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Environment International May 2024Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental...
INTRODUCTION
Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental effects on thyroid physiology and functioning have been described. Differences exist in the susceptibility of human sexes to the incidence of thyroid disorders, like autoimmune diseases or cancer.
METHODS
To study how different hormonal environments impact the thyroid response to endocrine disruptors, we exposed human embryonic stem cell-derived thyroid organoids to physiological concentrations of sex hormones resembling the serum levels of human females post-ovulation or males of reproductive age for three days. Afterwards, we added 10 µM benzo[a]pyrene or PCB153 for 24 h and analyzed the transcriptome changes via single-cell RNA sequencing with differential gene expression and gene ontology analysis.
RESULTS
The sex hormones receptors genes AR, ESR1, ESR2 and PGR were expressed at low levels. Among the thyroid markers, only TG resulted downregulated by benzo[a]pyrene or benzo[a]pyrene with the "male" hormones mix. Both hormone mixtures and benzo[a]pyrene alone upregulated ribosomal genes and genes involved in oxidative phosphorylation, while their combination decreased the expression compared to benzo[a]pyrene alone. The "male" mix and benzo[a]pyrene, alone or in combination, upregulated genes involved in lipid transport and metabolism (APOA1, APOC3, APOA4, FABP1, FABP2, FABP6). The combination of "male" hormones and benzo[a]pyrene induced also genes involved in inflammation and NFkB targets. Benzo[a]pyrene upregulated CYP1A1, CYP1B1 and NQO1 irrespective of the hormonal context. The induction was stronger in the "female" mix. Benzo[a]pyrene alone upregulated genes involved in cell cycle regulation, response to reactive oxygen species and apoptosis. PCB153 had a modest effect in presence of "male" hormones, while we did not observe any changes with the "female" mix.
CONCLUSION
This work shows how single cell transcriptomics can be applied to selectively study the in vitro effects of endocrine disrupters and their interaction with different hormonal contexts.
PubMed: 38763096
DOI: 10.1016/j.envint.2024.108748 -
International Journal of Molecular... Apr 2024Mitochondria are the energy factories of a cell, and depending on the metabolic requirements, the mitochondrial morphology, quantity, and membrane potential in a cell...
Mitochondria are the energy factories of a cell, and depending on the metabolic requirements, the mitochondrial morphology, quantity, and membrane potential in a cell change. These changes are frequently assessed using commercially available probes. In this study, we tested the suitability of three commercially available probes-namely 5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolo-carbocyanine iodide (JC-1), MitoTracker Red CMX Rox (CMXRos), and tetramethylrhodamine methyl ester (TMRM)-for assessing the mitochondrial quantity, morphology, and membrane potential in living human mesoangioblasts in 3D with confocal laser scanning microscope (CLSM) and scanning disk confocal microscope (SDCM). Using CLSM, JC-1, and CMXRos-but not TMRM-uncovered considerable background and variation. Using SDCM, the background signal only remained apparent for the JC-1 monomer. Repetitive imaging of CMXRos and JC-1-but not TMRM-demonstrated a 1.5-2-fold variation in signal intensity between cells using CLSM. The use of SDCM drastically reduced this variation. The slope of the relative signal intensity upon repetitive imaging using CLSM was lowest for TMRM (-0.03) and highest for CMXRos (0.16). Upon repetitive imaging using SDCM, the slope varied from 0 (CMXRos) to a maximum of -0.27 (JC-1 C1). Conclusively, our data show that TMRM staining outperformed JC-1 and CMXRos dyes in a (repetitive) 3D analysis of the entire mitochondrial quantity, morphology, and membrane potential in living cells.
Topics: Humans; Mitochondria; Microscopy, Confocal; Imaging, Three-Dimensional; Fluorescent Dyes; Membrane Potential, Mitochondrial; Carbocyanines; Rhodamines
PubMed: 38732037
DOI: 10.3390/ijms25094819 -
Medicine May 2024Ultrasound therapy is a method of applying ultrasonic energy to the stimulation produced by human body to change the function and tissue state of the body in order to...
Ultrasound therapy is a method of applying ultrasonic energy to the stimulation produced by human body to change the function and tissue state of the body in order to achieve the purpose of treating diseases. Chronic venous ulcer is a common chronic skin ulcer. GSE222503 for ultrasound therapy of chronic venous ulcers was downloaded from gene expression omnibus database, which were used to identify differentially expressed genes. Weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis and construction and analysis of protein-protein interaction network were performed. Draw gene expression heatmaps. Comparative toxicogenomics database analysis was performed. Two hundred thirty-five differentially expressed genes were obtained. According to gene ontology analysis, in biological process analysis, they were mainly enriched in positive regulation of cellular biosynthetic process, reproductive cell development, vasculogenesis, vascular morphogenesis, and inflammatory response. In cellular component analysis, they were mainly enriched in leading edge of growing cell, extracellular matrix binding organelle, F-actin capping protein complex. In molecular function analysis, they were mainly concentrated in receptor ligand activity, cytokine receptor binding. In Kyoto encyclopedia of genes and genomes analysis, they were mainly enriched in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, HIF-1 signaling pathway, heme biosynthesis. In weighted gene co-expression network analysis, the soft threshold power was set to 9. Thirty modules were generated. PF4, NR1I2, TTC16, H3C12, KLRB1, CYP21A2 identified by 4 algorithms (MCC, EPC, closeness, stress). Heatmap of core gene expression showed that H3C12, KLRB1, PF4, NR1I2 were all underexpressed in samples of ultrasound-treated chronic venous ulcers and overexpressed in samples of untreated chronic venous ulcers. Comparative toxicogenomics database analysis showed that H3C12, KLRB1, PF4, NR1I2 are associated with thrombophlebitis, phlebitis, vascular malformations, metabolic syndrome, ulcers, and inflammation. In samples of chronic venous ulcer tissue treated with ultrasound, NR1I2 shows low expression, while in samples of chronic venous ulcer tissue without ultrasound treatment, it shows high expression. This finding suggests a potential role of NR1I2 in the process of ultrasound therapy for chronic venous ulcers, which may be related to the therapeutic effect of ultrasound therapy on chronic venous ulcers.
Topics: Humans; Ultrasonic Therapy; Varicose Ulcer; Chronic Disease; Protein Interaction Maps; Gene Ontology; Gene Expression Profiling
PubMed: 38728468
DOI: 10.1097/MD.0000000000038092 -
Medicine May 2024Colorectal cancer is a common malignant tumor in intestinal tract, the early symptoms are not obvious. Gastric cancer is a malignant tumor originating from the gastric...
Colorectal cancer is a common malignant tumor in intestinal tract, the early symptoms are not obvious. Gastric cancer is a malignant tumor originating from the gastric mucosal epithelium. However, the role of MYC and non-SMC condensin II complex subunit G2 (NCAPG2) in colorectal cancer and gastric cancer remains unclear. The colorectal cancer datasets GSE49355 and gastric cancer datasets GSE19826 were downloaded from gene expression omnibus database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Functional enrichment analysis, gene set enrichment analysis (GSEA) and immune infiltration analysis was performed. Construction and analysis of protein-protein interactions (PPI) network. Survival analysis and comparative toxicogenomics database (CTD) were performed. A heat map of gene expression was drawn. A total of 751 DEGs were obtained. According to the gene ontology (GO) analysis, in Biological process (BP) analysis, they are mainly enriched in cell differentiation, cartilage development, and skeletal development. In cellular component (CC) analysis, they are mainly enriched in the cytoskeleton of muscle cells and actin filaments. In molecular function (MF) analysis, they are mainly concentrated in Rho GTPase binding, DNA binding, and fibronectin binding. In Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, they are mainly enriched in the MAPK signaling pathway, apoptosis, and cancer pathways. The soft threshold power for WGCNA analysis was set to 9, resulting in the generation of 40 modules. Ultimately, 2 core genes (MYC and NCAPG2) were identified. The heatmap of core gene expression showed high expression of MYC and NCAPG2 in colorectal cancer tissue samples and low expression in normal tissue samples, while they were core molecules in gastric cancer. Survival analysis indicated that MYC and NCAPG2 were risk factors, showing an upregulation trend with increasing risk scores. CTD analysis revealed associations of MYC and NCAPG2 with colorectal cancer, gastric cancer, inflammation, and immune system diseases. MYC and NCAPG2 are highly expressed in colorectal cancer. The higher the expression of MYC and NCAPG2, the worse the prognosis. MYC and NCAPG2 are core molecules in gastric cancer.
Topics: Humans; Stomach Neoplasms; Colorectal Neoplasms; Protein Interaction Maps; Proto-Oncogene Proteins c-myc; Gene Expression Regulation, Neoplastic; Cell Cycle Proteins; Gene Expression Profiling
PubMed: 38701261
DOI: 10.1097/MD.0000000000038029 -
Medicine May 2024Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis... (Observational Study)
Observational Study
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally and often develops on the foundation of chronic liver disease or cirrhosis. Cirrhosis is a clinically prevalent chronic progressive liver disease characterized by diffuse liver damage resulting from long-term or repeated actions of 1 or more etiological factors. However, the impact of CENPF and nuclear division cycle 80 (NDC80) genes on rehabilitation nursing of HCC and cirrhosis remains unclear. HCC and cirrhosis datasets GSE63898 and GSE89377 profile files were downloaded from the gene expression omnibus database generated on platforms GPL13667 and GPL6947, respectively. Differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), survival analysis, immune infiltration analysis, and comparative toxicogenomics database (CTD) analysis were conducted. Gene expression heatmaps were plotted. miRNAs regulating central DEGs were selected through TargetScan. A total of 626 DEGs were identified. According to gene ontology (GO) analysis, they were primarily enriched in small molecule metabolic processes, drug metabolic processes, binding of identical proteins, and lipid metabolic processes. Kyoto Encyclopedia of Gene and Genome (KEGG) analysis results indicated that the target genes were mainly enriched in metabolic pathways, phagosomes, glycine, serine, and threonine metabolism. The construction and analysis of the PPI network revealed 3 core genes (NDC80, CENPF, RRM2). Gene expression heatmaps showed that core genes (CENPF, NDC80) were highly expressed in HCC and cirrhosis samples. CTD analysis found that 2 genes (CENPF and NDC80) were associated with liver, jaundice, ascites, fever, dyspepsia, and hepatic encephalopathy. CENPF and NDC80 are highly expressed in HCC and cirrhosis, and CENPF and NDC80 might be the biomarkers of rehabilitation nursing of HCC and cirrhosis.
Topics: Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Cirrhosis; Nuclear Proteins; Protein Interaction Maps; Gene Expression Profiling; Cytoskeletal Proteins
PubMed: 38701255
DOI: 10.1097/MD.0000000000037984 -
Environmental Toxicology and... Apr 2024Non-smokers exposed to second-hand smoke (SHS) present risk of developing tobacco smoke-associated pathologies. To investigate the airway molecular response to SHS...
Non-smokers exposed to second-hand smoke (SHS) present risk of developing tobacco smoke-associated pathologies. To investigate the airway molecular response to SHS exposure that could be used in health risk assessment, comparative shotgun proteomics was performed on nasal epithelium from a group of healthy restaurant workers, non-smokers (never and former) exposed and not exposed to SHS in the workplace. HIF1α-glycolytic targets (GAPDH, TPI) and proteins related to xenobiotic metabolism, cell proliferation and differentiation leading to cancer (ADH1C, TUBB4B, EEF2) showed significant modulation in non-smokers exposed. In never smokers exposed, enrichment of glutathione metabolism pathway and EEF2-regulating protein synthesis in genotoxic response were increased, while in former smokers exposed, proteins (LYZ, ATP1A1, SERPINB3) associated with tissue damage/regeneration, apoptosis inhibition and inflammation that may lead to asthma, COPD or cancer, were upregulated. The identified proteins are potential response and susceptibility/risk biomarkers for SHS exposure.
PubMed: 38685369
DOI: 10.1016/j.etap.2024.104459 -
World Journal of Diabetes Apr 2024The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend....
BACKGROUND
The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.
AIM
To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.
METHODS
To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both and . To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD).
RESULTS
A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (, , and ). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both and , consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with and were identified based on the CTD.
CONCLUSION
Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both and , consistent with our bioinformatics results. We discovered 11 compounds associated with and . These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
PubMed: 38680704
DOI: 10.4239/wjd.v15.i4.735 -
Metabolites Apr 2024Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called...
Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called endocrine-disrupting chemicals (EDCs). The thyroid gland is an important target of these compounds. The objective of this study was to analyze public data on the human thyroid transcriptome and investigate potential new targets of EDCs in the embryonic and adult thyroid glands. We compared the public transcriptome data of adult and embryonic human thyroid glands and selected 100 up- or downregulated genes that were subsequently subjected to functional enrichment analysis. In the embryonic thyroid, the most highly expressed gene was PRMT6, which methylates arginine-4 of histone H2A (86.21%), and the downregulated clusters included plasma lipoprotein particles (39.24%) and endopeptidase inhibitory activity (24.05%). For the adult thyroid gland, the most highly expressed genes were related to the following categories: metallothionein-binding metals (56.67%), steroid hormone biosynthetic process (16.67%), and cellular response to vascular endothelial growth factor stimulus (6.67%). Several compounds ranging from antihypertensive drugs to enzyme inhibitors were identified as potentially harmful to thyroid gland development and adult function.
PubMed: 38668354
DOI: 10.3390/metabo14040226 -
Medicine Apr 2024Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is...
Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.
Topics: Humans; Carcinoma, Squamous Cell; CDC2 Protein Kinase; Computational Biology; Cyclin A2; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Head and Neck Neoplasms; MicroRNAs; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 38640322
DOI: 10.1097/MD.0000000000037831 -
Medicine Apr 2024Atherosclerosis is a chronic, progressive vascular disease. The relationship between CASP1 gene expression and atherosclerosis remains unclear. The atherosclerosis...
Atherosclerosis is a chronic, progressive vascular disease. The relationship between CASP1 gene expression and atherosclerosis remains unclear. The atherosclerosis dataset GSE132651 and GSE202625 profiles were downloaded from gene expression omnibus. Differentially expressed genes (DEGs) were screened. The construction and analysis of protein-protein interaction network, functional enrichment analysis, gene set enrichment analysis, and Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEG. 47 DEGs were identified. According to gene ontology analysis, they were mainly enriched in the regulation of stimulus response, response to organic matter, extracellular region, extracellular region, and the same protein binding. Kyoto Encyclopedia of Gene and Genome analysis results showed that the target cells were mainly enriched in the PI3K-Akt signaling pathway, Ras signaling pathway, and PPAR signaling pathway. In the enrichment project of Metascape, vascular development, regulation of body fluid levels, and positive regulation of cell motility can be seen in the gene ontology enrichment project. Eleven core genes (CASP1, NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A) were obtained. IRS1, PPARG, APOE, FGF2, CCR2, and HIF1A genes are identified as core genes. Gene expression heatmap showed that CASP1 was highly expressed in atherosclerosis samples and low expressed in normal samples. NLRP3, MRC1, IRS1, PPARG, APOE, IL13, FGF2, CCR2, ICAM1, HIF1A were low expressed in atherosclerosis samples. CTD analysis showed that 5 genes (CASP1, NLRP3, CCR2, ICAM1, HIF1A) were found to be associated with pneumonia, inflammation, cardiac enlargement, and tumor invasiveness. CASP1 gene is highly expressed in atherosclerosis. The higher the CASP1 gene, the worse the prognosis.
Topics: Humans; Apolipoproteins E; Atherosclerosis; Computational Biology; Fibroblast Growth Factor 2; Gene Expression Profiling; Gene Regulatory Networks; Interleukin-13; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphatidylinositol 3-Kinases; PPAR gamma; Caspase 1
PubMed: 38640260
DOI: 10.1097/MD.0000000000037616