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https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#1
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29158052/baicalin-attenuates-non-alcoholic-steatohepatitis-by-suppressing-key-regulators-of-lipid-metabolism-inflammation-and-fibrosis-in-mice
#2
Junli Zhang, Haiming Zhang, Xiaoling Deng, Ning Zhang, Beibei Liu, Shengliang Xin, Guixin Li, Keshu Xu
AIMS: Baicalin (BA), an active flavonoid compound originating from the herb of Scutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis. MAIN METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4weeks...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29155314/mesenchymal-stromal-cell-irradiation-interferes-with-the-adipogenic-osteogenic-differentiation-balance-improving-their-hematopoietic-supporting-ability
#3
Silvia Preciado, Sandra Muntión, Ana Rico, Luis A Pérez Romasanta, Teresa L Ramos, Rebeca Ortega, Javier Borrajo, Luis A Corchete, Concepción Rodríguez, María Díez-Campelo, Luis I Sánchez-Abarca, María-Consuelo Del Cañizo, Fermín Sánchez-Guijo
Bone marrow-mesenchymal stromal cells are precursors of adipocytes and osteoblasts and key regulators of hematopoiesis. Irradiation is widely used in conditioning regimens. Despite mesenchymal stromal cells are radio-resistant, the effects of low-dose irradiation on their behavior have not been extensively explored. Our aim was to evaluate the effect of 2.5 Gy on mesenchymal stromal cells. Cells from 25 healthy donors were either irradiated or not (the latter were used as controls). Cells were characterized following ISCT criteria, including in vitro differentiation assays...
November 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29154388/systematic-review-of-the-effect-of-denosumab-on-children-with-osteogenesis-imperfect-showed-inconsistent-findings
#4
Guowei Li, Yanling Jin, Mitchell A H Levine, Heike Hoyer-Kuhn, Leanne Ward, Jonathan D Adachi
Osteogenesis imperfecta (OI) is a rare, inherited disorder characterised by increased bone fragility, reduced bone mass and often short stature. Most cases are due to mutations in one of the two genes encoding collagen type-1 - COL1A1 and COL1A2 (1) - and the signs and symptoms vary substantially with the disease severity. The risk of fractures is 100 times higher than the general population, even in patients with mild OI. Bisphosphonates are the current standard pharmacotherapy for managing and treating patients with severe OI, but concerns about their long-term safety have been raised (1)...
November 20, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/29152605/hepatic-natural-killer-t-cell-and-cd8-t-cell-signatures-in-mice-with-nonalcoholic-steatohepatitis
#5
Jashdeep Bhattacharjee, Michelle Kirby, Samir Softic, Lili Miles, Rosa-Maria Salazar-Gonzalez, Pranav Shivakumar, Rohit Kohli
Hepatic inflammation is a key pathological feature of Nonalcoholic Steatohepatitis (NASH). Natural Killer T-cells (NKT) and CD8+ T-cells are known to play an important role in obesity related adipose tissue inflammation. We hypothesized that these same inflammatory phenotypes would be present in progressive NASH. We used a previously established high fat high carbohydrate (HFHC) murine obesogenic diet model of progressive NASH to investigate the role of NKT cells and CD8+ T-cells in C57Bl6/J mice. Further, to better understand the impact of these cell populations; CD1d-deficient and CD8+ T-cell depleted mice were subjected to HFHC diet for 16 weeks...
June 2017: Hepatol Commun
https://www.readbyqxmd.com/read/29152129/protective-effect-of-dehydroandrographolide-on-obstructive-cholestasis-in-bile-duct-ligated-mice
#6
Zhiyong Weng, Xuefeng Liu, Jiehua Hu, Jingzhou Mu, Jing Xie, Chenjuan Yao, Lihua Li
Background: Dehydroandrographolide (DA) is the main contributor to the therapeutic properties of the medicinal plant Andrographis paniculata (AP). However, it is unknown whether DA has a hepatoprotective effect on obstructive cholestasis in mice and humans. Methods: We administered DA to mice for 5 days prior to bile duct ligation (BDL) and for the 7 days. Liver function markers, liver histology and necrosis, compensatory responses of hepatocytes, liver fibrosis and the expression of hepatic fibrogenesis markers were evaluated in BDL mice and/or human LX-2 cells...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150909/genetic-analysis-of-osteogenesis-imperfecta-in-the-palestinian-population-molecular-screening-of-49-affected-families
#7
Osama Essawi, Sofie Symoens, Maha Fannana, Mohammad Darwish, Mohammad Farraj, Andy Willaert, Tamer Essawi, Bert Callewaert, Anne De Paepe, Fransiska Malfait, Paul J Coucke
BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous hereditary connective tissue disorder clinically hallmarked by increased susceptibility to bone fractures. METHODS: We analyzed a cohort of 77 diagnosed OI patients from 49 unrelated Palestinian families. Next-generation sequencing technology was used to screen a panel of known OI genes. RESULTS: In 41 probands, we identified 28 different disease-causing variants of 9 different known OI genes...
November 18, 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29146302/mechanisms-involved-in-bone-resorption-regulated-by-vitamin-d
#8
REVIEW
Yuko Nakamichi, Nobuyuki Udagawa, Tatsuo Suda, Naoyuki Takahashi
Active forms of vitamin D enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblast-lineage cells consisting of osteoblasts and osteocytes. This pro-resorptive activity was evident basically with higher concentrations of active vitamin D than those expected in physiological conditions. Nevertheless, vitamin D compounds have been used in Japan for treating osteoporosis to increase bone mineral density (BMD). Of note, the increase in BMD by long-term treatment with pharmacological (=near-physiological) doses of vitamin D compounds was caused by the suppression of bone resorption...
November 13, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29144435/dysregulated-collagen-homeostasis-by-matrix-stiffening-and-tgf-%C3%AE-1-in-fibroblasts-from-idiopathic-pulmonary-fibrosis-patients-role-of-fak-akt
#9
Alícia Giménez, Paula Duch, Marta Puig, Marta Gabasa, Antoni Xaubet, Jordi Alcaraz
Idiopathic pulmonary fibrosis (IPF) is an aggressive disease in which normal lung parenchyma is replaced by a stiff dysfunctional scar rich in activated fibroblasts and collagen-I. We examined how the mechanochemical pro-fibrotic microenvironment provided by matrix stiffening and TGF-β1 cooperates in the transcriptional control of collagen homeostasis in normal and fibrotic conditions. For this purpose we cultured fibroblasts from IPF patients or control donors on hydrogels with tunable elasticity, including 3D collagen-I gels and 2D polyacrylamide (PAA) gels...
November 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29140881/pdgfb-rearrangements-in-dermatofibrosarcoma-protuberans-of-the-vulva-a-study-of-11-cases-including-myxoid-and-fibrosarcomatous-variants
#10
Khadijeh Jahanseir, Deyin Xing, Patricia T Greipp, William R Sukov, Gary L Keeney, Brooke E Howitt, J Kenneth Schoolmeester
Dermatofibrosarcoma protuberans (DFSP) is a low-grade fibroblastic sarcoma that tends to arise in young to middle age adults and involve the trunk and proximal extremities. Rare examples of vulvar DFSP have been reported, including myxoid, myoid, and fibrosarcomatous variants, but detection of the characteristic t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion has not been evaluated in a large series of primary vulvar tumors. The clinical, morphologic, immunohistochemical, and molecular cytogenetic features of 11 cases were examined...
November 14, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#11
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29137225/circular-rna-expression-profile-and-potential-function-of-hsa_circrna_101238-in-human-thoracic-aortic-dissection
#12
Meisheng Zou, Chixiong Huang, Xinzhong Li, Xiang He, Yanmei Chen, Wangjun Liao, Yulin Liao, Jie Sun, Ze Liu, Lintao Zhong, Jianping Bin
Objective: To assess the circular RNAs (circRNAs) expression profile and explore the potential functions in human thoracic aortic dissection (TAD). Methods: The differentially expressed circRNAs profiles of the aortic segments between human type A TAD patients (n=3) and age-matched normal donors (NA; n=3) were analyzed using the Arraystar human circRNAs microarray. Quantitative real-time PCR was used to validate the expression pattern of circRNAs, parental genes, and hsa-miR-320a; Western blotting confirmed MMP9 expression with additional samples...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133362/three-month-endothelial-human-endothelin-1-overexpression-causes-blood-pressure-elevation-and-vascular-and-kidney-injury
#13
Suellen C Coelho, Olga Berillo, Antoine Caillon, Sofiane Ouerd, Júlio C Fraulob-Aquino, Tlili Barhoumi, Stefan Offermanns, Pierre Paradis, Ernesto L Schiffrin
Endothelium-derived endothelin (ET)-1 has been implicated in the development of hypertension and end-organ damage, but its exact role remains unclear. We have shown that tamoxifen-inducible endothelium-restricted human ET-1 overexpressing (ieET-1) mice exhibited blood pressure rise after a 3-week induction in an ET type A (ETA) receptor-dependent manner, in absence of vascular and renal injury. It is unknown whether long-term ET-1 overexpression results in sustained blood pressure elevation and vascular and renal injury...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29129790/in-vitro-osteogenesis-by-intracellular-uptake-of-strontium-containing-bioactive-glass-nanoparticles
#14
Parichart Naruphontjirakul, Alexandra E Porter, Julian R Jones
Monodispersed strontium containing bioactive glass nanoparticles (Sr-BGNPs) with two compositions were synthesised, through a modified sol-gel Stöber process, wherein silica nanoparticles (SiO2-NPs) were formed prior to incorporation of calcium and strontium, with diameters of 90 ± 10 nm. The osteogenic response of a murine preosteoblast cell line, MC3T3-E1, was investigated in vitro for a nanoparticle concentration of 250 µg/mL with compositions of 87 mol% SiO2, 7 mol% CaO, 6 mol% SrO and 83 mol% SiO2, 3 mol% CaO, 14 mol% SrO...
November 9, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29121396/role-of-gut-derived-endotoxin-on-type-i-collagen-production-in-the-rat-pancreas-after-chronic-alcohol-exposure
#15
Hongyan Li, Ming Xiu, Shuhua Wang, David R Brigstock, Li Sun, Limei Qu, Runping Gao
BACKGROUND: Pancreatic fibrosis is a key pathological feature of alcoholic chronic pancreatitis (ACP). Bacterial endotoxin lipopolysaccharide (LPS) is considered as an important cofactor in the fibrogenesis of ACP. However, there are limitations in the use of exogenous LPS for evaluating the role of endotoxin in ACP pathogenesis. In this study we determined the relationship between the concentration of LPS in the portal vein and pancreatic type I collagen (Col1) content in chronic alcohol-fed rats...
November 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29116170/injection-of-high-dose-botulinum-toxin-a-leads-to-impaired-skeletal-muscle-function-and-damage-of-the-fibrilar-and-non-fibrilar-structures
#16
Jessica Pingel, Mikkel Schou Nielsen, Torsten Lauridsen, Kristian Rix, Martin Bech, Tine Alkjaer, Ida Torp Andersen, Jens Bo Nielsen, R Feidenhansl
Botulinum-toxin A (BoNT/A) is used for a wide range of conditions. Intramuscular administration of BoNT/A inhibits the release of acetylcholine at the neuromuscular junction from presynaptic motor neurons causing muscle-paralysis. The aim of the present study was to investigate the effect of high dose intramuscular BoNT/A injections (6 UI = 60 pg) on muscle tissue. The gait pattern of the rats was significantly affected 3 weeks after BoNT/A injection. The ankle joint rotated externally, the rats became flat footed, and the stride length decreased after BoNT/A injection...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109031/pge2-induces-apoptosis-of-hepatic-stellate-cells-and-attenuates-liver-fibrosis-in-mice-by-downregulating-mir-23a-5p-and-mir-28a-5p
#17
R Brea, O Motiño, D Francés, C García-Monzón, J Vargas, M Fernández-Velasco, L Boscá, M Casado, P Martín-Sanz, N Agra
MicroRNAs (miRNAs), small noncoding RNAs modulating messenger RNA (mRNA) and protein expression, have emerged as key regulatory molecules in chronic liver diseases, whose end stage is hepatic fibrosis, a major global health burden. Pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, what makes it necessary to establish a better understanding of the molecular mechanisms underlying its pathogenesis. In this context, we have recently shown that cyclooxygenase-2 (COX-2) expression in hepatocytes restricts activation of hepatic stellate cells (HSCs), a pivotal event in the initiation and progression of hepatic fibrosis...
November 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29106524/cardiac-myocyte-%C3%AE-3-adrenergic-receptors-prevent-myocardial-fibrosis-by-modulating-oxidant-stress-dependent-paracrine-signaling
#18
Nerea Hermida, Lauriane Michel, Hrag Esfahani, Emilie Dubois-Deruy, Joanna Hammond, Caroline Bouzin, Andreas Markl, Henri Colin, Anne Van Steenbergen, Christophe De Meester, Christophe Beauloye, Sandrine Horman, Xiaoke Yin, Manuel Mayr, Jean-Luc Balligand
Aims: Human and mouse cardiac beta3-adrenergic receptors (beta3AR) exert antipathetic effects to those of beta1-2AR stimulation. We examined their role in modulating myocardial remodelling, particularly fibrosis in response to haemodynamic stress. Methods and results: Mice with cardiac myocyte-specific expression of beta3AR (ADRB3-tg) or tamoxifen-inducible homozygous deletion (c-Adrb3-ko, with loxP-targeted Adrb3) were submitted to transaortic constriction. A superfusion assay was used for proteomic analysis of paracrine mediators between beta3AR-expressing cardiac myocytes and cardiac fibroblasts cultured separately...
July 6, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29104083/development-and-evaluation-of-a-pan-sarcoma-fusion-gene-detection-assay-using-the-nanostring-ncounter-platform
#19
Kenneth T E Chang, Angela Goytain, Tracy Tucker, Aly Karsan, Cheng-Han Lee, Torsten O Nielsen, Tony L Ng
The NanoString nCounter assay is a high-throughput hybridization technique using target-specific probes that can be customized to test for numerous fusion transcripts in a single assay using RNA from formalin-fixed, paraffin-embedded material. We designed a NanoString assay targeting 174 unique fusion junctions in 25 sarcoma types. The study cohort comprised 212 cases, 96 of which showed fusion gene expression by the NanoString assay, including all 20 Ewing sarcomas, 11 synovial sarcomas, and 5 myxoid liposarcomas tested...
November 17, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29104038/extremely-low-level-of-serum-pigment-epithelium-derived-factor-is-a-special-biomarker-of-chinese-osteogenesis-imperfecta-patients-with-serpinf1-mutations
#20
Jian-Yi Wang, Lu-Jiao Li, Qian Zhang, Yi Liu, Fang Lv, Xiao-Jie Xu, Yu-Wen Song, Ou Wang, Yan Jiang, Wei-Bo Xia, Xiao-Ping Xing, Mei Li
BACKGROUNDS: SERPINF1 mutations caused deficiency of pigment epithelium-derived factor (PEDF) and would lead to osteogenesis imperfecta (OI) type VI. However, serum PEDF levels were unclear in Chinese OI patients who had clear molecular diagnosis. OBJECTIVE: To assess PEDF levels in different genotypes of OI, to evaluate the influencing factors of PEDF in Chinese OI patients with clear molecular diagnosis. METHODS: Known candidate genes of OI were examined by a targeted next generation sequence...
November 2, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
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