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https://www.readbyqxmd.com/read/28548935/hdac4-stimulates-mrtf-a-expression-and-drives-fibrogenesis-in-hepatic-stellate-cells-by-targeting-mir-206
#1
Xinrui Han, Chenzhi Hao, Luyang Li, Jianfei Li, Mingming Fang, Yuanlin Zheng, Jun Lu, Ping Li, Yong Xu
Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrogenesis. We have previously shown that the transcriptional modulator MRTF-A contributes to liver fibrosis by programming epigenetic activation of HSCs. In the present study we investigated the mechanism whereby MRTF-A expression is regulated in this process. We report here that MRTF-A protein levels, but not mRNA levels, were up-regulated in vivo in the livers of mice induced to develop hepatic fibrosis. Pro-fibrogenic stimuli (TGF-β and PDGF-BB) also activated MRTF-A expression post-transcriptionally in vitro in cultured HSCs...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28547848/effect-of-ceramic-calcium-phosphorus-ratio-on-chondrocyte-mediated-biosynthesis-and-mineralization
#2
Margaret K Boushell, Nora T Khanarian, Raquel Z LeGeros, Helen H Lu
The osteochondral interface functions as a structural barrier between cartilage and bone, maintaining tissue integrity post injury and during homeostasis. Regeneration of this calcified cartilage region is thus essential for integrative cartilage healing, and hydrogel-ceramic composite scaffolds have been explored for calcified cartilage formation. The objective of this study is to test the hypothesis that Ca/P ratio of the ceramic phase of the composite scaffold regulates chondrocyte biosynthesis and mineralization potential...
May 25, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28547295/high-loading-dose-of-microencapsulated-gliclazide-formulation-exerted-a-hypoglycaemic-effect-on-type-1-diabetic-rats-and-incorporation-of-a-primary-deconjugated-bile-acid-diminished-the-hypoglycaemic-antidiabetic-effect
#3
Svetlana Golocorbin-Kon, Jelena Calasan, Boris Milijasevic, Sasa Vukmirovic, Mladena Lalic-Popovic, Momir Mikov, Hani Al-Salami
BACKGROUND AND OBJECTIVE: Gliclazide is a drug commonly used in type 2 diabetes mellitus. Recently, gliclazide has shown desirable pharmacological effects such as immunoregulatory and anti-clotting effects, which suggests potential applications in type 1 diabetes mellitus (T1DM). Gliclazide has variable absorption after oral administration, and thus using targeted-delivery techniques, such as microencapsulation, may optimise gliclazide absorption and potential applications in T1DM. Bile acids such as cholic acid have shown microcapsule-stabilising and controlled-release effects, and thus their incorporation into gliclazide microcapsules may further optimise gliclazide release, absorption and antidiabetic effects...
May 25, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28546552/melatonin-mediated-mitophagy-protects-against-early-brain-injury-after-subarachnoid-hemorrhage-through-inhibition-of-nlrp3-inflammasome-activation
#4
Shenglong Cao, Sudeep Shrestha, Jianru Li, Xiaobo Yu, Jingyin Chen, Feng Yan, Guangyu Ying, Chi Gu, Lin Wang, Gao Chen
The NLRP3 inflammasome is activated in the early period following subarachnoid hemorrhage(SAH), resulting in inflammatory responses. Recent studies have shown that activation of NLRP3 inflammasome is suppressed by autophagy, but the potential mechanism is unclear. In this study, we examined whether mitophagy was involved in the beneficial effect of melatonin and its relationship with NLRP3 inflammasome activation after SAH. In total, 130 adult-male SD rats were randomly divided into four groups: sham group, SAH + vehicle group, SAH + melatonin group, and SAH + 3-methyladenine (3-MA) + melatonin group...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546026/the-crustin-like-peptide-plays-opposite-role-in-shrimp-immune-response-to-vibrio-alginolyticus-and-white-spot-syndrome-virus-wssv-infection
#5
Baozhen Sun, Zhi Wang, Fei Zhu
Crustin is an antimicrobial peptide (AMP) that plays a key role in innate immunity of crustaceans. In this study, we cloned the entire 660 bp crustin-like sequence with a 507 bp open reading frame encoding a 168 amino acid from Marsupenaeus japonicus. The crustin-like gene was primarily expressed in gills and over-expressed in shrimp hemocytes after challenge with WSSV or Vibrio alginolyticus. After knockdown crustin-like gene using specific double-stranded RNA (CRU-dsRNA), IMD, Rab7, L-lectin, mitogen-activated protein kinase, p53, prophenoloxidase and Rho were down-regulated and nitric oxide synthase, myosin and tumor necrosis factor-α were up-regulated in hemocytes at 24 h post dsRNA treatment...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28545202/memantine-inhibits-degradation-of-the-articular-cartilage-extracellular-matrix-induced-by-advanced-glycation-end-products-ages
#6
Jijun Zhao, Yinghao Yu, Zhaofeng Wu, Ling Wang, Wei Li
The accumulation of inflammation and cartilage damage induced by advanced glycation end products (AGEs) are important hallmarks of osteoarthritis (OA). Memantine is a clinically licensed drug used for the treatment of moderate and severe Alzheimer's disease. To date, little information has been reported regarding the effects of memantine on cartilage destruction. In this study, we investigated the protective effects of memantine on AGE-induced degradation of collagen II and aggrecans in human SW1353 chondrocytes...
May 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28545138/sumo-4-a-novel-functional-candidate-in-the-human-placental-protein-sumoylation-machinery
#7
Dora Baczyk, Melanie C Audette, Sascha Drewlo, Khrystyna Levytska, John C Kingdom
BACKGROUND: Small ubiquitin-like modifiers (SUMOs) conjugate to proteins post-translationally, thereby affecting target localization, activity and stability. Functional SUMO family members identified in the human placenta include SUMO-1 to SUMO-3, which are elevated in pre-eclampsia. Whether the fourth isoform, SUMO-4, plays a role in placental development and function remains unknown. OBJECTIVES: We tested the hypothesis that SUMO-4 is expressed in the human placenta and demonstrates altered SUMOylation in pre-eclamptic pregnancies...
2017: PloS One
https://www.readbyqxmd.com/read/28545005/the-efficacy-of-trauma-management-therapy-a-controlled-pilot-investigation-of-a-three-week-intensive-outpatient-program-for-combat-related-ptsd
#8
Deborah C Beidel, B Christopher Frueh, Sandra M Neer, Carl W Lejuez
Despite the 8-18.5% of returning Operation Iraqi Freedom (OIF), Operation Enduring Freedom (OEF) and Operation New Dawn (OND) veterans who are suffering from posttraumatic stress disorder (PTSD), few receive empirically supported treatments. Among those that do, the dropout rate is high and more than 50% retain their diagnosis after treatment. This study evaluated the efficacy of Trauma Management Therapy (TMT), delivered in a 3-week intensive outpatient (IOP) format. TMT combines virtual-reality augmented individual exposure therapy with a group intervention to address social isolation, anger, and depression...
May 11, 2017: Journal of Anxiety Disorders
https://www.readbyqxmd.com/read/28544504/the-impact-of-telephone-delivered-cognitive-behaviour-therapy-and-befriending-on-mood-disorders-in-people-with-chronic-obstructive-pulmonary-disease-a-randomized-controlled-trial
#9
Colleen Doyle, Sunil Bhar, Marcia Fearn, David Ames, Debra Osborne, Emily You, Alex Gorelik, David Dunt
OBJECTIVES: The main objectives of this pragmatic randomized controlled trial were to investigate the impact of cognitive behaviour therapy (CBT) and an active social control (befriending) on depression and anxiety symptoms in people with chronic obstructive pulmonary disease (COPD). METHODS: Eligible participants were randomly allocated to receive eight weekly telephone interventions of CBT (n = 54) or befriending (n = 56). Repeated-measures ANOVA was used to assess changes in scores and Cohen's d was used to assess effect sizes...
May 22, 2017: British Journal of Health Psychology
https://www.readbyqxmd.com/read/28544332/fibroblast-growth-factor-2-protects-against-renal-ischaemia-reperfusion-injury-by-attenuating-mitochondrial-damage-and-proinflammatory-signalling
#10
Xiao-Hua Tan, Xiao-Meng Zheng, Li-Xia Yu, Jian He, Hong-Mei Zhu, Xiu-Ping Ge, Xiao-Li Ren, Fa-Qing Ye, Saverio Bellusci, Jian Xiao, Xiao-Kun Li, Jin-San Zhang
Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28544272/ensemble-variant-interpretation-methods-to-predict-enzyme-activity-and-assign-pathogenicity-in-the-cagi4-naglu-human-n-acetyl-glucosaminidase-and-ube2i-human-sumo-ligase-challenges
#11
Yizhou Yin, Kunal Kundu, Lipika R Pal, John Moult
CAGI (Critical Assessment of Genome Interpretation) conducts community experiments to determine the state of the art in relating genotype to phenotype. Here we report results obtained using newly-developed ensemble methods to address two CAGI4 challenges: enzyme activity for population missense variants found in NAGLU (Human N-acetyl-glucosaminidase) and random missense mutations in Human UBE2I (Human SUMO E2 ligase), assayed in a high throughput competitive yeast complementation procedure. The ensemble methods are effective, ranked 2(nd) for SUMO-ligase and 3(rd) for NAGLU, according to the CAGI independent assessors...
May 24, 2017: Human Mutation
https://www.readbyqxmd.com/read/28543747/oxazolo-4-5-b-pyridine-based-piperazinamides-as-gsk-3%C3%AE-inhibitors-with-potential-for-attenuating-inflammation-and-suppression-of-pro-inflammatory-mediators
#12
Mushtaq A Tantray, Imran Khan, Hinna Hamid, Mohammad Sarwar Alam, Abhijeet Dhulap, Ajaz Ahmad Ganai
Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was synthesized and evaluated for in vitro GSK-3β inhibitory and in vivo anti-inflammatory activity. The compounds 7d, 7e, 7g, and 7c displayed the best GSK-3β inhibitory activity among all the synthesized compounds, with corresponding IC50 values of 0.34, 0...
May 22, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28542502/in-vivo-transduction-of-neurons-with-tat-uch-l1-protects-brain-against-controlled-cortical-impact-injury
#13
Hao Liu, Marie E Rose, Xiecheng Ma, Sherman Culver, C Edward Dixon, Steven H Graham
Many mechanisms or pathways are involved in secondary post-traumatic brain injury, such as the ubiquitin-proteasome pathway (UPP), axonal degeneration and neuronal cell apoptosis. UCH-L1 is a protein that is expressed in high levels in neurons and may have important roles in the UPP, autophagy and axonal integrity. The current study aims to evaluate the role of UCH-L1 in post-traumatic brain injury (TBI) and its potential therapeutic effects. A novel protein was constructed that fused the protein transduction domain (PTD) of trans-activating transduction (TAT) protein with UCH-L1 (TAT-UCH-L1) in order to promote neuronal transduction...
2017: PloS One
https://www.readbyqxmd.com/read/28542479/preliminary-study-of-hypoxia-related-cardiovascular-mediator-markers-in-patients-with-end-stage-renal-disease-with-and-without-diabetes-and-the-effects-of-haemodialysis
#14
A Treweeke, J Hall, S Lambie, S J Leslie, I L Megson, S M MacRury
BACKGROUND: Evidence points to activation of pro-inflammatory and pro-thrombotic stimuli during the haemodialysis process in end-stage renal disease (ESRD) with potential to predispose to cardiovascular events. Diabetes is associated with a higher incidence of cardiovascular disease in haemodialysis patients. We tested the hypothesis that a range of mediators and markers that modulate cardiovascular risk are elevated in haemodialysis patients with diabetes compared to those without. METHODS: Men and women with diabetes (n = 6) and without diabetes (n = 6) aged 18-90 years receiving haemodialysis were recruited...
2017: PloS One
https://www.readbyqxmd.com/read/28542320/the-ik1-kir2-1-channel-agonist-zacopride-prevents-and-cures-acute-ischemic-arrhythmias-in-the-rat
#15
Xu-Wen Zhai, Li Zhang, Yun-Fei Guo, Ying Yang, Dong-Ming Wang, Yan Zhang, Pan Li, Yi-Fan Niu, Qi-Long Feng, Bo-Wei Wu, Ji-Min Cao, Qing-Hua Liu
Arrhythmogenesis in acute myocardial infarction (MI) is associated with depolarization of resting membraine potential (RMP) and decrease of inward rectifier potassium current (IK1) in cardiomyocytes. However, clinical anti-arrhythmic agents that primarily act on RMP by enhancing the IK1 channel are not currently available. We hypothesized that zacopride, a selective and moderate agonist of the IK1/Kir2.1 channels, prevents and cures acute ischemic arrhythmias. To test this viewpoint, adult Sprague-Dawley (SD) rats were subjected to MI by ligating the left main coronary artery...
2017: PloS One
https://www.readbyqxmd.com/read/28542129/adar1-mediated-3-utr-editing-and-expression-control-of-antiapoptosis-genes-fine-tunes-cellular-apoptosis-response
#16
Chang-Ching Yang, Yi-Tung Chen, Yi-Feng Chang, Hsuan Liu, Yu-Ping Kuo, Chieh-Tien Shih, Wei-Chao Liao, Hui-Wen Chen, Wen-Sy Tsai, Bertrand Chin-Ming Tan
Adenosine-to-inosine RNA editing constitutes a crucial component of the cellular transcriptome and critically underpins organism survival and development. While recent high-throughput approaches have provided comprehensive documentation of the RNA editome, its functional output remains mostly unresolved, particularly for events in the non-coding regions. Gene ontology analysis of the known RNA editing targets unveiled a preponderance of genes related to apoptosis regulation, among which proto-oncogenes XIAP and MDM2 encode two the most abundantly edited transcripts...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28542026/combination-drug-therapy-of-pioglitazone-and-d-cycloserine-attenuates-chronic-orofacial-neuropathic-pain-and-anxiety-by-improving-mitochondrial-function-following-trigeminal-nerve-injury
#17
Danielle N Lyons, Liping Zhang, Jignesh D Pandya, Robert J Danaher, Fei Ma, Craig S Miller, Patrick G Sullivan, Cristian Sirbu, Karin N Westlund
OBJECTIVES: The study aim was to determine how peripheral trigeminal nerve injury affects mitochondrial respiration and to test efficacy of combined treatment with two FDA approved drugs with potential for improving mitochondrial bioenergetics, pain and anxiety related behaviors in a chronic orofacial neuropathic pain mouse model. METHODS: Efficacy of (R)-(+)-4-amino-3-isoxazolidinone (D-cycloserine, DCS), an NMDA antagonist/agonist, and Pioglitazone (PIO), a selective agonist of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was investigate in the trigeminal inflammatory compression (TIC) neuropathic nerve injury mouse model...
May 24, 2017: Clinical Journal of Pain
https://www.readbyqxmd.com/read/28539821/stabilization-of-4e-bp1-by-pi3k-kinase-and-its-involvement-in-chk2-phosphorylation-in-the-cellular-response-to-radiation
#18
Zi-Jian Yu, Hui-Hui Luo, Zeng-Fu Shang, Hua Guan, Bei-Bei Xiao, Xiao-Dan Liu, Yu Wang, Bo Huang, Ping-Kun Zhou
Objectives: 4E-BP1 is a family member of eIF4E binding proteins (4E-BPs) which act as the suppressors of cap-dependent translation of RNA via competitively associating with cap-bound eIF4E. RNA translation regulation is an important manner to control the cellular responses to a series of stress conditions such as ionizing radiation (IR)-induced DNA damage response and cell cycle controlling. This study aimed to determine the mechanism of 4E-BP1 stabilization and its potential downstream target(s) in the response to IR...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539438/discovery-of-a-prefusion-rsv-f-specific-monoclonal-antibody-that-provides-greater-in-vivo-protection-than-the-murine-precursor-of-palivizumab
#19
Min Zhao, Zi-Zheng Zheng, Man Chen, Kayvon Modjarrad, Wei Zhang, Lu-Ting Zhan, Jian-Li Cao, Yong-Peng Sun, Jason S McLellan, Barney S Graham, Ning-Shao Xia
Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the RSV F glycoprotein, is the only prophylactic agent approved for RSV. However, its relatively low neutralizing potency and high cost has limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F trimer...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28538984/accuracy-of-medical-claims-for-identifying-cardiovascular-and-bleeding-events-after-myocardial-infarction-a-secondary-analysis-of-the-translate-acs-study
#20
Patricia O Guimarães, Arun Krishnamoorthy, Lisa A Kaltenbach, Kevin J Anstrom, Mark B Effron, Daniel B Mark, Patrick L McCollam, Linda Davidson-Ray, Eric D Peterson, Tracy Y Wang
Importance: Pragmatic clinical trial designs have proposed the use of medical claims data to ascertain clinical events; however, the accuracy of billed diagnoses in identifying potential events is unclear. Objectives: To compare the 1-year cumulative incidences of events when events were identified by medical claims vs by physician adjudication and to assess the accuracy of bill-identified events using physician adjudication as the criterion standard. Design, Setting, and Participants: This post hoc analysis of a clinical trial assessed the medical claims forms and records for all rehospitalizations at 233 US hospitals within 1 year of the index acute myocardial infarction (MI) of 12 365 patients enrolled in the Treatment With Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study between April 1, 2010, and October 31, 2012...
May 24, 2017: JAMA Cardiology
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