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https://www.readbyqxmd.com/read/29154981/egfr-family-inhibition-identifies-p38-mapk-as-a-potential-therapeutic-target-in-bladder-cancer
#1
Regina Mora Vidal, Sergio Regufe da Mota, Annette Hayden, Hannah Markham, James Douglas, Graham Packham, Simon J Crabb
Objective To investigate perturbations in downstream signalling pathway activation and potential resistance mechanisms to EGFR and/or HER2 inhibition in cell line models of bladder cancer. Methods We undertook a structured screening approach by phosphokinase array, followed by validation steps, to detect activated downstream signalling pathway nodes after therapeutic inhibition of EGFR and/or HER2 in bladder cancer cell lines. Results Erlotinib treatment of RT112 cells induced phosphorylation of 9 activated phospho-protein targets (p38 MAPK (Thr180/Tyr182), GSK-3α/β (Ser21/9), MEK1/2 (Ser218/222, Ser222/226), Akt (Ser473), TOR (Ser2448), Src (Tyr419), p27 (Thr198), p27 (Thr157) and PLCγ-1 (Tyr783)) whereas STAT4 (Tyr693) phosphorylation was reduced...
November 15, 2017: Urology
https://www.readbyqxmd.com/read/29154192/resveratrol-attenuates-testicular-apoptosis-in-type-1-diabetic-mice-role-of-akt-mediated-nrf2-activation-and-p62-dependent-keap1-degradation
#2
Yuguang Zhao, Wenjing Song, Zhenyu Wang, Zongqiang Wang, Xing Jin, Jiancheng Xu, Ling Bai, Yuying Li, Jiuwei Cui, Lu Cai
Infertility is a common complication in diabetic men, mainly due to the loss of germ cells by apoptotic cell death. However, effective and safe approaches to prevent diabetic induction of testicular apoptosis for diabetic patients have not been available. Resveratrol (RSV), a group of compounds called polyphenols from plants, has been indicated its promising used clinically for cancers and cardiovascular diseases. Therefore, the present study aimed determining whether RSV attenuates type 1 diabetes (T1D)-induced testicular apoptotic cell death in a mouse model...
November 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/29152576/meningococcal-antigen-typing-system-mats-based-neisseria-meningitidis-serogroup-b-coverage-prediction-for-the-menb-4c-vaccine-in-the-united-states
#3
Gowrisankar Rajam, Maria Stella, Ellie Kim, Simon Paulos, Giuseppe Boccadifuoco, Laura Serino, George Carlone, Duccio Medini
Neisseria meningitidis is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against N. meningitidis serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States...
November 2017: MSphere
https://www.readbyqxmd.com/read/29151980/synbiotic-effects-of-%C3%AE-glucans-from-cauliflower-mushroom-and-lactobacillus-fermentum-on-metabolic-changes-and-gut-microbiome-in-estrogen-deficient-rats
#4
Seong-Yeop Jeong, Suna Kang, Cao Shi Hua, Zhang Ting, Sunmin Park
Background: We investigated whether the long-term consumption of a symbiotic formulation with Lactobacillus fermentum (probiotic) and β-glucan from cauliflower mushroom (prebiotic) would delay the progression of post-menopausal symptoms in ovariectomized (OVX) rats and explored their mechanisms of action, including changes in gut microbiota. Methods: OVX rats were fed with high-fat diets containing 1% dextrin (control), 1% lyophilized cauliflower mushroom extract (CFM), 0...
2017: Genes & Nutrition
https://www.readbyqxmd.com/read/29148041/fscn1-predicts-survival-and-is-regulated-by-a-pi3k-dependent-mechanism-in-renal-cell-carcinoma
#5
Mengping Zhang, Zhijian Zhao, Xiaolu Duan, Ping Chen, Zhenwei Peng, Huijuan Qiu
While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo...
November 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29144001/biological-evaluation-and-energetic-analyses-of-novel-gsk-3%C3%AE-inhibitors
#6
Denan Zhang, Lei Liu, Lin Pang, Qing Jin, Kehui Ke, Ming Hu, Jingbo Yang, Weifang Ma, Hongbo Xie, Xiujie Chen
Glycogen synthase kinase-3 beta (GSK-3β) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK-3β activity have been implicated in diabetes, heart disease, Parkinson disease and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK-3β were identified by virtual screening and bioassay. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29141245/roscovitine-a-cdk5-inhibitor-alleviates-sevoflurane-induced-cognitive-dysfunction-via-regulation-tau-gsk3%C3%AE-and-erk-ppar%C3%AE-creb-signaling
#7
Jianhui Liu, Junjun Yang, Yinhua Xu, Gang Guo, Li Cai, Heng Wu, Yanhong Zhao, Xiaoqing Zhang
BACKGROUND/AIMS: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. METHODS: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups...
November 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29140945/a-retrospective-cohort-study-of-the-incidence-health-care-resource-utilization-and-costs-of-international-classification-of-diseases-clinical-modification-9th-revision-diagnosed-influenza-and-related-complications-in-us-children
#8
Philip O Buck, David M Smith, Rahul Shenolikar, Debra E Irwin
BACKGROUND: There is a paucity of data on the clinical and economic impact of seasonal influenza in children. This study estimated the incidence of diagnosed influenza and related complications and associated health care resource utilization and costs in US children. METHODS: Children ≥6 months and <18 years old diagnosed with influenza using International Classification of Diseases, Clinical Modification, 9th revision codes and enrolled in a health plan during at least one influenza season between 2010 and 2014 were matched to similar patients without diagnosed influenza (GSK study identifier: HO-15-15728)...
December 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29138567/resveratrol-ameliorates-chronic-unpredictable-mild-stress-induced-depression-like-behavior-involvement-of-the-hpa-axis-inflammatory-markers-bdnf-and-wnt-%C3%AE-catenin-pathway-in-rats
#9
Xin-Hua Yang, Su-Qi Song, Yun Xu
Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29137265/c-met-creb1-and-egfr-are-involved-in-mir-493-5p-inhibition-of-emt-via-akt-gsk-3%C3%AE-snail-signaling-in-prostate-cancer
#10
Song Wang, Xiao Wang, Jiangfeng Li, Shuai Meng, Zhen Liang, Xin Xu, Yi Zhu, Shiqi Li, Jian Wu, Mingjie Xu, Alin Ji, Yiwei Lin, Ben Liu, Xiangyi Zheng, Bo Xie, Liping Xie
miR-493-5p downregulation has emerged as a critical player in cancer progression yet, the underlying mechanisms of miR-493-5p expression pattern and its function in prostate cancer remains to be elucidated. Here, we illustrate that miR-493-5p is frequently downregulated in prostate cancer, at least partially due to altered DNA methylation. miR-493-5p functions as a tumor suppressor in prostate cancer cells. c-Met, CREB1 and EGFR are downstream target genes of miR-493-5p. miR-493-5p inhibits EMT via AKT/GSK-3β/Snail signaling in prostate cancer...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137190/spirulina-maxima-extract-ameliorates-learning-and-memory-impairments-via-inhibiting-gsk-3%C3%AE-phosphorylation-induced-by-intracerebroventricular-injection-of-amyloid-%C3%AE-1-42-in-mice
#11
Eun-Jeong Koh, Kui-Jin Kim, Ji-Hyeon Song, Jia Choi, Hyeon Yong Lee, Do-Hyung Kang, Ho Jin Heo, Boo-Yong Lee
Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-β 1-42 (Aβ1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aβ1-42 in mice...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136173/high-levels-of-gsk-3%C3%AE-signaling-reduce-osteogenic-differentiation-of-stem-cells-in-osteonecrosis-of-femoral-head
#12
Lu Huang, Ying Wang, Yangzi Jiang, Yan Wu, Changchang Hu, Hongwei Ouyang
Osteonecrosis of the femoral head (ONFH) is a common but intractable disease. In this study, we investigated the mechanisms regulating alterations in mesenchymal stem cell (MSC) differentiation in ONFH. Five patients who were diagnosed with ONFH were enrolled in this study. BMSCs were isolated from the osteonecrotic zone in the femoral head (FH-pMSCs) and from the normal zone in the pelvis (hMSCs) of the same patient. Morphology, cell proliferation, and expression of mediators of the Wnt signaling pathway were evaluated...
November 10, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29132216/curcumin-decreases-hyperphosphorylation-of-tau-by-down-regulating-caveolin-1-gsk-3%C3%AE-in-n2a-app695swe-cells-and-app-ps1-double-transgenic-alzheimer-s-disease-mice
#13
Jieyun Sun, Xiong Zhang, Chen Wang, Zhipeng Teng, Yu Li
Caveolin-1, the marker protein of membranal caveolae, is not only involved in cholesterol regulation, but also participates in the cleavage of amyloid [Formula: see text]-protein precursor (APP) and the generation of [Formula: see text]-amyloid peptide. It has been reported to be tightly related with Tau. In our previous studies, curcumin has been confirmed to play a neuroprotective role in Alzheimer's disease (AD), but its effects on Caveolin-1, Tau and their correlation, and the mechanism is still unknown...
November 13, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29131030/n-cadherin-mediated-activation-of-pi3k-akt-gsk-3%C3%AE-signaling-attenuates-nucleus-pulposus-cell-apoptosis-under-high-magnitude-compression
#14
Pei Li, Zherui Liang, Gang Hou, Lei Song, Ruijie Zhang, Yibo Gan, Chengmin Zhang, Yichun Xu, Qiang Zhou
BACKGROUND/AIMS: Mechanical overloading-induced nucleus pulposus (NP) apoptosis plays an important role in the pathogenesis of intervertebral disc degeneration. N-cadherin (N-CDH)-mediated signaling preserves normal NP cell phenotype. This study aims to investigate the effects of N-CDH on NP cell apoptosis under high-magnitude compression and the underlying mechanism behind this process. METHODS: Rat NP cells seeded on scaffold were perfusion-cultured using a self-developed perfusion bioreactor for 5 days and experienced different magnitudes (2% and 20% compressive deformation, respectively) of compression at a frequency of 1...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129621/tdcpp-protects-cardiomyocytes-from-hypoxia-reoxygenation-injury-induced-apoptosis-through-mitigating-calcium-overload-and-promotion-gsk-3%C3%AE-phosphorylation
#15
Xiju He, Shoutian Li, Xiaoxia Fang, Yanhong Liao
TDCPP, Tris (1, 3-dichloro-2-propyl) phosphate belongs to a group of chemicals known as triester organophosphate flame retardants, It can alter calcium homeostasis at much lower concentrations in normal conditions, but the mechanism is unclear till now. Calcium overload is a leading cause of apoptosis in myocardial ischemia/reperfusion (I/R) injury, thus how to mitigate Ca(2+)-overload is deserved to be investigated. We therefore hypothesized that TDCPP could attenuate cardiomyocytes apoptosis in I/R injury...
November 9, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29129566/pediatric-glioblastoma-cells-inhibit-neurogenesis-and-promote-astrogenesis-phenotypic-transformation-and-migration-of-human-neural-progenitor-cells-within-cocultures
#16
Kurt Farrell, Gautam Mahajan, Parthasarathy Srinivasan, Moo-Yeal Lee, Chandrasekhar R Kothapalli
Neural progenitor cell (NPC) fate is influenced by a variety of biological cues elicited from the surrounding microenvironment and recent studies suggest their possible role in pediatric glioblastoma multiforme (GBM) development. Since a few GBM cells also display NPC characteristics, it is not clear whether NPCs transform to tumor cell phenotype leading to the onset of GBM formation, or NPCs migrate to developing tumor sites in response to paracrine signaling from GBM cells. Elucidating the paracrine interactions between GBM cells and NPCs in vivo is challenging due to the inherent complexity of the CNS...
November 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29128606/salvianic-acid-a-sodium-protects-huvec-cells-against-tert-butyl-hydroperoxide-induced-oxidative-injury-via-mitochondria-dependent-pathway
#17
Dan Jia, Tian Li, Xiaofei Chen, Xuan Ding, Yifeng Chai, Alex F Chen, Zhenyu Zhu, Chuan Zhang
Salvianic acid A (Danshensu) is a major water-soluble component in Salvia miltiorrhiza (Danshen), which has been widely used in clinic in China for treatment of cardiovascular diseases (CVDs). This study aimed to investigate the protective effects of salvianic acid A sodium (SAAS) against tert-butyl hydroperoxide (t-BHP) induced human umbilical vein endothelial cell (HUVEC) oxidative injury and the potential molecular mechanisms. In the antioxidant activity-assessing models, SAAS significantly prevented t-BHP induced cell proliferation inhibition and apoptosis...
November 8, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29128381/early-impact-of-rotavirus-vaccination-in-children-less-than-five-years-of-age-in-mozambique
#18
Nilsa de Deus, Jorfélia José Chilaúle, Marta Cassocera, Miguel Bambo, Jerónimo Sozinho Langa, Ezequias Sitoe, Assucênio Chissaque, Elda Anapakala, Júlia Sambo, Esperança Lourenço Guimarães, Diocreciano Matias Bero, Eva Dora João, Idalécia Cossa-Moiane, Jason M Mwenda, Goitom G Weldegebriel, Umesh D Parashar, Jacqueline E Tate
BACKGROUND: Mozambique introduced rotavirus vaccine (Rotarix, GSK Biologicals) in the National Immunization Program in September 2015 with the objective of reducing the burden of total diarrheal disease and specifically severe rotavirus disease. This study aimed to evaluate the early impact of rotavirus vaccine in reducing all-cause diarrhea and rotavirus-specific hospitalizations. METHODS: We analysed stool specimens collected from children under five years old, between January 2014 and June 2017 within the National Surveillance for Acute Diarrhea...
November 8, 2017: Vaccine
https://www.readbyqxmd.com/read/29125105/sequence-analysis-and-comparison-of-the-key-genes-of-domestic-live-attenuated-varicella-vaccine
#19
Ya-Ru Quan, Zhen Chen, Ping Qiu, Xiao-Yu Cui, Chang-Gui Li, Li-Yong Yuan
Objective To analyze the safety and consistency of domestic live attenuated varicella vaccines (LAVVs) at gene level.Methods The key genes (ORF38,ORF54,and ORF62) of LAVVs produced by four Chinese manufacturers were amplified by polymerase chain reaction (PCR) and sequenced.The sequencing results were compared with the sequences of Dumas,P-Oka,and V-Oka strains in GenBank and with the sequences of Varilrix (GSK) and Varivax (Merck).Results The ORF38 and ORF54 gene sequences of four domestic LAVVs were the same as each other and completely consistent with the sequences of V-Oka and Varilrix;however,it was different from Varivax (Merck) at one site...
October 30, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29123923/root-securing-and-brain-fortifying-liquid-upregulates-caveolin-1-in-cell-model-with-alzheimer-s-disease-through-inhibiting-tau-phosphorylation
#20
Depei Yuan, Chuhua Zeng, Qianfeng Chen, Fengjie Wang, Lin Yuan, Yaoqian Zhu, Ziyang Shu, Ning Chen
In order to explore the effect of root-securing and brain-fortifying Liquid- (RSBFL-) mediated caveolin-1 (CAV-1) on phosphorylation of Tau protein and to uncover underlying mechanisms of RSBFL for the prevention and treatment of Alzheimer's disease (AD), hippocampal neurons isolated from neonatal SD rats and cultured in DMEM-F12 medium were induced by exogenous Aβ1-42 to establish a cell model with AD. Meanwhile, pEGFP-C1-CAV1 and CAV1-shRNA plasmids were transfected into hippocampal neurons for CAV-1 overexpression and silence, respectively...
2017: Neurology Research International
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