Exploring m6A-linked aging genes in osteoarthritis and broad cancer spectrum: Prospects for diagnostic and therapeutic advancements.

Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.

MicroRNA 148a-3p promotes Thrombospondin-4 expression and enhances angiogenesis during tendinopathy development by inhibiting Krüppel-like factor 6.

Tendinopathy is a common musculoskeletal disorder with characteristic hypervascularity. The mechanism of angiogenesis in tendinopathy remains unclear. The present study aimed to investigate the roles of miR-148a-3p in angiogenesis development of tendinopathy. In this study, we demonstrated that miR-148a-3p expression was increased in tendinopathy tissues and positively correlated with CD34 levels which is a specific marker for angiogenesis. We identified Krüppel-like factor 6 (KLF6) as a direct target gene of miR-148a-3p in tenocytes. Furthermore, reduced levels of KLF6 in tendinopathy tissues was showed using qRT-PCR and immunohistochemical analysis, compared with controls. A negative correlation between the levels of KLF6 mRNA and miR-148a-3p was observed. Then, we verified that miR-148a-3p could regulate Tsp-4 expression by targeting KLF6 in tenocyte and was positively correlated with Tsp-4 levels in tendinopathy tissues. In a coculture system of tenocytes with endothelial cells (ECs), we observed that transfection of Lv-miR-148a-3p markedly upregulated EC angiogenesis. In summary, our data establish a novel molecular mechanism by which miR-148a-3p upregulates Tsp-4 expression in tenocytes to promote EC angiogenesis by targeting KLF6, which could be helpful for the treatment of tendinopathy in the future.

Do Nonsteroidal Anti-Inflammatory Drugs Affect Tissue Healing After Arthroscopic Anterior Cruciate Ligament Reconstruction?

BACKGROUND Experimental studies have reported nonsteroidal anti-inflammatory drugs (NSAIDs) could impair tendon healing. The purpose of this study was to investigate whether NSAIDs could affect recovery of knee joint function in patients after anterior cruciate ligament (ACL) reconstruction. MATERIAL AND METHODS We enrolled 40 patients treated with celecoxib and 40 patients treated with tramadol, who underwent ACL reconstruction from January 2011 to December 2017. Visual analogue scale (VAS) and functional outcomes were collected and evaluated. The follow-up period was 12 months. RESULTS In both groups, all patients obtained pain release after surgery, compared with that before surgery. But no significant differences were observed between the 2 groups in VAS scores. We also did not find any differences between the 2 groups at 1 year of follow-up, in terms of anterior drawer test, Lachman test, side-to-side laxity assessed by KT-2000, IKDC score, Lysholm score, and Tegner scale. However, the celecoxib group showed a reduced incidence of nausea compared to the tramadol group (P=0.048). CONCLUSIONS The use of NSAIDs after ACL reconstruction is relatively safe and could decrease adverse side effects which were caused by opioid drugs.

Efficacy Analysis of Arthroscopic Surgery Combined with Intra-articular Chitosan Injection for Stage II-III Knee Osteoarthritis in Patients with Abnormal Body Weight.

OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.

Course-based intra-articular injection of medical chitosan mitigates excessive deposition of triacylglycerides in the synovial tissue of the knee osteoarthritis.

BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: Sixty patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scoring, and American Knee Society (AKS) scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the presurgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced more reductions in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.

miR-195 inhibits esophageal cancer cell proliferation and promotes apoptosis by downregulating YAP1.

OBJECTIVE: Yes-associated protein 1 (YAP1) regulates a variety of genes related to cell proliferation, cycle and apoptosis, and plays a role in the pathogenesis of esophageal cancer. It was found that the expression of miR-195 was significantly decreased in esophageal cancer tissues, suggesting its anti-cancer effect. Bioinformatics analysis revealed the targeted relationship between miR-195 and the 3'-UTR of YAP1. This study investigated the role of miR-195 in regulating YAP1 expression and affecting proliferation and apoptosis of esophageal cancer cells. METHODS: The tumor tissue and the adjacent tissue of patients with esophageal cancer were collected to detect the expressions of miR-195 and YAP1. Dual luciferase reporter gene assay was adopted to validate the targeted regulation between miR-195 and YAP1. Esophageal cancer EC9706 cells and normal esophageal epithelial HEEC cells were cultured in vitro to measure the expression of miR-195 and YAP1. EC9706 cells were divided into miR-NC group and miR-195 mimic group followed by analysis of cell apoptosis by flow cytometry and cell proliferation by EdU staining. RESULTS: Compared with adjacent tissues, miR-195 was significantly decreased, while YAP1 mRNA and protein were significantly upregulated in esophageal cancer tissues. Dual luciferase reporter gene assay confirmed that there was a targeted relationship between miR-195 and YAP1. Compared with HEEC cells, miR-195 expression was declined, whereas YAP1 was elevated in EC9706 cells. Transfection of miR-195 mimic significantly downregulated YAP1 expression, resulting in increased apoptosis and decreased proliferation of EC9706 cells. CONCLUSION: Decreased expression of miR-195 plays a regulatory role in increasing YAP1 expression and promoting the pathogenesis of esophageal cancer. Elevation of miR-195 inhibites the expression of YAP1, restrains cell proliferation, and promotes cell apoptosis.