Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance.

Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting to methyl donor for the methylation of DNA, RNA and protein. However, it remains unclear whether methionine affects drug resistance by influencing YAP activity.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

Background & Aims: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH.

Tripartite motif 8 promotes the progression of hepatocellular carcinoma via mediating ubiquitination of HNF1α.

Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function.

Abrogating K458 acetylation enhances hepatocyte nuclear factor 4α (HNF4α)-induced differentiation therapy for hepatocellular carcinoma.

Objectives: In this study we aimed to assess the impact of acetylation of hepatocyte nuclear factor 4α (HNF4α) on lysine 458 on the differentiation therapy of hepatocellular carcinoma (HCC).

Methods: Periodic acid-Schiff (PAS) staining, Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake, and senescence-associated β-galactosidase (SA-β-gal) activity analysis were performed to assess the differentiation of HCC cells. HNF4α protein was detected by western blot and immunohistochemistry (IHC).

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP.

miR-541 is associated with the prognosis of liver cirrhosis and directly targets JAG2 to inhibit the activation of hepatic stellate cells.

Background: The activation of hepatic stellate cells (HSCs) has been emphasized as a leading event of the pathogenesis of liver cirrhosis, while the exact mechanism of its activation is largely unknown. Furthermore, the novel non-invasive predictors of prognosis in cirrhotic patients warrant more exploration. miR-541 has been identified as a tumor suppressor in hepatocellular carcinoma and a regulator of fibrotic disease, such as lung fibrosis and renal fibrosis.

TRIB3-TRIM8 complex drives NAFLD progression by regulating HNF4α stability.

Background & Aims: Endoplasmic reticulum (ER) stress of hepatocytes plays a causative role in non-alcoholic fatty liver disease (NAFLD). Reduced expression of hepatic nuclear factor 4α (HNF4α) is a critical event in the pathogenesis of NAFLD and other liver diseases. Whether ER stress regulates HNF4α expression remains unknown.

Rifaximin treatment shapes a unique metagenome-metabolism network in patients with decompensated cirrhosis.

Background: Patients with decompensated cirrhosis face poor prognosis and increased mortality risk. Rifaximin, a non-absorbable antibiotic, has been shown to have beneficial effects in preventing complications and improving survival in these patients. However, the underlying mechanisms of rifaximin's effects remain unclear.

Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

Objectives: Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients.

Skeletal muscle alterations indicate poor prognosis in cirrhotic patients: a multicenter cohort study in China.

Introduction: We aimed to determine the diagnostic criteria of myosteatosis in a Chinese population and investigate the effect of skeletal muscle abnormalities on the outcomes of cirrhotic patients.

Methods: Totally 911 volunteers were recruited to determine the diagnostic criteria and impact factors of myosteatosis, and 480 cirrhotic patients were enrolled to verify the value of muscle alterations for prognosis prediction and establish new noninvasive prognostic strategies.

Results: Multivariate analysis showed age, sex, weight, waist circumference, and biceps circumference had a remarkable influence on the L3 skeletal muscle density (L3-SMD).

Prevalence and risk factors of covert hepatic encephalopathy in cirrhotic patients: A multicenter study in China.

Objective: We aimed to investigate the prevalence of covert hepatic encephalopathy (CHE) in cirrhotic patients in China and its risk factors.

Methods: A multicenter prospective observational study was conducted from January 2021 to March 2022 at 16 medical centers across China to investigate the risk factors of CHE and establish a prediction model for CHE episodes.

Results: A total of 528 patients were enrolled in the study.

Depletion of Tgfbr2 in hepatocytes alleviates liver fibrosis and restores hepatic function in fibrotic mice.

Objectives: Previous studies have demonstrated the pivotal role of transforming growth factor (TGF)-β signaling in activating hepatic stellate cells during liver fibrosis. In this study we aimed to demonstrate the effects and underlying mechanism of TGF-β signaling in hepatocytes on hepatic fibrogenesis.

Methods: Hepatocyte-specific Tgfbr2-knockout (Tgfbr2 ) mice were generated by AAV8-TBG-Cre injection via the tail vein of Tgfbr2 mice.

Sulodexide attenuates liver fibrosis in mice by restoration of differentiated liver sinusoidal endothelial cell.

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms.

Sustained ameliorating effects and autonomic mechanisms of transcutaneous electrical acustimulation at ST36 in patients with chronic constipation.

Background And Aims: The treatment of chronic constipation is still a great challenge in clinical practice. This study aimed to determine the efficacy and sustained effects of transcutaneous electrical acustimulation (TEA) at acupoint ST36 on the treatment of chronic constipation and explore possible underlying mechanisms.

Methods: Forty-four patients with chronic constipation were recruited and randomly assigned to a TEA group or sham-TEA group.

In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations.

In vitro models of liver (patho)physiology, new technologies, and experimental approaches are progressing rapidly. Based on cell lines, induced pluripotent stem cells or primary cells derived from mouse or human liver as well as whole tissue (slices), such in vitro single- and multicellular models, including complex microfluidic organ-on-a-chip systems, provide tools to functionally understand mechanisms of liver health and disease. The International Society of Hepatic Sinusoidal Research (ISHSR) commissioned this working group to review the currently available in vitro liver models and describe the advantages and disadvantages of each in the context of evaluating their use for the study of liver functionality, disease modeling, therapeutic discovery, and clinical applicability.

Effects of Low-dose and High-dose Rifaximin in the Treatment of Covert Hepatic Encephalopathy.

Background And Aims: Rifaximin is effective in preventing and treating hepatic encephalopathy (HE). This study aimed to investigate the efficacy and safety of different dosages of rifaximin in the treatment of cirrhotic patients with covert HE (CHE).

Methods: In this single-center, randomized, controlled, open-label study, CHE was diagnosed using a combination of the psychometric HE score and the EncephalApp Stroop test.

Inhibition of protein arginine methyltransferase 1 alleviates liver fibrosis by attenuating the activation of hepatic stellate cells in mice.

Protein arginine methyltransferase 1 (PRMT1) has been reported to be involved in various diseases. The expression of PRMT1 was increased in cirrhotic livers from human patients. However, the role of PRMT1 in hepatic fibrogenesis remains largely unexplored.

Gut Microbial Profile in Asymptomatic Gallstones.

There are few studies on the changes of gut microbiota in patients with gallstones, especially in patients with asymptomatic gallstones, and there are some deficiencies in these studies, for instance, the effects of metabolic factors on gut microbiota are not considered. Here, we selected 30 asymptomatic gallstone patients from the survey population, and 30 controls according to the age and BMI index matching principle. The 16SrDNA technology was used to detect and compare the structural differences in the gut microbiota between the two groups.

15-Month Health Outcomes and the Related Risk Factors of Hospitalized COVID-19 Patients From Onset: A Cohort Study.

Objective: The long-term impact of COVID-19 on patient health has been a recent focus. This study aims to determine the persistent symptoms and psychological conditions of patients hospitalized with COVID-19 15 months after onset, that patients first developed symptoms. The potential risk factors were also explored.

Rifaximin Ameliorates Non-alcoholic Steatohepatitis in Mice Through Regulating gut Microbiome-Related Bile Acids.

Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease (NAFLD). The non-absorbable antibiotic rifaximin has been used for treatment of irritable bowel syndrome, traveling diarrhea, and hepatic encephalopathy, but the efficacy of rifaximin in NASH patients remains controversial. This study investigated the effects and underlying mechanisms of rifaximin treatment in mice with methionine and choline deficient (MCD) diet-induced NASH.