Diagnostic value of microRNAs in active tuberculosis based on quantitative and enrichment analyses.

BACKGROUND: Tuberculosis (TB) infection remains a crucial global health challenge, with active tuberculosis (ATB) representing main infection source. MicroRNA (miRNA) has emerged as a potential diagnostic tool in this context. This study aims to identify candidate miRNAs for ATB diagnosis and explore their possible mechanisms. METHODS: Differentially expressed miRNAs in ATB were summarized in qualitative analysis. The diagnostic values of miRNAs for ATB subtypes were assessed by overall sensitivity, specificity, and area under the curve. Additionally, we conducted enrichment analysis on miRNAs and target genes. RESULTS: Over 100 differentially expressed miRNAs were identified, with miR-29 family being the most extensively studied. The miR-29 family demonstrated sensitivity, specificity, and area under the curve of 80 %, 80 % and 0.86 respectively for active pulmonary TB (PTB). The differentially expressed miR-29-target genes in PTB were enriched in immune-related pathways. CONCLUSIONS: The miR-29 family exhibits good diagnostic value for active PTB and shows association with immune process.

The causal associations of altered inflammatory proteins with sleep duration, insomnia and daytime sleepiness.

STUDY OBJECTIVES: Growing evidence linked inflammation with sleep. This study aimed to evaluate the associations and causal effects of sleep traits including insomnia, excessive daytime sleepiness (EDS), and sleep duration (short: <7 h; normal: 7-9 h; long: ≥9 h), with levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins. METHODS: Standard procedures of quantitative analysis were applied to estimate the expression differences for each protein in compared groups. Then, a two-sample Mendelian randomization (MR) analysis was performed to explore their causal relationships with published genome-wide association study summary statistics. The inverse-variance weighted was used as the primary method, followed by several complementary approaches as sensitivity analyses. RESULTS: A total of 44 publications with 51 879 participants were included in the quantitative analysis. Our results showed that the levels of CRP, interleukin-1ß (IL-1ß), IL-6, and TNF-α were higher from 0.36 to 0.58 (after standardization) in insomnia compared with controls, while there was no significant difference between participants with EDS and controls. Besides, there was a U/J-shaped expression of CRP and IL-6 with sleep durations. In MR analysis, the primary results demonstrated the causal effects of CRP on sleep duration (estimate: 0.017; 95% confidence intervals [CI], [0.003, 0.031]) and short sleep duration (estimate: -0.006; 95% CI, [-0.011, -0.001]). Also, IL-6 was found to be associated with long sleep duration (estimate: 0.006; 95% CI, [0.000, 0.013]). These results were consistent in sensitivity analyses. CONCLUSIONS: There are high inflammatory profiles in insomnia and extremes of sleep duration. Meanwhile, elevated CRP and IL-6 have causal effects on longer sleep duration. Further studies can focus on related upstream and downstream mechanisms.

Computational Modeling of Immune Response Triggering Immunogenic Peptide Vaccine Against the Human Papillomaviruses to Induce Immunity Against Cervical Cancer.

Papillomaviruses are placed within the family Papillomaviride, and the members of this family have a double-stranded circular DNA genome. Every year, ∼30% of cancers are reported to be human papillomavirus (HPV) related, which represents 63,000 cancers of all infectious agent-induced cancers. HPV16 and HPV18 are reported to be associated with 70% of cervical cancers. The quest for an effective drug or vaccine candidate still continues. In this study, we aim to design B cell and T cell epitope-based vaccine using the two structural major capsid protein L1 and L2 as well as other three important proteins (E1, E2, and E6) against HPV strain 16 (HPV16). We used a computational pipeline to design a multiepitope subunit vaccine and tested its efficacy using in silico computational modeling approaches. Our analysis revealed that the multiepitope subunit vaccine possesses antigenic properties, and using in silico cloning method revealed proper expression and downstream processing of the vaccine construct. Besides this, we also performed in silico immune simulation to check the immune response upon the injection. Our results strongly suggest that this vaccine candidate should be tested immediately for the immune response against the cervical cancer-causing agent. The safety, efficacy, expression, and immune response profiling makes it the first choice for experimental and in vivo setup.