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关键词： IL-37   inflammatory response   macrophages   NF-kappa B   omicron  

摘要： The expression levels of macrophage-associated cytokines are significantly greater in COVID-19 patients than in healthy individuals. Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection-induced pneumonia. Treatment with interleukin-37 (IL-37), an anti-inflammatory factor, has unique anti-inflammatory and antiviral effects on infections caused by various pathogens. In this study, we investigated the effect of IL-37 treatment on the SARS-CoV-2 Omicron-infection induced inflammatory response and its molecular mechanism. Our results demonstrated that IL-37 treatment effectively alleviated symptoms, reduced viral loads, suppressed the production of proinflammatory cytokines and chemokines both systemically (in serum) and locally (in the lungs), and attenuated lung lesions and inflammatory cell infiltration in Omicron-infected mice. The suppressed proinflammatory factors were macrophage-related, particularly CCL3 and CCL4, which were significantly inhibited. Furthermore, treatment with IL-37 significantly reduced the proportion of M1-type macrophages in lungs of Omicron-infected mice. In addition, we found that IL-37 targeted M1 macrophages through modulation of the NF-kappa B signaling pathway to suppress the production of proinflammtory factors during Omicron infection. This study elucidated the anti-inflammatory effect of IL-37 treatment on the Omicron-induced inflammatory response while identifying its specific target site, thereby providing fundamental insights for exploring potential clinical therapeutic interventions.

关键词： MCP-1   PTMCs   Rats   Testis   Chemokine   IL-1 signaling  

摘要： Mono-(2-ethylhexyl) phthalate (MEHP) is a metabolite of the diester parent compound Di(2-ethylhexyl) phthalate (DEHP), a widespread environmental toxicant known for its harmful effects on Sertoli cells and the subsequent loss of germ cells through apoptosis in postnatal animals. Peritubular myoid cells (PTMCs) produce various signaling factors, including the chemokine monocyte chemotactic protein 1 (MCP-1);however, the MEHP exposure-induced BTB disruption followed by MCP-1 secretion by PTMCs, the recruitment, and activation of macrophages as well as molecular mechanisms that initiate the secretion in the testis has yet to be closely examined. In this study, we demonstrate for the first time that PTMCs generate MCP-1 via the interleukin-1 signaling pathway upon MEHP exposure. Primary PTMCs isolated from the testis of peripubertal rats were cultured and exposed to 100 mu M and 200 mu M MEHP. Total RNA was used for bulk RNA sequencing, qRT-PCR, and protein lysates for proteomic analysis. Testis and their interstitial fluid (IF) were obtained from MEHP-exposed animals to evaluate the levels of pro-inflammatory cytokines and chemokines in IF through a multiplex assay and in tissue sections through immunofluorescence studies. The RNA sequencing data show significant enrichment of the interleukin-1 signaling pathway after MEHP (200 mu M) exposure for 48 hours. This finding is further supported by the qRT-PCR results for select genes associated with the IL-1 signaling pathway, highlighting the crucial role of this pathway in the response of PTMCs to MEHP exposure. In summary, MEHP exposure stimulates MCP-1 production by PTMCs, and mechanistically, the IL-1 signal transduction pathway governs this response. Keywords: MCP-1, PTMCs, Rats, Testis, Chemokine, IL-1 signaling

关键词： IL-17 A   Pulmonary tuberculosis   Polymorphism  

摘要： Objectives: The present study aimed to investigate the association between certain interleukin-17 A (IL-17 A) polymorphisms, specifically rs2275913 and rs8193036, and the susceptibility to pulmonary tuberculosis (PTB). Considering the function of IL-17 A in regulating immunological responses, especially regarding bacterial infections, we sought to determine if variations in the IL-17 A gene effect on PTB in the examined group. Methods: We performed a case-control study with 100 individuals who were confirmed to have PTB and 100 control subjects. Genotyping for the IL-17 A SNPs rs2275913 and rs8193036 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra-primer Amplification Refractory Mutation System (Tetra-ARMS PCR) methodologies. A statistical analysis encompassing odds ratios (OR) and 95 % confidence intervals (CI) was conducted to assess the association between the polymorphisms and the risk of PTB Results: Our data indicated a significant connection between the rs2275913 polymorphism and elevated susceptibility to PTB (OR = 1.69, 95 % CI: 1.09-2.61;p = 0.031). Also, a significant association between the rs8193036 polymorphism and increased susceptibility to PTB (OR = 2.18, 95 % CI: 1.46-3.27;p < 0.001). Conclusion: The IL-17 A polymorphisms rs2275913 and rs8193036 strongly correlate with increased susceptibility to PTB, according to this study. This suggests a potential genetic risk factor in the progression of the disease.

关键词： Fentanyl   Overdose deaths   COVID-19   Spatiotemporal analysis   Chicago  

摘要： Overdose deaths involving fentanyl represent a major public health crisis in the USA. This study investigates the spatiotemporal dynamics of fentanyl-involved deaths before, during, and after the COVID-19 pandemic and examines how sociodemographic factors influence these deaths across geographic regions. Using a retrospective ecological approach, we analyzed data on ZIP code-level fentanyl-related deaths in Cook County, IL, between 2018 and 2023, obtained from the Medical Examiner's Office and linked with sociodemographic data from the American Community Survey. We first mapped area-level death rates to assess their distribution and then conducted global and local clustering analyses to identify spatial autocorrelations and the locations of high- or low-death-rate areas. A geographically weighted Poisson regression (GWPR) model evaluated the associations between area-level fentanyl-related death rates and the area-level proportion of young adults, males, and individuals with at least a college degree, disability rate, and poverty rate. Spatial analyses found stronger spatial autocorrelations during (2020-2021) and after (2022-2023) the pandemic. Initially, high death rates were concentrated in the downtown area of Chicago, and they expanded to the surrounding areas during and after the pandemic. The GWPR model revealed that an increase in the area-level proportions of poverty, disability, and young adult residents increased the fentanyl-related death rates in most of the areas. Our findings highlight the urgent need to address the evolving dynamics of fentanyl-related overdoses through tailored public health interventions that account for the unique socioeconomic determinants of different regions. Importantly, a comprehensive approach to addressing differences in overdose death rates and their risk factors will be crucial to mitigating this public health crisis.

关键词： Real-world evidence   Remission   Observational studies/ registry   biological DMARD   Prognostic factors  

关键词： Cognitive Function and Mental Health   Registries   Telemedicine   digital health   and measuring health   Disease-modifying Drugs (DMARDs)  

关键词： HLA alleles   Immune system   Polymorphism   Genetic diversity   Ecuador   Distribution   Population  

摘要： The Major Histocompatibility Complex (MHC) comprises over 220 genes encoding proteins that are vital for the functioning of the immune system. These genes are divided into three classes: HLA class I, II, and III. The polymorphism of MHC genes serves to enhance the immune response by increasing the diversity of antigen presentation. In Ecuador, a country with a diverse population comprising numerous ethnic groups, it is crucial to comprehend the distribution of HLA alleles in order to facilitate several health approaches such as personalized medicine and organ transplantation. The present study employed data from Ecuador's National Institute of Organ, Tissue, and Cell Donation and Transplantation (INDOT) from 2017 to 2022. The data were analyzed to determine the distribution of HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, DRB3, DRB4, DQB1) alleles. A total of 1530 HLA alleles were identified among the 2352 patients included in the study. The highest variability was observed in Class I alleles, with HLA-A02 (32 %) and HLA-B35 (21 %) being the most common. In the case of class II, the most prevalent alleles were DRB104 and DQB103, with frequencies of 25.1 % and 48 %, respectively. It is notable that significant regional variations in allele frequencies were observed across Ecuador. The findings of this comprehensive study provide valuable insights into Ecuador's HLA allele distribution, contributing to genetic research, personalized medicine, and organ transplant matching. However, the results also highlight the need for further studies to better understand genetic diversity and improve public health strategies.

关键词： Biologics   periodontal diseases   periodontal therapy   psoriasis   skin diseases  

摘要： Aim To assess the adjunctive effect of periodontal therapy on psoriasis-related outcomes in a combined experimental model of ligature-induced periodontitis and Imiquimod (IMQ)-induced psoriasis. Also, this experiment aimed to study the impact of TNF-alpha inhibitors on the periodontium. Methods Fifty-six C57/BL6J mice were randomly allocated to seven experimental groups: (a) control group (P-Pso-) with no treatment;(b) periodontitis (P+Pso-) with periodontal therapy;(c) periodontitis (P+Pso-) with TNF-alpha inhibitor;(d) psoriasis (P-Pso+) with TNF-alpha inhibitor;(e) periodontitis and psoriasis (P+Pso+) with periodontal therapy;(f) P+Pso+ with TNF-alpha inhibitor;and (g) P+Pso+ with both periodontal therapy and TNF-alpha inhibitor. Samples (maxilla, dorsal skin and blood) were harvested immediately after death. Measures of periodontitis distance between the cemento-enamel junction and alveolar bone crest (CEJ-ABC) and number of osteoclasts and psoriasis (epidermal thickness and infiltrate cells (per 0.03mm2)) severity, as well as systemic inflammation (IL-6, IL-17A and TNF-alpha) were collected. Results In the P+Pso+ group, a significant adjunctive effect of periodontal therapy to TNF-alpha inhibitors was found in the reduction of epidermal thickening and inflammatory infiltrate of the dorsal skin (p < 0.05). Similarly, treatment with TNF-alpha inhibitor resulted in a significant adjunctive effect to periodontal therapy in the reduction of alveolar bone loss (p < 0.05). These changes were accompanied by a significant decrease in the circulating levels of IL-6 and IL-17A when both periodontal therapy and TNF-alpha inhibitor were administered. Conclusions The combination of periodontal therapy and TNF-alpha inhibitor showed a positive synergetic effect in the treatment of comorbid experimental ligature-induced periodontitis and IMQ-induced psoriasis via the reduction of systemic inflammation.

关键词： Imaging   Randomized controlled trial   Outcome measures   Disease-modifying Drugs (DMARDs)   Clinical Trial   Outcome measures   Disease-modifying Drugs (DMARDs)   Clinical Trial   Imaging   Randomized controlled trial  

关键词： biological DMARD   Disease-modifying Drugs (DMARDs)   Randomised controlled trial   Clinical Trial  

摘要： Background: Bimekizumab (BKZ) is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. Patients with psoriatic arthritis (PsA) who experience prior inadequate response or intolerance to tumour necrosis factor inhibitors (TNFi-IR) typically experience reduced efficacy with second-line biologic treatments when compared with biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients [1, 2]. Sustained and consistent efficacy and safety have been demonstrated up to 2 years in patients with active PsA who had prior TNFi-IR or were bDMARD-naïve [3]. Objectives: To assess long-term efficacy and safety of BKZ treatment up to 3 years in patients with active PsA who had prior TNFi-IR. Methods: In BE COMPLETE (NCT03896581), patients with PsA who had prior TNFi-IR were randomised 2:1 to subcutaneous BKZ 160 mg every 4 weeks (Q4W) or placebo (PBO). Patients completing Week 16 were eligible for entry into BE VITAL (open-label extension [OLE]; NCT04009499) for a period of up to 140 weeks. At Week 16, PBO patients entering BE VITAL switched to BKZ (PBO/BKZ). Efficacy and safety data reported here are from the BE COMPLETE/BE VITAL study. Efficacy outcomes are reported to Week 156 for patients in the BKZ Total group (PBO/BKZ patients and BKZ-randomised patients; providing a total duration of therapy of 140 or 156 weeks, respectively). Missing data were imputed using modified non-responder (mNRI; binary), multiple (MI; continuous) or worst-category (WCI; categorical) imputation. mNRI considered all visits following discontinuation due to adverse events or lack of efficacy as non-response; all other missing data were imputed with MI and the response derived from the imputed values. Safety data are reported to Week 156 for all randomised patients who received at least one dose of BKZ (BKZ-treated patients). All treatment-emergent adverse events (TEAEs) were classified using the Medical Dictionary for Regulatory Activities v19.0. Resul