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关键词： 牛结节性皮肤病病毒   山羊痘病毒   A33R蛋白   多克隆抗体   病毒复制  

摘要： 为获得牛结节性皮肤病病毒（LSDV）A33R蛋白的多克隆抗体，并进行免疫学鉴定，本研究利用293F表达系统表达A33R蛋白并验证蛋白的抗原性，将纯化后的重组A33R蛋白作为免疫原3次免疫BALB /c小鼠，获得多克隆抗体。包被不同来源的6种抗原检测多抗的特异性，包被A33R蛋白及灭活羊痘AV41病毒测定其效价，利用中和实验测定多抗的中和效价。此外，利用该抗体测定灭活LSDV及灭活羊痘AV41复制过程中A33R的表达情况。结果表明，本研究成功表达了A33R蛋白并制备了A33R多抗，A33R多抗与LSDV的其它蛋白L1R、A27L、P32不反应，也不与其它常见感染牛或羊的ORFV B2L蛋白、BCoV S蛋白、PPRV N蛋白反应；包被A33R蛋白，多抗效价为1:1 968 300，包被灭活AV41，多抗效价为1:800；进一步测定A33R多抗血清表明血清具有中和效应，且中和效价为 1:64。病毒感染6 h，没有检测到A33R的表达，但是24 h后在LSDV和AV41感染的细胞中均检测到A33R的大量表达。本研究成功的研究结果不仅为进一步研制A33R的单克隆抗体奠定了基础，也为LSDV等痘病毒的复制感染规律的研究和后续疫苗的研发奠定了基础。

摘要： We developed a cell type-specific proteogenomic approach to reveal novel or unannotated open reading frames (nuORFs) using transcriptomics, ribosomal profiling, and proteomic analysis of human pancreatic β-cells using stem cell-derived β-cells and/or cadaveric islets. Our analysis revealed translational regulation of β-cell-specific pathways during differentiation and identified 965 nuORFs, with a majority exhibiting protein support and substantial β-cell specificity. A primate-specific ORF located in the 5' untranslated region of the type 1 diabetes risk gene TYK2 may act as a translational activator. We provide HLA class I immunopeptidomic data from cytokine-stimulated human β-cells and demonstrate their utility in coculture assays with autoreactive T-cell transductants. Taken together, our results define the human β-cell translatome, an important resource to the research field.

关键词： 肥大细胞   MST1   I型超敏反应   综述  

摘要： 超敏反应，是指机体接触抗原并致敏后，再次受到相同抗原刺激时表现出的敏感性增高的免疫反应。其中，由免疫球蛋白E （IgE）和肥大细胞介导的超敏反应称为I型超敏反应。肥大细胞广泛分布于体内各种组织器官的结缔组织和黏膜层，是I型超敏反应中的重要效应细胞。在这一过程中，肥大细胞再次与特异性过敏原蛋白接触时，IgE会与之交联，诱发细胞的激活并脱颗粒，随后产生组胺、细胞因子、趋化因子，以及新合成的花生四烯酸和多种蛋白质来调节I型超敏反应。巨噬细胞刺激因子1（MST1）在细胞生物学过程中扮演着多种重要角色，涉及多种细胞的迁移凋亡、增殖、代谢和细胞骨架调控等领域。本综述将探讨MST1激酶的调控机制以及其对I型超敏反应的影响，以期为过敏性疾病的机制和防控研究提供新的思路。

关键词： psoriasis   psoriatic arthritis   guselkumab   therapy   transcriptome  

摘要： Objectives: The aim of this study was to evaluate the transcriptome of peripheral blood mononuclear cells (PBMCs) derived from patients affected by psoriasis (PSO) and psoriatic arthritis (PSA) following treatment with guselkumab, an interleukin (IL)-23 inhibitor. Methods: mRNA was extracted by PBMCs, before and after 24 weeks of treatment with guselkumab, and RNA sequencing was performed in paired-end mode by Illumina technology using the Novaseq6000 platform. log2FoldChange > 1 and p(adj) < 0.05 were the established cutoff to discriminate genes differentially expressed between pre- and post-therapy. For annotation and predictive enrichment analysis of deregulated genes in biological pathways, RStudio was used, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were queried. Cytoscape_v3.10.3 was used for the development of the network between deregulated genes. Results: Six na & iuml;ve active patients with PSO and PSA, diagnosed with a duration <2 years, were assessed before and after 24 weeks of treatment with guselkumab. Performing the quality check and filtering analyses, we found 506 transcripts deregulated between pre- and post-therapy, of which 129 were upregulated and 377 were downregulated. The most upregulated mRNAs included SYTL3, CPT1A, TMEM208, GINS4, and TNFRSF13C. The most downregulated mRNAs included CCR2, TPT1, MYCBP, CMPK1, and TMEM65. Enrichment with the GO database showed the following main deregulated processes: "protein targeting", "the establishment of protein localization to membrane", and "metabolism of fatty acids". The analysis of the main macro-process showed the several pathways deregulated after therapy, including signaling related to ethanol metabolism, thermogenesis, oxidative phosphorylation, and fatty acid metabolism (KEGG). Conclusions: Our findings may give further insights into manipulated mechanistic pathways by IL-23 inhibition in patients with PSO and PSA.

关键词： Graves' disease   methylation   CpG   IL-10   machine learning model  

摘要： Objective: Epigenetic modifications, particularly deoxyribonucleic acid (DNA) methylation, regulate the expression of immune-mediated factors. This study aimed to investigate the methylation landscape of the interleukin-10 (IL10) gene in Graves' disease (GD). Methods: This study quantitatively profiled DNA methylation levels within the IL-10 gene using peripheral blood samples from GD patients and healthy controls. Machine learning models were constructed based on CpG methylation features to classify disease status. Furthermore, correlation between specific CpG sites methylation and clinical indicators were analyzed. Results: This study enrolled 60 patients diagnosed with GD and 51 healthy controls. Methylation analysis revealed significantly elevated methylation at multiple IL-10 CpG sites in the GD group compared to the healthy controls (p < 0.01), forming a hypermethylated cluster. Interestingly, the newly-diagnosed GD (NGD) group also showed higher methylation at specific sites compared to the recurrent GD (RGD) group. Correlation analysis showed that methylation at chr1_206947188_R and chr1_206947135_R were positively correlated with FT3 and TRAb levels, indicating that site-specific methylation changes were associated with disease severity and immune activity in GD. Conclusions: Our findings highlight distinct methylation patterns of the IL-10 gene in GD, with specific CpG sites carrying potential implications for disease diagnosis, stratification, and monitoring.

关键词： circRNAs   HuR   NSCLC   SFPQ   ubiquitylation  

摘要： Among lung cancers, non-small-cell lung cancer (NSCLC) is the most common type. Evidence demonstrates that abnormal expression of circular RNAs (circRNAs) is associated with cancer progression through interactions with RNA-binding proteins (RBPs). Therefore, further elucidation of the role of circular RNAs may provide new therapeutic targets for NSCLC patients. This study identified a novel circRNA, circHMGCS1 (hsa_circ_0072387), using circRNA microarrays. Validation and characterization of circHMGCS1 were performed by Sanger sequencing and RNase R treatment. CCK-8 and Transwell assays were used to determine the function of circHMGCS1 in cell proliferation and migration. The interaction between circHMGCS1 and human antigen R (HuR) protein was verified by RNA pull-down and RNA immunoprecipitation (RIP) assays. The effect of HuR on the stability of splicing factor proline- and glutamine-rich (SFPQ) mRNA was verified by dual-luciferase reporter gene assay and actinomycin D treatment. We found that circHMGCS1 was upregulated in NSCLC cells and tissues. Mechanistically, circHMGCS1 binds to HuR, and its high expression stabilizes HuR by inhibiting its ubiquitin-mediated degradation. HuR was shown to mediate the stability of SFPQ mRNA and promote the progression of NSCLC. RNA sequencing analysis indicated that SFPQ may inhibit apoptosis by suppressing tumor necrosis factor (TNF) signaling. This study revealed that circHMGCS1 contributes to NSCLC progression by stabilizing oncogenic HuR and promoting post-transcriptional upregulation of SFPQ, highlighting its potential as a diagnostic and prognostic biomarker for NSCLC.

摘要： Neoadjuvant immunotherapy is a first-line treatment for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). However, only a fraction of patients with advanced HNSCC benefit from immunotherapy. Identifying accurate and accessible biomarkers is essential for optimal patient selection. In this study, we integrated single-cell RNA sequencing and T-cell receptor sequencing to comprehensively characterize the tumor immune microenvironment (TIME) of HNSCC biopsies prior to a phase II neoadjuvant immunotherapy clinical trial. Tumor-specific MHC-II (tsMHC-II) was identified as a superior predictor of response to neoadjuvant immunotherapy in HNSCC compared with PD-L1. Mechanistically, tsMHC-II ignited a hot TIME and enhanced the effect of PD-1 blockade by recruiting T cells through the induction of chemokines, particularly CCL5. Moreover, tsMHC-II triggered a Th1 response and activated CD4+ and CD8+ T-cell expansion, suppressing HNSCC growth in a CD4+ T-cell-dependent manner. Simultaneously, tsMHC-II facilitated an increase in PD-1+CD4+ T cells and a modest elevation in tumor PD-L1, thereby enhancing sensitivity to anti-PD-1 therapy. This study highlights that tsMHC-II, by generating an inflamed TIME, is crucial in enhancing the effectiveness of neoadjuvant immunotherapy in ***: scRNA-seq analysis identifies tumor-specific MHC-II as a predictor for neoadjuvant immunotherapy response in HNSCC and provides insights into the complex networks that ignite a hot tumor immune microenvironment and regulate T-cell infiltration.

关键词： 儿童   EBF1-PDGFRB阳性   Ph-like ALL   中枢神经系统白血病   TKIs   达沙替尼   药学监护  

摘要： 报道了1例儿童EBF1-PDGFRB融合基因阳性费城染色体样急性淋巴细胞白血病（Ph-like ALL）合并中枢神经系统白血病（CNSL）的临床病例。患儿在初诊后接受中国儿童白血病协作组（CCLG）-ALL-2018标准化疗方案诱导治疗未获缓解，后续采用含二代酪氨酸激酶抑制剂（TKI）达沙替尼的挽救治疗方案。治疗期间通过治疗药物监测（TDM）及不良反应监测动态调整达沙替尼用药方案，联合方案疗效显著，患儿PDGFRB融合基因及脑脊液微小残留病灶（MRD）持续维持阴性状态。CCLG-ALL-2018化疗方案联合达沙替尼是治疗此类患儿的有效手段，临床药师参与方案优化及实施药学监护对保障用药安全合理至关重要。

摘要： In the original publication [...].

关键词： neuroendocrine tumors   peptide receptor radionuclide therapy   IL-33   sST2  

摘要： Despite a high disease control rate in the treatment of unresectable or metastatic well-differentiated, somatostatin receptor-positive neuroendocrine tumors (NETs) with peptide receptor radionuclide therapy (PRRT), a certain percentage of patients will experience an unfavorable outcome. Besides clinical, hematological, and biochemical parameters, including widely used inflammatory markers, as well as literature-recognized inflammatory indices, there is a growing need for the identification of novel biomarkers as prognostic factors of therapeutic response. In this prospective single-center study, 51 NET patients treated with PRRT were included and divided into two groups: responders and non-responders in accordance with therapeutic outcome. Cytokine, clinical, and biochemical data were analyzed. Non-responders had significantly higher serum concentrations of IL-33 and IL-4 in comparison to responders, while sST2 was increased in responders. A positive correlation was measured between IL-33 and IL-4, as well as between IL-33 and disease progression. A negative correlation was noted between IL-33 and the neutrophil count %. ROC curve analysis identified values of IL-33 >146.5 pg/mL as a predictor of poor early therapeutic response, and logistic regression confirmed its independent prognostic value. Elevated IL-33 and IL-4 favor the development of a type 2 immune response associated with unfavored therapeutic outcome, while increased sST2 mitigates the IL-33's effect in responders, contributing to a more favorable response. These findings emphasize IL-33 as an important biomarker of early response in NET patients undergoing PRRT.