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https://www.readbyqxmd.com/read/28438154/network-based-analysis-reveals-novel-gene-signatures-in-peripheral-blood-of-patients-with-chronic-obstructive-pulmonary-disease
#1
Ma'en Obeidat, Yunlong Nie, Virginia Chen, Casey P Shannon, Anand Kumar Andiappan, Bernett Lee, Olaf Rotzschke, Peter J Castaldi, Craig P Hersh, Nick Fishbane, Raymond T Ng, Bruce McManus, Bruce E Miller, Stephen Rennard, Peter D Paré, Don D Sin
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death and there is a huge unmet clinical need to identify disease biomarkers in peripheral blood. Compared to gene level differential expression approaches to identify gene signatures, network analyses provide a biologically intuitive approach which leverages the co-expression patterns in the transcriptome to identify modules of co-expressed genes. METHODS: A weighted gene co-expression network analysis (WGCNA) was applied to peripheral blood transcriptome from 238 COPD subjects to discover co-expressed gene modules...
April 24, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28437633/microrna-500a-promotes-migration-and-invasion-in-hepatocellular-carcinoma-by-activating-the-wnt-%C3%AE-catenin-signaling-pathway
#2
Yuntao Guo, Liwen Chen, Chengyi Sun, Chao Yu
Increased expression of microRNA-500a (miR-500a) has been reported in the serum of hepatocellular carcinoma (HCC) patients. However, the biological effects and mechanisms of miR-500a in hepatoma cells remain unclear. In this study, we found that miR-500a expression was up-regulated in HCC cell lines and tissues, and that high levels of miR-500a was associated with poor prognosis. We found that miR-500a upregulation promoted migration and invasion in two hepatoma cell lines, HCCLM3 and SMMC7721, while miR-500a downregulation had the opposite effect...
April 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28431381/zeaxanthin-ameliorates-high-glucose-induced-mesangial-cell-apoptosis-through-inhibiting-oxidative-stress-via-activating-akt-signalling-pathway
#3
Changjiang Ying, Lei Chen, Shanshan Wang, Yizhen Mao, Hongwei Ling, Wei Li, Xiaoyan Zhou
Oxidative stress is a critical factor in the pathophysiology of diabetic kidney disease. Previous study shows that hyperglycaemia aggravates renal injury through oxidative stress in diabetic model, and antioxidants have beneficial effect on diabetic kidney disease. However, the role of antioxidants in the progression of diabetic kidney disease is poorly understood. The aim of this study was to clarify whether zeaxanthin, an antioxidant, could ameliorate mesangial cell injury and if so, identify the related mechanism underlying this protective effect...
April 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28430783/shigella-dysenteriae-infection-activates-proinflammatory-response-through-%C3%AE-catenin-nf-%C3%AE%C2%BAb-signaling-pathway
#4
Ashidha Gopal, Iyer Soumya Chidambaram, Niranjali Devaraj, Halagowder Devaraj
Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity during S.dysenteriae infection in rat ileal loop model...
2017: PloS One
https://www.readbyqxmd.com/read/28430655/a-study-on-the-anti-tumor-mechanism-of-total-flavonoids-from-radix-tetrastigmae-against-additional-cell-line-based-on-cox-2-mediated-wnt-%C3%AE-catenin-signaling-pathway
#5
Li Qinglin, Xin Wenxiu, Zhong Like, Fangluo, Cao Gang, Huang Ping
This study is to explore the effect of total flavonoids from Radix Tetrastigmae (TF) against hepatic cancer and discuss the acting mechanism. Proliferation of HepG2 cells was promoted by PGE2 and Butaprost. Using AH6809 as the positive control, the inhibitory effect of TF on additional cell line was detected through a CCK-8 assay, the apoptosis rate was detected by flow cytometry, and the nuclear morphology of cells were observed by Hochest33258 staining. Then PCR was applied to determine the mRNA expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430602/fluoxetine-attenuates-the-impairment-of-spatial-learning-ability-and-prevents-neuron-loss-in-middle-aged-appswe-psen1de9-double-transgenic-alzheimer-s-disease-mice
#6
Jing Ma, Yuan Gao, Lin Jiang, Feng-Lei Chao, Wei Huang, Chun-Ni Zhou, Wei Tang, Lei Zhang, Chun-Xia Huang, Yi Zhang, Yan-Min Luo, Qian Xiao, Hua-Rong Yu, Rong Jiang, Yong Tang
Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429187/curcumin-reverses-the-depressive-like-behavior-and-insulin-resistance-induced-by-chronic-mild-stress
#7
Ji-Duo Shen, Yu Wei, Yu-Jie Li, Jing-Yi Qiao, Yu-Cheng Li
Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity...
April 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28423558/biological-basis-and-clinical-study-of-glycogen-synthase-kinase-3%C3%AE-targeted-therapy-by-drug-repositioning-for-glioblastoma
#8
Takuya Furuta, Hemragul Sabit, Yu Dong, Katsuyoshi Miyashita, Masashi Kinoshita, Naoyuki Uchiyama, Yasuhiko Hayashi, Yutaka Hayashi, Toshinari Minamoto, Mitsutoshi Nakada
BACKGROUND: Glycogen synthase kinase (GSK)-3β has emerged as an appealing therapeutic target for glioblastoma (GBM). Here, we investigated the therapeutic effect of the current approved drugs against GBM via inhibition of GSK3β activity both, in experimental setting and in a clinical study for recurrent GBM patients by repositioning existent drugs in combination with temozolomide (TMZ). MATERIALS AND METHODS: Progression-free and overall survival rates were compared between patients with low or high expression of active GSK3β in the primary tumor...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422767/pseudolaric-acid-b-induces-endometrial-cancer-ishikawa-cell-apoptosis-and-inhibits-metastasis-through-akt-gsk-3%C3%AE-and-erk1-2-signaling-pathways
#9
Dan Wang, Yanqiu Tian, Wenhua Feng, Li Zhao, Mingyi Zhao, Ju Liu, Qiuyu Wang
Pseudolaric acid B (PAB) is the most active constituent extracted from the bark of Pseudolarix kaempferi, which has been used as an antifungal remedy in traditional Chinese medicine. It is reported to have cytotoxicity to many tumor cell lines. In this study, we investigated the effects of PAB against human endometrial cancer Ishikawa cells. We found that PAB inhibited Ishikawa cell proliferation, and induced cell apoptosis and G2/M phase arrest through a mechanism involving AKT-GSK-3β and ERK1/2 signaling pathways...
April 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#10
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421341/insufficient-activation-of-akt-upon-reperfusion-because-of-its-novel-modification-by-reduced-pp2a-b55%C3%AE-contributes-to-enlargement-of-infarct-size-by-chronic-kidney-disease
#11
Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura
Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28419994/degradation-of-mcl-1-through-gsk-3%C3%AE-activation-regulates-apoptosis-induced-by-bufalin-in-non-small-cell-lung-cancer-h1975-cells
#12
Xiao-Hong Kang, Jing-Hang Zhang, Qing-Qin Zhang, Yan-Hui Cui, Ying Wang, Wei-Zheng Kou, Zhan-Hui Miao, Ping Lu, Li-Fang Wang, Zhen-Ye Xu, Fei Cao
BACKGROUND/AIMS: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. METHODS: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting...
April 14, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28418865/anti-helminthic-niclosamide-inhibits-ras-driven-oncogenic-transformation-via-activation-of-gsk-3
#13
Sung Yong Ahn, Ji Hye Yang, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Jun Seop Yun, Hee Eun Kang, Yoonmi Lee, Jiwon Choi, Hyun Sil Kim, Jong In Yook
Despite the importance of Ras oncogenes as a therapeutic target in human cancer, their 'undruggable' tertiary structures limit the effectiveness of anti-Ras drugs. Canonical Wnt signaling contributes to Ras activity by glycogen synthase kinase 3 (GSK-3)-dependent phosphorylation at the C-terminus and subsequent degradation. In the accompanying report, we show that the anti-helminthic niclosamide directly binds to GSK-3 and inhibits Axin functions in colon cancer cells, with reversion of Snail-mediated epithelial-mesenchymal transition...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417055/potential-involvement-of-glycogen-synthase-kinase-gsk-3%C3%AE-in-a-rat-model-of-multiple-sclerosis-evidenced-by-lithium-treatment
#14
Meejung Ahn, Jeongtae Kim, Changnam Park, Jinhee Cho, Youngheun Jee, Kyungsook Jung, Changjong Moon, Taekyun Shin
Glycogen synthase kinase (GSK)-3β has been known as a pro-inflammatory molecule in neuroinflammation. The involvement of GSK-3β remains unsolved in acute monophasic rat experimental autoimmune encephalomyelitis (EAE). The aim of this study was to evaluate a potential role of GSK-3β in central nervous system (CNS) autoimmunity through its inhibition by lithium. Lithium treatment significantly delayed the onset of EAE paralysis and ameliorated its severity. Lithium treatment reduced the serum level of pro-inflammatory tumor necrosis factor a but not that of interleukin 10...
March 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28416463/glucocorticoids-activate-a-synapse-weakening-pathway-culminating-in-tau-phosphorylation-in-the-hippocampus
#15
Jee Hyun Yi, Christopher Brown, Garry Whitehead, Thomas Piers, Young Seok Lee, Celia Martinez Perez, Philip Regan, Daniel J Whitcomb, Kwangwook Cho
Evidence suggests that the stress hormones glucocorticoids (GCs) can cause cognitive deficits and neurodegeneration. Previous studies have found GCs facilitate physiological synapse weakening, termed long-term depression (LTD), though the precise mechanisms underlying this are poorly understood. Here we show that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse weakening signals. Critically, this ultimately leads to phosphorylation of the microtubule associated protein tau, specifically at the serine 396 residue, and this is a causal factor in the GC-mediated impairment of synaptic function...
April 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28411439/neuropeptide-y-enhances-proliferation-and-prevents-apoptosis-in-rat-bone-marrow-stromal-cells-in-association-with-activation-of-the-wnt-%C3%AE-catenin-pathway-in-vitro
#16
Jianqun Wu, Song Liu, Huan Meng, Tianyu Qu, Su Fu, Zhao Wang, Jianguo Yang, Dan Jin, Bin Yu
Neuropeptide Y (NPY) exhibits a critical but poorly understood regulatory signaling function and has been shown to promote proliferation, vascularization and migration in several types of cells and tissues. However, little is known about the specific role of NPY in the proliferation and apoptosis of bone marrow stromal cells (also known as bone marrow-derived mesenchymal stem cells, BMSCs), which contain a subpopulation of multipotent skeletal stem cells. Based on BrdU incorporation tests, Cell Counting Kit-8, flow cytometry, quantitative polymerase chain reaction and western blotting, we showed that NPY significantly promoted the proliferation of BMSCs in a concentration-dependent manner, with a maximal effect observed at a concentration of 10(-10)M for pro-proliferative and 10(-12)M for anti-apoptotic activities...
April 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28411054/salidroside-protects-rat-liver-against-ischemia-reperfusion-injury-by-regulating-the-gsk-3%C3%AE-nrf2-dependent-antioxidant-response-and-mitochondrial-permeability-transition
#17
Linlin Cai, Yonghua Li, Qingqing Zhang, Haijing Sun, Xiaodi Yan, Tong Hua, Qiufeng Zhu, Haitao Xu, Hailong Fu
Salidroside (Sal) is a natural antioxidant that elicits cardioprotective and neuroprotective effects in vivo and in vitro; however, its impact on hepatic ischemia/reperfusion (I/R) injury remains unclear. The purpose of this study was to investigate the hepatoprotective effects of salidroside against segmental (70%) warm hepatic I/R injury in rats. Animals were randomized into Sham, Sham+salidroside pretreatment (Sal), Sham+Sal+carboxyatractyloside (CATR), Sham+CATR, I/R, I/R+Sal, I/R+Sal+CATR and I/R+CATR groups...
April 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28410959/the-involvement-of-bdnf-creb-signaling-pathways-in-the-pharmacological-mechanism-of-combined-ssri-antipsychotic-treatment-in-schizophrenia
#18
Reef Einoch, Orly Weinreb, Nina Mandiuk, Moussa B H Youdim, Warren Bilker, Henry Silver
Previous studies into the mechanism of SSRI-antipsychotic synergism in our laboratory identified unique changes in the brain, particularly in the γ-aminobutyric acid (GABA)-A receptor and its modulators. This study examined the role of brain derived neurotrophic factor (BDNF)-cAMP response element binding (CREB) protein signaling pathways, including protein kinase B (AKT), glycogen synthase kinase (GSK)-3β and related molecules in the molecular response to haloperidol, fluvoxamine, combined haloperidol+fluvoxamine and clozapine treatments in rat frontal cortex, hippocampus and primary cortical neuronal cultures...
April 11, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28402933/pdk1-inhibitor-gsk2334470-exerts-antitumor-activity-in-multiple-myeloma-and-forms-a-novel-multitargeted-combination-with-dual-mtorc1-c2-inhibitor-pp242
#19
Chunmei Yang, Xianbo Huang, Hui Liu, Feng Xiao, Jueying Wei, Liangshun You, Wenbin Qian
A deeper understanding of the complex pathogenesis of multiple myeloma (MM) continues to lead to novel therapeutic approaches. Prior studies suggest that 3-phosphoinositide-dependent kinase 1 (PDK1) is expressed and active, acting as a crucial regulator of molecules that are essential for myelomagenesis. In the present study, we show that GSK2334470 (GSK-470), a novel and highly specific inhibitor of PDK1, induces potent cytotoxicity in MM cell lines including Dexamethasone-resistant cell line, but not in human normal cells...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28399054/pneumococcal-immune-response-in-infants-whose-mothers-received-tdap-vaccination-during-pregnancy
#20
Kirsten Maertens, Polly Burbidge, Pierre Van Damme, David Goldblatt, Elke Leuridan
BACKGROUND: Maternal immunization with a tetanus, diphtheria and acellular pertussis (Tdap) vaccine may blunt infant pneumococcal immune responses after a primary series of vaccines. METHODS: As part of a prospective controlled cohort trial of Tdap (Boostrix®, GSK Biologicals) vaccination in pregnancy, infants born to vaccinated mothers and controls were immunized at 8 and 16 weeks and 12 months of age with 13-valent pneumococcal conjugate vaccine (Prevenar13®, Pfizer)...
April 10, 2017: Pediatric Infectious Disease Journal
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