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关键词： hepatocellular carcinoma   IL-22   liver fibrosis   liver regeneration   viral hepatitis  

摘要： Interleukin-22 (IL-22), a cytokine from the IL-10 family produced by T cells and innate lymphoid cells, plays a crucial role in immune responses and tissue regeneration. Its association with liver disease has garnered significant attention;however, its exact impact remains controversial. This review aims to enhance the current understanding of the dual role of IL-22 in liver disease by exploring its protective and pathogenic effects. First, we provide an overview of IL-22 biology, including its source, receptors, and signaling pathways. Subsequently, we offer a comprehensive overview of the dual function of IL-22 in non-neoplastic liver disease, emphasizing its antiapoptotic and regenerative properties. We also discuss the applicability of the conclusions drawn from studies on nonalcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease. Furthermore, we elaborate on the intricate role of IL-22 in hepatocellular carcinoma, particularly its influence on the tumor microenvironment, proliferation, and immune evasion. In conclusion, IL-22 is paradoxical in liver disease, acting as a friend and foe. It is imperative to understand this paradox to develop targeted therapies that capitalize on the beneficial effects of IL-22 while mitigating its detrimental effects.

关键词： biologics   eosinophils   rhinosinusitis  

摘要： Background: Type 2 inflammation dominates eosinophilic chronic rhinosinusitis (eCRS) and adult onset asthma. IL-4, -5, and -13 are prominent disease mediators. Disease control can be achieved with biologic therapies. However, despite some patients entering remission, others experience poor control. Aim: We aimed to describe eCRS patients treated with anti-IL-5R antibody (benralizumab) and assess characteristics between responders and those requiring class switching to anti-IL-4/13R (dupilumab). Method: A retrospective cohort study was performed on consecutive adult patients with eCRS and asthma who had commenced benralizumab. Disease control was defined as controlled or poorly controlled (EPOS2020 partly control/uncontrolled). Poorly controlled patients were switched to dupilumab. Baseline and post-IL-5R characteristics including age, sex, 22-item Sinonasal Outcome Test (SNOT-22), Asthma Control Questionnaire (ACQ) score, and serum/tissue eosinophilia were assessed. Disease control post-class switching was reassessed. Factors predicting poorly controlled disease on anti-IL-5R therapy were sought. Results: Fifty patients were assessed (51.44 +/- 12.73 years, 56% female). Poorly controlled disease on anti-IL-5R requiring class switch to dupilumab was seen in 42%. Poorly controlled patients were younger (46.14 +/- 10.76 vs. 55.28 +/- 12.83 years, p = 0.01) with higher baseline SNOT-22 (61.42 +/- 19.19 vs. 42.32 +/- 21.55, p < 0.01). Baseline ACQ scores and eosinophil count (0.78 +/- 0.49 vs. 0.62 +/- 0.34 x 10(9 )cells/L, p = 0.23) and were similar between groups. In the poorly controlled patients on anti-IL-5R therapy, eosinophilia had reduced in both serum (0.78 +/- 0.5 vs. 0.02 +/- 0.1 x 10(9 ) cells/L, p < 0.01) and tissue (>100 cells/HPF: 100% vs. 29%, p = 0.01). Class switching resulted in disease control for 65%. Conclusion: Neither eosinophilia nor its reduction predicted a non-responder group to anti-IL-5R therapy. While the eosinophil population may be a good

关键词： HLA‐C*01:257N   next‐generation sequencing   novel allele  

摘要： HLA-C*01:257N differs from the HLA-C*01:02:01:01 allele by one nucleotide substitution in exon 4.

关键词： Glioblastoma   Synergism   Curcumin   2-deoxyglucose   Glial stem cells   Potentiate  

摘要： Glioblastoma is the most lethal brain tumor;despite available multimodal therapies. This poor survival is an outcome of many contributing factors the major is resistance due to inflammation and the presence of a subset of cells called glial stem-cells (GSCs). A rationale combination of drugs which act by targeting multiple mechanisms to inhibit cancer cells and GSCs would be more potent in abrogating chemoresistance. In this study, we aimed to target cancer hallmarks using a natural polyphenol in combination with 2-deoxyglucose, a glycolytic inhibitor on the heterogeneous human U-87 Glioblastoma model. The U-87 glioblastoma cells were treated with curcumin, 2-deoxyglucose and combination of both. Cell proliferation was determined by MTT assay and combination index was analyzed. Cell cycle inhibition and apoptosis were assessed by flow cytometry. The tumorigenicity of the cells was evaluated by clonogenic and soft agar assay. Migration efficacy of the cells was assessed by wound healing assay while the inflammation trigger Il-6 was assessed by ELISA. The changes in expression of molecular marker of stemness were analyzed by immuno-cytochemistry. Curcumin enhanced the cytotoxic effect of 2-deoxyglucose in GB cancer cells. The combination of CUR (20 mu M) and 2-DG (4mM) showed a synergistic effect in reducing cell viability with a combination index of less than 0.9. The polyphenol induced apoptosis, arrested the cells in S and G2/M phase of the cell cycle, inhibited anchorage dependent, anchorage independent clone forming efficacy, cell migration capacity as well as stemness while 2-DG downregulated IL-6 expression potently. Our novel combination exhibited the potential to reduce glio-oncogenesis trigger Il-6 and inhibit GSCs responsible for relapse and resistance. The study suggests that our tailor-made combination using established drugs can target multiple cancer signaling molecules to yield optimal therapeutic outcome and is the right approach to address stemness a

关键词： HLA‐B*18:247   HLA   NGS   new methods   novel allele  

摘要： HLA-B*18:247 differs from the HLA-B*18:01:01:01 allele by one nucleotide substitution in codon 193 in exon 4.

关键词： Jujube polysaccharides   Ulcerative colitis   Interleukin-33   Tumorigenicity 2 suppression   MYD88  

摘要： Jujube is a medicinal herb and daily food. Polysaccharides extracted from jujube possesses immune regulatory activity. In this study, we investigated whether jujube polysaccharides (JP) could ameliorate ulcerative colitis (UC), an inflammatory disease, and explore the potential mechanism of UC. We first extracted and characterized the structure JP, using dextran sulfate sodium-induced UC mice model to verify the pharmacological function. Research proved that JP treatment could ease UC mice symptoms and pathological injury. According to transcriptomics analysis, majority genes were enriched to cytokines-cytokines receptors signal pathway. Results showed that the increasing proinflammatory cytokines in UC mice colon were declined after JP intervention. Meanwhile, the receptor of interleukin-33 (IL-33), tumorigenicity 2 suppression (ST2) and downstream protein MYD88 expression in UC mice colon were corrected by JP intervention. As a result, according to immunohistochemistry detection, JP downregulated UC mice colon T cells expression (labeled by CD3+). We further employed flow cytometry to validate that JP could suppress CD4+ high expression on Jurkat cell stimulated by IL-33. In conclusion, JP could ameliorate UC mice symptoms, the mechanism of which was related to the regulation of IL-33/ST2 axis.

关键词： Rheumatoid Arthritis   JAK3   Molecular docking   DFT calculations   Molecular dynamics simulations  

摘要： Rheumatoid Arthritis (RA) is a persistent autoimmune disease affecting approximately 0.5-1 percent of the world population. RA prevalence is higher in woman aged between 35 and 50 years than in age matched men, though this difference is less evident among elderly patients. The profound immune specific effects of disrupted JAK 3 (Janus kinase 3) signaling highlight the possibility of therapeutic targeting of JAK3 as a highly specific mode of immune system suppression. To address the above problem which is unendurable to patients and in the hope to cater some respite to such suffering we have targeted JAK 3 protein and JAK/STAT signaling pathway with compounds downloaded from FDA database, and performed screening of all available compounds docked against JAK3 protein. The difference between the target protein and other proteins of the same family was studied using cross docking and the compounds having higher binding affinity to JAK3 protein also showed more selectivity towards the particular protein. Density functional theory and molecular dynamics simulation study was done to study the compounds at their atomic level to know more about their drug likeliness. At the end of the study and based on our analysis we have come up with three FDA approved drugs that can be proposed as a treatment option for Rheumatoid Arthritis.

关键词： Alpha-toxin   Staphylococcus aureus   Hla toxoids   Red blood cells   Vaccines   Pore-forming toxin   HS-AFM  

摘要： Alpha-toxin (Hla) variants, such as the toxoids HlaH35A, HlaH35L, and HlaH35LH48L, have been shown to lack hemolytic activity and present promising antigen sources for vaccine development against S. aureus. The His35 site is critical in the oligomerization process of Hla during transmembrane pore formation, leading to cell lysis. This study employed high-speed atomic force microscopy (HS-AFM) to image the structures of HlaH35A, HlaH35L, and HlaH35LH48L proteins on POPC/Chol lipid membranes. Single-site His35 mutations (HlaH35A, HlaH35L) could form oligomer structures, whereas the double-site HlaH35LH48L mutation resulted in the monomer state. These HS-AFM findings confirm that the region between His35 and His48 is crucial for protomerprotomer interactions essential for oligomerization and pore formation. Hemolytic activity of wild-type Hla on red blood cells (RBCs) was significantly reduced when mixed with HlaH35A, HlaH35L, or HlaH35LH48L at weight ratios 1:5 (HlaWT:toxoid) or higher. However, these toxoids exhibited weak neutralization activities at lower mixing ratios with HlaWT. The increased anti-Hla antibodies (IgG) in mice treated with these Hla toxoids have emerged as a potential treatment avenue to neutralize the hemolytic activity of the HlaWT toxin on RBCs. Serum analysis from mice injected with HlaH35A, HlaH35L, and HlaH35LH48L toxoids showed that these sera could neutralize the hemolytic activity of the HlaWT toxin. Thus, these Hla variants are promising candidates for developing supportive treatments for S. aureus infections.

关键词： HLA   HLA-DPB1*29:01:02   new methods   NGS   novel allele  

摘要： HLA-DPB1*29:01:02 differs from HLA-DPB1*29:01:01 by a single synonymous substitution in exon 2.