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

ObjectiveTo explore the efficacy and safety of Iguratimod intervention in Primary Sjogren’s syndrome (pSS).MethodsMany 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.ResultsTwenty-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.ConclusionBased 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 Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42020220770

Urotensin II promotes the proliferation and secretion of vascular endothelial growth factor in rat dermal papilla cells by activating the Wnt-β-catenin signaling pathway

Introduction. Urotensin II (U II) is a kind of active peptide with a variety of biological effects, such as promoting cell proliferation and endocrine effects. The aim of this study is to investigate the effect of urotensin II on the proliferation and secretion of vascular endothelial growth factor (VEGF) in cultured rat dermal papilla cells (DPCs), and to explore its molecular mechanism. Materials and Methods. We used the DPCs isolated from the thoracic aortas of Wistar-Kyoto rats to run the CCK8 and ELISA assay, RC-PCR and Western blotting techniques to identify the effect of Urotensin II on the proliferation and secretion of VEGF in DPCs, data were analyzed by one-way ANOVA or t-test. Results. U II can increase the mRNA expression of proliferation markers Ki67 and PCNA. In addition, the Wnt/β-catenin pathway was activated by U II, but Wnt inhibitor DKK1 reversed the effect of U II. Conclusions. U II promoted the proliferation and secretion of VEGF in rat DPCs through activation of the Wnt-β-catenin signaling pathway

Research progress on the clinical application and mechanism of iguratimod in the treatment of autoimmune diseases and rheumatic diseases

Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future

Efficacy of RADA16-Based Self-Assembling Peptides on Wound Healing: A Meta-Analysis of Preclinical Animal Studies

Objectives: This analysis aims to provide evidence supporting the feasibility of clinical application of self-assembling peptides for skin wound healing. Methods: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, and Cochrane Library were searched (up to June 17, 2024). The primary outcome, wound closure rate at 7 and 14 days post-injury, was pooled using a random-effects meta-analysis. The risk of bias (ROB) assessment and meta-analysis were performed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE)’s ROB tool for animal studies and RevMan software. Results: A total of 502 unique records were identified from our search, with 12 experimental animal studies meeting the prespecified inclusion criteria (n = 272 animals). The RADA16 interventions promoted wound closure rate compared to controls (saline or no treatment group) in both diabetic and non-diabetic animal models (Mean Difference (MD) = 11.25, 95% Confidence Interval (CI): 5.73 to 16.78, p < 0.0001; MD = 9.48, 95% CI: 4.75 to 14.22, p < 0.0001 at 7 and 14 days post-injury, respectively). Healing was further enhanced using RADA16-based functional self-assembling peptides compared to RADA16 group in both diabetic and non-diabetic animal models (MD = 27.25, 95% CI: 22.68 to 31.83, p < 0.00001; MD = 29.11, 95% CI: 24.30 to 33.91, p < 0.00001 at 7 and 14 days after injury, respectively). The ROB was uncertain for most studies due to insufficient reporting. Conclusions: RADA16-based self-assembling peptides, particularly those modified with functional peptide motifs, represent a promising treatment for non-diabetic and diabetic wounds in pre-clinical studies, and translation to the clinical domain appears warranted

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.</jats:p

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.</jats:p