Macrophages are the most abundant immune cells within the synovial joints, and also the main innate immune effector cells triggering the initial inflammatory responses in the pathological process of osteoarthritis (OA). The transition of synovial macrophages between pro-inflammatory and anti-inflammatory phenotypes can play a key role in building the intra-articular microenvironment. The pro-inflammatory cascade induced by TNF-α, IL-1β, and IL-6 is closely related to M1 macrophages, resulting in the production of pro-chondrolytic mediators. However, IL-10, IL1RA, CCL-18, IGF, and TGF are closely related to M2 macrophages, leading to the protection of cartilage and the promoted regeneration. The inhibition of NF-κB signaling pathway is central in OA treatment via controlling inflammatory responses in macrophages, while the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway appears not to attract widespread attention in the field. Nrf2 is a transcription factor encoding a large number of antioxidant enzymes. The activation of Nrf2 can have antioxidant and anti-inflammatory effects, which can also have complex crosstalk with NF-κB signaling pathway. The activation of Nrf2 can inhibit the M1 polarization and promote the M2 polarization through potential signaling transductions including TGF-β/SMAD, TLR/NF-κB, and JAK/STAT signaling pathways, with the regulation or cooperation of Notch, NLRP3, PI3K/Akt, and MAPK signaling. And the expression of heme oxygenase-1 (HO-1) and the negative regulation of Nrf2 for NF-κB can be the main mechanisms for promotion. Furthermore, the candidates of OA treatment by activating Nrf2 to promote M2 phenotype macrophages in OA are also reviewed in this work, such as itaconate and fumarate derivatives, curcumin, quercetin, melatonin, mesenchymal stem cells, and low-intensity pulsed ultrasound.

Osteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.

Objectives: To examine the effects of Tai Chi on balance and functional mobility in people with Parkinson’s disease, and determine whether fall incidence could be reduced by the Tai Chi exercise. Design: Single blinded randomized control trial with 6 months’ follow-up. Setting: A hospital and general community. Participants: Patients ( n=76) diagnosed with idiopathic Parkinson’s disease, over 40 years old, able to walk independently and fell at least one time during the past 12 months. Interventions: The Tai Chi group ( n=37) received 24-form Yang style Tai Chi exercise for 60 minutes each time, three times a week and lasted for 12 weeks. The control group ( n=39) received no intervention. Main outcome measures: Berg Balance Scale (BBS), Unified Parkinson’s Disease Rating Scale (UPDRS) III, Timed Up&Go (TUG) and occurrences of falls. Results: The Tai Chi group improved more than the control group on the BBS ( p0.05). During the 6-month follow-up, only 8 (21.6%) out of 37 patients in the Tai Chi group had experience of falls comparing to 19 (48.7%) out of 39 patients in the control group ( p<0.05). The average times of falls were 0.30±0.62 in the Tai Chi group compared with 0.64±0.74 in the control group ( p<0.05). Conclusions: Our findings suggested that Tai Chi exercise could improve the balance and decrease the fall risks in patients with Parkinson’s disease.

Epigenetic modifications have been identified as critical molecular determinants influencing macrophage plasticity and heterogeneity. Among these, histone lactylation is a recently discovered epigenetic modification. Research examining the effects of histone lactylation on macrophage activation and polarization has grown substantially in recent years. Evidence increasingly suggests that lactate-mediated changes in histone lactylation levels within macrophages can modulate gene transcription, thereby contributing to the pathogenesis of various diseases. This review provides a comprehensive analysis of the role of histone lactylation in macrophage activation, exploring its discovery, effects, and association with macrophage diversity and phenotypic variability. Moreover, it highlights the impact of alterations in macrophage histone lactylation in diverse pathological contexts, such as inflammation, tumorigenesis, neurological disorders, and other complex conditions, and demonstrates the therapeutic potential of drugs targeting these epigenetic modifications. This mechanistic understanding provides insights into the underlying disease mechanisms and opens new avenues for therapeutic intervention.

Background: Osteoarthritis (OA) is a chronic, debilitating, and degenerative joint disease. However, it is difficult for patients with knee OA to access conventional rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies to provide a means combining monitoring, guidance, and treatment for patients with knee OA. Objective: The aim of this study was to conduct a systematic review and meta-analysis for assessing the effect of internet-based rehabilitation programs on pain and physical function in patients with knee OA. Methods: Keywords related to knee OA and internet-based rehabilitation were systematically searched in the Web of Science, MEDLINE, EMBASE, CENTRAL, Scopus, PEDro (Physiotherapy Evidence Database), CNKI, SinoMed, and WANFANG databases from January 2000 to April 2020. Only randomized controlled trials were included. The authors independently screened the literature. The main outcome measures were focused on pain and physical function. A meta-analysis was performed on the collected data. Review Manager (RevMan, version 5.3) was used for all analyses. Results: The systematic review identified 6 randomized controlled trials, 4 of which were included in the meta-analysis, comprising a total of 791 patients with knee OA. The meta-analysis with the fixed-effects model showed that the internet-based rehabilitation programs could significantly alleviate the osteoarthritic pain for patients compared with conventional rehabilitation (standardized mean difference [SMD] –0.21, 95% CI −0.4 to –0.01, P=.04). No significant difference was found in the improvement of physical function in patients with knee OA compared with conventional rehabilitation within 2 to 12 months (SMD –0.08, 95% CI −0.27 to 0.12, P=.43). Conclusions: This systematic review shows that internet-based rehabilitation programs could improve the pain but not physical function for patients with knee OA. However, there was a very small number of studies that could be included in the review and meta-analysis. Thus, further studies with large sample sizes are warranted to promote the effectiveness of internet-based rehabilitation and to develop its personalized design.