Enhanced In Vitro Recapitulation of In Vivo Liver Regeneration by Co-Culturing Hepatocyte Organoids with Adipose-Derived Mesenchymal Stem Cells, Alleviating Steatosis and Apoptosis in Acute Alcoholic Liver Injury.

Hepatocyte organoids (HOs) have superior hepatic functions to cholangiocyte-derived organoids but suffer from shorter lifespans. To counteract this, we co-cultured pig HOs with adipose-derived mesenchymal stem cells (A-MSCs) and performed transcriptome analysis. The results revealed that A-MSCs enhanced the collagen synthesis pathways, which are crucial for maintaining the three-dimensional structure and extracellular matrix synthesis of the organoids.

Adipose Tissue-Derived Mesenchymal Stem Cells Extend the Lifespan and Enhance Liver Function in Hepatocyte Organoids.

In this study, we generated hepatocyte organoids (HOs) using frozen-thawed primary hepatocytes (PHs) within a three-dimensional (3D) Matrigel dome culture in a porcine model. Previously studied hepatocyte organoid analogs, spheroids, or hepatocyte aggregates created using PHs in 3D culture systems have limitations in their in vitro lifespans. By co-culturing adipose tissue-derived mesenchymal stem cells (A-MSCs) with HOs within a 3D Matrigel dome culture, we achieved a 3.

Potential Application of Muscle Precursor Cells from Male Specific-Pathogen-Free (SPF) Chicken Embryos in In Vitro Agriculture.

This study examined the potential benefits of male specific-pathogen-free (SPF) White Leghorn embryos in cellular agriculture for sustainable and ethical poultry meat production-addressing traditional farming challenges, including disease outbreaks of and Avian influenza. We isolated myogenic precursor cells (MPCs) from the thigh muscles () of 12.5-day-old embryos from 10 SPF White Leghorns that tested negative for .

SOX9 is a key component of RUNX2-regulated transcriptional circuitry in osteosarcoma.

Background: The absence of prominent, actionable genetic alternations in osteosarcomas (OS) implies that transcriptional and epigenetic mechanisms significantly contribute to the progression of this life-threatening form of cancer. Therefore, the identification of potential transcriptional events that promote the survival of OS cells could be key in devising targeted therapeutic approaches for OS. We have previously shown that RUNX2 is a transcription factor (TF) essential for OS cell survival.

Autophagy Inhibition as a Potential Therapeutic Strategy for Breast Cancer with Mitochondrial Translation Defect Caused by CBFB-Deficiency.

AMPK, AMP-activated protein kinase; BioID, biotinylation identification; CBFB, core-binding factor subunit beta; HCQ, hydroxychloroquine; HNRNPK, heterogeneous nuclear ribonucleoprotein K; PDX, patient-derived xenograft; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; TUFM, Tu translation elongation factor, mitochondrial; ETC, electron transport chain.

Effect of Serum and Oxygen on the In Vitro Culture of Hanwoo Korean Native Cattle-Derived Skeletal Myogenic Cells Used in Cellular Agriculture.

Skeletal muscle-derived myogenic cells (SKMCs) are novel protein sources capable of replacing animal meat. However, SKMCs have not been commercialized owing to poor productivity and the high cost of in vitro cell culture. Therefore, we cultured SKMCs in varying serum (5-20%) and oxygen concentrations (5-20%) to investigate the parameters that most impact cell productivity (serum, hypoxia, and culture medium) and examined cell proliferation ability and genes involved in myogenesis/proliferation/apoptosis/reactive oxygen species (ROS).

Dysregulation of Mitochondrial Translation Caused by CBFB Deficiency Cooperates with Mutant PIK3CA and Is a Vulnerability in Breast Cancer.

Unlabelled: Understanding functional interactions between cancer mutations is an attractive strategy for discovering unappreciated cancer pathways and developing new combination therapies to improve personalized treatment. However, distinguishing driver gene pairs from passenger pairs remains challenging. Here, we designed an integrated omics approach to identify driver gene pairs by leveraging genetic interaction analyses of top mutated breast cancer genes and the proteomics interactome data of their encoded proteins.

Effect of radiofrequency exposure on body temperature: Real-time monitoring in normal rats.

Radiofrequency radiation (RFR) can generate heat in living organisms. In this study, we monitored the body temperature of healthy animals during RFR exposure in real time using an implantable iButton data logger. A reverberation chamber system for small animals was used for this radiofrequency (RF) exposure in vivo study.

Immunosuppression-enhancing effect of the administration of allogeneic canine adipose-derived mesenchymal stem cells (cA-MSCs) compared with autologous cA-MSCs .

Background: Recently, mesenchymal stem cells therapy has been performed in dogs, although the outcome is not always favorable.

Objectives: To investigate the therapeutic efficacy of mesenchymal stem cells (MSCs) using dog leukocyte antigen (DLA) matching between the donor and recipient .

Methods: Canine adipose-derived MSCs (cA-MSCs) isolated from the subcutaneous tissue of Dog 1 underwent characterization.

Structural Investigation of Self-Assembly and Target Binding of Anti-CRISPR AcrIIC2.

Anti-CRISPR (Acr) proteins are phage-borne inhibitors of the CRISPR-Cas immune system in archaea and bacteria. AcrIIC2 from prophages of disables the nuclease activity of type II-C Cas9, such that dimeric AcrIIC2 associates with the bridge helix (BH) region of Cas9 to compete with guide RNA loading. AcrIIC2 in solution readily assembles into oligomers of variable lengths, but the oligomeric states are not clearly understood.

Fatty acid oxidation is required for embryonic stem cell survival during metabolic stress.

Metabolic regulation is critical for the maintenance of pluripotency and the survival of embryonic stem cells (ESCs). The transcription factor Tfcp2l1 has emerged as a key factor for the naïve pluripotency of ESCs. Here, we report an unexpected role of Tfcp2l1 in metabolic regulation in ESCs-promoting the survival of ESCs through regulating fatty acid oxidation (FAO) under metabolic stress.

CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer.

The CBFB gene is frequently mutated in several types of solid tumors. Emerging evidence suggests that CBFB is a tumor suppressor in breast cancer. However, our understanding of the tumor suppressive function of CBFB remains incomplete.

Effect of sex-specific differences on function of induced hepatocyte-like cells generated from male and female mouse embryonic fibroblasts.

Background: The liver is one of the vital organs involved in detoxification and metabolism. The sex-based differences between the functionality of male and female liver have been previously reported, i.e.

Induction of the differentiation of porcine bone marrow mesenchymal stem cells into premature hepatocyte-like cells in an indirect coculture system with primary hepatocytes.

Liver transplantation is currently the only option for patients with end-stage liver disease. Thus, other alternate therapeutic strategies are needed. Bone marrow mesenchymal stem cells (BM-MSCs) are nonhematopoietic cells present in the bone marrow stroma that serve as precursors cells for various other cells.

Determinants of PB1 Domain Interactions in Auxin Response Factor ARF5 and Repressor IAA17.

Auxin is a plant hormone that is central to plant growth and development from embryogenesis to senescence. Auxin signaling is mediated by auxin response transcription factors (ARFs) and Aux/IAA repressors that regulate the expression of a multitude of auxin response genes. ARF and Aux/IAA proteins assemble into homomeric and heteromeric complexes via their conserved PB1 domains.

Transdifferentiation of α-1,3-galactosyltransferase knockout pig bone marrow derived mesenchymal stem cells into pancreatic β-like cells by microenvironment modulation.

Objective: To evaluate the pancreatic differentiation potential of α-1,3-galactosyltransferase knockout (GalTKO) pig-derived bone marrow-derived mesenchymal stem cells (BM-MSCs) using epigenetic modifiers with different pancreatic induction media.

Methods: The BM-MSCs have been differentiated into pancreatic β-like cells by inducing the overexpression of key transcription regulatory factors or by exposure to specific soluble inducers/small molecules. In this study, we evaluated the pancreatic differentiation of GalTKO pig-derived BM-MSCs using epigenetic modifiers, 5-azacytidine (5-Aza) and valproic acid (VPA), and two types of pancreatic induction media - advanced Dulbecco's modified Eagle's medium (ADMEM)-based and N2B27-based media.

Stable Regulation of Senescence-Related Genes in Galactose-alpha1,3-galactose Epitope Knockout and Human Membrane Cofactor Protein hCD46 Pig.

Background: Pigs are considered suitable animal donor models for xenotransplantation. For successful organ transplantation, immune rejection must be overcome. Xenotransplantation has recently been successfully performed using galactose-alpha1,3-galactose epitopes knockout (GalTKO) and a human membrane cofactor protein (hCD46) in a pig model.

Anti-CRISPR AcrIIC3 discriminates between Cas9 orthologs via targeting the variable surface of the HNH nuclease domain.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems constitute the adaptive immunity of bacteria and archaea, degrading nucleic acids of invading phages and plasmids. In response, phages employ anti-CRISPR (Acr) proteins as a counterdefense mechanism to neutralize the host immunity. AcrIIC3 directly inhibits target DNA cleavage of type II-C Cas9 of Neisseria meningitidis.

Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis.

While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder.

CST3 and GDF15 ameliorate renal fibrosis by inhibiting fibroblast growth and activation.

The final strategies to care patients with end-stage renal fibrosis rely on dialysis and kidney transplantation. Because such treatments are invasive and cause health problems eventually, it is necessary to develop new therapeutic strategies for delaying the disease progress. We here searched for cytokines showing an anti-fibrotic activity in cell-based experiments.

Molecular immunology profiles of monkeys following xenografting with the islets and heart of α-1,3-galactosyltransferase knockout pigs.

Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old). The immunosuppressive regimen included administration of cobra venom factor, anti-thymocyte globulin, rituximab, and anti-CD154 monoclonal antibodies to recipients before and after grafting.

ITF2 prevents activation of the β-catenin-TCF4 complex in colon cancer cells and levels decrease with tumor progression.

Background & Aims: Immunoglobulin transcription factor 2 (ITF2) was believed to promote neoplastic transformation via activation of β-catenin. However, ITF2 recently was reported to suppress colon carcinogenesis. We investigated the roles of ITF2 in colorectal cancer cell lines and tumor formation and growth in mice.

Mad1 mediates hypoxia-induced doxorubicin resistance in colon cancer cells by inhibiting mitochondrial function.

Cancer cells acquire resistance to chemotherapy under hypoxia, which is mainly driven by the transcription factor HIF (hypoxia-inducible factor). Yet, it is uncertain which molecules mediate such resistance. While profiling gene expression in colon cancer cells, we found that Mad1 (MAX dimerization protein 1) is substantially induced during hypoxia.

Clinical comparison of the predictive value of the simple skull x-ray and 3 dimensional computed tomography for skull fractures of children.

Objective: In the pediatric population the skull has not yet undergone ossification and it is assumed that the diagnostic rate of skull fractures by simple X-rays are lower than that of adults. It has been recently proposed that the diagnostic rates of skull fractures by 3-dimensional computer tomography (3D-CT) are higher than simple X-rays. The authors therefore attempted to compare the diagnostic rates of pediatric skull fractures by simple X-rays and 3D-CTs with respect to the type of fracture.