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关键词： Crohn's disease   ulcerative colitis   adalimumab   infliximab  

摘要： Background: This study aimed to evaluate the effect of overweight and obesity at the start of anti-TNF therapy on treatment response and relapse rate in children with inflammatory bowel disease (IBD). Methods: This multicenter, retrospective cohort study included 22 IBD centers in 14 countries. Children diagnosed with IBD in whom antitumor necrosis factor (anti-TNF) was introduced were included;those who were overweight/obese were compared with children who were well/undernourished. Results: Six hundred thirty-seven children (370 [58%] males;mean age 11.5 +/- 3.5 years) were included;140 (22%) were in the overweight/obese group (OG) and 497 (78%) had BMI <= 1 SD (CG). The mean follow-up time was 141 +/- 78 weeks (median 117 weeks). There was no difference in the loss of response (LOR) to anti-TNF between groups throughout the follow-up. However, children in OG had more dose escalations than controls. Male sex and lack of concomitant immunomodulators at the start of anti-TNF were risk factors associated with the LOR. There was no difference in the relapse rate in the first year after anti-TNF introduction;however, at the end of the follow-up, the relapse rate was significantly higher in the OG compared with CG (89 [64%] vs 218 [44%], respectively, P < .001). Univariate and multivariate analysis revealed that being overweight/obese, having UC, or being of male sex were factors associated with a higher risk for relapse. Conclusions: Overweight/obese children with IBD were not at a higher risk of LOR to anti-TNF. Relapse in the first year after anti-TNF was introduced, but risk for relapse was increased at the end of follow-up.

关键词： cetirizine   IL-33   inflammation   mast cell   preterm birth  

摘要： Problem: In order to gain a deeper understanding of the mechanisms underlying LPS-mediated preterm birth, it is crucial to investigate the relationship between preterm birth and mast cells (MCs). Moreover, the role of antihistamines in inflammatory processes during pregnancy remains incompletely understood. Method of Study: CD-1 female mice were administered intrauterine lipopolysaccharide (LPS) via midline laparotomy to establish an inflammation-induced preterm birth model. The experimental groups (n = 6 per group) were formed as Nonpregnant and pregnant control, Sham, PBS, LPS, Cetirizine (CET) control, and two CET treatment groups (CET 10 mg/kg-low dose, and CET 20 mg/kg-high dose with LPS administration). Tissue samples were analyzed using immunohistochemistry and Western blot techniques. Results: Our findings suggest that MCs play a significant role in preterm birth, with LPS administration inducing MC dysfunction in the reproductive tract during pregnancy. Additionally, high doses of CET may support inflammatory responses. A particularly notable result was the reduction in interleukin-33 (IL-33) expression in the cervix during LPS-induced preterm birth. This suggests that IL-33 may serve as a potential biomarker for preterm birth in the cervix. Conclusions: The effects of CET during LPS-mediated preterm birth appear to be dose-dependent, warranting further exploration of their role in this context.

关键词： Key Words   Indoleamine 2   3-Dioxygenase 1   Anti-inflammation   Peptide nucleic acids   Cell penetration   Antisense oligonucleotides   Normal human keratinocytes  

摘要： Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon gamma (IFN gamma)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

关键词： Lentinan   IL-22   ILC3s   Fucosylation   Macrophages   Barrier function   Ulcerative colitis  

摘要： Ulcerative colitis (UC) involves chronic, complex pathology of the intestinal mucosa. Current treatments are limited in efficacy and associated with adverse effects, highlighting the urgent need for improved therapeutic options. Lentinan (LNT), a polysaccharide drug commonly used in clinical immune modulation therapies, shows potential for UC treatment, though its specific targets and mechanisms remain unclear. In this study, LNT administration effectively mitigated DSS-induced colitis in mice, enhanced mucosal barrier function and antimicrobial defense. Specifically, LNT modulated the balance between tissue-resident and infiltrating macrophages, thereby improving pathogen clearance and enhancing the immunological barrier. Notably, we identified a novel effect of LNT in regulating the macrophage Dectin-1-ILC3 axis to increase IL-22 secretion. This led to the modulation of epithelial O-glycan fucosylation, antimicrobial peptides, and epithelial stem cells, thereby strengthening antimicrobial defenses and the physicochemical barrier. Neutralization with anti-IL-22 antibodies diminished the therapeutic effect of LNT in UC, underscoring the critical role of IL-22 in LNT-mediated treatment. Overall, this study highlights the potential of LNT as a novel therapeutic agent for UC, offering new insights into its molecular mechanisms and clinical application.

关键词： Peritoneal macrophages   M1 and M2 macrophages   Interleukins   Liposomes   IL-2   IL-2R alpha   Apoptosis   Inflammation  

摘要： Inflammatory diseases pose a global challenge due to the critical role of macrophages in their pathogenesis. This study evaluated the effects of cationic liposomes encapsulating IL-2 (LIP-IL-2) on murine peritoneal macrophages (MP) polarized towards M1 and M2 phenotypes. M1 MP (CD86+), which overexpressed IL-2R alpha and CD14 receptors, underwent apoptosis following LIP-IL-2 treatment, whereas M2 MP (CD206+) were unaffected. Furthermore, LIP-IL-2 significantly reduced the secretion of pro-inflammatory cytokines, including IL-6, TNF-alpha, IFN-gamma, and IL-12, exclusively in M1 macrophages. These findings suggest that LIP-IL-2 could serve as a promising therapeutic tool for chronic inflammatory diseases by selectively inducing apoptosis in pro-inflammatory M1 macrophages without affecting M2 ones, opening avenues for targeted therapies in diseases where chronic macrophage-mediated inflammation is a key factor.

关键词： acute rejection   amino acid mismatches   EMMA   Eplet   HLA compatibility   HLA mismatch   HLA serotypes   molecular mismatches   PIRCHE  

摘要： The purpose of this single-center case-control study was to investigate the association between HLA serotype mismatch (MM), compared to other HLA MM modalities, and the occurrence of acute rejection (AR) within the first year after deceased donor kidney transplantation. The study included 198 transplants in 99 pairs of recipients of kidneys from the same donor, where one recipient experienced AR and the other survived the first year without AR. Donors and recipients were typed with NGS for 11 HLA loci at high resolution. HLA MM categories included allele groups, alleles, serotypes, amino acids, EMMA, eplet and PIRCHE-II. Additionally, we investigated Cytomegalovirus LIL peptide (CMV LIL) MM. Recipients with AR presented higher frequencies of pre-transplant HLA-ABDR DSA (20.2% vs. 6.1%, p = 0.005) and CMV LIL MM (24.2% vs. 10.1%, p = 0.01). Univariate and multivariate Cox proportional hazards regression for matched-pair analyses were used to test the association between HLA MM and AR. Univariate analyses indicated significant association with DRB1 ST, HLA-DQB1 AG, HLA-DQB1 AL, EMMA C, EMMA DQB1, Eplet ABC and Eplet DQ MM. Different models were tested in multivariate analyses, all including pre-transplant HLA-ABDR DSA and CMV LIL MM. The models were compared using the Akaike Information Criterion (AIC). The best estimate for AR prediction (AIC = 97.6) was the model that included pre-transplant HLA-ABDR DSA (HR = 11.97;p = 0.003), CMV LIL MM (HR = 367.2;p < 0.001), HLA-DRB1 serotype MM (9.65;p = 0.002) and HLA-DQB1 allele MM (HR = 3.54;p = 0.033). In conclusion, this original report demonstrates an association between the HLA-DRB1 serotype MM and AR, highlighting that serotypes are clinically relevant.

关键词： Fibrosis   IFN alpha   Mortality   Systemic sclerosis   Type I IFN  

关键词： HLA-C*08:296   new allele   NGS   relative  

摘要： HLA-C*08:296 differs from HLA-C*08:02:01:01 by two nucleotide changes, one in an exon and one in an intron.