Phytochemicals targeting matrix metalloproteinases regulating tissue degradation in inflammation and rheumatoid arthritis.
- 作者列表："Alamgeer","Hasan UH","Uttra AM","Qasim S","Ikram J","Saleem M","Niazi ZR
PURPOSE:Matrix metalloproteinases, zinc dependent proteolytic enzymes, have significant implications in extracellular matrix degradation associated with tissue damage in inflammation and Rheumatoid arthritis. Numerous orchestrated pathways affects instigation and blockade of metalloproteinases as well as various factors that increase the expression of MMPs including inflammatory cytokines, hormones and growth factors. Direct inhibition of these proteolytic enzymes or modulation of these pathways can provide protection against tissue destruction in inflammation and rheumatoid arthritis. Inclination towards use of plant derived phytochemicals to prevent tissue damage has been increasing day by day. Diversity of phytochemicals have been known to directly inhibit metalloproteinases. Hence, thorough knowledge of phytochemicals is very important in novel drug discovery. METHODS:Present communication evaluates various classes of phytochemicals, in effort to unveil the lead molecules as potential therapeutic agents, for prevention of MMPs mediated tissue damage in inflammation and rheumatoid arthritis. Data have been analyzed through different search engines. RESULTS:Numerous phytochemicals have been studied for their role as MMPs inhibitors which can be processed further to develop into useful drugs for the treatment of inflammation and rheumatoid arthritis. CONCLUSION:In search of new drugs, phytochemicals like flavonoids, glycosides, alkaloids, lignans & terpenes offer a wide canvas to develop into valuable forthcoming medicaments.
目的: 基质金属蛋白酶，锌依赖性蛋白水解酶，在与炎症和类风湿关节炎组织损伤相关的细胞外基质降解中具有重要意义。众多编排的途径影响金属蛋白酶的刺激和阻断，以及增加MMPs表达的各种因素，包括炎性细胞因子、激素和生长因子。直接抑制这些蛋白水解酶或调节这些途径可以在炎症和类风湿性关节炎中提供对组织破坏的保护。使用植物来源的植物化学物质来防止组织损伤的倾向日益增加。已知植物化学物质的多样性可直接抑制金属蛋白酶。因此，植物化学物质的彻底知识在新药发现中非常重要。 方法: 目前通讯评估了各种植物化学物质，努力揭示铅分子作为潜在的治疗药物，用于预防炎症和类风湿关节炎中MMPs介导的组织损伤。数据已经通过不同的搜索引擎进行了分析。 结果: 许多植物化学物质被研究为它们作为MMPs抑制剂的作用，它们可以被进一步加工以开发成用于治疗炎症和类风湿关节炎的有用药物。 结论: 在寻找新药时，黄酮类、苷类、生物碱、木脂素和萜烯等植物化学物质为开发有价值的即将上市的药物提供了广阔的前景。
METHODS:OBJECTIVE:Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality. METHODS:We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration). RESULTS:The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24). CONCLUSION:This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists.
METHODS:OBJECTIVE:We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS:Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS:We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION:In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
METHODS:OBJECTIVE:Reducing pain is one of the main health priorities for children and young people with juvenile idiopathic arthritis (JIA); however, some studies indicate that pain is not routinely assessed in this patient group. The aim of this study was to explore health care professionals' (HCPs) beliefs about the role of pain and the prioritization of its assessment in children and young people with JIA. METHODS:Semi-structured interviews were conducted with HCPs who manage children and young people with JIA in the UK (including consultant and trainee pediatric rheumatologists, nurses, physical therapists, and occupational therapists). Data were analyzed qualitatively following a framework analysis approach. RESULTS:Twenty-one HCPs participated. Analyses of the data identified 6 themes, including lack of training and low confidence in pain assessment, reluctance to engage in pain discussions, low prioritization of pain assessment, specific beliefs about the nature of pain in JIA, treatment of pain in JIA, and undervaluing pain reports. Assessment of pain symptoms was regarded as a low priority and some HCPs actively avoided conversations about pain. CONCLUSION:These findings indicate that the assessment of pain in children and young people with JIA may be limited by knowledge, skills, and attitudinal factors. HCPs' accounts of their beliefs about pain in JIA and their low prioritization of pain in clinical practice suggest that a shift in perceptions about pain management may be helpful for professionals managing children and young people with this condition.