International Journal of Molecular Sciences

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Open AccessReview

Small-Nucleic-Acid-Based Therapeutic Strategy Targeting the Transcription Factors Regulating the Vascular Inflammation, Remodeling and Fibrosis in Atherosclerosis

by Sung Won Youn and Kwan-Kyu Park

Int. J. Mol. Sci. 2015, 16(5), 11804-11833; https://doi.org/10.3390/ijms160511804 - 22 May 2015

Cited by 15 | Viewed by 6513

Abstract

Atherosclerosis arises when injury to the arterial wall induces an inflammatory cascade that is sustained by a complex network of cytokines, together with accumulation of lipids and fibrous material. Inflammatory cascades involve leukocyte adherence and chemotaxis, which are coordinated by the local secretion [...] Read more.

Atherosclerosis arises when injury to the arterial wall induces an inflammatory cascade that is sustained by a complex network of cytokines, together with accumulation of lipids and fibrous material. Inflammatory cascades involve leukocyte adherence and chemotaxis, which are coordinated by the local secretion of adhesion molecules, chemotactic factors, and cytokines. Transcription factors are critical to the integration of the various steps of the cascade response to mediators of vascular injury, and are induced in a stimulus-dependent and cell-type-specific manner. Several small-nucleic-acid-based therapeutic strategies have recently been developed to target transcription factors: antisense oligodeoxynucleotides, RNA interference, microRNA, and decoy oligodeoxynucleotides. The aim of this review was to provide an overview of these particular targeted therapeutic strategies, toward regulation of the vascular inflammation, remodeling and fibrosis associated with atherosclerosis. Full article

(This article belongs to the Section Biochemistry)

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Open AccessReview

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

by Masayuki Ishihara, Satoko Kishimoto, Makoto Takikawa, Hidemi Hattori, Shingo Nakamura and Masafumi Shimizu

Int. J. Mol. Sci. 2015, 16(5), 11785-11803; https://doi.org/10.3390/ijms160511785 - 22 May 2015

Cited by 16 | Viewed by 7764

Abstract

Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields [...] Read more.

Low molecular weight heparin (LMWH)/protamine (P) nano/micro particles (N/MPs) (LMWH/P N/MPs) were applied as carriers for heparin-binding growth factors (GFs) and for adhesive cells including adipose-derived stromal cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs). A mixture of LMWH and P yields a dispersion of N/MPs (100 nm–3 μm in diameter). LMWH/P N/MPs can be immobilized onto cell surfaces or extracellular matrix, control the release, activate GFs and protect various GFs. Furthermore, LMWH/P N/MPs can also bind to adhesive cell surfaces, inducing cells and LMWH/P N/MPs-aggregate formation. Those aggregates substantially promoted cellular viability, and induced vascularization and fibrous tissue formation in vivo. The LMWH/P N/MPs, in combination with ADSCs or BMSCs, are effective cell-carriers and are potential promising novel therapeutic agents for inducing vascularization and fibrous tissue formation in ischemic disease by transplantation of the ADSCs and LMWH/P N/MPs-aggregates. LMWH/P N/MPs can also bind to tissue culture plates and adsorb exogenous GFs or GFs from those cells. The LMWH/P N/MPs-coated matrix in the presence of GFs may provide novel biomaterials that can control cellular activity such as growth and differentiation. Furthermore, three-dimensional (3D) cultures of cells including ADSCs and BMSCs using plasma-medium gel with LMWH/P N/MPs exhibited efficient cell proliferation. Thus, LMWH/P N/MPs are an adequate carrier both for GFs and for stromal cells such as ADSCs and BMSCs, and are a functional coating matrix for their cultures. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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Open AccessArticle

Supramolecular Phase-Selective Gelation by Peptides Bearing Side-Chain Azobenzenes: Effect of Ultrasound and Potential for Dye Removal and Oil Spill Remediation

by Jürgen Bachl, Stefan Oehm, Judith Mayr, Carlos Cativiela, José Juan Marrero-Tellado and David Díaz Díaz

Int. J. Mol. Sci. 2015, 16(5), 11766-11784; https://doi.org/10.3390/ijms160511766 - 22 May 2015

Cited by 39 | Viewed by 7419

Abstract

Phase selective gelation (PSG) of organic phases from their non-miscible mixtures with water was achieved using tetrapeptides bearing a side-chain azobenzene moiety. The presence of the chromophore allowed PSG at the same concentration as the minimum gelation concentration (MGC) necessary to obtain the [...] Read more.

Phase selective gelation (PSG) of organic phases from their non-miscible mixtures with water was achieved using tetrapeptides bearing a side-chain azobenzene moiety. The presence of the chromophore allowed PSG at the same concentration as the minimum gelation concentration (MGC) necessary to obtain the gels in pure organic phases. Remarkably, the presence of the water phase during PSG did not impact the thermal, mechanical, and morphological properties of the corresponding organogels. In the case of miscible oil/water mixtures, the entire mixture was gelled, resulting in the formation of quasi-hydrogels. Importantly, PSG could be triggered at room temperature by ultrasound treatment of the mixture or by adding ultrasound-aided concentrated solution of the peptide in an oil-phase to a mixture of the same oil and water. Moreover, the PSG was not affected by the presence of salts or impurities existing in water from natural sources. The process could be scaled-up, and the oil phases (e.g., aromatic solvents, gasoline, diesel fuel) recovered almost quantitatively after a simple distillation process, which also allowed the recovery and reuse of the gelator. Finally, these peptidic gelators could be used to quantitatively remove toxic dyes from aqueous solutions. Full article

(This article belongs to the Special Issue Supramolecular Interactions)

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Open AccessArticle

Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

by Keshab R. Parajuli, Qiuyang Zhang, Sen Liu and Zongbing You

Int. J. Mol. Sci. 2015, 16(5), 11750-11765; https://doi.org/10.3390/ijms160511750 - 22 May 2015

Cited by 9 | Viewed by 6561

Abstract

Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in [...] Read more.

Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in industry as gelling, viscosity and stabilizer; its exposure is associated with developmental and reproductive toxicities in both rodents and humans. MAA has been reported to suppress prostate cancer cell growth by inducing growth arrest and apoptosis. However, it is unknown whether AMPA and MAA can inhibit cancer cell growth. In this study, we found that AMPA and MAA inhibited cell growth in prostate cancer cell lines (LNCaP, C4-2B, PC-3 and DU-145) through induction of apoptosis and cell cycle arrest at the G1 phase. Importantly, the AMPA-induced apoptosis was potentiated with the addition of MAA, which was due to downregulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2), leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the apoptosis of prostate cancer cells, suggesting that they can be used as potential therapeutic drugs in the treatment of prostate cancer. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Chemical-Induced Toxicity and Carcinogenesis)

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Open AccessReview

Soy and Breast Cancer: Focus on Angiogenesis

by Lenka Varinska, Peter Gal, Gabriela Mojzisova, Ladislav Mirossay and Jan Mojzis

Int. J. Mol. Sci. 2015, 16(5), 11728-11749; https://doi.org/10.3390/ijms160511728 - 22 May 2015

Cited by 136 | Viewed by 14865

Abstract

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one [...] Read more.

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G₂/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms. Full article

(This article belongs to the Special Issue Bioactive Phytochemicals in Functional Foods for Cancer Prevention)

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Open AccessArticle

Intravital FRET: Probing Cellular and Tissue Function in Vivo

by Helena Radbruch, Daniel Bremer, Ronja Mothes, Robert Günther, Jan Leo Rinnenthal, Julian Pohlan, Carolin Ulbricht, Anja E. Hauser and Raluca Niesner

Int. J. Mol. Sci. 2015, 16(5), 11713-11727; https://doi.org/10.3390/ijms160511713 - 21 May 2015

Cited by 21 | Viewed by 6771

Abstract

The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss [...] Read more.

The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice. Full article

(This article belongs to the Special Issue Förster Resonance Energy Transfer (FRET) 2015)

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Open AccessArticle

MicroRNA-24 Regulates Osteogenic Differentiation via Targeting T-Cell Factor-1

by Weigong Zhao, Caijun Wu, Yanying Dong, Yunfeng Ma, Yaofeng Jin and Yanhong Ji

Int. J. Mol. Sci. 2015, 16(5), 11699-11712; https://doi.org/10.3390/ijms160511699 - 21 May 2015

Cited by 21 | Viewed by 5255

Abstract

MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, [...] Read more.

MicroRNAs (miRNAs) have been reported to have diverse biological roles in regulating many biological processes, including osteogenic differentiation. In the present study, we identified that miR-24 was a critical regulator during osteogenic differentiation. We found that overexpression of miR-24 significantly inhibited osteogenic differentiation, which decreased alkaline phosphatase activity, matrix mineralization and the expression of osteogenic differentiation markers. In contrast, inhibition of miR-24 exhibited an opposite effect. Furthermore, we delineated that miR-24 regulates post-transcriptionals of T-cell factor-1 (Tcf-1) via targeting the 3'-untranslated region (UTR) of Tcf-1 mRNA. MiR-24 was further found to regulate the protein expression of Tcf-1 in the murine osteoprogenitors cells and bone mesenchymal stem cells. Additionally, the positive effect of miR-24 suppression on osteoblast differentiation was apparently abrogated by Tcf-1 silencing. Taken together, our data suggest that miR-24 participates in osteogenic differentiation by targeting and regulating Tcf-1 expression in osteoblastic cells. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

by Sieglinde Zelzer, Harald Mangge, Sabine Pailer, Herwig Ainoedhofer, Petra Kieslinger, Tatjana Stojakovic, Hubert Scharnagl, Florian Prüller, Daniel Weghuber, Christian Datz, Johannes Haybaeck, Barbara Obermayer-Pietsch, Christian Trummer, Johanna Gostner and Hans-Jürgen Gruber

Int. J. Mol. Sci. 2015, 16(5), 11689-11698; https://doi.org/10.3390/ijms160511689 - 21 May 2015

Cited by 3 | Viewed by 5189

Abstract

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n [...] Read more.

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility

by Guangyuan Chen, Xiuhua Fu, Guangyu Wang, Guiyou Liu and Xiuping Bai

Int. J. Mol. Sci. 2015, 16(5), 11678-11688; https://doi.org/10.3390/ijms160511678 - 21 May 2015

Cited by 11 | Viewed by 5261

Abstract

Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported [...] Read more.

Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10⁻²², odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10⁻⁵³, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples. Full article

(This article belongs to the Section Biochemistry)

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Open AccessArticle

Acute Toxicity-Supported Chronic Toxicity Prediction: A k-Nearest Neighbor Coupled Read-Across Strategy

by Swapnil Chavan, Ran Friedman and Ian A. Nicholls

Int. J. Mol. Sci. 2015, 16(5), 11659-11677; https://doi.org/10.3390/ijms160511659 - 21 May 2015

Cited by 26 | Viewed by 6816

Abstract

A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD₅₀)-based [...] Read more.

A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD₅₀)-based classes as a response and using a series of eight PaDEL software-derived fingerprints as predictor variables. A model developed using Estate type fingerprints correctly predicted the LD₅₀ classes for 70 of 94 training set chemicals and 19 of 24 test set chemicals. An individual category was formed for each of the chemicals by extracting its corresponding k-analogs that were identified by k-NN classification. These categories were used to perform the read-across study for prediction of the chronic toxicity, i.e., Lowest Observed Effect Levels (LOEL). We have successfully predicted the LOELs of 54 of 70 training set chemicals (77%) and 14 of 19 test set chemicals (74%) to within an order of magnitude from their experimental LOEL values. Given the success thus far, we conclude that if the k-NN model predicts LD₅₀ classes correctly for a certain chemical, then the k-analogs of such a chemical can be successfully used for data gap filling for the LOEL. This model should support the in silico prediction of repeated dose toxicity. Full article

(This article belongs to the Section Molecular Toxicology)

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Open AccessArticle

The Influence of PSCA Gene Variation on Its Expression and Gastric Adenocarcinoma Susceptibility in the Northwest Chinese Population

by Wentao Zhang, Ping Liang, Weihua Wang, Peng Dai, Qin Wang, Wei Yan, Jinrong Zhao, Jianbin Sun, Yong Peng, Daxiang Cui and Zhen Yan

Int. J. Mol. Sci. 2015, 16(5), 11648-11658; https://doi.org/10.3390/ijms160511648 - 21 May 2015

Cited by 9 | Viewed by 5951

Abstract

Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA [...] Read more.

Gastric adenocarcinoma (GAC) imposes a considerable health burden around the world. Gene variation in prostate stem cell antigen gene (PSCA) has been identified to be associated with GAC risk, while the results showed regional variation. To explore the influence of PSCA gene variation on its expression and GAC risk in the Northwest Chinese population, four single nucleotide polymorphisms (SNPs) of PSCA were genotyped in 476 GAC cases and 481 controls using MassARRAY system. Two SNPs of rs2294008 (C>T) and rs2976392 (G>A) were identified to be associated with GAC risk. rs2294008, rs2976392 and rs10216533 made up two statistically significant haplotypes (Hap-CGG and Hap-TAG). Additionally, PSCA expression was analyzed by quantitative real time PCR, immunohistochemistry and tissue microarray. The results showed that PSCA expression was decreased in GAC tissues compared with adjacent normal tissues. For normal tissues, PSCA expression was higher with Hap-TA than that with Hap-CG. For GAC tissues, the differentiation degree of Hap-TA was higher than that of Hap-CG. The expression distribution of PSCA in multiple human organs showed disparity. These results suggest that PSCA gene variation has a potential effect on its expression and GAC risk in the Northwest Chinese population. Full article

(This article belongs to the Special Issue Human Single Nucleotide Polymorphisms and Disease Diagnostics)

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Open AccessArticle

Optimization of NaOH Molarity, LUSI Mud/Alkaline Activator, and Na₂SiO₃/NaOH Ratio to Produce Lightweight Aggregate-Based Geopolymer

by Rafiza Abdul Razak, Mohd Mustafa Al Bakri Abdullah, Kamarudin Hussin, Khairul Nizar Ismail, Djwantoro Hardjito and Zarina Yahya

Int. J. Mol. Sci. 2015, 16(5), 11629-11647; https://doi.org/10.3390/ijms160511629 - 21 May 2015

Cited by 33 | Viewed by 7963

Abstract

This paper presents the mechanical function and characterization of an artificial lightweight geopolymer aggregate (ALGA) using LUSI (Sidoarjo mud) and alkaline activator as source materials. LUSI stands for LU-Lumpur and SI-Sidoarjo, meaning mud from Sidoarjo which erupted near the Banjarpanji-1 exploration well in [...] Read more.

This paper presents the mechanical function and characterization of an artificial lightweight geopolymer aggregate (ALGA) using LUSI (Sidoarjo mud) and alkaline activator as source materials. LUSI stands for LU-Lumpur and SI-Sidoarjo, meaning mud from Sidoarjo which erupted near the Banjarpanji-1 exploration well in Sidoarjo, East Java, Indonesia on 27 May 2006. The effect of NaOH molarity, LUSI mud/Alkaline activator (LM/AA) ratio, and Na₂SiO₃/NaOH ratio to the ALGA are investigated at a sintering temperature of 950 °C. The results show that the optimum NaOH molarity found in this study is 12 M due to the highest strength (lowest AIV value) of 15.79% with lower water absorption and specific gravity. The optimum LUSI mud/Alkaline activator (LM/AA) ratio of 1.7 and the Na₂SiO₃/NaOH ratio of 0.4 gives the highest strength with AIV value of 15.42% with specific gravity of 1.10 g/cm³ and water absorption of 4.7%. The major synthesized crystalline phases were identified as sodalite, quartz and albite. Scanning Electron Microscope (SEM) image showed more complete geopolymer matrix which contributes to highest strength of ALGA produced. Full article

(This article belongs to the Section Materials Science)

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Open AccessArticle

Spontaneous γH2AX Foci in Human Solid Tumor-Derived Cell Lines in Relation to p21^WAF1 and WIP1 Expression

by Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W. Wang, Robert H. Weiss and David Murray

Int. J. Mol. Sci. 2015, 16(5), 11609-11628; https://doi.org/10.3390/ijms160511609 - 20 May 2015

Cited by 18 | Viewed by 8977

Abstract

Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been [...] Read more.

Phosphorylation of H2AX on Ser139 (γH2AX) after exposure to ionizing radiation produces nuclear foci that are detectable by immunofluorescence microscopy. These so-called γH2AX foci have been adopted as quantitative markers for DNA double-strand breaks. High numbers of spontaneous γH2AX foci have also been reported for some human solid tumor-derived cell lines, but the molecular mechanism(s) for this response remains elusive. Here we show that cancer cells (e.g., HCT116; MCF7) that constitutively express detectable levels of p21^WAF1 (p21) exhibit low numbers of γH2AX foci (<3/nucleus), whereas p21 knockout cells (HCT116p21−/−) and constitutively low p21-expressing cells (e.g., MDA-MB-231) exhibit high numbers of foci (e.g., >50/nucleus), and that these foci are not associated with apoptosis. The majority (>95%) of cells within HCT116p21−/− and MDA-MB-231 cultures contain high levels of phosphorylated p53, which is localized in the nucleus. We further show an inverse relationship between γH2AX foci and nuclear accumulation of WIP1, an oncogenic phosphatase. Our studies suggest that: (i) p21 deficiency might provide a selective pressure for the emergence of apoptosis-resistant progeny exhibiting genomic instability, manifested as spontaneous γH2AX foci coupled with phosphorylation and nuclear accumulation of p53; and (ii) p21 might contribute to positive regulation of WIP1, resulting in dephosphorylation of γH2AX. Full article

(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)

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Open AccessReview

Vasa Vasorum in Atherosclerosis and Clinical Significance

by Junyan Xu, Xiaotong Lu and Guo-Ping Shi

Int. J. Mol. Sci. 2015, 16(5), 11574-11608; https://doi.org/10.3390/ijms160511574 - 20 May 2015

Cited by 99 | Viewed by 20705

Abstract

Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes [...] Read more.

Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. Full article

(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)

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Open AccessArticle

De Novo Assembly and Characterization of the Transcriptome of the Chinese Medicinal Herb, Gentiana rigescens

by Xiaodong Zhang, Andrew C. Allan, Caixia Li, Yuanzhong Wang and Qiuyang Yao

Int. J. Mol. Sci. 2015, 16(5), 11550-11573; https://doi.org/10.3390/ijms160511550 - 20 May 2015

Cited by 40 | Viewed by 8982

Abstract

Gentiana rigescens is an important medicinal herb in China. The main validated medicinal component gentiopicroside is synthesized in shoots, but is mainly found in the plant’s roots. The gentiopicroside biosynthetic pathway and its regulatory control remain to be elucidated. Genome resources of gentian [...] Read more.

Gentiana rigescens is an important medicinal herb in China. The main validated medicinal component gentiopicroside is synthesized in shoots, but is mainly found in the plant’s roots. The gentiopicroside biosynthetic pathway and its regulatory control remain to be elucidated. Genome resources of gentian are limited. Next-generation sequencing (NGS) technologies can aid in supplying global gene expression profiles. In this study we present sequence and transcript abundance data for the root and leaf transcriptome of G. rigescens, obtained using the Illumina Hiseq2000. Over fifty million clean reads were obtained from leaf and root libraries. This yields 76,717 unigenes with an average length of 753 bp. Among these, 33,855 unigenes were identified as putative homologs of annotated sequences in public protein and nucleotide databases. Digital abundance analysis identified 3306 unigenes differentially enriched between leaf and root. Unigenes found in both tissues were categorized according to their putative functional categories. Of the differentially expressed genes, over 130 were annotated as related to terpenoid biosynthesis. This work is the first study of global transcriptome analyses in gentian. These sequences and putative functional data comprise a resource for future investigation of terpenoid biosynthesis in Gentianaceae species and annotation of the gentiopicroside biosynthetic pathway and its regulatory mechanisms. Full article

(This article belongs to the Special Issue Molecular Research in Plant Secondary Metabolism 2015)

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Open AccessArticle

Optimal Scanning Protocols for Dual-Energy CT Angiography in Peripheral Arterial Stents: An in Vitro Phantom Study

by Abdulrahman Almutairi, Zhonghua Sun, Zakariya Al Safran, Abduljaleel Poovathumkadavi, Suha Albader and Husam Ifdailat

Int. J. Mol. Sci. 2015, 16(5), 11531-11549; https://doi.org/10.3390/ijms160511531 - 20 May 2015

Cited by 20 | Viewed by 5714

Abstract

Objective: To identify the optimal dual-energy computed tomography (DECT) scanning protocol for peripheral arterial stents while achieving a low radiation dose, while still maintaining diagnostic image quality, as determined by an in vitro phantom study. Methods: Dual-energy scans in monochromatic spectral imaging mode [...] Read more.

Objective: To identify the optimal dual-energy computed tomography (DECT) scanning protocol for peripheral arterial stents while achieving a low radiation dose, while still maintaining diagnostic image quality, as determined by an in vitro phantom study. Methods: Dual-energy scans in monochromatic spectral imaging mode were performed on a peripheral arterial phantom with use of three gemstone spectral imaging (GSI) protocols, three pitch values, and four kiloelectron volts (keV) ranges. A total of 15 stents of different sizes, materials, and designs were deployed in the phantom. Image noise, the signal-to-noise ratio (SNR), different levels of adaptive statistical iterative reconstruction (ASIR), and the four levels of monochromatic energy for DECT imaging of peripheral arterial stents were measured and compared to determine the optimal protocols. Results: A total of 36 scans with 180 datasets were reconstructed from a combination of different protocols. There was a significant reduction of image noise with a higher SNR from monochromatic energy images between 65 and 70 keV in all investigated preset GSI protocols (p < 0.05). In addition, significant effects were found from the main effect analysis for these factors: GSI, pitch, and keV (p = 0.001). In contrast, there was significant interaction on the unstented area between GSI and ASIR (p = 0.015) and a very high significant difference between keV and ASIR (p < 0.001). A radiation dose reduction of 50% was achieved. Conclusions: The optimal scanning protocol and energy level in the phantom study were GSI-48, pitch value 0.984, and 65 keV, which resulted in lower image noise and a lower radiation dose, but with acceptable diagnostic images. Full article

(This article belongs to the Section Biochemistry)

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Open AccessBrief Report

Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

by Fahad Benthani, Phuong N. Tran, Nicola Currey, Irvin Ng, Marc Giry-Laterriere, Louise Carey, Maija R. J. Kohonen-Corish and Laurent Pangon

Int. J. Mol. Sci. 2015, 16(5), 11522-11530; https://doi.org/10.3390/ijms160511522 - 19 May 2015

Cited by 3 | Viewed by 6883

Abstract

Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated [...] Read more.

Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC) protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions. Full article

(This article belongs to the Section Biochemistry)

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Periodic CO₂ Dosing Strategy for Dunaliella salina Batch Culture

by Kezhen Ying, D. James Gilmour and William B. Zimmerman

Int. J. Mol. Sci. 2015, 16(5), 11509-11521; https://doi.org/10.3390/ijms160511509 - 19 May 2015

Cited by 10 | Viewed by 5798

Abstract

A periodic CO₂ dosing strategy for D. salina 19/30 batch culture is proposed. A model of periodic CO₂ dosing including dosing time calculation, dosing interval estimation and final chlorophyll yield prediction was established. In experiments, 5% CO₂/95% N₂ [...] Read more.

A periodic CO₂ dosing strategy for D. salina 19/30 batch culture is proposed. A model of periodic CO₂ dosing including dosing time calculation, dosing interval estimation and final chlorophyll yield prediction was established. In experiments, 5% CO₂/95% N₂ gas was periodically dosed into D. salina culture. Two different gas dosing flow rates were tested. The corresponding dosing time for each flow rate was estimated via the model (10 min·d⁻¹ for 0.7 L·min⁻¹ and 36 min·d⁻¹ for 0.3 L·min⁻¹). Daily pH measurements showed that the pH of these cultures dosed periodically was always kept between 7.5 and 9.5, which highlights that periodic gas supply can maintain a suitable range of pH for microalgal growth without expensive buffers. Notably the culture dosed for set daily intervals was seen to have similar growth to the culture supplied constantly, but with much higher CO₂ capture efficiency (11%–18%) compared to continuous dosing (0.25%). It shows great potential for using periodic gas supply to reduce cost, wasted gas and energy use. Full article

(This article belongs to the Special Issue Microalgal Biotechnology)

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Microwave-Assisted Synthesis of Glutathione-Capped CdTe/CdSe Near-Infrared Quantum Dots for Cell Imaging

by Xiaogang Chen, Liang Li, Yongxian Lai, Jianna Yan, Yichen Tang and Xiuli Wang

Int. J. Mol. Sci. 2015, 16(5), 11500-11508; https://doi.org/10.3390/ijms160511500 - 19 May 2015

Cited by 20 | Viewed by 7100

Abstract

These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). [...] Read more.

These glutathione (GSH)-conjugated CdTe/CdSe core/shell quantum dot (QD) nanoparticles in aqueous solution were synthesized using a microwave-assisted approach. The prepared type II core/shell QD nanoparticles were characterized by UV–Vis absorption, photoluminescence (PL) spectroscopy, X-ray powder diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). Results revealed that the QD nanoparticles exhibited good dispersity, a uniform size distribution and tunable fluorescence emission in the near-infrared (NIR) region. In addition, these nanoparticles exhibited good biocompatibility and photoluminescence in cell imaging. In particular, this type of core/shell NIR QDs may have potential applications in molecular imaging. Full article

(This article belongs to the Special Issue Bioactive Nanoparticles)

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Anti-Fibrotic Effects of Class I HDAC Inhibitor, Mocetinostat Is Associated with IL-6/Stat3 Signaling in Ischemic Heart Failure

by Hikmet Nural-Guvener, Liudmila Zakharova, Lorraine Feehery, Snjezana Sljukic and Mohamed Gaballa

Int. J. Mol. Sci. 2015, 16(5), 11482-11499; https://doi.org/10.3390/ijms160511482 - 19 May 2015

Cited by 67 | Viewed by 7889

Abstract

Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects [...] Read more.

Background: Recent studies have linked histone deacetylases (HDAC) to remodeling of the heart and cardiac fibrosis in heart failure. However, the molecular mechanisms linking chromatin remodeling events with observed anti-fibrotic effects are unknown. Here, we investigated the molecular players involved in anti-fibrotic effects of HDAC inhibition in congestive heart failure (CHF) myocardium and cardiac fibroblasts in vivo. Methods and Results: MI was created by coronary artery occlusion. Class I HDACs were inhibited in three-week post MI rats by intraperitoneal injection of Mocetinostat (20 mg/kg/day) for duration of three weeks. Cardiac function and heart tissue were analyzed at six week post-MI. CD90⁺ cardiac fibroblasts were isolated from ventricles through enzymatic digestion of heart. In vivo treatment of CHF animals with Mocetinostat reduced CHF-dependent up-regulation of HDAC1 and HDAC2 in CHF myocardium, improved cardiac function and decreased scar size and total collagen amount. Moreover, expression of pro-fibrotic markers, collagen-1, fibronectin and Connective Tissue Growth Factor (CTGF) were reduced in the left ventricle (LV) of Mocetinostat-treated CHF hearts. Cardiac fibroblasts isolated from Mocetinostat-treated CHF ventricles showed a decrease in expression of collagen I and III, fibronectin and Timp1. In addition, Mocetinostat attenuated CHF-induced elevation of IL-6 levels in CHF myocardium and cardiac fibroblasts. In parallel, levels of pSTAT3 were reduced via Mocetinostat in CHF myocardium. Conclusions: Anti-fibrotic effects of Mocetinostat in CHF are associated with the IL-6/STAT3 signaling pathway. In addition, our study demonstrates in vivo regulation of cardiac fibroblasts via HDAC inhibition. Full article

(This article belongs to the Special Issue Improvement of Cardiac Function in Heart Failure)

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Gene Expression Signature in Endemic Osteoarthritis by Microarray Analysis

by Xi Wang, Yujie Ning, Feng Zhang, Fangfang Yu, Wuhong Tan, Yanxia Lei, Cuiyan Wu, Jingjing Zheng, Sen Wang, Hanjie Yu, Zheng Li, Mikko J. Lammi and Xiong Guo

Int. J. Mol. Sci. 2015, 16(5), 11465-11481; https://doi.org/10.3390/ijms160511465 - 19 May 2015

Cited by 4 | Viewed by 6612

Abstract

Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based [...] Read more.

Kashin-Beck Disease (KBD) is an endemic osteochondropathy with an unknown pathogenesis. Diagnosis of KBD is effective only in advanced cases, which eliminates the possibility of early treatment and leads to an inevitable exacerbation of symptoms. Therefore, we aim to identify an accurate blood-based gene signature for the detection of KBD. Previously published gene expression profile data on cartilage and peripheral blood mononuclear cells (PBMCs) from adults with KBD were compared to select potential target genes. Microarray analysis was conducted to evaluate the expression of the target genes in a cohort of 100 KBD patients and 100 healthy controls. A gene expression signature was identified using a training set, which was subsequently validated using an independent test set with a minimum redundancy maximum relevance (mRMR) algorithm and support vector machine (SVM) algorithm. Fifty unique genes were differentially expressed between KBD patients and healthy controls. A 20-gene signature was identified that distinguished between KBD patients and controls with 90% accuracy, 85% sensitivity, and 95% specificity. This study identified a 20-gene signature that accurately distinguishes between patients with KBD and controls using peripheral blood samples. These results promote the further development of blood-based genetic biomarkers for detection of KBD. Full article

(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)

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A Solid-State NMR Study of Selenium Substitution into Nanocrystalline Hydroxyapatite

by Joanna Kolmas, Marzena Kuras, Ewa Oledzka and Marcin Sobczak

Int. J. Mol. Sci. 2015, 16(5), 11452-11464; https://doi.org/10.3390/ijms160511452 - 19 May 2015

Cited by 21 | Viewed by 5928

Abstract

The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA₃₀₀) and selenate (HA₃₀₀ [...] Read more.

The substitution of selenium oxyanions in the hydroxyapatite structure was examined using multinuclear solid-state resonance spectroscopy (ssNMR). The study was supported by powder X-ray diffractometry (PXRD) and wavelength dispersion X-ray fluorescence (WD-XRF). Samples of pure hydroxyapatite (HA₃₀₀) and selenate (HA₃₀₀-1.2SeO₄) or selenite (HA₃₀₀-1.2SeO₃) substituted hydroxyapatites were synthesized using the standard wet method and heated at 300 °C to remove loosely bonded water. PXRD data showed that all samples are single-phase, nanocrystalline hydroxyapatite. The incorporation of selenite and selenate ions affected the lattice constants. In selenium-containing samples the concentration of Se was very similar and amounted to 9.55% and 9.64%, for HA₃₀₀-1.2SeO₄ and HA₃₀₀-1.2SeO₃, respectively. PXRD and ssNMR data showed that the selenite doping significantly decreases the crystallite size and crystallinity degree. ³¹P and ¹H NMR experiments demonstrated the developed surface hydrated layer in all samples, especially in HA₃₀₀-1.2SeO₃. ¹H NMR studies showed the dehydroxylation of HA during the selenium oxyanions substitution and the existence of hydrogen bonding in structural hydroxyl group channels. ¹H→⁷⁷Se cross polarization NMR experiments indicated that selenites and selenates are located in the crystal lattice and on the crystal surface. Full article

(This article belongs to the Special Issue Biomaterials for Tissue Engineering)

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Visfatin Mediates SCLC Cells Migration across Brain Endothelial Cells through Upregulation of CCL2

by Tingting Liu, Ziwei Miao, Jiusheng Jiang, Shuai Yuan, Wengang Fang, Bo Li and Yuhua Chen

Int. J. Mol. Sci. 2015, 16(5), 11439-11451; https://doi.org/10.3390/ijms160511439 - 18 May 2015

Cited by 22 | Viewed by 5591

Abstract

Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been [...] Read more.

Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular mechanisms of SCLC cells penetrating the blood–brain barrier (BBB) are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis. Full article

(This article belongs to the Section Biochemistry)

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Identification and Expression Analysis of Candidate Genes Associated with Defense Responses to Phytophthora capsici in Pepper Line “PI 201234”

by Pingyong Wang, Xiaodan Liu, Jinju Guo, Chen Liu, Nan Fu and Huolin Shen

Int. J. Mol. Sci. 2015, 16(5), 11417-11438; https://doi.org/10.3390/ijms160511417 - 18 May 2015

Cited by 20 | Viewed by 6203

Abstract

Phytophthora capsici (Leonian), classified as an oomycete, seriously threatens the production of pepper (Capsicum annuum). Current understanding of the defense responses in pepper to P. capsici is limited. In this study, RNA-sequencing analysis was utilized to identify differentially expressed genes in [...] Read more.

Phytophthora capsici (Leonian), classified as an oomycete, seriously threatens the production of pepper (Capsicum annuum). Current understanding of the defense responses in pepper to P. capsici is limited. In this study, RNA-sequencing analysis was utilized to identify differentially expressed genes in the resistant line “PI 201234”, with 1220 differentially expressed genes detected. Of those genes, 480 were up-regulated and 740 were down-regulated, with 211 candidate genes found to be involved in defense responses based on the gene annotations. Furthermore, the expression patterns of 12 candidate genes were further validated via quantitative real-time PCR (qPCR). These genes were found to be significantly up-regulated at different time points post-inoculation (6 hpi, 24 hpi, and 5 dpi) in the resistant line “PI 201234” and susceptible line “Qiemen”. Seven genes were found to be involved in cell wall modification, phytoalexin biosynthesis, symptom development, and phytohormone signaling pathways, thus possibly playing important roles in combating exogenous pathogens. The genes identified herein will provide a basis for further gene cloning and functional verification studies and will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici. Full article

(This article belongs to the Special Issue Plant Molecular Biology)

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Comparative Analysis of Anther Transcriptome Profiles of Two Different Rice Male Sterile Lines Genotypes under Cold Stress

by Bin Bai, Jun Wu, Wen-Tao Sheng, Bo Zhou, Li-Jie Zhou, Wen Zhuang, Dong-Ping Yao and Qi-Yun Deng

Int. J. Mol. Sci. 2015, 16(5), 11398-11416; https://doi.org/10.3390/ijms160511398 - 18 May 2015

Cited by 69 | Viewed by 10395

Abstract

Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice [...] Read more.

Rice is highly sensitive to cold stress during reproductive developmental stages, and little is known about the mechanisms of cold responses in rice anther. Using the HiSeq™ 2000 sequencing platform, the anther transcriptome of photo thermo sensitive genic male sterile lines (PTGMS) rice Y58S and P64S (Pei’ai64S) were analyzed at the fertility sensitive stage under cold stress. Approximately 243 million clean reads were obtained from four libraries and aligned against the oryza indica genome and 1497 and 5652 differentially expressed genes (DEGs) were identified in P64S and Y58S, respectively. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted for these DEGs. Functional classification of DEGs was also carried out. The DEGs common to both genotypes were mainly involved in signal transduction, metabolism, transport, and transcriptional regulation. Most of the DEGs were unique for each comparison group. We observed that there were more differentially expressed MYB (Myeloblastosis) and zinc finger family transcription factors and signal transduction components such as calmodulin/calcium dependent protein kinases in the Y58S comparison group. It was also found that ribosome-related DEGs may play key roles in cold stress signal transduction. These results presented here would be particularly useful for further studies on investigating the molecular mechanisms of rice responses to cold stress. Full article

(This article belongs to the Special Issue Abiotic Stress and Gene Networks in Plants)

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Polymorphisms of the Ovine BMPR-IB, BMP-15 and FSHR and Their Associations with Litter Size in Two Chinese Indigenous Sheep Breeds

by Weimin Wang, Shijia Liu, Fadi Li, Xiangyu Pan, Chong Li, Xiaoxue Zhang, Youji Ma, Yongfu La, Rui Xi and Tingfu Li

Int. J. Mol. Sci. 2015, 16(5), 11385-11397; https://doi.org/10.3390/ijms160511385 - 18 May 2015

Cited by 45 | Viewed by 7097

Abstract

The Small Tailed Han sheep and Hu sheep are two prolific local sheep in China. In this study, the polymorphisms of BMPR-IB (Bone morphogenetic protein receptor IB), BMP-15 (Bone morphogenetic protein 15) and FSHR (follicle stimulating hormone receptor) were investigated to check whether [...] Read more.

The Small Tailed Han sheep and Hu sheep are two prolific local sheep in China. In this study, the polymorphisms of BMPR-IB (Bone morphogenetic protein receptor IB), BMP-15 (Bone morphogenetic protein 15) and FSHR (follicle stimulating hormone receptor) were investigated to check whether they are associated with litter size in Small Tailed Han sheep and Hu sheep. Consequently, three polymorphisms, FecB mutation in BMPR-IB (c.746A>G), FecG mutation in BMP-15 (c.718C>T) and the mutation (g. 47C>T) in FSHR were found in the above two sheep breeds with a total number of 1630 individuals. The single marker association analysis showed that the three mutations were significantly associated with litter size. The ewes with genotype FecB^B/FecB^B and FecB^B/FecB⁺ had 0.78 and 0.58 more lambs (p < 0.01) than those with genotype FecB⁺/FecB⁺, respectively. The heterozygous Han and Hu ewes with FecX^G/FecX⁺ genotype showed 0.30 (p = 0.05) more lambs than those with the FecX⁺/FecX⁺ genotype. For FSHR gene, the ewes with genotype CC had 0.52 (p < 0.01) and 0.75 (p < 0.01) more lambs than those with genotypes TC and TT, respectively. Combined effect analyses indicated an extremely significant interaction (p < 0.01) between the random combinations of BMPR-IB, BMP-15 and FSHR genes on litter size. In addition, the Han and Hu ewes with BB/G+/CC genotype harbor the highest litter size among ewes analyzed in current study. In conclusion, BMPR-IB, BMP-15 and FSHR polymorphisms could be used as genetic markers in multi-gene pyramiding for improving litter size in sheep husbandry. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes

by Mei-Yueh Lee, Kun-Der Lin, Wei-Hao Hsu, Hsiu-Ling Chang, Yi-Hsin Yang, Pi-Jung Hsiao and Shyi-Jang Shin

Int. J. Mol. Sci. 2015, 16(5), 11369-11384; https://doi.org/10.3390/ijms160511369 - 18 May 2015

Cited by 31 | Viewed by 6549

Abstract

Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether [...] Read more.

Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58–0.98), 0.72 (95% CI, 0.58–0.91) and 0.76 (95% CI, 0.60–0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes. Full article

(This article belongs to the Section Biochemistry)

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Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease

by Hyung Gon Je, Bo Hyun Kim, Kyoung Im Cho, Jae Sik Jang, Yong Hyun Park and John Spertus

Int. J. Mol. Sci. 2015, 16(5), 11355-11368; https://doi.org/10.3390/ijms160511355 - 18 May 2015

Cited by 13 | Viewed by 5247

Abstract

Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial [...] Read more.

Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. Full article

(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

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Influence of Regular Exercise on Body Fat and Eating Patterns of Patients with Intermittent Claudication

by Anthony Leicht, Robert Crowther and Jonathan Golledge

Int. J. Mol. Sci. 2015, 16(5), 11339-11354; https://doi.org/10.3390/ijms160511339 - 18 May 2015

Cited by 7 | Viewed by 5000

Abstract

This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- [...] Read more.

This study examined the impact of regular supervised exercise on body fat, assessed via anthropometry, and eating patterns of peripheral arterial disease patients with intermittent claudication (IC). Body fat, eating patterns and walking ability were assessed in 11 healthy adults (Control) and age- and mass-matched IC patients undertaking usual care (n = 10; IC-Con) or supervised exercise (12-months; n = 10; IC-Ex). At entry, all groups exhibited similar body fat and eating patterns. Maximal walking ability was greatest for Control participants and similar for IC-Ex and IC-Con patients. Supervised exercise resulted in significantly greater improvements in maximal walking ability (IC-Ex 148%–170% vs. IC-Con 29%–52%) and smaller increases in body fat (IC-Ex −2.1%–1.4% vs. IC-Con 8.4%–10%). IC-Con patients exhibited significantly greater increases in body fat compared with Control at follow-up (8.4%–10% vs. −0.6%–1.4%). Eating patterns were similar for all groups at follow-up. The current study demonstrated that regular, supervised exercise significantly improved maximal walking ability and minimised increase in body fat amongst IC patients without changes in eating patterns. The study supports the use of supervised exercise to minimize cardiovascular risk amongst IC patients. Further studies are needed to examine the additional value of other lifestyle interventions such as diet modification. Full article

(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

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Immunohistochemical Analysis of Paraoxonases and Chemokines in Arteries of Patients with Peripheral Artery Disease

by Anna Hernández-Aguilera, Julio Sepúlveda, Esther Rodríguez-Gallego, Maria Guirro, Anabel García-Heredia, Noemí Cabré, Fedra Luciano-Mateo, Isabel Fort-Gallifa, Vicente Martín-Paredero, Jorge Joven and Jordi Camps

Int. J. Mol. Sci. 2015, 16(5), 11323-11338; https://doi.org/10.3390/ijms160511323 - 18 May 2015

Cited by 23 | Viewed by 5262

Abstract

Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as [...] Read more.

Oxidative damage to lipids and lipoproteins is implicated in the development of atherosclerotic vascular diseases, including peripheral artery disease (PAD). The paraoxonases (PON) are a group of antioxidant enzymes, termed PON1, PON2, and PON3 that protect lipoproteins and cells from peroxidation and, as such, may be involved in protection against the atherosclerosis process. PON1 inhibits the production of chemokine (C–C motif) ligand 2 (CCL2) in endothelial cells incubated with oxidized lipoproteins. PON1 and CCL2 are ubiquitously distributed in tissues, and this suggests a joint localization and combined systemic effect. The aim of the present study has been to analyze the quantitative immunohistochemical localization of PON1, PON3, CCL2 and CCL2 receptors in a series of patients with severe PAD. Portions of femoral and/or popliteal arteries from 66 patients with PAD were obtained during surgical procedures for infra-inguinal limb revascularization. We used eight normal arteries from donors as controls. PON1 and PON3, CCL2 and the chemokine-binding protein 2, and Duffy antigen/chemokine receptor, were increased in PAD patients. There were no significant changes in C–C chemokine receptor type 2. Our findings suggest that paraoxonases and chemokines play an important role in the development and progression of atherosclerosis in peripheral artery disease. Full article

(This article belongs to the Special Issue Advances in Peripheral Artery Disease)

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