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关键词： 辅酶Q10   法舒地尔   不稳定型心绞痛   IL-6   sST2   BNP  

摘要： 探究对不稳定型心绞痛患者采用辅酶Q10联合法舒地尔治疗在改善患者生理指标方面的作用。方法 在本院近两年接收的冠心病患者中选取100例不稳定型心绞痛患者,随机分为观察组(n=50)和对照组(n=50)。对比两组心功能指标、炎症因子水平、sST2及BNP以及治疗效果。结果 观察组患者心功能、sST2、BNP改善程度更好,炎症因子水平更低,整体治疗效果更为显著,p<0.05。结论 对不稳定型心绞痛患者使用辅酶Q10联合法舒地尔治疗,可降低炎症因子水平,降低sST2和BNP指标,改善心功能,有效提升治疗效果,有利于患者心血管健康。

关键词： Biological sciences   Biochemistry methods   Immunology   Proteomics  

摘要： Recent studies suggest that CD4+ T cells can exert potent anti-tumor effects and improve immunotherapy efficacy by aiding CD8+ T cells. However, characterizing the mechanism of CD4+ T cells' anti-tumor activity has been challenging due to inaccurate major histocompatibility complex class II (MHC-II) peptide prediction algorithms and the lack of high-quality reagents for immune monitoring. To address this, we developed MHC2-substitution of CLIP and analytical LCMS evaluation (MHC2-SCALE), a streamlined approach combining affinity optimized class II-associated invariant chain peptide (CLIP) exchange technology, high throughput 2D-LCMS analysis, and rapid generation of peptide-bound MHC-II monomers for subsequent multimer assembly. We validated MHC-II peptide candidates predicted by the immune epitope database (IEDB) algorithm, as well as uncovered many true and immunogenic MHC-II binders that were not predicted by IEDB. Thus, MHC2-SCALE expands the opportunities for discovering, tracking, and phenotyping antigen-specific CD4+ T cells in preclinical and clinical settings, thereby improving therapies for cancer, autoimmunity, or infectious diseases.

关键词： welding and metal fumes   zinc (Zn)   copper (Cu)   metal (nano)particle exposure   nanotoxicology   oxidative stress   inflammatory response   cytokines (IL-6   IL-8   MIP-1 beta/CCL4   TNF-alpha)   early-stage marker   occupational health  

摘要： Zinc (Zn)- and copper (Cu)-containing welding fumes elevate inflammatory markers (CRP, TNF-alpha, IL-6, IL-8) in healthy individuals and welders. Zn- and Cu-containing nanoparticles are toxic to human macrophages. Therefore, ZnO exposure limits are under discussion. In this study, the effects of Zn/Cu-containing welding fume suspensions on A549 alveolar epithelial cells (exposure concentrations: 0.01/0.1/1/10/100 mu g/mL) and THP-1 macrophages (additionally 0.001 mu g/mL) were investigated over a period of 48 h. Effects on apoptosis, cytotoxicity, genotoxicity, superoxide dismutase (SOD) activity, and cytokine levels (IL-6, IL-8, MIP-1 beta/CCL4, TNF-alpha) were evaluated. Welding fume exposure increased SOD activity, and it increased Annexin-V binding and cytotoxicity effects starting at 10 mu g/mL in A549 cells and particularly in THP-1 macrophages. A549 cells showed increased IL-6 at 10 and 100 mu g/mL, and significant IL-8 release occurred at 10 mu g/mL for A549 and 0.1 mu g/mL for macrophages. Exposed macrophages released TNF-alpha at 1 mu g/mL after 24 and 48 h and MIP-1 beta/CCL4 at 0.01 mu g/mL after 6 h and at 0.001 mu g/mL after 48 h. No genotoxic effects were detected. MIP-1 beta/CCL4 is a sensitive new biomarker for human macrophages exposed to Zn/Cu-containing welding fumes. The findings suggest that Zn/Cu particles affect lung cells already at doses below current occupational thresholds.

关键词： 根治性放疗   比卡鲁胺   前列腺癌   血清前列腺特异抗原   骨转移  

摘要： 根治性放疗联合比卡鲁胺对前列腺癌患者血清前列腺特异抗原水平及骨转移发生率的影响。方法 2021年60例前列腺癌患者随机单盲分组,对照组根治性放疗,观察组根治性放疗联合比卡鲁胺治疗,对比效果。结果 治疗后观察组PSA、F-PSA、血清睾酮水平下降更多(P<0.05),治疗1年、3年后最大尿流率、EPIC评分高于对照组(P<0.05),并发症发生率和治疗1年、3年后的骨转移发生率均低于对照组(P<0.05)。结论 根治性放疗联合比卡鲁胺用于前列腺癌患者治疗中有效,可以降低其特异性的肿瘤相关指标,包括PSA、F-PSA等,减少放疗生活质量的不良影响,改善最大尿流率,还能降低骨转移风险,并发症发生率比单一放疗更低。

关键词： Periodontitis   DNA methylation   Immune cells   Neutrophils   Gene expression   Methyltransferases   Inflammatory diseases   Protein-protein interactions  

摘要： Background Periodontitis is a typical oral disease. Polymorphonuclear neutrophils (PMNs) are crucial immune cells in periodontal tissues, relating to infection, inflammation, and innate immunity. We herein aimed to explore important periodontitis PMN related genes. Methods Periodontitis and control samples were downloaded from Gene Expression Omnibus database, including GSE173082 (methylation data, n=72), GSE10334 (n=127), GSE43525 (n=23), GSE16134 (n=134). Differential expression analysis and differential methylation analysis was employed to find candidate genes. Receiver operating characteristic analysis was performed to evaluate the diagnostic value of the hub gene. The functional pathways were determined by gene set enrichment analysis. Using CIBERSORT software, the immune cell infiltration landscape of periodontitis tissue was explored. The mRNA and protein levels of target gene in clinical tissue samples were determined employing RT-qPCR and western blotting. All statistical analyses were conducted in R software. Results After integrating DNA methylation with transcriptome profiles, GRASP, HLA-DMB, HLA-DMA, CAB39, NCOA2 and TLE4 were identified as candidate genes in periodontitis PMNs. HLA-DMB showed the highest correlation with core DNA methyltransferase DNMT3B (p < 0.05). Between high and low HLA-DMB expression samples, multiple immune related pathways were enriched, and differential immune cell infiltration was observed (p < 0.05). HLA-DMB exhibited significantly higher expressions in both public database and clinical tissue samples (p < 0.05). HLA-DMB was a diagnostic marker for periodontitis (GSE43525 AUC=0.777 and GSE16134 AUC=0.783). Conclusions Significantly higher HLA-DMB expression was noticed in PMNs of periodontitis, which probably contributed to the development of periodontitis. HLA-DMB is a promising diagnostic marker for periodontitis.

关键词： Preeclampsia   HLA-F   Trophoblast   Proliferation   PKM2   Lactylation  

摘要： BackgroundThe regulatory molecule Human Leukocyte Antigen F (HLA-F) has been implicated in trophoblast proliferation during pregnancy, and reduced levels of this antigen have been identified in trophoblast cells of patients with preeclampsia. This study aimed to analyze the effect and mechanism of HLA-F on the proliferation of trophoblast and the underlying mechanism of reduced HLA-F involved in ***-PCR, Western blot (WB), and Immunohistochemistry (IHC) were used to detect the expression of HLA-F and Pyruvate Kinase Muscle isoform 2 (PKM2) in placenta tissues. Jar cells were transfected with overexpression lentivirus, specific siRNA, and shRNA to regulate corresponding genes. Immunofluorescence was used to analyze the expression and distribution of HLA-F and PKM2. Extracellular and intracellular lactate, pyruvate, and enzymatic activity of PKM2 were measured using the corresponding assay kits. Cell proliferation was measured by CCK8, MTT, colony formation assay, and Mini patient-derived xenograft (Mini-PDX). Chromatin Immunoprecipitation and deep sequencing (ChIP-seq) and 4-dimensional label-free quantitative proteomics (4D-LFQP-LA) were used to analyze the HLA-F-binding DNA sequences and the differential lactylation proteins in HLA-F-overexpression Jar and its *** expression of HLA-F is reduced in extravillous trophoblast and villous cytotrophoblast from patients with preeclampsia. Over-expression of HLA-F promoted proliferation while under-expression inhibited it. Further experiments demonstrated that over-expression of HLA-F promoted expression of the PKM2 protein and its enzymatic activity, resulting in enhanced glycolysis in Jar cells. Specifically, we determined that HLA-F regulated the expression of PKM2 by binding the promoter of PKM, and promoted PKM2 enzyme activity by down-regulating the lactylation of residue K305. Moreover, silencing PKM2 with siRNA reduced HLA-F-mediated glycolysis and proliferation in HLA-F-overexpress

摘要： In recent years, circRNAs have garnered increasing attention for their role in cervical cancer. However, the functions of many newly identified circRNAs remain unclear and require further exploration. In this study, we investigated the expression and oncogenic potential of the novel circRNA circSTX6 in cervical cancer. Our findings revealed that circSTX6 is highly expressed in cervical cancer (CC) and is significantly associated with poor patient prognosis, promoting cell survival, proliferation, invasion, and migration. Mechanistically, circSTX6 enhances the stability of the transcription factor SPI1 by binding to it, thereby upregulating IL6 transcription and activating the JAK2/STAT3 signaling pathway. Additionally, METTL3-mediated N6-methyladenosine (m6A) modification stabilizes circSTX6 through recognition by YTHDC1, forming a positive feedback regulatory loop among METTL3, circSTX6, and SPI1. These findings not only deepen our understanding of the biological mechanisms underlying CC but also highlight circSTX6 as a potential target for molecular therapies.

关键词： Cardiac insulin resistance   Nuclear factor kappa B   Tumor necrosis factor alpha   Suppressor of cytokine signaling 3   Inducible nitric oxide synthase   Sodium-potassium ATPase pump  

摘要： Our previously published results have proven that low-intensity exercise, equivalent to brisk walking, is beneficial in managing cardiac insulin resistance in post-weaning male rats exposed to a fructose-rich diet. Still, its role in protecting against cardiac inflammation is unclear. This experiment was designed to investigate the preventive effect of low-intensity exercise on cardiac inflammation in male post-weaning rats exposed to a fructose-rich diet (10%). Male Wistar rats were randomly assigned to a sedentary control group, a sedentary group with fructose overload, and a fructose overload group subjected to treadmill exercise for nine weeks. Protein expression of cardiac inducible nitric oxide synthase (iNOS), matrix metalloproteinase 9, as well as cellular localization/phosphorylation of nuclear factor kappa B (NF-kappa B), and alpha 1 and alpha 2 subunits of sodium-potassium ATPase pump (Na/K-ATPase) was determined. Additionally, gene expression of tumor necrosis factor alpha (TNF alpha) and suppressor of cytokine signaling 3 (SOCS3) was examined. The results demonstrate that a chronic fructose-rich diet in sedentary rats elevates the expression of key inflammatory markers, including SOCS3, TNF alpha, NF-kappa B, and iNOS, as well as the plasma membrane alpha 1 and alpha 2 subunits. Exercise prevented alterations induced by a fructose-rich diet, except iNOS expression. Additionally, exercise increased the protein expression of the alpha 1 and alpha 2 subunits of Na/K-ATPase in the lysate of fructose-fed rats. These findings suggest that low-intensity exercise is an effective non-invasive strategy for cardioprotection, helping to prevent inflammation by modulating TNF alpha and NF-kappa B expression in insulin-resistant hearts of post-weaning male rats.

关键词： HLA infertility   HLA   IVF   Unexplained infertility   HLA similarity  

摘要： Objective: To examine whether the rate of HLA similarity among 609 primarily infertile couples is higher than would be expected by chance. Design: Clinical Trial. Subjects: 609 primary infertile couples (mean age women: 34.35 years, men: 37.59 years) were recruited before undergoing IVF or ICSI therapy. Couples with former pregnancies, tubal factor, azoospermia or donor therapies were excluded. Intervention: For each of the partners, exons encoding the corresponding antigen recognition sites of HLA-A,-B,-C,-DRB1,-DQB1, and-DPB1 were sequenced by using next-generation sequencing. HLA similarity between partners was determined based on the probability of homozygous offspring and the observed probability of heterozygous offspring in the sample of primary infertile couples was comparted to the probability for random pairing using bootstrapping. Main outcome measures: HLA similarity of infertile couples compared to randomly assigned couples. Results: In each of the loci, infertile pairs shared more alleles than expected by chance. This result was significant for all HLA class 2 loci (-DRB1,-DQB1,-DPB1), as well as for the HLA class I locus-C, while HLA-A and-B showed a nonsignificant trend towards higher similarity. Conclusion: These data suggest that HLA similarity between couples relates to primary infertility.