RESUMEN
This study aimed to investigate the mechanisms of LACTB2 in colorectal cancer (CRC). Microarrays and sequencing data of CRC were acquired from UCSC Xena, GTEx, Gene Expression Omnibus, and TCGA. Pooled analysis of the mRNA expression of LACTB2 in CRC was performed using Stata software. The protein expression of LACTB2 in CRC tissues was evaluated by immunohistochemistry. The relationship between immune cell infiltration and LACTB2 expression was investigated using CIBERSORT. The potential signaling pathways and biological mechanisms of LACTB2 were explored using GSEA, KEGG, and GO. Subsequently, further screening of small molecular compounds with potential therapeutic effects on CRC was conducted through the HERB database, followed by molecular docking studies of these compounds with the LACTB2 protein. The integration and analysis of expression data obtained from 2294 CRC samples and 1286 noncancerous colorectal samples showed that LACTB2 was highly expressed in CRC. Immunohistochemistry performed on in-house tissue samples confirmed that LACTB2 protein expression was upregulated in CRC. CIBERSORT revealed lower B cell infiltration levels in the high LACTB2 expression group than in the low expression group. GO, KEGG, and GSEA analyses showed that LACTB2 expression and genes positively correlating with it were mainly related to DNA synthesis and repair, mitochondrial translational elongation and translational termination, phosphorylation, and mTORC1 signaling. Finally, molecular docking simulations confirmed the ability of quercitin to target and bind to LACTB2. This is the first study to demonstrate that LACTB2 is upregulated in CRC. LACTB2 promotes colorectal tumorigenesis and tumor progression.
RESUMEN
OBJECTIVE: The prevalence and mortality of cardiovascular diseases remain ranked first worldwide. Myocardial infarction (MI) is the central cause of death from cardiovascular diseases, seriously endangering human health. The clinical implication of toll-like receptor 2 (TLR2) remains contradictory, and its mechanism is still unknown. Hence, the objective of this study was to elucidate the clinical value and molecular mechanism of TLR2 in MI. METHODS: All high-throughput datasets and eligible literature were screened, and the expression levels of TLR2 were collected from the MI. The integrated expression level of TLR2 was displayed by calculating the standardized mean difference (SMD) and the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC). The related TLR2 genes were sent for pathway analyses by gene ontology (GO), Kyoto encyclopedia of genes and genome (KEGG), and disease ontology (DO). Single-cell RNA-seq was applied to ascertain the molecular mechanism of TLR2 in MI. RESULTS: Nine microarrays and four reported data were available to calculate the comprehensive expression level of TLR2 in MI, including 325 cases of MI and 306 cases of controls. The SMD was 2.55 (95% CI = 1.35-3.75), and the AUC was 0.76 (95% CI = 0.72-0.79), indicating the upregulation of TLR2 in MI. The related TLR2 genes were primarily enriched in the pathways of atherosclerosis, arteriosclerotic cardiovascular disease, and arteriosclerosis, suggesting the clinical role of TLR2 in the progression of MI. Afterward, TLR2 was upregulated in myeloid cells in MI. CONCLUSIONS: TLR2 may have a crucial role in progressing from coronary atherosclerosis to MI. The upregulation of TLR2 may have a favorable screening value for MI.
Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Receptor Toll-Like 2 , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Ontología de Genes , Humanos , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Regulación hacia ArribaRESUMEN
Propensity score matching (PSM) is a popular method in clinical researches to create a balanced covariate distribution between treated and untreated groups. However, the balance diagnostics are often not appropriately conducted and reported in the literature and therefore the validity of the findings from the PSM analysis is not warranted. The special article aims to outline the methods used for assessing balance in covariates after PSM. Standardized mean difference (SMD) is the most commonly used statistic to examine the balance of covariate distribution between treatment groups. Because SMD is independent of the unit of measurement, it allows comparison between variables with different unit of measurement. SMD can be reported with plot. Variance is the second central moment and should also be compared in the matched sample. Finally, a correct specification of the propensity score model (e.g., linearity and additivity) should be re-assessed if there is evidence of imbalance between treated and untreated. R code for the implementation of balance diagnostics is provided and explained.
RESUMEN
BACKGROUND AND OBJECTIVE: The evidence regarding the association between serum/plasma vitamin D (VitD) concentrations and systemic lupus erythematosus (SLE) is inconsistent. The study was based on relevant results from literatures that were identified and evaluated. The aim of this meta-analysis is to determine circulating VitD in SLE patients and explore influencing factors. METHODS: Studies examining VitD levels in SLE patients were identified through targeted searches in the PubMed and EMBASE databases (up to December 2017). Data extracted from eligible studies was synthesized to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI). A fixed or a random effects model was applied to calculate the pooled SMDs and ORs depending on heterogeneity across studies. RESULTS: A total of 24 studies, including 6017 patients and 18,417 controls were included. The pooled analysis suggested that VitD levels were significantly lower in SLE patients compared with those in controls [SMD= -0.09, 95%CI= -0.12 to -0.06, P < 0.001]. When the studies were stratified by ethnicity, VitD concentrations were also significantly lower in Asian, Caucasian and African patients. When the studies were stratified by age, gender, VitD level was lower in patients than that in controls. Subgroup analyses stratified by measurement type (expect for radioimmunoassay) also demonstrated consistent results. Moreover, VitD insufficiency was more prevalent in SLE patients than healthy controls [OR=6.57, 95%CI=4.64-9.29]. CONCLUSION: Compared with healthy controls, SLE patients had lower concentration of VitD. Additionally, the prevalence of VitD insufficiency is more common in SLE patients.