Dissecting causal relationships between primary biliary cholangitis and extrahepatic autoimmune diseases based on Mendelian randomization.

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types.

Indoleamine 2, 3-dioxygenase 1 activation in macrophage exacerbates hepatic ischemia-reperfusion injury by triggering hepatocyte ferroptosis.

Background: Hepatic Ischemia-reperfusion (I/R) injury, critical challenge in liver surgery and transplantation, exerts a significant impact on the prognosis and survival of patients. Inflammation and cell death play pivotal roles in pathogenesis of hepatic I/R injury. Indoleamine 2, 3-dioxygenase 1 (IDO-1), a key enzyme involved in the kynurenine pathway, has been extensively investigated for its regulatory effects on innate immune responses and cell ferroptosis.

Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system.

Background: Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients.

STING modulates iron metabolism to promote liver injury and inflammation in acute immune hepatitis.

The pathogenesis of Autoimmune Hepatitis (AIH) is closely associated with perturbations in iron ion metabolism, during which Stimulator of Interferon Genes (STING) plays an important role. However, the precise regulatory mechanism remains elusive. In this study, we investigated the relationship between iron dysregulation and STING activation in Concanavalin A (ConA)-induced AIH liver injury.

Endogenous Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy.

Background: Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF-β-induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs.

Mesenchymal stem cell-derived exosomes protect against liver fibrosis via delivering miR-148a to target KLF6/STAT3 pathway in macrophages.

Background: Despite emerging evidence on the therapeutic potential of mesenchymal stem cells (MSCs) for liver fibrosis, the underlying mechanisms remain unclear. At present, MSC-derived exosomes (MSC-EXOs) are widely accepted as crucial messengers for intercellular communication. This study aimed to explore the therapeutic effects of MSC-EXOs on liver fibrosis and identify the mechanisms underlying the action of MSC-EXOs.

A novel angiographic classification of pseudoaneurysms of the pulmonary chronic inflammatory cavity based on selective angiograms and therapeutic implications.

Background: Hemoptysis is a common clinical symptom. In the chronic tuberculosis cavity and chronic necrotizing pneumonia cavity, pseudoaneurysms (Pas) easily form and are prone to massive hemoptysis and repeated hemoptysis and can even endanger patient's life. However, it remains to be further analyzed whether Pas of the pulmonary chronic inflammatory cavity selectively affect the peripheral pulmonary branches.

Poria cocos polysaccharides rescue pyroptosis-driven gut vascular barrier disruption in order to alleviates non-alcoholic steatohepatitis.

Ethnopharmacological Relevance: Poria cocos polysaccharides (PCP) are abundant in Poria cocos (Schw.) Wolf (Poria). This is a common traditional Chinese medicine used to treat gastrointestinal and liver diseases.

Identification and validation a costimulatory molecule gene signature to predict the prognosis and immunotherapy response for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Costimulatory molecules have been proven to be the foundation of immunotherapy. However, the potential roles of costimulatory molecule genes (CMGs) in HCC remain unclear.

Immunoglobulin M: A Neglected Serum Biomarker in Treatment-Naive Primary Biliary Cholangitis With Normal Alkaline Phosphatase.

The diagnosis of primary biliary cholangitis (PBC) in patients with seropositive anti-mitochondrial antibody (AMA) but normal alkaline phosphatase (ALP) depends on a liver biopsy. We aimed to reveal potential serum biomarkers that could suggest the necessity of a liver biopsy in such patients. Retrospective analysis was performed.

Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes.

Hepatocellular carcinoma (HCC), a highly aggressive tumor, has high incidence and mortality rates. Recently, immunotherapies have been shown to be a promising treatment in HCC. The results of either the CheckMate-040 or IMbrave 150 trials demonstrate the importance of immunotherapy in the systemic treatment of liver cancer.

Indoleamine 2, 3-dioxygenase 1 aggravates acetaminophen-induced acute liver failure by triggering excess nitroxidative stress and iron accumulation.

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1).

Systematic Construction and Validation of an RNA-Binding Protein-Associated Model for Prognosis Prediction in Hepatocellular Carcinoma.

Background: Evidence from prevailing studies show that hepatocellular carcinoma (HCC) is among the top cancers with high mortality globally. Gene regulation at post-transcriptional level orchestrated by RNA-binding proteins (RBPs) is an important mechanism that modifies various biological behaviors of HCC. Currently, it is not fully understood how RBPs affects the prognosis of HCC.

An enhanced level of LAMP-2A participates in CD4T cell hyperactivity in patients with primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis, in which T cell homeostasis plays an important role. Lysosomal-associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4T cell responses.

Methods: We comprehensively evaluated the immunobiology of CD4T cells in patients with PBC (PBC, n=42), chronic hepatitis B (CHB, n=20), and healthy control subjects (HC, n=20) by flow cytometry including activation status and LAMP-2A expression.

A nomogram based on pretreatment clinical parameters for the prediction of inadequate biochemical response in primary biliary cholangitis.

Background: Ursodeoxycholic acid (UDCA) has been widely recommended as the first-line drug for primary biliary cholangitis (PBC) in the current guidelines. However, its therapeutic effects are poor in nearly one-third of patients. The early identification and intervention of these patients is crucial for delaying disease progression.

Caveolin-1 protects against DSS-induced colitis through inhibiting intestinal nitrosative stress and mucosal barrier damage in mice.

Caveolin-1 (Cav-1) is a multifunctional protein and critical for the production of nitric oxide (NO) in intestinal physiological and pathological conditions, but its role in the inflammatory bowel disease(IBD) are still controversial. In this study we tested the hypothesis that Cav-1 could be an important cellular defense against IBD through inhibiting nitrosative stress and mucosal barrier damage. Male wild-type mice and Cav-1 knockout (Cav-1) mice were subjected to 3% dextran sodium sulfate(DSS) for 7d to establish the experimental colitis model.

Association of short-term exposure to sulfur dioxide and hospitalization for ischemic and hemorrhagic stroke in Guangzhou, China.

Background: In developing countries, ambient sulfur dioxide (SO) is a serious air pollutant concern, but there is no enough and consistent epidemiological evidence about its health effects on stroke hospitalization.

Methods: We collected the daily air pollution data, meteorological data and number of daily hospital admissions for ischemic and hemorrhagic stroke, in Guangzhou from January 1st 2009 to December 31st 2014. Then we applied generalized additive model with a quasi-Poisson link to assess the relationship between short-term SO exposure and the total number of hospital admissions for ischemic and hemorrhagic stroke.

Indoleamine 2, 3-dioxygenase 1enhanceshepatocytes ferroptosis in acute immune hepatitis associated with excess nitrative stress.

Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms of ferroptosis in acute immune hepatitis (AIH) are largely unknown. In this study, we investigated the classical ferroptotic events in the livers of mice with concanavalin A (ConA) to induce AIH.

Caveolin-1 dictates ferroptosis in the execution of acute immune-mediated hepatic damage by attenuating nitrogen stress.

Ferroptosis is a new regulated cells death manner defined as results of iron-dependent accumulation of lipid peroxidation. However, the specific mechanisms of regulating ferroptosis remain unclear. In our present study, we demonstrated that Caveolin-1 (Cav-1) played a central role in protecting hepatocytes against ferroptosis in autoimmunity-mediated hepatitis (AIH).

Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease.

Danon disease (DD) is caused by the absence or malfunction of lysosomal-associated membrane protein 2 (LAMP2). Although Lamp2-deficient mice and DD patients have similar characteristics, these mice have clear limitations and are clinically inconsistent. The aim of our paper is to outline the characteristics of Lamp2-deficient rats and to contrast this model with currently available DD mouse models.

A Critical Evaluation of Liver Pathology in Humans with Danon Disease and Experimental Correlates in a Rat Model of LAMP-2 Deficiency.

Danon disease is a genetic deficiency in lysosome-associated membrane protein 2 (LAMP-2), a highly glycosylated constituent of the lysosomal membrane and characterized by a cardiomyopathy, skeletal muscle myopathy, and cognitive impairment. Patients, however, often manifest hepatic abnormalities, but liver function has not been well evaluated and the syndrome is relatively uncommon. Hence, we have taken advantage of a rat that has been deleted of LAMP-2 to study the relative role of LAMP-2 on liver function.

Percutaneous transhepatic balloon-assisted transjugular intrahepatic portosystemic shunt for chronic, totally occluded, portal vein thrombosis with symptomatic portal hypertension: procedure technique, safety, and clinical applications.

Objectives: To introduce a modified transjugular intrahepatic portosystemic shunt (TIPS) procedure, percutaneous transhepatic balloon-assisted TIPS (BA-TIPS), and to evaluate its feasibility and efficacy in patients with chronic totally occluded portal vein thrombosis (CTO-PVT) with symptomatic portal hypertension.

Methods: Eighteen patients (12 men, six women; mean age 49 years [range, 34-68 years]) with CTO-PVT with symptomatic portal hypertension undergoing BA-TIPS between July 2011 and June 2014 were enrolled in this retrospective study. Rates of technical success, efficacy, and complications were evaluated, and pre- and post-procedure portosystemic gradients compared.

T-Stenting-and-Small-Protrusion Technique for Bifurcation Stenoses After End-to-Side Anastomosis of Transplant Renal Artery and External Iliac Artery: Report of Two Cases.

Bifurcation stenoses after end-to-side anastomosis of transplant renal artery (TRA) and external iliac artery (EIA), including stenoses at the anastomosis and the iliac artery proximal to the TRA, are rare. In the present article, we report two successfully managed cases of bifurcation stenoses after end-to-side anastomosis of the TRA and EIA using the technique of T-stenting and small protrusion (TAP stenting).