CircRELL1 promotes osteoarthritis progression by regulating miR-200c-3p.

Background: There is a growing body of evidence indicating a potential association between circular RNA and the pathogenesis of human osteoarthritis (OA). Nevertheless, the precise extent of their involvement in OA remains largely unexplored. Hence, the objective of this investigation is to elucidate the function of Circular (Circ) RELL1 in the context of OA. Methods: 24 OA tissue samples and 11 normal tissue samples were collected. The inflammatory OA-like conditions were established by Destabilized Medial Meniscus (DMM) operation in mice and LPS-induced C28/I2 cells. OA severity and articular cartilage degradation were assessed by Safranin-O staining, hematoxylin-eosin (H&E) staining, and International Society for Osteoarthritis Research (OARSI) criteria. CircRELL1, miR-200c-3p, and TCF4 were measured by RT-qPCR and Immunoblot. The cell viability and apoptosis rate were measured by MTT and flow cytometry, respectively. The levels of cytokines interleukin (IL)-1ß, IL-6, and TNF-α were determined by ELISA. Apoptosis-associated proteins (cleaved caspase-3, Bax, and Bcl-2) and extracellular matrix (ECM) degradation-associated proteins (MMP13, collagen II, and Aggrecan) were detected by Immunoblot. The interaction between miR-200c-3p and circRELL1 or TCF4 was verified by dual luciferase reporter assay and RIP assay. Results: CircRELL1 expression was upregulated in OA patients, and the results were consistent in DMM mice and LPS-treated C28/I2 cells. Silencing circRELL1 improved cartilage injury caused by DMM and contributed to a lower OARSI score. Silencing CircRELL1 increased the activity of OA chondrocytes in vivo and in vitro and inhibited cellular inflammatory responses and ECM degradation. In terms of mechanism, circRELL1 functioned by targeting miR-200c-3p, leading to the suppression of inflammatory factor production, cell apoptosis, and ECM degradation, thus inhibiting the progression of OA. Conclusion: CircRELL1 may promote the progression of OA by regulating the miR-200c-3p.

Diosmetin inhibits subchondral bone loss and indirectly protects cartilage in a surgically-induced osteoarthritis mouse model.

Osteoarthritis (OA) is a common degenerative disease characterized by articular cartilage destruction, subchondral bone remodeling, ectopic osteophyte formation and synovitis. It is now recognized that the integrity of the underlying subchondral bone is crucial for the maintenance of the overlying articular cartilage. Therapeutic agents that can prevent subchondral bone loss are demonstrate potential in the prevention and treatment of OA. Diosmetin (DIOS; 3',5,7 -trihydroxy-4'-methoxy flavone), a natural flavonoid, has been shown to exert anti-oxidative, anti-inflammatory, anti-apoptotic and anticancer properties. In this study, we found that diosmetin suppressed the DMM-induced subchondral bone loss and reduced subsequent cartilage degradation in vivo. Cellular-based assays showed that diosmetin inhibited RANKL-induced osteoclast formation and bone resorption,but did not affect IL-1ß-induced chondrocyte hypertrophy. Biochemical analyses demonstrated that the anti-osteoclastic effect of diosmetin was at least in part due to the suppression of RANKL-induced activation of the ERK, p38, and JNK MAPK signaling pathways. Collectively, our results show that diosmetin have potential as a therapeutic agent the treatment of abnormal subchondral bone loss and cartilage degradation associated with the onset of OA.

Activity and Stability Boosting of an Oxygen-Vacancy-Rich BiVO4 Photoanode by NiFe-MOFs Thin Layer for Water Oxidation.

The introduction of oxygen vacancies (Ov) has been regarded as an effective method to enhance the catalytic performance of photoanodes in oxygen evolution reaction (OER). However, their stability under highly oxidizing environment is questionable but was rarely studied. Herein, NiFe-metal-organic framework (NiFe-MOFs) was conformally coated on oxygen-vacancy-rich BiVO4 (Ov-BiVO4 ) as the protective layer and cocatalyst, forming a core-shell structure with caffeic acid as bridging agent. The as-synthesized Ov-BiVO4 @NiFe-MOFs exhibits enhanced stability and a remarkable photocurrent density of 5.3±0.15 mA cm-2 at 1.23 V (vs. RHE). The reduced coordination number of Ni(Fe)-O and elevated valence state of Ni(Fe) in NiFe-MOFs layer greatly bolster OER, and the shifting of oxygen evolution sites from Ov-BiVO4 to NiFe-MOFs promotes Ov stabilization. Ovs can be effectively preserved by the coating of a thin NiFe-MOFs layer, leading to a photoanode of enhanced photocurrent and stability.

A population-based propensity-matched study of regional dissections in patients with metastatic osteosarcoma.

BACKGROUND: The survival rates of patients with metastatic osteosarcoma are poor, and the prognosis is closely related to the choice of treatment, especially surgery. This study aimed to evaluate the survival outcomes of patients with metastatic osteosarcoma undergoing regional dissections. METHODS: We collected data on patients with metastatic osteosarcoma between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS), while univariate and multivariate Cox regression analyses were used to evaluate outcomes. Propensity score matching (PSM) was used to minimize the effects of confounding factors. RESULTS: The SEER database had records of 2768 patients diagnosed with osteosarcoma, of whom 398 were included in our study. Of the included patients, 116 (29.15%) underwent regional dissections, while 282 (70.85%) underwent non-regional dissections. The univariate and multivariate Cox regression analyses, prior to PSM, showed that OS (hazard ratio (HR): 0.34, 95% confidence interval (CI): 0.26-0.44, P<0.001 and HR: 0.47, 95% CI: 0.35-0.64, P<0.001, respectively) and CSS (HR: 0.33, 95% CI: 0.25-0.43, P<0.001 and HR: 0.46, 95% CI: 0.34-0.63, P<0.001, respectively) were better in patients who underwent regional dissections than those who underwent non-regional dissections. Compared with non-regional dissections, regional dissections, which included both primary tumour resection (PTR) and primary tumour and metastatic site resection (PTMR), were associated with better OS (P<0.001) and CSS (P<0.001) . However, the survival outcomes following PTR and PTMR showed no significant difference. After PSM, patients in the regional dissection group still had a higher OS (P<0.001) and CSS (P<0.001) than those in the non-regional dissection group. CONCLUSIONS: Compared with non-regional dissection, regional dissection resulted in better survival in patients with metastatic osteosarcoma.