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摘要： Accurate prediction of symptomatic radiation therapy-induced pneumonitis (RT-IP) remains an important clinical challenge. Currently, mean lung dose and volume of the lungs receiving a 20 Gy threshold of ≤20 Gy and ≤35%, respectively, are utilized to reduce the incidence of pneumonitis to 20%. However, its occurrence is not entirely predictable even at the recommended threshold levels. Hence, in this study, we aimed to evaluate several biological markers, specifically chromosome aberrations by peptide nucleic acid fluorescence in situ hybridization (PNA-FISH), γH2AX, serum IL-6, and IL-17, as potential predictors of symptomatic (grade ≥2) radiation therapy-induced pneumonitis. We prospectively enrolled patients with locally advanced lung cancer. Peripheral blood samples were collected from eleven patients before, during (2 Gy, 20 Gy, 60/66 Gy), and one month after chemoradiotherapy. We then compared these biomarkers between overreactors (grade ≥2 RT-IP) and non-overreactors (grade 0 to 1 RT-IP). Our findings show that chromosome aberration frequency, serum IL-6, and IL-17 after 20 Gy are higher in overreactors than in non-overreactors. Moreover, overreactors accumulated more complex aberrations, such as tricentrics, quadricentrics, and quintacentrics. While chromosome aberration frequency correlated with mean lung dose and IL-17, a pneumonitis marker, IL-6 correlated with the irradiated volume after 20 Gy. Receiver operating characteristic curve analysis further showed that chromosome aberration frequency and IL-6 have the highest specificity for predicting grade ≥2 RT-IP among the assays. In conclusion, we demonstrated the superior predictive capability of PNA-FISH-based chromosome aberration frequency and serum IL-6 for radiation therapy-induced pneumonitis in lung cancer patients. This supports the usefulness of these biomarkers for predicting radiation therapy-induced pneumonitis. © 2025 by Radiation Research Society.

关键词： N6-methyladenosine (m(6)A)   epitranscriptome   RNA methylation   STEMI   inflammation   tocilizumab  

摘要： Background Epitranscriptomics, with m6A as the most prevalent in mammals, is a novel treatment target for inflammatory diseases, including cardiovascular diseases. However, little is known about m6A RNA-regulation during myocardial infarction (MI). Methods In this explorative sub-study of the ASSAIL-MI trial, we used whole blood samples from patients with acute ST-elevation MI (STEMI) (n=6) at admission and after 3-7 days, and from healthy control subjects (n=3). RNA was isolated, and m6A sites were analyzed using human m6A single nucleotide resolution microarray analysis. mRNA levels were analyzed using RNA sequencing analysis. Results Compared with controls, patients with STEMI had a strikingly different pattern of m6A deposition. In total, 845 m6A methylation sites in whole blood RNA were hypomethylated and 36 were hypermethylated compared with controls. Of the hypomethylated transcripts, 194 transcripts were lower expressed, while 197 transcripts were higher expressed. The m6A pattern changed from an overall hypomethylation at admission to an overall hypermethylation 3-7 day after admission. Anti-inflammatory treatment with tocilizumab further altered the m6A deposition. Conclusions In this hypothesis generating study, m6A deposition differs STEMI patients and healthy controls. The m6A pattern changes over the course of 3-7 days. This response is, at least to some degree, is modulated by blocking the IL-6 receptor. Our data may suggest that this post-transcriptional regulation of RNA is involved in the immune response during STEMI, highlighting its potential as a target for therapy in MI.

关键词： Immune Checkpoint Inhibitor   Head and Neck Cancer   Macrophage   JAK-STAT   Immunotherapy  

摘要： Background Immune checkpoint blockade therapy has shown limited efficacy in head and neck squamous cell carcinoma (HNSCC). Sialic acid binding immunoglobulin-like lectin (Siglec)-15 has been identified as a novel immune evasion biomarker, while the role of Siglec-10 in the specific immune suppressive tumor microenvironment remains largely *** Immunohistochemical assays were employed to investigate the correlation of the expressions of Siglec-10 and Siglec-15 with the clinicopathological features as well as the prognosis of immunotherapy in patients with HNSCC. The Gene Expression Omnibus datasets were used to identify the upstream transcriptional regulators of SIGLEC10 in tumor-associated macrophages (TAMs) and the downstream biological functions it mediates. These findings were then validated through in vitro and in vivo experiments. The impact of Siglecg deficiency on the efficacy of immunotherapy and the activation of CD8+T cells was analyzed in mouse HNSCC tumor-bearing *** The expression of Siglec-G/10, rather than that of Siglec-15, was positively correlated with immune suppressive marker programmed death-ligand 1 (PD-L1) expression and was associated with cervical lymph node metastasis, poorer pathologic stage, and lower sensitivity to immunotherapy. Siglecg deficiency rescued the immune suppressive tumor microenvironment, as evidenced by decreased TAM-associated phenotype and increased CD8+T cell infiltration and activation, which inhibited tumor growth significantly. Single-cell sequence and transcription factor prediction revealed that signal transducer and activator of transcription 6 (STAT6) could induce Siglec-G/10 transcription. Interleukin (IL)-4 could upregulate Siglec-G/10 expression significantly via STAT6 activation, as proved by overexpression and inhibition of STAT6. Signal transduction mechanism revealed that Siglec-G/10 could promote TAM differentiation and activation via increasing HIF1 alpha (hypoxia-inducible factor 1

关键词： terpinen-4-ol   HepG2   network pharmacology   HIF-1 alpha   TGF-beta 1   IL-6  

摘要： Background and Objective: Alcoholic liver disease (ALD) is a major health burden caused by chronic alcohol consumption, leading to oxidative stress, inflammation, and fibrosis. Current treatments are limited, highlighting the need for novel therapeutic agents. This study investigated the hepatoprotective effects of 'Terpinen-4-ol (T4OL)', a natural monoterpene from tea tree oil, against ethanol-induced liver injury, focusing on its molecular and cellular mechanisms. Materials and Methods: Network pharmacology and molecular docking were employed to predict T4OL's interaction with ALD-associated targets. Human HepG2 cells were used to validate the in silico findings. Cells were exposed to ethanol (8%) prior to treatment with T4OL or silymarin (SIL), and cytotoxicity was assessed through MTT, crystal violet, and trypan blue assays. Moreover, ELISA and qPCR were conducted to evaluate antioxidant, inflammatory, and fibrotic markers. Results: Network pharmacology analysis suggested that T4OL exerts its hepatoprotective effects by suppressing inflammatory and fibrotic mediators (HIF-1 alpha, TGF-beta 1, and TNF-alpha). Docking studies also exhibited a strong binding affinity of T4OL to key ALD targets, with docking scores comparable to SIL. In addition, T4OL (13-1300 mu M) dose-dependently protected HepG2 cells from ethanol-induced damage, restoring viability by up to 80% at 650 mu M. It significantly elevated antioxidant levels (GSH by 2.5-fold, SOD by 1.8-fold) and suppressed pro-inflammatory and fibrotic markers (IL-6, COL1A1, TIMP-1) by 40-60%. At higher concentrations (650-1300 mu M), T4OL outperformed SIL in cytoprotection and anti-fibrotic effects. Conclusions: T4OL mitigates ethanol-induced liver injury by targeting oxidative stress, inflammation, and fibrosis pathways, demonstrating superior efficacy to SIL at optimal doses. Its multi-target action supports its potential as a therapeutic candidate for ALD.

关键词： Artemisia annua   Allergic rhinitis   IL-17A   Sublingual immunotherapy (SLIT)  

摘要： The mechanisms underlying immune tolerance induction during sublingual immunotherapy (SLIT) of seasonal allergic rhinitis (SAR) remain insufficiently understood. This study aimed to investigate the molecular and immunological process involved in SLIT. RNA sequencing (RNA-seq) and bioinformatics analyses were performed to examine the functions of differentially expressed genes (DEGs) in leukocytes from 11 SAR patients at three time points: baseline, peak pollen phase (PPP), and end-of-treatment. Patients received a 4-month SLIT course with Artemisia annua (A. annua) extract (n = 5) or placebo (n = 6). Plasma cytokine levels were measured in a validation cohort of 15 SAR patients (9 in the SLIT group and 6 in the placebo group) using Luminex assays. The results showed that A. annua SLIT inhibited the upregulation of IL-17A-associated pathways and the expression of inflammatory mediators, including CXCL1, CCL7, and PLPP3, while enhancing myeloid immune cell function by increasing the expression of CD36, TYROBP, FCGR1A, and FCER1G. Additionally, A. annua SLIT reactivated myeloid immune cell-associated genes that were downregulated during PPP and significantly reduced IL-17A and GRO-β levels in plasma, compared to the placebo group. These findings suggest that A. annua SLIT alleviates SAR by modulating IL-17A pathways, reducing inflammatory responses, and enhancing myeloid immune cell function.

关键词： Spinal cord injury   PRP-Derived exosomes   Cerebrolysin   Drug delivery   Target therapy  

摘要： Context/objectiveSpinal cord injury (SCI) is a severe condition characterized by neuronal apoptosis and inflammation, with limited therapeutic options. This study aimed to assess the effects of platelet-rich plasma (PRP)-derived exosomes (Exo), Cerebrolysin (CBL), and Cerebrolysin-loaded exosomes (CLE) on inflammation, apoptosis, tissue organization, and motor function recovery in a mouse model of compression *** experimental study using a mouse model of SCI, investigating the effects of Exo, CBL, and CLE ***-based research in a controlled *** healthy adult female BALB/c mice, aged 8-10 weeks, weighing 24 +/- 2 g were used. SCI was induced via compression to model *** with induced SCI were treated with Exo, CBL, or CLE. Apoptosis was assessed by Bax and Bcl2 expression. Inflammatory markers TNF-alpha and IL-10 were measured. Histological analysis examined tissue organization, and motor function recovery was evaluated using the Basso-Beattie-Bresnahan (BBB) locomotor *** measuresThe study measured Bax and Bcl2 expression, TNF-alpha and IL-10 levels, tissue organization, and motor function *** treatment significantly modulated Bax and Bcl2 expression, reducing apoptosis and enhancing neuronal survival. TNF-alpha levels decreased, indicating reduced inflammation, while IL-10 levels increased, showing anti-inflammatory effects. Histological assessment revealed improved tissue organization, and motor function recovery was significantly enhanced as measured by BBB *** showed neuroprotective and anti-inflammatory effects, reducing apoptosis and inflammation while promoting tissue repair and motor function recovery in SCI, making it a promising therapeutic candidate.

关键词： A型口蹄疫病毒   VP1基因   单克隆抗体   cELISA检测方法   血清型特异性  

摘要： 旨在解决传统口蹄疫病毒（FMDV）多克隆抗体ELISA检测中存在的非特异性反应问题，开发针对中国和东南亚地区流行的A型FMDV SEA-97拓扑型毒株的高特异性单克隆抗体的制备与检测方法。通过基于亚洲流行的A型FMDV SEA-97拓扑型毒株的VP1基因，构建重组表达质粒，用原核系统高效表达并纯化VP1蛋白。采用三步筛选策略（间接ELISA初筛、竞争ELISA验证、血清型特异性鉴定），从免疫的BALB/c小鼠中筛选出稳定分泌A型FMDV特异性单克隆抗体的杂交瘤细胞系（10H2-F2），亚型鉴定为IgG1/κ。建立基于单克隆抗体的竞争ELISA，优化抗原包被条件，显著提升检测性能。与O型FMDV及其他9种偶蹄动物病原体（如猪瘟病毒、猪繁殖和呼吸综合征病毒、猪细小病毒、猪圆环病毒、伪狂犬病病毒、蓝舌病病毒、牛病毒性腹泻病毒、羊痘病毒、赤羽病病毒）无交叉反应（抑制率≤22%）；可检测A型FMDV阳性血清256倍稀释样本，较现有方法提升2倍；与血清中和试验的总符合率达97.3%（Kappa=0.945 2）；单克隆抗体在4℃和－20℃保存6个月后抑制率变异系数<0.3%，批间重复性优异（F=0.2，P>0.8）。所以，建立的竞争ELISA方法具有高度特异性、敏感性及稳定性，为亚洲地区A型FMDV抗体精准检测、疫苗免疫效果评估及疫情监测提供了可靠技术支撑，填补了针对区域性流行毒株的特异性诊断工具的空白。

关键词： Melanoma   Bispecific T cell engager - BiTE   Immunotherapy  

摘要： Background Melanoma is a highly aggressive skin cancer, especially in advanced stages. While current treatments such as targeted therapies and immunotherapies have made significant progress, challenges like drug resistance and limited effectiveness in some patients persist. Therefore, ongoing development of novel therapies, particularly for late-stage melanoma, is *** In this study, we explored the expression of interleukin-13 receptor subunit alpha-2 (IL13R alpha 2) in melanoma patient-derived xenograft models. We investigated IL13R alpha 2 as a potential target for melanoma treatment by employing an IL13R alpha 2-CD3 bispecific T-cell engager (BTE). We tested the effect of IL13R alpha 2-CD3 BTE on T cell activity by flow cytometry. We studied the potency of IL13R alpha 2-CD3 BTE in tumor killing assay in vitro. For in vivo studies, we administered DNA expression cassettes encoding IL13R alpha 2-CD3 BTE (IL13R alpha 2-CD3 DNA encoding BTE (dBTE)) into immunodeficient mice for direct in vivo expression. The mice were challenged with A375 cells and then treated with IL-13R alpha 2-CD3 dBTE versus control and reconstituted with human peripheral blood mononuclear cells (PBMCs) or T cells. Tumor development was monitored, and T cell infiltration in the tumor was analyzed throughflow *** Our findings revealed heterogeneous expression of IL-13R alpha 2, particularly in samples from advanced stages of melanoma. The IL13R alpha 2-CD3 BTE facilitated T-cell activation and proliferation by bridging melanoma cells and T cells. We also observed the ability of IL13R alpha 2-CD3 BTE to direct T cells to kill multiple melanoma patient-derived cell lines through xCELLigence assay in vitro, including those with various mutations associated with late-stage metastatic melanoma. IL13R alpha 2-CD3 dBTE expressed in vivo led to notable tumor regression through inducing increased T-cell infiltration and activation within the tumor *** The

关键词： IFNγ ELISpot   SCAR   cotrimoxazole   oral challenge   patch test  

摘要：