Dysregulated Activation of Hippo-YAP1 Signaling Induces Oxidative Stress and Aberrant Development of Intrahepatic Biliary Cells in Biliary Atresia.

The canonical Hippo-YAP1 signaling pathway is crucial for liver development and regeneration, but its role in repair and regeneration of intrahepatic bile duct in biliary atresia (BA) remains largely unknown. YAP1 expression in the liver tissues of patients with BA and Rhesus rotavirus-induced experimental BA mouse models were examined using quantitative reverse transcriptase-PCR and double immunofluorescence. Mouse EpCAM-expressing cell-derived liver organoids were generated and treated with Hippo-YAP1 pathway activators (Xmu-mp-1 and TRULI) or an inhibitor (Peptide17).

Abnormally activated wingless/integrated signaling modulates tumor-associated macrophage polarization and potentially promotes hepatocarcinoma cell growth.

In this article, we comment on the article by Huang . The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer. Tumor-associated macrophages (TAMs), primarily of the M2 subtype, are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways, including the wingless/integrated (Wnt) pathway.

Animal and organoid models to elucidate the anti-fibrotic effect of steroid on biliary atresia.

Purpose: We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism.

Methods: BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34.

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes.

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes.

Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids.

Background: Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients.

Bioengineering Liver Organoids for Diseases Modelling and Transplantation.

Organoids as three-dimension (3D) cellular organizations partially mimic the physiological functions and micro-architecture of native tissues and organs, holding great potential for clinical applications. Advances in the identification of essential factors including physical cues and biochemical signals for controlling organoid development have contributed to the success of growing liver organoids from liver tissue and stem/progenitor cells. However, to recapitulate the physiological properties and the architecture of a native liver, one has to generate liver organoids that contain all the major liver cell types in correct proportions and relative 3D locations as found in a native liver.

Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia.

Background: Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.

Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.

Mesenchymal stem cells (MSCs) are multipotent stem cells with the capacity of self-renewal, homing, and low immunogenicity. These distinct biological characteristics have already shown immense potential in regenerative medicine. MSCs also possess immunomodulatory properties that can maintain immune homeostasis when the immune response is over-activated or under-activated.

Regenerative medicine: postnatal approaches.

Paper 2 of the paediatric regenerative medicine Series focuses on recent advances in postnatal approaches. New gene, cell, and niche-based technologies and their combinations allow structural and functional reconstitution and simulation of complex postnatal cell, tissue, and organ hierarchies. Organoid and tissue engineering advances provide human disease models and novel treatments for both rare paediatric diseases and common diseases affecting all ages, such as COVID-19.

Regenerative medicine: prenatal approaches.

This two-paper Series focuses on recent advances and applications of regenerative medicine that could benefit paediatric patients. Innovations in genomic, stem-cell, and tissue-based technologies have created progress in disease modelling and new therapies for congenital and incurable paediatric diseases. Prenatal approaches present unique opportunities associated with substantial biotechnical, medical, and ethical obstacles.

CD177 cells produce neutrophil extracellular traps that promote biliary atresia.

Background & Aims: We have previously reported on the potential pathogenic role of neutrophils in biliary atresia (BA). Herein, we aimed to delineate the role of CD177+ neutrophils in the pathogenesis of BA.

Methods: Immune cells from the livers of mice with rhesus rotavirus-induced BA were analysed.

Pathogenesis of Choledochal Cyst: Insights from Genomics and Transcriptomics.

Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, "pancreaticobiliary maljunction" and "congenital stenosis of bile ducts" proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is still poorly understood.

Pattern of anatomic disorder and surgical management of anorectal prolapse in anorectal malformation.

Aim: Due to the paucity of data and controversy regarding the etiology and surgical approach for managing anorectal prolapse (ARP) after anorectoplasty, we sought to investigate the underlying anatomic disorder and the surgical outcome in managing this challenging complication.

Methods: We performed a retrospective study on 83 patients with ARP related to anorectal malformations (ARM). Logistic regression analyses were performed to detect the risk factors for the ARP severity.

Comprehensive analysis of recessive carrier status using exome and genome sequencing data in 1543 Southern Chinese.

Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.

Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents.

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19.

Sequencing of a Chinese tetralogy of Fallot cohort reveals clustering mutations in myogenic heart progenitors.

Tetralogy of Fallot (TOF) is the most common cyanotic heart defect, yet the underlying genetic mechanisms remain poorly understood. Here, we performed whole-genome sequencing analysis on 146 nonsyndromic TOF parent-offspring trios of Chinese ethnicity. Comparison of de novo variants and recessive genotypes of this data set with data from a European cohort identified both overlapping and potentially novel gene loci and revealed differential functional enrichment between cohorts.

Biliary Atresia - emerging diagnostic and therapy opportunities.

Biliary Atresia is a devastating pediatric cholangiopathy affecting the bile ducts of the liver. In this review, we describe recent progress in the understanding of liver development with a focus on cholangiocyte differentiation and how use of technical platforms, including rodent, zebrafish and organoid models, advances our understanding of Biliary Atresia. This is followed by a description of potential pathomechanisms, such as autoimmune responses, inflammation, disturbed apical-basal cell polarity, primary cilia dysfunction as well as beta-amyloid accumulation.