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https://www.readbyqxmd.com/read/28220272/exposure-to-chronic-hyperglycemic-conditions-results-in-ras-related-c3-botulinum-toxin-substrate-1-rac1-mediated-activation-of-p53-and-atm-kinase-in-pancreatic-%C3%AE-cells
#1
Vaibhav Sidarala, Anjaneyulu Kowluru
Chronic hyperglycemia (HG) promotes pancreatic islet dysfunction which leads to the onset of T2DM. This study is aimed at defining regulatory roles of Rac1, a small G-protein, in the activation of p53 and ATM kinase in pancreatic β-cells, under the duress of HG conditions. We report significant stimulatory effects of HG (20 mM; 24 h) on p53 activation in INS-1 832/13 cells, normal rodent and human islets. Pharmacological inhibition of Rac1 (EHT1864 or NSC23766) significantly suppressed HG-induced p53 activation in INS-1 832/13 cells and rat islets, suggesting novel roles for this small G-protein in the activation of p53...
February 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28211523/pedf-mediates-pathological-neovascularization-by-regulating-macrophage-recruitment-and-polarization-in-the-mouse-model-of-oxygen-induced-retinopathy
#2
Sha Gao, Changwei Li, Yanji Zhu, Yanuo Wang, Ailing Sui, Yisheng Zhong, Bing Xie, Xi Shen
Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205565/entorhinal-cortex-dysfunction-can-be-rescued-by-inhibition-of-microglial-rage-in-an-alzheimer-s-disease-mouse-model
#3
Chiara Criscuolo, Veronica Fontebasso, Silvia Middei, Martina Stazi, Martine Ammassari-Teule, Shirley ShiDu Yan, Nicola Origlia
The Entorhinal cortex (EC) has been implicated in the early stages of Alzheimer's disease (AD). In particular, spreading of neuronal dysfunction within the EC-Hippocampal network has been suggested. We have investigated the time course of EC dysfunction in the AD mouse model carrying human mutation of amyloid precursor protein (mhAPP) expressing human Aβ. We found that in mhAPP mice plasticity impairment is first observed in EC superficial layer and further affected with time. A selective impairment of LTP was observed in layer II horizontal connections of EC slices from 2 month old mhAPP mice, whereas at later stage of neurodegeneration (6 month) basal synaptic transmission and LTD were also affected...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199960/cancer-suppression-by-systemic-inactivation-of-p38mapk
#4
EDITORIAL
Anna Brichkina, Dmitry V Bulavin
No abstract text is available yet for this article.
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#5
Alessandra Soriani, Cristiana Borrelli, Biancamaria Ricci, Rosa Molfetta, Alessandra Zingoni, Cinzia Fionda, Silvia Carnevale, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Giuseppe La Regina, Erica Di Cesare, Patrizia Lavia, Romano Silvestri, Rossella Paolini, Marco Cippitelli, Angela Santoni
The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194826/mapping-out-p38mapk
#6
Elizabeth A Bonney
To generate new hypotheses, sometimes a "systems" approach is needed. In this review, I focus on the mitogen-activated kinase p38 because it has been recently shown to play an important role in the developmental programing and senescence of normal and stressed reproductive tissues. What follows is an overview of (i) pathways of p38 activation and their involvement in basic biological processes, (ii) evidence that p38 is involved in the homeostasis of reproductive tissues, (iii) how focus on p38 can be incorporated into investigation of normal and stressed pregnancies...
February 13, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28194607/il-17a-monoclonal-antibody-partly-reverses-the-glucocorticoids-insensitivity-in-mice-exposed-to-ozonec
#7
Xia Fei, Peng-Yu Zhang, Xue Zhang, Guo-Qing Zhang, Wu-Ping Bao, Ying-Ying Zhang, Min Zhang, Xin Zhou
Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0...
February 13, 2017: Inflammation
https://www.readbyqxmd.com/read/28187175/hspa6-augments-garlic-extract-induced-inhibition-of-proliferation-migration-and-invasion-of-bladder-cancer-ej-cells-implication-for-cell-cycle-dysregulation-signaling-pathway-alteration-and-transcription-factor-associated-mmp-9-regulation
#8
Seung-Shick Shin, Jun-Hui Song, Byungdoo Hwang, Dae-Hwa Noh, Sung Lyea Park, Won Tae Kim, Sung-Soo Park, Wun-Jae Kim, Sung-Kwon Moon
Although recent studies have demonstrated the anti-tumor effects of garlic extract (GE), the exact molecular mechanism is still unclear. In this study, we investigated the molecular mechanism associated with the inhibitory action of GE against bladder cancer EJ cell responses. Treatment with GE significantly inhibited proliferation of EJ cells dose-dependently through G2/M-phase cell cycle arrest. This G2/M-phase cell cycle arrest by GE was due to the activation of ATM and CHK2, which appears to inhibit phosphorylation of Cdc25C (Ser216) and Cdc2 (Thr14/Tyr15), this in turn was accompanied by down-regulation of cyclin B1 and up-regulation of p21WAF1...
2017: PloS One
https://www.readbyqxmd.com/read/28176763/p190-b-rhogap-and-intracellular-cytokine-signals-balance-hematopoietic-stem-and-progenitor-cell-self-renewal-and-differentiation
#9
Ashwini Hinge, Juying Xu, Jose Javier, Eucabeth Mose, Sachin Kumar, Reuben Kapur, Edward F Srour, Punam Malik, Bruce J Aronow, Marie-Dominique Filippi
The mechanisms regulating hematopoietic stem and progenitor cell (HSPC) fate choices remain ill-defined. Here, we show that a signalling network of p190-B RhoGAP-ROS-TGF-β-p38(MAPK) balances HSPC self-renewal and differentiation. Upon transplantation, HSPCs express high amounts of bioactive TGF-β1 protein, which is associated with high levels of p38(MAPK) activity and loss of HSC self-renewal in vivo. Elevated levels of bioactive TGF-β1 are associated with asymmetric fate choice in vitro in single HSPCs via p38MAPK activity and this is correlated with the asymmetric distribution of activated p38MAPK...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28176369/morin-inhibits-proliferation-migration-and-invasion-of-bladder-cancer-ej-cells-via-modulation-of-signaling-pathways-cell-cycle-regulators-and-transcription-factor-mediated-mmp-9-expression
#10
Seung-Shick Shin, Se Yeon Won, Dae-Hwa Noh, Byungdoo Hwang, Wun-Jae Kim, Sung-Kwon Moon
Preclinical Research Previous studies have shown that morin exerts diverse pharmacological activities. In this study, we investigated the inhibitory activity of morin on bladder cancer EJ cells. Morin significantly inhibited EJ cell proliferation, which was related to the G1-phase cell cycle arrest together with the reduced expression of cyclin D1, cyclin E, CDK2, and CDK4 via increased expression of p21WAF1. Morin also increased ERK1/2 phosphorylation and decreased JNK and AKT phosphorylation without altering the p38MAPK phosphorylation levels...
February 8, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28176142/hmgb1-tlr4-axis-plays-a-regulatory-role-in-the-pathogenesis-of-mesial-temporal-lobe-epilepsy-in-immature-rat-model-and-children-via-the-p38mapk-signaling-pathway
#11
Weihong Yang, Jing Li, Yun Shang, Li Zhao, Mingying Wang, Jipeng Shi, Shujun Li
The HMGB1-TLR4 axis is activated in adult mouse models of acute and chronic seizure. Nevertheless, whether HMGB1 was involved in the pathogenesis of mesial temporal lobe epilepsy (MTLE) remains unknown. In this study, we first measured the dynamic expression patterns of HMGB1 and TLR4 in the hippocampi of a rat model and in children with MTLE, as well as the levels of TNF-α and IL-1β. In addition, HMGB1 was added to mimic the process of inflammatory response in neurons. Neuronal somatic size and dendritic length were measured by immunohistochemistry and digital imaging...
February 7, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28170408/tnf%C3%AE-alters-occludin-and-cerebral-endothelial-permeability-role-of-p38mapk
#12
Yawen Ni, Tao Teng, Runting Li, Agnes Simonyi, Grace Y Sun, James C Lee
Occludin is a key tight junction (TJ) protein in cerebral endothelial cells (CECs) playing an important role in modulating blood-brain barrier (BBB) functions. This protein (65kDa) has been shown to engage in many signaling pathways and phosphorylation by both tyrosine and threonine kinases. Despite yet unknown mechanisms, pro-inflammatory cytokines and endotoxin (lipopolysaccharides, LPS) may alter TJ proteins in CECs and BBB functions. Here we demonstrate the responses of occludin in an immortalized human cerebral endothelial cell line (hCMEC/D3) to stimulation by TNFα (10 ng/mL), IL-1β (10 ng/mL) and LPS (100 ng/mL)...
2017: PloS One
https://www.readbyqxmd.com/read/28164119/sodium-ferulate-protects-against-angiotensin-ii-induced-cardiac-hypertrophy-in-mice-by-regulating-the-mapk-erk-and-jnk-pathways
#13
Bo Hu, Jian-Tao Song, Xian-Fei Ji, Zun-Qi Liu, Mu-Lin Cong, Dong-Xing Liu
Background and Objective. It has been reported that sodium ferulate (SF) has hematopoietic function against anemia and immune regulation, inflammatory reaction inhibition, inhibition of tumor cell proliferation, cardiovascular and cerebrovascular protection, and other functions. Thus, this study aimed to investigate the effects of SF on angiotensin II- (AngII-) induced cardiac hypertrophy in mice through the MAPK/ERK and JNK signaling pathways. Methods. Seventy-two male C57BL/6J mice were selected and divided into 6 groups: control group, PBS group, model group (AngII), model + low-dose SF group (AngII + 10 mg/kg SF), model + high-dose SF group (AngII + 40 mg/kg SF), and model + high-dose SF + agonist group (AngII + 40 mg/kg SCU + 10 mg/kg TBHQ)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28155868/a-critical-role-for-p38mapk-signalling-pathway-during-reprogramming-of-human-fibroblasts-to-ipscs
#14
Irina Neganova, Valeria Chichagova, Lyle Armstrong, Majlinda Lako
Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) holds enormous promise for regenerative medicine. Reprogramming is a stepwise process with well-defined stages of initiation, maturation and stabilisation which are critically dependent on interactions between key pluripotency transcription factors, epigenetic regulators and signalling pathways. In this manuscript we have investigated the role of p38 MAPK signalling pathway and have shown a subpopulation- and phase-specific pattern of activation occurring during the initiation and maturation stage of reprogramming in partially and fully reprogrammed cells respectively...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28145888/adamts18-deficiency-promotes-colon-carcinogenesis-by-enhancing-%C3%AE-catenin-and-p38mapk-erk1-2-signaling-in-the-mouse-model-of-aom-dss-induced-colitis-associated-colorectal-cancer
#15
Tiantian Lu, Suying Dang, Rui Zhu, Ying Wang, Zongying Nie, Tao Hong, Wei Zhang
ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of β-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28145433/dendritic-cell-mst1-inhibits-th17-differentiation
#16
Chunxiao Li, Yujing Bi, Yan Li, Hui Yang, Qing Yu, Jian Wang, Yu Wang, Huilin Su, Anna Jia, Ying Hu, Linian Han, Jiangyuan Zhang, Simin Li, Wufan Tao, Guangwei Liu
Although the differentiation of CD4(+)T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4(+)T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4(+)T cells, whereas ectopic MST1 expression in DCs inhibits it...
February 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28144715/cardioprotective-effects-of-irbesartan-in-polymicrobial-sepsis-the-role-of-the-p38mapk-nf-%C3%AE%C2%BAb-signaling-pathway
#17
N G Yousif, N R Hadi, F Al-Amran, Q A Zigam
BACKGROUND: Sepsis is a systemic inflammatory response usually correlated with multi-organ failure. Myocardial dysfunction is one of the adverse outcomes in septic patients and results in high mortality rates. The aim of this study was to investigate the impact of irbesartan in attenuation of cardiac depression during polymicrobial sepsis via decreased activation of the phospho-p38MAPK/nuclear factor (NF)-κB signaling pathway. MATERIALS AND METHODS: A model of polymicrobial sepsis induced via cecal ligation and puncture (CLP) with 8- to 12-week-old albino mice was used...
January 31, 2017: Herz
https://www.readbyqxmd.com/read/28122021/the-effect-of-tacrolimus-and-mycophenolic-acid-on-cd14-monocyte-activation-and-function
#18
Nynke M Kannegieter, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Ajda T Rowshani, Pieter J M Leenen, Carla C Baan
Monocytes and macrophages play key roles in many disease states, including cellular and humoral rejection after solid organ transplantation (SOT). To suppress alloimmunity after SOT, immunosuppressive drug therapy is necessary. However, little is known about the effects of the immunosuppressive drugs tacrolimus and mycophenolic acid (MPA) on monocyte activation and function. Here, the effect of these immunosuppressants on monocytes was investigated by measuring phosphorylation of three intracellular signaling proteins which all have a major role in monocyte function: p38MAPK, ERK and Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28119235/cordycepin-inhibits-airway-remodeling-in-a-rat-model-of-chronic-asthma
#19
Xia Fei, Xue Zhang, Guo-Qing Zhang, Wu-Ping Bao, Ying-Ying Zhang, Min Zhang, Xin Zhou
The potential suppression role of cordycepin (Cor) on airway remodeling in a rat model of chronic asthma was investigated in this paper. We evaluated the anti-remodeling of Cor (50mg/kg) combined with or without budesonide (BUD) and investigated the possible underlying molecular mechanisms. We found that Cor attenuated immunoglobulin (Ig) E, alleviated the airway wall thickness, and decreased eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF). Notably, Cor reduced the up-regulation of IL-5, IL-13 and TNF-α in the BALF...
January 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28118517/the-significance-of-the-washout-period-in-preconditioning
#20
Ruduwaan Salie, Amanda Lochner, Dirk J Loubser
Exposure of the heart to 5 min global ischaemia (I) followed by 5 min reperfusion (R) (ischaemic preconditioning, IPC) or transient Beta 2-adrenergic receptor (B2-AR) stimulation with formoterol (B2PC), followed by 5 min washout before index ischaemia, elicits cardioprotection against subsequent sustained ischaemia. Since the washout period during preconditioning is essential for subsequent cardioprotection, the aim of this study was to investigate the involvement of protein kinase A (PKA), reactive oxygen species (ROS), extracellular signal-regulated kinase (ERK), PKB/Akt, p38 MAPK and c-jun N-terminal kinase (JNK) during this period...
January 24, 2017: Cardiovascular Therapeutics
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