MiR-203a-3p attenuates apoptosis and pyroptosis of chondrocytes by regulating the MYD88/NF-κB pathway to alleviate osteoarthritis progression.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease that imposes a significant socioeconomic burden worldwide. Our previous studies revealed a down-regulation of miR-203a-3p in the knee tissues of OA patients. However, the underlying mechanism through which miR-203a-3p mediates the pathological process of OA remains unknown. Thus, we aimed to determine the effects of miR-203a-3p in the progression of OA. METHODS: Rat primary chondrocytes were stimulated with 10 µg/mL lipopolysaccharide (LPS) for 24 hours, followed by transfection with 50 nM miR-203a-3p mimic, inhibitor, and siRNA for MYD88 or consistent negative controls for 48 hours. To evaluate the effects of miR-203a-3p on cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis in chondrocytes, various techniques such as immunofluorescence staining, biochemical analysis, Western blotting, and the TUNEL staining were utilized. In the rat OA model, all rats were randomly divided into four groups: Sham, OA, OA+Agomir negative control (NC), and OA+Agomir. They received intra-articular injections of 25 nmol miR-203a-3p agomir, agomir NC, or normal saline twice a week for the duration of 8 weeks after OA induction. Immunofluorescence staining was performed to evaluate the effects of miR-203a-3p on cartilage matrix degradation in rats. RESULTS: MiR-203a-3p was down-regulated in LPS-treated rat chondrocytes and OA cartilage, and directly targeted MYD88. Moreover, miR-203a-3p significantly inhibited LPS-induced cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes via targeting MYD88. Mechanistically, miR-203a-3p exerted protective effects via the inhibition of the MYD88/NF-κB pathway. In the rat OA model, intra-articular injections of miR-203a-3p agomir also significantly inhibited cartilage matrix degradation, thereby alleviating OA progression. Furthermore, the miR-203a-3p agomir-treated arthritic rat dramatically exhibited better articular tissue morphology and lower OARSI scores. CONCLUSIONS: MiR-203a-3p plays a role in alleviating the progression of OA by regulating the MYD88/NF-κB pathway, thereby inhibiting cartilage matrix degradation, oxidative stress, apoptosis, and pyroptosis of chondrocytes. It highlights the potential significance of miR-203a-3p as an important regulator of OA.

Elucidating the role of ubiquitination and deubiquitination in osteoarthritis progression.

Osteoarthritis is non-inflammatory degenerative joint arthritis, which exacerbates disability in elder persons. The molecular mechanisms of osteoarthritis are elusive. Ubiquitination, one type of post-translational modifications, has been demonstrated to accelerate or ameliorate the development and progression of osteoarthritis via targeting specific proteins for ubiquitination and determining protein stability and localization. Ubiquitination process can be reversed by a class of deubiquitinases via deubiquitination. In this review, we summarize the current knowledge regarding the multifaceted role of E3 ubiquitin ligases in the pathogenesis of osteoarthritis. We also describe the molecular insight of deubiquitinases into osteoarthritis processes. Moreover, we highlight the multiple compounds that target E3 ubiquitin ligases or deubiquitinases to influence osteoarthritis progression. We discuss the challenge and future perspectives via modulation of E3 ubiquitin ligases and deubiquitinases expression for enhancement of the therapeutic efficacy in osteoarthritis patients. We conclude that modulating ubiquitination and deubiquitination could alleviate the osteoarthritis pathogenesis to achieve the better treatment outcomes in osteoarthritis patients.

Thermal environment investigation of asymmetric radiation coupled with convection heating.

The couple of radiation with convection heating owned advantages of less energy utilization, healthier and more comfortable indoor environment. However, local thermal discomfort was often induced by large vertical temperature difference and radiation asymmetry temperature. This work studied indoor thermal environment characteristics under different coupling ways of radiation and convection heating terminals through experiments and CFD simulation. The studied five scenarios were denoted as: (I) lateral air supply + adjacent side wall radiation, (II) lateral air supply + opposite side wall radiation, (III) lateral air supply + floor radiation, (IV) lateral air supply + adjacent side wall radiation + floor radiation, and (V) lateral air supply + opposite side wall radiation + floor radiation. The overall thermal comfort indices (including air diffusion performance index (ADPI), predicted mean vote (PMV), and predicted percent of dissatisfaction (PPD)) and local thermal comfort indices under different scenarios were investigated. For Scenarios I-III, the local dissatisfaction rates caused by vertical air temperature difference were 0.4%, 0.1%, and 0.2%, respectively, which belonged to "A" class according to the ISO-7730 Standard. While the vertical asymmetric radiation temperature of Scenario I/II was about 6.5 °C lower than that of Scenario III/IV/V. The ADPI for Scenarios III-V were about respectively 5.7%, 16.7%, and 21.0% higher than that of Scenarios I-II, indicating that a large radiation area and radiation angle coefficient could reduce the discomfort caused by radiant temperature asymmetry. The coupling mode improved local discomfort by decreasing vertical temperature difference and radiation asymmetry temperature wherefore improving the PMV from -1.6 to -1. The lateral air supply coupled with asymmetric radiation heating could potentially improve the thermal comfort of occupied area, while the comprehensive effect of thermal environmental improvement, energy-saving, and cost-effectiveness needes to be further investigated.

Effectiveness of extracorporeal shock wave therapy in patients with tennis elbow: A meta-analysis of randomized controlled trials.

BACKGROUND: The aim of the present study was to investigate the effectiveness of Extracorporeal Shock Wave (ECSW) in the treatment of lateral epicondylitis (LE) of humerus. HYPOTHESIS: ECSW therapy in people with LE effectively reduces the pain and gains functional rehabilitation. MATERIALS/METHODS: Databases of PubMed, EMBASE, Web of Science and the Cochrane Library from inception to April 2020 was searched to identify all relevant RCTs comparing ECSW therapy with any other conservative treatment, including injection and local anesthetic versus placebo or control in patients aged 18 with LE. The primary outcome is the mean overall pain score at 12 weeks after treatment. Another secondary outcome mainly included Thomsen test, 50% pain reduction, grip strength and adverse effect at 12 weeks after treatment. RESULTS: Nine studies were included in the meta-analysis. Compared with the placebo group, ECSW cannot significantly reduce the pain score (mean deviation [MD] = -4.23, 95% confidence interval [CI]: -8.78 to 0.32, P = .07), but make more people acquire 50% pain reduction (MD = 1.38, 95% CI: 1.09 to 1.75, P = .008). There was no significant difference between ECSW and control in decreasing the pain score of Thomsen test (MD = -3.22, 95% CI: -14.06 to 7.62, P = .56). ECSW was more effective in Grip strength as compared with control at 12 weeks-3 months (MD = 3.52, 95% CI: 2.43 to 4.60, P < .00001) CONCLUSIONS:: Results suggested that ECSW cannot effectively reduce the mean overall pain, but it showed more people acquire 50% pain reduction and might be a better option for the treatment of LE. Because of study limitations, additional high level of evidence, more rigorously designed large-samples and high-quality randomized controlled trials are needed to guide clinical practice.