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https://www.readbyqxmd.com/read/29155261/the-phosphodiesterase-4-inhibitor-fcpr16-attenuates-ischemia-reperfusion-injury-in-rats-subjected-to-middle-cerebral-artery-occlusion-and-reperfusion
#1
Jiajia Chen, Hui Yu, Jiahong Zhong, Hongfang Feng, Haitao Wang, Yufang Cheng, Zhengqiang Zou, Chang Huang, Zhongzhen Zhou, Wenhua Zheng, Jiangping Xu
Current phosphodiesterase-4 (PDE4) inhibitors exert beneficial effects in central nervous system diseases via anti-inflammatory and anti-apoptotic properties, but many of them are plagued by side effects like nausea and emesis. FCPR16, a novel PDE4 inhibitor synthesized in our lab, has potential anti-inflammatory property. In the present study, we aimed to investigate the effects of FCPR16 in a rat model of ischemic stroke and evaluate its emetogenic potential. Our results showed that FCPR16 treatment improved neurological function, reduced cerebral infarct volume, and attenuated brain histological changes in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R)...
November 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#2
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#3
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29146239/innately-activated-tlr4-signal-in-the-nucleus-accumbens-is-sustained-by-crf-amplification-loop-and-regulates-impulsivity
#4
Irina Balan, Kaitlin T Warnock, Adam Puche, Marjorie C Gondre-Lewis, Laure Aurelian
Cognitive impulsivity is a heritable trait believed to represent the behavior that defines the volition to initiate alcohol drinking. We have previously shown that a neuronal Toll-like receptor 4 (TLR4) signal located in the central amygdala (CeA) and ventral tegmental area (VTA) controls the initiation of binge drinking in alcohol-preferring P rats, and TLR4 expression is upregulated by alcohol-induced corticotropin-releasing factor (CRF) at these sites. However, the function of the TLR4 signal in the nucleus accumbens shell (NAc-shell), a site implicated in the control of reward, drug-seeking behavior and impulsivity and the contribution of other signal-associated genes, are still poorly understood...
November 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29145650/loss-of-p300-and-cbp-disrupts-histone-acetylation-at-the-mouse-sry-promoter-and-causes-xy-gonadal-sex-reversal
#5
Gwenn-Aël Carré, Pam Siggers, Marilena Xipolita, Paul Brindle, Beat Lutz, Sara Wells, Andy Greenfield
CREB-binding protein (CBP, CREBBP, KAT3A) and its closely related paralogue p300 (EP300, KAT3B), together termed p300/CBP, are histone/lysine acetyl-transferases that control gene expression by modifying chromatin-associated proteins. Here, we report roles for both of these chromatin-modifying enzymes in mouse sex determination, the process by which the embryonic gonad develops into a testis or an ovary. By targeting gene ablation to embryonic gonadal somatic cells using an inducible Cre line, we show that gonads lacking either gene exhibit major abnormalities of XY gonad development at 14...
November 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#6
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29141249/%C3%AE-catenin-cooperates-with-creb-binding-protein-to-promote-the-growth-of-tumor-cells
#7
Wendan Yu, Liren Li, Fufu Zheng, Wenjing Yang, Shilei Zhao, Chunfang Tian, Wenwen Yin, Yiming Chen, Wei Guo, Lijuan Zou, Wuguo Deng
BACKGROUND/AIMS: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. METHODS: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays...
November 15, 2017: Cellular Physiology and 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
#8
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/29137290/expression-of-protein-kinase-a-and-the-kappa-opioid-receptor-in-selected-brain-regions-and-conditioned-place-aversion-in-morphine-dependent-rats
#9
Xiuhua Song, Wenqiang Li, Yuzhong Shi, Jingdan Zhang, Yi Li
This study examined adaptive changes in protein kinase A (PKA) and kappa opioid receptor (KOR) in selected addiction-related brain regions before and after conditioned place aversion (CPA). Seventy-two male SD rats were randomly assigned to an experimental group (morphine + naloxone, "MN") and 2 control groups: MS (morphine + saline) and SN (saline + naloxone). MN rats were intraperitoneally injected with morphine twice per day for 6.5 days and naloxone once and trained to establish CPA model. MS and SN rats were injected with equivalent volumes of morphine plus saline and saline plus naloxone, respectively...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132537/nfil3-is-a-negative-regulator-of-hepatic-gluconeogenesis
#10
Geon Kang, Hye-Sook Han, Seung-Hoi Koo
OBJECTIVE: Nuclear factor interleukin-3 regulated (NFIL3) has been known as an important transcriptional regulator of the development and the differentiation of immune cells. Although expression of NFIL3 is regulated by nutritional cues in the liver, the role of NFIL3 in the glucose metabolism has not been extensively studied. Thus, we wanted to explore the potential role of NFIL3 in the control of hepatic glucose metabolism. MATERIALS/METHODS: Mouse primary hepatocytes were cultured to perform western blot analysis, Q-PCR and chromatin immunoprecipitation assay...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29131133/sulphonated-formononetin-induces-angiogenesis-through-vascular-endothelial-growth-factor-camp-response-element-binding-protein-early-growth-response-3-vascular-cell-adhesion-molecule-1-and-wnt-%C3%AE-catenin-signaling-pathway
#11
Zhaoju Dong, Yanan Shi, Huijuan Zhao, Ning Li, Liang Ye, Shuping Zhang, Haibo Zhu
BACKGROUND: Sodium formononetin-3'-sulphonate (Sul-F) is a derivative of the isoflavone formononetin. In this study, we investigated whether Sul-F can regulate angiogenesis and the potential mechanism in vitro. METHODS: We examined the effects of Sul-F on cell proliferation, cell invasion, and tube formation in the human umbilical vein endothelial cell line (HUVEC). To better understand the mechanism involved, we investigated effects of the following compounds: cAMP response element-binding protein (CREB) inhibitor 2-naphthol-AS-E-phosphate (KG-501), early growth response 3 (Egr-3) siRNA, vascular endothelial growth factor (VEGF) antagonist soluble VEGF receptor 1 (sFlt-1), VEGF receptor 2 blocker SU-1498, Wnt5a antagonist WIF-1 recombinant protein (WIF-1), and inhibitor of Wnt/β-catenin recombinant Dickkopf-1 protein (DKK-1)...
October 31, 2017: Pharmacology
https://www.readbyqxmd.com/read/29129697/dual-mechanisms-for-balancing-th17-and-treg-cell-fate-by-creb
#12
Antony Symons, Wenjun Ouyang
Th17 cells, which express the cytokine IL-17A, and master regulator RORγt, are important in the inflammatory response to fungal and bacterial pathogens, but also have a pathogenic role in many inflammatory disorders. In contrast, regulatory T cells (Treg), expressing the Foxp3 transcription factor, have a suppressive function and can dampen an immune response. The appropriate balance of these distinct effector functions is critical for an effective immune response and autoimmunity can arise if this process goes awry...
November 2017: EBioMedicine
https://www.readbyqxmd.com/read/29129208/augmented-gene-expression-triggered-by-na-k-atpase-inhibition-role-of-ca-2-i-mediated-and-independent-excitation-transcription-coupling
#13
Larisa V Smolyaninova, Svetlana V Koltsova, Svetlana V Sidorenko, Sergei N Orlov
In rat vascular smooth muscle cells (RVSMC), 3-h Na(+),K(+)-ATPase inhibition by ouabain or in K(+)-free medium resulted in the inversion of the [Na(+)]i/[K(+)]i ratio and elevation up to 7-fold the content of Egr1, Atf3, Nr4a1 and Ptgs2 mRNAs. Ouabain increased the rate of 45Ca(2+) influx by 2-fold that was abolished by L-type voltage-gated Ca(2+) channel blocker nicardipine, but it was resistant to Na(+)/Ca(2+) exchanger inhibitor KB-R7943. To study the role of Ca(2+)-mediated signaling in the expression of Na(+)i/K(+)i-sensitive genes we used intracellular Ca(2+) chelator BAPTA and incubated RVSMC in Ca(2+)-free medium...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29127035/the-high-production-volume-fungicide-pyraclostrobin-induces-triglyceride-accumulation-associated-with-mitochondrial-dysfunction-and-promotes-adipocyte-differentiation-independent-of-ppar%C3%AE-activation-in-3t3-l1-cells
#14
Anthony L Luz, Christopher D Kassotis, Heather M Stapleton, Joel N Meyer
Pyraclostrobin is one of the most heavily used fungicides, and has been detected on a variety of produce, suggesting human exposure occurs regularly. Recently, pyraclostrobin exposure has been linked to a variety of toxic effects, including neurodegeneration and triglyceride (TG) accumulation. As pyraclostrobin inhibits electron transport chain complex III, and as mitochondrial dysfunction is associated with metabolic syndrome (cardiovascular disease, type II diabetes, obesity), we designed experiments to test the hypothesis that mitochondrial dysfunction underlies its adipogenic activity...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29126931/phytochemical-allylguaiacol-exerts-a-neuroprotective-effect-on-hippocampal-cells-and-ameliorates-scopolamine-induced-memory-impairment-in-mice
#15
Hye-Sun Lim, Bu-Yeo Kim, Yu Jin Kim, Soo-Jin Jeong
Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H2O2)-treated HT22 hippocampal cells...
November 7, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29125684/magnesium-boosts-the-memory-restorative-effect-of-environmental-enrichment-in-alzheimer-s-disease-mice
#16
Ying Huang, Xian Huang, Ling Zhang, Fang Han, Ke-Liang Pang, Xue Li, Jian-Ying Shen
BACKGROUND: Environmental enrichment (EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease (AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and AD mice. AIM: To study the additive therapeutic effect of EE combined with MgT (EM) and the potential mechanism underlying the effects. MATERIALS AND METHODS: APP/PS1 mice were treated with EE, MgT, or combination of EE and MgT (EM) and compared for restored memory function...
November 10, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29121799/pueraria-lobate-inhibits-rankl-mediated-osteoclastogenesis-via-downregulation-of-creb-pgc1%C3%AE-c-fos-nfatc1-signaling
#17
Keun Ha Park, Dong Ryun Gu, Su Hyun Jin, Chi-Su Yoon, Wonmin Ko, Youn Chul Kim, Seoung Hoon Lee
Puerariae radix, the dried root of Pueraria lobate Ohwi, is known to prevent bone loss in ovariectomized mice; however, the precise molecular mechanisms are not understood. In this study, we investigated the effects and underlying mechanisms of action of Puerariae radix extract (PRE) on receptor activator of NF-[Formula: see text]B ligand (RANKL)-induced osteoclastogenesis. PRE dose-dependently inhibited osteoclast differentiation and formation, decreased the bone-resorbing activity of osteoclasts, and downregulated the expression of osteoclast differentiation marker genes...
November 9, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29121798/angelica-sinensis-exerts-angiogenic-and-anti-apoptotic-effects-against-cerebral-ischemia-reperfusion-injury-by-activating-p38mapk-hif-1-formula-see-text-vegf-a-signaling-in-rats
#18
Chin-Yi Cheng, Tin-Yun Ho, Chien-Yun Hsiang, Nou-Ying Tang, Ching-Liang Hsieh, Shung-Te Kao, Yu-Chen Lee
This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia...
November 9, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29118262/stress-hormones-promote-egfr-inhibitor-resistance-in-nsclc-implications-for-combinations-with-%C3%AE-blockers
#19
Monique B Nilsson, Huiying Sun, Lixia Diao, Pan Tong, Diane Liu, Lerong Li, Youhong Fan, Alissa Poteete, Seung-Oe Lim, Kathryn Howells, Vincent Haddad, Daniel Gomez, Hai Tran, Guillermo Armaiz Pena, Lecia V Sequist, James C Yang, Jing Wang, Edward S Kim, Roy Herbst, J Jack Lee, Waun Ki Hong, Ignacio Wistuba, Mien-Chie Hung, Anil K Sood, John V Heymach
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance mediated by T790M-independent mechanisms remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). We identified a targetable mechanism of EGFR inhibitor resistance whereby stress hormones activate β2-adrenergic receptors (β2-ARs) on NSCLC cells, which cooperatively signal with mutant EGFR, resulting in the inactivation of the tumor suppressor, liver kinase B1 (LKB1), and subsequently induce interleukin-6 (IL-6) expression...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29118086/creb-crtc2-controls-glp-1-dependent-regulation-of-glucose-homeostasis
#20
Ji-Hyun Lee, Xianlan Wen, Hana Cho, Seung-Hoi Koo
Glucagon-like peptide 1 (GLP-1) is a major incretin that controls glucose homeostasis. The secretion of mature GLP-1 is regulated via GPCRs, including bile acid receptor G protein-coupled bile acid receptor 1, which uses cAMP signaling to enhance the exocytosis of GLP-1-containing vesicles. However, the role of cAMP-mediated transcription has not been clearly demonstrated to date. In this study, we explored the role of cAMP response element-binding protein/CREB-regulated transcription coactivator 2 (CREB/CRTC2)-dependent transcription on GLP-1 secretion in the L cells...
November 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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