Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results.     

The Extraction Solvent Influences the Anti-Inflammatory Effects of Jakyakgamcho-Tang in Lipopolysaccharide-Stimulated Macrophages and Mice with Gouty Arthritis

Jakyakgamcho-Tang (JGT) is a traditional medicine used to treat muscular tension, spasm, and pain. Several studies have reported its clinical use as an anti-inflammatory and in gynaecological treatment. This study aimed to compare the anti-inflammatory effects of JGT according to extraction solvent, water (JGTW) and 30% EtOH (JGTE) on lipopolysaccharide (LPS)—stimulated macrophages and in mice with monosodium urate (MSU)—induced gouty arthritis. We evaluated the production of inflammatory mediators and cytokines and the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. We also examined oedema, pain, and inflammation in MSU-induced mice by measuring affected hind paw swelling, weight-bearing, pro-inflammatory cytokines levels, and myeloperoxidase (MPO) activity. In LPS-stimulated RAW264.7 cells, JGTW and JGTE significantly decreased prostaglandin (PG) E2(PGE2) production via suppressing COX-2 expression and cytokines interleukin-1β and interleukin-6. Only JGTE reduced the production of NO and cytokines and the mRNA levels of iNOS and cytokines. In MSU-induced mice, JGTE and JGTW efficiently decreased paw swelling and attenuated joint pain. JGTE (200 and 300 mg/kg) effectively suppressed inflammation by downregulating pro-inflammatory cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) and MPO activity, which were only slightly reduced by JGTW. Our data demonstrate the anti-inflammatory activity of JGT in macrophage and gouty arthritis animal models and show that JGTE is more effective than JGTW at lower concentrations.     

Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation,in vitro and in vivo evaluation

Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.     

A Variant in the Osteoprotegerin Gene Is Associated with Coronary Atherosclerosis in Patients with Rheumatoid Arthritis: Results from a Candidate Gene Study

Objective: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, but there is limited information about the genetic contribution to atherosclerosis in this population. Therefore, we examined the association between selected genetic polymorphisms and coronary atherosclerosis in patients with RA. Methods: Genotypes for single-nucleotide polymorphisms (SNPs) in 152 candidate genes linked with autoimmune or cardiovascular risk were measured in 140 patients with RA. The association between the presence of coronary artery calcium (CAC) and SNP allele frequency was assessed by logistic regression with adjustment for age, sex, and race. To adjust for multiple comparisons, a false discovery rate (FDR) threshold was set at 20%. Results: Patients with RA were 54 ± 11 years old and predominantly Caucasian (89%) and female (69%). CAC was present in 70 patients (50%). A variant in rs2073618 that encodes an Asn3Lys missense substitution in the osteoprotegerin gene (OPG, TNFRSF11B) was significantly associated with the presence of CAC (OR = 4.09, p < 0.00026) and withstands FDR correction. Conclusion: Our results suggest that a polymorphism of the TNFRSF11B gene, which encodes osteoprotegerin, is associated with the presence of coronary atherosclerosis in patients with RA. Replication of this finding in independent validation cohorts will be of interest.     

Dendritic Nanotheranostic for the Delivery of Infliximab: A Potential Carrier in Rheumatoid Arthritis Therapy

Antibodies are macromolecules that specifically recognize their target, making them good candidates to be employed in various therapies. The possibility of attaching a drug to an immunoglobulin makes it possible to release it specifically into the affected tissue as long as it overexpresses the target. However, chemical coupling could affect the functionality (specificity and affinity) of the antibody. It has been observed that the use of intermediaries, such as dendrimers, could resolve this issue. Because carbosilane dendrimers have aroused great interest in the field of biomedicine, this report describes the synthesis of an anionic carbosilane dendrimer with a fluorochrome on its surface that then forms a conjugate with an antibody. It has been used as immunoglobulin and infliximab, whose target is TNF-α, which is a cytokine that is overexpressed in the inflamed area or even in the blood of patients with autoimmune diseases, such as rheumatoid arthritis. In addition, the integrity and functionality of the antibody has been studied to see if they have been affected after the chemical coupling process.     

E26 Transformation-Specific-1 (ETS1) and WDFY Family Member 4 (WDFY4) Polymorphisms in Chinese Patients with Rheumatoid Arthritis

E26 transformation-specific-1 (ETS1) and WDFY family member 4 (WDFY4) are closely related with systemic lupus erythematosus. We hypothesized that ETS1 and WDFY4 polymorphisms may contribute to rheumatoid arthritis (RA) susceptibility. We studied ETS1 rs1128334 G/A and WDFY4 rs7097397 A/G gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. When the WDFY4 rs7097397 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly increased risk for RA. In the dominant model, when the WDFY4 rs7097397 AA homozygote genotype was used as the reference group, the AG/GG genotypes were associated with a significant increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the WDFY4 rs7097397 AG genotype was evident among female patients, younger patients, C-reactive protein (CRP) negative patients and both anti-cyclic citrullinated peptide antibody (ACPA) positive patients and negative patients compared with the WDFY4 rs7097397 AA genotype. These findings suggested that WDFY4 rs7097397 A/G may be associated with the risk of RA, especially among younger, female patients, CRP-negative patients and both ACPA positive and negative patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. To confirm these findings, validation by a larger study from a more diverse ethnic population is needed.     

类风湿关节炎下转运体表达及活性的变化

机体发生炎症时会释放大量的炎性细胞因子,并伴随药物转运体表达和活性的改变。转运体的表达和活性改变时,会影响药物的吸收、分布、消除,机体内血药浓度、蓄积情况、药物的治疗有效性等也会发生改变,甚至产生多药耐药、药物-药物相互作用等现象。类风湿关节炎是一种常见的炎症疾病,会释放大量的炎性细胞因子,伴随转运体表达和活性的改变,从而影响治疗效果,因此研究炎症状态下药物转运体表达和活性的改变至关重要。本文就类风湿关节炎下转运体的变化进行综述,以期为类风湿关节炎的治疗提供新的方向。     

Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib

Objective: The present study discusses folic acid-etoricoxib-bovine serum albumin nanoparticles (F-ETX-NPs) using folic acid as an over expressed folate receptor ligand for activated macrophages in targeting of rheumatoid arthritis.

Materials and methods: For this purpose etoricoxib-loaded BSA nanoparticles (ETX-NPs) were prepared by desolvation method and activated folic acid conjugation with free amine group of BSA was confirmed by FTIR study and zeta potential measurements.

Results: The F-ETX-NPs showed spherical in shape with 215.8?±?3.2?nm average size?+?7.8?mV zeta potential, 72?±?1.3% etoricoxib entrapment efficiency and showed 93.1?±?2.2% cumulative etoricoxib release upto 72?h. The etoricoxib concentration from F-ETX-NPs was found to be 9.67?±?0.34?µg/g in inflamed joint after 24?h administration revealed remarkably targeting potential to the activated macrophages cells and keep at a high level during the experiment.

Discussion and conclusion: These results suggest that F-ETX-NPs are potentially vector for activated macrophages cells targeting of rheumatoid arthritis.     

抗环瓜氨酸肽抗体阳性银屑病关节炎伴肺间质病变1例

银屑病关节炎是一种与银屑病相关的关节炎，属脊柱关节炎范畴，兼具或先后出现银屑病皮疹和关节及周围软组织疼痛、肿胀等表现。抗CC抗体是类风湿关节炎诊断及预后判断的重要指标，PsA中也有阳性报道。风湿病相关肺间质病变常见于系统性硬化症、干燥综合征、皮肌炎/肌炎、类风湿关节炎等，PsA相关肺间质病变报道少见。本文收录1例PsA患者，抗CCP抗体阳性，同时伴弥漫性肺间质病变，文献少有报道。