Our data showed that MSCs ameliorated the immune response with decrease of inflammatory cytokines and increase anti-inflammatory IL-10; moreover, inhibited splenocytes apoptosis and, consequently, inhibited tissue damage during sepsis.

Background/Aim The interactions between the gut and liver have been described in the progression of non-alcoholic steatohepatitis (NASH). The aim of this study was to develop an experimental nutritional model of NASH simulating metabolic changes occurring in humans. Materials and Methods Adult male Sprague Dawley rats were randomized into two groups: controls (standard diet) and intervention (high-fat and choline-deficient diet) for 16 weeks, each experimental group with 10 animals. Biochemical analysis, hepatic lipid content, microRNAs, inflammatory, gut permeability markers and gut microbiota were measured. Results Animals in the intervention group showed significantly higher delta Lee index ( p =0.017), abdominal circumference ( p <0.001), abdominal adipose tissue ( p <0.001) and fresh liver weight ( p <0.001), as well as higher serum levels of alanine aminotransferase ( p =0.010), glucose ( p =0.013), total cholesterol ( p =0.033), LDL cholesterol ( p =0.011), and triglycerides ( p =0.011), and lower HDL cholesterol ( p =0.006) compared to the control group. Higher TLR4 ( p =0.041), TLR9 ( p =0.033), MyD88 ( p =0.001), Casp1 ( p <0.001), NLPR3 ( p =0.019), liver inflammation index interleukin (IL)-1β/IL10 ( p <0.001), IL6/IL10 ( p =0.002) and TNFα/IL10 ( p =0.001) were observed in the intervention group, and also lower permeability markers Ocln ( p =0.003) and F11r ( p =0.041). Gene expression of miR-122 increased ( p =0.041) and miR-145 ( p =0.010) decreased in the intervention group. Liver steatosis, inflammation and fibrosis, along with collagen fiber deposition increment ( p <0.001), were seen in the intervention group. Regarding gut microbiota, Bray-Curtis dissimilarity index and number of operational taxonomic units were significantly different ( p <0.001) between the groups. Composition of the gut microbiota showed a significant correlation with histopathological score of NAFLD (r=0.694) and index IL-1β/IL-10 (r=0.522). Conclusion This experimental model mimicking human NASH demonstrated gut and liver interaction, with gut microbiota and intestinal permeability changes occurring in parallel with systemic and liver inflammation, miRNAs regulation and liver tissue damage.

Platelets enhance survival of animals with 90% PH, probably by an early protective effect on hepatocytes and the increase in growth factor receptors.

Ethanol is a widely used drug, and excess or even moderate consumption of ethanol is associated with changes in several neurotransmitter systems, including the cholinergic system. The incidence of alcoholic dementia and its insults are well supported by multiple studies, although the mechanisms of neurotoxicity are still poorly understood. Considering that zebrafish have a complete central nervous system (CNS) and that several signaling systems have already been identified in zebrafish, this neurotoxicological model has become useful. In the present study, we investigated the long-term effects of ethanol consumption on the cholinergic system, on oxidative stress, and on inflammatory parameters in the zebrafish brain. Animals were exposed to 0.5% (v/v) ethanol for 7, 14, and 28 days. Ethanol inhibited choline acetyltransferase activity after 7 and 14 days but not after 28 days. Acetylcholinesterase activity did not change after any of the exposure periods. When compared to the control group, thiobarbituric acid reactive species and dichlorodihydrofluorescein levels were increased after chronic ethanol exposure. Antioxidant activity promoted by the CAT/SOD ratio was altered after chronic ethanol exposure, suggesting that EtOH can induce oxidative damage in the zebrafish brain. In contrast, nitrate and nitrite levels and sulfhydryl content were not altered. Ethanol did not modify gene expression of the inflammatory cytokines il-1b, il-10, or tnf-α in the zebrafish brain. Therefore, the cholinergic system and the oxidative balance were targeted by chronic ethanol toxicity. This neurochemical regulatory mechanism may play an important role in understanding the effects of long-term ethanol consumption and tolerance in zebrafish model studies.

This study suggests that hypoxia-ischemia is present in the livers of patients with BA, progresses over time and leads to a decreased cholangiocyte mass.

Background and Aims. The use of bone marrow cells has been suggested as an alternative treatment for acute liver failure. In this study, we investigate the effect of encapsulated whole bone marrow cells in a liver failure model. Methods. Encapsulated cells or empty capsules were implanted in rats submitted to 90% partial hepatectomy. The survival rate was assessed. Another group was euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy to study expression of cytokines and growth factors. Results. Whole bone marrow group showed a higher than 10 days survival rate compared to empty capsules group. Gene expression related to early phase of liver regeneration at 6 hours after hepatectomy was decreased in encapsulated cells group, whereas genes related to regeneration were increased at 12, 24, and 48 hours. Whole bone marrow group showed lower regeneration rate at 72 hours and higher expression and activity of caspase 3. In contrast, lysosomal-β-glucuronidase activity was elevated in empty capsules group. Conclusions. The results show that encapsulated whole bone marrow cells reduce the expression of genes involved in liver regeneration and increase those responsible for ending hepatocyte division. In addition, these cells favor apoptotic cell death and decrease necrosis, thus increasing survival.

AIMTo evaluate the effects of chronic exposure to ethanol in the liver and the expression of inflammatory genes in zebrafish.METHODSZebrafish (n = 104), wild type, adult, male and female, were divided into two groups: Control and ethanol (0.05 v/v). The ethanol was directly added into water; tanks water were changed every two days and the ethanol replaced. The animals were fed twice a day with fish food until satiety. After two and four weeks of trial, livers were dissected, histological analysis (hematoxilin-eosin and Oil Red staining) and gene expression assessment of adiponectin, adiponectin receptor 2 (adipor2), sirtuin-1 (sirt-1), tumor necrosis factor-alpha (tnf-a), interleukin-1b (il-1b) and interleukin-10 (il-10) were performed. Ultrastructural evaluations were conducted at fourth week.RESULTSExposing zebrafish to 0.5% ethanol developed intense liver steatosis after four weeks, as demonstrated by oil red staining. In ethanol-treated animals, the main ultrastructural changes were related to cytoplasmic lipid particles and droplets, increased number of rough endoplasmic reticulum cisterns and glycogen particles. Between two and four weeks, hepatic mRNA expression of il-1b, sirt-1 and adipor2 were upregulated, indicating that ethanol triggered signaling molecules which are key elements in both hepatic inflammatory and protective responses. Adiponectin was not detected in the liver of animals exposed and not exposed to ethanol, and il-10 did not show significant difference.CONCLUSIONData suggest that inflammatory signaling and ultrastructural alterations play a significant role during hepatic steatosis in zebrafish chronically exposed to ethanol.

BACKGROUND Cardiovascular disease is the main cause of death in metabolic-associated fatty liver disease, and gut microbiota dysbiosis is associated with both of them. AIM To assess the relationship between gut dysbiosis and cardiovascular risk (CVR) in an experimental model of steatohepatitis. METHODS Adult male Sprague-Dawley rats were randomized to a control group ( n = 10) fed a standard diet and an intervention group ( n = 10) fed a high-fat choline-deficient diet for 16 wk. Biochemical, molecular, hepatic, and cardiac histopathology. Gut microbiota variables were evaluated. RESULTS The intervention group had a significantly higher atherogenic coefficient, Castelli’s risk index (CRI)-I and CRI-II, interleukin-1β, tissue inhibitor of metalloproteinase-1 (all P < 0.001), monocyte chemoattractant protein-1 ( P = 0.005), and plasminogen activator inhibitor-1 ( P = 0.037) than the control group. Gene expression of miR-33a increased ( P = 0.001) and miR-126 ( P < 0.001) decreased in the intervention group. Steatohepatitis with fibrosis was seen in the intervention group, and heart computerized histological imaging analysis showed a significant decrease in the percentage of cardiomyocytes with a normal morphometric appearance ( P = 0.007), reduction in the mean area of cardiomyocytes ( P = 0.037), and an increase of atrophic cardiomyocytes ( P = 0.007). There were significant correlations between the cardiomyocyte morphometry markers and those of progression and severity of liver disease and CVR. The intervention group had a lower Shannon diversity index and fewer changes in the structural pattern of gut microbiota (both P < 0.001) than controls. Nine microbial families that are involved in lipid metabolism were differentially abundant in intervention group and were significantly correlated with markers of liver injury and CVR. CONCLUSION The study found a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.