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Objective:To investigate the differential expression of brain-expressed X-linked (BEX) family genes in pan-cancer and its value in diagnosis and prognosis of pan-cancer.Methods:RNA sequencing (RNA-seq) data, survival data, immune subtypes, the stem cell scores based on RNA and DNA methylation of 33 different tumors from The Cancer Genome Atlas (TCGA) database were downloaded from the online database of University of California, Santa Cruz (UCSC Xena) on April 10, 2022. The limma package of R software (V.4.2.0) was used to analyze the expression of BEX family genes in the TCGA database. The differential expression of BEX family genes in pan-cancer tissues and normal tissues was compared by using Wilcox test. Pan-cancer patients were divided into high expression group and low expression group according to the median expression level of BEX family genes; Kaplan-Meier survival analysis was used to evaluate the relationship between the expression of BEX family genes and the overall survival (OS) of patients; Cox proportional risk model was used to analyze the effect of the expression of BEX family genes on OS in pan-cancer patients and then the forest map was drawn. The correlation of the expression of BEX family genes with tumor microenviroment and tumor stem cells in pan-cancer patients was analyzed based on the correlation index Cor value. Spearman correlation analysis was used to analyze the correlation between the expression of BEX family genes and tumor microenviroment and cancer stem cell index in gastric cancer tissues. The RNA-seq of different tumor cell lines and drug sensitivity data download from the CellMiner database were used to analyze the correlation between the expression of BEX family genes and drug sensitivity. The correlation of pan-cancer and gastric cancer immune subtypes with the expression of BEX family genes was analyzed by using Kruskal test.Results:BEX3 was highly expressed in pan-cancer tissues in TCGA database, BEX2 and BEX4 were moderately expressed in pan-cancer tissues, and BEX1 and BEX5 were relatively low expressed in pan-cancer tissues. The expressions of BEX2, BEX3 and BEX4 were the highest in cholangiocarcinoma, the expression of BEX5 was the highest in endometrial neoplasms, and the expression of BEX1 was the highest in invasive breast cancer. Compared with normal tissue samples, the expressions of BEX family genes were up-regulated or down-regulated in various cancers (all P < 0.05). Survival analysis showed that the expressions of BEX family genes were associated with the OS of various cancers. Some tumor patients with high expressions of BEX1, BEX3, BEX4 and BEX5 had better OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Other patients with high expression of BEX family genes had worse OS compared with those with low expressions, and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that the high expression of BEX1 for stomach neoplasms; the high expression of BEX2 for acute myeloid leukemia, thymoma and endometrial neoplasms; the expression high of BEX3 for squamous cell carcinoma of head and neck,sarcoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX4 for rectal adenocarcinoma, stomach neoplasms and endometrial neoplasms; the high expression of BEX5 for renal suspicious cell carcinoma and thymoma were risk factors for OS (all P < 0.05).The expression of BEX family genes was negatively correlated with the stromal score of most cancers (all P < 0.05), and positively correlated with the stem cell score (all P < 0.05). The expression of BEX family genes was negatively correlated with cancer stem cell index of gastric cancer ( P < 0.05), and was positively correlated with matrix score and estimated total score (all P < 0.05). Among different tumor cell lines in CellMiner database, BEX family genes were closely related to drug resistance of vemurafenib (Cor = -0.368, P = 0.004), Kahalide f (Cor = -0.391, P = 0.002), O-6-benzylguanine (Cor = -0.375, P = 0.003) and other drugs. All genes in the BEX family were related to the immune subtypes of pan-cancer and were highly expressed in C5 subtype (all P < 0.05).For gastric cancer, all genes showed high expression in the C3 subtype (all P < 0.05), except BEX5 ( P = 0.24). Conclusions:The expression of BEX family genes is closely related to the prognosis of pan-cancer patients, and has an impact on the tumor microenvironment, cancer stem cells and drug sensitivity. BEX family genes may be potential biomarkers for diagnosis and prognosis of pan-cancer.
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Objective:To examine the relationship between meaning in life (MIF) and social support in Chinese hospitalized patients with advanced lung cancer (ALC).Methods:Totally, 231 ALC patients from Shanghai Pulmonary Hospital Affiliated to Tongji University were recruited to complete the Meaning in life Questionnaire (MIFQ) and Social Support Rating Scale (SSRS) from December 2018 to December 2019.Results:The total score of MIFQ in ALC patients was (97.81 ± 15.74), and the total score of SSRS was (27.47 ± 6.37), with the former and its each dimension positively correlated to the latter ( r = 0.275-0.417, P<0.01), genders (female), marital status (married), ocupational status and total score of social support were the important factors of the life meaning ( F = 9.82, P<0.001), which accounted for 23.6% of the changes of life meaning. Conclusion:ALC patients sensed the middle level of social support and MIF. Patients who were females, married, the higher the degree of social support, tended to have higher level of MIF. Medical workers need to value the social support system of ALC patients, in an effort to improve MIF of patients.
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Background@#and Purpose Collateral circulation is considered an important factor affecting the risk of stroke, but the factors that affect collateral circulation remain unclear. This study was performed to identify the factors associated with collateral circulation, especially blood lipids. @*Methods@#The study involved patients who had undergone digital subtraction angiography and were confirmed as having severe unilateral stenosis or occlusion of the internal carotid artery (ICA). We classified the collateral circulation status of each patient as good (Grade 3 or 4) or poor (Grade 0, 1, or 2) according to the grading system of the American Society of Interventional and Therapeutic Neuroradiology/American Society of Interventional Radiology. We collected data on patients’ characteristics and identified the factors that affect collateral circulation. @*Results@#This study included 212 patients. The multivariate logistic regression analysis showed that the high-density lipoprotein cholesterol (HDL-C) concentration and a complete anterior half of the circle of Willis were independent protective factors for good collateral circulation, whereas elevated lipoprotein(a) [Lp(a)] and serum creatinine concentrations were independent risk factors for good collateral circulation. The area under the receiver operating characteristics curve (AUC) was 0.68 (95% confidence interval [CI], 0.61–0.76) for HDL-C and 0.69 (95% CI, 0.62–0.76) for Lp(a). A binary logistic regression model analysis of the joint factor of HDL-C and Lp(a) yielded an AUC of 0.77 (95% CI, 0.71–0.84). @*Conclusions@#In patients with severe unilateral ICA stenosis or occlusion, the combination of HDL-C and Lp(a) is a useful predictor of collateral circulation.
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Objective:To investigate the differential expression of four-jointed box kinase 1 (FJX1) gene in colorectal cancer and its relationship with prognosis and the related mechanisms.Methods:On July 16, 2021, the transcriptome data and clinical data of colorectal cancer were downloaded from The Cancer Genome Atlas (TCGA) database to analyze the expressions of FJX1 mRNA in colorectal cancer tissues and paracancerous tissues, and the relationship between FJX1 mRNA and clinicopathological characteristics and prognosis of patients. Receiver operating characteristic (ROC) curve was drawn to evaluate the value of FJX1 mRNA in predicting the survival of patients with colorectal cancer. Cox proportional hazards model was used to evaluate whether FJX1 mRNA was an independent influencing factor for prognosis of colorectal cancer. The overall survival (OS) time and survival status of colorectal cancer patients were downloaded from the Gene Expression Omnibus (GEO) database, and the relationship between FJX1 mRNA and prognosis of patients was analyzed. The methylation data of colorectal cancer was downloaded from the University of California, Santa Cruz (UCSC xena) database to determine the degree of methylation at each site of FJX1 mRNA and the correlation between the expression of FJX1 mRNA and the degree of methylation at each site. Signaling pathways associated with FJX1 mRNA in colorectal cancer were analyzed by using the Gene Set Enrichment Analysis (GSEA) (4.1.0). The correlation between FJX1 mRNA and tumor-infiltrating immune cells was investigated by using the Tumor Immunity Evaluation Resource (TIMER) database. Spearman analysis and small molecule/drug sensitivity analysis were used to explore the correlation between FJX1 mRNA expression and drug sensitivity.Results:In the transcriptome data of 612 colorectal cancer cases in TCGA database, the expression of FJX1 mRNA in colorectal cancer tissues was higher than that in the paracancerous tissues ( P < 0.001). In 549 colorectal cancer patients with complete data, FJX1 mRNA expression was correlated with M stage ( P = 0.007), pathological stage (stage Ⅳ vs. stage Ⅰ, P = 0.016; stage Ⅳ vs. stage Ⅱ, P = 0.03; stage Ⅳ vs. stage Ⅲ, P = 0.012), but it was not correlated with age, gender, T stage and N stage (all P > 0.05). In TCGA database and GEO database, the patients were divided into high expression group and low expression group according to the median expression of FJX1 mRNA. The OS in FJX1 mRNA high expression group was worse than that in low expression group (all P<0.05). The ROC curve of FJX1 mRNA expression on the 1-, 3-, and 5-year OS rates of colorectal cancer patients was drawn by using the data in TCGA database, and the areas under the curve (AUC) were 0.595, 0.625 and 0.764, respectively. Multivariate Cox regression analysis showed that age ( HR = 1.050, 95% CI 1.028-1.073, P < 0.001), T stage ( HR = 1.787, 95% CI 1.090-2.927, P = 0.021) and high FJX1 mRNA expression ( HR = 1.160, 95% CI 1.049-1.282, P = 0.004) were independent influencing factors for poor OS in colorectal cancer. The gene set enrichment analysis found that FJX1 mRNA was related to colorectal cancer, TGF-β signaling pathway, VEGF signaling pathway, Wnt signaling pathway, etc. The expression of FJX1 mRNA in colon cancer was negatively correlated with the degree of methylation of FJX1 mRNA ( r = -0.16, P < 0.001), and the expression of FJX1 mRNA in rectal cancer was positively correlated with the degree of methylation of FJX1 mRNA ( r = 0.33, P < 0.001). The expression of FJX1 mRNA was related to the infiltration of resting memory CD4 + T cells, M0 macrophages and resting dendritic cells. FJX1 mRNA was significantly associated with the resistance of various chemotherapeutic drugs and tumor-targeted drugs such as methotrexate, 5-fluorouracil, gefitinib, etc. Conclusions:FJX1 mRNA may be a potential biomarker of colorectal cancer and is associated with the infiltration of immune cells.
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OBJECTIVE@#To study the protective effect of enhanced peroxisome proliferator activated receptor γ (PPARγ) pathway against apoptosis of long-term cultured primary nerve cells.@*METHODS@#A natural aging model was established in primary rat nerve cells by long-term culture for 22 days. The cells were divided into control group, 0.1, 1.0, 5.0, and 10 μmol/L GW9662 intervention groups, and 0.1, 1.0, 5.0, and 10 μmol/L pioglitazone intervention groups. The cell viability was assessed using MTT assay and the cell morphological changes were observed after the treatments to determine the optimal concentrations of GW9662 and pioglitazone. Double immunofluorescence labeling and flow cytometry were used to observe the changes in the number of viable cells and cell apoptosis following the treatments; immunocytochemical staining was used to assess the changes in the anti-oxidation ability of the treated cells.@*RESULTS@#The optimal concentrations of GW9662 and pioglitazone determined based on the cell viability and morphological changes were both 1 μmol/L. Compared with the control group, GW9662 treatment significantly lowered while pioglitazone significantly increased the total cell number and nerve cell counts ( < 0.05), and nerve cells in the cell cultures maintained a constant ratio at about 80% in all the groups ( > 0.05). GW9662 significantly enhanced while pioglitazone significantly lowered the cell apoptosis rates compared with the control group ( < 0.05). GW9662 obviously lowered SOD activity and GSH content in G group ( < 0.05) and increased MDA content in the cells ( < 0.05), and pioglitazone resulted in reverse changes in SOD, GSH and MDA contents in the cells ( < 0.05).@*CONCLUSIONS@#Activation of PPARγ pathway protects long-term cultured primary nerve cells by enhancing cellular anti-oxidant capacity and reducing cell apoptosis, suggesting a potential strategy for anti-aging treatment of the nervous system through intervention of the PPARγ pathway.
Subject(s)
Animals , Rats , Anilides , Pharmacology , Apoptosis , Cell Proliferation , Cell Survival , Cells, Cultured , Cellular Senescence , Physiology , Neurons , Cell Biology , PPAR gamma , Metabolism , Pioglitazone , PharmacologyABSTRACT
Aim To investigate the effect of hesperidin on human lung cancer cell A549 and the possible mechanism.Methods The cell apoptosis and necrosis of A549 treated with hesperidin were measured by the Hoechst 33342/PI fluorescent dye based on microfluidic chip technology.Cell cycle and apoptosis rate were evaluated by flow cytometry(FCM).The expressions of the related genes were detected through the real-time fluorescent quantitative PCR technology(RT-PCR) including VEGF, PI3K and PTEN.The protein expressions of Bcl-2, Cyclin B1, PI3K, Akt and PTEN were detected by Western blot after hesperidin intervention.Results The proliferation of A549 cells was significantly inhibited by hesperidin in a dose-dependent manner.FCM results showed that hesperidin could not only influence the G0/G1 phase and S phase, but also promote the apoptosis of lung cancer cells.Meanwhile, the apoptosis and necrosis rate was increased from(6.7±0.6)% to(27.9±1.1)% compared with that of control group(P<0.05).From the level of molecular, the gene expressions of VEGF and PI3K were decreased, while the PTEN was increased after hesperidin stimulation.Western blot results showed that the expression of protein Bcl-2, Cyclin B1 and Akt were decreased, which all showed close relationship with cell apoptosis, cell cycle and PI3K-Akt signaling pathway.The expression of PI3K was increased, but the change of PTEN was not statistically significant compared with that of control group.Conclusion Hesperidin induces lung cancer cell apoptosis through PI3K-Akt signaling pathway, which blocks cancer cell division and destroys the balance of related protein expression.