ABSTRACT
OBJECTIVE: This research aimed to explore IL-21/miR-361-5p/MAP3K9 expression in shoulder arthritis and identify its regulatory pathways. METHODS: We established a rat shoulder arthritis model, then quantified IL21 and miR-361-5p in synovial fluid using ELISA and monitored the arthritis development. Additionally, IL21's effect on miR-361-5p levels in cultured human chondrocytes (HC-a) was assessed. Chondrocyte cell cycle status and apoptosis were measured via flow cytometry. Interactions between miR-361-5p and MAP3K9 were confirmed through dual-luciferase reporting and bioinformatic scrutiny. Protein levels of MAP3K9, p-ERK1/2, p-NF-κB, MMP1, and MMP9 were analyzed by Western blots. RESULTS: IL21 levels were elevated, while miR-361-5p was reduced in the synovial fluid from arthritic rats compared to healthy rats. IL21 was shown to suppress miR-361-5p in chondrocytes leading to hindered cell proliferation and increased apoptosis. Western blots indicated that miR-361-5p curbed MAP3K9 expression, reducing MMP activity by attenuating the ERK1/2/NF-κB pathway in chondrocytes. CONCLUSION: IL21 upregulation and miR-361-5p downregulation characterize shoulder arthritis, resulting in MAP3K9 overexpression. This chain of molecular events boosts MMP expression in chondrocytes and exacerbates the condition's progression.
Subject(s)
Chondrocytes , MAP Kinase Kinase Kinases , MicroRNAs , Animals , Humans , Male , Rats , Apoptosis/genetics , Cell Proliferation/genetics , Chondrocytes/metabolism , Disease Progression , Interleukins/metabolism , Interleukins/genetics , MAP Kinase Kinase Kinases/metabolism , MAP Kinase Kinase Kinases/genetics , MicroRNAs/metabolism , MicroRNAs/genetics , Rats, Sprague-DawleyABSTRACT
The current meta-analysis searched the literature connected to different tranquilizers used to treat elderly people and assessed it in terms of dose, types of outcomes and adverse effects, to determine a safe and acceptable tranquilizer and its optimal dose. A systematic literature review was undertaken for randomized controlled trials, case-control, retrospective and prospective studies on the use of tranquilizers in elderly patients, using PubMed, Ebsco, SCOPUS and Web of Science. PICOS criteria were used to select studies, and pertinent event data was collected. This meta-analysis includes 16 randomized control trials spanning the years 2000 to 2022, using the data from 2224 patients. The trials that were included used various tranquilizers such as diazepam, alprazolam, temazepam and lorazepam, and indicated high treatment efficacy and low adverse effects. With a p-value of 0.853 for Egger's test and 0.13 for Begg's test, the current meta-analysis shows a minimal probability of publication bias. A recent meta-analysis supports the use of tranquilizers in older people to treat sleeplessness, epilepsy or anxiety, but only at modest doses, because large doses are harmful and produce numerous withdrawal symptoms.
