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关键词： Anatolian propolis   curcumin   IL-25   MMP-2   VEGF   BCM  

摘要： Background: Nasal steroids are commonly prescribed in ear, nose, and throat clinics. It is observed that the use of nasal steroids is increasing due to the prevalence of allergic rhinitis. Because beclomethasone (BCM) toxicity is low, it is highly preferred in allergic rhinitis. The rate of toxicity increases with the increase in the duration and dose of BCM use. However, the protective mechanism of Anatolian propolis (AP) and curcumin (Cur) against BCM toxicity has not been fully explained. Aim: The study evaluates the potential BCM-induced toxicity effect on VEGF, MMP-2, IL-25, and IL-10 parameters after Cur and AP treatment. Materials and Methods: Cell viability, oxidative stress, and gene expression were used for toxicity evaluation. Results: AP 2.5 mg/mL and Cur 16 mu g/mL show high viability and antioxidant capacity. BCM increased the levels of IL-25, IL-10, and MMP-2, and a decrease was detected in the expression levels of FGF-2 and VEGF. Conclusions: AP and Cur show effective healing, and AP has been shown to improve inflammation more effectively than Cur. However, the combination of AP and Cur significantly improved the induced toxicity effects.

关键词： Gut bacteria   Gastrointestinal tract   Mycobacterium tuberculosis   Immune response   Antibiotics   Mycobacterium bovis   Respiratory infections   Bacterial pathogens  

摘要： Tuberculosis is one of the leading causes of global mortality, and the standard, prolonged, and intensive treatment can affect intestinal homeostasis. This study investigated amoxicillin-induced bacterial gut dysbiosis and its impact on the immune response of C57BL/6 mice to pulmonary infection by Mycobacterium bovis-BCG. It was observed that amoxicillin treatment resulted in bacterial gut dysbiosis, characterized by an increase in the phylum Proteobacteria and a reduction in Bacteroidetes and Firmicutes. This alteration was associated with a decrease in the animals' body weight and a reduction in the expression of pro-inflammatory cytokines such as IL-1 beta and IL-6, suggesting a compromised immune response. Additionally, microstructural analysis revealed significant alterations in the caecum and pulmonary structure of the mice, indicating tissue damage associated with intestinal dysbiosis. The results indicate that amoxicillin-induced bacterial gut dysbiosis may negatively affect pulmonary immunity and exacerbate M. bovis-BCG infection, highlighting the need to consider the impacts of intestinal microbiota on the development and control of tuberculosis. This study contributes to the understanding of the interaction between intestinal microbiota, antibiotic treatment, and immunity in pulmonary infections.

关键词： Multiple sclerosis   Haplotypes   Sensory perception   Brainstem   Medical risk factors   Major histocompatibility complex   Autoimmune diseases   Central nervous system  

摘要： Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS). The pathogenesis of MS is characterized by neuronal axonal degeneration and demyelination. Among the genes that raises MS risk are the HLA-class II genes. The goals of this study were to investigate the role of the HLA-DRB1 and HLA-DQB1 genes (for the first time) in Jordanian MS patients and their association with MS disease. The association of these genes with other clinical features, such as optic neuritis, sensory impairment, and brainstem symptoms in MS patients was investigated as well using PCR-SSP techniques. Our findings indicated an association between HLA-DRB1 * 03:01 (Pc = 0.01) and HLA-DRB1 * 04:01 (Pc = 0.004) alleles with Jordanian MS patients. In addition, a significant linkage between HLA-DRB1 * 15:01 and HLA-DQB1 * 06:01 alleles (Pc <= 0.001 and Pc = 0.012, respectively) were presented among Jordanian MS patients with optic neuritis compared to Jordanian MS patients without optic neuritis. Moreover, HLA-DQB1 * 05:01 and HLA-DQB1 * 06:02 alleles (Pc <= 0.001 and Pc = 0.006, respectively) was found to be related with sensory impairment in MS patients. Additionally, HLA-DRB1 * 07:01 allele indicates a positive correlation in MS patients with brainstem symptoms (Pc < 0.001). Moreover, our results indicated that there is no association on the HLA-DRB1 similar to HLA-DQB1 haplotype level and MS disease. Knowing the genes that are linked to MS, they may facilitate MS diagnosis, prevention, and treatment at earlier stage. Also, these results may serve in the development of more potent therapeutic regimens for MS and its related complications, such as optic neuritis, sensory impairment, and brainstem symptoms.

关键词： atopic dermatitis   autoinflammatory syndrome   basiliximab   IL-2R inhibitors   monoclonal antibody   precision medicine  

摘要： Options for pediatric patients with severe atopic dermatitis who do not respond to biologics remain limited. We report the case of a 10-year-old boy with severe, recalcitrant atopic dermatitis associated with episodic fever, joint pains, and elevated serum IL-2R, which responded to basiliximab. To our knowledge, this is the first reported use of basiliximab for atopic dermatitis in a pediatric patient. This case highlights the potential for basiliximab as a therapy for severe cases of atopic dermatitis and the potential for precision medicine in dermatology.

关键词： maternal-fetal immune tolerance   endometrial receptivity   embryonic development   eomesodermin   methionine   methylation   transcription   IL-5  

摘要： Endometrial receptivity and maternal-fetal immune tolerance are two crucial processes for a successful pregnancy. However, the molecular mechanisms of nutrition involved are largely unexplored. Here, we showed that maternal methionine supply significantly improved pregnancy outcomes, which was closely related to interleukin-5 (IL-5) concentration. Mechanistically, methionine induced embryonic IL-5 secretion, which enhanced the conversion of CD4+ T cells to IL-5+ Th2 cells in the uterus, thereby improving maternal-fetal immune tolerance. Meanwhile, methionine-mediated IL-5 secretion activated the nuclear factor kB (NF-kB) pathway and enhanced integrin avb3 expression in endometrial cells, which improved endometrial receptivity. Further, methionine strongly influenced the DNA methylation and transcription levels of the transcription factor eomesodermin (Eomes), which bound directly to the IL-5 promoter region and inhibited IL-5 transcription. Methionine modulated IL-5 transcription, maternal-fetal immune tolerance, and endometrial receptivity via its effects on Eomes. This study reveals the crucial functions of methionine and IL-5 and offers a potential nutritional strategy for successful pregnancy.

关键词： CRTH2   HLA-DR   atopic dermatitis   eosinophilia   eosinophils   phenotype   siglec-8  

摘要： Atopic dermatitis (AD) as well as other type 2 immune response (T2) diseases are often linked to elevated eosinophil (Eos) levels in the blood. Although the role of Eos in AD pathophysiology is suspected, it remains unclear. The development of new treatments targeting the T2 response, particularly cytokines involved in Eos activation and chemotaxis, makes it necessary to identify potential Eos profiles in AD that may respond to these treatments. A prospective study was conducted comparing blood Eos phenotypes in moderate-to-severe AD patients (n=19) without recent systemic treatment to healthy individuals (HI, n=19). The primary outcome was the membranous phenotypic signature of Eos, assessed by flow cytometry. Most AD patients (84%) had early onset in childhood, a severe disease (mean SCORAD of 57.5), and elevated blood Eos counts (310 per µl in AD vs 120 in HI, p<0.0001). AD patients exhibited lower CRTH2 on Eos but higher levels of HLA-DR and Siglec-8 compared to HI. Other surface proteins showed no significant differences. Clustering analysis confirmed increased Siglec-8 in AD patients. Additionally, AD patients had higher serum levels of T2 immune response-markers as eotaxin-2, IL-5, IL-3, and TARC. Circulating Eos in AD patients show a distinct phenotypic profile, suggesting a role in AD pathophysiology and potential involvement in differential treatment responses.

关键词： Autoimmunity   Immunotherapy   Interleukin-18   Interleukin-1β   MAS825   Macrophage activation syndrome   Still's disease   Systemic juvenile idiopathic arthritis  

摘要： Graphical abstract

关键词： dendritic cells   GRASP55   antigen presentation   MHC transport   phagosomes  

摘要： Dendritic cells (DCs) present exogenous antigens via major histocompatibility complex class I (MHC-I) and MHC class II (MHC-II) molecules, activating CD8+ and CD4+ T cells. A critical but poorly understood step in this process is the trafficking of peptide-loaded MHC molecules from the endocytic system to the cell surface. In this study, we demonstrate that the Golgi reassembly-stacking protein of 55 kDa (GRASP55), which has been shown to have no role in stacking, is essential for antigen presentation. Using soluble, bead-coated, and bacterial-bound antigens, we found significantly impaired exogenous antigen presentation in GRASP55deficient bone-marrow-derived DCs (BMDCs). Notably, GRASP55 was recruited to late phagosomes, and our data suggest that it is crucial for sorting MHC-I and MHC-II molecules, facilitating their trafficking to the plasma membrane. Our findings highlight the vital role of GRASP55 in the intracellular transport of MHC molecules bound to their respective peptides during exogenous antigen presentation.

关键词： celiac disease   HLA   diagnosis   potential CeD   pediatric  

摘要： Objectives Diagnosis of celiac disease (CeD), an immune-mediated disorder, is based on clinical presentation, a panel of serological markers, and the histopathological findings in duodenal biopsies. Commonly, pediatric CeD patients fulfill these criteria for diagnosis. However, lack of correlation between serology tests and histology, or no accessible biopsies because of clinical conditions or during the COVID pandemic, are conditions that led to inconclusive diagnoses. Since the majority of CeD patients carry HLA-DQ2 and/or DQ8 alleles, HLA testing is used as a complementary tool in diagnosis though is costly and not broadly available for gastroenterology *** We performed a retrospective study to assess the performance of HLA testing when applied to selected groups of patients who could not be definitely diagnosed following the common algorithm. Eighty patients underwent testing for CeD-related HLA-DQ2 and DQ8 *** HLA typing contributed to diagnosis in 34 patients with positive serology but normal mucosa or those who presented negative serology or slightly positive serology (less than 3 times ULN) and duodenal histopathological changes. In patients with normal histology and negative or slightly positive serology, or those who did not undergo intestinal biopsy (39 in total), HLA typing contributed to CeD diagnosis in 23 cases, only 16 patients were admitted for a clinical follow-up *** HLA-DQ typing supported the diagnosis in 57 of 80 children (71.2%) with previously inconclusive results, providing a beneficial approach for diagnosing celiac disease (CeD) in selected cases.

关键词： RV   resistance   pathogenesis   receptor   tropism   Atoh1   Muc2   secretory cell   MHC II  

摘要： Enteric pathogen rotavirus (RV) primarily infects mature enterocytes at the tips of the intestinal villi;however, the role of secretory Paneth and goblet cells in RV pathogenesis remains unappreciated. Atoh1 knockout mice (Atoh1cKO) were used to conditionally delete Paneth, goblet, and enteroendocrine cells in the epithelium to investigate the role of secretory cells in RV infection. Unexpectedly, the number of infected enterocytes and the amount of RV shedding in the stool were greatly decreased following secretory cell deletion. Resistance to RV infection persisted for 7 days after virus inoculation, and Atoh1 knockout mice co-housed with infected wild-type mice were uninfected, based on lack of shedding virus, despite the highly infectious nature of RV. This response was directly proportional to the extent of secretory cell deletion, with infection predominantly occurring in areas containing intact secretory cells. RV infection of Muc2 knockout mice recapitulated the secretory cell deletion phenotype, indicating that goblet cell loss is responsible for attenuated infection. Transcriptome analysis of Atoh1cKO intestine via single-cell RNA sequencing revealed downregulation of MHC II molecules specifically in tip enterocytes, and MHC II-/- mice were likewise resistant to RV infection. These data suggest a previously unknown role for both MUC2 and MHC II expression in susceptibility to RV infection.