Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics.

To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-ß signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

The Effectiveness and Safety of Mesenchymal Stem Cells in the Treatment of Osteoarthritis: A Systematic Review and Meta-analysis of 28 Randomized Controlled Trials.

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), P = 0.02. VAS: -1.11 (-1.53, -0.68), P < 0.00001], and the effect lasts for at least 12 months [WOMAC pain: -4.29 (-7.12, -1.47), P = 0.003. VAS: -1.77 (-2.43, -1.12), P < 0.00001]. MSCs may also reduce WOMAC stiffness and physical function at the 6th-month follow-up [WOMAC stiffness: -1.12 (-2.09, -0.14), P = 0.03. WOMAC physical function: -4.40 (-6.84, -1.96), P = 0.0004], and the effect lasts for at least 12 months [WOMAC stiffness: -0.99 (-1.95, -0.03), P = 0.04. WOMAC physical function: -3.26 (-5.91, -0.61), P = 0.02]. 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), P = 0.002]. For adverse events, there is no significant difference in the safety of MSC injection and the control group [1.20 (0.97, 1.48), P = 0.09]. 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.

Research on the Mechanism of Liuwei Dihuang Decoction for Osteoporosis Based on Systematic Biological Strategies.

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 ß-catenin mRNA expression (P < 0.05). (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.

A Systematic Review and Meta-Analysis of 19 Randomized Controlled Trials of Iguratimod Combined With Other Therapies for Sjogren's Syndrome.

Objective: To explore the efficacy and safety of Iguratimod intervention in Primary Sjogren's syndrome (pSS). Methods: Many databases were searched to collect the RCTs. Three independent reviewers extracted data and assessed the quality of the studies based on the Cochrane Handbook. The statistical analysis was done by RevMan 5.3 and STATA. The quality of evidence was evaluated by GRADE tool. Results: Twenty-nine RCTs with 2258 participants were included in this review. The meta-analysis shows that: iguratimod experiment group can reduce the ESSPRI score (WMD -1.93 [-2.33, -1.52], P<0.00001), ESSDAI score (WMD -1.39 [-1.81, -0.98], P<0.00001), Schirmer's test (WMD 1.77 [0.85, 2.70], P=0.0002), RF (WMD -5.78 [-7.59, -3.97], P<0.00001), and decrease the ESR level (WMD -7.05 [-9.84, -4.26], P<0.00001). Meanwhile, the summary result showed the addiction of Iguratimod may not increase the adverse events. The adverse events were mainly gastrointestinal discomfort, abnormal liver function, and rash and itching. The quality of evidence of adverse events was moderate. Referring to minimal clinically important difference (MCID), the improvement of ESSPRI is clinically significant, and the improvement of ESSDAI for patients older than 60 years old may be clinically significant. Conclusion: Based on current evidence, iguratimod can effectively reduce ESSPRI score, ESSDAI score, Schirmer's test score and decrease systemic inflammatory response (such as ESR level and RF level) without increasing the probability of adverse events. The recommended course of treatment is at least 12 weeks. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220770.

Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials.

Objective: To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Methods: Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software. Results: A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet 's disease (BD) involves one RCT, Crohn 's disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ' s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs. Conclusion: Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.

Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

Background: Modern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis. Methods: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis. Results: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA. Conclusion: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.

Efficacy and Safety of Mesenchymal Stem Cell Transplantation in the Treatment of Autoimmune Diseases (Rheumatoid Arthritis, Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Multiple Sclerosis, and Ankylosing Spondylitis): A Systematic Review and Meta-Analysis of Randomized Controlled Trial.

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), P = 0.003], urine protein [-0.93 (-1.04, -0.81), P < 0.00001], and complement C3 [0.31 (0.19, 0.42), P < 0.00001]. For inflammatory bowel disease, the results showed that mesenchymal stem cell transplantation may improve clinical efficacy [2.50 (1.07, 5.84), P = 0.03]. 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.

The Effectiveness and Safety of Probiotic Supplements for Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Preclinical Trials.

BACKGROUND: Patients with psoriasis need long-term medication to control their condition. Recent studies suggest that changing the intestinal flora may be a potential treatment. METHODS: The databases were utilized to search the randomized controlled trials (RCTs) and preclinical trials about probiotic supplement in the treatment of psoriasis. The retrieval time is from the establishment of these databases to December 2020. RevMan5.3 was used for the risk assessment of bias and meta-analysis. This systematic review was registered in PROSPERO (CRD42021232756). RESULTS: A total of 3 RCTs involving 164 participants were included. Two RCTs showed that probiotics can improve PASI and thereby improve the condition. For inflammation-related indicators, only one RCT showed that probiotics can improve the levels of CRP and TNF-α but have no obvious improvement effect on IL6. One RCT demonstrated the total effective rate of probiotics in the treatment of psoriasis. For adverse events, one RCT showed that the incidence of adverse events of probiotic treatment was low. Preclinical studies showed that continuous intervention with oral probiotics can significantly improve the progression of psoriasis and reduce the expression of inflammatory factors. The meta-analysis showed that the PASI between two groups was of no statistical significance (SMD 1.83 [-0.41, 4.07], P = 0.11). Meanwhile, probiotics may improve skin thickness (SMD -5.87 [-11.34, -0.41], P = 0.04) in animal model. CONCLUSION: Prebiotics may have a positive effect on alleviating the clinical symptoms of psoriasis, but a large sample of RCTs is still needed to support its therapeutic effect in psoriasis.

The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To explore the efficacy of antioxidative stress therapy on oxidative stress levels in rheumatoid arthritis (RA) by a systematic review and meta-analysis of randomized controlled trials. METHODS: Chinese and English databases such as PubMed, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature were searched, mainly searching for clinical randomized controlled trials of antioxidant therapy for rheumatoid arthritis. The search time is from the establishment of the database to July 2021. Two researchers independently carried out literature search, screening, and data extraction. The bias risk tool provided by the Cochrane Collaboration was used to evaluate the bias risk of all the included literature, and the RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 24 RCTs (28 records) and 1277 participants were included. The time span of randomized controlled trials (RCTs) is from 1986 to 2020. These RCTs involve 14 types of antioxidants or antioxidant therapies, and these therapies have varying degrees of improvement on oxidative stress in RA patients. The summary results showed that the MDA in the experiment group is lower (SMD -0.82, 95% CI -1.35 to -0.28, P = 0.003). The difference of TAC, SOD, NO, GPx, CAT, and GSH between two groups was of no statistical significance (TAC (SMD 0.27, 95% CI -0.21 to 0.75, P = 0.27), SOD (SMD 0.12, 95% CI -0.16 to 0.40, P = 0.41), NO (SMD -2.03, 95% CI -4.22 to 0.16, P = 0.07), GPx (SMD 0.24, 95% CI -0.07 to 0.54, P = 0.13), CAT (SMD 2.95, 95% CI -2.6 to 8.51, P = 0.30), and GSH (SMD 2.46, 95% CI -0.06 to 4.98, P = 0.06)). For adverse events, the summary results showed that the difference was of no statistical significance (RR 1.16, 95% CI 0.79 to 1.71, P = 0.45). In addition, antioxidant therapy has also shown improvement in clinical efficacy indexes (number of tender joints, number of swollen joints, DAS28, VAS, and HAQ) and inflammation indexes (ESR, CRP, TNF-α, and IL6) for RA patients. CONCLUSION: The existing evidence shows potential benefits, mainly in reducing MDA and increasing TAC and GSH in some subgroups. However, more large samples and higher quality RCTs are needed to provide high-quality evidence, so as to provide more clinical reference information for the antioxidant treatment of RA.

Exploring the Mechanism of Resveratrol in Reducing the Soft Tissue Damage of Osteoarthritis Based on Network Pharmacology and Experimental Pharmacology.

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 (P < 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced (P < 0.05); caspase-9 and Bax protein levels were significantly reduced (P < 0.05), and Bcl-2 was significantly increased (P < 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.

The Improving Effect and Safety of Probiotic Supplements on Patients with Osteoporosis and Osteopenia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials.

AIM: Probiotics are considered to be bone metabolism regulators, and their efficacy as an adjuvant treatment option for osteoporosis is still controversial. The purpose of this study is to compare the available data from randomized controlled trials (RCT) of probiotics in the treatment of osteoporosis and osteopenia. METHODS: As of June 2021, databases such as Medline, Embase, Web of Science, and Central Cochrane Library have been used for English-language literature searches and CNKI and China Biomedical Database have been used for Chinese-language literature searches. RevMan 5.3 was used for bias risk assessment, heterogeneity detection, and meta-analysis. This research has been registered in PROSPERO (CRD42020085934). RESULTS: This systematic review and meta-analysis included 10 RCTs involving 1156. Compared with the placebo, the absolute value of lumbar spine's BMD was not statistically significant (WMD 0.04 (-0.00, 0.09), P=0.07, random effect model), while the percentage of lumbar spine's BMD was higher (SMD 1.16 (0.21, 2.12), P=0.02, random effect model). Compared with the control group, the percentage of total hip's BMD was not statistically significant (SMD 0.52 (-0.69, 1.73), P=0.40, random effect model). The safety analysis showed that, compared with control group, the adverse events in the experimental group were not statistically significant (RR 1.02 (0.92, 1.12), P=0.70, fixed effect model). CONCLUSION: Probiotics may be safety supplements to improve the lumbar spine's BMD of patients with osteoporosis and osteopenia. More large-sample, random-controlled, high-quality RCTs are needed to further verify the effectiveness and safety of probiotics in intervening osteoporosis or osteopenia.

The efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of Curcuma longa extract and curcumin supplements on osteoarthritis (OA). METHODS: The databases such as Pubmed and Cochrane Library were searched to collect the article about Curcuma longa extract and curcumin in the treatment of OA. Then, randomized controlled trials (RCTs) were selected and their data were extracted. Finally, the RevMan5.3 was utilized for risk of bias assessment and meta-analysis, the STATA15.0 were utilized for publication bias assessment, and GRADE tool were used for the evidence quality assessment of primary outcomes. RESULTS: A total of 15 RCTs involving 1621 participants were included. (1) Compared with placebo, Curcuma longa extract and curcumin (C.) can decrease the visual analog scale (VAS) and The Western Ontario and McMaster Universities (WOMAC) score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, Curcuma longa extract and curcumin are comparable with those of placebo. (2) Compared with non-steroidal anti-inflammatory drugs (NSAIDs), Curcuma longa extract and curcumin have similar effects on joint pain, function and stiffness. The incidence of adverse events in Curcuma longa extract and curcumin was lower. (3) Compared with the NSAIDs group, C.+NSAIDs can also decrease the VAS and WOMAC score-pain, the WOMAC score-function and the WOMAC score-stiffness. In terms of adverse events, the addition of Curcuma longa extract and curcumin to NSAIDs did not increase adverse events. CONCLUSION: Curcuma longa extract and curcumin may be a safer and effective supplement for OA patients. It is recommended to use Curcuma longa extract and curcumin supplement for OA patients for more than 12 weeks.

The Effect and Safety of Iguratimod Combined With Methotrexate on Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Based on a Randomized Controlled Trial.

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with inflammatory synovitis. Iguratimod (IGU) combined with methotrexate (MTX) therapy may have better efficacy and safety. Methods: First, we searched randomized controlled trials (RCTs) of IGU + MTX in the treatment of RA through literature databases (such as PubMed, Corkland Library, CNKI, etc.) and then conducted RCT quality assessment and data extraction. Finally, we used RevMan 5.3 for meta-analysis, STATA 15.0 for publication bias assessment, and GRADE tool for the evidence quality assessment of primary outcomes. This systematic review and meta-analysis were registered in PROSPERO (CRD42021220780). Results: This systematic review and meta-analysis included 31 RCTs involving 2,776 patients. Compared with MTX alone, the ACR20, ACR50, and ACR70 of IGU + MTX are higher, while DAS28 is lower [ACR20: (RR 1.55, 95% CI 1.14-2.13, p = 0.006); ACR50: (RR 2.04, 95% CI 1.57-2.65, p < 0.00001); ACR70: (RR 2.19, 95% CI 1.44-3.34, p = 0.00003); DAS28: (weighted mean difference (WMD) -1.65, 95% CI -2.39 to -0.91, p < 0.0001)]. Compared with MTX + leflunomide, IGU + MTX has no significant difference in improving ACR20, ACR50, ACR70, but IGU + MTX improves DAS28 more significantly [ACR20: (RR 1.09, 95% CI 0.79-1.89, p = 0.59); ACR50: (RR 1.07, 95% CI 0.64-1.78, p = 0.81); ACR70: (RR 1.17, 95% CI 0.44-3.10, p = 0.76); DAS28: (WMD -0.40, 95% CI -0.42 to -0.38, p < 0.0001)]. Compared with the MTX + tripterygium subgroup and MTX-only subgroup, the incidence of adverse events of the IGU + MTX group is of no statistical significance [MTX only: (RR 0.99, 95% CI 0.87-1.13, p = 0.90); MTX + Tripterygium: (RR 0.73, 95% CI 0.29-1.85, p = 0.50)]. However, compared with MTX + leflunomide, the incidence of adverse events in the IGU + MTX group was lower (RR 0.74, 95% CI 0.62-0.88, p = 0.0009). The quality of ACR70 was high; the quality of adverse events and ACR50 test was moderate. Conclusion: Compared with conventional therapy, IGU + MTX may be a safer and more effective therapy for RA patients. When the intervention method is (IGU 25 mg Bid, MTX 10-25 mg once a week), and the intervention lasts for at least 12 weeks, the curative effect may be achieved without obvious adverse events.

Exploring the Mechanism of Icariin in Osteoporosis Based on a Network Pharmacology Strategy.

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.

Effectiveness of Boswellia and Boswellia extract for osteoarthritis patients: a systematic review and meta-analysis.

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.