Background: Osteoarthritis (OA) is the commonest form of inflammatory joint disease. Unfortunately, to date, there is no appropriate treatment for OA. Boswellia serrata was considered as a potent anti-inflammatory, anti-arthritic and analgesic agent that may be a drug for OA. Methods: In this meta-analysis, data from randomized controlled trials were obtained to assess the effects of Boswellia or its extract versus placebo or western medicine in patients with OA. The primary outcomes included visual analogue score (VAS), WOMAC pain, WOMAC stiffness, WOMAC function and lequesne index. Result: Seven trials involving 545 patients were included. Compared with the control group, Boswellia and its extract may relieve the pain [VAS: (WMD -8.33; 95% CI -11.19, − 5.46; P<0.00001); WOMAC pain: (WMD -14.22; 95% CI -22.34, − 6.09; P = 0. 0006)] and stiffness [WOMAC stiffness: (WMD -10.04; 95% CI -15.86, − 4.22; P = 0. 0007)], and improve the joint’s function [WOMAC function: (WMD -10.75; 95% CI -15.06, − 6.43; P<0. 00001); lequesne index: (WMD -2.27; 95% CI -3.08, − 1.45; P<0. 00001)]. Conclusion: Based on current evidence, Boswellia and its extract may be an effective and safe treatment option for patient with OA, and the recommended duration of treatment with Boswellia and its extract is at least 4 weeks.

Objective. To evaluate the efficacy and safety of mesenchymal stem cell (MSC) transplantation in the treatment of autoimmune diseases. Methods. The Chinese and English databases were searched for clinical research on the treatment of autoimmune diseases with mesenchymal stem cells. The search time range is from a self-built database to October 1, 2021. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted data, and evaluated the bias of the included studies. RevMan 5.3 analysis software was used for meta-analysis. Results. A total of 18 RCTs involving 5 autoimmune diseases were included. The 5 autoimmune disease were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease, ankylosing spondylitis, and multiple sclerosis. For RA, the current randomized controlled trials (RCTs) still believe that stem cell transplantation may reduce disease activity, improve the clinical symptoms (such as DAS28), and the percentage of CD4+CD 25+Foxp3+Tregs in the response group increased and the percentage of CD4+IL-17A+Th17 cells decreased. The total clinical effective rate of RA is 54%. For SLE, the results showed that mesenchymal stem cell transplantation may improve SLEDAI [-2.18 (-3.62, -0.75), ], urine protein [-0.93 (-1.04, -0.81), ], and complement C3 [0.31 (0.19, 0.42), ]. For inflammatory bowel disease, the results showed that mesenchymal stem cell transplantation may improve clinical efficacy [2.50 (1.07, 5.84), ]. For ankylosing spondylitis, MSC treatment for 6 months may increase the total effective rate; reduce erythrocyte sedimentation rate, intercellular adhesion molecules, and serum TNF-α; and improve pain and activity. For multiple sclerosis, the current research results are still controversial, so more RCTs are needed to amend or confirm the conclusions. No obvious adverse events of mesenchymal stem cell transplantation were found in all RCTs. Conclusion. MSCs have a certain effect on different autoimmune diseases, but more RCTs are needed to further modify or confirm the conclusion.

Aim. To explore the mechanism of resveratrol in reducing the soft tissue damage of osteoarthritis (OA) based on network pharmacology. Methods. Pharmmapper was used to predict the target of resveratrol, OMIM and Genecards were used to collect OA-related disease genes, and David ver 6.8 was used for enrichment analysis. Then, animal experiments were carried out for verification. The rat OA model was established and the rats were randomly divided into 4 groups: model group, resveratrol low-dose group, resveratrol high-dose group, and blank control group for follow-up experiments. Hematoxylin-eosin (HE) staining was used to detect the degree of pathological damage of rat bones and joints. Enzyme-linked immunosorbent assay (ELISA) was used for the content of inflammatory factors. Western blot was used to detect the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), nuclear factor kappa B protein (NF-κB), cysteine protease-9 (CASP-9), Bcl-2 protein, and Bax protein. Results. Through network pharmacological analysis, this study found that resveratrol may regulate the TLR4 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Osteoclast differentiation, Rheumatoid arthritis, etc. Animal experiments showed that compared with the model group, the pathological damage of bone and joint in the resveratrol low-dose and high-dose groups was significantly improved. Compared with the model group, the serum levels of IL-1beta, IL-6, IL-17, TNF-α, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced ( < 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced ( < 0.05); caspase-9 and Bax protein levels were significantly reduced ( < 0.05), and Bcl-2 was significantly increased ( < 0.05). Conclusion. Resveratrol may inhibit the activation of the TLR4-mediated NF-κB signaling pathway and has a repairing effect on soft tissue damage in OA.

Objective. To evaluate the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of osteoarthritis (OA). Methods. Chinese databases (such as CNKI and SinoMed) and English databases (such as PubMed and Embase) were searched to collect randomized controlled trials (RCTs) of MSCs in the treatment of OA. The retrieval time is from inception to October 10, 2021. The literature was strictly selected according to the inclusion and exclusion criteria, data was extracted, and the quality was evaluated. RevMan 5.3 software was used for meta-analysis. STATA was used to evaluate publication bias. The registration number of this systematic review and meta-analysis is CRD42021277145. Results. A total of 28 RCTs involving 1494 participants were included. The primary outcomes showed that MSCs may reduce WOMAC pain and VAS at the 3rd-month follow-up [WOMAC pain: -3.81 (-6.95, -0.68), . VAS: -1.11 (-1.53, -0.68), ], and the effect lasts for at least 12 months [WOMAC pain: -4.29 (-7.12, -1.47), . VAS: -1.77 (-2.43, -1.12), ]. MSCs may also reduce WOMAC stiffness and physical function at the 6th-month follow-up [WOMAC stiffness: -1.12 (-2.09, -0.14), . WOMAC physical function: -4.40 (-6.84, -1.96), ], and the effect lasts for at least 12 months [WOMAC stiffness: -0.99 (-1.95, -0.03), . WOMAC physical function: -3.26 (-5.91, -0.61), ]. The improvement of WOMAC pain, VAS, WOMAC stiffness, and WOMAC physical function may be clinically significant. Meanwhile, after the MSC injection, Lequesne had been reduced compared with the control group [-4.49 (-8.21, -0.77), ]. For adverse events, there is no significant difference in the safety of MSC injection and the control group [1.20 (0.97, 1.48), ]. The quality of WOMAC physical function and adverse events were moderate. Conclusion. Based on current evidence, MSCs may be a safety therapy that have a good curative effect in the treatment of OA, the onset time is no later than 3 months, and the time to maintain the curative effect is no less than 12 months. However, these results should be generalized with caution due to the generally low quality of evidence and RCTs.

BACKGROUND With the aging of the world's population, the incidence of osteoporosis (OP) has become a public health problem of worldwide concern. Research shows that icariin may have a therapeutic effect on OP. MATERIAL AND METHODS PharmMapper was utilized to predict the potential targets of icariin. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used for the collection of OP genes. The STRING database was utilized to obtain the protein-protein interaction (PPI) data. We used Cytoscape 3.7.2 to construct and analyze the networks. The genes and targets in the networks were input into the Database for Annotation, Visualization and Integrated Discovery (DAVID) to undergo Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the prediction results of this study. RESULTS A total of 297 icariin potential targets and 262 OP genes were obtained, and an icariin-OP PPI network was constructed and analyzed. The results of the GO enrichment analysis showed that icariin can regulate the steroid hormone-mediated signaling pathway, skeletal system development, extracellular space, cytosol, and steroid hormone receptor activity. The results of the pathway enrichment analysis showed that icariin can regulate osteoclast differentiation, FoxO, estrogen, and PPAR signaling pathways. The results of the experiments showed that icariin can increase estradiol, ß-catenin, and Receptor Activator of Nuclear Factor-к B Ligand (RANKL)/osteoprotegerin (OPG) ratio in postmenopausal OP rats (P<0.05). CONCLUSIONS This research found that the icariin can regulate OP-related biological processes, cell components, molecular functions, and signaling pathways.

Background. Osteoporosis is an important health problem worldwide. Liuwei Dihuang Decoction (LDD) and its main ingredients may have a good clinical effect on osteoporosis. Meanwhile, its mechanism for treating osteoporosis needs to be further revealed in order to provide a basis for future drug development. Methods. A systematic biological methodology was utilized to construct and analyze the LDD-osteoporosis network. After that, the human transcription data of LDD intervention in patients with osteoporosis and protein arrays data of LDD intervention in osteoporosis rats were collected. The human transcription data analysis, protein arrays data analysis, and molecular docking were performed to validate the findings of the prediction network (LDD-osteoporosis PPI network). Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. Results. (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and β-catenin mRNA expression ( ). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1. Conclusion. LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research.