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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： African trypanosomiasis   DNA vaccine   immune response   immunisation   major surface protease-B (MSP-B)   Trypanosoma brucei brucei  

摘要： As an effort towards vaccine development against African trypanosomiasis, we studied key parasite molecules that mediate VSG functions, specifically the major surface protease-B of Trypanosoma brucei that catalyses proteolytic removal of old VSGs for expression of new ones, an important stage-specific function that allows the parasite to survive in its host, thus making it an attractive candidate for vaccine development. Herein, the Tbmsp-b gene was cloned into a pVAX-1 plasmid to produce the pVAX-1-Tbmsp-b construct for DNA vaccine trials. BALB/c mice were immunised by intradermal injection with a 100 mu g dose of the construct thrice on Days 0, 21 and 42, then inoculated with 2000 parasites on Day 56. Anti-trypanosome-specific antibody (IgG) and cytokine (IFN-gamma) were monitored by ELISA from sera of immunised and unimmunised mice. Immunised mice showed significantly (p < 0.05) higher IgG and IFN-gamma responses, lower parasitaemia (by 75% and 51.2% of parasitaemic scores on the first and fifth week of infection) and longevity by up to 22 days compared to unimmunised mice. These results showed that the construct provided partial protection to virulent T. b. brucei (Federe strain) infection in susceptible BALB/c mice, suggesting the potential for using MSP-B as an antigen in DNA vaccine development against African trypanosomiasis.

关键词： Neutrophils   interleukin-6   interleukin-6 receptor signaling   bone fracture healing   inflammation  

摘要： Background: Neutrophils are the predominant immune cell type in the early fracture hematoma, playing key roles in orchestrating the immune response and bone repair by clearing pathogens and debris, producing extracellular traps and proteases, and releasing various signaling molecules. However, neutrophil roles in fracture healing remain incompletely understood. They are a key source of interleukin-6 (IL-6) and the soluble IL-6 receptor (sIL-6R), driving both IL-6 classic signaling via membrane-bound IL-6R and trans-signaling via sIL-6R. Classic signaling drives neutrophil infiltration into the fracture hematoma and is crucial for bone repair, whereas trans-signaling impairs healing after severe trauma. Here, we examined neutrophil-specific IL-6 signaling in fracture healing. Methods: We used male mice with neutrophil-specific deletion of IL-6 or IL-6R. Physiological bone phenotype and effects on fracture healing (external fixator stabilized femur osteotomy) were assessed in 12-week-old mice by flow cytometry, cytokine multiplex analysis, biomechanical testing, micro-computed tomography, and histomorphometry. Results: While neutrophil-specific deletion of IL-6 or IL-6R did not affect bone under physiological conditions, IL-6R deletion led to a reduction in neutrophils and macrophages and an increase in T lymphocytes. The immune response to fracture was unaffected by either deletion, because cytokine levels in the fracture hematoma and serum remained unchanged compared to controls after 6 h. Additionally, the biomechanical properties of fractured femurs together with structural and cellular bone parameters on day 21 did not differ compared to controls. Conclusions: Neutrophil-induced IL-6 signaling appears nonessential for physiological bone turnover and fracture healing. Its role in impaired healing under conditions of excessive inflammation remains to be determined.

关键词： alpha-olefins   Fischer-Tropsch synthesis   green separation technology   ionic liquids   microwave-assisted extraction  

摘要： The actual applications of extraction methods for alpha-olefins separation are limited by their long time and high energy consumption. Hence, this study employs microwave technology to intensify the extraction process using Ag-based ionic liquid (Ag-IL), where the influence of microwave irradiation and the mechanism of microwave-assisted ionic liquid extraction (MAILE) are investigated, along with a comprehensive techno-economic analysis of process feasibility. The results of COSMO-RS and DFT simulations demonstrate the dominant role of pi-complexation in identifying Ag-IL with high selectivity, indicating the possible enhancement caused by microwave irradiation. The subsequent kinetic experiments show that compared with conventional routes, the MAILE accelerated the extraction process by approximately 89.72%. As a result, the total annual cost of unit product of the overall process is reduced by 6.43% according to techno-economic analysis by Aspen Plus, indicating that MAILE is a cost-effective, scalable, and sustainable approach to alpha-olefin separation, offering process efficiency and environmental sustainability.

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： asymptomatic esophageal eosinophilia   brain-derived neurotrophic factor   EoE diagnostic panel   eosinophilic esophagitis   IL-13   iPSC-derived sensory neurons   neuropathic and inflammatory pain panel   neurotrophic receptor tyrosine kinase 2  

摘要： Dysregulated levels of pro-inflammatory cytokines such as interleukin (IL)-23 have been linked to multiple inflammatory diseases, including psoriatic arthritis (PsA) and ankylosing spondylitis. This systematic review explored the effect of IL-12 and/or IL-23 inhibitors on the aetiology of axial PsA (axPsA) and axial spondyloarthritis (axSpA). We conducted a literature review of published articles up to June 2023. The outcomes assessed included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI-50, and modified BASDAI. Given the heterogeneity of study populations, designs, and outcome measures of the included studies, we performed a narrative synthesis. The data from the limited literature did not find any efficacy of IL-12 and/or IL-23 inhibitors for the management of axSpA, except for one observational study. However, reported data showed improvements in BASDAI, modified BASDAI, and Ankylosing Spondylitis Disease Activity Score for patients with axPsA. Limited and heterogeneous data currently leaves the effectiveness of IL-12 and/or IL-23 inhibitors for axSpA inconclusive. Yet, improvements in disease activity scores for patients with axPsA hint at the potential of IL-12 and/or IL-23 inhibitors in managing this condition. More extensive studies with larger samples are needed to definitively confirm the role of IL-12 and/or IL-23 inhibitors in axSpA and PsA.

关键词： eosinophilic esophagitis   interferon-gamma   interleukin-10   regulatory B cells  

摘要： Background: Eosinophilic Esophagitis (EoE) is a chronic food allergy that causes esophageal inflammation and fibrosis and manifests with symptoms of reflux, chest pain, swallowing difficulty, and food impactions. Though the prevalence of EoE is increasing by similar to 15% each year, our understanding of EoE immunopathology is limited. A noted feature of EoE is the presence of food-specific IgG4 antibodies in the circulation and esophageal tissue. Production of IgG4 is confined to IL-10+ B cells (Bregs) in other allergic diseases, suggesting Bregs may be present in EoE. Methods: We examined circulating Bregs in patients with EoE milk allergy. In parallel, we performed mechanistic investigations of the role of Bregs in a murine model of food-antigen-dependent EoE. Flow cytometry and histologic analyses were used to assess esophageal and draining lymph node immune cells, and in vitro assays were used to evaluate Breg functional capacity. Results: Breg frequency was reduced in both EoE milk allergic subjects and an EoE disease model. Murine Breg suppressive capacity was impaired during EoE-like inflammation. Inducible deletion of Breg-derived IL-10 worsened EoE-like inflammation, while adoptive transfer of IL-10 sufficient Bregs suppressed DC activation and improved esophageal eosinophilia. IFN gamma was sufficient to suppress Breg expansion and IL-10 production in vitro and contributed to Breg dysfunction and esophageal inflammation in vivo. Conclusion: Bregs play an immunoregulatory role during EoE by controlling esophageal eosinophilia but are functionally impaired due to IFN gamma-mediated signaling. These findings have important implications for understanding EoE's etiology and implementing future therapies that target IFN gamma.

关键词： Cytokines   Interleukin 6   Tumor necrosis factor alpha   Early molecular response  

摘要： The study aimed to study the correlation of inflammatory cytokines TNF alpha and IL6 with early molecular response (EMR) in Indian CML patients on Imatinib. Methods-A tertiary hospital based cross sectional observational study included 47 patients with newly diagnosed CML over a period of 18 months. Plasma levels of TNF alpha and IL6 along with levels of BCR-ABL were done at baseline and at 3 month of therapy. Results- TNF alpha at baseline was the better predictor of EMR not achieved at cut off point of > 109 pg/ml and IL6 at 3 month was the better predictor of EMR not achieved at cut off point of > 45 pg/ml Conclusion- The combination of high TNF and IL-6 levels at baseline and at 3 months identifies a high risk subset of CML patients with significantly lower EMR. Mesurement of these cytokines at above time points may allow treatment intensity to be individualised based on the patient's risk profile.

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