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https://www.readbyqxmd.com/read/28527416/ochratoxin-a-induces-nephrotoxicity-and-immunotoxicity-through-different-mapk-signaling-pathways-in-pk15-cells-and-porcine-primary-splenocytes
#1
Fang Gan, Yaojiao Zhou, Lili Hou, Gang Qian, Xingxiang Chen, Kehe Huang
Ochratoxin A (OTA) is reported to be a potent nephrotoxin and immunotoxin in animals and humans. However, the mechanisms underlying OTA toxicity have not been clearly determined until now. Toxicity of OTA and its mechanism was investigated in PK15 cells and in porcine primary splenocytes. The results showed that OTA at 2.0-8.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in PK 15 cells. OTA at 0.5-4.0 μg/mL for 24 h induced cytotoxicity and apoptosis in a dose-dependent manner in porcine primary splenocytes...
May 9, 2017: Chemosphere
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#2
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28527346/inhibitory-effects-of-2-oxo-2h-chromen-4-yl-4-methylbenzenesulfonate-on-allergic-inflammatory-responses-in-rat-basophilic-leukemia-cells
#3
Gaeun Yoo, Kooyeon Lee, Deug-Chan Lee
Mast cells play crucial roles in the initiation of allergic inflammatory responses by releasing various mediators such as histamines, cytokines, and leukotrienes. In addition, signaling cascade pathways, such as the mitogen-activated protein kinase (MAPK) pathway, contribute to the regulation of mast cell degranulation. Accordingly, different research strategies have been pursued to develop anti-inflammatory and anti-allergic drugs by regulating these signaling pathways. The development of new drugs that inhibit mast cell degranulation may help in the treatment of allergies...
May 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28527294/activation-of-hypoxia-signaling-in-stromal-progenitors-impairs-kidney-development
#4
Katharina Gerl, Dominik Steppan, Michaela Fuchs, Charlotte Wagner, Carsten Willam, Armin Kurtz, Birgül Kurt
Intrauterine hypoxia is a reason for impaired kidney development. The cellular and molecular pathways along which hypoxia exerts effects on nephrogenesis are not well understood. They are likely triggered by hypoxia-inducible transcription factors (HIFs), and their effects appear to be dependent on the cell compartment contributing to kidney formation. In this study, we investigated the effects of HIF activation in the developing renal stroma, which also essentially modulates nephron development from the metanephric mesenchyme...
May 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28527291/haplotypes-in-ccr5-ccr2-ccl3-and-ccl5-are-associated-with-natural-resistance-to-hiv-1-infection-in-a-colombian-cohort
#5
Jorge A Vega, Simón Villegas-Ospina, Wbeimar Aguilar-Jiménez, María T Rugeles, Gabriel Bedoya, Wildeman Zapata
INTRODUCTION: Variants in genes encoding for HIV-1 co-receptors and their natural ligands have been individually associated to natural resistance to HIV-1 infection. However, the simultaneous presence of these variants has been poorly studied. OBJECTIVE: To evaluate the association of single and multilocus haplotypes in genes coding for the viral co-receptors CCR5 and CCR2, and their ligands CCL3 and CCL5, with resistance or susceptibility to HIV-1 infection. MATERIALS AND METHODS: Nine variants in CCR5-CCR2, two SNPs in CCL3 and two in CCL5 were genotyped by PCR-RFLP in 35 seropositive (cases) and 49 HIV-1-exposed seronegative Colombian individuals (controls)...
June 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527256/-stat3-activation-by-hypoxia-in-in-vitro-models-of-cervix-cancer-and-endothelial-cells
#6
Óscar Ortega, Alejandro Ondo-Méndez, Ruth Garzón
INTRODUCTION: The biological behavior of cancer cells is influenced by the tumor microenvironment in which they develop. In this context, stressor stimuli such as hypoxia are considered critical for tumor development and therapeutic management. Cellular response to various stimuli is evidenced in the activation of intracellular signaling pathways such as JAK/STAT, which is one of the most important for its effects in differentiation and cell proliferation. OBJECTIVE: To evaluate the condition of the JAK/STAT pathway through the expression/activation of the STAT3 protein in cervix cancer cells (HeLa) and endothelial cells (EA...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527218/the-mechanisms-of-action-of-curcumin-in%C3%A2-alzheimer-s-disease
#7
Mengxi Tang, Changiz Taghibiglou
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb, to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid-β plaques, attenuates the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity, inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527132/gankyrin-as-a-potential-therapeutic-target-for-cancer
#8
REVIEW
Chongchong Wang, Li Cheng
Gankyrin is an oncoprotein that plays a central role in the development of cancer. Although researchers have increasingly focused on the relationships of gankyrin with carcinogenesis, metastasis and prognosis of different cancers, the molecular mechanisms are still unclear. In recent years, several interacting partners of gankyrin and cell signaling pathways regulated by gankyrin have been elucidated. In addition, accumulating evidence has indicated the contribution of microRNAs to regulating gankyrin expression in tumor cells...
May 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28527041/mechanisms-of-acupuncture-therapy-for-cerebral-ischemia-an-evidence-based-review-of-clinical-and-animal-studies-on-cerebral-ischemia
#9
REVIEW
Wen Zhu, Yang Ye, Yi Liu, Xue-Rui Wang, Guang-Xia Shi, Shuai Zhang, Cun-Zhi Liu
Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply...
May 19, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28526936/fingerprint-of-long-non-coding-rna-regulated-by-cyclic-mechanical-stretch-in-human-aortic-smooth-muscle-cells-implications-for-hypertension
#10
Laura-Eve Mantella, Krishna K Singh, Paul Sandhu, Crystal Kantores, Azza Ramadan, Nadiya Khyzha, Adrian Quan, Mohammed Al-Omran, Jason E Fish, Robert P Jankov, Subodh Verma
Emerging evidence suggests that long non-coding RNAs (lncRNAs) represent a cellular hub coordinating various cellular processes that are critical in health and disease. Mechanical stress triggers changes in vascular smooth muscle cells (VSMCs) that in turn contribute to pathophysiological changes within the vasculature. We sought to evaluate the role that lncRNAs play in mechanical stretch-induced alterations of human aortic smooth muscle cells (HASMCs). RNA (lncRNA and mRNA) samples isolated from HASMCs that had been subjected to 10 or 20% elongation (1 Hz) for 24 h were profiled with the Arraystar Human LncRNA Microarray V3...
May 19, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28526921/glp-1-signalling-compensates-for-impaired-insulin-signalling-in-regulating-beta-cell-proliferation-in-%C3%AE-irko-mice
#11
Dan Kawamori, Jun Shirakawa, Chong Wee Liew, Jiang Hu, Tomoaki Morioka, Alokesh Duttaroy, Bryan Burkey, Rohit N Kulkarni
AIMS/HYPOTHESIS: We aimed to investigate potential interactions between insulin and glucagon-like peptide (GLP)-1 signalling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. METHODS: Beta cell-specific insulin receptor knockout (βIRKO) mice, which exhibit beta cell dysfunction and an age-dependent decrease in beta cell mass, were treated with the dipeptidyl peptidase-4 inhibitor vildagliptin...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28526890/a-heteromeric-molecular-complex-regulates-the-migration-of-lung-alveolar-epithelial-cells-during-wound-healing
#12
Manik C Ghosh, Patrudu S Makena, Joseph Kennedy, Bin Teng, Charlean Luellen, Scott E Sinclair, Christopher M Waters
Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526854/induction-of-senescence-in-primary-glioblastoma-cells-by-serum-and-tgf%C3%AE
#13
Ritesh Kumar, Alexander Gont, Theodore J Perkins, Jennifer E L Hanson, Ian A J Lorimer
Glioblastoma is the most common type of adult brain tumour and has a median survival after diagnosis of a little more than a year. Glioblastomas have a high frequency of mutations in the TERT promoter and CDKN2A locus that are expected to render them resistant to both replicative and oncogene-induced senescence. However, exposure of PriGO8A primary glioblastoma cells to media with 10% serum induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526849/interleukin-22-attenuated-angiotensin-ii-induced-acute-lung-injury-through-inhibiting-the-apoptosis-of-pulmonary-microvascular-endothelial-cells
#14
Zhiyong Wu, Zhipeng Hu, Xin Cai, Wei Ren, Feifeng Dai, Huagang Liu, Jinxing Chang, Bowen Li
Apoptosis of pulmonary microvascular endothelial cells (PMVECs) was considered to be closely related to the pathogenesis of acute lung injury (ALI). We aim to investigate whether IL-22 plays protective roles in lung injury through inhibiting the apoptosis of PMVECs. ALI model was induced through subcutaneous infusion of angiotensin II (Ang II). Lung injury and infiltration of inflammatory cells were evaluated by determining the PaO2/FiO2, calculation of dry to weight ratio in lung, and immunohistochemisty analysis...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526827/activated-hepatic-stellate-cells-secrete-periostin-to-induce-stem-cell-like-phenotype-of-residual-hepatocellular-carcinoma-cells-after-heat-treatment
#15
Rui Zhang, Rong-Rong Yao, Jing-Huan Li, Gang Dong, Min Ma, Qiong-Dan Zheng, Dong-Mei Gao, Jie-Feng Cui, Zheng-Gang Ren, Rong-Xin Chen
Some evidences show that residual tumor after thermal ablation will progress rapidly. However, its mechanisms remain unclear. Here, we assessed whether activated HSCs could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Human HCC cell lines were exposed to sublethal heat treatment to simulate the peripheral zone of thermal ablation. After residual HCC cells were cultured with conditional medium (CM) from activated HSCs, parameters of the stem cell-like phenotypes were analyzed...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526789/a-novel-iron-dependent-enzyme-that-catalyzes-the-initial-step-in-the-biodegradation-of-n-nitroglycine-by-variovorax-sp-strain-js1663
#16
Kristina M Mahan, Hangping Zheng, Tekle T Fida, Ronald J Parry, David E Graham, Jim C Spain
Nitramines are key constituents of most of the explosives in current use and consequently contaminate soil and groundwater at many military facilities around the world. Toxicity from nitramine contamination poses a health risk to plants and animals, thus understanding how nitramines are biodegraded is critical to environmental remediation. The biodegradation of synthetic nitramine compounds such as hexahydro-1,3,5-trinitro-1,3,5- triazine (RDX) has been studied for decades, but little is known about the catabolism of naturally produced nitramine compounds...
May 19, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28526744/combining-properties-of-different-classes-of-pi3k%C3%AE-inhibitors-to-understand-molecular-features-that-confer-selectivity
#17
Grace Q Gong, Jackie D Kendall, James Mj Dickson, Gordon W Rewcastle, Christina M Buchanan, William A Denny, Peter R Shepherd, Jack U Flanagan
Phosphoinositide 3-kinases (PI3K) are major regulators of many cellular functions, and hyperactivation of PI3K cell signalling pathways is a major target for anticancer drug discovery. PI3Kα is the isoform most implicated in cancer, and our aim is to selectively inhibit this isoform, which may be more beneficial than concurrent inhibition of all Class I PI3Ks. We have used structure-guided design to merge high selectivity and high affinity characteristics found in existing compounds. Molecular docking including the prediction of water-mediated interactions, was used to model interactions between the ligands and the PI3Kα affinity pocket...
May 19, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28526728/genetic-subtraction-profiling-identifies-candidate-mirnas-involved-in-rice-female-gametophyte-abortion
#18
Liyu Yang, Ya Wu, Wenliang Wang, Bigang Mao, Bingran Zhao, Jianbo Wang
Female gametophyte is an important participant in sexual reproduction of plants. The molecular mechanism of its development has received much attention in recent years. As important regulators of gene expression, miRNAs have been certified to play a significant role in many biological processes of plants including sexual reproduction. In this study, to investigate the potential regulatory effects of miRNAs on rice female gametophytes abortion, we used the high-throughput sequencing method to compare the miRNA transcriptome in ovules of a high frequency female-sterile line (fsv1) and a rice wild-type line (Gui 99) during ovule development...
May 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28526703/mir156-regulated-taspls-interact-with-tad53-to-regulate-tatb1-and-taba1-expression-in-bread-wheat
#19
Jie Liu, Xiliu Cheng, Pan Liu, Jiaqiang Sun
Genetic and environmental factors affect bread wheat plant architecture, which determines grain yield. In this study, we demonstrate that miR156 controls bread wheat plant architecture. We show that overexpression of tae-miR156 in bread wheat cultivar Kenong199 leads to increased tiller number and severe defects in spikelet formation, probably due to the tae-miR156-mediated repression of a group of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes. Furthermore, we found that the expression of two genes TaBA1 and TaTB1, whose orthologous genes in diverse plant species play conserved roles in regulating plant architecture, is markedly reduced in the tae-miR156-OE bread wheat plants...
May 19, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28526701/netrin-1-preserves-blood-brain-barrier-integrity-through-deleted-in-colorectal-cancer-focal-adhesion-kinase-rhoa-signaling-pathway-following-subarachnoid-hemorrhage-in-rats
#20
Zongyi Xie, Budbazar Enkhjargal, Cesar Reis, Lei Huang, Weifeng Wan, Jiping Tang, Yuan Cheng, John H Zhang
BACKGROUND: Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. METHODS AND RESULTS: A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH...
May 19, 2017: Journal of the American Heart Association
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