Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain.

Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters.

ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features.

Idol Depletion Protects against Spontaneous Atherosclerosis in a Hamster Model of Familial Hypercholesterolemia.

Inducible degrader of low-density lipoprotein (LDL) receptor (Idol) is an E3 ubiquitin ligase coded by , the target gene of liver X receptor (LXR), which primarily mediates the ubiquitination and lysosomal degradation of low-density lipoprotein receptor (LDLR). Previous studies from independent groups have shown that plasma cholesterol regulation by the LXR-Idol-LDLR axis is tissue- and species-specific, indicating that the precise molecular mechanism by which Idol modulates lipid metabolism has not been completely understood and needs to be further validated in other species. Hamster, a small rodent animal model expressing endogenous cholesterol ester transfer protein (CETP), possesses many metabolic characteristics that are different from mouse but similar to human.

Targeting ApoC3 Paradoxically Aggravates Atherosclerosis in Hamsters With Severe Refractory Hypercholesterolemia.

Rationale: ApoC3 plays a central role in the hydrolysis process of triglyceride (TG)-rich lipoproteins mediated by lipoprotein lipase (LPL), which levels are positively associated with the incidence of cardiovascular disease (CVD). Although targeting ApoC3 by antisense oligonucleotide (ASO), Volanesorsen markedly reduces plasma TG level and increase high-density lipoprotein cholesterol (HDL-C) in patients with hypertriglyceridemia (HTG), the cholesterol-lowering effect of ApoC3 inhibition and then the consequential outcome of atherosclerotic cardiovascular disease (ASCVD) have not been reported in patients of familial hypercholesterolemia (FH) with severe refractory hypercholesterolemia yet.

Objective: To investigate the precise effects of depleting ApoC3 on refractory hypercholesterolemia and atherosclerosis, we crossed ApoC3-deficient hamsters with a background of LDLR deficiency to generate a double knockout (DKO) hamster model (LDLR, XApoC3, DKO).

Genetically-engineered hamster models: applications and perspective in dyslipidemia and atherosclerosis-related cardiovascular disease.

Cardiovascular disease is the leading cause of morbidity and mortality in both developed and developing countries, in which atherosclerosis triggered by dyslipidemia is the major pathological basis. Over the past 40 years, small rodent animals, such as mice, have been widely used for understanding of human atherosclerosis-related cardiovascular disease (ASCVD) with the advantages of low cost and ease of maintenance and manipulation. However, based on the concept of precision medicine and high demand of translational research, the applications of mouse models for human ASCVD study would be limited due to the natural differences in metabolic features between mice and humans even though they are still the most powerful tools in this research field, indicating that other species with biological similarity to humans need to be considered for studying ASCVD in future.

STAT6 up-regulation amplifies M2 macrophage anti-inflammatory capacity through mesenchymal stem cells.

Extensive infiltration of M2 macrophages plays a crucial role in repairing acute liver failure (ALF), however, the molecular pathways whereby mesenchymal stem cells (MSCs) induce M2 macrophage polarization remains unknown. We investigated the molecular pathways involved in MSC-induced M2 polarization and describe the potential therapeutic effects of M2 macrophages on ALF. The expression of M2 macrophage markers was significantly increased after M0 macrophages were co-cultured with MSCs in vitro.

Programmed death 1, ligand 1 and 2 correlated genes and their association with mutation, immune infiltration and clinical outcomes of hepatocellular carcinoma.

Background: The exact regulation network of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma (HCC).

Aim: To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.

[Study on differentiation of human mesenchymal stem cells into epidermal cells].

Objective: To investigate the possibility of differentiation of human mesenchymal stem cells (hMSC) into epidemic cells in vitro.

Methods: hMSCs were segregated from normal adult human bone marrow by Percoll solution (1.073 g/ml) , and were cultured, purified, and amplified to 3th passage in vitro.

[Isolation, culturation and adipogenisis committed differentiation of adult human mesenchymal stem cell].

Objective: To isolate MSCs from adult human bone marrow cells and to induce them into adipocytes.

Methods: MSCs were isolated from adult human bone marrow aspirated by Percoll and expanded in L-DMEM. The surface antigen of MSCs, CD14, CD34, CD45, CD44, VLA-1, HLA-DR and cell cycle were analysed on a FACScan flow cytometer.