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Mianli Bian, Xingran Chen, Chenxi Zhang, Huanhuan Jin, Feixia Wang, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Varied pathogenetic elements have been touched upon the liver fibrosis, including inflammatory, stress, apoptosis and unfolded proteins aggregation. Magnesium Isoglycyrrhizinate (MgIG) has been accepted to be a neuroprotective effect, hepatoprotective and anti-inflammatory molecule. In our vitro researches, MgIG was considered to activate hepatic stellate cells (HSCs) apoptosis by promoting endoplasmic reticulum stress (ERS) detrimental response to a certain extent. Consequently, MgIG showed its potential therapeutic capacity in fibrogenesis and counteracted the pathogenetic aspects, which were involved in integrating current treatments correcting liver fibrosis...
October 19, 2017: BioFactors
Xin Ma, Fangping Liu, Minmin Li, Zhi Li, Yuexia Lin, Rui Li, Changwen Li, Yicong Chang, Changwei Zhao, Qing Han, Qiong Zhou, Yulin Zhao, Dening Wang, Jingli Liu
In the present study, three models of acute liver injury in mice were induced via the administration of CCl4 (35 mg/kg, 24 h), acetyl-para-aminophenol (APAP; 200 mg/kg, 12 h) and ethanol (14 ml/kg, 8 h) to study the effect of glutathione S-transferase A1 (GSTA1) on acute liver injury. The serum levels of alanine transaminase, aspartate transaminase and liver homogenate indicators (superoxide dismutase, glutathione and glutathione peroxidase) were significantly lower in model groups compared with the control group (P<0...
October 2017: Experimental and Therapeutic Medicine
Yuan Ding, Lizhou Wang, Jie Song, Shi Zhou
Ellagic acid has been proven to have anticancer, antimutation, antimicrobial and antiviral functions. The present study investigated whether treatment with ellagic acid was able to prevent tetrachloride (CCl4)-induced cirrhosis through the inhibition of reactive oxygen species (ROS) formation and angiogenesis. CCl4 diluted in olive oil at a final concentration of 10% was used to induce a cirrhosis model. A total of 40 mice were random allocated into four groups, as follows: Control, cirrhosis model, 7.5 mg/kg ellagic acid and 15 mg/kg ellagic acid groups...
October 2017: Experimental and Therapeutic Medicine
Carmen Lefaucheur, Denis Viglietti, Luis G Hidalgo, Lloyd E Ratner, Serena M Bagnasco, Ibrahim Batal, Olivier Aubert, Babak J Orandi, Federico Oppenheimer, Oriol Bestard, Paolo Rigotti, Anna V Reisaeter, Nassim Kamar, Yvon Lebranchu, Jean-Paul Duong Van Huyen, Patrick Bruneval, Denis Glotz, Christophe Legendre, Jean-Philippe Empana, Xavier Jouven, Dorry L Segev, Robert A Montgomery, Adriana Zeevi, Philip F Halloran, Alexandre Loupy
Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these antibodies induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 kidney recipients for complement-activating DSAs and used histopathology, immunostaining, and allograft gene expression to assess rejection phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the effect of complement inhibition on kidney allograft rejection phenotype and the clinical response to complement inhibition in 116 independent kidney recipients with DSAs at transplant receiving rejection prophylaxis with eculizumab or standard of care (plasma exchange and intravenous Ig) at ten international centers...
October 17, 2017: Journal of the American Society of Nephrology: JASN
Tianqi Zhao, Yu Peng, Quanlong Miao, Baicheng Li, Kun Liang, Ru Yang, Dejun Han
We present a one-dimensional (1-D) single-photon position-sensitive silicon photomultiplier (PS-SiPM) that can perform both photon number and position discriminations. The device, which features epitaxial quenching resistors and a continuous cap resistive layer for charge division, possesses two cathodes on top and one anode at the bottom. The PS-SiPM shows an active size of 2.2 mm × 2.2 mm and micro avalanche photodiode cell pitch of ~10 μm. The position measurement error (PME) and position resolution of the device are analyzed...
September 18, 2017: Optics Express
Jianlin He, Kaikai Bai, Bihong Hong, Feng Zhang, Shizhong Zheng
Fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has been reported to exert beneficial health effects, including hepatoprotection. However, the effect of DHA alone has not been well studied, and the mechanism is not fully understood. In the present study, we reported the protective effect of DHA on carbon tetrachloride (CCl4) induced hepatic fibrosis. Compared with the control group, the CCl4 group showed hepatic damage as evidenced by histological changes and elevation in serum transaminase activity, fibrosis, inflammation and oxidative stress levels...
October 13, 2017: International Immunopharmacology
Lei Tian, Weiyang Li, Le Yang, Na Chang, Xiaoting Fan, Xiaofang Ji, Jieshi Xie, Lin Yang, Liying Li
Macrophage M1/M2 polarization mediates tissue damage and inflammatory responses. Cannabinoid receptor (CB) 1 participated in liver fibrogenesis by affecting bone marrow (BM)-derived monocytes/macrophages (BMMs) activation. However, the knowledge of whether CB1 is involved in the polarization of BMMs remains limited. Here, we found M1 gene signatures (including CD86, MIP-1β, tumor necrosis factor, IL-6, and inducible nitric oxide synthase) and the amount of M1 macrophages (CD86(+) cells, gated by F4/80) were significantly elevated in carbon tetrachloride (CCl4)-induced mouse injured livers, while that of M2 type macrophages had little change by RT-qPCR and fluorescence-activated cell sorting (FACS)...
2017: Frontiers in Immunology
Chi-Hao Zhang, Lei Zheng, Liang Gui, Jia-Yun Lin, Yi-Ming Zhu, Wen-Sheng Deng, Meng Luo
BACKGROUND/AIMS: Fibrosis and increased intrahepatic vascular resistance are the hallmarks of chronic inflammatory disorders of the liver and cirrhosis. Inhibitors of the enzyme soluble epoxide hydrolase reduce fibrosis in several disease models. The present study aimed at investigating the effects of soluble epoxyhydrolase inhibition with t-TUCB in tetrachloride-induced cirrhosis in rats. METHODS: The models were established by CCl4 (2ml/kg) given subcutaneously for 14 weeks...
October 11, 2017: Clinics and Research in Hepatology and Gastroenterology
Markus Blaess, Nelly Bibak, Ralf A Claus, Matthias Kohl, Gabriel A Bonaterra, Ralf Kinscherf, Stefan Laufer, Hans-Peter Deigner
Ceramide generation is involved in signal transduction of cellular stress response, in particular during stress-induced apoptosis in response to stimuli such as minimally modified Low-density lipoproteins, TNFalpha and exogenous C6-ceramide. In this paper we describe 48 diverse synthetic products and evaluate their lysosomotropic and acid sphingomyelinase inhibiting activities in macrophages. A stimuli-induced increase of C16-ceramide in macrophages can be almost completely suppressed by representative compound NB 06 providing an effective protection of macrophages against apoptosis...
September 21, 2017: European Journal of Medicinal Chemistry
Raghuram Kandimalla, Suvakanta Dash, Ashim Chandra Bhowal, Sanjeeb Kalita, Narayan Chandra Talukdar, Sarathi Kundu, Jibon Kotoky
In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs...
2017: International Journal of Nanomedicine
Neil P Dufton, Claire R Peghaire, Lourdes Osuna-Almagro, Claudio Raimondi, Viktoria Kalna, Abhishek Chuahan, Gwilym Webb, Youwen Yang, Graeme M Birdsey, Patricia Lalor, Justin C Mason, David H Adams, Anna M Randi
The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (Erg (cEC-Het) ) and inducible homozygous deficient mice (Erg (iEC-KO) ), in a SMAD3-dependent manner...
October 12, 2017: Nature Communications
Abhishek Satishchandran, Aditya Ambade, Sitara Rao, Ying-Chao Hsueh, Arvin Iracheta-Vellve, David Tornai, Patrick Lowe, Benedek Gyongyosi, Jia Li, Donna Catalano, Li Zhong, Karen Kodys, Jun Xie, Shashi Bala, Guangping Gao, Gyongyi Szabo
BACKGROUND & AIMS: Chronic, excessive alcohol consumption leads to alcoholic liver disease (ALD) characterized by steatosis, inflammation, and eventually cirrhosis. The hepatocyte specific microRNA 122 (MIR122) regulates hepatocyte differentiation and metabolism. We investigated whether an alcohol-induced decrease in level of MIR122 contributes to development of ALD. METHODS: We obtained liver samples from 12 patients with ALD and cirrhosis and 9 healthy individuals (controls) and analyzed them by histology and immunohistochemistry...
October 4, 2017: Gastroenterology
Chen Zhang, Yan Li, Xiang-Yu Zhang, Lei Liu, Hai-Zhou Tong, Ting-Lu Han, Wan-di Li, Xiao-Lei Jin, Ning-Bei Yin, Tao Song, Hai-Dong Li, Juan Zhi, Zhen-Min Zhao, Lin Lu
Liver disease is a serious problem affecting millions of people with continually increasing prevalence. Stem cell therapy has become a promising treatment for liver dysfunction. We previously reported on human minor salivary gland mesenchymal stem cells (hMSGMSCs), which are highly self-renewable with multi-potent differentiation capability. In this study, keratinocyte-like cells with self-regeneration and hepatic differentiation potential were isolated and characterized, and named human minor salivary gland epithelial progenitor cells (hMSG-EpiPCs)...
October 5, 2017: Scientific Reports
Lili Zhu, Mingliang Cheng, Yongmei Liu, Yumei Yao, Zixin Zhu, Baofang Zhang, Qiuju Mou, Yiju Cheng
Liver fibrosis is a necessary stage for chronic liver diseases, and serious threat to human health. Hepatic fibrosis is a necessary stage for chronic liver diseases. Hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Thymosin beta 4 (Tβ4) has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs, however, the underlying mechanisms are not fully elucidated. Herein, we investigated the potential role of Tβ4 in liver fibrosis by describing the effects of Tβ4, and we discuss the possible signaling pathway regulated by Tβ4...
September 15, 2017: Oncotarget
Guiju Tang, Zhihong Weng, Jun Song, Yixiong Chen
The role of the Notch ligand Jagged1 in hepatic fibrosis remains to be elucidated. In the current study, we investigated the role of Jagged1 in the activation of hepatic stellate cells (HSCs) and development of hepatic fibrosis in rats. In vitro, Jagged1 in HSCs was downregulated and upregulated by Jagged1 siRNA and pcDNA3.1 Jagged1, respectively. The levels of epithelial-mesenchymal transition (EMT) markers and HSC activation markers were assessed using western blot analysis. The proliferation and migration capacity of HSCs were assessed using 5-ethynyl-2'-deoxyuridine (EdU) incorporation and Transwell migration assays...
September 22, 2017: Oncotarget
Shigekazu Takemura, Hideki Azuma, Mayuko Osada-Oka, Shoji Kubo, Toshihiko Shibata, Yukiko Minamiyama
S-allyl-glutathione (SAG) is one of the metabolites of diallyl sulfide (DAS), a component of garlic. DAS has shown preventative effects on carcinogenesis in animal models. However, whether synthetic SAG can improve liver fibrosis has not been investigated. We examined the potential preventive effects of SAG on acute and chronic models of liver fibrosis by chronic carbon tetrachloride (CCl4) administration. SAG inhibited liver fibrogenesis induced by CCl4 in a dose-dependent manner and reduced heat shock protein 47 (HSP47), a collagen-specific chaperone and other fibrosis markers...
September 28, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
Min Li, Wenxuan Hong, Chenzhi Hao, Luyang Li, Dongmei Wu, Aiguo Shen, Jun Lu, Yuanlin Zheng, Ping Li, Yong Xu
Hepatic stellate cells (HSCs) are a major source of fibrogenesis in the liver contributing to cirrhosis. When activated, HSCs transdifferentiate into myofibroblast and undergo profound functional alterations paralleling an overhaul of the transcriptome, the mechanism of which remains largely undefined. We investigated the involvement of the class III deacetylase sirtuin (silent information regulator 1, SIRT1) in HSC activation and liver fibrosis. SIRT1 levels were down-regulated in the livers in mouse models of liver fibrosis, in patients with cirrhosis, and in activated HSCs as opposed to quiescent HSCs...
September 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Saima Ali, Muhammad Rashid Khan, Moniba Sajid
The current study aimed at exploring hepatoprotective potential of Parrotiopsis jacquemontiana leaves methanol extract (PJM) in rat. PJM constituted of significant amount of total phenolic and total flavonoid content. PJM and ethyl acetate fraction (PJE) exhibited strong antioxidant potential (DPPH, hydroxyl ion, nitric oxide, iron chelating, β-carotene, reducing power and phosphomolybdate assay) in comparison to other extracts. CCl4 toxicity displayed significant (p<0.05) increase in level of TBARS, H2O2, nitrite while a decrease in SOD, CAT, POD and GSH in liver samples of CCl4 treated group...
September 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ji Hyun Lee, Yoon-Jae Jeon, Jung Hye Choi, Hae Young Kim, Tae-Yoon Kim
BACKGROUND: VitabridC(12) is newly developed and composed of vitamin C and Vitabrid (lamellar, hydrated zinc oxide). OBJECTIVE: In this study, we aimed to investigate the effects of VitabridC(12) on psoriasis and atopic dermatitis. METHODS: Mice with imiquimod-induced psoriasis or Dermatophagoides farinae-induced atopic dermatitis were applied with VitabridC(12). The effects of VitabridC(12) were evaluated by clinical features, histology, and immunologic features by examining cytokines and chemokines...
October 2017: Annals of Dermatology
Yuheng Hong, Qingbin Yao, Lina Zheng
Thymosin β4 (Tβ4) has been shown to have beneficial effects in a number of pathological processes. Although there was research reporting the endogenous expression of Tβ4 influences hepatic stellate cells (HSCs) activation, the effect of exogenous administration of Tβ4 in hepatic fibrosis remains unclear. In the current study, we used CCl4-induced liver fibrosis model mice to investigate the effect of Tβ4 administration on fibrosis in vivo and the underlying mechanism. Our study indicates that Tβ4 attenuates hepatic fibrosis and down-regulates the expression of fibrogenic genes in hepatic liver...
September 28, 2017: Biochemical and Biophysical Research Communications
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