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1.
International Journal of Oral Science ; (4): 9-9, 2024.
Article in English | WPRIM | ID: wpr-1010722

ABSTRACT

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.


Subject(s)
Humans , Carcinoma, Squamous Cell/metabolism , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms/metabolism , Immunosuppression Therapy , Transforming Growth Factor beta , Head and Neck Neoplasms , Gene Expression Profiling , Tumor Microenvironment
2.
Neuroscience Bulletin ; (6): 65-78, 2024.
Article in English | WPRIM | ID: wpr-1010670

ABSTRACT

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.


Subject(s)
Humans , Ischemic Stroke , Brain/metabolism , Macrophages , Brain Ischemia/metabolism , Microglia/metabolism , Gene Expression Profiling , Anti-Inflammatory Agents , Neuronal Plasticity/physiology , Infarction/metabolism
3.
Chinese Journal of Traumatology ; (6): 34-41, 2024.
Article in English | WPRIM | ID: wpr-1009508

ABSTRACT

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.


Subject(s)
Rats , Animals , Lung Injury/genetics , Goats/genetics , Keratin-4 , Gene Expression Profiling , Gene Expression
4.
São Paulo; s.n; 2023. 241 p.
Thesis in Portuguese | LILACS | ID: biblio-1526964

ABSTRACT

Introdução: Exposições químicas podem variar em populações geograficamente distintas, com diferentes hábitos, estilos de vida e características individuais. Alguns elementos químicos encontrados no ambiente são capazes de alterar a expressão gênica humana. Objetivos: a) quantificar as concentrações de elementos potencialmente tóxicos (EPTs: As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, e Zn) na urina da população de Limeira, e nas peças de joias e pó de solda; b) quantificar as concentrações de EPTs no sangue dos participantes de Limeira e Volta Redonda; c) avaliar os riscos de doenças associadas à exposição ocupacional; d) avaliar o impacto da exposição ocupacional na expressão gênica de trabalhadores formais e informais. Métodos: O grupo Exposto foi composto por trabalhadores informais que realizam soldagem de joias e bijuterias em ambiente domiciliar na cidade de Limeira, SP; e por trabalhadores formais da Companhia Siderúrgica Nacional, em Volta Redonda, RJ. O grupo Controle incluiu moradores dos mesmos bairros dos trabalhadores, mas que não desenvolviam nenhuma atividade diretamente relacionada à exposição química. Amostras de sangue foram coletadas para quantificação de glicose, insulina, perfil lipídico, EPTs e para análise transcriptômica. Em Limeira, também foi quantificada a concentração de EPTs na urina. Para transcriptômica, o RNA foi extraído e hibridizado com Agilent SurePrint G3 Human Gene Expression 8x60K v2 Microarray. O pré-processamento, análise estatística e de vias de interesse foram realizados no software GeneSpring GX. Todos os participantes preencheram questionários sobre hábitos, percepção de risco, morbidade referida e exposição ocupacional. A associação entre exposição a EPTs e desfechos de saúde foi testada por modelo de regressão de Poisson multivariado. Resultados: Nos trabalhadores informais, foram detectados 16 genes superexpressos e 33 subexpressos em comparação com os controles (fold-change > 2). A análise de vias indicou genes enriquecidos em vias do processo inflamatório (quimiocinas MAPK, receptor Toll-like e NF-kappa B). Nos trabalhadores formais, foram encontrados 20 genes superexpressos e 50 subexpressos, com vias relacionadas à resposta imune e ao processo de aterosclerose. O único gene diferencialmente expresso (DEG) em comum nas duas populações foi o IFI27 relacionado na literatura a diferentes tipos de câncer. A produção informal de joias de Limeira foi associada a exposição dos trabalhadores ao Cd, com concentrações significativamente maiores na urina e no sangue dos trabalhadores comparado aos controles. Além disso, foi observada uma associação positiva entre as concentrações de Cd no sangue e a glicemia. As concentrações de As e Pb também foram maiores no sangue dos trabalhadores informais comparado aos controles, sendo que participantes com concentrações de Pb superiores a 2,6 µg dL-1 apresentaram prevalência de manifestações neurológicas 2,3 vezes maior (IC 95%: 1,17 - 4,58; p = 0,02). Não foram observadas diferenças significativas nos EPTs entre os grupos de Volta Redonda, provavelmente devido ao uso de equipamentos de proteção individual e à poluição ambiental na região. Conclusão: As diferenças na expressão gênica relacionadas à exposição ocupacional estão associadas, principalmente, à inflamação e à resposta imune. Os resultados sugerem que a exposição ocupacional prolongada a elementos tóxicos pode levar a consequências negativas para a saúde, como por exemplo, um aumento da prevalência de manifestações neurológicas. Os resultados exploratórios desta tese são um ponto de partida para estudos em populações sensíveis e pouco estudadas, especialmente, de países em desenvolvimento. Análises adicionais devem ser realizadas para investigar efeitos diretos e validar associações causais.


Introduction: Chemical exposures may vary in geographically distinct populations, with different habits, lifestyles, and individual characteristics. Objectives: a) to determine potentially toxic elements' (EPTs: As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn) in the urine of the population of Limeira, and in jewelry pieces and soldering powder; b) determine the PTEs concentrations in the participants' blood from Limeira and Volta Redonda municipalities; c) investigate disease risks associated with occupational exposure; d) to evaluate the impact of occupational exposure on gene expression profile. Methods: The exposed group was composed of informal workers who perform soldering of jewelry inside their houses in the city of Limeira, SP; and formal workers from a steel company in the city of Volta Redonda, RJ. Control participants were recruited from the same neighborhoods without occupational chemical exposure. Blood samples were collected for blood glucose, insulin, lipid profile, and PTE determinations, and for transcriptomic analysis. In Limeira, PTE concentration in urine was also determined. RNA was extracted and hybridized to Agilent SurePrint G3 Human Gene Expression 8x60K v2 Microarray for transcriptomics analysis. Pre-processing, statistical, and pathway analysis were performed in GeneSpring GX software. All participants completed questionnaires about household risk, reported morbidity, and occupational exposure. The association between PTEs exposure and health outcomes was tested by a multivariable robust Poisson regression model. Results: 16 up- and 33 down-regulated genes (fold-change > 2) were observed in the informal workers. Pathway analysis revealed genes enriched in inflammatory process (MAPK, Toll-like receptor, and NF-kappa B chemokine signaling pathways). In formal workers, 20 up- and 50 down-regulated genes were found with pathways related to immune response and atherosclerosis development. The gene IFI27 which has been associated with various types of cancer was the only one commonly differentially expressed between informal and formal workers. Informal jewelry production in Limeira increased exposure to Cd, with significantly higher concentrations in the urine and blood of informal exposed workers compared to controls. Furthermore, a positive association was observed between blood Cd concentrations and glycemia. The blood concentration of As and Pb were also Participants with Pb concentrations higher than 2.6 µg dL-1 showed a prevalence of neurological manifestations 2.3 times higher (95% CI: 1.17 - 4.58; p = 0.02) than those with lower lead concentrations. No significant differences were observed between formal workers from Volta Redonda and their control group, probably, because of the use of individual protection equipment and the environmental pollution in the region. Conclusion: Differences in gene expression related to occupational exposure are mainly associated with inflammation and immune response. The results suggest that prolonged occupational exposure to toxic elements could lead to negative health outcomes, such as higher prevalence of neurological manifestations. These exploratory results are a starting point for analysis in sensitive and understudied populations, especially in developing countries. Further analysis should be carried out to investigate its direct effects and to validate causal associations.


Subject(s)
Humans , Occupational Exposure , Occupational Health , Toxic Substances , Gene Expression Profiling , Exposome
5.
Acta cir. bras ; 38: e385723, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1519884

ABSTRACT

Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys. Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated. Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression. Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.


Subject(s)
Animals , Rats , Xylazine/administration & dosage , DNA , Gene Expression Profiling , Anesthesia , Ketamine/administration & dosage
6.
Braz. j. biol ; 83: e242603, 2023. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1355852

ABSTRACT

Abstract Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.


Resumo Fatores de transcrição (FT) são uma ampla classe de genes em plantas e podem regular a expressão de outros genes em resposta a vários estresses ambientais (estresses bióticos e abióticos). No presente estudo, a atividade do fator de transcrição na cana-de-açúcar foi examinada durante o estresse pelo frio. Inicialmente, as leituras de transcrição de RNA de duas cultivares de cana-de-açúcar (ROC22 e GT08-1108) sob estresse frio foram baixadas do banco de dados SRA NCBI. As leituras foram alinhadas em um genoma de referência e as análises de expressão diferencial foram realizadas com o pacote R / Bioconductor edgeR. Com base em nossas análises no cultivar ROC22, 963 genes TF foram significativamente regulados positivamente sob estresse pelo frio entre um total de 5.649 genes regulados positivamente, enquanto 293 genes TF foram regulados negativamente entre um total de 3.289 genes regulados negativamente. No cultivar GT08-1108, 974 genes TF foram identificados entre 5.649 genes regulados positivamente e 283 genes TF foram encontrados entre 3.289 genes regulados negativamente. Os fatores de transcrição, em sua maioria, foram anotados com categorias GO relacionadas à ligação de proteína, ligação de fator de transcrição, ligação específica de sequência de DNA, complexo de fator de transcrição, atividade de fator de transcrição em RNA polimerase II, atividade de fator de transcrição de ligação de ácido nucleico, atividade de corepressor de transcrição, sequência específica da região reguladora, atividade do fator de transcrição da RNA polimerase II, atividade do cofator do fator de transcrição, atividade do fator de transcrição do promotor do plastídio, atividade do fator de transcrição do promotor da RNA polimerase I, polimerase II e RNA polimerase III. As descobertas dos resultados acima ajudarão a identificar fatores de transcrição expressos diferencialmente durante o estresse pelo frio. Ele também fornece uma análise abrangente da regulação da atividade de transcrição de muitos genes. Portanto, este estudo fornece base molecular para melhorar a tolerância ao frio em cana-de-açúcar e outras gramíneas economicamente importantes.


Subject(s)
Saccharum/genetics , Saccharum/metabolism , Cold-Shock Response/genetics , Stress, Physiological/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Cold Temperature , Gene Expression Regulation, Plant , Gene Expression Profiling
7.
Journal of Southern Medical University ; (12): 680-693, 2023.
Article in Chinese | WPRIM | ID: wpr-986977

ABSTRACT

OBJECTIVE@#To explore the driving gene of hepatocellular carcinoma (HCC) occurrence and progression and its potential as new therapeutic target of HCC.@*METHODS@#The transcriptome and genomic data of 858 HCC tissues and 493 adjacent tissues were obtained from TCGA, GEO, and ICGC databases. Gene Set Enrichment Analysis (GSEA) identified EHHADH (encoding enoyl-CoA hydratase/L-3-hydroxyacyl-CoA dehydrogenase) as the hub gene in the significantly enriched differential pathways in HCC. The downregulation of EHHADH expression at the transcriptome level was found to correlate with TP53 mutation based on analysis of the TCGA- HCC dataset, and the mechanism by which TP53 mutation caused EHHADH downregulation was explored through correlation analysis. Analysis of the data from the Metascape database suggested that EHHADH was strongly correlated with the ferroptosis signaling pathway in HCC progression, and to verify this result, immunohistochemical staining was used to examine EHHADH expression in 30 HCC tissues and paired adjacent tissues.@*RESULTS@#All the 3 HCC datasets showed signficnatly lowered EHHADH expression in HCC tissues as compared with the adjacent tissues (P < 0.05) with a close correlation with the degree of hepatocyte de-differentiation (P < 0.01). The somatic landscape of HCC cohort in TCGA dataset showed that HCC patients had the highest genomic TP53 mutation rate. The transcriptomic level of PPARGC1A, the upstream gene of EHHADH, was significantly downregulated in HCC patients with TP53 mutation as compared with those without the mutation (P < 0.05), and was significantly correlated with EHHADH expression level. GO and KEGG enrichment analyses showed that EHHADH expression was significantly correlated with abnormal fatty acid metabolism in HCC. The immunohistochemical results showd that the expression level of EHHADH in HCC tissues was down-regulated, and its expression level was related to the degree of hepatocytes de-differentiation and the process of ferroptosis.@*CONCLUSION@#TP53 mutations may induce abnormal expression of PPARGC1A to cause downregulation of EHHADH expression in HCC. The low expression of EHHADH is closely associated with aggravation of de-differentiation and ferroptosis escape in HCC tissues, suggesting the potential of EHHADH as a therapeutic target for HCC.


Subject(s)
Humans , Carcinoma, Hepatocellular/genetics , Transcriptome , Liver Neoplasms/genetics , Gene Expression Profiling , Fatty Acids , Peroxisomal Bifunctional Enzyme
8.
Journal of Central South University(Medical Sciences) ; (12): 1136-1151, 2023.
Article in English | WPRIM | ID: wpr-1010337

ABSTRACT

OBJECTIVES@#Laryngeal cancer (LC) is a globally prevalent and highly lethal tumor. Despite extensive efforts, the underlying mechanisms of LC remain inadequately understood. This study aims to conduct an innovative bioinformatic analysis to identify hub genes that could potentially serve as biomarkers or therapeutic targets in LC.@*METHODS@#We acquired a dataset consisting of 117 LC patient samples, 16 746 LC gene RNA sequencing data points, and 9 clinical features from the Cancer Genome Atlas (TCGA) database in the United States. We employed weighted gene co-expression network analysis (WGCNA) to construct multiple co-expression gene modules. Subsequently, we assessed the correlations between these co-expression modules and clinical features to validate their associations. We also explored the interplay between modules to identify pivotal genes within disease pathways. Finally, we used the Kaplan-Meier plotter to validate the correlation between enriched genes and LC prognosis.@*RESULTS@#WGCNA analysis led to the creation of a total of 16 co-expression gene modules related to LC. Four of these modules (designated as the yellow, magenta, black, and brown modules) exhibited significant correlations with 3 clinical features: The age of initial pathological diagnosis, cancer status, and pathological N stage. Specifically, the yellow and magenta gene modules displayed negative correlations with the age of pathological diagnosis (r=-0.23, P<0.05; r=-0.33, P<0.05), while the black and brown gene modules demonstrated negative associations with cancer status (r=-0.39, P<0.05; r=-0.50, P<0.05). The brown gene module displayed a positive correlation with pathological N stage. Gene Ontology (GO) enrichment analysis identified 77 items, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis identified 30 related signaling pathways, including the calcium signaling pathway, cytokine-cytokine receptor interaction, neuro active ligand-receptor interaction, and regulation of lipolysis in adipocytes, etc. Consequently, central genes within these modules that were significantly linked to the overall survival rate of LC patients were identified. Central genes included CHRNB4, FOXL2, KCNG1, LOC440173, ADAMTS15, BMP2, FAP, and KIAA1644.@*CONCLUSIONS@#This study, utilizing WGCNA and subsequent validation, pinpointed 8 genes with potential as gene biomarkers for LC. These findings offer valuable references for the clinical diagnosis, prognosis, and treatment of LC.


Subject(s)
Humans , Laryngeal Neoplasms/genetics , Rosaniline Dyes , Biomarkers , Adipocytes , Gene Regulatory Networks , Gene Expression Profiling
9.
Chinese Journal of Cellular and Molecular Immunology ; (12): 592-598, 2023.
Article in Chinese | WPRIM | ID: wpr-981904

ABSTRACT

Objective To investigate the effects of lipopolysaccharide (LPS) on human pulmonary vascular endothelial cells (HPVECs) cytoskeleton and perform biological analysis of the microRNA (miRNA) spectrum. Methods The morphology of HPVECs was observed by microscope, the cytoskeleton by FITC-phalloidin staining, and the expression of VE-cadherin was detected by immunofluorescence cytochemical staining; the tube formation assay was conducted to examine the angiogenesis, along with cell migration test to detect the migration, and JC-1 mitochondrial membrane potential to detect the apoptosis. Illumina small-RNA sequencing was used to identify differentially expressed miRNAs in NC and LPS group. The target genes of differentially expressed miRNAs were predicted by miRanda and TargetScan, and the functional and pathway enrichment analysis was performed on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Further biological analysis of related miRNAs was carried out. Results After the LPS got induced, the cells became round and the integrity of cytoskeleton was destroyed. The decreased expression of VE-cadherin was also observed, along with the decreased ability of angiogenesis and migration, and increased apoptosis. Sequencing results showed a total of 229 differential miRNAs, of which 84 miRNA were up-regulated and 145 miRNA were down-regulated. The target gene prediction and functional enrichment analysis of these differential miRNA showed that they were mainly concentrated in pathways related to cell connection and cytoskeleton regulation, cell adhesion process and inflammation. Conclusion In vitro model of lung injury, multiple miRNAs are involved in the process of HPVECs cytoskeleton remodeling, the reduction of barrier function, angiogenesis, migration and apoptosis.


Subject(s)
Humans , Lipopolysaccharides/pharmacology , Endothelial Cells/metabolism , MicroRNAs/metabolism , Lung/metabolism , Cytoskeleton , Gene Expression Profiling
10.
Chinese Journal of Cellular and Molecular Immunology ; (12): 509-515, 2023.
Article in Chinese | WPRIM | ID: wpr-981893

ABSTRACT

Objective To identify immune-related molecular markers in an attempt to predict prognosis of colon adenocarcinoma (COAD). Methods Immune related genes (IREGs) was analyzed based on the TCGA database. Weighted gene co-expression network analysis (WGCNA) and Cox regression analysis were used to establish risk models. According to the median risk score, COAD patients were divided into high risk and low risk groups. The prognostic difference were compared between the two groups. The function of the model was validated using GEO. Results A total of 1015 IREGs was obtained. The established model consisted of three genes: RAR related orphan receptor C (RORC), leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) and lectin galactoside-binding soluble galectin 4 (LGALS4). The high-risk group had significantly poorer prognosis than low-risk group in the GEO database, and it was validated using a GEO database. Further analysis via univariate and multivariate Cox regression analyses revealed that risk model could function as independent prognostic factor for COAD patients. Conclusion The risk model based on IREGs can predict the prognosis of patients with COAD.


Subject(s)
Humans , Prognosis , Adenocarcinoma/genetics , Colonic Neoplasms/genetics , Gene Expression Profiling , Lectins
11.
Chinese Journal of Oncology ; (12): 44-49, 2023.
Article in Chinese | WPRIM | ID: wpr-969804

ABSTRACT

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.


Subject(s)
Humans , Neoplasms, Unknown Primary/genetics , Carcinoma/drug therapy , Gene Expression Profiling/methods , Microarray Analysis , Prognosis
12.
Chinese Journal of Biotechnology ; (12): 4982-4995, 2023.
Article in Chinese | WPRIM | ID: wpr-1008073

ABSTRACT

The aldo-keto reductase super family (AKRs) has a wide range of substrate specificity. However, the systematic identification of insect AKR gene family members has not been reported. In this study, bioinformatics methods were used to predict the phylogenetic evolution, physical and chemical properties, chromosome location, conserved motifs, and gene structure of AKR family members in Bombyx mori (BmAKR). Transcriptome data or quantitative real time polymerase chain reaction (qRT-PCR) were used to analyze the expression level of BmAKR genes during different organizational periods and silkworm eggs in different developmental states. Moreover, Western blotting was used to detect the expression level of the BmAKR in silkworm eggs. The results showed that 11 BmAKR genes were identified. These genes were distributed on 4 chromosomes of the silkworm genome, all of which had the (α/β) 8-barrel motif, and their physical and chemical characteristics were relatively similar. Phylogenetic analysis showed that the BmAKR genes could be divided into 2 subgroups (AKR1 and AKR2). Transcriptome data analysis showed that the expression of BmAKR genes were quite different in different tissues and periods. Moreover, the expression analysis of BmAKR genes in silkworm eggs showed that some genes were expressed significantly higher in nondiapause eggs than in diapause eggs; but another gene, BmAKR1-1, was expressed significantly higher in diapause eggs than in nondiapause eggs. The detection of protein level found that the difference trend of BmAKR1-1 in diapause eggs and non-diapause eggs was consistent with the results of qRT-PCR. In conclusion, BmAKR1-1 was screened out as candidates through the identification and analysis of the BmAKR genes in silkworm, which may regulate silkworm egg development is worthy of further investigation.


Subject(s)
Animals , Bombyx/metabolism , Phylogeny , Diapause , Genes, Insect , Gene Expression Profiling , Insect Proteins/metabolism
13.
West China Journal of Stomatology ; (6): 533-540, 2023.
Article in English | WPRIM | ID: wpr-1007936

ABSTRACT

OBJECTIVES@#To investigate possible cross-talk genes, associated pathways, and transcription factors between chronic periodontitis (CP) and chronic obstructive pulmonary disease (COPD).@*METHODS@#The gene expression profiles of CP (GSE10334 and GSE16134) and COPD (GSE76925) were downloaded from the GEO database. Differential expression and functional clustering analyses were performed. The protein‑protein interaction (PPI) network was constructed. The core cross-talk genes were filtered using four topological analysis algorithms and modular segmentation. Then, functional clustering analysis was performed again.@*RESULTS@#GSE10334 detected 164 differentially expressed genes (DEGs) (119 upregulated and 45 downregulated). GSE16134 identified 208 DEGs (154 upregulated and 54 downregulated). GSE76925 identified 1 408 DEGs (557 upregulated and 851 downregulated). The PPI network included 21 nodes and 20 edges. The final screening included seven cross-talk genes: CD79A, FCRLA, CD19, IRF4, CD27, SELL, and CXCL13. Relevant pathways included primary immunodeficiency, the B-cell receptor signaling pathway, and cytokine-cytokine receptor interaction.@*CONCLUSIONS@#This study indicates the probability of shared pathophysiology between CP and COPD, and their cross-talk genes, associated pathways, and transcription factors may offer novel concepts for future mechanistic investigations.


Subject(s)
Humans , Chronic Periodontitis/genetics , Gene Regulatory Networks , Gene Expression Profiling , Protein Interaction Maps/genetics , Pulmonary Disease, Chronic Obstructive/genetics
14.
Chinese Medical Journal ; (24): 2974-2982, 2023.
Article in English | WPRIM | ID: wpr-1007584

ABSTRACT

BACKGROUND@#High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC.@*METHODS@#Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages.@*RESULTS@#Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively).@*CONCLUSIONS@#This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.


Subject(s)
Humans , Female , Ovarian Neoplasms/pathology , Prognosis , Gene Expression Profiling , Transcriptome , Tumor Microenvironment , Receptors, G-Protein-Coupled/therapeutic use , Tetraspanins/genetics , Protein Kinases , Integrin beta1/therapeutic use
15.
Frontiers of Medicine ; (4): 939-956, 2023.
Article in English | WPRIM | ID: wpr-1010802

ABSTRACT

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.


Subject(s)
Animals , Mice , Diploidy , Heart , Myocytes, Cardiac/metabolism , Cell Communication , Gene Expression Profiling , Mitochondria , Regeneration , Mammals/genetics
16.
International Journal of Oral Science ; (4): 45-45, 2023.
Article in English | WPRIM | ID: wpr-1010700

ABSTRACT

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.


Subject(s)
Animals , Mice , Neurons , Proprioception , Gene Expression Profiling , Pain , Sequence Analysis, RNA
17.
Chinese Medical Sciences Journal ; (4): 20-28, 2023.
Article in English | WPRIM | ID: wpr-981591

ABSTRACT

Objective To screen antigen targets for immunotherapy by analyzing over-expressed genes, and to identify significant pathways and molecular mechanisms in esophageal cancer by using bioinformatic methods such as enrichment analysis, protein-protein interaction (PPI) network, and survival analysis based on the Gene Expression Omnibus (GEO) database.Methods By screening with highly expressed genes, we mainly analyzed proteins MUC13 and EPCAM with transmembrane domain and antigen epitope from TMHMM and IEDB websites. Significant genes and pathways associated with the pathogenesis of esophageal cancer were identified using enrichment analysis, PPI network, and survival analysis. Several software and platforms including Prism 8, R language, Cytoscape, DAVID, STRING, and GEPIA platform were used in the search and/or figure creation.Results Genes MUC13 and EPCAM were over-expressed with several antigen epitopes in esophageal squamous cell carcinoma (ESCC) tissue. Enrichment analysis revealed that the process of keratinization was focused and a series of genes were related with the development of esophageal cancer. Four genes including ALDH3A1, C2, SLC6A1,and ZBTB7C were screened with significant P value of survival curve.Conclusions Genes MUC13 and EPCAM may be promising antigen targets or biomarkers for esophageal cancer. Keratinization may greatly impact the pathogenesis of esophageal cancer. Genes ALDH3A1, C2, SLC6A1,and ZBTB7C may play important roles in the development of esophageal cancer.


Subject(s)
Humans , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/metabolism , Epithelial Cell Adhesion Molecule/metabolism , Gene Expression Profiling/methods , Gene Regulatory Networks , Gene Expression , Gene Expression Regulation, Neoplastic , Intracellular Signaling Peptides and Proteins
18.
China Journal of Chinese Materia Medica ; (24): 1916-1926, 2023.
Article in Chinese | WPRIM | ID: wpr-981411

ABSTRACT

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1β and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1β, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.


Subject(s)
Animals , Zebrafish/genetics , Interleukin-6/genetics , Gene Expression Profiling , Cytokines/genetics , Macrophages , Transcriptome
19.
China Journal of Chinese Materia Medica ; (24): 1840-1850, 2023.
Article in Chinese | WPRIM | ID: wpr-981402

ABSTRACT

Uridine diphosphate glycosyltransferase(UGT) is a highly conserved protein in plants, which usually functions in secondary metabolic pathways. This study used the Hidden Markov Model(HMM) to screen out members of UGT gene family in the whole genome of Dendrobium officinale, and 44 UGT genes were identified. Bioinformatics was used to analyze the structure, phylogeny, and promoter region components of D. officinale genes. The results showed that UGT gene family could be divided into four subfamilies, and UGT gene structure was relatively conserved in each subfamily, with nine conserved domains. The upstream promoter region of UGT gene contained a variety of cis-acting elements related to plant hormones and environmental factors, indicating that UGT gene expression may be induced by plant hormones and external environmental factors. UGT gene expression in different tissues of D. officinale was compared, and UGT gene expression was found in all parts of D. officinale. It was speculated that UGT gene played an important role in many tissues of D. officinale. Through transcriptome analysis of D. officinale mycorrhizal symbiosis environment, low temperature stress, and phosphorus deficiency stress, this study found that only one gene was up-regulated in all three conditions. The results of this study can help understand the functions of UGT gene family in Orchidaceae plants and provide a basis for further study on the molecular regulation mechanism of polysaccharide metabolism pathway in D. officinale.


Subject(s)
Dendrobium/genetics , Plant Growth Regulators , Glycosyltransferases/metabolism , Gene Expression Profiling , Mycorrhizae , Phylogeny , Plant Proteins/metabolism
20.
Chinese Journal of Biotechnology ; (12): 3015-3036, 2023.
Article in Chinese | WPRIM | ID: wpr-981246

ABSTRACT

To explore the differentially expressed genes (DEGs) related to biosynthesis of active ingredients in wolfberry fruits of different varieties of Lycium barbarum L. and reveal the molecular mechanism of the differences of active ingredients, we utilized Illumina NovaSeq 6000 high-throughput sequencing technology to conduct transcriptome sequencing on the fruits of 'Ningqi No.1' and 'Ningqi No.7' during the green fruit stage, color turning stage and maturity stage. Subsequently, we compared the profiles of related gene expression in the fruits of the two varieties at different development stages. The results showed that a total of 811 818 178 clean reads were obtained, resulting in 121.76 Gb of valid data. There were 2 827, 2 552 and 2 311 DEGs obtained during the green fruit stage, color turning stage and maturity stage of 'Ningqi No. 1' and 'Ningqi No. 7', respectively, among which 2 153, 2 050 and 1 825 genes were annotated in six databases, including gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and clusters of orthologous groups of proteins (KOG). In GO database, 1 307, 865 and 624 DEGs of green fruit stage, color turning stage and maturity stage were found to be enriched in biological processes, cell components and molecular functions, respectively. In the KEGG database, the DEGs at three developmental stages were mainly concentrated in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interaction. In KOG database, 1 775, 1 751 and 1 541 DEGs were annotated at three developmental stages, respectively. Searching the annotated genes against the PubMed database revealed 18, 26 and 24 DEGs related to the synthesis of active ingredients were mined at the green fruit stage, color turning stage and maturity stage, respectively. These genes are involved in carotenoid, flavonoid, terpenoid, alkaloid, vitamin metabolic pathways, etc. Seven DEGs were verified by RT-qPCR, which showed consistent results with transcriptome sequencing. This study provides preliminary evidences for the differences in the content of active ingredients in different Lycium barbarum L. varieties from the transcriptional level. These evidences may facilitate further exploring the key genes for active ingredients biosynthesis in Lycium barbarum L. and analyzing their expression regulation mechanism.


Subject(s)
Flavonoids/metabolism , Fruit/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Plant , Lycium/metabolism , Metabolic Networks and Pathways , Transcriptome
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