This study aims to investigate influencing factors of quality of life (QoL) and depression among COVID-19 survivors during convalescence. A cross-sectional study was conducted in November 2020 in ...Wuhan, China. Information on social support, physical activity, QoL and depressive symptoms were assessed using self-administered questionnaires. Multivariate linear regression and multivariate logistic regression were used to assess the risk factors of subdomains of QoL (physical component score (PCS) and mental component score (MCS)) and depression, respectively. A total of 151 COVID-19 survivors (68 males) aged 53.21 (SD: 12.70) years participated in the study. Multivariate linear regression showed that age (β=−0.241), history of chronic disease (β=−0.4.774), physical activity (β = 2.47) and social support (β = 0.147) were significantly associated with PCS, while having a spouse (β = 9.571), monthly income (β = 0.043) and social support (β = 0.337) were significantly associated with MCS. Logistic regression suggested that participants aged 40-60 years (OR = 10.20, 95%CI: 1.41-73.82) or above 60 years (OR = 15.63, 95%CI: 1.87-131.00), with high school or above education (OR = 5.81, 95%CI: 1.24-27.20), with low/moderate physical activity (low, OR = 2.97, 95%CI: 1.14-7.77; moderate, OR = 3.42, 95%CI: 1.07-10.91) and low/medium social support (low, OR = 4.81, 95% CI: 2.02-11.43; medium, OR = 9.70, 95%CI: 1.17-80.10) were more likely to be depressed, while higher monthly income (≥3000 Yuan RMB/month) was associated with lower risk for depression (OR = 0.27, 95%CI: 0.09-0.82). These findings indicate COVID-19 survivors with older age, having chronic conditions, without a spouse, low monthly income, low level of physical activity and social support had significantly increased risks for poor QoL and depression, and more attention should be given to this population.
Methylation is an important mechanism contributing to cancer pathology. Methylation of tumor suppressor genes and oncogenes has been closely associated with tumor occurrence and development. New ...insights regarding the potential role of the adenosine receptor-independent pathway in the epigenetic modulation of DNA methylation offer the possibility of new interventional strategies for cancer therapy. Targeting DNA methylation of cancer-related genes is a promising therapeutic strategy; drugs like 5-Aza-2'-deoxycytidine (5-AZA-CdR, decitabine) effectively reverse DNA methylation and cancer cell growth. However, current anti-methylation (or methylation modifiers) are associated with severe side effects; thus, there is an urgent need for safer and more specific inhibitors of DNA methylation (or DNA methylation modifiers). The adenosine signaling pathway is reported to be involved in cancer pathology and participates in the development of tumors by altering DNA methylation. Most recently, an adenosine metabolic clearance enzyme, adenosine kinase (ADK), has been shown to influence methylation on tumor suppressor genes and tumor development and progression. This review article focuses on recent updates on ADK and its two isoforms, and its actions in adenosine receptor-independent pathways, including methylation modification and epigenetic changes in cancer pathology.
Background. Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted ...glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value. Methods. In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples. Results. We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. Conclusion. Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation.
Glutathione S-transferase mu 1 (
) is one of the major glutathione conjugation enzymes. Its expression and activity have been suggested to correlate with the occurrence of colon cancer; however, the ...role of
in tumor immunity remains unclear.
Relevant data downloaded from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) was used to perform a multi-dimensional expression analysis of
in colon adenocarcinoma (COAD). The correlation between
and tumor immunity was analyzed with multiple online tools. Then protein-protein interaction (PPI) network and functional enrichment analyses of
-associated immunomodulators were performed. Further, we developed the Cox regression model based on the
-related immunomodulators. Finally, a
-based clinical nomogram and a calibration curve was established to predict the probability and accuracy of long-term survival.
was significantly downregulated in COAD versus normal tissues. Infiltration levels of B cells, CD8
T cells, and dendritic cells were closely correlated to
gene copy number deletion, and
expression levels in COAD positively correlated with dendritic cell, B cell, neutrophil, and macrophage infiltration. Functional enrichment analysis indicated 36
-related immunomodulators are involved in immune-related pathways of regulating T cell activation and lymphocytic activation. A 2-gene prognostic risk signature based on the 36
-related immunomodulators was built using the Cox regression model, and the risk signature in combination with stage had an area under the curve (AUC) value of 0.747 by the receiver operating characteristic method. patients with higher risk scores-calculated based on 2 gene prognostic risk characteristics and further identified as an independent prognostic factor-were associated with worse survival using the Kaplan-Meier analysis. Together, the clinical nomogram and calibration curve based on
suggested a good prediction accuracy for long-term survival probability.
Our study provided evidence supporting the significant role of
in COAD immunity and suggests
as a potential novel target for COAD immunotherapy.
Objective To investigate the anti⁃tumoral effect of ACT001, a novel antitumor compound, on the nuclear factor⁃κB (NF⁃κB) pathway and programmed cell death protein ligand 1 (PDL1) expression in U87 ...glioblastoma cell line. Methods We analyzed the correlation between the expression of P65 and PDL1, pathological grade, and prognosis by introducing The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. CCK⁃8 was used to observe the effect of ACT001 on the proliferation of U87 cells, and calculate the median inhibition concentration (IC50). Immunofluorescence staining was used to detect the effect of ACT001 on nuclear translocation of the transcription factor P65. U87 cells were transfected with small interference RNA (siRNA), and P65 knockdown efficiency was determined by quantitative real⁃time polymerase chain reaction (qRT⁃PCR). The relative expression of P65, phospho⁃P65 (p⁃P65) and PDL1 in different transfected groups and drug treatment groups were determined by Western blotting. Results 1) Bioinformatics analysis showed that gliomas with higher pathological grade hourbored higher P65 and PDL1 expression (P＜0.05, for all). Moreover, patients with high expression of P65 and PDL1 mRNA predicted poor prognosis (P＜0.05, for all). 2) CCK⁃8 assay showed that treatment with different concentrations of ACT001 (5, 10, 20, 40, 80, 160 and 320 μmol/L), the inhibition rates of U87 cells were (9.01±4.75)%, (17.03±2.91)%, (28.50±4.85)%, (45.50±5.15)%, (67.67±8.46)% , (83.02±5.79)% and (94.33±1.59)% , respectively, and the IC50 was about 42.98 μmol/L. 3) Immunofluorescence staining showed that ACT001 inhibited nuclear translocation of P65. 4) qRT⁃PCR showed that the P65 mRNA expression of U87 cells in different siRNA transfected groups was statistically significant (F=164.200, P=0.000), and the mRNA expression of P65 in si⁃P65⁃1 group (t=13.290, P=0.000) and si⁃P65⁃2 group (t=12.730, P=0.000) was lower than that of si⁃NC group. 5) Western blotting showed that the relative expression of P65 (F=681.300, P=0.000), p⁃P65 (F=128.800, P=0.000) and PDL1 (F=20.470, P=0.002) in U87 cells of different siRNA transfection groups were statistically significant different. Among them, P65 (t=59.630, P=0.000; t=29.380, P=0.000), p⁃P65 (t=24.370, P=0.000; t=13.460, P=0.000) and PDL1 (t=6.025, P=0.004; t=6.728, P=0.003) in si⁃P65⁃1 group and si⁃P65⁃2 group were lower than those in si⁃NC group. 6) There were statistically significant differences in the relative expression of p⁃P65 (F=269.700, P=0.000) and PDL1 (F=128.800, P=0.000) in U87 cells treated with different concentrations of drugs. P⁃P65 (t=19.750, P=0.000; t=24.640, P=0.000) and PDL1 (t=12.690, P=0.000; t=19.230, P=0.000) in ACT001 25 μmol/L group and 50 μmol/L group were lower than those in normal control group, ACT001 50 μmol/L group were also lower than those of 25 μmol/L group (t=5.288, P=0.006; t=2.868, P=0.046). Conclusions ACT001 can inhibit the proliferation of U87 glioma cells. By inhibiting the phosphorylation and nuclear translocation of P65 in U87 cells, ACT001 decreased the expression of PDL1 to improve the immunosuppressive environment of glioblastoma and thus inhibit the progression of glioblastoma.
To explore the effects of phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) signal pathway on the proliferation, apoptosis and invasiveness of colon cancer cell line SW480 and explore its ...possible mechanisms.
SW480 cells were cultured with various concentrations (0, 5, 10, 20 and 40 µmol/L) of LY294002 and methyl thiazolyl tetrazolium (MTT) assay was conducted after 24, 48 and 72 hours. SW480 cells were cultured for 24 hours with various concentrations (0, 10, 20 and 40 µmol/L) of LY294002. The apoptotic rate was measured by flow cytometry (FCM). The difference of invasiveness was examined by Transwell invasion test. Western blotting was used to examine the expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9). One-way ANOVA was used for statistical analysis.
MTT assay showed that the proliferation rate of all SW480 cells except for the lowest concentration group (5 µmol/L) was lower than the control group (0 µmol/L) and a time-dosage dependence existed (all P
Background： The primary cause of ischemic heart failure （HF） is myocardial infarction （MI） resulting in left ventricle （LV） wall motion abnormality secondary to ventricular remodeling. A prospective, ...nonrandomized study conducted in China was designed to assess safety and efficacy of the percutaneous ventricular restoration therapy using Parachute device （CardioKinetix, lnc., CA, USA） in ischemic HF patients as a result of LV remodeling after anterior wall M1. Methods： Thirty-one patients with New York Heart Association （NYHA） Class I1, I11 ischemic HF, ejection traction between 15% and 40%, and dilated akinetic or dyskinetic anterior-apical wall without the need to be revascularized were enrolled from seven sites in China from October to December 2014. The Parachute device was implanted through femoral artery. All patients received low-dose aspirin and anticoagulation with warfarin tbr at least 12 months postdevice implantation. The primary end-point was the assessment of efficacy as measured by the reduction in LV end-systolic volume index （LVESVI） against baseline LVESVI at 3 months postdevice implantation, determined by the echocardiography and measured by echocardiography core laboratory. Quality of life was assessed using EQ-SD and visual analog scale （VAS）. For quantitative data comparison, paired t-test （normality data） and signed-rank test （abnormality data） were used： application of signed-rank test was tbr the ranked data comparison. Results： A change in LVESVI as measured by echocardiography from the preimplant baseline to 3-month postdevice implantation revealed a statistically significant reduction from 77.5 ~ 20.0 ml/m-＇ to 53,1 ~ 17.0 ml/m-＂ （P 〈 0.0001 ）, The trial met its primary end-point. Of the 31 patients, the procedural success was 96.8%. Overall, NYHA HF class assessment results showed an improvement of more than halfa class at 3 months （P 〈 0.001 ）. Quality of life assessed by the VAS value increased 11.5 points （P 〈 0.01 ）, demonstrating improvement at 3 months.Conclusion： The favorable outcomes observed in the high-risk patients provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for ischemic HF patients. Trial Registration： ClinicalTrials.gov, NCT02240940; https：// clinicaltrials.gov/ct2/show/NCT02240940.
Background Myocyte apoptosis is considered to be the major causative factor of left ventricular （LV） remodeling following myocardial infarction （MI）. We previously reported that 3＇, ...4＇-dihydroxyflavonol （DiOHF）, was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study.
Methods Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF （2 mg/kg; i.v., daily） groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays.
Results LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dtrnax. Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle.
Conclusions Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.
AIM:To assess the efficacy and safety of combination therapy based on S-1,a novel oral fluoropyrimidine,vs S-1 monotherapy in advanced gastric cancer(AGC).METHODS:We searched PubMed,EMBASE and the ...Cochrane Library for eligible studies published before March 2013.Our analysis identified four randomized controlled trials involving 790 participants with AGC.The outcome measures were overall survival(OS),progression-free survival(PFS),overall response rate(ORR)and grade 3-4 adverse events.RESULTS:Meta-analysis showed that S-1-based combination therapy significantly improved OS(HR=0.77,95%CI:0.66-0.91,P=0.002),PFS(HR=0.58,95%CI:0.46-0.72,P=0.000)and ORR(OR=2.23,95%CI:1.54-3.21,P=0.000).Sensitivity analysis further confirmed this association.Lower incidence of grade 3-4 leucopenia(OR=4.06,95%CI:2.11-7.81),neutropenia(OR=3.94,95%CI:2.1-7.81)and diarrhea(OR=2.41,95%CI:1.31-4.44)was observed in patients with S-1 monotherapy.CONCLUSION:S-1-based combination therapy is superior to S-1 monotherapy in terms of OS,PFS and ORR.S-1 monotherapy is associated with less toxicity.
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