A High-Throughput Microphysiological Liver Chip System to Model Drug-Induced Liver Injury Using Human Liver Organoids.

Background And Aims: Drug-induced liver injury (DILI) is a major failure mode in pharmaceutical development. This study aims to address the limitations of existing preclinical models by assessing a high-throughput, microfluidic liver-on-a-chip system, termed "Curio Barrier Liver Chips," and its capacity to recapitulate the effects of chronic hepatotoxic drug treatment through metabolic and phenotypic characterization.

Methods: Curio Barrier liver chips (Curiochips), fabricated in an 8 × 2 well configuration, were utilized to establish three dimensional liver organoid cultures.

Association Between Dysphagia and Depressive Symptoms: Propensity Score Matching Approaches.

The co-occurrence of depression and dysphagia is obvious to clinicians and has been the focus of several research investigations. Dysphagia not only leads to physical complications but also exerts a negative emotional impact, resulting in a decline in quality of life. The purpose of the study was to investigate the association between dysphagia and depressive symptoms at the population level while accounting for various demographics and health conditions.

Patient-derived tumor spheroid-induced angiogenesis preclinical platform for exploring therapeutic vulnerabilities in cancer.

This study addresses the demand for research models that can support patient-treatment decisions and clarify the complexities of a tumor microenvironment by developing an advanced non-animal preclinical cancer model. Based on patient-derived tumor spheroids (PDTS), the proposed model reconstructs the tumor microenvironment with emphasis on tumor spheroid-driven angiogenesis. The resulting microfluidic chip system mirrors angiogenic responses elicited by PDTS, recapitulating patient-specific tumor conditions and providing robust, easily quantifiable outcomes.

Characterizing On-Chip Angiogenesis Induction in a Microphysiological System as a Functional Measure of Mesenchymal Stromal Cell Bioactivity.

Mesenchymal stromal cells (MSCs) continue to be proposed for clinical investigation to treat myriad diseases given their purported potential to stimulate endogenous regenerative processes, such as angiogenesis. However, MSC functional heterogeneity has hindered clinical success and still poses a substantial manufacturing challenge from a product quality control perspective. Here, a quantitative bioassay based on an enhanced-throughput is described, microphysiological system (MPS) to measure the specific bioactivity of MSCs to stimulate angiogenesis as a potential measure of MSC potency.

First-in-human study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors.

Preclinical models suggest anticancer activity of IM156, a novel biguanide mitochondrial protein complex 1 inhibitor of oxidative phosphorylation (OXPHOS). This first-in-human dose-escalation study enrolled patients with refractory advanced solid tumors to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Eligible patients received oral IM156 every other day (QOD) or daily (QD) and were assessed for safety, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary signals of efficacy.

Evaluation of an Oral Health Management Project in Connection to a Non-Communicable Disease Prevention and Management Project: A Case Study in South Korea.

This study aimed to develop, pilot, and evaluate a three-year integrated preventive management project focused on chronic diseases and oral health prevalence. A total of 1148 users of the health care office of the G Public Health Center with dental risk factors were selected for this study and connected to the dental counseling department. Respondents were classified into a group that would receive counseling-type self-education on oral care and a second group that needed dental care.

Modulation of Oxidative Phosphorylation with IM156 Attenuates Mitochondrial Metabolic Reprogramming and Inhibits Pulmonary Fibrosis.

Metabolic reprogramming of the myofibroblast plays a fundamental role in the pathogenesis of fibrosing interstitial lung diseases. Here, we characterized the in vitro and in vivo metabolic and antifibrotic effects of IM156, an oxidative phosphorylation (OXPHOS) modulator that acts by inhibiting protein complex 1. In vitro, IM156 inhibited transforming growth factor (TGF)-dependent increases in mitochondrial oxygen consumption rate and expression of myofibroblast markers in human pulmonary fibroblasts without altering cell viability or adding to TGF-induced increases in the extracellular acidification rate.

Repression of LKB1 by Sensitizes -Dependent Lymphoma to Biguanide Treatment.

Cancer cells display metabolic plasticity to survive stresses in the tumor microenvironment. Cellular adaptation to energetic stress is coordinated in part by signaling through the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Here, we demonstrate that miRNA-mediated silencing of LKB1 confers sensitivity of lymphoma cells to mitochondrial inhibition by biguanides.

The effect of project-based learning modules on a community dental hygiene practicum in South Korea.

Purpose: The goal of this study is to develop and apply learning modules to help community dental hygienists acquire the necessary competencies and verify the effectiveness of the modules.

Methods: On the basis of 12 domestic and international reference papers, the concept of a community dental hygiene process of care was defined, and 393 learning goals were found to perform the primary and secondary categorization processes. The final 52 learning goals were assigned as a 15-week module series to develop project-based learning modules.

A novel and safe small molecule enhances hair follicle regeneration by facilitating metabolic reprogramming.

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism.

Identification of potent CNS-penetrant thiazolidinones as novel CGRP receptor antagonists.

Calcitonin gene-related peptide (CGRP) has been implicated in acute migraine pathogenesis. In an effort to identify novel CGRP receptor antagonists for the treatment of migraine, we have discovered thiazolidinone 49, a potent (Ki=30 pM, IC50=1 nM), orally bioavailable, CNS-penetrant CGRP antagonist with good pharmacokinetic properties.

Refolding and characterization of a soluble ectodomain complex of the calcitonin gene-related peptide receptor.

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of two membrane proteins: calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). CLR is a class B G-protein-coupled receptor (GPCR), possessing a characteristic large amino-terminal extracellular domain (ECD) important for ligand recognition and binding. Dimerization of CLR with RAMP1 provides specificity for CGRP versus related agonists.

Genetic selection for modulators of the MAP kinase and beta-catenin growth-control pathways in mammalian cells.

Transdominant genetic selections can yield protein fragment and peptide modulators of specific biochemical pathways. In yeast, such screens have been highly successful in targeting the MAP (mitogen-activated protein) kinase growth-control pathway. We performed a similar type of selection aimed at recovery of modulators of the mammalian MAP kinase cascade.