In patients with nonalcoholic steatohepatitis (NASH), PNPLA3 GG compared to CC was associated with higher AST levels [38.4±25.3 versus 36.7±40.1IU/L, p=0.0395)] and with the presence of liver fibrosis (≥F2 fibrosis, p=0.0272).
Dysbiosis-induced NASH was associated with cognitive impairment and a probiotic (LP EMCC-1039) supplementation has beneficial effect through modulation of TLR4/BDNF signaling pathway.
Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination and acting alone or on the background of potent statin therapy which is recommended in T2DM, might contribute substantially to NAFLD/NASH amelioration, possibly reducing not only liver specific but also cardiovascular morbidity.
There were significant negative correlations of the serum serine with the liver fat fraction, serum alanine transaminase, and triglyceride levels among patients with FLD.
Following administration of the miR-182-5p mimic into the livers of HFD-induced NASH mice, we determined the in vivo expression of TLR4, TNFa, and IL-6 and assessed the histologic features of the livers.
We used real-time polymerase chain reaction (RT-PCR) analysis to evaluate the hepatic and intestinal expression level of all genes studied (TLR2, TLR4, TLR9, LXRα, SREBP1C, ACC1, FAS, PPARα, CPT1α, CROT, SREBP2, ABCA1, ABCG1 and FXR in the liver; TLR2, TLR4, TLR5, TLR9, GLP-1R, DPP-4, FXR and PPARɣ in the jejunum) in 82 women with MO with normal liver histology (NL, n = 29), SS (n = 32), and NASH (n = 21).
In fibrotic NASH, treatment with miR-223 3p led to a remarkable mitigation of fibrosis development and activation of hepatic stellate cells (HSCs). miR-223 3p disrupted the activation of the NLRP3 inflammasome by impairing the synthesis of cleaved interleukin-1β (IL-1β), mature IL-1β, and NLRP3, and the activation of caspase-1 p10 in both EAH and fibrotic NASH.
Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination and acting alone or on the background of potent statin therapy which is recommended in T2DM, might contribute substantially to NAFLD/NASH amelioration, possibly reducing not only liver specific but also cardiovascular morbidity.
Conclusion: These results suggest that Lys6-linked polyubiquitination of ASK1 by TRAF6 represents a mechanism underlying ASK1 activation in hepatocytes and a key driving force of proinflammatory and profibrogenic responses in NASH.
Several noninvasive clinical models/scores and plasma biomarkers were measured to identify NASH and advanced fibrosis (NASH: alanine aminotransferase [ALT], cytokeratin-18, NashTest 2, HAIR, BARD, and OWLiver; advanced fibrosis: AST, fragments of propeptide of type III procollagen [PRO-C3], FIB-4, APRI, NAFLD fibrosis score, and FibroTest).
Collectively, our findings indicate that opposite effects of MSCS on NASH progression are mediated by differential modulation of PPARγ and its-associated M1/M2 polarization in hepatic macrophages, depending on exposure time points.
Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination and acting alone or on the background of potent statin therapy which is recommended in T2DM, might contribute substantially to NAFLD/NASH amelioration, possibly reducing not only liver specific but also cardiovascular morbidity.
Multivariate analyses adjusted for age, sex, smoking status, PNPLA3, TM6SF2, and VAT/SAT areas demonstrated an independent and dose-dependent relationship between the body size-metabolic phenotype and NASH or significant fibrosis.
Newer antidiabetic drugs (SPPARMs, GLP-1 RA and SGLT2i) alone or in combination and acting alone or on the background of potent statin therapy which is recommended in T2DM, might contribute substantially to NAFLD/NASH amelioration, possibly reducing not only liver specific but also cardiovascular morbidity.
In this study, we evaluated the therapeutic effect of the synthetic miR-223 analog miR-223 3p in a murine model of lipopolysaccharide (LPS)/D-GalN-induced endotoxin acute hepatitis (EAH) or fibrotic NASH resultant of long-term feeding with a high-fat, fructose, and cholesterol (FFC) diet. miR-223 3p ameliorated the infiltration of monocytes, neutrophils, and early activated macrophages and downregulated the transcriptional expression of the pro-inflammatory cytokines Il6 and Il12 and the chemokines Ccl2, Ccl3, Cxcl1, and Cxcl2 in EAH.
We used real-time polymerase chain reaction (RT-PCR) analysis to evaluate the hepatic and intestinal expression level of all genes studied (TLR2, TLR4, TLR9, LXRα, SREBP1C, ACC1, FAS, PPARα, CPT1α, CROT, SREBP2, ABCA1, ABCG1 and FXR in the liver; TLR2, TLR4, TLR5, TLR9, GLP-1R, DPP-4, FXR and PPARɣ in the jejunum) in 82 women with MO with normal liver histology (NL, n = 29), SS (n = 32), and NASH (n = 21).
Intrahepatic NK cells, recruited through CXCL10-CXCR3 interaction, play a protective role against the fibrosis progression in NASH, which provide us with a better understanding of the immunopathogenesis of NASH.
We aimed to explore whether SGLT2 inhibitor added to the usual care for patients with type 2 diabetes mellitus (T2DM) and biopsy-proven nonalcoholic steatohepatitis (NASH) will benefit NASH histology.
Sirtuin1 (SIRT1) is a crucial regulator of metabolism and it is implicated in the metabolic pathophysiology of several disorders inclusive of Type 2 diabetes and fatty liver disease (NAFLD).