Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice.

BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by loss of joint function, which seriously reduces the quality of life of the elderly and imposes a heavy socioeconomic burden worldwide. Monotropein (MON), the main active ingredient of Morinda officinalis F.C. How, has exhibited therapeutic effects in different disease models. However, its potential effects on chondrocytes in an arthritic model remain unclear. This study aimed to evaluate the effects of MON in chondrocytes and a mouse model of OA, and explore the potential mechanisms. MATERIALS AND METHODS: Murine primary chondrocytes were pretreated with 10 ng/ml interleukin (IL)-1ß for 24 h to establish an in vitro model of OA, and then treated with different concentrations of MON (0, 25, 50 and 100 µM) for 24 h. The proliferation of the chondrocytes was assayed using ethynyl-deoxyuridine (EdU) staining. Immunofluorescence staining, western blotting and TUNEL staining were performed to assess the effects of MON on cartilage matrix degradation, apoptosis and pyroptosis. The mouse model of OA was constructed by surgical destabilization of the medial meniscus (DMM), and the animals were randomly divided into the sham-operated, OA and OA + MON groups. Following OA induction, the mice were given intraarticular injection of 100 µM MON or equal volume of normal saline twice a week for 8 weeks. The effects of MON on cartilage matrix degradation, apoptosis and pyroptosis were assessed as indicated. RESULTS: MON significantly accelerated the proliferation of chondrocytes, and inhibited cartilage matrix degradation, apoptosis and pyroptosis in the IL-1ß-stimulated cells by blocking the nuclear factor-kappa B (NF-κB) signaling pathway. In the mouse model as well, MON treatment alleviated OA progression and promoted cartilage repair by inhibiting cartilage matrix degradation, and chondrocyte apoptosis and pyroptosis through the inactivation of the NF-κB signaling pathway. Furthermore, the MON-treated arthritic mice exhibited better articular tissue morphology and lower OARSI scores. CONCLUSIONS: MON alleviated OA progression by inhibiting cartilage matrix degradation, and the apoptosis and pyroptosis of chondrocytes via NF-κB pathway inactivation, and is a promising alternative for the treatment of OA.

Andrographolide contributes to spinal cord injury repair via inhibition of apoptosis, oxidative stress and inflammation.

Background: Spinal cord injury (SCI) is a common disorder of the central nervous system with considerable socio-economic burden. Andrographolide (Andro), the main active component of Andrographis paniculata, has exhibited neuroprotective effects in different models of neurological diseases. The aim of this study was to evaluate the neuroprotective effects of Andro against SCI and explore the related mechanisms. Methods: SCI was induced in rats by the Allen method, and the modeled animals were randomly divided into sham-operated, SCI, SCI + normal saline (NS) and SCI + Andro groups. The rats were injected intraperitoneally with Andro (1 mg/kg) or the same volume of NS starting day one after the establishment of the SCI model for 28 consecutive days. Post-SCI tissue repair and functional recovery were evaluated by measuring the spinal cord water content, footprint tests, Basso-Beattie-Bresnahan (BBB) scores, hematoxylin-eosin (HE) staining and Nissl staining. Apoptosis, oxidative stress and inflammation, as well as axonal regeneration and remyelination were analyzed using suitable markers. The in vitro model of SCI was established by treating cortical neurons with H2O2. The effects of Andro on apoptosis, oxidative stress and inflammation were evaluated as indicated. Results: Andro treatment significantly improved tissue repair and functional recovery after SCI by reducing apoptosis, oxidative stress and inflammation through the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf-2/HO-1) and nuclear factor-kappa B (NF-κB) signaling pathways. Furthermore, Andro treatment promoted M2 polarization of the microglial cells and contributed to axonal regeneration and remyelination to improve functional recovery after SCI. In addition, Andro also attenuated apoptosis, oxidative stress and inflammation in H2O2-stimulated cortical neurons in vitro. Conclusion: Andro treatment alleviated SCI by reducing apoptosis, oxidative stress and inflammation in the injured tissues and cortical neurons, and promoted axonal regeneration and remyelination for functional recovery.

Integrated Analysis of miRNAs and Gene Expression Profiles Reveals Potential Biomarkers for Osteoarthritis.

Purpose: Currently, the early diagnosis and treatment of osteoarthritis (OA) remain a challenge. In the present study, we attempted to explore potential biomarkers for the diagnosis and treatment of OA. Methods: The differentially expressed genes (DEGs) were identified based on three mRNA datasets of synovial tissues for OA patients and normal controls downloaded from the Gene Expression Omnibus (GEO) database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used for evaluating gene function related categories. Then, miRNA sequencing was performed for differentially expressed miRNAs' identification. Finally, weighted gene co-expression network analysis (WGCNA) was performed for genes detected by the three mRNA datasets and a competing endogenous RNA (ceRNA) network with DEGs and differentially expressed microRNAs (miRNAs) was constructed for central genes identification. In addition, the relationship between central gene expression and immune infiltration was analyzed, and the candidate agents for OA were predicted based on the Connectivity Map database. Quantitative RT-PCR (qRT-PCR), Western blotting analysis, and immunofluorescent staining were performed to validate the expression levels of differentially expressed miRNAs and differentially expressed target genes in normal and OA tissues and chondrocytes. MiRNA-mRNA network was also validated in chondrocytes in vitro. Results: A total of 259 DEGs and 26 differentially expressed miRNAs were identified, among which 94 miRNA-mRNA interactions were predicted. The brown module in WGCNA was most closely correlated with the clinical traits of OA. After overlapping the brown module genes with miRNA-mRNA pairs, 27 miRNA-mRNA pairs were obtained. A ceRNA network was constructed with 5505 lncRNA-miRNA-mRNA interactions. B-cell translocation gene 2(BTG2), Abelson-related gene (ABL2), and vascular endothelial growth factor A (VEGFA) were identified to be the central genes with good predictive performance, which were significantly correlated with immune cell infiltration in OA, reflected by declined activated dendritic cells (aDCs), and elevated contents of B cells, macrophages, neutrophils, and T helper cells. Anisomycin, MG-132, thapsigargin, and lycorine were predicted to be the potential candidate agents for OA intervention. In vitro, the expression levels of differentially expressed miRNAs and biomarkers identified in the present study were consistent with the results obtained in normal or OA knee cartilage tissues and chondrocytes. Furthermore, BTG2 was identified to be negatively regulated by miR-125a-5p. Conclusion: BTG2, ABL2, and VEGFA can be regarded as potential predictive and treatment biomarkers for OA, which might guide the clinical therapy of OA.

Bibliometric and visualized analysis of electroacupuncture in the past 10 years.

BACKGROUND: There are many studies that have interrogated the evolution and use of electroacupuncture (EA). We aimed to evaluate the research status, cooperation and development of EA in the past 10 years. METHODS: We obtained data on the EA from the Web of Science core collection database. CiteSpace 5.7. R1 software was used to assess research cooperation through analysis of authors, institutions and countries. In addition, keyword cluster analysis, references and burst detection were analyzed to explore research hotspots and trends in the field of EA. RESULTS: We included a total of 3019 citing literature and 78,235 cited literature for analysis. The data showed that there has been a rise in the global number of EA studies in the past decade. Besides, the data demonstrated that China has made outstanding contribution in the development of EA. Whereas there is inter-agency cooperation in China, there is less cooperation with other countries. In addition, we showed frequent use of keywords such as "expression", "stimulation", or "pain". Besides, neuroscience was the main research area, followed by general medicine and oncology. Furthermore, with the improved research methods and technologies, there is enhanced overall quality of the studies. CONCLUSION: Taken together, our findings demonstrate a steady increase in the studies involving EA. However, the studies are unevenly distributed among countries and thus there is need for closer international cooperation.

Free bone grafting improves clinical outcomes in anterior shoulder instability with bone defect: a systematic review and meta-analysis of studies with a minimum of 1-year follow-up.

BACKGROUND: Evidence on the efficacy and safety of the free bone grafting in treating anterior shoulder instability is limited. The purpose of this study was to systematically evaluate the clinical and imaging results of free bone grafting in treating anterior shoulder instability with glenoid bone defect and to explore the incidence of complications in clinically relevant subgroups. METHODS: This systematic review was conducted per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The PubMed, Embase, and Cochrane Library databases were searched up to January 29, 2021, for studies that had reported on free bone grafting in treating anterior shoulder instability with glenoid bone defect with a minimum of 1-year follow-up. Two researchers independently screened studies and extracted data. A random-effects model was used to pool data on clinical function scores, imaging results, and incidence of complications (recurrent instability and non-instability-related complications). Meta-regression analysis was used to evaluate the incidence of complications in different subgroups and investigate the sources of heterogeneity. RESULTS: A total of 29 studies were included in the meta-analysis, comprising 840 patients (845 shoulders) with average ages ranging from 21 to 34.6 years. Compared with preoperatively, free bone grafting increased the postoperative Rowe score, American Shoulder and Elbow Surgeons score, Constant score, Subjective Shoulder Value, and Oxford Shoulder Instability Score by 53.16, 31.80, 20.81, 38.63, and 4.07 points, respectively, and reduced the visual analog scale pain score by 3 points on average. During the postoperative follow-up period, the rates of return to sport and return to preoperative levels were 84.2% and 73.1%, respectively. The imaging results showed that the free bone healing rate was 98.9% and the incidence of osteoarthritis was 10.9%. The incidence rates of recurrent instability and non-instability-related complications were 3.4% and 5.6%, respectively. Meta-regression analysis showed no evidence of effect modification by the year, follow-up time, proportion of male patients, autograft or allograft, and arthroscopy or open surgery on the incidence of complications. Subgroup analysis showed that the incidence rates of recurrent instability for open surgery, arthroscopy, allograft, autograft, Latarjet revision, and non-bone block revision were 4.1%, 2.3%, 1.5%, 4.4%, 10.3%, and 3.5%, respectively. CONCLUSION: The application of free bone grafting in treating anterior shoulder instability with glenoid bone defect can effectively improve shoulder joint function and is associated with a high return-to-sport rate and a low overall recurrence rate, but there were some differences in the complications of recurrent instability and non-instability-related complications among the subgroups. Given that these results need to be confirmed via head-to-head comparisons, we recommend that future clinical and biomechanical studies focus on comparing and investigating the advantages and disadvantages of different surgical approaches, thus providing a basis for orthopedic surgeons to make reliable choices.

Excellent outcomes with Oxford Uni-compartmental knee arthroplasty in anteromedial osteoarthritis patients (≤60 years) at mid-term follow-up.

BACKGROUND: The use of Oxford uni-compartmental knee arthroplasty (UKA) has rapidly increased worldwide,however,the relevance of younger patients for postoperative function after Oxford UKA remains unclear. The main purpose of our study is to clarify the effectivemess of Oxford UKA in the younger Chinese patients with anteromedial osteoarthritis (AMOA). METHODS: We retrospectively enrolled 252 consecutive patients who underwent Oxford UKA for AMOA with a minimum follow-up of 5 years between March 2013 and December 2016. The patients were divided into the younger (≤60 years) and elderly (> 60 years) age groups. The demographic data and surgery variables were recorded and compared. Patient satisfaction grade, range of motion (ROM), Oxford knee score (OKS), Hospital for Special Surgery (HSS) score, Western Ontario and McMaster (WOMAC) Universities Osteoarthritis Index score and postoperative complications were recorded. The 5-year survival of the implants were also compared with TKA revision as the endpoint. RESULTS: A total of 252 consecutive patients were recruited, including 96 aged 60 years or less and 156 aged over 60 years. The mean follow-up duration in the younger and elderly groups were 73.6 months (SD,standard deviation, 4.1) and 74.7 months (SD 6.2) respectively. Patient satisfaction rate was high in both groups (P = 0.805). Furthermore, no significant differences were observed in postoperative ROM(P = 0.299), OKS(P = 0.117), HSS(P = 0.357) and WOMAC scores(P = 0.151) between the younger and elderly groups (P>0.05). However, the incidence of joint stiffness (P = 0.033) and delayed wound dehiscence (P = 0.026) were significantly different between both groups. Five-year implant survival without revision were also similar in both groups (96.9% vs 97.4%, P = 0.871), and that for the entire cohort was 97.2% (95% CI 95.4-99.6). CONCLUSION: Oxford UKA for AMOA demonstrated favorable results in younger patients aged ≤60 years at a minimum 5-year follow-up in terms of patient satisfaction, functional outcomes, implant survival and postoperative complications. Therefore, younger patients might not be considered as an absolute contraindication to Oxford UKA.