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关键词： diabetes   wound healing   mast cell   IL-1 beta   annexin A1  

摘要： Chronic, non-resolving inflammation is a major contributor to impaired wound healing in diabetes. Annexin A1 (AnxA1), a pro-resolving mediator, and its mimetic peptide Ac2-26 have demonstrated therapeutic potential in modulating inflammatory responses. In this study, we evaluated the effects of topical Ac2-26 hydrogel in a streptozotocin-induced diabetic wound model. Treatment significantly accelerated wound closure, improved tissue architecture, and reduced leukocyte infiltration. Immunohistochemical analysis revealed diminished mast cell accumulation and IL-1 beta expression in treated wounds. Complementary transcriptomic profiling supported the downregulation of pro-inflammatory genes, including Il1b and mast cell-related mediators, confirming the peptide's regulatory effect on the wound immune landscape. Mounting evidence suggests that dysregulated mast cell activity plays a role in the heightened inflammatory tone and delayed tissue repair observed in diabetic wounds. In our model, Ac2-26 hydrogel treatment attenuated IL-1 beta expression, suggesting an indirect downregulation of NLRP3 inflammasome activation, potentially mediated through mast cell modulation, though effects on other cell types within the wound microenvironment cannot be excluded. While definitive causality cannot be assigned, the integration of histological and transcriptomic data highlights mast cells as contributors to the IL-1 beta-driven inflammatory burden in diabetic wounds. These findings underscore the immunomodulatory capacity of Ac2-26 and its potential to restore resolution pathways in chronic wound settings, positioning it as a promising candidate for future therapeutic development.

关键词： ultramarathon   interleukin-6 (IL-6)   C-reactive protein (CPR)   tumor necrosis factor-alpha (TNF-alpha)   cytokine response   endurance exercise  

摘要： Ultramarathon running elicits a profound inflammatory response, characterized by significant increases in interleukin-6 (IL-6) and C-reactive protein (CRP), with comparatively modest changes in tumor necrosis factor-alpha (TNF-alpha). We reviewed approximately 80 field studies of ultramarathon events (distances >42.2 km) that measured IL-6, CRP, and TNF-alpha before and after races. IL-6 typically spiked immediately post-race-often rising dozens or even thousands of times above baseline-then rapidly declined, usually returning to near baseline within 24-48 h. CRP, an acute-phase protein, exhibited a slower, sustained elevation, peaking 24-72 h after race completion and remaining above baseline for 2-3 days before gradually returning to normal. TNF-alpha responses were variable: some studies reported small but significant post-race increases (roughly 1.2-1.7-fold above baseline), while others found no significant change in circulating TNF-alpha despite the extreme effort. Longer race durations and distances generally correlated with higher peak IL-6 and CRP levels. Experienced ultramarathon runners tended to exhibit attenuated inflammatory responses compared with less-trained individuals, and anti-inflammatory cytokines (e.g., IL-10) increased in tandem with IL-6 in well-trained athletes, helping to mitigate TNF-alpha elevations. In total, 28 studies were included in the final synthesis, and their quality was assessed using the Newcastle-Ottawa Scale. Visual synthesis tools, including a PRISMA flowchart and time course plots, are provided to enhance the narrative's interpretability. In summary, ultramarathon running elicits a robust systemic inflammatory response with distinct temporal patterns for IL-6, CRP, and TNF-alpha. These findings have important implications for athlete recovery, monitoring, and understanding the physiological limits of the inflammatory response to extreme endurance stress.

关键词： melanoma   synergistic treatment   controlled release   chemotherapy   immunotherapy   curcumin   interferon alpha   A375 melanoma cells  

摘要： Background/Objectives: Skin cancer remains a significant global health issue, driving the development of new treatment strategies to improve clinical outcomes and prevent recurrence. Traditional monotherapies often face obstacles such as bioactive resistance, prompting interest in combination therapies that enhance efficacy, while minimizing side effects. This study investigated the use of a co-nanoparticle approach of iron oxide nanoparticles (NPs) surface-functionalized with curcumin (Cur-FeONPs) delivered with prolonged-release interferon alpha (IFN alpha)-loaded PLGA NPs (IFN alpha-PLGANPs) for the synergistic treatment of malignant melanoma tested in A375 cells. Methods: Extensive in vitro characterization studies of the Cur-FeONPs and IFN alpha-PLGANPs were performed, including zeta-size profiling, morphological studies, and structural validation, in addition to cytotoxicity assessments on A375 melanoma and NIH-3T3 fibroblast cells. Results: The Cur-FeONP and IFN alpha-PLGANPs synthesis processes yielded NPs with an average size of 111.0 nm and 97.0 nm, respectively. Morphological and structural validation studies determined the successful synthesis of the nanoparticulate systems, with cell viability analyses displaying significant cytotoxicity against A375 melanoma cells for the combination treatment, when compared to the individual platforms, with a minimal effect on NIH-3T3 fibroblast cells. Conclusions: The results of this study present a promising synergistic approach for enhanced anticancer activity in A375 melanoma skin cancer cells, providing a potential platform for future preclinical and clinical studies.

关键词： mBSA   IL-1β   炎症性单关节炎   关节炎   动物模型   巨噬细胞  

摘要： 目的 构建mBSA/IL-1β诱导的炎症性单关节炎模型，探讨重组人源IL-1β和重组鼠源IL-1β联合mBSA诱导炎症性单关节炎小鼠模型的差异，为研究关节炎发病机理及药物治疗提供实验依据。方法 将20只C57BL/6小鼠随机分为两组，造模关节为左膝关节。一组为mBSA+重组人源IL-1β组（10只），一组为mBSA+重组鼠源IL-1β组（10只）。观察小鼠膝关节肿胀程度和体质量变化，HE检测膝关节病理变化，番红固绿O检测膝关节软骨损伤情况，免疫组化检测膝关节滑膜组织巨噬细胞表达。结果 与对照关节（右膝关节）相比，两组小鼠左膝关节均出现关节肿胀。与重组鼠源IL-1β组相比，重组人源IL-1β组小鼠体质量下降更明显，膝关节病理及软骨损伤明显加重，且左膝关节滑膜组织中巨噬细胞明显增多。结论 重组人源IL-1β与重组鼠源IL-1β联合mBSA在C57BL/6小鼠中诱导炎症性单关节炎，相比于重组鼠源IL-1β，重组人源IL-1β诱导的关节炎更严重，提示重组人源IL-1β联合mBSA更有利于炎症性单关节炎模型的建立。

关键词： 系统性红斑狼疮   ANA抗体谱检验   血清体液免疫检验   免疫系统   阳性率  

摘要： 目的 研究系统性红斑狼疮应用抗核抗体(ANA)谱检验和血清体液免疫检验的价值.方法 收集2023 年 1 月至 2024 年 12 月医院收治的 70 例系统性红斑狼疮患者作为研究对象,记为实验组,另选择同期在医院进行体检的70例健康者作为参照组.两组分别进行ANA抗体谱检验和血清体液免疫检验,之后比较两组体液免疫检验结果、体液免疫检验阳性率、ANA 抗体谱检验阳性率三项指标.结果 实验组与参照组两组体液免疫检验结果对比存在明显差异(P＜0.05);实验组体液免疫检验阳性率高于参照组(P＜0.05);实验组ANA抗体谱检验阳性率高于参照组(P＜0.05).结论 ANA抗体谱检验和血清体液免疫检验均能有效鉴别系统性红斑狼疮患者与正常人群,具有较大的临床推广价值.

关键词： Hematopoietic stem cell transplant   eplet   HLA eplet mismatch   epitope   haploidentical transplantation   reduced-intensity conditioning   outpatient transplantation  

摘要： BackgroundMolecular typing before hematopoietic stem cell transplantation (HSCT) at the eplet level is an emerging method to optimize HLA *** and methodsPatients who received outpatient haploidentical HSCT (Haplo-HSCT) from a sibling after reduced intensity conditioning (RIC) were studied. HLA class I and II mismatched eplets (MEs) load was determined using HLAMatchmaker software. A cutoff > or < 10 MEs was used to assess ***114 patients were studied. A locus B MEs load > 10 was associated with decreased overall survival (OS), (p = 0.049), and increased graft failure (GF) (p = 0.004). Mortality was higher with > 10 MEs in HLA-I locus B (p = 0.025), and HLA-II DRB1 (p = 0.026);chronic GVHD was higher with > 10 MEs in DRB1 (p = 0.009). Anti-HLA donor-specific antibodies (DSA) were more frequent in recipients with > 10 MEs load at locus C (p = 0.021) and DRB1 (p = 0.002). MEs load > 10 at locus C and DRB1 were associated with anti-HLA DSA. Infection (p = 0.012), DSA (p = 0.014), and relapse (p = 0.001) were associated with lower OS, while multitransfusion (p = 0.035), aGVHD (p = 0.035) and infection (p = 0.021) with reduced event-free survival (EFS).ConclusionHLA MEs load > 10 in locus B was associated with reduced OS, and in locus DRB1 with higher death rate and cGVHD after outpatient sibling haplo-HSCT using RIC.

关键词： Lung cancer   tumor necrosis factor-alpha (TNF-alpha)   interleukin-1 beta (IL-1 beta)   Wilms' tumor 1 (WT1   interleukin-10 (IL-10)  

摘要： Background: Lung cancer is driven by complex interactions between oncogenes and the inflammatory microenvironment. In particular, the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1(3), and their modulation of key regulators like Wilms' tumor 1 (WT1) and interleukin-10 (IL-10) remain underexplored. This study aims to investigate the role of these cytokines in WT1 and IL-10 regulation during lung cancer progression. Methods: A total of 982 lung cancer patient samples from The Human Protein Atlas were analyzed. In vitro, RAW264.7 macrophages were transfected with a WT1 plasmid (pWT1) and treated with TNF-alpha, IL-1(3, and lipopolysaccharide (LPS). WT1 and IL-10 expression was evaluated in A549, B16-F10, and J774.2 cell lines using reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and enzymelinked immunosorbent assay (ELISA). Immunofluorescence was employed to assess WT1 localization and phosphorylation, while immunohistochemistry was used to evaluate the correlation between WT1 and IL-10 in patient samples. Results: WT1 expression progressively increased from stage I to IV lung cancer and positively correlated with IL-10 in stages II and IV. WT1 overexpression in RAW264.7 cells treated with LPS led to a 12.9-fold increase in IL-10 expression. Proinflammatory cytokines decreased WT1 in A549 and B16-F10 cells but increased it in J774.2 macrophages, leading to cytoplasmic localization and phosphorylation. Patient sample analysis revealed a positive correlation between WT1 and IL-10 in advanced stages. Conclusions: These findings suggest that WT1 and IL-10 are modulated by inflammatory cytokines in a stage-dependent manner in lung cancer. WT1 upregulation is associated with increased IL-10 expression, particularly in advanced stages, highlighting potential therapeutic targets for modulating the immune response in lung cancer.

关键词： haplotypes   HLA-DR7   HLA-DRB4*01:01   polymorphism   Saudi Arabia  

摘要： This study investigates the distribution of human leukocyte antigen (HLA)-DRB4 alleles in HLA-DRB1*07:01-positive haplotypes within a Saudi cohort of 313 individuals. It identifies strong linkage disequilibrium between HLA-DRB1*07:01 and specific alleles. The most prevalent HLA-DRB1 similar to DQB1 combination identified is DRB1*07:01 similar to DQB1*02:02. Additionally, for the HLA-DRB1*07:01 similar to DQB1*03:03 association, DRB4*01:01 was found to be more common than the DRB4*01:03N allele. The most frequently observed extended haplotype is HLA-A*02:01 similar to C*06:02 similar to B*50:01 similar to DRB1*07:01 similar to DRB4*01:03 similar to DQA1*02:01 similar to DQB1*02:02 similar to DPA1*01:03 similar to DPB1*04:01. These findings emphasize the distinct genetic characteristics of the Saudi population and contribute to understanding haplotypic diversity, particularly the prevalence of HLA-DR7-related alleles and their implications for disease susceptibility and transplantation compatibility.

关键词： GBM   TMZ   ADAM12   TNF-alpha   DNA damage response  

摘要： Development of temozolomide (TMZ) resistance is a critical factor contributing to a poor prognosis in glioma patients. TMZ resistance is also closely associated with the phosphorylation level of NF-kappa B, yet targeted inhibition of NF-kappa B activity in glioma can be leveraged to overcome TMZ resistance. ADAM12, a protein significantly overexpressed in glioma cells, is implicated in the pathogenesis and progression of glioma, yet its role in the development of TMZ resistance is completely understood. We found that knockdown of ADAM12 was shown to arrest the glioma cell cycle, enhance apoptosis, inhibit DNA damage repair mechanisms, and sensitize glioma cells to TMZ. Targeting ADAM12 in vivo was found to increase the sensitivity of glioma cells to TMZ. Survival analysis indicated that ADAM12 serves as a prognostic marker for TMZ treatment. Using ELISA and protein interaction predictions via docking simulation, we identified the TNF-alpha shedding function of ADAM12 as a critical regulator of glioma progression. Furthermore, in glioma cell lines with unmethylated MGMT, the knockdown of ADAM12 enhanced sensitivity to TMZ by inhibiting the TNF-alpha/NF-kappa B pathway and reducing MGMT expression. In all, these results demonstrated that ADAM12 aids in shedding of membrane-bound TNF-a to drive TMZ resistance in glioma.

关键词： CD8(+) T cells   high-mobility group protein B1   programmed cell death ligand 1  

摘要： T cells are the most important cytotoxic cells involved in antitumor immune responses. After recognizing the major histocompatibility complex (MHC)-peptide complex, cytokines including interferon-gamma (IFN-gamma) are released to kill tumor cells. However, IFN-gamma can also induce tumor cells to express PD-L1. This molecule can bind to PD-1 on the surface of T cells to exert inhibitory functions. In response to stimuli, like chemoradiotherapy or immunotherapy, tumor cells release damage-associated molecular patterns, including high-mobility group protein B1 (HMGB1). Our previous studies revealed that HMGB1 can increase the antitumor activity of T cells and enhance the secretion of cytokines, including IFN-gamma. However, the effect of HMGB1 on PD-L1 expression in non-small cell lung cancer remains unclear. Here, we examined the expression of HMGB1 and PD-L1 in tumor tissue slices of patients with non-small cell lung cancer with high expression of IFN-gamma and observed that they exhibited a negative correlation, which was also verified by our analysis in The Cancer Genome Atlas. In vitro experiments demonstrated that HMGB1 could bind to RAGE (receptor for advanced glycation end products) and inhibit IFN-gamma induction of PD-L1 by inhibiting the JAK1/STAT3 pathway. In vitro and in vivo experiments indicated that HMGB1 enhanced the antitumor effects of chimeric antigen receptor T cells and inhibited tumor growth. These results showed that HMGB1 inhibited IFN-gamma-induced PD-L1 expression, thereby enhancing the antitumor effects of T cells, and confirmed the role of HMGB1 as a prognostic indicator for lung cancer treated with chimeric antigen receptor T cells.