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关键词： cytokines   Galleria mellonella   inflammation   NF-kappa B   periodontitis   phthalocyanine   TNF-alpha  

摘要： Aim: This study investigated the activity and mechanism of action of the iron tetracarboxyphthalocyanine (FeTcPc) on tumor necrosis factor alpha (TNF-alpha) production and its impact on experimental periodontitis. Methods: RAW 264.7 macrophages were treated with FeTcPc, activated with lipopolysaccharide (LPS) at 10 ng/mL, and the TNF-alpha levels were measured, as well as the nuclear factor kappa B (NF-kappa B) activation. Subsequently, a mouth gel containing 1% FeTcPc was topically administered to the gingival tissue of mice with periodontitis-induced ligatures. Bone loss and the gene expression of Tnf alpha, p65 (NF-kappa B), and receptor-activating nuclear factor kappa B ligand (Rankl) were quantified in gingival tissue. Finally, the systemic toxicity of FeTcPc was estimated in Galleria mellonella larvae. Results: In an activated RAW 264.7 macrophage culture, 100 mu M FeTcPc reduced TNF-alpha release and NF-kappa B activation. Regarding experimental periodontitis, topical application of mouth gel containing 1% FeTcPc blocked alveolar bone loss. Additionally, 1% FeTcPc reduced the expression of Tnf alpha, p65 (NF-kappa B), and Rankl in gingival tissue. Finally, administration FeTcPc at doses ranging from 1 to 1000 mg/kg did not cause acute systemic toxicity in G. mellonella. Conclusion: Overall, we demonstrated the potential of mouth gel containing FeTcPc as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.

关键词： Ketogenic diet   NLRP3   cytokines   modified Atkins diet   tetralogy of Fallot  

摘要： Cardiopulmonary bypass in tetralogy of Fallot (TOF) corrective surgery induces hyperinflammation by activating NLRP3, caspase-1, and interleukin-ιβ (IL-ιβ), subsequently triggering an interleukin-10 (IL-10) response. Despite its known metabolic and anti-inflammatory effects, the impact of the modified Atkins diet (MAD) in pediatric cardiac surgery remains unexplored, with no studies on its use in TOF patients undergoing open-heart surgery. The aim of this study was to assess the effect of MAD on the expression of NLRP3, caspase-1, IL-ιβ, and IL-10, in TOF patients undergoing open-heart surgery. A double-arm, randomized-controlled trial was conducted with 44 TOF patients. The treatment group (n = 22) received the MAD, a low-carbohydrate, high-fat regimen with unrestricted fat and protein intake for at least 14 days preoperatively, while the control group (n = 22) followed a standard diet without carbohydrate restriction. Blood plasma and infundibulum heart tissues were collected for analysis. Whole blood samples were collected using a winged infusion needle before the intervention, an Abbocath infusion needle after 14 days of intervention, and a syringe without a needle connected to an arterial line in patients undergoing open-heart surgery at 6, 24, and 48  hours post-surgical correction. Infundibulum heart tissues were collected during the open-heart surgery. This study demonstrated significant differences in NLRP3 protein expression (p = 0.015), caspase-1 protein expression (p = 0.001), and IL-10 levels between after intervention and 6-, 24-, and 48-hours post-surgery in the MAD group compared to the control group. In contrast, no significant differences in IL-10 levels were observed in the control group between after intervention and 48  hours post-surgery (p = 0.654). In conclusion, MAD may modulate perioperative inflammation in TOF patients undergoing open-heart surgery by downregulating NLRP3 and caspase-1 expression while sustaining IL-10 levels. Despite redu

关键词： LncRNA NEAT1   LncRNA MIAT   TNF   Diabetic nephropathy  

摘要： Background: Diabetic nephropathy (DN) is a significant driver of end-stage renal disease, requiring kidney replacement therapies such as transplantation and dialysis. Given the critical importance of understanding the onset and progression of DN, we sought to explore the expression levels of tumor necrosis factor (TNF) and related long noncoding RNAs (lncRNAs) in diabetic patients with and without DN, as well as in pre-diabetic individuals, compared to healthy controls. We further explored the involvement of TNF and TNF-related lncRNAs in high glucose (HG)-induced apoptosis of human embryonic kidney (HEK)-293 cells. Material and method: In the current cross-sectional investigation, we compare the expression levels of lncRNA myocardial infarction-associated transcript (MIAT), lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and TNF in 50 healthy individuals, 50 people with prediabetes, 50 patients with type 2 diabetes mellitus (T2DM), and 50 patients with T2DM- DN. We cultured HEK293 cells in a HG condition (100 mM glucose) to establish a cellular model of DN, while HEK293 cells cultured in a normal-glucose environment (5 mM glucose) served as controls. We further assess apoptosis in HEK293 cells via flow cytometry analysis. Moreover, we evaluated the expression levels of lncRNA MIAT, lncRNA NEAT1, and TNF in HG and normal-glucose (NG) groups to investigate their potential involvement in HEK293 cell apoptosis and the pathogenesis of DN. Result: Our findings reveal a significant upregulation of lncRNA MIAT, lncRNA NEAT1, and TNF in T2DM and T2DM-associated DN groups compared to prediabetic individuals and healthy controls (p < 0.05). Furthermore, HG conditions significantly increased the apoptotic rate of HEK293 cells. Additionally, the expression levels of TNF, lncRNA MIAT, and lncRNA NEAT1 were increased in HEK-293 cells cultured in a HG. Conclusion: In conclusion, our findings indicate a significant role for the TNF gene and associated lncRNAs, such as lnc

关键词： autoantibodies   clinical application   single-sample test   type I interferons   VIDAS  

摘要： Autoantibodies neutralizing Type I interferons increase the risk of severe viral diseases and are linked to autoimmune conditions. The automated VIDAS assay is suitable for anti-IFN-α2 IgGs quantification, offering a swift, reliable, user-friendly, single test for clinical management.

关键词： Anti-TNF-alpha   Cartilage   Equine osteoarthritis   GAGs   LDH   MMP-2   MMP-9  

摘要： Osteoarthritis (OA) is the most common pathology in sport horses, presenting a chronic and recurrent course. Traditional anti-inflammatory treatments provide only temporary clinical improvement and pain relief;however, they have been associated with metabolic disorders in articular cartilage in the medium term. In this study, we generated a llama polyclonal antibody against equine TNF-alpha, which was used for intra-articular treatment in horses with OA. Treatment effects were assessed through clinical examination and the determination of inflammatory parameters (MMP-2, MMP-9, LDH, and GAGs) in synovial fluid prior to treatment (T0) and on day 30 (T30). Treated animals showed significant improvement in the clinical score, which decreased from 8.47 +/- 2.57 to 6.16 +/- 1.71 (mean +/- SD) on T30 (p < 0.001). Additionally, a reduction in the activity of MMP-2 (188 % +/- 82.99 to 147 % +/- 40.6 %, p < 0.05), MMP-9 (100 % +/- 61.28 to 74.37 % +/- 64.26, p < 0.05), and LDH (239.3 IU/l +/- 147.4 to 143 IU/l +/- 61.21, p < 0.01) was observed. Furthermore, on T30, GAGs levels were significantly increased (1.167 +/- 0.46 mg/ml to 1.439 +/- 0.267 mg/ml, p < 0.01). These results indicate that the local blockade of pro-inflammatory molecules such as TNF-alpha reduces pain and the levels of inflammatory molecules associated with catabolic processes and joint damage.

关键词： HLA-DQA1*05 genotype   IBD risk score   anti-tumor necrosis factor   treatment failure  

摘要： Introduction Carriage of the HLA-DQA1*05 allele is associated with development of antidrug antibodies (ADAs) to antitumor necrosis factor (anti-TNF) therapy in patients with Crohn's disease. However, ADA is not uniformly associated with treatment failure. We aimed to determine the impact of carriage of HLA-DQA1*05 allele on outcome of biologic therapy evaluated by drug persistence. Methods A multicenter, retrospective study of 877 patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy with HLA-DQA1*05 genotypes were generated by imputation from whole genome sequence using the HIBAG package, in R. Primary end point was anti-TNF therapy persistence, (time to therapy failure), segregated by HLA-DQA1*05 allele genotype and development of a risk score to predict anti-TNF therapy failure, incorporating HLA-DQA1*05 allele genotype status (LORisk score). Results In all, 877 patients receiving anti-TNF therapy were included in our study;543 (62%) had no copy, 281 (32%) one copy, and 53 (6%) 2 copies of HLA-DQA1*05 allele. Mean time to anti-TNF therapy failure in patients with 2 copies of HLA-DQA1*05 allele was significantly shorter compared with patients with 0 or 1 copy at 700 days' follow-up: 418 vs 541 vs 513 days, respectively (P = .012). Factors independently associated with time to anti-TNF therapy failure included carriage of HLA-DQA1*05 allele (hazard ratio [HR], 1.2, P = .02;female gender HR, 1.6, P < .001;UC phenotype HR, 1.4, P = .009;and anti-TNF therapy type [infliximab], HR, 1.5, P = .002). The LORisk score was significantly associated with shorter time to anti-TNF therapy failure (P < .001). Conclusions Carriage of 2 HLA-DQA1*05 alleles is associated with less favorable outcomes for patients receiving anti-TNF therapy with shorter time to therapy failure. HLA-DQA1*05 genotype status in conjunction with clinical factors may aid in therapy selection in patients with IBD.

关键词： Chronic periodontitis   gingival crevicular fluid   IL-1 beta   periodontal diseases   scaling & root planning  

摘要： Periodontitis is a chronic inflammatory periodontal lesion, characterised by progressive destruction of connective tissue and continuous loss of marginal bone surrounding the teeth. Cytokines and chemokines play a role in the pathogenesis of chronic periodontitis (CP). Among these, IL-1 beta is considered one of the most important inflammatory factors and tissue-destructive cytokines. Despite numerous investigations identifying the role of IL-1 beta in gingival crevicular fluid (GCF) in bone resorption and connective tissue destruction, the efficacy of GCF IL-1 beta in assisting the diagnosis and predicting the progression of CP remains undetermined. The objective of this study was to ascertain whether IL-1 beta can be used as a diagnostic and progressive biomarker for CP. To this end, GCF IL-1 beta levels were compared between periodontally healthy controls and subjects diagnosed with CP, as well as between subjects before and after scaling and root planning (SRP) for CP. Additionally, the correlations between GCF IL-1 beta levels and various clinical parameters, including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), plaque index (PI), and gingival index (GI), were analysed within the CP group. A comprehensive search of the PubMed, Embase and Cochrane databases was conducted from their inception up to 1 April 2022. The electronic search terms employed were 'periodontitis OR periodontal diseases' AND 'Interleukin-1 beta OR IL-1 beta' AND 'gingival crevicular fluid'. The review includes cross-sectional, case series, single arm studies, prospective and retrospective cohort studies, as well as randomised controlled trials (RCTs) and non-RCTs. The studies that compared IL-1 beta levels (either the concentration or the total amount) between healthy controls and subjects with CP, or between subjects with CP before and after SRP, were included in the review. The meta-analysis was conducted using Review Manager 5.3. The analysis included d

关键词： HLA-B   NGS   novel allele   russian  

摘要： Nine novel HLA-B alleles were detected during the routine HLA typing process.

关键词： HLA-DQB1*03:01:01:65 novel allele   HLA-DQB1*05:02:01:18 novel allele   Illumina   next-generation sequencing  

摘要： HLA-DQB1*03:01:01:65 and -DQB1*05:02:01:18 were detected in a Greek individual.