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关键词： HLA-B   HLA-B*38:125   NGS   novel HLA allele  

摘要： HLA-B*38:125 differs from HLA-B*38:02:01:01 by one nucleotide substitution in codon 248 (GTG>ATG) in exon 4.

关键词： B cell development   CD25   class switch recombination   germinal centers  

摘要： The cytokine IL-2 plays a pivotal role in the immune system, specifically in the proliferation of T, B, and NK cells. The alpha subunit of the IL-2 receptor, IL-2R alpha (CD25), is known to regulate the expansion and differentiation of T lymphocytes. CD25 is also expressed in developing B cells;however, its B cell intrinsic role remains undefined. We generated a mouse model with a B cell-specific deletion of CD25 to ascertain its role in B cell development and function. Unexpectedly, we found that the loss of CD25 had no impact on B cell development, homeostasis, or immune response to model antigens. Additionally, while CD25 expression was upregulated in activated splenic B cells, its absence did not affect class switch recombination in vitro or in vivo. We conclude that in contrast to its critical role in T cell differentiation and function, and despite its expression in developing and activated B cells, CD25 does not have any significant role in B cell development and adaptive immune functions.

关键词： Aerocyte   Alarmin   Alveolar   COVID-19   IL-33   Viral LRTD  

摘要： Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33red)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33ox)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33red, IL-33ox and IL-33/sST2 complexes in samples from patients hospitalised with COVID-19. Immunohistochemistry and multiomics were used to characterise lung samples. Elevated IL-33 in the airway and IL-33/sST2 complex in the circulation correlated with poor clinical outcomes (death, need for intensive care or mechanical ventilation). IL-33 was localised to airway epithelial and endothelial barriers, whereas IL1RL1 was expressed on aerocytes, alveolar endothelial cells specialised for gaseous exchange. IL-33 increased expression of mediators of neutrophilic inflammation, immune cell infiltration, interferon signalling and coagulation in endothelial cell cultures. Endothelial IL-33 signatures were strongly related with signatures associated with viral LRTD. Increased IL-33 release following respiratory viral infections is associated with poor clinical outcomes and might contribute to alveolar dysfunction. Although this does not show a causal relationship with disease, these results provide a rationale to evaluate pathological roles for IL-33 in viral LRTD.

关键词： insomnia   androgen-deprivation therapy   metastatic disease   biomarker   inflammation  

摘要： Objectives: The purpose of this study was to ascertain whether sleep quality is altered in patients with prostate cancer (PCa) during androgen deprivation therapy (ADT) and whether sleep impairment associates with depressive symptoms, cognitive function or frailty syndrome, and if this varies between patients with localized or metastatic disease. The pro-inflammatory cytokine, IL-1$ is involved in sleep regulation, we assessed whether sleep quality, depressive symptoms, cognitive function or frailty syndrome are associated with IL-1$ concentration. Methods: Sleep quality was assessed using the Athens Insomnia Scale (AIS), depressive symptoms using the Yesavage Scale (GDS), and cognitive functions using the MiniMental State Exam (MMSE) and the level of frailty was measured based on the Fried criteria. Plasma IL-1$ was measured by enzyme-linked immunoassay. Linear regression lanalyses were performed to determine which variables predict plasma IL-1$ is involved in poor sleep quality and higher IL-1$ concentration. Results: A cross-sectional study was carried out between 2021 and 2023. Sixty-seven men with PCa (N=36 (53.7%) with localized disease and N=31 (46.3%) with metastatic disease) were enrolled in the study. Plasma IL-1$ concentration correlated with poorer sleep quality in all sample and, men with metastatic PCa had poorer sleep quality compared to men with localized disease. Analysis of self-reported sleep quality revealed that half of them had insomnia symptoms and 19.4% reported clinically relevant insomnia disorder (mean value of AIS 3.39 0.44). Poor sleep quality significantly predicted the concentration of IL-1$ in plasma. In contrast, a better cognitive function significantly (P = .037) predicted IL-1$ concentration. Detailed analysis of AIS items showed that score in the item "Sleep induction" and "Sleepiness during the da) significantly predicted IL-1$ concentrations (P = .001 and P0=.044, respectively). Conclusions: Plasma IL-1$ levels may be useful to

关键词： Engineered bacteria   IL-15 & 15R alpha   VNP20009   Bladder cancer  

摘要： Surgical resection combined with intravesical instillation of chemotherapeutics or Bacillus Calmette-Guerin (BCG) to remove residual cancer cells is the gold standard for the clinical treatment of patients with bladder cancer. In a recent clinical trial, a new super-agonist complex of IL-15- N803, has shown promising results when used in combination with BCG to treat patients with bladder cancer who do not respond to BCG. Herein, we used temperature-controlled pBV220 plasmid encoding Interleukin-15 and its receptor alpha subunit (IL-15 & 15R alpha) to transform VNP20009, an attenuated salmonella typhimurium strain, obtaining engineered bacteria named 15 & 15R alpha@VNP. After induction at 42 degrees C, 15 & 15R alpha@VNP can secrete functional IL-15 & 15R alpha stably. It was found that intravesical instillation of thermally activated 15 & 15R alpha@VNP could inhibit the growth of bladder tumors if used alone. Moreover, the sequential intravesical instillation of epirubicin (EPI), a first-line bladder cancer drug, followed by thermally activated 15 & 15R alpha@VNP, could achieve further improved therapeutic responses, without causing significant side effects. Therefore, this study shows that 15 & 15R alpha@VNP can be effectively used in the treatment of bladder cancer and can be used as a complementary therapy to chemotherapy agents, promising for potential clinical translation in bladder cancer treatment.

关键词： Syringic acid   osteoarthritis   ATDC5 cells   MMPs   Akt/NF-kappa B   treatment of OA  

摘要： Background Osteoarthritis (OA) is a chronic progressive joint ailment that is largely predominant worldwide. However, it typically gets worse over time, occurs more frequently, and becomes more *** Syringic acid (SA) is a well-known phenolic compound reported to suppress inflammation, cell proliferation, and apoptosis of various cancer cells. Since the role of SA in OA remains unknown, there is a need to hypothesize the anti-inflammatory activities of SA on IL-1 beta-induced ATDC5 chondrocyte-like cells and to elucidate its protective action against *** The cytotoxicity, inflammatory mediators, mRNA expression of MMPs, ADAMTS, COX-2, and Akt/NF-kappa B protein expression of SA activity on ATDC5 cells were examined through CCK-8 assay, ELISA, RT-qPCR, and western blot. It was found that SA (10, 20, and 30 mu M) did not show any inhibitory effects on the viability of the ATDC5 cells in a concentration dependent *** SA markedly reduced the inflammatory mediators, cytokines, PGE2, MMPs, COX-2, and ADAMTS in a concentration-dependent manner. Likewise, SA expressively attenuated IL-1 beta-stimulated Akt phosphorylation and NF-kappa B activation as well as IL-1 beta- induced ATDC5 *** This study revealed that SA is a novel candidate applicable for the treatment of OA.

关键词： HLA   HLA-DRB1*14:268   novel allele   sequencing-based typing  

摘要： HLA-DRB1*14:268 differs from HLA-DRB1*14:54:01:03 by one nucleotide substitution in codon 213 in exon 4.

关键词： Enteric nervous system   Inflammatory bowel disease   Adalimumab   Anti-TNF-alpha  

摘要： BackgroundInflammatory bowel diseases (IBD) affect both enteric neurons and enteric glia, with tumor necrosis factor-alpha (TNF-alpha) playing a role as an inflammatory *** the effects of the anti-TNF monoclonal antibody on the myenteric plexus in an experimental model of ***57BL/6 mice received 3% dextran sodium sulfate (DSS) in drinking water for 7 days in both the DSS and DSS + ADA groups. The Sham group received water. The DSS + ADA group received ADA anti-TNF-alpha on day 2 of DSS intake. The ADA group was given water throughout the period and received an anti-TNF-alpha injection on day 2. The study evaluated the number of neurons per ganglion, and the area of the neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), pan-neuronal marker (PGP9.5), and tumor necrosis factor receptor 2 (TNFR2) immunoreactive (-ir). Double labeling of PGP9.5 with an enteric glial marker (GFAP) was also *** successfully induced experimental colitis (EC). TNFR2 was detected in the myenteric neurons in all groups. EC affected the enteric neurons, showing a decrease in the number of TNFR2-ir, ChAT-ir, nNOS-ir, and PGP9.5-ir neurons, whereas enteric glial cells increased in both the DSS and DSS + ADA groups. The DSS + ADA group showed number of nNOS-ir, ChAT-ir, and PGP9.5-ir neurons per ganglion similar to Sham group. EC also affected the neuronal profile, resulting in smaller areas in the DSS and DSS + ADA *** neurons are immunoreactive to the TNFR2. DSS altered the myenteric plexus, and anti-TNF monoclonal antibody treatment proved effective against EC due to preventing the pathology from developing.