Global Journal of Digestive Diseases

Description

Pathophysiology of chronic liver disease as a result of the lack of human-like experimental models. Due to a lack of biomarkers that can identify the disease at an early stage, patients' diagnoses are also very poor. As a result, the formation of a multidisciplinary group with a direct translation from various nations is of the utmost interest. The meeting of the 2021 Iberoamerican Consortium for the Study of Liver Cirrhosis, which took place online in October 2021, is reported here. Cell pathobiology and liver regeneration, as well as molecular and cellular targets involved in non-alcoholic hepatic steatohepatitis, alcoholic liver disease (ALD), both ALD and western diet, end-stage liver cirrhosis, and hepatocellular carcinoma, were the primary topics of discussion at the meeting. The meeting also talked about recent developments in targeted novel technology and new therapeutic possibilities in this area of research. There are no blood biomarkers that can help diagnose cirrhosis patients with covert hepatic encephalopathy (CHE). Hepatic encephalopathy is primarily caused by astrocyte swelling. As a result, we hypothesized that the major intermediate filament of astrocytes, glial fibrillary acidic protein (GFAP), might help with early diagnosis and treatment. The purpose of this study was to determine whether serum GFAP (sGFAP) levels can be used as a biomarker for CHE. In this bicentric study, 15 healthy controls, 21 patients with cirrhosis and ongoing harmful alcohol use, and 135 cirrhosis patients were recruited. The psychometric hepatic encephalopathy score was used to diagnose CHE.

Therapeutic Targets for Reversing Early Cirrhosis

A highly sensitive single-molecule array (SiMoA) immunoassay was used to measure sGFAP levels. There are no blood biomarkers that can help diagnose cirrhosis patients with covert hepatic encephalopathy (CHE). We were able to demonstrate in this study that CHE is correlated with sGFAP levels in cirrhosis patients. As a possible new biomarker, these findings suggest that patients with cirrhosis and subclinical cognitive deficits may already experience astrocyte injury. One or more factors can lead to cirrhosis, a progressive chronic liver disease characterized by pseudolobules, regenerated nodules, and diffuse fibrosis. When a condition progresses to hepatic decompensation, the liver and other organs lose their ability to function normally and are nearly impossible to recover from. As a result, many people end up in hospitals, have poorer quality of life, and die early. However, cirrhosis reversal appears to be possible in the early stages of the disease. The intestinal microbiota and the activation of toll-like receptor (TLR) pathways, which may regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation, are linked to the onset of cirrhosis. The onset, progression, and complications of cirrhosis may be affected by focusing on the regulation of the intestinal microbiota and TLR pathways. The dynamic changes in intestinal microbiota and TLRs as cirrhosis progresses are first discussed in this paper. And went on to talk about how they interact with potential therapeutic targets for reversing early cirrhosis. In response to inflammation, macrophages exhibit distinct phenotypes that are either pro-inflammatory (M1) or anti-inflammatory (M2). In this study, we attempted to determine how macrophage phenotypes are altered by lipopolysaccharide (LPS)-induced intestinal inflammation via interferon regulatory factor 7 (IRF7). Lipopolysaccharide (LPS) was used as the stimulus for the intestinal inflammation model in mice, and mice's intestinal epithelial cells and bone marrow-derived macrophages (BMDMs) were chosen for in vitro testing. IRF7 deficiency suppressed macrophage M1 polarization and reduced intestinal inflammation in mice, whereas IRF7 was highly expressed in the mouse model of intestinal inflammation. IRF7 expression was boosted by the synergistic promotion of H3K4me3 methylation by p65 and SET domain bifurcated 1 (SETDB1), which in turn triggered the Nod-like receptor (NLR) pathway and caused macrophage M1 polarization. In BMDMs, this mechanism allowed IRF7 to accelerate the apoptosis and release of pro-inflammatory proteins in intestinal epithelial cells. In addition, the in vivo validation of the promoting effect of p65 and SETDB1 on LPS-induced intestinal inflammation.

Creatinine and Blood Urea Nitrogen

In conclusion, LPS-induced intestinal inflammation was exacerbated by NF-B p65 and SETDB1 facilitating IRF7-mediated macrophage M1 polarization. As a result, the attractiveness of these factors as anti-inflammatory targets is highlighted in this study. Male Wistar rats were subjected to simultaneous oral and intramuscular administration of the ginsenosides Rg1 and Rg3 for three days to induce AKI. On human embryonic kidney epithelial (HEK-293), the therapeutic potential of Rg1 and Rg3 was also examined. To determine how harmful Rg1 and Rg3 are, HEK-293 cells were subjected to cell viability and LDH assay tests. At various time points, the rat serum was used to evaluate important kidney damage markers like creatinine and blood urea nitrogen (BUN). Tissues from the kidney were subjected to histopathological examination. To obtain the results, we also carried out procedures like the ELISA assay, immunohistochemistry, immunofluorescence staining, COMET assay, western blotting, the TUNEL assay, and flow cytometry. Dose-dependently, Rg1 and Rg3 significantly decreased the expression of markers of kidney damage like creatinine and BUN. In glycerol treatment groups, histopathological examination revealed damage to the glomerulus, tubules, and collecting duct, resulting in kidney dysfunction. However, tubular necrosis was significantly reduced at both 10 and 20 mg/kg in the Rg1 and Rg3 treated groups. ER stress and oxidative stress markers were also markedly reduced. In addition, we discovered Nrf2 nuclear translocations that were more pronounced in kidney tissues. Immunoblotting for intrinsic apoptosis markers, immunofluorescence staining for p53, the TUNEL assay, and flow cytometry all demonstrated that Rg1 and Rg3 also prevented apoptotic cell death in vivo and in vitro.