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https://www.readbyqxmd.com/read/28449155/mitochondrial-dysfunction-in-diabetic-cardiomyopathy-effect-of-mesenchymal-stem-cell-with-ppar-%C3%AE-agonist-or-exendin-4
#1
Mohamed Abd Elaziz Wassef, Ola M Tork, Laila A Rashed, Walaa Ibrahim, Heba Morsi, Dina Mohamed Mekawy Rabie
Therapy targeting mitochondria may provide novel ways to treat diabetes and its complications. Bone marrow-derived mesenchymal stem cells (MSCs), the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists and exendin-4; an analog of glucagon-like peptide-1 have shown cardioprotective properties in many cardiac injury models. So, we evaluated their effects in diabetic cardiomyopathy (DCM) in relation to mitochondrial dysfunction. This work included seven groups of adult male albino rats: the control group, the non-treated diabetic group, and the treated diabetic groups: one group was treated with MSCs only, the second with pioglitazone only, the third with MSCs and pioglitazone, the forth with exendin-4 only and the fifth with MSCs and exendin-4...
April 27, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28449117/the-lxr-ligand-t0901317-acutely-inhibits-insulin-secretion-by-affecting-mitochondrial-metabolism
#2
Jonas Maczewsky, Jelena Sikimic, Cita Bauer, Peter Krippeit-Drews, Carmen Wolke, Uwe Lendeckel, Winfried Barthlen, Gisela Drews
The role of liver X receptor (LXR) in pancreatic beta-cell physiology and pathophysiology is still unclear. It has been postulated that chronic LXR activation in beta-cells induces lipotoxicity, a key step in the development of beta-cell dysfunction which accompanies type-2 diabetes mellitus. In most of these studies, the LXR ligand T0901317 has been administered chronically in the µmolar range to study the significance of LXR activation.In the present study, we have evaluated acute effects of T0901317 on stimulus-secretion coupling of beta-cells...
April 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28447738/telmisartan-suppresses-cardiac-hypertrophy-by-inhibiting-cardiomyocyte-apoptosis-via-the-nfat-anp-bnp-signaling-pathway
#3
Xiurong Li, Yuhuai Lan, Yan Wang, Minghao Nie, Yanhong Lu, Eryang Zhao
Telmisartan, a type of angiotensin II (Ang II) receptor inhibitor, is a common agent used to treat hypertension in the clinic. Hypertension increases cardiac afterload and promotes cardiac hypertrophy. However, the ventricular Ang II receptor may be activated in the absence of hypertension. Therefore, telmisartan may reduce cardiac hypertrophy by indirectly ameliorating hypertensive symptoms and directly inhibiting the cardiac Ang II receptor. Nuclear factor of activated T‑cells (NFAT) contributes to cardiac hypertrophy via nuclear translocation, which induces a cascade of atrial natriuretic peptide (ANP) and brain/B‑type natriuretic peptide (BNP) expression and cardiomyocyte apoptosis...
March 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447716/par1%C3%A2-mediated-c%C3%A2-jun-activation-promotes-heat-stress%C3%A2-induced-early-stage-apoptosis-of-human-umbilical-vein-endothelial-cells
#4
Shuang Zhang, Yanan Liu, Zhenglian Wang, Jingxian Liu, Zhengtao Gu, Qiulin Xu, Lei Su
Our previous study indicated that when human umbilical vein endothelial cells (HUVECs), which are involved in endothelial barrier function, are heat stressed, levels of protease‑activated receptor 1 (PAR1) are increased significantly. In the present study, it was demonstrated that PAR1 serves a vital role in heat stress‑induced HUVEC apoptosis. When the PAR1 inhibitor, SCH79797 (SCH), or a small interfering RNA (siRNA) targeting PAR1 were used to inhibit PAR1 signaling, a marked decrease in cell apoptosis, caspase‑3 activity and the expression of the pro‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) associated X (Bax), as well as increased expression of the anti‑apoptotic Bcl‑2 family member, myeloid cell leukemia 1 (Mcl‑1), were observed...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447579/glucan-phosphate-inhibits-hmgb-1-release-from-rat-myocardial-h9c2-cells-in-sepsis-via-tlr4-nf-%C3%B0%C2%BAb-signal-pathway
#5
Haizhu Wang, Zhifei Cui, Fei Sun, Huayong Ding
PURPOSE: The effect of glucan phosphate (GP) on the release of HMGB-1 from rat myocardial cells (H9C2) during lipopolysaccharide-induced sepsis, and the underlying mechanisms, were investigated. METHODS: H9C2 cells were divided into three groups: normal; lipopolysaccharide (LPS) (1 mg/ml LPS); and, LPS+GP (2 mg/ml GP). Western blot was used to determine toll-like receptor 4 (TLR4) levels, and electrophoretic mobility-shift assays (EMSA) was used to determine nuclear factor-кB (NF-кB) activity 3, 6 and 9 h after treatment...
April 26, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/28446509/inhibition-of-the-all-trans-retinoic-acid-hydroxylases-cyp26a1-and-cyp26b1-results-in-dynamic-tissue-specific-changes-in-endogenous-atra-signaling
#6
Faith Stevison, Cathryn Hogarth, Sasmita Tripathy, Travis Kent, Nina Isoherranen
all-trans-retinoic acid (atRA), the active metabolite of vitamin A, is a ligand for several nuclear receptors and acts as a critical regulator of many physiological processes. The cytochrome P450 family 26 (CYP26) enzymes are responsible for atRA clearance, and are potential drug targets to increase concentrations of endogenous atRA in a tissue-specific manner. Talarozole is a potent inhibitor of CYP26A1 and CYP26B1, and has shown some success in clinical trials. Yet, it is not known what magnitude of change is needed in tissue atRA concentrations to promote atRA signaling changes...
April 26, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28445967/lactobacillus-casei-zhang-and-vitamin-k2-prevent-intestinal-tumorigenesis-in-mice-via-adiponectin-elevated-different-signaling-pathways
#7
Yong Zhang, Chen Ma, Jie Zhao, Haiyan Xu, Qiangchuan Hou, Heping Zhang
The incidence of colon cancer has increased considerably and the intestinal microbiota participate in the development of colon cancer. We showed that the L. casei Zhang or vitamin K2 (Menaquinone-7) intervention significantly alleviated intestinal tumor burden in mice. This was associated with increased serum adiponectin levels in both treatments. But osteocalcin level was only increased by L. casei Zhang. Furthermore, the anti-carcinogenic actions of L. casei Zhang were mediated by hepatic Chloride channel-3(CLCN3)/Nuclear Factor Kappa B(NF-κB) and intestinal Claudin15/Chloride intracellular channel 4(CLIC4)/Transforming Growth Factor Beta(TGF-β) signaling, while the vitamin K2 effect involved a hepatic Vitamin D Receptor(VDR)-phosphorylated AMPK signaling pathway...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445928/regulation-of-angiogenic-behaviors-by-oxytocin-receptor-through-gli1-indcued-transcription-of-hif-1%C3%AE-in-human-umbilical-vein-endothelial-cells
#8
Ji Zhu, Huiyan Wang, Xiaoyan Zhang, Yin Xie
Angiogenesis is a dynamic hypoxia-stimulated process playing a key role in tissue growth and repair under various pathophysiological circumstances. Abnormal angiogenesis contributes to the pathogenesis of many human diseases. Oxytocin receptor is a classical G-protein-coupled receptor expressed on endothelial cells. The present study was aimed to investigate how oxytocin receptor regulated the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). We found that oxytocin at 0.1μM significantly increased cell proliferation, upregulated the mRNA and protein expression of CD31 and vWF (two important endothelial markers), and enhanced the tuber formation capacity in HUVECs...
April 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28445828/targeting-the-aryl-hydrocarbon-receptor-nuclear-translocator-complex-with-dmog-and-stemregenin-1-improves-primitive-hematopoietic-stem-cell-expansion
#9
Carlo Stephan Jackson, Chrisna Durandt, Ilse Janse van Rensburg, Vincent Praloran, Philippe Brunet de la Grange, Michael Sean Pepper
Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O2, the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR)...
April 20, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28445782/the-immunohistochemical-distribution-of-the-gabaa-receptor-%C3%AE-1-%C3%AE-2-%C3%AE-3-%C3%AE-2-3-and-%C3%AE-2-subunits-in-the-human-thalamus
#10
H J Waldvogel, M Munkle, W van Roon-Mom, H Mohler, R L M Faull
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups...
April 23, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28445727/environmental-enrichment-induces-pericyte-and-iga-dependent-wound-repair-and-lifespan-extension-in-a-colon-tumor-model
#11
Benjamin D Bice, Megan R Stephens, Stephanie J Georges, Ashlee R Venancio, Peter C Bermant, Annika V Warncke, Kajsa E Affolter, Julio R Hidalgo, Melinda L Angus-Hill
Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior, and social interactions. Using a Tcf4(Het/+)Apc(Min/+)-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4(Het/+)Apc(Min/+) males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor (NHR) signaling, both of which are common in the wound repair process...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445593/nr5a2-discovering-compounds-that-block-tumor-growth-in-pdac
#12
REVIEW
Robert Fletterick
Pancreatic cancers depend on driver molecules, oncogene proteins such as RAS. NR5A2 protein is a transcription factor and either activates or inhibits transcription through actions at hundreds of enhancers. It has unusual properties with effects appearing in multiple signaling networks. NR5A2 is a pluripotency reprogramming factor in the class nuclear receptor. Its controlling hormone is PIP3. Experiments suggest NR5A2 activation drives PDAC and inhibitors blunt cancer cell proliferation.
April 26, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28445259/the-role-of-stat3-and-ahr-in-the-differentiation-of-cd4-t-cells-into-th17-and-treg-cells
#13
Xingxing Liu, Hui Hu, Heng Fan, Dongmei Zuo, Zhexing Shou, Yi Liao, Zhen Nan, Qing Tang
BACKGROUND: This study aimed to investigate the role of aryl hydrocarbon receptor (AhR) and STAT3 gene during the differentiation of cluster of differentiation (CD)4 T cells into T helper (Th)17 and T regulatory (Treg) cells. METHODS: First, CD4 T cells were isolated from the spleen of BALB/c mice. Then, stable CD4 T cells expressing STAT3 shRNA were constructed. CD4 T cells were assigned to one of the following treatments: Th17 group: antibodies against CD3 and CD28, 2...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28445239/aldosterone-and-vascular-mineralocorticoid-receptors-in-murine-endotoxic-and-human-septic-shock
#14
Fouad Fadel, Gwennan André-Grégoire, Basile Gravez, Brigitte Bauvois, Sandrine Bouchet, Catalina Sierra-Ramos, Andrea Polito, Arnaud Mansart, Diego Alvarez de la Rosa, Djillali Annane, Frédéric Jaisser
OBJECTIVES: Vascular mineralocorticoid receptors play a role in vascular tone and blood pressure regulation, might participate in the pathophysiology of circulatory failure during sepsis, and represent a potential therapeutic target in this disease. We aimed to study the effects of mineralocorticoids and the involvement of vascular mineralocorticoid receptors in murine endotoxic and human septic shock. DESIGN: Experimental study. SETTING: Translational investigation including animal research and in vitro experiments using human vascular cells and plasma from septic patients...
April 25, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28444658/comparing-the-immune-genomic-effects-of-vilazodone-and-paroxetine-in-late-life-depression-a-pilot-study
#15
Harris Eyre, Prabha Siddarth, Natalie Cyr, Hongyu Yang, Steve Cole, Malcolm Forbes, Helen Lavretsky
Vilazodone is a novel antidepressant agent that combines selective serotonin (5-HT) reuptake inhibitor (SSRI) activity and 5-HT(1A) receptor partial agonist activity. A pilot study was conducted to compare vilazodone (novel compound) and paroxetine (gold standard) on antidepressant effects, tolerability, and inflammation and immune modulation. A 12-week, double-blind, randomized clinical trial was conducted with 56 nondemented older adults diagnosed with major depressive disorder (MDD). Between-group differences in mood, tolerability, and safety, as well as genomic markers of inflammation and immune modulation, were examined...
April 25, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28443100/-epigallocatechin-gallate-targets-notch-to-attenuate-the-inflammatory-response-in-the-immediate-early-stage-in-human-macrophages
#16
Tengfei Wang, Zemin Xiang, Ya Wang, Xi Li, Chongye Fang, Shuang Song, Chunlei Li, Haishuang Yu, Han Wang, Liang Yan, Shumei Hao, Xuanjun Wang, Jun Sheng
Inflammation plays important roles at different stages of diabetes mellitus, tumorigenesis, and cardiovascular diseases. (-)-Epigallocatechin gallate (EGCG) can attenuate inflammatory responses effectively. However, the immediate early mechanism of EGCG in inflammation remains unclear. Here, we showed that EGCG attenuated the inflammatory response in the immediate early stage of EGCG treatment by shutting off Notch signaling and that the effect did not involve the 67-kDa laminin receptor, the common receptor for EGCG...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28442630/discovering-relationships-between-nuclear-receptor-signaling-pathways-genes-and-tissues-in-transcriptomine
#17
Lauren B Becnel, Scott A Ochsner, Yolanda F Darlington, Apollo McOwiti, Wasula H Kankanamge, Michael Dehart, Alexey Naumov, Neil J McKenna
We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biology in these pathways using this tool. Transcriptomine currently contains about 45 million data points encompassing more than 2000 experiments in a reference library of nearly 550 data sets retrieved from public archives and systematically curated...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28442602/molecular-basis-of-metabolism-mediated-conversion-of-pk11195-from-an-antagonist-to-an-agonist-of-the-constitutive-androstane-receptor
#18
Bryan Mackowiak, Linhao Li, Matthew A Welch, Daochuan Li, Jace W Jones, Scott Heyward, Maureen A Kane, Peter W Swaan, Hongbing Wang
The constitutive androstane receptor (CAR) plays an important role in xenobiotic metabolism, energy homeostasis, and cell proliferation. Antagonism of CAR represents a key strategy for studying its function and may have potential clinical applications. However, specific human CAR (hCAR) antagonists are limited and conflicting data on the activity of these compounds have been reported. PK11195, a typical peripheral benzodiazepine receptor ligand, has been established as a potent hCAR deactivator in immortalized cells; whether it inhibits hCAR activity under physiologically-relevant conditions remains unclear...
April 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28442574/the-r753q-polymorphism-in-toll-like-receptor-2-tlr2-attenuates-innate-immune-responses-to-mycobacteria-and-impairs-myd88-adapter-recruitment-to-tlr2
#19
Goutham Pattabiraman, Rahul Panchal, Andrei E Medvedev
Toll-like receptor (TLR) 2 plays a critical role in host defenses against mycobacterial infections. The Arg753Gln (R753Q) TLR2 polymorphism has been associated with increased incidence of tuberculosis and infections with non-tuberculous mycobacteria in human populations, but the mechanisms by which this polymorphism affects TLR2 signaling are unclear. In this study, we determined the impact of the R753Q TLR2 polymorphism on macrophage sensing of Mycobacterium smegmatis. Upon infection with M. smegmatis, macrophages from knock-in (KI) mice harboring R753Q TLR2 expressed lower levels of TNF-α, IL-1β, IL-6 and IL-10 compared to cells from wild-type (WT) mice but both R753Q TLR2 and WT mice exhibited comparable bacterial burdens...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28442041/cytokine-gene-expression-at-the-maternal-fetal-interface-after-somatic-cell-nuclear-transfer-pregnancies-in-small-ruminants
#20
Heloisa M Rutigliano, Amanda Wilhelm, Justin Hall, Bi Shi, Qinggang Meng, Rusty Stott, Thomas D Bunch, Kenneth L White, Christopher J Davies, Irina A Polejaeva
The present retrospective study investigated pregnancy rates, the incidence of pregnancy loss and large offspring syndrome (LOS) and immune-related gene expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We hypothesised that significantly higher pregnancy losses observed in sheep compared with goat SCNT pregnancies are due to the increased amounts of T-helper 1 cytokines and proinflammatory mediators at the maternal-fetal interface. Sheep and goat SCNT pregnancies were generated using the same procedure...
April 2017: Reproduction, Fertility, and Development
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