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关键词： Tripterygium hypoglaucum   Celastraceae   Flavanol-hydroxytyrosol hybrids and   diterpenoids   Anti-neuroinflammatory activity   NF   kappa B and IL-1 beta  

摘要： The study aimed to identify the anti-neuroinflammatory compounds present in the rhizomes of Tripterygium hypoglaucum (Levl.) Hutch while simultaneously elucidating their mechanisms of action against neuroinflammation in vitro. Seven previously undescribed compounds, including a pair of flavanol-hydroxytyrosol hybrids (1-2) and three diterpenoids (5-7), were isolated from T. hypoglaucum rhizomes through sequential chromatographic methods under the guidance of LC-MS analyses. Their structures were determined by HRESIMS, NMR spectroscopic analysis combined with quantum-chemical ECD calculations. The anti-neuroinflammation activities of the isolates on LPS-induced BV-2 cells were evaluated that compounds 1-7 notably suppressed NO production to demonstrate anti-neuroinflammatory effects. Compounds 1-4 attenuated the expression of phosphorylated NF-kappa B, thereby mitigating NF-kappa B activation, whereas compounds 5-7 inhibited IL-1 beta expression to exhibit anti-neuroinflammatory activity. Compound 5 further inhibited the generation of inflammatory factors IL-6, IL-10, and COX-2. The results of molecular docking complemented the in vitro findings related to antineuroinflammation, demonstrating that all compounds exhibited strong binding affinity to the associated targets, characterized by high energy values, as well as favorable composite Log P values, NHBD, and NHBR. Collectively, these structurally diverse compounds expand the repertoire of candidate molecules for the development of drugs aimed at treating neurodegenerative diseases.

关键词： Oreochromis niloticus   IL-4/13A   Proliferation   Apoptosis   IgT plus B cells  

摘要： Interleukin-4/13 (IL-4/13) is a kind of bony fish cytokine, which is the homolog of Th2 cytokines IL-4 or IL-13 in mammals. Produced by activated T cells, these Th2 cytokines regulate B cell proliferation, survival, and antibody responses. Although IL-4/13 has been shown to participate in immune responses in bony fish, whether and how it regulates the teleost-specific IgT+ B cell subset, a lineage unique to bony fish remains unclear. In present study, we identified two conserved IL-4/13 from the Nile tilapia Oreochromis niloticus (OnIL-4/13A1 and OnIL-4/13A2), and suggested their wide expression in immunological tissues. OnIL-4/13A1 transcription was markedly upregulated in spleen and liver leukocytes upon bacterial infection, and can be dramatically induced by PHA-or CD3 mAb-induced T cell activation, suggesting activated T cells are a key cellular source of this cytokine. More importantly, we found that 2-or 4-days' in vivo administration of the recombinant OnIL-4/13A1 (rOnIL-4/13A1) caused an obvious expansion of IgT+ but not IgM+ B cells in tilapia. Further investigation demonstrated that this expansion was due to cellular proliferation, because the BrdU incorporation in IgT+ B cells was obviously increased, while the Erk1/2 and NF-kappa B phosphorylation that contributing to the proliferation was also enhanced in IgT+ B cells. Interestingly, as revealed by the Annexin V staining, we found that rOnIL-4/13A1 treatment elevated the apoptosis of IgT+ B cells, probably by initiating the Caspase-8/Caspase-3 pathway. Therefore, our results suggest that IL-4/13A1 involves in the anti-bacterial immune response of tilapia by promoting IgT+ B cell proliferation and maintaining IgT+ B cell hemostasis, thus shed novel light on the B cells response in bony fish.

关键词： Chronic inflammation   Bleomycin induced scleroderma   Oxazolone induced dermatitis   Dihydromyricetin   T cells   ROR gamma t  

摘要： Systemic sclerosis is a chronic inflammatory disease affecting the connective tissue of the human body by inducing fibrosis mainly in skin and lungs. Atopic dermatitis is another chronic inflammatory skin diseases that affects one-fifth of the population in developed countries. Dysregulation of the immune cells are one of the major characteristic features behind establishment of these two diseases. Several medicines are used to treat these diseases, but they have several side effects and high production cost. Low side effect and easy availability has generated renewed interest in studying plant derived medicines. Dihydromyricetin (Ampelopsin), a flavonoid compound extracted from stem and leaves of Ampelopsis grossedentata has shown potent anti-inflammatory property in vitro . In this study, bleomycin induced scleroderma and oxazolone induced dermatitis model were established in male BALB/c mice to check the in vivo efficacy of dihydromyricetin. Immunophenotyping and cytokine production were investigated by flow cytometry;immunofluorescence of skin was studied using confocal microscopy. We observed oral application of dihydromyricetin significantly reduced the inflammatory parameters in both diseases. We also found that dihydromyricetin dose dependently reduced the percentage of IL17A producing T cell population and reduced the total expression of ROR gamma t in diseased T cells. Furthermore, we also found stable and strong binding of dihydromyricetin-ROR gamma t protein complex. Stability of protein-ligand complex was examined by MD simulation study. We suggest that dihydromyricetin alleviates scleroderma and dermatitis symptoms by regulating the ROR gamma t pathway. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： Chicken interferon-gamma   Monoclonal antibody   ELISPOT   IFN-gamma-secreting T cells  

摘要： Cellular immune responses play critical roles in the control of pathogenic infection. The measurement of antigenspecific IFN-gamma-secreting T cells via an enzyme-linked immunospot assay (ELISPOT) is a valuable method for the evaluation of cellular immune responses. However, in chicken, few of monoclonal antibodies (mAbs) against chicken IFN-gamma (chIFN-gamma) are suitable for this application. In this study, three anti-chIFN-gamma mAbs (2B10, 3F10, 5A7) were generated by immunization with pcDNA-chIFN-gamma plasmid and recombinant Hela cell line stably expressing chIFN-gamma (Hela-chIFN-gamma). Indirect immunofluorescence assay showed that these mAbs specifically recognized eukaryotically-expressed chIFN-gamma in DF-1 cells and natural chIFN-gamma secreted by mitogen-activated chicken splenocytes. Furthermore, using 3F10 as a capture antibody and biotinylated 5A7 as a detection antibody, an ELISPOT assay was established for numerating IFN-gamma-secreting T cells of chicken. This chIFN-gamma ELISPOT assay had higher reactivity than a commercially available kit and showed no cross-reactivity with activated lymphocytes from geese and ducks. This assay was further applied to detect the frequency of MDV antigenspecific IFN-gamma-secreting T cells in the spleen of CVI988-immunized chickens. Collectively, we developed and validated an ELISPOT assay for detecting IFN-gamma-secreting T cells in chickens using novel anti-chIFN-gamma mAbs. Our study provides an important immunological tool for in-depth analysis of cellular immune response in chicken after infection or vaccination.

关键词： Prostate cancer   Interleukin   Gene polymorphism   Inflammation   Tetra-ARMS PCR   Haplotype  

摘要： Background: Prostate cancer is one of the most frequently diagnosed cancers in men globally. Chronic inflammation is a major contributor to the development of cancer, with interleukins as key players in regulating inflammatory pathways. This study aims to explore the association between IL1, IL6, IL10, IL16, and IL28 gene polymorphisms and the risk of prostate cancer in the Iraqi population. Methods: This case-control study included 290 histologically confirmed prostate cancer patients and 350 age-matched healthy controls recruited from Al-Diwaniyah Teaching Hospital between February 2024 and December 2024. Genotyping for IL1B-511 C>T (rs16944), IL6-174 G>C (rs1800795), IL10-1082 A>G (rs1800896), IL16-295 T > C (rs4778889), and IL28B C>T (rs12979860) polymorphisms was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). Statistical analyses included odds ratios (ORs) with 95 % confidence intervals (CIs) and haplotype analysis. Results: Significant associations with prostate cancer risk were observed for the IL1B-511 TT genotype (OR=1.76, 95 % CI: 1.18-2.63, p = 0.006), IL6-174 GG genotype (OR=1.66, 95 % CI: 1.12-2.45, p = 0.011), IL10-1082 GG genotype (OR=1.82, 95 % CI: 1.20-2.76, p = 0.005), IL16-295 CC genotype (OR=1.88, 95 % CI: 1.27-2.79, p = 0.002), and IL28B TT genotype (OR=1.79, 95 % CI: 1.22-2.63, p = 0.003). Haplotype analysis revealed that the TGGCT haplotype was associated with a 2.35-fold increased risk of prostate cancer (OR=2.35, 95 % CI: 1.51-3.66, p < 0.001). Stratified analyses demonstrated stronger associations between these polymorphisms and aggressive disease characteristics, including higher Gleason scores, advanced tumor stages, and elevated PSA levels. Conclusion: In this study, we identified proliferative inflammatory lesions of the prostate in Iraqi patients, suggesting that polymorphisms in the IL1B, IL6, IL10, IL16, and IL28B genes significantly increased prostate cancer risk and exa

关键词： Interleukin-33   Systemic lupus erythematosus   Follicular helper T cell  

摘要： Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.

关键词： Cognitive function   Type 2 diabetes   Physical exercise   Cytokine   Immune system  

摘要： Diabetes, via chronic metabolic and inflammatory dysregulation, may impair immune function and contribute to cognitive decline, particularly in executive functions. In this study, we examined changes in the cytokines IL-10 and TNF, as well as their balance, alongside executive function, physical performance, and diabetes-related indices following a combined, dual-task, home-based exercise training program. A total of 85 inactive women aged 50-75 years with type 2 diabetes were randomly assigned to either an exercise training group or a control group. During the preand post-test phases, assessments were conducted in both groups to measure executive function, physical performance, levels of IL-10 and TNF, their ratio, and diabetes-related indices. The dual-tasked home-based exercise program improved physical performance and body composition (P < 0.05). Executive function significantly improved in the exercise group (Effect size (ES) = 0.44, P < 0.05), accompanied by reductions in IL-10 (ES = 1.11, P < 0.05) and TNF levels (ES = 0.76, P < 0.05). However, no significant changes were observed in the balance of these two cytokines or diabetes-related indices (P > 0.05), except for HDL levels (ES = 0.87, P < 0.05). Based on the results of the present study, engaging in multi-task home-based exercise training can enhance executive function and reduce inflammatory cytokines in women with type 2 diabetes. However, this training did not significantly affect the balance between IL-10 and TNF, which may be due to the moderate intensity of the exercises. Further long-term studies that take into account additional factors-such as nutrition, medication use, and cognitive status-are warranted to gain a clearer understanding of the cytokinemodulating effects of dual-task exercise training in individuals with type 2 diabetes.

摘要： Axial spondyloarthritis (axSpA) manifests with inflammatory back pain and is diagnosed predominantly in subjects carrying the human leucocyte antigen (HLA)-B27 allele. While not diagnostic for the disease or a predictive biomarker in the general population, there is convincing data on the pathogenic role of HLA-B27 in axSpA via different proinflammatory mechanisms. Similar to other chronic conditions, axSpA requires lifelong treatments, including biologics and small molecules, to treat inflammation and ultimately halt disease progression by achieving sustained disease remission. There is currently no cure for axSpA, but one fascinating thesis is that gene therapy may hold the potential to reverse the disease. We provide herein a comprehensive and critical review of the advances in gene therapy strategies, including gene-editing techniques, RNA interference, and viral vector-mediated delivery systems, with a focus on the possible future developments in HLA-B27-related mechanisms. Understanding these novel approaches may pave the way for more effective, personalized treatments capable of solving the HLA-B27-positive axSpA conundrum.

关键词： Interferon gamma   Inflammatory skin disease   Immunomodulatory enzyme   Psoriasis   Streptococcal C5a peptidase   Preclinical  

摘要： Psoriasis is an incurable, immune-mediated inflammatory disease characterized by the hyperproliferation, abnormal differentiation of keratinocytes and a strong interferon gamma inflammatory signature. Interferon gamma plays a crucial role in various cellular processes, including activation of dendritic cells, antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production. These cellular processes are also integral components in the pathogenesis of psoriasis. To gain a deeper understanding of the pathogenesis of interferon gamma-induced psoriasis, psoriatic human epidermis equivalents were developed by stimulating healthy human epidermis equivalents with interferon gamma. Subsequently, the psoriatic human epidermis equivalents were treated with a novel enzyme, Streptococcal C5a peptidase, and compared to treatment using an established psoriasis drug, retinoic acid. Histological evaluation and barrier function assays, including lucifer yellow and biotin penetration assays, revealed that the integrity of the cellular barrier was compromised in samples treated with Interferon gamma alone, whereas treatment with Streptococcal C5a peptidase and retinoic acid successfully restored barrier function. Consistently, immunofluorescence and gene expression analysis of accepted biomarkers of psoriatic pathogenesis indicated that treatment with both drugs markedly reduced the psoriatic human epidermis equivalents phenotype, with greater efficacy observed for Streptococcal C5a peptidase. Thus, Streptococcal C5a peptidase demonstrated a robust modulating ability in restoring skin health in interferon gamma-induced skin psoriasis.

关键词： Neuro-Beh & ccedil   et disease   IL-35   Cerebrospinal fluid   IL-1 alpha   IL-18   IL-33   36   Tregs  

摘要： Background: IL-35 is a recently discovered immunoregulatory cytokine that inhibits inflammatory cytokines by suppressing their lineage-specific transcription factors. The objective of this study was to investigate the expression of IL-35 in the cerebrospinal fluid (CSF) of patients with Neuro-Beh & ccedil;et Disease (NBD). An immunocomparative analysis was performed between parenchymal NBD (pNBD) and non-parenchymal NBD (npNBD). Methods: We are investigating CSF IL-35 levels in 45 patients with (NBD), comprising 25 patients with pNBD and 20 with npNBD, compared to 27 patients with multiple sclerosis (MS) and 20 patients with non-inflammatory neurological diseases (NIND). We assessed the inflammatory cytokines (IL-1 alpha, IL-18, IL-33, IL-36), Foxp3 and CD4+ CD25+ Foxp3+ regulatory Treg T cells (Tregs). The following methodologies were employed: flow cytometry, ELISA, and real-time polymerase chain reaction (RT-PCR). For RT-PCR analysis, we calculated relative gene expression in target genes using the comparative CT method with the equation 2-Delta Delta Ct. We employed a receiver operating characteristic (ROC) curve to investigate the predictive value of IL-35 levels. Results: Protein and relative mRNA expression of IL-35 were significantly decreased in NBD and MS patients compared to the NIND group. Significantly lower CSF IL-35 mRNA (p = 0.0001) and protein (p = 0.0004) were observed in patients with pNBD compared to npNBD. The study revealed that NBD patients exhibited low Treg counts, and a significant positive correlation was identified between Treg numbers and CSF IL-35 (r = 0.554, p = 0.0001). Negative associations were observed between Tregs and CRP (r =- 0.518;p = 0.0001) and ESR (r = -0.571;p = 0.0001) in NBD. Levels of the pro-inflammatory mediators were found to be elevated in contrast to a low Foxp3 level in NBD, which was more reduced in pNBD compared to npNBD. In vitro cultured memory T cells from pNBD patients stimulated with LPS showed high levels