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Tao Tian, Weiliang Tian, Fan Yang, Risheng Zhao, Qian Huang, Yunzhao Zhao
BACKGROUND: Sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptors (S1PRs) signaling plays a key role in inflammatory responses. Lei et al. showed that SphK1 inhibition presented a hepatoprotective effect on acute liver damage via decreasing hepatic high-mobility group box 1 (HMGB1) cytoplasmic translocation. OBJECTIVE: We aim to determine whether SphK1 or S1PRs inhibition improves lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced acute liver failure by inhibiting the mitogen-activated protein kinases (MAPKs) pathway...
October 2016: United European Gastroenterology Journal
Jun Yamada, Shozo Jinno
Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA just detects N-acetyl-D -galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan-based PNNs around five subclasses of parvalbumin-positive (PV+) GABAergic neurons in the CA1 and CA3 regions of the mouse hippocampus...
October 7, 2016: Journal of Comparative Neurology
Xueting Bai, Peixuan Yang, Qiaoling Zhou, Bozhi Cai, Manon Buist-Homan, He Cheng, Jiyang Jiang, Daifei Shen, Lijun Li, Xiajiong Luo, Klaas Nico Faber, Han Moshage, Ganggang Shi
BACKGROUND AND PURPOSE: Liver diseases are mostly accompanied by inflammation and hepatocyte death. Therapeutic approaches targeting both hepatocyte injury and inflammation are not available. Natural compounds are considered as potential treatment for inflammatory liver diseases. Hesperetin, a flavonoid component of citrus fruits has been reported to have anti-inflammatory properties. The aim of this study was to evaluate the cytoprotective and anti-inflammatory properties of hesperetin both in vitro and in models of fulminant hepatitis...
October 7, 2016: British Journal of Pharmacology
Xiaolan Cui, Qian Chen, Zhen Dong, Longmei Xu, Tianfei Lu, Dawei Li, Jiangjun Zhang, Ming Zhang, Qiang Xia
Sirtuin 1 (Sirt1) is a deacetylase that regulates many cellular processes in the liver, and so far its role in endotoxemic liver injury is elusive. So we conditionally inactivate Sirt1 in murine hepatocytes to determine its role in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver damage, which is a well-established experimental model mimicking septic liver injury and fulminant hepatitis. Ablation of Sirt1 shows remarkable protection against GalN/LPS-induced liver injury, which is a result of enhanced NF-κB response because knockdown of RelA/p65 negates the protective effect of Sirt1 knockout...
October 6, 2016: Cell Death & Disease
Zongmei Wen, Zhen Lei, Lu Yao, Ping Jiang, Tao Gu, Feng Ren, Yan Liu, Chunyan Gou, Xiuhui Li, Tao Wen
Acute liver failure (ALF) is a life-threatening systemic disorder. Here we investigated the impact of circulating histones, recently identified inflammatory mediators, on systemic inflammation and liver injury in murine models and patients with ALF. We analyzed histone levels in blood samples from 62 patients with ALF, 60 patients with chronic liver disease, and 30 healthy volunteers. We incubated patients' sera with human L02 hepatocytes and monocytic U937 cells to assess cellular damage and cytokine production...
2016: Cell Death & Disease
Gosia Malgorzata-Miller, Lena Heinbockel, Klaus Brandenburg, Jos W M van der Meer, Mihai G Netea, Leo A B Joosten
The pattern recognition receptor TLR4 is well known as a crucial receptor during infection and inflammation. Several TLR4 antagonists have been reported to inhibit the function of TLR4. Both natural occurring antagonists, lipopolysaccharide (LPS) from Gram-negative bacteria as well as synthetic compounds based on the lipid A structure of LPS have been described as potent inhibitors of TLR4. Here, we have examined the characteristics of a natural TLR4 antagonist, isolated from Bartonella quintana bacterium by elucidating its chemical primary structure...
September 27, 2016: Scientific Reports
H Gao, X Y Zhang, L Y Yue, Z Y Liu, N N Jia, D X Chen, Z P Duan, F Ren
Objective: To study the role of endoplasmic reticulum (ER) stress-mediated glycogen synthase kinase 3β (GSK3β) activity in the pathological process of liver injury in acute liver failure (ALF) mice. Methods: ALF model was established by intraperitoneal injection of D-galactosamine/lipopolysaccharide (D-GalN/LPS) in C57BL/6 mice. The mice were divided into control group (n=10), ALF model group (n=18), 4-phenylbutyrate (4-PBA, an ER stress inhibitor) group (n=18) and SB216763 (a specific inhibitor of GSK3β) group (n=16)...
September 13, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Ming-Wei Liu, Rong Liu, Hai-Yin Wu, Wei Zhang, Jing Xia, Min-Na Dong, Wen Yu, Qiang Wang, Feng-Mei Xie, Rui Wang, Yun-Qiao Huang, Chuan-Yun Qian
Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)‑induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury...
September 23, 2016: International Journal of Molecular Medicine
Samantha Banford, David J Timson
UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in O-glycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer...
September 22, 2016: Current Cancer Drug Targets
Arjun Balakrishnan, Priya DasSarma, Oindrilla Bhattacharjee, Jong Myoung Kim, Shiladitya DasSarma, Dipshikha Chakravortty
Bactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs...
2016: Scientific Reports
Xin Zhao, Xiaolei Shi, Zhiheng Zhang, Hucheng Ma, Xianwen Yuan, Yitao Ding
BACKGROUND: The imbalance of immunity is an important pathogenesis of acute liver failure (ALF). Neutrophils are the hallmark of acute inflammation, which have an essential role in immune regulation. Mesenchymal stem cell (MSC) transplantation is a promising therapy in ALF treatment. Recent studies indicated a considerable connection between MSCs and neutrophils in immune regulation. AIM: To investigate changes in neutrophils in ALF rats after MSC transplantation, and to explore the therapeutic effect and mechanism of the combined treatment with MSC transplantation and neutrophil depletion in ALF...
September 13, 2016: Clinics and Research in Hepatology and Gastroenterology
Muhammad Jahangir Hossen, Mi-Yeon Kim, Jae Youl Cho
Xanthium strumarium L. (Asteraceae), a traditional Chinese medicine, is prescribed to treat arthritis, bronchitis, and rhinitis. Although the plant has been used for many years, the mechanism by which it ameliorates various inflammatory diseases is not yet fully understood. To explore the anti-inflammatory mechanism of methanol extracts of X. strumarium (Xs-ME) and its therapeutic potential, we used lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells and human monocyte-like U937 cells as well as a LPS/D-galactosamine (GalN)-induced acute hepatitis mouse model...
2016: American Journal of Chinese Medicine
Qijue Lu, Li Xu, Chunguang Li, Yang Yuan, Shengdong Huang, Hezhong Chen
Previous studies verified that miR-214 is of great significance in the invasion and migration of a variety of cancers. It has been demonstrated that UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7(GALNT7) is a putative target of miR-214. We performed this study to figure out how miR-214 and GALNT7 play their roles in the invasion and migration of esophageal squamous cell carcinoma (ESCC). The expression of miR-214 was significantly downregulated in tumors compared to the corresponding non-tumor tissues while GALNT7 showed an opposite tendency...
September 12, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hong-Min Ni, Mitchell R McGill, Xiaojuan Chao, Benjamin L Woolbright, Hartmut Jaeschke, Wen-Xing Ding
How different cell death modes and cell survival pathways cross talk remains elusive. We determined the interrelation of apoptosis, necrosis, and autophagy in tumor necrosis factor (TNF)-α/actinomycin D (ActD) and lipopolysaccharide/D-galactosamine (GalN)-induced hepatotoxicity in vitro and in vivo. We found that TNF-α/ActD-induced apoptosis was completely blocked by a general caspase inhibitor ZVAD-fmk at 24 hours but hepatocytes still died by necrosis at 48 hours. Inhibition of caspases also protected mice against lipopolysaccharide/GalN-induced apoptosis and liver injury at the early time point, but this protection was diminished after prolonged treatment by switching apoptosis to necrosis...
October 2016: American Journal of Pathology
Hui-Juan Dai, Da-Wei Li, Ya-Xiang Wang, Ai-Jun Sun, Yi-Xian Lu, Xin- Ding, Ming- Zhang, Yong-Gang Song, Xuan-Dong Huang
Heat shock proteins (Hsps) are critical for cell survival under adverse environmental conditions. Bicyclol is a novel hepatoprotectant that has been shown to protect against liver injury by inducing Hsps, including Hsp27 and Hsp70. Although the role of Hsp70 in protecting against acute hepatic failure has been clearly explored, the precise function of Hsp27 in this setting is poorly defined. This study was undertaken to evaluate the role of Hsp27 in bicyclol-mediated hepatoprotection. Both primary hepatocytes and bone marrow-derived macrophages were subjected to bicyclol treatment, followed by detection of Hsp27 expression...
September 3, 2016: European Journal of Pharmacology
Young-Su Yi, Jae Youl Cho, Daewon Kim
ETHNOPHARMACOLOGICAL RELEVANCE: Cerbera manghas L. (Apocynaceae) is a medicinal plant traditionally used to ameliorate the clinical signs of inflammatory diseases and hypertension. AIM OF STUDY: Although C. manghas L. has long been used as a traditional remedy for various diseases, the underlying molecular and cellular mechanisms are poorly understood. A detailed investigation of these mechanisms is necessary to demonstrate the ethnopharmaceutical utility of this plant...
August 22, 2016: Journal of Ethnopharmacology
Emil Glibstrup, Christian Marcus Pedersen
An improved and scalable synthesis of orthogonally protected d-glucosamine and d-galactosamine building blocks from inexpensive d-glucosamine has been developed. The key reaction is an inversion/migration step providing access to a fully orthogonal protecting group pattern, which is required for microbial oligosaccharide synthesis. The method can be carried out on a multigram scale as several of the reactions can be purified by crystallization to give anomerically pure products.
September 2, 2016: Organic Letters
Danxiao Wu, Yu Shi, Cheng Wang, Hanwen Chen, Qiaoyun Liu, Jianhua Liu, Lihuang Zhang, Yihua Wu, Dajing Xia
Myeloid-derived suppressor cells (MDSCs) confer immunosuppressive properties, but their roles in fulminant hepatitis have not been well defined. In this study, we systematically examined the distribution of MDSCs in bone marrow (BM), liver and spleen, and their functional and differentiation status in an acute fulminant hepatitis mouse model induced by lipopolysaccharide and D-galactosamine (LPS-GalN). Moreover, the interaction between NKT cells and MDSCs was determined. Our study revealed that BM contained the largest pool of MDSCs during pathogenesis of fulminant hepatitis compared with liver and spleen...
August 6, 2016: Immunobiology
Ying Wang, Yumeng Wan, Guihong Ye, Pu Wang, Xiaowen Xue, Guanzhong Wu, Boping Ye
Adiponectin is an antidiabetic and antiatherogenic adipokine, which plays distinct roles in the balance of energy homoeostasis. As an insulin sensitizing hormone, adiponectin exerts multiple biological effects by the specific receptors (AdipoR1 and AdipoR2), through activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR)α pathways. AdipoRon, an orally active synthetic small-molecule AdipoR agonist, shows very similar effects to adiponectin in vitro and in vivo, which could be a promising therapeutic approach for obesity-related disorders...
October 10, 2016: European Journal of Pharmaceutical Sciences
Yong-Tao Li, Cheng-Bo Yu, Dong Yan, Jian-Rong Huang, Lan-Juan Li
BACKGROUND: Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days...
August 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
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