Air-ventilated normothermic mechanical perfusion improves susceptibility to donation after circulatory death and cold preservation-induced cholestatic liver injury through PPAR-γ/UGT1A1 axis.

End-ischemic normothermic mechanical perfusion (NMP) could provide a curative treatment to reduce cholestatic liver injury from donation after circulatory death (DCD) in donors. However, the underlying mechanism remains elusive. Our previous study demonstrated that air-ventilated NMP could improve functional recovery of DCD in a preclinical NMP rat model.

Astaxanthin Alleviates Autoimmune Hepatitis by Modulating CD8 T Cells: Insights From Mass Cytometry and Single-Cell RNA Sequencing Analyses.

Astaxanthin (ASX) is an oxygen-containing non-vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA).

Role of MIC levels and 23S rRNA mutation sites to clarithromycin in 14-day clarithromycin bismuth quadruple therapy for eradication: A prospective trial in Beijing.

Background: Rising clarithromycin resistance undermines () treatment efficacy. We aimed to determine clarithromycin's minimum inhibitory concentration (MIC) levels and identify specific mutation sites in the 23S ribosomal subunit (23S rRNA) that predict treatment outcomes in a 14-day regimen of clarithromycin bismuth quadruple therapy (amoxicillin 1g, clarithromycin 500 mg, rabeprazole 10 mg, and colloidal bismuth pectin 200 mg).

Materials And Methods: We included adult patients who hadn't previously undergone clarithromycin-based treatment, either as initial or rescue therapy.

Adelmidrol ameliorates liver ischemia-reperfusion injury through activating Nrf2 signaling pathway.

Liver ischemia/reperfusion (I/R) injury commonly occurs after various liver surgeries. Adelmidrol, an N- palmitoylethanolamide analog, has anti-inflammatory, anti-oxidant, and anti-injury properties. To investigate whether adelmidrol could reduce liver I/R injury, we established a mouse of liver I/R injury and an AML12 cell hypoxia-reoxygenation model to perform experiments using multiple indicators.

Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses.

Air-ventilated normothermic machine perfusion alleviates hepatic injury from DCD rat through CYP1A2.

Background: Normothermic machine perfusion (NMP) could provide protection to organs from donation after circulatory death (DCD) before transplantation, and its molecular mechanism remains unclear. Our previous study discovered that the air-ventilated NMP confers a better DCD liver recovery than oxygen-ventilated NMP. The purpose in the current study was to investigate the protective mechanism of air-ventilated NMP in a rat model of DCD liver by , and to select biomarker to predict liver function recovery.

Global Trends of Gastrointestinal Endoscopy Anesthesia/Sedation: A Bibliometric Study (from 2001 to 2022).

Background: Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades.

Methods: The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database.

m A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m A-EGFR/STAT3 axis and EMT.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of tumor-related deaths worldwide. N6-methyladenosine (m A) mediates RNA metabolism in tumor biology. However, the regulatory role of YTHDF3, an m A reader, in HCC progression and its underlying mechanisms remains unclear.

Mitogen activated protein kinase phosphatase 5 alleviates liver ischemia-reperfusion injury by inhibiting TAK1/JNK/p38 pathway.

Mitogen activated protein kinase phosphatase 5 (MKP5) is a member of the MKP family and has been implicated in diverse biological and pathological conditions. However, it is unknown what role MKP5 plays in liver ischemia/reperfusion (I/R) injury. In the present study, we used MKP5 global knockout (KO) and MKP5 overexpressing mice to establish a liver I/R injury model in vivo, and MKP5 knockdown or MKP5 overexpressing HepG2 cells to establish a hypoxia-reoxygenation (H/R) model in vitro.

LATS-regulated nuclear-cytoplasmic translocation of SREBP2 inhibits hepatocellular carcinoma cell migration and invasion via epithelial-mesenchymal transition.

Abnormal cholesterol synthesis plays a crucial role in the development of hepatocellular carcinoma (HCC). Sterol regulatory element-binding protein 2 (SREBP2) is involved in cholesterol synthesis by translocating to the nucleus where it stimulates the transcription of genes encoding enzymes involved in the cholesterol synthesis pathway. However, the function and regulatory mechanism of SREBP2 in HCC remain unclear.

Charged multivesicular body protein 2B ameliorates biliary injury in the liver from donation after cardiac death rats via autophagy with air-oxygenated normothermic machine perfusion.

Normothermic machine perfusion (NMP) could provide a curative treatment to reduce biliary injury in donation after cardiac death (DCD) donor livers; however, the underlying mechanisms remain poorly understood. In a rat model, our study compared air-oxygenated NMP to hyperoxygenated NMP and found that air-oxygenated NMP improved DCD functional recovery. Here, we found that the charged multivesicular body protein 2B (CHMP2B) expression was substantially elevated in the intrahepatic biliary duct endothelium of the cold-preserved rat DCD liver after air-oxygenated NMP or in biliary endothelial cells under hypoxia/physoxia.

The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease but still lacks a preclinical strategy to identify it. The diagnostic value of intestinal mucosal α-synuclein (αSyn) in PD has not drawn a uniform conclusion. The relationship between the alteration of intestinal mucosal αSyn expression and mucosal microbiota is unclear.

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma and .

Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-β pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-β pathway.

The reasonable therapeutic modality for biliary duct-to-duct anastomotic stricture after liver transplantation: ERCP or PTC?

Objective: To compare the initial success rate, feasibility, and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) versus percutaneous transhepatic cholangiography (PTC) for anastomotic biliary stricture after liver transplantation (LT).

Methods: We retrospectively analyzed the data collected during January 2015 to December 2021 from liver transplantation recipients who developed anastomotic biliary stricture after liver transplantation and treated by ERCP and/or PTC. The success rate, complications and patients' survival rate of ERCP and PTC procedures was evaluated.

PD-1/PD-L1 inhibition promotes hepatic regeneration in small-for-size liver following extended hepatectomy.

Background: Small-for-size syndrome following liver surgery is characterized by compromised liver regeneration. Liver macrophages play key roles in initiating liver regeneration, and modulation of the immune microenvironment through macrophages may accelerate liver regeneration. In our current study, we aimed to explore the involvement of innate immunity after extended hepatectomy in rats and humans, and to test the effect of immunity modulation on small-for-size liver regeneration in rats.

Evaluation of commonly used cardiovascular drugs in inhibiting vonoprazan metabolism and .

As a novel acid-suppressing drug, vonoprazan shows the potential to replace traditional proton-pump inhibitors. With its widespread use, some adverse effects that require further study have emerged due to drug-drug interactions. Our study is the first experiment that evaluated the drug-drug interactions of eleven common cardiovascular drugs that inhibit vonoprazan metabolism and .

CD8+ T cell trajectory subtypes decode tumor heterogeneity and provide treatment recommendations for hepatocellular carcinoma.

Introduction: Mounting evidence has revealed that the interactions and dynamic alterations among immune cells are critical in shaping the tumor microenvironment and ultimately map onto heterogeneous clinical outcomes. Currently, the underlying clinical significance of immune cell evolutions remains largely unexplored in hepatocellular carcinoma (HCC).

Methods: A total of 3,817 immune cells and 1,750 HCC patients of 15 independent public datasets were retrieved.

Necroptosis throws novel insights on patient classification and treatment strategies for hepatocellular carcinoma.

Introduction: Necroptosis is a novel pattern of immunogenic cell death and has triggered an emerging wave in antitumor therapy. More evidence has suggested the potential associations between necroptosis and intra-tumoral heterogeneity. Currently, the underlying role of necroptosis remains elusive in hepatocellular carcinoma (HCC) at antitumor immunity and inter-tumoral heterogeneity.

Significance of Liver Zonation in Hepatocellular Carcinoma.

Liver zonation is fundamental to normal liver function, and numerous studies have investigated the microstructure of normal liver lobules. However, only a few studies have explored the zonation signature in hepatocellular carcinoma (HCC). In this study, we investigated the significance of liver zonation in HCC with the help of single-cell RNA sequencing (scRNA-seq) and multicolor immunofluorescence staining.

Effects of Simvastatin on the Metabolism of Vonoprazan in Rats Both in vitro and in vivo.

Purpose: To study the potential drug-drug interactions between simvastatin and vonoprazan and to provide the scientific basis for rational use of them in clinical practice.

Methods: An incubation system was established with rat liver microsomes, and the main metabolite of vonoprazan M-I was detected by UPLC-MS/MS. The IC value of simvastatin was then calculated and its inhibitory mechanism against vonoprazan was also analyzed.

Identification of Context-Specific Fitness Genes Associated With Metabolic Rearrangements for Prognosis and Potential Treatment Targets for Liver Cancer.

Liver cancer is the most frequent fatal malignancy. Furthermore, there is a lack of effective therapeutics for this cancer type. To construct a prognostic model for potential beneficiary screens and identify novel treatment targets, we used an adaptive daisy model (ADaM) to identify context-specific fitness genes from the CRISPR-Cas9 screens database, DepMap.

Cytochrome P450 2E1 predicts liver functional recovery from donation after circulatory death using air-ventilated normothermic machine perfusion.

The optimal oxygen concentration is unclear for normothermic machine perfusion (NMP) of livers from donation after circulatory death (DCD). Our purposes were to investigate the effect of air-ventilated NMP on the DCD liver, analyze the underlying mechanism and select the targets to predict liver functional recovery with NMP. NMP was performed using the NMP system with either air ventilation or oxygen ventilation for 2 h in the rat liver following warm ischemia and cold-storage preservation.