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1.
CienciaUAT ; 18(2): 107-121, ene.-jun. 2024. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1569024

ABSTRACT

Resumen: El gel de Aloe vera es considerado una fuente natural de múltiples beneficios, originados por la acción combinada de vitaminas, aminoácidos, compuestos fenólicos, enzimas, minerales, ácidos orgánicos, lípidos y carbohidratos, que se relacionan con la mejora de enfermedades neuro-degenerativas como Alzheimer. Los ensayos in vitro e in silico permiten confirmar e identificar posibles beneficios de esta planta y sus compuestos en enfermedades. El objetivo del presente trabajo fue evaluar la actividad antioxidante del gel de A. vera y mediante análisis in silico, establecer el potencial terapéutico de sus compuestos bioactivos en la enfermedad de Alzheimer. Se obtuvieron hojas de A. vera, de las que se extrajo el gel, retirando el exocarpio, se liofilizó y almacenó hasta su uso. Se caracterizó la capacidad antioxidante, se cuantificaron los compuestos fenólicos y flavonoides y se analizó la relación que existe entre los parámetros mediante correlación de Pearson. Mediante análisis in silico se evaluó el potencial de interacción de 8 compuestos del gel con la proteína gamma secretasa. El gel de A. vera obtuvo alta capacidad antioxidante por ABTS, DPPH, radical OH y poder reductor, usando bajas concentraciones para inhibir el 50 % de los radicales, y correlaciones positivas con fenoles totales y flavonoides. En el estudio in silico el compuesto que presentó mejor unión con gamma secretasa fue aloe-emodina, con menor energía libre de unión y menor concentración de constante de inhibición, sugiriendo su potencial uso como coadyuvante en el tratamiento de la enfermedad de Alzheimer.


Abstract: Aloe vera gel is considered a natural source of multiple benefits, originated by the combined action of vitamins, amino acids, phenolic compounds, enzymes, minerals, organic acids, lipids and carbohydrates, which are related to the improvement of neuro-degenerative diseases such as Alzheimer's. In vitro and in silico tests allow us to confirm and identify possible benefits of this plant and its compounds in diseases. The objective of the present study was to evaluate the antioxidant activity of A. vera gel and, through in silico analysis, to establish the therapeutic potential of its bioactive compounds in Alzheimer's disease. A. vera leaves were obtained, from which the gel was extracted, removing the exocarp, lyophilized and stored until use. The antioxidant capacity was characterized, the phenolic compounds and flavonoids were quantified, and the relationship between the parameters was analyzed using Pearson correlation. The interaction potential of 8 compounds in the gel with the gamma secretase protein was evaluated through in silico analysis. The A. vera gel obtained high antioxidant capacity due to ABTS, DPPH, OH radical and reducing power, using low concentrations to inhibit 50 % of the radicals, and positive correlations with total phenols and flavonoids. In the in silico study, the compound that showed the best binding with gamma secretase was aloe-emodin, with lower binding free energy and lower inhibition constant concentration, suggesting its potential use as an adjuvant in the treatment of Alzheimer's disease.

2.
Int. j. morphol ; 42(1): 173-184, feb. 2024.
Article in English | LILACS | ID: biblio-1528836

ABSTRACT

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.


El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.


Subject(s)
Humans , Stomach Neoplasms/metabolism , Adenocarcinoma/metabolism , Chloride Channels/metabolism , Prognosis , Stomach Neoplasms/immunology , Immunohistochemistry , Adenocarcinoma/immunology , Biomarkers, Tumor , Survival Analysis , Chloride Channels/genetics , Chloride Channels/immunology , Computational Biology , Mutation
3.
Braz. j. med. biol. res ; 57: e13339, fev.2024. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1557311

ABSTRACT

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

4.
Article in Chinese | WPRIM | ID: wpr-1006283

ABSTRACT

In order to promote the innovative application of Sanjiao theory and Yingwei theory, this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases, integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body, and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi, and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion, which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis, which contributes to T cell exhaustion and is correlated with nutrient deprivation, lipid accumulation, and high lactate levels in the immunosuppressed tumor microenvironment, as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction, Shengming decoction, and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation, and hypoxia inducible factor-1α (HIF-1α) may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.

5.
Article in Chinese | WPRIM | ID: wpr-1016841

ABSTRACT

ObjectiveKey microRNAs (miRNAs) of colorectal adenoma (CRA) were identified and analyzed by bioinformatics methods, and differentially expressed genes (DEGs) were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus (GEO) database of intestinal mucosal tissue of CRA patients, and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan, miRTarbase, and miRDB databases were used to predict the target genes of the differentially expressed miRNAs, and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software, and the TRRUST database was used to predict downstream binding transcription factors (TFs). The mRNA intersection was enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs, and the key signaling pathways were selected for animal experiments. In animal experiments, the CRA mice model was established by using sodium glycan sulfate (DSS) drinking combined with intraperitoneal injection of azomethane oxide (AOM), and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phosphoryl-PI3K (p-PI3K), phosphoryl-Akt (p-Akt), and B cell lymphoma (Bcl)-2 were detected by Western blot. The expression of Cyclin D1 (CCND1) was detected by immunohistochemistry (IHC). In situ terminal transferase labeling (TUNEL) was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset, and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them, GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex, RNA polymerase Ⅱ transcriptional regulatory complex, enzyme-linked receptor protein signaling pathway, and DNA-binding transcriptional activator activity, cancer pathway, PI3K/Akt pathway, etc. miR-34a-5p is mainly enriched in PI3K/Akt, cell cycle, and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database, among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 (E2F1) and tumor protein P53 (TP53) were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p, down-regulate the expression of PI3K, Akt, Bcl-2, p-PI3K, and p-Akt proteins in the intestinal tissue of CRA mice, down-regulate the positive expression rate of CCND1, and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway, thus playing a role in the prevention of CRA.

6.
Article in Chinese | WPRIM | ID: wpr-1016842

ABSTRACT

ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes (FRGs) closely related to ulcerative colitis (UC), and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes (DEGs) of colonic mucosa tissue of UC patients were obtained from the GEO database, and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis, minimum absolute contraction and selection operator (LASSO) regression, and receiver operating characteristic curve (ROC) curve analysis. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of E3 ubiquitin ligase (FBXW7), zinc finger protein (ZFP36), solute carrier family 7 member 11 (SLC7A11), and Toll-like receptor 4 (TLR4) in colon tissue. The protein expression levels of FBXW7, ZFP36, SLC7A11, and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database, and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis, LASSO regression, and ROC analysis, core FRGs (FBXW7, ZFP36, SLC7A11, and TLR4) were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells, M1 macrophages, plasma cells, and M2 macrophages in the colonic mucosa tissue of UC mice, and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine, while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group, the protein and mRNA expressions of FBXW7, ZFP36, SLC7A11, and TLR4 in the model group were significantly increased, and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7, ZFP36, SLC7A11, and TLR4 are ferroptosis genes closely related to the pathogenesis of UC, and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.

7.
Article in Chinese | WPRIM | ID: wpr-1016843

ABSTRACT

ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.

8.
Article in Chinese | WPRIM | ID: wpr-1017334

ABSTRACT

Objective:To screen the aging genes closely associated with pelvic organ prolapse(POP)by bioinformatics techniques,and to clarify the potential clinical significance and value of key genes.Methods:Gene Expression Omnibus(GEO)Database was used to download the datasets GSE53868 and GSE151188 for POP-related genes with the keyword"pelvic organ prolapse".The aging-related genes were obtained from Aging Atlas,CellAge,and the Human Ageing Genomic Resources(HAGR)Databases;the intersection of genes related with POP in two groups provided a list of differentially expressed genes(DEGs)associated with aging in POP;gene Set Enrichment Analysis(GSEA)was conducted with R software version 4.2.1;Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis of DEGs were conducted by the Database for Annotation,Visualization and Integrated Discovery(DAVID);the protein-protein interaction(PPI)network was constructed with Cytoscape 3.9.1 software;the top 10 Hub genes were selected by cytoHubba plugin;the infiltration of 22 types of immune cells in the patients in POP group and control group was analyzed by CIBERSORT deconvolution method using R software;the key genes were further screened by LASSO regression algorithm;the correlation and diagnostic efficacy between key genes and immune cell infiltration were analyzed.Results:From the Aging Atlas,CellAge,and HAGR Databases,724 aging-related genes were identified.Intersection with the POP expression profile yielded an aging gene expression matrix related to POP containing 624 genes,and 29 POP-related DEGs were identified after differential analysis,including 2 upregulated genes and 27 downregulated genes.The GSEA results showed that the upregulated pathways were mainly related to diabetes and cellular senescence,whereas the downregulated pathways included Alzheimer's disease and hypoxia-inducible factor-1(HIF-1)signaling pathways.The GO functional enrichment analysis mainly enriched in the biological processes such as the response of the cells to lipopolysaccharide,inflammatory response,and negative regulation of cell proliferation.The KEGG signaling pathway enrichment analysis mainly enriched in interleukin-17(IL-17),tumor necrosis factor(TNF),and nuclear factor-kappa B(NF-κB)signaling pathways.The PPI network analysis got 10 Hub genes including interleukin-6(IL-6),interleukin-1B(IL-1B),prostaglandin-endoperoxide synthase 2(PTGS2),and NF-kappa-B inhibitor alpha(NFKBIA).The CIBERSORT deconvolution method results showed a relatively higher infiltration proportion of neutrophils and activated mast cells in the patients in POP group,the activated mast cells had a positive correlation with most of the DEGs(r>0.5)and the macrophages had a significant positive correlation with IL-1B(r>0.6).The key genes Jun D proto-oncogene(JUND),Snail homolog 1(SNAI1),amphiregulin(AREG),Lamin A/C(LMNA),and superoxide dismutase 2(SOD2)selected by LASSO regression analysis had high diagnostic efficacies,and the area under receiver operating characteristic curve(ROC)(AUC)were all greater than 0.75.Conclusion:During the aging process,the genes such as JUND,SNAI1,AREG,LMNA,and SOD2 may participate in the pathophysiology of POP through various pathways,including inflammation-related pathways,transcription regulation,and affecting collagen secretion and metabolism,thereby influence the connective tissue support function and promote the occurrence and development of POP.

9.
Article in Chinese | WPRIM | ID: wpr-1017336

ABSTRACT

Objective:To select the differential prognostic lactic acid metabolism-related genes(LRGs)of the head and neck squamous cell carcinoma(HNSCC)to construct the LRGs prognostic model of HNSCC,and to clarify the potential mechanism.Methods:The HNSCC gene expression and clinical data were obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)Databases,the LRGs were identified through GeneCards Database,and R software was used to screen out the LRGs of HNSCC;univariate Cox regression analysis was used to identify prognosis-related genes;two different subtypes were identified based on the prognostis-related LRGs;Kaplan-Meier(K-M)curve analysis was used to compare the prognosis of the patients between two groups;CIBERSORT algorithm was used to perform the immuno-correlation analysis between two groups;multivariate Cox regression analysis and LASSO regression analysis were used to construct the prognostic model;receiver operating characteristic curve(ROC)and K-M survival curve were used to assess the relationship between LRGs and survival and prognosis of the HNSCC patients.The prognostic model was validated by GSE27020,GSE41613,and GSE65858 datasets.The experiment were grouped based on risk score,and immune-related analysis and tumor score analysis were performed.Results:The TCGA Database differential analysis results showed that 1 196 LRGs were identified from HNSCC samples;univariate Cox regression analysis selected 27 differentially expressed genes(DEGs)associated with the prognosis of the HNSCC patients.Two different LRGs subtypes(Group 1 and Group 2)were identified according to the prognosis-related genes.The K-M survival curves results showed that the overall survival(OS)of the patients in Group 2 was significantly higher than that in Group 1,and the immune cell expression amount of the patients in Group 2 was also higher than that in group 1.The multivariate Cox regression and LASSO regression analysis results screened out 9 LRGs,including hypoxanthine phosphoribosyltransferase 1(HPRT1),amyloid precursor protein(APP),glycogen phosphorylase L(PYGL),urokinase-type plasminogen activator(PLAU),cannabinoid receptor 2(CNR2),stanniocalcin 2(STC2),nucleotide binding oligomerization domain-like receptor protein 1(NLRP1),integrin-linked kinase(ILK),and forkhead box B1(FOXB1);the prognostic model was constructed.The K-M and ROC curve results indicated that the expression levels of above 9 genes were associated with the survival and prognosis of the HNSCC patients,providing good 1-year,2-year,and 3-year survival prediction effect,and the area under ROC curve(AUC)values were all greater than 0.650.Furthermore,the predictive ability of the prognosis model was validated in GSE27020,GSE41613,and GSE65858 datasets.The patients classified based on the risk scores had distinguishable immune statuses.Conclusion:The differentially expressed LRGs of HNSCC screened by bioinformatics methods are related to the survival and prognosis of the HNSCC patients;the prognostic model constructed by 9 LRGs can predict the survival status and treatment response of the HNSCC patients.

10.
Article in Chinese | WPRIM | ID: wpr-1018267

ABSTRACT

Objective:To explore the relationship between irritable bowel syndrome (IBS) and premature ejaculation (PE) from 5-HT; To predict the natural drugs with therapeutic effect.Methods:Targets related to IBS and PE were screened in the GeneCards, DisGeNET, TTD, OMIM, DrugBank databases. After removing duplicates, the two disease targets were intersected and imported into STRING platform, and the protein interaction network between IBS and PE targets related to 5-HT receptor was obtained. GO enrichment analysis was carried out on the intersected targets by R language, and Coremine Medical platform was used for predicting natural drugs.Results:5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C and 5-HT3A were the common targets related to 5-HT in IBS and PE. GO function enrichment yielded 250 gene function related information, mainly enriched in serotonin receptor signaling pathways, cell response to dopamine, and response to dopamine. The prediction of natural drugs obtained 14 kinds of Chinese materia medica, including Nelumbinis Semen, Nelumbinis Rhizomatis Nodus, Nelumbinis Receptaculum, Nelumbinis Stamen, Nelumbinis Folium, Nelumbinis Plumula, Ginkgo Semen, and Ginkgo Folium.Conclusions:Abnormal 5-HT levels can affect gastrointestinal motility, ejaculation latency, and glans sensitivity. Elevated central 5-HT levels are a common pathogenesis of IBS and PE. The interaction between receptors such as 5-HT1A and 5-HT3A and 5-HT can regulate gastrointestinal motility and secretion activities, intestinal nervous system, and reduce intestinal hypersensitivity; increasing the sensitivity of the 5-HT1A receptor can reduce the ejaculation threshold and promote ejaculation, while increasing the sensitivity of the 5-HT2C receptor can increase the ejaculation threshold.

11.
Article in Chinese | WPRIM | ID: wpr-1018332

ABSTRACT

Objective:To study the potential mechanism of Ganwei Baihe Decoction in the treatment of gastric ulcer (GU) based on bioinformatics and validate it through animal experiments.Methods:TCMSP, DisGeNET, and GeneCards databases were used to retrieved active components and action targets of Ganwei Baihe Decoction. After obtaining the intersection, protein interaction data of the intersection genes were obtained through the STRING database. A PPI network was constructed by Cytoscape 3.10.0 software and the key genes and key components were obtained. DAVID online analysis database was used for GO functional enrichment and KEGG pathway enrichment analysis of key targets. Animal experiments were used for verification. Totally 36 SD rats were divided into blank group, model group, Omeprazole group and Ganwei Baihe Decoction group according to the random number table method, with 9 rats in each group. After 7 days of gavage of the corresponding drugs to each group of rats, they fasted and but with water for 24 hours, and then re-gavaged once. After 1 hour of administration, a gastric ulcer rat model was prepared by gavage of 80 mg/kg of indomethacin. After 3 hours of administration, anesthesia was used to extract the sample. The expression level of Caspase-3 protein in the gastric tissue of rats was to be determined by Western blot method.Results:There were 234 effective active components with 290 targets in Ganwei Baihe Decoction, and 6 496 therapeutic targets for GU. 213 potential targets for GU were screened out. There were 437 GO function and 153 KEGG pathway enriched entries. Compared with the model group, the protein expression of Caspase-3 in the Ganwei Baihe Decoction group and Omeprazole group decreased ( P<0.05). Conclusion:The mechanism of Ganwei Baihe Decoction in treating GU may be through key components such as quercetin and β-sitosterol acting on key targets such as AKT1 and CASP3, regulating the Apoptosis pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc. to exert inhibitory effects on apoptosis.

12.
Article in Chinese | WPRIM | ID: wpr-1019065

ABSTRACT

Objective To identify inflammation-related genes in atrial fibrillation(AF)and explore the possible role and mechanism of these genes and infiltrating immune cells in the development of AF.Methods A series of bioinformatics analysis combined with machine learning algorithms to identify biomarkers of AF,the receiver operating characteristic(ROC)curves were used to verify the prediction and diagnostic value of key genes,and Spearman correlation analysis was used to clarify the correlation between key genes and infiltrating immune cells.Results 593 differential genes(| log2(fold change,FC)|>1,P<0.05),7 immune cell subtypes(P<0.05)were selected,190 immune-related differential genes were obtained,3 biomarkers(IGF1,PTGS 2 and PPARG),and the correlation analysis showed that 3 markers were significantly associated with infiltrating immune cells(P<0.05).Conclusion IGF1,PTGS2 and PPARG are inflammation-related genes of AF,which are speculated to be closely related to the process and pathway of immune cell infiltration.

13.
Article in Chinese | WPRIM | ID: wpr-1019556

ABSTRACT

Objective·To explore the relationship between osteoarthritis and nicotinamide metabolism-related genes using bioinformatics analysis,and identify key genes with diagnostic value and therapeutic potential.Methods·By using"Osteoarthritis"as a search term,GSE12021,GSE55235,and GSE55457 were obtained from the GEO database,with GSE55457 being used as the validation set.After removing batch effects from the GSE12021 and GSE55235 datasets,the standardized combined dataset was obtained and used as the training dataset.Differentially expressed genes(DEGs)were identified from the training dataset.All nicotinamide metabolism-related genes(NMRGs)were obtained from the GeneCards and MSigDB databases.The intersection of DEGs and NMRGs was taken to obtain nicotinamide metabolism-related differentially expressed genes(NMRDEGs).Gene set enrichment analysis(GSEA)was performed on the training dataset,while gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed on NMRDEGs.Key genes were selected by using least absolute shrinkage and selection operator(LASSO)and support vector machine(SVM)analysis in NMRDEGs to build an osteoarthritis diagnosis model which was validated by using the GSE55457 dataset.Single sample gene set enrichment analysis(ssGSEA)was used to analyze the immune cell infiltration type.Interactions networks and drug molecule predictions were obtained for these key genes'mRNA with the DGIdb,ENCORI,and CHIPBase databases.siRNA was used to knock down the key genes in chondrocytes,and then real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of chondrogenesis-related genes.Results·Seven NMRDEGs,including NAMPT,TIPARP,were discovered.GO and KEGG analysis enriched some signaling pathways,such as nuclear factor-κB signaling pathway and positive regulation of interleukin-1-mediated signaling pathway.GSEA enriched pathways such as Hif1 Tfpathway and syndecan 1 pathway.Key genes NPAS2,TIPARP,and NAMPT were identified through LASSO and SVM analysis,and used to construct an osteoarthritis diagnostic model.The validated results showed that the diagnostic model had high accuracy.Immune infiltration analysis results obtained by ssGSEA showed significant differences(all P<0.05)in 15 types of immune cells,including macrophages.Seven potential small molecules targeting key genes were identified,along with 19 miRNAs with the sum of upstream and downstream>10,19 transcription factors with upstream and downstream>7,and 27 RNA binding proteins with clusterNum>19.The results of RT-qPCR showed that knocking down key genes reduced the expression of chondrogenesis-related genes.Conclusion·Through bioinformatics analysis,key genes related to nicotinamide metabolism,NPAS2,TIPARP,and NAMPT,are discovered,and an osteoarthritis diagnostic model is constructed.

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Article in Chinese | WPRIM | ID: wpr-1019887

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Objective To observe the intervention effect of acupuncture at"Zusanli"(ST36)or"Neiguan"(PC6)on the ulcerative colitis(UC)model mice.And to analyze the similarities and differences of gene transcription expression between the diseased colon and the non-diseased heart after acupuncture intervention by using transcriptomics,to explore whether there are efficacy differences between the two acupoints.Methods The UC mouse model was established by inducing dextran sulfate sodium salt(DSS).After successful modeling,the mice were randomly divided into model group,Zusanli group,and Neiguan group,with 9 mice in each group.Zusanli group and Neiguan group intervened with acupuncture at"Zusanli"and"Neiguan",respectively,30 min each time,once a day,for 5 consecutive days.The control and model groups were only bound without acupuncture.Observe the general situation of mice in each group,calculate the disease activity index(DAI),observe the morphological changes of colon tissue by HE staining.Use transcriptome sequencing technology to sequence and biologically analyze the colon tissue of mice in each group,and compare and study whether the two acupoints have differences in acupoint efficacy from the perspective of diseased tissue.At the same time,take the heart tissues of each group for comparative analysis,and discuss whether the effects of the two acupoints are different from the perspective of non-diseased tissue.Results Compared with control group,the DAI score of the model group increased significantly(P<0.001),and HE staining results showed significant pathological damage;after acupuncture at Zusanli or Neiguan,the DAI scores of UC mice were reduced considerably(P<0.05),and the pathological damage was significantly improved.The results of transcriptome sequencing and bioinformatics analysis showed that the effects of acupuncture at Zusanli or Neiguan on the colon of diseased tissue involved multiple genes,and 825 differential genes with similar changes(co-DEGs)were mainly enriched in white blood cells and chemokine pathways;there were 168 differentially expressed genes(ST36 only-DEGs)affected only by Zusanli,which were enriched to gastric acid secretion and other pathways;there were 325 differentially expressed genes(PC6 only-DEGs)only affected by Neiguan,which were enriched in cytokine-cytokine receptor interaction and other pathways.There were 95 co-DEGs in the heart of non-diseased tissue,which were mainly enriched in positive regulation of defense response and response to interleukin-1;there were 28 ST36 only-DEGs;there were114 PC6 only-DEGs,which were enriched in cardiovascular diseases and other pathways.Conclusion Acupuncture of"Zusanli"and"Neiguan"could improve UC mice's symptoms and pathological colon changes.However,through transcriptomic analysis,it was found that the two acupoints had differences in gene transcription effects on the colon of diseased tissue and the heart of non-diseased tissue,suggesting that acupoints with different distribution positions had some similarities in macro efficacy.Still,there were some differences at a micro level.

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Article in Chinese | WPRIM | ID: wpr-1019908

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Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.

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Article in Chinese | WPRIM | ID: wpr-1019911

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Objective To analyze the expression and role of the disulfidptosis-related gene PDZ and LIM domain protein 1(PDLIM1)in various tumors.Methods The expression of PDLIM1 mRNA was analyzed by Xiantao website.The diagnostic and prognostic capabilities of PDLIM1 in 33 types of tumors were explored using the Xiantao website and Sangerbox 3.0 data analysis platform.The correlation between PDLIM1 and clinical classification and its staging was analyzed by the TISIDB database.The correlation between PDLIM1 and tumor immunity was analyzed by Sangerbox 3.0 data analysis platform and Kaplan-Meier Plotter database.Protein-protein interaction networks(PPI)were constructed by STRING database and Cytoscape,and were enriched by Sangerbox 3.0 data analysis platform.Finally,the GSCA website was applied to acquire the expression of PDLIM1 mRNA and its sensitivity to drugs.Results There was heterogeneity in the expression of PDLIM1 mRNA among 33 tumors.PDLIM1 had good diagnostic ability in cholangiocarcinoma(CHOL),glioblastoma multiforme(GBM),kidney renal clear cell carcinoma(KIRC),lung adenocarcinoma(LUAD),ovarian cancer(OV),pancreatic cancer(PAAD),skin cutaneous melanoma(SKCM)and testicular germ cell tumor(TGCT).High expression of PDLIM1 mRNA in glioma,low-grade glioma(LGG),KIPAN,GBM,uveal melanoma(UVM),and adrenocortical carcinoma(ACC)suggested poor prognosis,while low expression in sarcoma suggested poor prognosis.PALIM1 mRNA expression was correlated with the classification of head and neck squamous cell carcinoma(HNSC),kidney renal papillary cell carcinoma(KIRP),uterine corpus endometrial carcinoma(UCEC),uterine carcinosarcomas(UCS),and UVM as well as the staging of cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC),HNSC,UCEC,and LGG.PDLIM1 was significantly associated with immune infiltration of 36 tumors led by prostateadenocarcinoma(PRAD),and was found to have a relatively good prognosis after immunotherapy in patients with high PDLIM1 mRNA expression.PDLIM1 exerted effects on organisms mainly through its involvement in the regulation of actin cytoskeleton,cell adhesion,and cancer-related pathways,and was sensitive to various drugs led by Isoliquiritigenin.Conclusion PDLIM1 was closely related to the clinical prognosis and immune infiltration of a variety of tumors,and it is expected to be a cancer diagnostic and prognostic biomarker or therapeutic target.

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Article in Chinese | WPRIM | ID: wpr-1019953

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Objective To screen differentially expressed microRNAs(miRNAs)in plasma exosomes of active rheumatoid arthritis(RA)patients and healthy controls and conduct bioinformatics analysis for exploring the role and potential clinical application value of miRNAs in the pathogenesis of RA.Methods From January 2023 to April 2023,39 RA patients who visited the Rheumatology and Immunology Department of the Second Affiliated Hospital of Soochow University were selected as the study subjects,while 39 healthy individuals were selected as normal controls.The expression levels of miRNAs in plasma exosomes were detected by Illumina high-throughput sequencing technology,and the differentially expressed miRNAs were obtained by log2(Fold Change)absolute value>1 and P value<0.05.Six miRNAs were selected by the order from small to large P-value for bioinformatics analysis and validated using quantitative real-time fluorescence PCR(qRT-PCR).Results Compared with healthy controls,22 aberrantly expressed miRNAs were detected in plasma exosomes of RA patients,of which 4 were up-regulated and 18 were down-regulated.Among them,miR-30b-5p,miR-144-3p,miR-20a-5p,miR-223-5p,miR-425-3p,and miR-589-5p showed changed significantly.GO and KEGG enrichment analysis indicated that differentially expressed miRNAs may be involved in disease progression through regulation of signaling pathways such as TGF-β and PI3K/AKT,which were related to biological processes such as Th17 differentiation,intercellular interactions,and protein phosphorylation.The qRT-PCR validation results showed that the expression of miR-144-3p and miR-425-3p were significantly reduced in plasma exosomes of RA patients compared to healthy controls(t=3.617,3.595,all P<0.001),while the differences of miR-30b-5p,miR-223-5p,miR-589-5p,and miR-20a-5p expression were not statistically significant(t=1.956,1.331,1.662,1.861,all P>0.05).Conclusion The expression profile of plasma exosomal miRNAs changed in RA patients,which may be involved in disease progression through TGF-β and other signaling pathways.Exosome-derived miR-144-3p and miR-425-3p may be potential serological markers for RA diagnosis.

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Article in Chinese | WPRIM | ID: wpr-1019954

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Objective To construct N6-methyladenosine related long non-coding RNA(LncRNA)pairing model for renal cell carcinoma based on bioinformatics analysis of the cancer ganome atlas(TCGA)database and to explore its prognosis value.Methods Transcriptome data of RNA-sep for renal cell carcinoma and its related clinical information were downloaded from the TCGA database.Perl software was used to organize and separate LncRNA and messenger RNA(mRNA)from the transcriptome data.A total of 564 tissues from renal cell carcinoma cases and 72 normal tissues were obtained,and thus 540 renal cancer patients were eventually included.Random data table method was used to divide 540 patients with renal cancer into a training group(n=275)and a validation group(n=265)by caret.M6A related LncRNA pairing models were established based on the single factor and multivariate COX regression analysis.The risk assessment equation was obtained using the LASSO regression algorithm.The risk scores were calculated based on this equation,and the optimal critical point of the median risk value was applied to divide all patients into high-risk and low-risk groups.Kaplan-Meier survival analysis was used to make a survival curve for the differences between high and low risk groups in the overall sample.The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were conducted using the Cluster Profiler software package.The relationship between N6-methyladenosine related LncRNA pairing model and immune cell infiltration was analyzed by R software.Results Kaplan-Meier survival analysis showed the total survival time of patients in the low-risk group was significantly higher than that of patients in the high-risk group of the training group(P<0.05).Compared with high risk group,the overall survival time of patients(G1~2,G3~4,Ⅰ~Ⅱ,or Ⅲ~Ⅳ,age≤65 years,or patients>65 years old)in low risk group was higher(P<0.05).Differential gene enrichment analysis was obtained for high and low risk groups,which mainly enriched with many differential genes such as muscle contraction,rhabdomytic cell differentiation,myofibril,receptor activation activity,and vascular smooth muscle contraction.The highest driver genes in high risk group and low risk group exhibited mutation frequency and mutation information,and their risk score was positively correlated with the degree of T cell and plasma cell infiltration(r=0.638,P=0.001).Conclusion Bioinformatics-based analysis of the N6-methyladenosine related LncRNA pairing models can be helpful to predict the prognosis of patients with renal cancer.It provides new ideas for the prognosis evaluation and optimal treatment strategy of renal cancer,and contributes to further analyzing the molecular mechanism of the occurrence and development of gastric cancer in the future.

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Article in Chinese | WPRIM | ID: wpr-1020559

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Objective:To explore the differences of microenviroment between peri-implant tissue and oral mucosal tissue.Methods:The gene chip data GSE43744 was downloaded from the GEO database,bioinformatics tools were used to analyze the differentially ex-pressed genes between the peri-implant tissue and normal oral mucosal tissue in rat.Results:1315 differentially expressed important genes,including 797 upregulated genes and 518 downregulated genes,were screened out.Gene enrichment analysis showed that com-pared with normal oral mucosal tissue,the gene expression of innate immune activity,cell activation,inflammatory response,and func-tional expression related to external and bacterial stimuli in peri-implant tissue were significantly upregulated,while that of extracellular matrix tissue,adhesion,extracellular matrix polysaccharides,response to mechanical stimuli and response to toxic substances was sig-nificantly downregulated.Meanwhile,multiple molecular functions and biological pathways related to T cells were highly expressed,which may play an important role in the peri-implant microenvironment.In addition,PPI network was constructed,and screened 7 core genes including FCER1G,TYROBP,PTPRC,ITGB2,AIF1,EMR1 and RAC2,which may be target genes for studying peri-implant microenvironment.Conclusion:There is a significant difference of microenvironment characteristics between peri-implant tissue and o-ral mucosa.The target genes screened using PPI network may be the key to future research on the peri-implant microenvironment.

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Article in Chinese | WPRIM | ID: wpr-1021268

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BACKGROUND:The specific molecular mechanism of the transformation from normal healthy people to acute cervical spondylotic radiculopathy has not been clear,which needs to be further studied. OBJECTIVE:To investigate the differential expression of serum proteomics between normal healthy people and patients with acute cervical spondylotic radiculopathy,and to find and identify potential specific serum markers between them. METHODS:The serum samples of eight patients with acute cervical spondylotic radiculopathy and eight normal healthy people were collected,and the proteomic screening and analysis were performed by tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology,in order to explore and identify serum proteins differentially expressed in patients with acute cervical spondylotic radiculopathy. RESULTS AND CONCLUSION:A total of 183 significantly differential proteins were screened by tandem mass tag technology,and 11 significantly differential proteins were identified(P<0.05).Compared with normal healthy people,three differential proteins were significantly up-regulated,including human leukocyte antigen-A,secretoglobin family 1a member 1,and protein 4-hydroxyphenylpyruvate dioxygenase,and seven differential proteins were significantly down-regulated,such as immunoglobulin heavy constant gamma 3,skin factor,and myosin light chain 3,in patients with acute cervical spondylotic radiculopathy.Gene ontology enrichment analysis showed that these differential proteins participated in antigen binding,immunoglobulin receptor binding and other molecular functions.Protein-protein interaction analysis showed that among the common differential proteins between normal healthy people and patients with acute cervical spondylotic radiculopathy,HLA-A,HPD,PSMA3,DMKN,SCGB1A1,and MYL3 were located at the nodes of the functional network,and were closely related to the systems of body immunity,cellular inflammatory response,energy metabolism,and mechanical pressure.The significantly differential proteins HLA-A,HPD and MYL3 were verified by western blot,and the results were consistent with those of proteomics.To conclude,tandem mass tag combined with liquid chromatography-tandem mass spectrometry technology can be used to find the differentially expressed proteins in serum between normal healthy people and patients with acute cervical spondylotic radiculopathy.It is preliminarily believed that HLA-A,HPD and MYL3 may be specific serum markers of acute cervical spondylotic radiculopathy,providing a new direction for further research on its pathogenesis.

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