derived from pregnant women with diagnosed gestational diabetes mellitus (n = 18) and a matched control group (n = 13). The mass spectrometry-based analyses allowed to determine 42 free amino acids and low molecular-weight peptide profiles. Different expressions of several peptides and altered amino acid profiles were observed in the analyzed groups. The combination of proteomic and metabolomic data allowed obtaining the model with a high discriminatory power, where amino acids ethanolamine, l-citrulline, l-asparagine, and peptide ions with m/z 1488.59; 4111.89 and 2913.15 had the highest contribution to the model. The sensitivity (94.44%) and specificity (84.62%), as well as the total group membership classification value (90.32%) calculated from the post hoc classification matrix of a joint model were the highest when compared with a single analysis of either amino acid levels or peptide ion intensities. The obtained results indicated a high potential of integration of proteomic and metabolomics analysis regardless the sample size. This promising approach together with clinical evaluation of the subjects can also be used in the study of other diseases. Full article
(This article belongs to the collection Advances in Proteomic Research)
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Open AccessReview
Mesenchymal Stem Cell-Mediated Effects of Tumor Support or Suppression
Int. J. Mol. Sci. 2015, 16(12), 30015-30033; https://doi.org/10.3390/ijms161226215
Received: 23 September 2015 / Revised: 27 November 2015 / Accepted: 1 December 2015 / Published: 16 December 2015
Cited by 55 | Viewed by 3010 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Mesenchymal stem cells (MSCs) can exhibit a marked tropism towards site of tumors. Many studies have reported that tumor progression and metastasis increase by MSCs. In contrast, other studies have shown that MSCs suppress growth of tumors. MSCs contribute to tumor growth promotion [...] Read more.
Mesenchymal stem cells (MSCs) can exhibit a marked tropism towards site of tumors. Many studies have reported that tumor progression and metastasis increase by MSCs. In contrast, other studies have shown that MSCs suppress growth of tumors. MSCs contribute to tumor growth promotion by several mechanisms: (1) transition to tumor-associated fibroblasts; (2) suppression of immune response; (3) promotion of angiogenesis; (4) stimulation of epithelial-mesenchymal transition (EMT); (5) contribution to the tumor microenvironment; (6) inhibition of tumor cell apoptosis; and (7) promotion of tumor metastasis. In contrast to the tumor-promoting properties, MSCs inhibit tumor growth by increasing inflammatory infiltration, inhibiting angiogenesis, suppressing Wnt signaling and AKT signaling, and inducing cell cycle arrest and apoptosis. In this review, we will discuss potential mechanisms by which MSC mediates tumor support or suppression and then the possible tumor-specific therapeutic strategies using MSCs as delivery vehicles, based on their homing potential to tumors. Full article
(This article belongs to the collection Advances in Molecular Oncology)
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