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https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#1
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28815513/an-update-on-p2y13-receptor-signalling-and-function
#2
Raquel Pérez-Sen, Rosa Gómez-Villafuertes, Felipe Ortega, Javier Gualix, Esmerilda G Delicado, María Teresa Miras-Portugal
The distribution of nucleotide P2Y receptors across different tissues suggests that they fulfil key roles in a number of physiological and pathological conditions. P2Y13 is one of the latest P2Y receptors identified, a novel member of the Gi-coupled P2Y receptor subfamily that responds to ADP, together with P2Y12 and P2Y14. Pharmacological studies drew attention to this new ADP receptor, with a pharmacology that overlaps that of P2Y12 receptors but with unique features and roles. The P2RY12-14 genes all reside on human chromosome 3 at 3q25...
August 17, 2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28810562/anti-depressant-like-effects-of-jieyu-chufan-capsules-in-a-mouse-model-of-unpredictable-chronic-mild-stress
#3
Hui Zhao, Bingyu Liang, Linjie Yu, Yun Xu
Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810189/hydroxy-substituted-trans-cinnamoyl-derivatives-as-multifunctional-tools-in-the-context-of-alzheimer-s-disease
#4
Angela De Simone, Manuela Bartolini, Andrea Baschieri, Kim Y P Apperley, Huan Huan Chen, Melissa Guardigni, Serena Montanari, Tereza Kobrlova, Ondrej Soukup, Luca Valgimigli, Vincenza Andrisano, Jeffrey W Keillor, Manuela Basso, Andrea Milelli
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808322/neuroinflammation-alters-cellular-proteostasis-by-producing-endoplasmic-reticulum-stress-autophagy-activation-and-disrupting-erad-activation
#5
Cristina Pintado, Sandra Macías, Helena Domínguez-Martín, Angélica Castaño, Diego Ruano
Proteostasis alteration and neuroinflammation are typical features of normal aging. We have previously shown that neuroinflammation alters cellular proteostasis through immunoproteasome induction, leading to a transient decrease of proteasome activity. Here, we further investigated the role of acute lipopolysaccharide (LPS)-induced hippocampal neuroinflammation in cellular proteostasis. In particular, we focused on macroautophagy (hereinafter called autophagy) and endoplasmic reticulum-associated protein degradation (ERAD)...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808220/insensitivity-of-pi3k-akt-gsk3-signaling-in-peripheral-blood-mononuclear-cells-of-age-related-macular-degeneration-patients
#6
Xunxian Liu, Zemin Yao
Our recent studies with cultured retinal pigment epithelium cells suggested that overexpression of interleukin 17 receptor C (IL-17RC), a phenomenon observed in peripheral blood and chorioretinal tissues with age-related macular degeneration (AMD), was associated with altered activation of phosphatidylinositide 3-kinase (PI3K), Akt, and glycogen synthase kinase 3 (GSK3). We wondered whether or not altered PI3K, Akt, and GSK3 activities could be detected in peripheral blood mononuclear cells (PBMC) obtained from AMD patients...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#7
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28807209/induction-of-autophagy-reduces-ischemia-reperfusion-injury-in-steatotic-rat-livers
#8
Chunyi Kan, Anding Liu, Haoshu Fang, Olaf Dirsch, Uta Dahmen, Michael Boettcher
BACKGROUND: Steatotic livers are particularly vulnerable to ischemia/reperfusion injury (IRI). One of the reasons is an underlying impairment of autophagy. Autophagy is regulated by glycogen synthase kinase 3b (GSK3b) and extracellular signal-regulated kinases (ERK1/2) pathways. Both of them are target proteins of a cell-protective drug, lithium chloride. Lithium chloride treatment reduces IRI in many organs including liver. Therefore, we aimed to investigate the effect of lithium chloride treatment on autophagy induction in steatotic rat livers...
August 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28803855/elucidating-the-functions-of-brain-gsk3%C3%AE-possible-synergy-with-gsk3%C3%AE-upregulation-and-reversal-by-antidepressant-treatment-in-a-mouse-model-of-depressive-like-behaviour
#9
Dmitri Pavlov, Nataliia Markova, Lucien Bettendorff, Vladimir Chekhonin, Igor Pomytkin, Viktoria Lioudyno, Andrei Svistunov, Eugene Ponomarev, Klaus-Peter Lesch, Tatyana Strekalova
Glycogen synthase kinase 3 (GSK3) has been linked to the mechanisms of stress, mood regulation, and the effects of antidepressants. The functions of the GSK3β isoform have been extensively investigated, but little is known about the α-isoform, although they may functionally related. In a recently established modified swim test with a third delayed swim exposure, brain GSK3β mRNA expression positively correlated with floating behavior on the third test. A two-week-long pretreatment regime with imipramine (7...
August 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28802581/pkm2-aggravates-palmitate-induced-insulin-resistance-in-hepg2-cells-via-stat3-pathway
#10
Ling Chen, Zhuqi Tang, Xiaohua Wang, Hong Ma, Dandan Shan, Shiwei Cui
Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β)...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28798343/isoflurane-produces-antidepressant-effects-and-induces-trkb-signaling-in-rodents
#11
Hanna Antila, Maria Ryazantseva, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Ipek Yalcin, Jesse Lindholm, Liisa Vesa, Vinicius Sato, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Plinio Casarotto, Leonard Khiroug, Sari Lauri, Tomi Taira, Eero Castrén, Tomi Rantamäki
A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791398/pi3k-akt-signaling-pathway-activation-in-a-rat-model-of-migraine
#12
Yun-Yong Liu, Zi-Yao Jiao, Wei Li, Qian Tian
The present study aimed to investigate phosphatidylinositol 4,5-bisphosphate 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway activation in a rat model of migraine. A total of 60 male Sprague‑Dawley rats were randomly divided into three groups: Blank control; suspension control; and migraine model. The model group was subcutaneously injected with a glyceryl trinitrate suspension, using an optimized Tassorelli method to establish a rat model of migraine. The activation status of the PI3K/AKT signaling pathway was assessed via measurement of the phosphorylated (p)‑AKT level...
August 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28772167/glycogen-synthase-kinase-3-inhibition-sensitizes-human-induced-pluripotent-stem-cells-to-thiol-containing-antioxidants-induced-apoptosis
#13
Chengyi Tu, Robert Xu, Meghana Koleti, Janet Zoldan
Inhibition of glycogen synthase kinase 3 (GSK3) is an extensively used strategy to activate Wnt pathway for pluripotent stem cell (PSC) differentiation. However, the effects of such inhibition on PSCs, besides upregulating the Wnt pathway, have rarely been investigated despite that GSK3 is broadly involved in other cellular activities such as insulin signaling and cell growth/survival regulation. Here we describe a previously unknown synergistic effect between GSK3 inhibition (e.g., Chir99021 and LY2090314) and various normally non-toxic thiol-containing antioxidants (e...
July 22, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28765953/atorvastatin-protects-cardiomyocytes-against-ogd-r%C3%A2-induced-apoptosis-by-inhibiting-mir%C3%A2-199a%C3%A2-5p
#14
Yong Li, Ting Jiang, Xingli Fu, Hao Xu, Jianguo Ji
The present study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its underlying mechanisms. The direct cytotoxic effects of oxygen‑glucose deprivation/reperfusion (OGD/R) on cardiomyocytes with and without atorvastatin pretreatment were evaluated. The effects of atorvastatin on the expression of glycogen synthase kinase‑3β (GSK‑3β) and microRNA (miR)‑199a‑5p were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses...
July 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765892/production-of-bfgf-monoclonal-antibody-and-its-inhibition-of-metastasis-in-lewis-lung-carcinoma
#15
Yanqing Yang, Zhenming Luo, Yiyang Qin, Yu Zhou, Longcai Gong, Jianfang Huang, Hong Wang
Basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) are associated with drug resistance in lung cancer. In the present study, mouse monoclonal antibodies (mAb) against human bFGF, targeting the binding site of bFGF with FGFR1 were produced, and the antitumor activity and inhibition of metastasis was studied in Lewis lung carcinoma (LLC). A total of four hybridoma cell strains that stably secreted bFGF mAb were obtained. mAbE12 was selected as the most effective for use in the following studies, with a relative affinity constant of 5...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28765878/grifola-frondosa-polysaccharides-induce-breast-cancer-cell-apoptosis-via-the-mitochondrial-dependent-apoptotic-pathway
#16
Yizhi Zhang, Dejun Sun, Qingjin Meng, Wanxu Guo, Qiuhui Chen, Ying Zhang
Grifola frondosa, a type of food and medical fungus, has been shown to exhibit various pharmacological activities, including anticancer effects. As the most typical cancer diagnosed among female patients, breast cancer remains a huge concern threatening human health globally. In the present study, the anti-breast cancer effects of Grifola frondosa polysaccharides (GFPs) and the underlying mechanisms were investigated in MCF-7 and MDA-MB-231 cells, as well as in nude mice bearing MCF-7 tumor xenografts. GFPs exerted cytotoxic effects on the cells, as indicated by a decrease in cell viability, and an increase in the apoptototic rate, lactate dehydrogenase release and reactive oxygen species accumulation, inducing mitochondrial dysfunction...
July 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in-pancreatic-carcinoma
#17
Yangchun Xie, Shan Zhu, Meizuo Zhong, Minghua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of non-apoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
July 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28763058/a-novel-preventive-therapy-for-paclitaxel-induced-cognitive-deficits-preclinical-evidence-from-c57bl-6-mice
#18
P Huehnchen, W Boehmerle, A Springer, D Freyer, M Endres
Chemotherapy-induced central nervous system (CNS) neurotoxicity presents an unmet medical need. Patients often report a cognitive decline in temporal correlation to chemotherapy, particularly for hippocampus-dependent verbal and visuo-spatial abilities. We treated adult C57Bl/6 mice with 12 × 20 mg kg(-1) paclitaxel (PTX), mimicking clinical conditions of dose-dense chemotherapy, followed by a pulse of bromodesoxyuridine (BrdU) to label dividing cells. In this model, mice developed visuo-spatial memory impairments, and we measured peak PTX concentrations in the hippocampus of 230 nm l(-1), which was sevenfold higher compared with the neocortex...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28761074/antidepressant-like-effects-and-cognitive-enhancement-of-schisandra-chinensis-in-chronic-unpredictable-mild-stress-mice-and-its-related-mechanism
#19
Tingxu Yan, Bosai He, Shutong Wan, Mengjie Xu, Huilin Yang, Feng Xiao, Kaishun Bi, Ying Jia
The aim of this study was to evaluate whether Schisandra chinensis extract (SCE) administration influences chronic unpredictable mild stress (CUMS)-induced depression and cognitive impairment, and explores underlying mechanisms. Sucrose preference test (SPT) and forced swimming test (FST) were used for assessing depressive symptoms, and Y-maze, Morris water maze were used for evaluating cognition processes. The results showed that CUMS (4 weeks) was effective in producing both depression and memory deficits in mice...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759639/g-protein-coupled-receptor-kinase-2-promotes-cardiac-hypertrophy
#20
Philipp Schlegel, Julia Reinkober, Eric Meinhardt, Henrike Tscheschner, Erhe Gao, Sarah M Schumacher, Ancai Yuan, Johannes Backs, Patrick Most, Thomas Wieland, Walter J Koch, Hugo A Katus, Philip W Raake
The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure. Inhibition of GRK2 improved cardiac function and survival and diminished cardiac remodeling in various animal heart failure models. The aim of the present study was to investigate the effects of GRK2 on cardiac hypertrophy and dissect potential molecular mechanisms. In mice we observed increased GRK2 mRNA and protein levels following transverse aortic constriction (TAC)...
2017: PloS One
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