Electron transport chain inhibition increases cellular dependence on purine transport and salvage.

Mitochondria house many metabolic pathways required for homeostasis and growth. To explore how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts from patients with various mitochondrial disorders and cancer cells with electron transport chain (ETC) blockade. These analyses revealed extensive perturbations in purine metabolism, and stable isotope tracing demonstrated that ETC defects suppress de novo purine synthesis while enhancing purine salvage.

High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis.

Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies. Metastasis is a complicated multistep process, which is determined by complex genetic alterations. Despite the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging.

Electron transport chain inhibition increases cellular dependence on purine transport and salvage.

Cancer cells reprogram their metabolism to support cell growth and proliferation in harsh environments. While many studies have documented the importance of mitochondrial oxidative phosphorylation (OXPHOS) in tumor growth, some cancer cells experience conditions of reduced OXPHOS in vivo and induce alternative metabolic pathways to compensate. To assess how human cells respond to mitochondrial dysfunction, we performed metabolomics in fibroblasts and plasma from patients with inborn errors of mitochondrial metabolism, and in cancer cells subjected to inhibition of the electron transport chain (ETC).

Predictive value of early kinetics of ctDNA combined with cfDNA and serum CEA for EGFR-TKI treatment in advanced non-small cell lung cancer.

Background: Circulating tumor DNA (ctDNA) has made a breakthrough as an early biomarker in operable early-stage cancer patients. However, the function of ctDNA combined with cell-free DNA (cfDNA) as a predictor in advanced non-small cell lung cancer (NSCLC) remains unknown. Here, we explored its potential as a biomarker for predicting the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced NSCLC.

Compartmentalized metabolism supports midgestation mammalian development.

Mammalian embryogenesis requires rapid growth and proper metabolic regulation. Midgestation features increasing oxygen and nutrient availability concomitant with fetal organ development. Understanding how metabolism supports development requires approaches to observe metabolism directly in model organisms in utero.

Metabolic impact of pathogenic variants in the mitochondrial glutamyl-tRNA synthetase EARS2.

Glutamyl-tRNA synthetase 2 (encoded by EARS2) is a mitochondrial aminoacyl-tRNA synthetase required to translate the 13 subunits of the electron transport chain encoded by the mitochondrial DNA. Pathogenic EARS2 variants cause combined oxidative phosphorylation deficiency, subtype 12 (COXPD12), an autosomal recessive disorder involving lactic acidosis, intellectual disability, and other features of mitochondrial compromise. Patients with EARS2 deficiency present with variable phenotypes ranging from neonatal lethality to a mitigated disease with clinical improvement in early childhood.

A pathogenic UFSP2 variant in an autosomal recessive form of pediatric neurodevelopmental anomalies and epilepsy.

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders.

Functional Assessment of Lipoyltransferase-1 Deficiency in Cells, Mice, and Humans.

Inborn errors of metabolism (IEMs) link metabolic defects to human phenotypes. Modern genomics has accelerated IEM discovery, but assessing the impact of genomic variants is still challenging. Here, we integrate genomics and metabolomics to identify a cause of lactic acidosis and epilepsy.

Identification of the metastasis potential and its associated genes in melanoma multinucleated giant cells using the PHA-ECM830 fusion method.

Malignant melanoma causes skin cancer with high rates of mortality. Multinucleated giant cells (MGCs) are frequently observed in tumor pathological analysis, especially in metastasized sites, and are related to poor prognosis. However, the role of MGCs in melanoma development and metastasis is currently unknown.

Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates PDGF-induced activation of HSCs through MAPK pathway.

Acid-sensing ion channels (ASICs), a group of Na(+)-selective and Ca(2+)-permeant ligand-gated cation channels, can be transiently activated by extracellular acid. Among seven subunits of ASICs, acid-sensing ion channel 1a (ASIC1a), which is responsible for Ca(2+) transportation, is elevated in response to inflammation, tumor, and ischemic injury in central nervous system and non-neuronal tissues. In this study, we demonstrated for the first time the presence of ASIC1a in rat liver and hepatic stellate cells (HSCs).

Inhibition of ASICs reduces rat hepatic stellate cells activity and liver fibrosis: an in vitro and in vivo study.

Hepatic fibrosis is a chronic inflammation-associated disease, which is involved in the infiltration of inflammatory cells and releasing of proinflammatory cytokines. In the pathological process, protons are released by damaged cells and acidosis is considered to play a critical role in cell injury. Although the underlying mechanism (s) remain ill-defined, ASICs (acid-sensing ion channels) are assumed to be involved in this process.

Role of interleukin-22 in liver diseases.

Introduction: Interleukin (IL)-22, originally referred to as IL-TIF for IL-10-related T cell-derived inducible factor, is a member of the IL-10-like cytokine family. IL-22 is highly expressed by Th17 cells and is tightly linked to chronic inflammation, including inflammatory bowel disease and local intestinal inflammation among others.

Materials And Methods: A PubMed and Web of Science databases search was performed for studies providing evidences on the role of IL-22 in liver diseases.

Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis.

This study focused on exploring the antidepressant potential of resveratrol (RES) and its possible mechanisms of action. Cell injury was induced by corticosterone (CORT) and detected through cell viability and contents of lactate dehydrogenase (LDH) and malonaldehyde (MDA). A rat model of depression was established through 3weeks of consecutive chronic unpredictable mild stress (CUMS), and both the depression-like behaviors and the activity of the hypothalamic-pituitary-adrenal (HPA) axis were tested.

Anti-tumor effect of 4-Amino-2-Trifluoromethyl-Phenyl Retinate on human breast cancer MCF-7 cells via up-regulation of retinoid receptor-induced gene-1.

4-Amino-2-Trifluoromethyl-Phenyl Retinate (ATPR) is one of the retinoid derivatives designed and synthesized in our team. In this paper, we explored the potential anti-tumor effects of ATPR in breast cancer. Here we found that ATPR showed remarkable anti-proliferative effects in a dose- and time-dependent manner, caused cell cycle arrest in the G0/G1 phase and significantly increased the expression of retinoid receptor-induced gene-1 (RRIG1).

Simulated microgravity alters the metastatic potential of a human lung adenocarcinoma cell line.

Simulated microgravity (SM) has been implicated in affecting diverse cellular pathways. Although there is emerging evidence that SM can alter cellular functions, its effect in cancer metastasis has not been addressed. Here, we demonstrate that SM inhibits migration, gelatinolytic activity, and cell proliferation of an A549 human lung adenocarcinoma cell line in vitro.

Substituent effects on photosensitized splitting of thymine cyclobutane dimer by an attached indole.

In chromophore-containing cyclobutane pyrimidine dimer (CPD) model systems, solvent effects on the splitting efficiency may depend on the length of the linker, the molecular conformation, and the oxidation potential of the donor. To further explore the relationship between chromophore structure and splitting efficiency, we prepared a series of substituted indole-T< >T model compounds 2 a-2 g and measured their splitting quantum yields in various solvents. Two reverse solvent effects were observed: an increase in splitting efficiency in solvents of lower polarity for models 2 a-2 d with an electron-donating group (EDG), and vice versa for models 2 e-2 g with an electron-withdrawing group (EWG).

Fusion between tumor cells enhances melanoma metastatic potential.

Purpose: Malignant melanoma, characterized by early distant metastasis to the lungs and brain, is a leading cause of mortality related to skin cancer. Cell fusion and the subsequent aneuploidy, commonly observed in melanoma, are associated with poor prognosis. However, the pathological consequences of cell fusion in melanoma remain unknown.

Elimination of matrix effect and simultaneous determination of multi-components in complex systems by matrix coefficient non-linearity multivariate calibration based on single point response signals.

In order to deal with the matrix effect in the simultaneous determination of multi-components in a complex system, we have developed a novel method named matrix coefficient multivariate calibration method (MCMCM) for simultaneously determining n analytes in complex systems. The calibration models of n analytes, which are based on the experimental data of known samples, are first transformed into n linear equations, and then the equations are solved to obtain matrix calibration coefficients of the analytes in congeneric samples. In this way, the concentrations of n analytes in the unknown sample could be obtained easily and simultaneously by solving another n-variate linear equations with the help of the matrix calibration coefficients obtained-above.