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1.
J Cell Mol Med ; 28(7): e18219, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38509743

RESUMEN

The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.


Asunto(s)
MicroARNs , Traumatismos de la Médula Espinal , Animales , Necroptosis/genética , Biología Computacional , Perfilación de la Expresión Génica , MicroARNs/genética , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/genética
2.
J Gene Med ; 26(2): e3668, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38342959

RESUMEN

BACKGROUND: Colorectal cancer (CRC) poses a significant health challenge. This study aims to investigate the prognostic value of a regulatory T cell (Treg)-related gene signature in CRC. METHODS: We extracted the gene expression and clinical data on CRC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The gene module related to Treg was identified by weighted gene co-expression network analysis (WGCNA). The genes in the significant module were filtered by univariate Cox, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. A riskscore model was established in terms of the key Treg-related genes. The reliability of this riskscore model was validated using the external GEO dataset. The association of riskscore with clinical features, mutation patterns and signaling pathways was explored. RESULTS: Genes in the blue module showed the strongest association with Tregs. After a series of filtering cycles, seven Treg-related key genes, GDE1, GSR, HSPB1, AOC2, TBX19, TAMM41 and TIGD6, were selected to construct a riskscore model. This model performed well in evaluating the patients' survival in TCGA cohort, and was further affirmed by the GSE17536 validation cohort. For precise evaluation of the patients' survival, we established a nomogram in light of riskscore and clinical factors. Patients in different risk groups had distinct clinical features, mutation patterns and signaling pathway activities. The expression of five key genes was significantly associated with Treg infiltration in the CRC samples. CONCLUSION: We established a useful riskscore model in light of seven Treg-related genes. This model may contribute to the prognosis evaluation, direct tailored treatment, and hopefully improve clinical outcomes of the CRC patients.


Asunto(s)
Neoplasias Colorrectales , Linfocitos T Reguladores , Humanos , Reproducibilidad de los Resultados , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética
3.
J Gene Med ; 26(1): e3626, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37974510

RESUMEN

Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.


Asunto(s)
Aterosclerosis , Enfermedad de la Arteria Coronaria , Humanos , Ratones , Animales , Enfermedad de la Arteria Coronaria/genética , Macrófagos/metabolismo , Macrófagos/patología , Aterosclerosis/genética , Células Espumosas/metabolismo , Células Espumosas/patología
4.
Anal Biochem ; 691: 115534, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38621605

RESUMEN

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.


Asunto(s)
Medicamentos Herbarios Chinos , Hepatopatías Alcohólicas , Simulación del Acoplamiento Molecular , Farmacología en Red , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Animales , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Comprimidos , Ciclooxigenasa 2/metabolismo , Ratones Endogámicos C57BL , Cromatografía Líquida de Alta Presión , Hígado/metabolismo , Hígado/efectos de los fármacos
5.
Microb Ecol ; 87(1): 63, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691135

RESUMEN

Bacterial azoreductases are enzymes that catalyze the reduction of ingested or industrial azo dyes. Although azoreductase genes have been well identified and characterized, the regulation of their expression has not been systematically investigated. To determine how different factors affect the expression of azoR, we extracted and analyzed transcriptional data from the Gene Expression Omnibus (GEO) resource, then confirmed computational predictions by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results showed that azoR expression was lower with higher glucose concentration, agitation speed, and incubation temperature, but higher at higher culture densities. Co-expression and clustering analysis indicated ten genes with similar expression patterns to azoR: melA, tpx, yhbW, yciK, fdnG, fpr, nfsA, nfsB, rutF, and chrR (yieF). In parallel, constructing a random transposon library in E. coli K-12 and screening 4320 of its colonies for altered methyl red (MR)-decolorizing activity identified another set of seven genes potentially involved in azoR regulation. Among these genes, arsC, relA, plsY, and trmM were confirmed as potential azoR regulators based on the phenotypic decolorization activity of their transposon mutants, and the expression of arsC and relA was confirmed, by qRT-PCR, to significantly increase in E. coli K-12 in response to different MR concentrations. Finally, the significant decrease in azoR transcription upon transposon insertion in arsC and relA (as compared to its expression in wild-type E. coli) suggests their probable involvement in azoR regulation. In conclusion, combining in silico analysis and random transposon mutagenesis suggested a set of potential regulators of azoR in E. coli.


Asunto(s)
Elementos Transponibles de ADN , Proteínas de Escherichia coli , Escherichia coli , Regulación Bacteriana de la Expresión Génica , Nitrorreductasas , Elementos Transponibles de ADN/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Nitrorreductasas/genética , Nitrorreductasas/metabolismo , NADH NADPH Oxidorreductasas/genética , NADH NADPH Oxidorreductasas/metabolismo , Mutagénesis , Genoma Bacteriano , Biología Computacional , Mutagénesis Insercional
6.
Philos Trans A Math Phys Eng Sci ; 382(2276): 20230184, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38945164

RESUMEN

There is an ongoing discussion about how to forecast the maximum magnitudes of induced earthquakes based on operational parameters, subsurface conditions and physical process understanding. Although the occurrence of damage caused by induced earthquakes is rare, some cases have caused significant economic loss, injuries and even loss of life. We analysed a global compilation of earthquakes induced by hydraulic fracturing, geothermal reservoir stimulation, water disposal, gas storage and reservoir impoundment. Our analysis showed that maximum magnitudes scale with the characteristic length of pressure diffusion in the brittle Earth's crust. We observed an increase in the nucleation potential of larger-magnitude earthquakes with time and explained it by diffusion-controlled growth of the pressure-perturbed part of faults. Numerical and analytical fault size modelling supported our findings. Finally, we derived magnitude scaling laws to manage induced seismic hazard of upcoming energy projects prior to operation. This article is part of the theme issue 'Induced seismicity in coupled subsurface systems'.

7.
Int J Hyperthermia ; 41(1): 2290913, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38191150

RESUMEN

Some heat shock proteins (HSPs) have been shown to influence tumor prognosis, but their prognostic significance in colorectal cancer (CRC) remains unclear. This study explored the prognostic significance of HSP-related genes in CRC. Transcriptional data and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) database, and a literature search was conducted to identify HSP-related genes. Using Least Absolute Selection and Shrinkage Operator (LASSO) regression and univariate/multivariate Cox regression analyses, 12 HSP-related genes demonstrating significant associations with CRC survival were successfully identified and employed to formulate a predictive risk score model. The efficacy and precision of this model were validated utilizing TCGA and Gene Expression Omnibus (GEO) datasets, demonstrating its reliability in CRC prognosis prediction. gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant disparities between high- and low-risk groups in chromatin remodeling biological functions and neutrophil extracellular trap formation pathways. Single sample gene set enrichment analysis (ssGSEA) further revealed differences in immune cell types and immune functional status between the two risk groups. Differential analysis showed higher expression of immune checkpoints within the low-risk group, while the high-risk group exhibited notably higher Tumor Immune Dysfunction and Exclusion (TIDE) scores. Additionally, we predicted the sensitivity of different prognosis risk patients to various drugs, providing potential drug choices for tailored treatment. Combined, our study successfully crafted a novel CRC prognostic model that can effectively predict patient survival, immune landscape, and treatment response, providing important support and guidance for CRC patient prognosis.


Asunto(s)
Neoplasias Colorrectales , Proteínas de Choque Térmico , Humanos , Pronóstico , Reproducibilidad de los Resultados , Proteínas de Choque Térmico/genética , Análisis Multivariante , Neoplasias Colorrectales/genética
8.
Curr Genomics ; 25(2): 120-139, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38751599

RESUMEN

Background: Calebin-A is a minor phytoconstituent of turmeric known for its activity against inflammation, oxidative stress, cancerous, and metabolic disorders like Non-alcoholic fatty liver disease(NAFLD). Based on bioinformatic tools. Subsequently, the details of the interaction of critical proteins with Calebin-A were investigated using the molecular docking technique. Methods: We first probed the intersection of genes/ proteins between NAFLD and Calebin-A through online databases. Besides, we performed an enrichment analysis using the ClueGO plugin to investigate signaling pathways and gene ontology. Next, we evaluate the possible interaction of Calebin-A with significant hub proteins involved in NAFLD through a molecular docking study. Results: We identified 87 intersection genes Calebin-A targets associated with NAFLD. PPI network analysis introduced 10 hub genes (TP53, TNF, STAT3, HSP90AA1, PTGS2, HDAC6, ABCB1, CCT2, NR1I2, and GUSB). In KEGG enrichment, most were associated with Sphingolipid, vascular endothelial growth factor A (VEGFA), C-type lectin receptor, and mitogen-activated protein kinase (MAPK) signaling pathways. The biological processes described in 87 intersection genes are mostly concerned with regulating the apoptotic process, cytokine production, and intracellular signal transduction. Molecular docking results also directed that Calebin-A had a high affinity to bind hub proteins linked to NAFLD. Conclusion: Here, we showed that Calebin-A, through its effect on several critical genes/ proteins and pathways, might repress the progression of NAFLD.

9.
Eur Neurol ; 87(1): 36-42, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38228099

RESUMEN

INTRODUCTION: The integration of vestibular, visual, and somatosensory cues allows the perception of space through the orientation of our body and surrounding objects with respect to gravity. The main goal of this study was to identify the cortical networks recruited during the representation of body midline and the representation of verticality. METHODS: Thirty right-handed healthy participants were evaluated using fMRI. Brain networks activated during a subjective straight-ahead (SSA) task were compared to those recruited during a subjective vertical (SV) task. RESULTS: Different patterns of cortical activation were observed, with differential increases in the angular gyrus and left cerebellum posterior lobe during the SSA task, in right rolandic operculum and cerebellum anterior lobe during the SV task. DISCUSSION: The activation of these areas involved in visuo-spatial functions suggests that bodily processes of great complexity are engaged in body representation and vertical perception. Interestingly, the common brain networks involved in SSA and SV tasks were comprised of areas of vestibular projection that receive multisensory information (parieto-occipital areas) and the cerebellum, and reveal a predominance of the right cerebral and cerebellar hemispheres. The outcomes of this first fMRI study designed to unmask common and specific neural mechanisms at work in gravity- or body-referenced tasks pave a new way for the exploration of spatial cognitive impairment in patients with vestibular or cortical disorders.


Asunto(s)
Encéfalo , Percepción Espacial , Humanos , Percepción Espacial/fisiología , Encéfalo/diagnóstico por imagen , Lóbulo Parietal/fisiología , Mapeo Encefálico/métodos , Ego
10.
Skin Res Technol ; 30(6): e13808, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899746

RESUMEN

BACKGROUND: Dermatomyositis (DM) manifests as an autoimmune and inflammatory condition, clinically characterized by subacute progressive proximal muscle weakness, rashes or both along with extramuscular manifestations. Literature indicates that DM shares common risk factors with atherosclerosis (AS), and they often co-occur, yet the etiology and pathogenesis remain to be fully elucidated. This investigation aims to utilize bioinformatics methods to clarify the crucial genes and pathways that influence the pathophysiology of both DM and AS. METHOD: Microarray datasets for DM (GSE128470, GSE1551, GSE143323) and AS (GSE100927, GSE28829, GSE43292) were retrieved from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was used to reveal their co-expressed modules. Differentially expression genes (DEGs) were identified using the "limma" package in R software, and the functions of common DEGs were determined by functional enrichment analysis. A protein-protein interaction (PPI) network was established using the STRING database, with central genes evaluated by the cytoHubba plugin, and validated through external datasets. Immune infiltration analysis of the hub genes was conducted using the CIBERSORT method, along with Gene Set Enrichment Analysis (GSEA). Finally, the NetworkAnalyst platform was employed to examine the transcription factors (TFs) responsible for regulating pivotal crosstalk genes. RESULTS: Utilizing WGCNA analysis, a total of 271 overlapping genes were pinpointed. Subsequent DEG analysis revealed 34 genes that are commonly found in both DM and AS, including 31 upregulated genes and 3 downregulated genes. The Degree Centrality algorithm was applied separately to the WGCNA and DEG collections to select the 15 genes with the highest connectivity, and crossing the two gene sets yielded 3 hub genes (PTPRC, TYROBP, CXCR4). Validation with external datasets showed their diagnostic value for DM and AS. Analysis of immune infiltration indicates that lymphocytes and macrophages are significantly associated with the pathogenesis of DM and AS. Moreover, GSEA analysis suggested that the shared genes are enriched in various receptor interactions and multiple cytokines and receptor signaling pathways. We coupled the 3 hub genes with their respective predicted genes, identifying a potential key TF, CBFB, which interacts with all 3 hub genes. CONCLUSION: This research utilized comprehensive bioinformatics techniques to explore the shared pathogenesis of DM and AS. The three key genes, including PTPRC, TYROBP, and CXCR4, are related to the pathogenesis of DM and AS. The central genes and their correlations with immune cells may serve as potential diagnostic and therapeutic targets.


Asunto(s)
Aterosclerosis , Biomarcadores , Biología Computacional , Dermatomiositis , Mapas de Interacción de Proteínas , Humanos , Biología Computacional/métodos , Dermatomiositis/genética , Dermatomiositis/inmunología , Aterosclerosis/genética , Aterosclerosis/inmunología , Biomarcadores/metabolismo , Biomarcadores/análisis , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Redes Reguladoras de Genes
11.
BMC Public Health ; 24(1): 1732, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943127

RESUMEN

BACKGROUND: In Haiti, reported incidence and mortality rates for COVID-19 were lower than expected. We aimed to analyze factors at communal and individual level that might lead to an underestimation of the true burden of the COVID-19 epidemic in Haiti during its first two years. METHODS: We analyzed national COVID-19 surveillance data from March 2020 to December 2021, to describe the epidemic using cluster detection, time series, and cartographic approach. We performed multivariate Quasi-Poisson regression models to determine socioeconomic factors associated with incidence and mortality. We performed a mixed-effect logistic regression model to determine individual factors associated with the infection. RESULTS: Among the 140 communes of Haiti, 57 (40.7%) had a COVID-19 screening center, and the incidence was six times higher in these than in those without. Only 22 (15.7%) communes had a COVID-19 care center, and the mortality was five times higher in these than in those without. All the richest communes had a COVID-19 screening center while only 30.8% of the poorest had one. And 75% of the richest communes had a COVID-19 care center while only 15.4% of the poorest had one. Having more than three healthcare workers per 1000 population in the commune was positively associated with the incidence (SIR: 3.31; IC95%: 2.50, 3.93) and the mortality (SMR: 2.73; IC95%: 2.03, 3.66). At the individual level, male gender (adjusted OR: 1.11; IC95%: 1.01, 1.22), age with a progressive increase of the risk compared to youngers, and having Haitian nationality only (adjusted OR:2.07; IC95%: 1.53, 2.82) were associated with the infection. CONCLUSIONS: This study highlights the weakness of SARS-CoV-2 screening and care system in Haiti, particularly in the poorest communes, suggesting that the number of COVID-19 cases and deaths were probably greatly underestimated.


Asunto(s)
COVID-19 , Tamizaje Masivo , Humanos , Haití/epidemiología , COVID-19/epidemiología , COVID-19/mortalidad , Masculino , Femenino , Adulto , Persona de Mediana Edad , Incidencia , Tamizaje Masivo/estadística & datos numéricos , Adulto Joven , SARS-CoV-2 , Adolescente , Anciano , Factores Socioeconómicos , Prueba de COVID-19/estadística & datos numéricos
12.
Hum Hered ; 88(1): 18-28, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36913932

RESUMEN

INTRODUCTION: Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients. METHODS: GSE17612, GSE21935, and GSE53987 datasets, consisting of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patient. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores and patients in low-score groups if their hypoxia score was in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients. RESULTS: In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in the patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients. CONCLUSION: These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/genética , Predisposición Genética a la Enfermedad , Biomarcadores , Expresión Génica , Hipoxia/genética
13.
Environ Toxicol ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622876

RESUMEN

Osteosarcoma (OS), known for its high recurrence and metastasis rates, poses a significant challenge in oncology. Our research investigates the role of programmed cell death (PCD) genes in OS and develops a prognostic model using advanced bioinformatics. We analyzed single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify subpopulations, distinguish malignant from non-malignant cells, assess cell cycle phases, and map PCD gene distribution. Additionally, we applied consistency clustering to bulk sequencing data from GEO and TARGET (Therapeutically Applicable Research to Generate Effective Treatments) databases, facilitating survival analysis across clusters with the Kaplan-Meier method. We calculated PCD scores for each cluster using the Single-sample Gene Set Enrichment Analysis (ssGSEA), which enabled a detailed examination of PCD-related gene expression and pathway scores. Our study also explored drug sensitivity differences and conducted comprehensive immune cell infiltration analyses using various algorithms. We identified differentially expressed genes, leading to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses that provided insights into relevant biological processes and pathways. The prognostic model, based on five pivotal genes (BAMBI, TMCC2, NOX4, DKK1, and CBS), was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and validated in the TARGET-OS and GSE16091 datasets, showing significant predictive accuracy. This research enhances our understanding of PCD in OS and supports the development of effective treatments.

14.
Environ Toxicol ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682583

RESUMEN

BACKGROUND: Diabetes mellitus (DM) is a prevalent chronic disease marked by significant metabolic dysfunctions. Understanding its molecular mechanisms is vital for early diagnosis and treatment strategies. METHODS: We used datasets GSE7014, GSE25724, and GSE156248 from the GEO database to build a diagnostic model for DM using Random Forest (RF) and LASSO regression models. GSE20966 served as a validation cohort. DM patients were classified into two subtypes for functional enrichment analysis. Expression levels of key diagnostic genes were validated using quantitative real-time PCR (qRT-PCR) on Peripheral Blood Mononuclear Cells (PBMCs) from DM patients and healthy controls, focusing on CXCL12 and PPP1R12B with GAPDH as the internal control. RESULTS: After de-batching the datasets, we identified 131 differentially expressed genes (DEGs) between DM and control groups, with 70 up-regulated and 61 down-regulated. Enrichment analysis revealed significant down-regulation in the IL-12 signaling pathway, JAK signaling post-IL-12 stimulation, and the ferroptosis pathway in DM. Five genes (CXCL12, MXRA5, UCHL1, PPP1R12B, and C7) were identified as having diagnostic value. The diagnostic model showed high accuracy in both the training and validation cohorts. The gene set also enabled the subclassification of DM patients into groups with distinct functional traits. qRT-PCR results confirmed the bioinformatics findings, particularly the up-regulation of CXCL12 and PPP1R12B in DM patients. CONCLUSION: Our study pinpointed seven energy metabolism-related genes differentially expressed in DM and controls, with five holding diagnostic value. Our model accurately diagnosed DM and facilitated patient subclassification, offering new insights into DM pathogenesis.

15.
Genomics ; 115(3): 110619, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37019419

RESUMEN

BACKGROUND: Adenomyosis is a benign uterine disease and affected patients present with symptoms such as menorrhagia, chronic pelvic pain, abnormal uterine bleeding, and infertility. However, the specific mechanisms by which adenomyosis occurs need to be further studied. OBJECTIVE: Dataset of adenomyosis from our hospital and a public database were analyzed using bioinformatics. Corresponding differentially expressed genes (DEGs) and gene enrichment were detected to explore potential genetic adenomyosis targets. METHODS: Clinical data on adenomyosis were accessed based on the pathological specimens of patients with adenomyosis obtained from the Shengjing Hospital. R software was used to screen for DEGs, and volcano and cluster maps were drawn. Adenomyosis datasets (GSE74373) were downloaded from the GEO database. GEO2R online tool was used to screen for DEGs between adenomyosis and normal controls. Genes with P < 0.01 and |logFC| >1 were selected as DEGs. DAVID software was used for functional and pathway enrichment analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on common DEGs to obtain descriptions of the genes. The online database STRING was used for interaction gene retrieval. Moreover, Cytoscape software was used to construct a protein-protein interaction (PPI) network map for common DEGs to visualize potential gene interactions and screen the hub genes. RESULTS: A total of 845 DEGs were identified in the dataset obtained from Shengjing Hospital. A total of 175 genes were downregulated, and 670 genes were upregulated. In the GSE74373 database, 1679 genes were differentially expressed, 916 genes were downregulated, and 763 genes were upregulated. A total of 40 downregulated and 148 upregulated common DEGs showed potential gene interactions. The top ten upregulated hub genes were CDH1, EPCAM, CLDN7, ESRP1, RAB25, SPINT1, PKP3, TJP3, GRHL2, and CDKN2A. CONCLUSION: Genes involved in tight junction may be key in the development of adenomyosis and may provide a potential treatment strategy for adenomyosis.


Asunto(s)
Adenomiosis , Perfilación de la Expresión Génica , Femenino , Humanos , Mapeo de Interacción de Proteínas , Biomarcadores de Tumor/genética , Adenomiosis/genética , Regulación Neoplásica de la Expresión Génica , Endometrio/metabolismo , Biología Computacional , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismo , Proteínas de la Zonula Occludens/genética , Proteínas de la Zonula Occludens/metabolismo
16.
Ren Fail ; 46(2): 2371059, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38946402

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis. METHODS: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT. RESULTS: The expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells. CONCLUSIONS: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.


Asunto(s)
Biología Computacional , Glomerulonefritis , Células Mesangiales , ARN Circular , ARN Circular/genética , ARN Circular/metabolismo , Animales , Ratones , Células Mesangiales/metabolismo , Glomerulonefritis/genética , Glomerulonefritis/metabolismo , Análisis de Secuencia de ARN , Redes Reguladoras de Genes , ARN Mensajero/metabolismo , ARN Mensajero/genética , Mapas de Interacción de Proteínas/genética , Enfermedad Crónica , Citocinas/metabolismo , Lipopolisacáridos/farmacología , Perfilación de la Expresión Génica , Modelos Animales de Enfermedad
17.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931506

RESUMEN

Within research on the cross-view geolocation of UAVs, differences in image sources and interference from similar scenes pose huge challenges. Inspired by multimodal machine learning, in this paper, we design a single-stream pyramid transformer network (SSPT). The backbone of the model uses the self-attention mechanism to enrich its own internal features in the early stage and uses the cross-attention mechanism in the later stage to refine and interact with different features to eliminate irrelevant interference. In addition, in the post-processing part of the model, a header module is designed for upsampling to generate heat maps, and a Gaussian weight window is designed to assign label weights to make the model converge better. Together, these methods improve the positioning accuracy of UAV images in satellite images. Finally, we also use style transfer technology to simulate various environmental changes in order to expand the experimental data, further proving the environmental adaptability and robustness of the method. The final experimental results show that our method yields significant performance improvement: The relative distance score (RDS) of the SSPT-384 model on the benchmark UL14 dataset is significantly improved from 76.25% to 84.40%, while the meter-level accuracy (MA) of 3 m, 5 m, and 20 m is increased by 12%, 12%, and 10%, respectively. For the SSPT-256 model, the RDS has been increased to 82.21%, and the meter-level accuracy (MA) of 3 m, 5 m, and 20 m has increased by 5%, 5%, and 7%, respectively. It still shows strong robustness on the extended thermal infrared (TIR), nighttime, and rainy day datasets.

18.
Sensors (Basel) ; 24(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38676213

RESUMEN

The Stingray sensor system is a 15-camera optical array dedicated to the nightly astrometric and photometric survey of the geosynchronous Earth orbit (GEO) belt visible above Tucson, Arizona. The primary scientific goal is to characterize GEO and near-GEO satellites based on their observable properties. This system is completely autonomous in both data acquisition and processing, with human oversight reserved for data quality assurance and system maintenance. The 15 ZWO ASI1600MM Pro cameras are mated to Sigma 135 mm f/1.8 lenses and are controlled simultaneously by four separate computers. Each camera is fixed in position and observes a 7.6-by-5.8-degree portion of the GEO belt, for a total of a 114-by-5.8-degree field of regard. The GAIA DR2 star catalog is used for image astrometric plate solution and photometric calibration to GAIA G magnitudes. There are approximately 200 near-GEO satellites on any given night that fall within the Stingray field of regard, and all those with a GAIA G magnitude brighter than approximately 15.5 are measured by the automated data reduction pipeline. Results from an initial one-month survey show an aggregate photometric uncertainty of 0.062 ± 0.008 magnitudes and astrometric accuracy consistent with theoretical sub-pixel centroid limits. Provided in this work is a discussion of the design and function of the system, along with verification of the initial survey results.

19.
Sensors (Basel) ; 24(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38257483

RESUMEN

With the continuous operation of analog circuits, the component degradation problem gradually comes to the forefront, which may lead to problems, such as circuit performance degradation, system stability reductions, and signal quality degradation, which could be particularly evident in increasingly complex electronic systems. At the same time, due to factors, such as continuous signal transformation, the fluctuation of component parameters, and the nonlinear characteristics of components, traditional fault localization methods are still facing significant challenges when dealing with large-scale complex circuit faults. Based on this, this paper proposes a fault-diagnosis method for analog circuits using the ECWGEO algorithm, an enhanced version of the GEO algorithm, to de-optimize the 1D-CNN with an attention mechanism to handle time-frequency fusion inputs. Firstly, a typical circuit-quad op-amp dual second-order filter circuit is selected to construct a fault-simulation model, and Monte Carlo analysis is used to obtain a large number of samples as the dataset of this study. Secondly, the 1D-CNN network structure is improved for the characteristics of the analog circuits themselves, and the time-frequency domain fusion input is implemented before inputting it into the network, while the attention mechanism is introduced into the network. Thirdly, instead of relying on traditional experience for network structure determination, this paper adopts a parameter-optimization algorithm for network structure optimization and improves the GEO algorithm according to the problem characteristics, which enhances the diversity of populations in the late stage of its search and accelerates the convergence speed. Finally, experiments are designed to compare the results in different dimensions, and the final proposed structure achieved a 98.93% classification accuracy, which is better than other methods.

20.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38256187

RESUMEN

Depression and vitamin D deficiency are often co-occurring pathologies, the common pathogenetic ground of which includes an augmented inflammatory response. However, the molecular details of this relationship remain unclear. Here, we used a bioinformatic approach to analyze GEO transcriptome datasets of major depressive disorder (MDD) and vitamin D deficiency (VDD) to identify the hub genes within the regulatory networks of commonly differentially expressed genes (DEGs). The MDD-VDD shared regulatory network contains 100 DEGs (71 upregulated and 29 downregulated), with six hub genes (PECAM1, TLR2, PTGS2, LRRK2, HCK, and IL18) all significantly upregulated, of which PTGS2 (also known as COX2) shows the highest inference score and reference count. The subsequent analysis of the miRNA-transcription factors network identified COX2, miR-146a-5p, and miR-181c-5p as key co-regulatory actors in the MDD-VDD shared molecular pathogenic mechanisms. Subsequent analysis of published MDD and VDD transcriptome data confirmed the importance of the identified hub genes, further validating our bioinformatic analytical pipeline. Our study demonstrated that PTGS2 was highly upregulated in both depressive patients and patients with low vitamin D plasma levels. Therefore, regulators targeting PTGS2, like miR-146a-5p and miR181c-5p, may have great potential in controlling both diseases simultaneously, accentuating their role in future research.


Asunto(s)
Trastorno Depresivo Mayor , MicroARNs , Deficiencia de Vitamina D , Humanos , MicroARNs/genética , Ciclooxigenasa 2/genética , Trastorno Depresivo Mayor/genética , Depresión/genética , Factores de Transcripción/genética , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/genética
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