hADMSC-Evs attenuates depressive and anxiety - like behaviors in chronic liver disease via suppressing Liver-Brain Galectin3 signaling.

Chronic liver disease (CLD) is strongly associated with depression, affecting approximately 18-58% of patients and significantly worsening clinical outcomes. Although human adipose-derived mesenchymal stem cell extracellular vesicles (hADMSC-Evs) have demonstrated therapeutic potential in CLD, their ability to simultaneously alleviate depression in CLD remains unexplored. Here we report that hADMSC-Evs administration effectively attenuates both liver fibrosis and depression-like behavior in CLD mice.

Mesenchymal stem cell-derived extracellular vesicles attenuate periductal fibrosis by inhibiting Th17 differentiation in human liver multilineage organoids and Mdr2 mice.

Primary sclerosing cholangitis (PSC) pathogenesis involves immune dysregulation, genetic factors, and bile duct pathology; however, a comprehensive pathogenesis model and effective therapeutic strategies remain limited. Here, we develop a novel human liver multilineage organoid (Mulorg) model combined with Mdr2 mice to investigate the pro-fibrotic role of T helper 17 cells (Th17) and the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (EV) for PSC, particularly periductal fibrosis. EV alleviates interleukin-17A (IL-17A)-induced fibrotic Mulorgs (FibHOs) and mitigates periductal fibrosis in Mdr2 mice by inhibiting Th17 differentiation, decreasing Th17 numbers, and lowering intrahepatic IL-17A levels.

MELD 3.0 Improves Risk Stratification and Mortality Prediction in Hepatorenal Syndrome-Acute Kidney Injury: A Multicentre Study.

Background: Hepatorenal syndrome-acute kidney injury (HRS-AKI) is a life-threatening complication in decompensated cirrhosis with limited predictive tools for short-term prognosis. Traditional models such as MELD, MELD-Na and Child-Turcotte-Pugh (CTP) have notable limitations in this population.

Aims: This study aimed to evaluate the prognostic performance of the newly developed MELD 3.

Human placenta mesenchymal stromal cells alleviate intestinal inflammation and repair intestinal barrier function by activating AMPK-FXR pathway.

Crohn's disease (CD) has a complex pathogenesis; there is currently no effective treatment. Mesenchymal stromal cells (MSCs) are a potential therapeutic option for CD. It is important to systematically evaluate the safety and effectiveness of MSCs and their mechanism for the treatment of CD to support their clinical application.

Association between early antibiotic treatment after admission and mortality of acute-on-chronic liver failure patients with bacterial infection: A multicenter retrospective study.

Bacterial infection is a significant risk factor in the onset and development of acute-on-chronic liver failure (ACLF). Although early broad-spectrum antibiotic treatment is recommended, the optimal time to initiate antibiotic therapy remains unclear. This study aimed to investigate the relationship between the timing of antibiotic treatment and the prognosis of ACLF patients with bacterial infection.

aCCI-HBV-ACLF: A Novel Predictive Model for Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

Background: Early identification of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) holds crucial importance in guiding clinical management and reducing mortality. However, existing scoring systems often overlook patient's underlying clinical condition, which significantly impacts prognosis.

Aims: Use the age-adjusted Charlson comorbidity index (aCCI) to evaluate the patient's complications to develop a more precise model for predicting transplant-free mortality in HBV-ACLF patients.

Organoids: development and applications in disease models, drug discovery, precision medicine, and regenerative medicine.

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions of specific organs. Although the field of organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, and bioinstrumentation, a comprehensive and accurate overview of organoid applications remains necessary. This review offers a detailed exploration of the historical origins and characteristics of various organoid types, their applications-including disease modeling, drug toxicity and efficacy assessments, precision medicine, and regenerative medicine-as well as the current challenges and future directions of organoid research.

ROS-responsive nanoparticle delivery of obeticholic acid mitigate primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a challenging cholestatic liver disease marked by progressive bile duct inflammation and fibrosis that has no FDA-approved therapy. Although obeticholic acid (OCA) has been sanctioned for PSC, its clinical utility in PSC is constrained by its potential hepatotoxicity. Here, we introduce a novel therapeutic construct consisting of OCA encapsulated within a reactive oxygen species (ROS)-responsive, biodegradable polymer, further cloaked with human placenta-derived mesenchymal stem cell (hP-MSC) membrane (MPPFTU@OCA).

Serum metabolomics reveals the effectiveness of human placental mesenchymal stem cell therapy for Crohn's disease.

Mesenchymal stem cell (MSC) therapy offers a promising cure for Crohn's disease (CD), however, its therapeutic effects vary significantly due to individual differences. Therefore, identifying easily detectable biomarkers is essential to assess the efficacy of MSC therapy. In this study, SAMP1/Yit mice were used as a model of CD, which develop spontaneous chronic ileitis, closely resembling the characteristics present in CD patients.

Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells.

Background And Aims: The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression.

Approach And Results: Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation.

MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid-macrophage model.

Acute lung injury (ALI) is an inflammatory disease associated with alveolar injury, subsequent macrophage activation, inflammatory cell infiltration, and cytokine production. Mesenchymal stem cells (MSCs) are beneficial for application in the treatment of inflammatory diseases due to their immunomodulatory effects. However, the mechanisms of regulatory effects by MSCs on macrophages in ALI need more in-depth study.

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation.

Primary sclerosing cholangitis (PSC) is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis, with no curative treatment available, and liver transplantation is inevitable for end-stage patients. Human placental mesenchymal stem cell (hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis, inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease. Here, we prepared hpMSC-derived exosomes (Exo) and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2 mice and multicellular organoids established from PSC patients.

Co-delivery of azithromycin and ibuprofen by ROS-responsive polymer nanoparticles synergistically attenuates the acute lung injury.

Bacterial infection causes lung inflammation and recruitment of several inflammatory factors that may result in acute lung injury (ALI). During bacterial infection, reactive oxygen species (ROS) and other signaling pathways are activated, which intensify inflammation and increase ALI-related mortality and morbidity. To improve the ALI therapy outcome, it is imperative clinically to manage bacterial infection and excessive inflammation simultaneously.

Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2 Mice and Human Intrahepatic Cholangiocyte Organoid Models.

Primary sclerosing cholangitis (PSC) is a biliary disease accompanied by chronic inflammation of the liver and biliary stricture. Mesenchymal stem cells (MSCs) are used to treat liver diseases because of their immune regulation and regeneration-promoting functions. This study was performed to explore the therapeutic potential of human placental MSCs (hP-MSCs) in PSC through the Takeda G protein-coupled receptor 5 (TGR5) receptor pathway.

Mesenchymal stem cells shift the pro-inflammatory phenotype of neutrophils to ameliorate acute lung injury.

Background: Mesenchymal stem cell (MSC) treatment plays a major role in the management of acute lung injury (ALI), and neutrophils are the initial line of defense against ALI. However, the effect of MSCs on neutrophils in ALI remains mostly unknown.

Methods: We investigated the characteristics of neutrophils in lung tissue of ALI mice induced by lipopolysaccharide after treatment with MSCs using single-cell RNA sequencing.

A novel HIF2A mutation causes dyslipidemia and promotes hepatic lipid accumulation.

Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor responsible for regulating genes related to angiogenesis and metabolism. This study aims to explore the effect of a previously unreported mutation c.C2473T (p.

Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models.

Background: Although increasing preclinical studies have emphasized the benefits of exosome-related therapies, the efficacy of mesenchymal stromal cell (MSC)-derived extracellular vesicles (EV) for liver injury is unclear. In this work, a pooled analysis was conducted to explore the overall effect of MSC-EV in animal models.

Methods: A systematic search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases was performed, from initiation to February 2022, for preclinical studies with liver disease models.

Characteristic Analysis of Featured Genes Associated with Cholangiocarcinoma Progression.

The noninvasive diagnosis of cholangiocarcinoma (CCA) is insufficiently accurate. Therefore, the discovery of new prognostic markers is vital for the understanding of the CCA mechanism and related treatment. The information on CCA patients in The Cancer Genome Atlas database was used for weighted gene co-expression network analysis.

Efficacy and Safety of PD-1/PD-L1 Checkpoint Inhibitors versus Anti-PD-1/PD-L1 Combined with Other Therapies for Tumors: A Systematic Review.

Objective: In recent years, the anti-programmed cell death protein-1 and its ligand (PD-1/PD-L1) or combination therapies have been recommended as an alternative emerging choice of treatment for oncology patients. However, the efficacy and adverse events of different combination strategies for the treatment of tumors remain controversial.

Methods: PubMed, Embase, Cochrane Library, the American Society of Clinical Oncology (ASCO), and the European Society of Medicine Oncology (ESMO) were searched from database inception until 16 February 2022.