金黄散外敷联合吲哚美辛治疗急性痛风性关节炎临床观察

摘 要 目的：观察金黄散外敷联合吲哚美辛治疗急性痛风性关节炎（AGA）的临床疗效和安全性。方法：58例初发AGA患者随机分为两组。对照组给予吲哚美辛治疗,观察组在对照组基础上外敷金黄散。两组疗程均为7 d。观察两组患者的临床疗效、关节症状改善和实验室指标恢复情况及药品不良反应。结果：观察组总有效率为93.10%,明显高于对照组的72.41%(P＜0.05)。总体疗效比较,观察组优于对照组（P＜0.01）。治疗后,两组患者的关节疼痛、肿胀和活动受限评分及红细胞沉降率(ESR)、白细胞计数（WBC）和血尿酸（BUA）水平均较治疗前下降(P＜0.01);且观察组患者症状评分及实验室指标水平均优于对照组(P＜0.05 和P＜0.01)。两组药品不良反应症状均较轻微,发生率差异无统计学意义（P＞0.05）。结论：金黄散外敷联合吲哚美辛治疗AGA能有效改善关节症状,降低血尿酸及炎症指标水平,疗效显著。     

NLRP3和TLR4调控的细胞焦亡在痛风性关节炎中的作用

细胞焦亡是一种强烈促炎性的程序性细胞死亡过程,由半胱氨酸蛋白酶-1(caspase-1)介导,NOD样受体蛋白3(NLRP3)炎症小体和Toll样受体蛋白4(TLR4)信号通路共同调控,其在痛风性关节炎发病过程中扮演了重要角色.本文对痛风性关节炎中细胞焦亡的调控机制进行系统阐述,为新药研究提供方向.     

泼尼松择时释放片的制备及其体内外评价

目的 制备泼尼松择时释放片,评价其体内外的释药.方法 采用水不溶性包衣材料,干法压制包衣制备泼尼松择时释放片,用HPLC法测定泼尼松体外释放度,LC-MS/MS测定Beagle犬随机交叉口服单剂量泼尼松择时释放片与泼尼松普通速释片后血浆中泼尼松的浓度,计算药动学参数.结果 所制泼尼松择时释放片的体外时滞时间为4～5h,时滞后药物可达到0.5h内释放大于85％的爆破型脉冲释药效果.受试制剂与参比制剂泼尼松在Beagle犬体内的AUC0-t分别为62.01±3.57、59.96 ±2.72 ng·mL-1 ·h;AUC0-∞分别为63.35±3.51、62.76±3.27ng·mL-1 ·h;t1/2分别为1.00±0.16、1.22±0.54 h;Tmax分别为4.67±0.26、0.97±0.30 h;Cmax分别为27.84±3.03、28.05±1.94 ng·mL-1;Tlag分别为3.83±0.26、0h.结论 犬体内外的结果均证明该制剂具有延迟释放特性,其设计方案可行.     

Nanoparticle-facilitated delivery of BAFF-R siRNA for B cell intervention and rheumatoid arthritis therapy

The present study was designed to explore the effects of B-cell activating factor receptor (BAFF-R) siRNA encapsulated nanoparticles on collagen-induced arthritis (CIA). BAFF-R siRNA encapsulated nanoparticles (NP-_siBAFF-R) were constructed using a double emulsion method and was characterized by dynamic light scattering and transmission electron microscopy. Cellular uptake of nanoparticles was determined using flow cytometry. The CIA mouse model was established and the mice were intravenously injected with nanoparticles. NP-_siBAFF-R effectively decreased the expression of BAFF-R in B cells and facilitated the delivery of siRNA into B cells. Treatment of NP_siBAFF-R ameliorated rheumatoid arthritis (RA) symptoms in the CIA mouse model via decreasing the arthritis score, mean ankle diameter, the levels of anti-collagen IgG in serum and increasing the expression of collagen type II and osteocalcin in dissected joint tissues. Additionally, treatment of NP_siBAFF-R decreased the percentage and number of B cells and inhibited the production of pro-inflammatory cytokines in RA mice. These results demonstrate that NP-_siBAFF-R may provide an effective strategy for RA treatment.     

MicroRNA and long noncoding RNA involvement in gout and prospects for treatment

MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are both types of noncoding RNA. They have been demonstrated to be involved in the regulation of various human inflammatory diseases and can be used as biomarkers for disease diagnosis and prognosis, and even be developed into new drugs. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Recent studies have shown that miRNAs and lncRNAs mediate the progress of gout. Based on the pathogenesis of gout, including hyperuricemia, MSU deposition, acute gouty arthritis and gouty bone erosion, this paper reviewed the role of miRNAs and lncRNAs in the processes and the possible therapeutic targets of miRNAs and lncRNAs in gout.     

A directly GP130-targeting small molecule ameliorates collagen-induced arthritis (CIA) by inhibiting IL-6/GP130 signalling and Th17 differentiation

Rheumatoid arthritis is a chronic inflammatory disease associated with joint inflammation and destruction driven by T helper 17 (Th17) cells. Interleukin-6 (IL-6) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT-28 can suppress IL-6 signalling through direct binding to glycoprotein-130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT-28 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT-28 on rheumatoid arthritis through the IL-6 signalling pathway. LMT-28 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen-induced arthritis (CIA) mice. In mice with CIA, LMT-28 markedly decreased serum levels of IL-6, TNF and IL-1β compared to vehicle control. Moreover, LMT-28 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT-28 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT-28 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper-IL-6 in human fibroblast-like synoviocytes (FLS). Collectively, these results suggest that LMT-28 can inhibit differentiated/activated-Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT-28 can attenuate rheumatoid arthritis by inhibiting differentiation/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL-6/solubleIL-6 receptor complex stimulated FLS.     

Association between IL1B polymorphisms and the risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory synovitis dominated systemic disease with unknown etiology. The purpose of this study was to determine the relationship between IL1B polymorphisms and RA risk in a Chinese Han population. Four single-nucleotide polymorphisms (SNPs) of IL1B, rs2853550, rs1143643, rs3136558 and rs16944 were genotyped in 508 RA cases and 494 healthy controls using the Agena MassARRAY method. A genetic model analysis was performed to evaluate the relationships between the variants and RA risk. Haplotype analysis was used to evaluate the potential relationship between the genetic block and RA risk. We determined that rs1143643 was linked to a reduced risk of RA based on the results of the co-dominant model (OR = 0.67, 95%CI: 0.50–0.89, p = 0.006) and the dominant model (OR = 0.73, 95%CI = 0.56–0.96, p = 0.025). On the other hand, rs16944 was associated with an increased risk of RA in the co-dominant model (OR = 1.71, 95%CI = 1.53–1.97, p = 0.029) and the recessive model (OR = 1.41, 95%CI = 1.05–1.88, p = 0.021). Among individuals older than 50 years, we observed that rs2853550 was associated with an increased risk of RA, and that rs1143643 decreased RA risk. Furthermore, rs1143643 was associated with a decreased RA risk in female patients. However, rs16944 increased RA risk in both the co-dominant and the additive models in different age subgroups. In addition, rs16944-GA increased RA risk in males in the co-dominance model and rs16944-AA increased RA risk in females in the additive model. These results suggested that rs2853550, rs1143643, and rs16944 in the IL1B gene are associated with RA risk.     

Cinnamaldehyde suppresses NLRP3 derived IL-1β via activating succinate/HIF-1 in rheumatoid arthritis rats

Cinnamaldehyde (CA) is an essential component of cinnamon (Cinnamomum cassia Presland), which is often used as a flavoring condiment in beverages, pastries, perfumes, etc. Cinnamon is also used as herbal medicine in China and Southeast Asia to treat rheumatoid arthritis. However, the molecular mechanism is unclear. In this study, we aim to investigate its anti-inflammatory effects against Rheumatoid arthritis (RA) using activated macrophages (Raw246.7) in vitro and adjuvant arthritis rats (AA) in vivo. The results demonstrated that CA significantly reduced synovial inflammation in AA rats, possibly due to suppression of the expressions of pro-inflammatory cytokines, especially the IL-1β. Further investigation found that CA also suppressed the activity of HIF-1α by inhibiting the accumulation of succinate in cytoplasm. As we know, the reduction of HIF-1α nucleation slows down IL-1β production, because HIF-1α activates the expression of NLRP3, which is involved in the assembly of inflammasome and processing of IL-1β. In addition, CA also inhibited the expression of the succinate receptor GPR91, which in turn inhibited the activation of HIF-1α. In conclusions, our results suggested that CA might be a potential therapeutic compound to relieve rheumatoid arthritis progress by suppressing IL-1β through modulating succinate/HIF-1α axis and inhibition of NLRP3.     

Altered expression of microRNAs may predict therapeutic response in rheumatoid arthritis patients

BackgroundEpigenetic alternations of microRNAs (miRNAs) can contribute to the pathogenesis and progression of rheumatoid arthritis (RA). This study aimed to measure the expression level of peripheral blood miRNAs, as well as their target mRNAs, in RA patients and healthy controls (HCs), and to evaluate the potential of miRNAs as promising non-invasive biomarkers of treatment response.MethodsThe peripheral expression of miRNAs, including miR-146a, miR-146b, miR-150, miR-155, miR-125a-5p, miR-223, miR-26a, and miR-21, as well as their target mRNAs, was analyzed in 90 RA patients and 30 HCs via quantitative real-time polymerase chain reaction (RT-PCR) assay. We compared differences between the patients in terms of good response (GR; n = 55) and poor response (PR; n = 35) to the conventional therapeutic approach.ResultsAll miRNAs were significantly overexpressed in RA patients. The expression of miR-155, miR-150, miR-146a, miR-146b, miR-125a-5p, and miR-223 increased in both groups of RA patients, compared to HCs, and miR-26a and miR-21 were the only upregulated miRNAs in the GR group versus HCs. Among the upregulated miRNAs, miR-125a-5p expression significantly changed in GR and PR patients (P = 0.047). The ROC curve analysis indicated the potential involvement of miR-125a-5p in the pathogenesis of RA. We also observed the downregulated expression of GATA3, RORC, FOXP3, TBX21, STAT1, and TRAF6 in RA patients versus HCs.ConclusionOur findings indicated that different expression levels of miR-125a-5p in the GR and PR groups of patients may serve as a therapeutic response biomarker, which can be also used as a target for therapeutic interventions.