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关键词： AS   tumour necrosis factor inhibitors   cancer   recurrence   risk  

摘要： Objective To investigate the effect of tumour necrosis factor inhibitors (TNFi) on the risk of cancer recurrence in patients with AS and a history of *** We conducted a nested case-control study using a cohort derived from a nationwide database. The cohort consisted of patients with AS and a history of cancer after AS diagnosis. We determined cases of cancer recurrence and selected controls at a ratio of 1:1, matched for age, sex, date of index cancer diagnosis and follow-up time. Multivariable conditional logistic regression analysis was used to assess the effect of TNFi exposure on the risk of cancer *** A total of 2574 patients with AS and a history of cancer were included in the cohort. Among these, cancer recurred in 394 (15.3%) patients. The incidence rate of cancer recurrence was 4.87 (95% CI 4.40-5.34)/100 person-years. From this cohort, 254 cases and age-, sex-, index date- and follow-up time-matched 254 controls were included for the nested case-control study. The proportion of patients exposed to TNFi did not differ between the cases and controls (24.8% vs 24.4%, P = 0.918). In the multivariable conditional logistic regression analysis, TNFi exposure was not associated with an increased risk of cancer recurrence (adjusted odds ratio 1.157, 95% CI 0.734-1.825, P = 0.531).Conclusion TNFi exposure was not associated with an increased risk of cancer recurrence in patients with AS. Our findings suggest that TNFi may be used with caution in patients with AS and a history of cancer.

摘要： Encephalitis, an inflammatory disorder of the brain caused by infections or autoimmune responses, is still a major global health concern due to its high morbidity, mortality, and long-term neurological consequences. The available therapy alternatives are usually confined, and conventional drug discovery procedures are both resource-intensive and time-consuming. These challenges underscore the critical need for novel tools to speed up therapy development, which could revolutionize treatment regimens and enhance results for impacted people globally. To identify, optimize & selection of TNF-α inhibitors as anti-encephalitis candidates by using in silico assisted drug design approach. Computer-aided drug design (CADD) is a revolutionize tool for identifying potential anti-encephalitis candidates through its ability to simulate molecular interactions, predict drug-target affinities, and optimize pharmacokinetic properties with molecular dynamics simulation. In this study, we have employed comprehensive in silico method to find effective therapeutic compounds that targets the TNF-α receptor in encephalitis. An in silico screening of nearly 600 isatin derivatives were conducted by using data from the PubChem database. It was carried out using the Lipinski rule of five in addition to other criteria. After filtering, 48 Isatin derivatives were selected, and six compounds with binding affinities exceeding −8.0 kcal/mol were identified as potential candidates. Additionally it was subjected to ADME analysis using Swiss ADME software. Every contender demonstrated greater binding affinity and actively crossed the BBB. Protein–ligand complexes were subjected to molecular dynamics (MD) simulations using CABS-flexV2.0 and the iMOD server in order to assess the root-mean-square fluctuations (RMSFs) and quantify protein stability respectively. Hence, it is concluded that compounds with higher binding affinity and actively cross BBB values showed effective anti-encephalitis ag

关键词： antibody-mediated rejection   mean fluorescence intensity   non-donor-specific antibodies   pediatric kidney transplantation   viral infections  

摘要： While the pathogenic role of donor-specific anti-HLA antibodies (DSAs) in long-term immune-mediated injury after kidney transplantation is well established, the clinical relevance of non-donor-specific antibodies (nDSAs), also detected in transplant recipients, remains a subject of debate. This retrospective study evaluated the prognostic value of nDSAs in 92 pediatric kidney transplant recipients (89.1%, 9.8%, and 1.1% for first, second, and third transplants, respectively) at the University Hospital of Padua between January 2015 and December 2022, investigating the association between antibody development and clinical outcomes, including graft function, rejection episodes, and viral infections. Clinical, immunological, virological, and histopathological data were collected at 6, 12, and 24 months post-transplant. Antibody prevalence increased over time, with nDSAs being more frequent than DSAs at all timepoints. The combined presence of DSAs and nDSAs significantly increased the risk of ABMR (HR = 45.10;p < 0.001). Isolated nDSAs and DSAs were also associated with an increased risk of ABMR (HR = 6.43 and 12.10, respectively), suggesting a synergistic alloimmune effect. Viral infections also emerged as relevant cofactors in humoral alloimmunity. EBV viremia and intrarenal Parvovirus B19 (PVB19) infection were significantly associated with ABMR, with PVB19 also correlating with nDSA formation. In conclusion, integrated immunological and virological monitoring may support risk stratification and guide individualized post-transplant management. Larger multicenter studies are warranted to define the long-term impact of nDSAs in pediatric kidney transplantation.

摘要： Background Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has affected more than 1700 women. Treatment morbidity is reduced and survival improved by early detection and removal of implant and *** To address the need for early detection, we developed a multiplex lateral flow assay (LFA) for soluble IL-10 and CD30 in seromas surrounding *** The range of detection was determined with recombinant CD30 or IL-10 added to a benign seroma to simulate clinical conditions. Then clinical samples from 23 women with BIA-ALCL and 17 benign seromas were analyzed with a multiplex LFA detecting soluble IL-10 and *** When recombinant proteins were added to benign seromas, CD30 was detected down to a concentration of 0.5 ng/mL, and IL-10 could be detected to down to 5 ng/mL. Significant differences were found between CD30 and IL-10 test line/control line ratios (TL/CL) of 23 BIA-ALCL and 17 benign seromas. Visual inspection of LFAs resulted in 65% sensitivity, and improved to 87% with image *** We conclude that the multiplex IL-10/CD30 can detect BIA-ALCL with 100% specificity and 65% sensitivity in this group of 40 clinical seromas based on visual assessment of LFA strips. Sensitivity was improved to 87% with image analysis, which can provide a screening test for BIA-ALCL. The multiplex LFA demonstrated a perfect positive predictive value (100%), indicating that all positive results correctly identified BIA-ALCL cases. The negative predictive value of 99% can exclude BIA-ALCL.

关键词： psoriasis   psoriasis treatment   skin diseases  

关键词： anti-IL-5R   anti-IL4Ra   anti-IL5   anti-IgE   biological treatment   chronic rhinosinusitis with nasal polyps   network meta-analysis   sinus surgery  

关键词： IL-21   IL-2v   MT: Regular Issue   adenovirus   cancer vaccination   dendritic cell   gene therapy   high-capacity vectors   lymph node   targeted transduction   tumor vaccination  

摘要： Adenoviral vectors demonstrate encouraging clinical outcomes for B and T cell vaccines. With such approaches, multiple payloads can be delivered, beyond the antigen itself. Nevertheless, the human adenoviral vector serotype C5 (HAdV5) exhibits limited transduction efficiency to dendritic cells (DCs), therefore necessitating very high viral loads. Targeting antigen-presenting cells (APCs) has remained challenging. To solve this problem, we developed a versatile platform that employs modular retargeting adapters to enhance transduction of specific cell types, including challenging host cells. By rational design, we constructed a dual-adapter for DC-SIGN and CD11c and demonstrate successful targeting of HAdV5 to human and murine DCs. Our in vivo characterization highlights improved and specific transduction of DCs in draining lymph nodes. Moreover, a tumor vaccination study demonstrates the advantageous co-expression of T cell stimulatory cytokines (interleukin [IL]-2v or IL-21) locally in lymph nodes alongside a potent tumor antigen. Lymph node-directed gene therapy at significantly reduced vector loads may circumvent systemic toxicity of stimulating payloads. Our proposed low-dosage DC-targeted vaccine may offer an effective solution for patients and potentially minimize adenovirus-related side effects. The robust immunogenicity of HC-HAdV5, with its large coding capacity (37 kbp DNA), opens up exciting possibilities for future therapeutic combination strategies.

关键词： IL-24   Bregs   Tregs   endometriosis   plasmablasts   B10   immature B cells  

摘要： Problem Unbalanced production of pro- and anti-inflammatory cytokines by immune cells is a hallmark of endometriosis. IL-24, a member of the IL-10 family, is a pleiotropic cytokine produced by both non-immune cells like astrocytes, keratinocytes, pancreatic myofibroblasts, and endothelial cells and immune cells such as monocytes, macrophages, dendritic cells, NK cells, T cells (including Th2 and Th17), and B cells. However, its expression in regulatory T (Tregs) and B lymphocytes (Bregs) has not been explored. In this study, we determined the expression of IL-24 in Tregs and selected Breg subpopulations in women with endometriosis compared with healthy *** Percentages of Tregs, B10 cells, immature B cells, and plasmablasts that produce IL-24 were measured in the peripheral blood of women with endometriosis (n=24) and healthy women (n=24) using flow *** We observed an increased percentage of IL-24-producing Tregs in the total pool of women with endometriosis and in women with stages III and IV of endometriosis compared to controls. Within the Breg subpopulations, the percentages of IL-24-producing plasmablasts were higher in the overall endometriosis cohort as well as in women with stage IV endometriosis compared with healthy women. In contrast, the percentages of IL-24-producing immature B cells were lower in the endometriosis group than that in the control *** We have shown, for the first time, that Tregs and Bregs secrete IL-24 and that their percentages are altered in endometriosis. The significance of this cytokine secretion by regulatory cells is unclear, but we speculated that IL-24 may enhance the improper immunosuppressive activity of Tregs and plasmablasts in endometriosis, which enables the implantation and growth of endometrial lesions outside the uterus.

摘要： Background and Objectives Takayasu arteritis (TAK) is a rare large-vessel vasculitis primarily affecting young female patients, with pediatric cases being even rarer. Biologic therapies, such as anti-tumor necrosis factor (anti-TNF) and anti-interleukin-6 (anti-IL-6) agents, have become integral to TAK treatment;however, their use in children is not well supported by robust data due to the rarity of the disease. This systematic review aimed to evaluate the use, effectiveness, and safety of anti-TNF drugs and tocilizumab in the treatment of pediatric TAK. Methods We conducted a systematic literature search in PubMed/MEDLINE and Scopus databases from their inception until 15 December 2024. Studies were eligible if they included pediatric patients with TAK (diagnosed before 18 years of age) treated with anti-TNF or anti-IL-6 drugs and reported clinical outcomes. Clinical trials, observational studies, case series, and reports were included. Data were extracted independently by two reviewers. Only English articles were analyzed. Due to heterogeneity in study designs and reporting, a narrative synthesis was performed. Results A total of 94 reports involving 225 pediatric patients with TAK who received 262 treatment courses of biologic treatment were included. Anti-TNF drugs were more frequently used than tocilizumab (74.2% versus 36.9%, p < 0.001). Both groups showed comparable effectiveness, with clinical improvement observed in 64.9% of anti-TNF drug and 70.9% of tocilizumab treatment courses (p = 0.438). The frequency of relapse was also similar between the two groups (similar to 50% in both groups, p = 0.472). Hypertension was more prevalent in the anti-TNF group (p = 0.004), while concurrent glucocorticoid administration was more frequent in the tocilizumab group (p = 0.024). Infliximab was the most frequently used anti-TNF drug, with a higher proportion of patients showing improvement compared with adalimumab (71.1% versus 45.5%). Adverse events were only reported

关键词： Schizophrenia   Heavy metals   TNF-alpha   Severity   PANSS   Stroop test  

摘要： The presence of hazardous heavy metals (HMs) in the environment is well established, and numerous studies have explored their involvement in brain-related disorders. However, their potential impact on neuroinflammation, disease severity, and cognitive function in schizophrenia (SZ) remains largely unexplored. Therefore, this study aimed to investigate the potential pathophysiological role of environmental HMs in SZ. A total of 40 SZ patients and 40 healthy controls (HCs) were recruited from AIIMS Jodhpur, India. Blood samples were analyzed for lead (Pb), cadmium (Cd), arsenic (As), aluminium (Al), and TNF-alpha using atomic absorption spectroscopy and ELISA, while TNF-alpha gene expression was quantified using RT-qPCR. Patients exhibited notably elevated concentrations of Cd and Pb while decreased levels of As with median (IQR), 0.9 (0.40-1.72);1.11 (0.59-1.26);and 0.73 (0.46-0.89) compared to HCs with median (IQR), 0.75 (0.46-1.06);0.11 (0.04-0.18);and 0.92 (0.65-1.60) respectively. A significant positive relationship between TNF-alpha gene expression and blood As (rho = 0.33, p < 0.05) and a negative association between Pb and Al (rho = -0.34;p < 0.05) were reported in the patient group. Cognitive focus test scores were significantly lower in patients than in controls (p < 0.001). Cd levels negatively correlated with Stroop Word, Stroop Color, Color-Word, and Stroop Total scores (rho = - 0.28, - 0.36, - 0.28, - 0.33), indicating cognitive dysfunction. Additionally, PANSS score correlated negatively with Stroop Word (rho = - 0.36) and Stroop Total (rho = - 0.35), while PANSS Total scores showed negative correlations with Stroop Total (rho = - 0.33) and Stroop Color (rho = - 0.34), linking higher disease severity to poorer cognitive performance. In conclusion, these findings provide novel insights into SZ pathophysiology, highlighting the neurotoxic impact of heavy metals on TNF-alpha regulation, neuroinflammation, and cognition. The relationship between cognitive f