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Hepatocellular response to chemical stress in CD-1 mice: induction of early genes and gamma-glutamylcysteine synthetase.

Exposure of cells to toxic chemical species can result in reduced glutathione (GSH) depletion, generation of free radicals, and/or binding to critical cell determinants. Chemical stress is usually followed by a concerted cellular response aimed at restoring homeostasis, although the precise initial stimulus for the response is unclear. We have focused on one component of this stress response, the up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS) and the preceding molecular events involved in its regulation in an in vivo mouse model. Male CD-1 mice received buthionine sulphoximine

Identification of Important Genes of Keratoconus and Construction of the Diagnostic Model.

OBJECTIVE: The aim of the study is to investigate the potential role of keratoconus (KC) in the diagnosis of keratoconus (KC). METHODS: GSE151631 and GSE77938 were downloaded from the comprehensive gene expression database (GEO). By using the random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM), important immune-related genes were identified as biomarkers for KC diagnosis. RESULTS: Through the LASSO, RFE, and RF algorithms and comparing the three sets of DEGs, a total of 8 overlapping DEGs were obtained. We took 8 DEGs as the final optimal combinat

An H2 S-BMP6 Dual-Loading System with Regulating Yap/Taz and Jun Pathway for Synergistic Critical Limb Ischemia Salvaging Therapy.

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemi

Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β.

Genetic etiologies of chronic mucocutaneous candidiasis (CMC) disrupt human IL-17A/F-dependent immunity at mucosal surfaces, whereas those of connective tissue disorders (CTDs) often impair the TGF-β-dependent homeostasis of connective tissues. The signaling pathways involved are incompletely understood. We report a three-generation family with an autosomal dominant (AD) combination of CMC and a previously undescribed form of CTD that clinically overlaps with Ehlers-Danlos syndrome (EDS). The patients are heterozygous for a private splice-site variant of MAPK8, the gene encoding c-Jun N-termin

Establishment and characterization of CRISPR/Cas9-mediated NF2-/- human mesothelial cell line: Molecular insight into fibroblast growth factor receptor 2 in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM), a highly refractory tumor, is currently incurable due to the lack of an early diagnosis method and medication, both of which are urgently needed to improve the survival and/or quality of life of patients. NF2 is a tumor suppressor gene and is frequently mutated in MPM. Using a CRISPR/Cas9 system, we generated an NF2-knockout human mesothelial cell line, MeT-5A (NF2-KO). In NF2-KO cell clones, cell growth, clonogenic activity, migration activity, and invasion activity significantly increased compared with those in NF2-WT cell clones. Complementary DNA micro

Amphetamine activates connexin43 gene expression in cultured neonatal rat cardiomyocytes through JNK and AP-1 pathway.

OBJECTIVE: Amphetamine has been known to induce cardiac dysrhythmia and sudden death. However, the molecular mechanism for the induction of dysrhythmia is not known. Connexin43 (Cx43) plays an important role for arrhythmogenesis. This study was undertaken to test the hypothesis that amphetamine could induce Cx43 expression in cardiac myocytes. METHODS: Neonatal Wistar rat cardiac myocytes were cultured under the stimulation of amphetamine. Cx43 mRNA and protein expression were examined by Northern and Western blots, respectively. We used c-Jun N-terminal kinase (JNK) inhibitor, SP600125, and

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death.

Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE2

Induction of c-Jun mRNA without changes of estrogen and progesterone receptor expression in myometrium during human labor.

To elucidate the endocrine mechanism of human parturition, the expression of c-Jun and c-Fos mRNA were examined in relation to estrogen receptor (ER) and progesterone receptor (PR) in human myometrium. c-Jun mRNA was detected in all myometrial tissues (n=5) during labor but not before labor (n=5) and in oxytocin-resistant postterm pregnancy (n=3). c-Fos mRNA was detected in only one myometrial tissue from a woman in labor. The distribution and intensity of immunostaining for ER and PR were semiquantitatively scored. During the late pregnancies, no significant difference was seen in the recepto

Modulation of growth-related gene expression and growth inhibition by cyclic adenosine 3',5'-monophosphate-elevating agents in the insulin-producing cell line beta TC1.

We studied the involvement of the cAMP pathway in the regulation of beta TC1 cell growth with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the activator of adenylate cyclase forskolin. We examined the effect of the increase in cAMP content on the serum-induced resumption of the cell cycle of quiescent cells. IBMX and forskolin both inhibited the mitogenic effect of serum in a concentration-dependent manner. Intracellular cAMP levels were, respectively, enhanced 3.0- and 8.6-fold by IBMX (0.5 mM) and forskolin (20 microM) within 1 h. IBMX and forskolin were also induce

Identification of ferroptosis-associated genes exhibiting altered expression in response to cardiopulmonary bypass during corrective surgery for pediatric tetralogy of fallot.

BACKGROUND: Tetralogy of Fallot (ToF) is a life-threatening congenital cardiovascular disorder. Currently, the most effective therapeutic intervention for pediatric ToF remains corrective surgery with cardiopulmonary bypass (CPB). Ferroptosis is an iron-dependent form of regulated cell death, driven by an accumulation of lipid peroxides to levels sufficient to trigger cell death. Ferroptosis was recently linked to cardiac ischemia and reperfusion injury. However, few studies have examined CPB-associated ferroptosis. METHOD: In the current study, pediatric ToF patient pre- and post-CPB atrial

Transcriptomic responses to hypoxia in endometrial and decidual stromal cells.

Human reproductive success depends on a properly decidualized uterine endometrium that allows implantation and the formation of the placenta. At the core of the decidualization process are endometrial stromal fibroblasts (ESF) that differentiate to decidual stromal cells (DSC). As variations in oxygen levels are functionally relevant in endometrium both upon menstruation and during placentation, we assessed the transcriptomic responses to hypoxia in ESF and DSC. In both cell types, hypoxia-upregulated genes in classical hypoxia pathways such as glycolysis and the epithelial mesenchymal transit

Heroin addiction modulates transcription factor binding in regulatory regions of the human putamen.

The ongoing opioid crisis underscores the need to elucidate the neurobiology of addiction for improved treatments. Dynamic transcription factor (TF) binding is a key driver of substance use disorders (SUDs), yet its genome-wide patterns in human brain cell types remain poorly defined. We performed a computational re-analysis of publicly available ATAC-seq data (PRJNA561094) from post-mortem putamen samples of heroin users and matched non-users, where we profiled chromatin accessibility analyzing neuronal and glial cells separately. Genome-wide TF binding sites were identified and quantified, f

Macrophage Polarization Modulated by Porcine Circovirus Type 2 Facilitates Bacterial Coinfection.

Polarization of macrophages to different functional states is important for mounting responses against pathogen infections. Macrophages are the major target cells of porcine circovirus type 2 (PCV2), which is the primary causative agent of porcine circovirus-associated disease (PCVAD) leading to immense economic losses in the global swine industry. Clinically, PCV2 is often found to increase risk of other pathogenic infections yet the underlying mechanisms remain to be elusive. Here we found that PCV2 infection skewed macrophages toward a M1 status through reprogramming expression of a subset

The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways.

Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the

Pineal gene expression: dawn in a dark matter.

The mammalian pineal gland serves as a neuroendocrine interface to convert environmental lighting conditions into a humoral message, the nocturnally elevated synthesis of melatonin. Regulation and fine tuning of the circadian melatonin production in response to external cues requires complex interactions of transsynaptic signalling. These requirements are fulfilled by a high degree of plasticity on all levels between receptor activation and cellular response. Many receptors on pinealocytic membranes and enzymes involved in melatonin synthesis are linked to the second messenger cAMP. Crosstalk

Twenty-Four Genes are Upregulated in Patients with Hypospadias.

Hypospadias is a congenital hypoplasia of the penis, with displacement of the urethral opening along the ventral surface, and has been reported to be one of the most common congenital anomalies, occurring in approximately 1:250 to 1:300 live births. As hypospadias is reported to be an easily diagnosed malformation at the crossroads of genetics and environment, it is important to study the genetic component in order to elucidate its etiology. In this study, the gene expression profiles both in human hypospadias tissues and normal penile tissues were studied by Human Gene Expression Array. Twent

Идентификация и проверка генов, связанных со старением, у пациентов с множественной миеломой.

Это исследование было направлено на выявление и проверку связанных со старением генов (ARGs), связанных с множественной миеломой (MM), что способствовало более глубокому пониманию молекулярных механизмов, лежащих в основе этого заболевания. Для изучения функциональных ролей ARG в MM были проведены генной онтологии и Киото-Энциклопедии по обогащению генов и геномов. Потенциальные гены, выявленные с помощью наименьшего абсолютного сокращения и селекционного оператора (LASSO) логистической регрессии и рекурсивного устранения векторных функций (SVM-RFE), были сопоставлены с помощью диаграммы Венна

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… PPARG interacted with 12 genes, JUN with 11, and both MYC and HIF1A interacted with 10 genes. Correlation analysis of the expression levels of the 18 interacting genes showed significant associations between them. …

Integrated transcriptomics and molecular docking identify hub genes and statin regulators in Helicobacter pylori-associated gastric mucosal pathogenesis.

BACKGROUND: Helicobacter pylori (H. pylori), a spiral Gram-negative bacterium colonizing gastric mucosa, damages epithelial cells, driving chronic gastritis, peptic ulcers, and gastric cancer. Mechanisms of its malignant transformation remain unclear. METHODS: We identified differentially expressed genes (DEGs) and hub genes, pathway enrichment analysis, transcription factors (TFs), small-molecule drug and molecular docking prediction using gastric epithelial cells (GECs) infected with H. pylori strain 26695 and clinical sample datasets. RESULTS: H. pylori infection of GECs, multiple signali

AP-1-dependent fibrosis: Exploring its potential role in the pathogenesis of placental transmogrification of the lung (PTL) via tissue-level transcriptome analysis.

Placental transmogrification of the lung (PTL) is a rare pulmonary condition characterized by the presence of immature placental villous str … derscoring the importance of shared molecular pathways in the pathogenesis of PTL. Among the shared genes, JUND, COL4A2, COL6A2, IGFBP5, and IGFBP7 were consistently upregulated, highlighting the possible involvement of AP-1-mediated signaling and fibrotic changes in the pathogenesis of PTL. The present findings pave the way for further research into the mol …

Downregulation of ferroptosis-related ATF3 alleviates lupus nephritis progression.

BACKGROUND: The role of ferroptosis in lupus nephritis (LN) is unclear. This study aimed to explore the effects of ferroptosis-related genes in LN through bioinformatics prediction and experimental validation. METHODS: Sample data were collected from the GEO dataset and divided into glomeruli and tubulointerstitium. We collected 382 ferroptosis-related genes. The intersection of ferroptosis-related genes with glomeruli and tubulointerstitium data, respectively, was performed. Machine learning methods (including unsupervised cluster typing and random forests) were operated to identify ferropto