Prevalence of intrinsic capacity decline among community-dwelling older adults: a systematic review and meta-analysis.

BACKGROUND: The concept of intrinsic capacity (IC) was introduced to define healthy aging and active aging based on functional capacity, yet there is limited understanding of the risk of IC decline at a population level. AIMS: To consolidate existing evidence for rates of IC decline and risk factors among community-dwelling adults 60 years or older. METHODS: According to the PRISMA guidelines, the literature search was independently conducted by two researchers in 8 databases from inception to January 2024 without language restrictions using combinations of free words and subject words. Qualities of included studies were assessed using Joanna Briggs Institute's (JBI's) critical appraisal checklist for prevalence studies. To pool the data, a random-effect meta-analysis was performed, followed by subgroup analysis and sensitivity analysis. All analyses were performed by Stata14.0. RESULTS: From 1594 records, 15 studies were extracted with 33,070 participants for meta-analysis. The pooled prevalence of IC decline in community settings was 67.8% (95% CI: 57.0-78.5%; P < 0.001). The prevalence of IC decline in China (66.0%; 95% CI: 53.2-78.9%) was found to be slightly lower than in other countries/regions (73.0%; 95% CI: 59.8-86.3%); however, this difference was not statistically significant. Other subgroup analyses revealed no statistically significant differences in prevalence. Age, hypertension, diabetes, gender, education level, living status, smoking, regular exercise, marital status, and osteoarthritis are associated with IC decline. CONCLUSION: More than two-thirds of older adults in the community are affected by IC decline, and age, hypertension, diabetes, female sex, low education level, living alone, smoking, irregular exercise, unmarried, and osteoarthritis are all risk factors for IC decline.

RNA modification writers pattern in relation to tumor microenvironment and prognosis in prostate cancer.

Background: RNA modifications are important in the study of epigenetic regulatory mechanisms in immune responses and tumorigenesis. When RNA writers are mutated or disrupted in expression, the genes associated with the pathways they modify are also disrupted and can activate or repress related pathways, affecting tumorigenesis and progression. However, the potential role of RNA writers in prostate cancer is unclear. Methods: Based on data from three datasets, we describe 26 RNA writers that mediate gene expression and genetic mutation in prostate cancer and assess their expression patterns in 948 prostate cancer samples. Using principal component analysis algorithms, the RM Score was developed to quantify the RNA modification patterns of specific tumors. Results: Two different categories were determined by unsupervised clustering methods, and survival analysis showed significant differences in OS prognosis between these two categories. Differentially expressed genes between the different categories were detected and the RNA writers-mediated scoring model RM_Score were constructed based on this. Also, the RM_Score was analyzed in relation to clinical characteristics, immune infiltration level, drug response, and efficacy of chemotherapy and immunotherapy. Those results confirm that multilayer alterations in epitope-modified RNA writers are associated with patient prognosis and with immune cell infiltration characteristics. Finally, we examined differentially expressed mRNA, lncRNA and miRNA between high and low RM_Score groups, based on which a ceRNA regulatory network was constructed. Conclusion: This work is a comprehensive analysis of modified writers in prostate cancer and identified them to have a role in chemotherapy and immunotherapy.

Understanding Competitive Endogenous RNA Network Mechanism in Type 1 Diabetes Mellitus Using Computational and Bioinformatics Approaches.

BACKGROUND: Type 1 diabetes mellitus (T1DM), an autoimmune disease with a genetic tendency, has an increasing prevalence. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in disease pathogenesis. However, their roles in T1DM are poorly understood. The present study aimed at identifying signature lncRNAs and circRNAs and investigating their roles in T1DM using the competing endogenous RNA (ceRNA) network analysis. METHODS: The T1DM expression profile was downloaded from Gene Expression Omnibus (GEO) database to identify the differentially expressed circRNAs, lncRNAs, and mRNAs. The biological functions of these differentially expressed circRNAs, lncRNAs, and mRNAs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Targeting relationships of circRNA-miRNA, lncRNA-miRNA, and miRNA-mRNA were predicted, and the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network was established. Finally, qRT-PCR was applied to identify the effect of hsa_circ_0002202 inhibition on the IFN-I induced macrophage inflammation. RESULTS: A total of 178 circRNAs, 404 lncRNAs, and 73 mRNAs were identified to be abnormally expressed in T1DM samples. Functional enrichment analysis results indicated that the differentially expressed genes were mainly enriched in extracellular matrix components and macrophage activation. CeRNA regulatory network showed that circRNAs and lncRNAs regulate mRNAs through integrate multiple miRNAs. In addition, in vitro experiments showed that hsa_circ_0002202 inhibition suppressed the type I interferon (IFN-I)-induced macrophage inflammation. CONCLUSION: In the present study, the circRNA-lncRNA-miRNA-mRNA ceRNA regulatory network in T1DM was established for the first time. We also found that hsa_circ_0002202 inhibition suppressed the IFN-I-induced macrophage inflammation. Our study may lay a foundation for future studies on the ceRNA regulatory network in T1DM.

The differential neuroprotection of HSP70-hom gene single nucleotide polymorphisms: In vitro (neuronal hypoxic injury model) and in vivo (rat MCAO model) studies.

To investigate the effect of HSP70-hom+2437 single nucleotide polymorphisms (SNPs) on hypoxia and ischemia condition, we constructed the neuronal hypoxic injury model and the rat middle cerebral artery occlusion (MCAO) model to compare the inhibition rate of neurons and detect the infarct volume as well as the expression of related apoptotic proteins in order to explore the possible mechanisms. The neuroblastoma cells SHSY5Y were divided into the OE (transfected with the C allele) group, OEmu (transfected with the T allele) group and negative control (NC, transfected with the empty lentiviral vector CON195) group. Varying degrees of hypoxia were induced by deferoxamine (DFO). The inhibition rate of hypoxic neurons and the expression of related apoptotic proteins were detected in the three genotype groups. While in the rat MCAO model, we built five groups including the sham group, the blank control group (injected with physiological saline), the negative control group (injected with lentivirus and physiological saline), the C allele group and the T allele group (injected with lentivirus overexpressing C and T allele). The MCAO model operation was then underwent in all five groups, the infarct volume by TTC staining and the expression of related apoptotic proteins were detected after 24 h. The results in neuronal hypoxic injury model showed a significant difference in the inhibition rate between the three groups (P < 0.05), and the average inhibition rates for the OEmu, OE and NC groups were 13.2%, 19.2% and 23.3%, respectively. The inhibition rates also differed between lower and higher DFO concentrations (P < 0.05). Compared with the NC group, Bax decreased significantly in the OE and OEmu groups, whereas PI3K and HSPA1L (HSP70-hom) increased. However, the expression of Bax in the OEmu group decreased significantly more than in the OE group, whereas PI3K and HSPA1L levels showed no difference between the two groups. Corresponding with the results above, overexpressing HSP70-hom could reduce the infarct volume of ischemic injury by TTC staining in rat MCAO model and the T allele group also had less infarct volume than C allele group. Compared with the sham group, blank control group and negative control group, Bax decreased significantly in the C and T allele groups, while HSPA1L and p- AKT increased. Furthermore, the expression of Bax in the T allele group decreased significantly more than that in the C allele group, while there were no significant differences in HSPA1L and p-AKT levels between the two groups. Therefore, the overexpression of HSP70-hom+2437 could play a protective role in hypoxic neurons and ischemic brain tissue by upregulating the expression of HSPA1L and PI3K/p-AKT and downregulating the expression of BAX. The neuroprotective effect of the T allele was stronger than that of the C allele, which may be related to the strengthened downregulation of BAX.