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Serum IL-6 levels correlate with surgical stress factors in newborns with congenital diaphragmatic hernia 新生儿先天性膈疝患者血清IL-6水平与手术应激因素相关。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-15 DOI: 10.1016/j.cyto.2025.157053
Takao Kobayashi , Sota Iwatani , Toshihiko Ikuta, Seiji Yoshimoto

Background

Peri-operative management in congenital diaphragmatic hernia (CDH) remains a significant challenge associated with mortality and morbidity. Although interleukin-6 (IL-6) reflects surgical stress in adults, its peri-operative dynamics in newborns remain unclear. This study investigated changes in IL-6 levels in CDH newborns and their association with surgical stress factors and post-operative complications.

Methods

In this single-center study, CDH newborns who underwent surgical repair between 2010 and 2022 were retrospectively studied. Changes in serum IL-6 and C-reactive protein (CRP) levels from 72-h pre-operatively to 96-h post-operatively were assessed. Correlations between peak peri-operative IL-6/CRP levels and surgical stress-related factors or early post-operative complications were also explored in this preliminary analysis.

Results

Of 49 newborns, 20 had available data to evaluate peri-operative IL-6 and CRP levels. Serum IL-6 peaked [median: 122.7 (62–1898) pg/mL] at 10-h (1–42) postoperatively, while CRP peaked [median: 2.40 (0.24–8.31) mg/dL] at 38-h (12–47). Peak IL-6 levels correlated negatively with postnatal time (rs = −0.610) and positively with intra-operative blood loss and 24-h post-operative transfusion volumes (rs = 0.497 and 0.510).

Conclusions

In CDH newborns, serum IL-6 levels increase during the 24–48-h post-operative period and return to baseline by the 48–72-h period. Although this is a preliminary study with a limited sample size, assessing peak IL-6 levels may provide a useful indicator of surgical stress and help optimize peri-operative management, including transfusion strategies.
背景:先天性膈疝(CDH)的围手术期处理仍然是一个与死亡率和发病率相关的重大挑战。尽管白细胞介素-6 (IL-6)反映成人手术应激,但其在新生儿围手术期的动态尚不清楚。本研究探讨CDH新生儿IL-6水平的变化及其与手术应激因素和术后并发症的关系。方法:在这项单中心研究中,回顾性研究了2010年至2022年间接受手术修复的CDH新生儿。评估术前72 h至术后96 h血清IL-6和c -反应蛋白(CRP)水平的变化。本初步分析还探讨了围手术期IL-6/CRP峰值水平与手术应激相关因素或术后早期并发症的相关性。结果:49例新生儿中,20例有围手术期IL-6和CRP水平的可用数据。血清IL-6在术后10小时(1-42)达到峰值[中位数:122.7 (62-1898)pg/mL], CRP在术后38小时(12-47)达到峰值[中位数:2.40 (0.24-8.31)mg/dL]。IL-6峰值水平与产后时间呈负相关(rs = -0.610),与术中出血量和术后24小时输血量呈正相关(rs = 0.497和0.510)。结论:CDH新生儿术后24-48小时血清IL-6水平升高,48-72小时恢复至基线水平。虽然这是一项样本量有限的初步研究,但评估峰值IL-6水平可能提供一个有用的手术应激指标,并有助于优化围手术期管理,包括输血策略。
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引用次数: 0
The relationship of plasma netrin-1 level with disease activity and other parameters in patients with axial spondyloarthritis 轴型脊柱炎患者血浆netrin-1水平与疾病活动度等参数的关系
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-14 DOI: 10.1016/j.cyto.2025.157055
Fatih Serdar Baykal , Serdar Can Güven , Ahmet Kor , Funda Eren , Salim Neşelioğlu , Bünyamin Polat , Serdar Esmer , Berkan Armağan , Kevser Orhan , İsmail Doğan , Yüksel Maraş , Salih Başer , Özcan Erel , Şükran Erten
Aim of this study was to evaluate plasma netrin-1 levels in axial spondyloarthritis and to investigate relations between disease activity and other parameters. Axial spondyloarthritis is a term defining a form of the spondyloarthritis in which axial skeleton is predominantly affected. Netrin-1 is a laminin-like matrix protein belonging to the axonal guide protein family, controlling neuronal migration in the embryonic period and inhibiting leukocyte aggregation to provide neuronal protection in the tissue. Study was conducted cross-sectional. Patients with axial spondyloarthritis between ages of 18–65 who applied to our outpatient clinic were enrolled upon consent. A control group was formed by healthy volunteers. Demographics, clinic, laboratory, imaging data and disease activity scores were recorded. Spondyloarthritis patients were subgrouped as ankylosing spondylitis and non-radiographic axial spondyloarthritis. Serum netrin-1 was measured by a commercial kit in patient and control groups. A total of 60 spondyloarthritis patients and 56 healthy controls were enrolled. No significant differences in serum netrin-1 levels were observed among patient groups and controls. Netrin-1 levels had a significant positive correlation with disease activity parameters and found to be higher in patients with higher disease activity. Receiver operating curve analyses revealed fair discriminative power for active disease. Our results suggest a utility for netrin-1 as a novel biomarker for detecting disease activity in spondyloarthritis, for the first time to the best of our knowledge.
本研究的目的是评估轴型脊柱炎患者血浆netrin-1水平,并探讨疾病活动性与其他参数的关系。轴向脊柱炎是一个术语,定义了一种形式的脊柱炎,其中轴向骨骼主要受到影响。Netrin-1是一种层粘连蛋白样基质蛋白,属于轴突引导蛋白家族,在胚胎期控制神经元迁移,抑制白细胞聚集,在组织中提供神经元保护。研究是横断面进行的。年龄在18-65岁之间的轴性脊柱炎患者经同意进入我们的门诊。对照组由健康志愿者组成。记录人口统计学、临床、实验室、影像学数据和疾病活动评分。脊柱炎患者分为强直性脊柱炎和非放射性轴性脊柱炎。患者和对照组的血清netrin-1用商用试剂盒测定。共有60名脊椎关节炎患者和56名健康对照者被纳入研究。患者组与对照组血清netrin-1水平无显著差异。Netrin-1水平与疾病活动性参数呈显著正相关,疾病活动性越高,Netrin-1水平越高。受试者工作曲线分析显示,活动性疾病的鉴别能力尚可。我们的研究结果表明,据我们所知,netrin-1是一种新的生物标志物,可用于检测脊椎关节炎的疾病活动性。
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引用次数: 0
PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway PAX9和Col1A1可能通过与TGF-β1/Smad通路的相互作用调控结肠癌的进展。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-14 DOI: 10.1016/j.cyto.2025.157051
Chao huang, Bingjun Liang, Weizeng Shen

Objective

Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.

Methods

Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.

Results

A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (P < 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (R = 0.79, P < 0.001). High expression of COL1A1 tended to reduce overall survival (P = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (P < 0.05).

Conclusion

The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.
目的:转化生长因子-β1 (TGF-β1)通过下游Smad通路广泛参与晚期癌症的进展,但其潜在机制尚不完全清楚。本项目旨在探讨TGF-β1/Smad通路关键分子与结肠癌进展的关系及其上下游调控机制。方法:从TCGA-COAD、GEO、ENCODE等临床数据库和基因组文库中检索结肠癌患者的临床资料及相关基因表达数据。分析TGF-β1/Smad通路关键分子(TGF-β1、TGF-β1受体、SMAD2/3/4)在结肠癌/癌旁组织样本中的表达水平及其与预后的关系。使用R软件包和RStudio分析结肠癌与正常组织之间差异表达的基因以及Smad2/3结合的启动子区域。JASPAR和GO/KEGG富集用于预测TGF-β1/Smad通路的上游转录因子和下游调控基因。结果:共纳入459例结肠癌患者。不同TGF-β1表达水平显著影响结肠癌患者的总生存期(OS)和无病生存期(DFS) (P)结论:TGF-β1/Smad通路可能与多个上下游靶基因(包括PAX9、VDR、Col1A1)共同调控结肠癌的进展和预后,并与肿瘤分期有关。
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引用次数: 0
Decreased serum VEGF, NRG1, and Neuropilin-1 levels in male patients with treatment-resistant schizophrenia: implications for VEGF as a protective factor 治疗难治性精神分裂症男性患者血清VEGF、NRG1和Neuropilin-1水平降低:VEGF作为保护因子的意义
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-13 DOI: 10.1016/j.cyto.2025.157056
Lingshu Luan , Liuyang Lu , Li Xu , Wanming Chen , Qing Tian , Xiaobin Zhang , Haidong Yang

Background

Vascular endothelial growth factor (VEGF), Neuregulin-1 (NRG1), and Neuropilin-1 are important neurotrophic factors involved in neurodevelopment, synaptic plasticity, and neuroprotection processes implicated in schizophrenia pathophysiology. This study aimed to investigate the expression patterns of these markers and their clinical implications in male patients with treatment-resistant schizophrenia (TRS) and chronically medicated schizophrenia (CMS).

Methods

In this cross-sectional study, serum levels of VEGF, NRG1β1, neuropilin-1, S100B, and S100A8 were measured using the Luminex liquid suspension chip technology in 31 TRS patients, 47 CMS patients, and 47 healthy controls. Psychiatric symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results

VEGF levels were significantly lower in TRS versus controls (P < 0.001), with no significant difference between TRS-CMS (P = 0.053) or CMS-controls (P = 0.051). NRG1β1 was significantly reduced in both TRS (P = 0.003) and CMS (P < 0.001) groups compared to controls. Neuropilin-1 decreased significantly only in the TRS group versus controls (P = 0.029). No significant difference was observed in S100B and S100A8 levels across all groups (all P > 0.05). Correlation analysis revealed a negative association between NRG1β1 levels and positive scores (r = −0.355, P = 0.014), and a significant positive correlation between VEGF levels and language function (r = 0.313, P = 0.032) in CMS patients. Additionally, VEGF demonstrated potential protective properties in TRS patients (B = -1.098, RR = 0.333, 95 %CI: 0.131–0.849, P = 0.021).

Conclusion

VEGF may serve as a protective factor against TRS, with its reduction possibly contributing to treatment resistance. The positive correlation between VEGF and language function suggests its role in cognitive processes, highlighting its potential as a biomarker in schizophrenia treatment.
背景:血管内皮生长因子(VEGF)、神经调节蛋白-1 (NRG1)和神经匹林-1是重要的神经营养因子,参与神经发育、突触可塑性和精神分裂症病理生理相关的神经保护过程。本研究旨在探讨这些标志物在男性难治性精神分裂症(TRS)和慢性药物性精神分裂症(CMS)患者中的表达模式及其临床意义。方法:采用Luminex液悬芯片技术检测31例TRS患者、47例CMS患者和47例健康对照者血清中VEGF、NRG1β1、neuropilin-1、S100B、S100A8的水平。采用Positive and Negative Syndrome Scale (PANSS)和Repeatable Battery for Assessment of Neuropsychological Status (RBANS)评估精神症状和认知功能。结果:TRS组VEGF水平明显低于对照组(P < 0.05)。相关分析显示,CMS患者NRG1β1水平与阳性评分呈负相关(r = -0.355, P = 0.014), VEGF水平与语言功能呈显著正相关(r = 0.313, P = 0.032)。此外,VEGF在TRS患者中显示出潜在的保护作用(B = -1.098, RR = 0.333, 95% CI: 0.131-0.849, P = 0.021)。结论:VEGF可能是抗TRS的保护因子,其降低可能与治疗耐药有关。VEGF与语言功能之间的正相关表明其在认知过程中的作用,突出了其作为精神分裂症治疗生物标志物的潜力。
{"title":"Decreased serum VEGF, NRG1, and Neuropilin-1 levels in male patients with treatment-resistant schizophrenia: implications for VEGF as a protective factor","authors":"Lingshu Luan ,&nbsp;Liuyang Lu ,&nbsp;Li Xu ,&nbsp;Wanming Chen ,&nbsp;Qing Tian ,&nbsp;Xiaobin Zhang ,&nbsp;Haidong Yang","doi":"10.1016/j.cyto.2025.157056","DOIUrl":"10.1016/j.cyto.2025.157056","url":null,"abstract":"<div><h3>Background</h3><div>Vascular endothelial growth factor (VEGF), Neuregulin-1 (NRG1), and Neuropilin-1 are important neurotrophic factors involved in neurodevelopment, synaptic plasticity, and neuroprotection processes implicated in schizophrenia pathophysiology. This study aimed to investigate the expression patterns of these markers and their clinical implications in male patients with treatment-resistant schizophrenia (TRS) and chronically medicated schizophrenia (CMS).</div></div><div><h3>Methods</h3><div>In this cross-sectional study, serum levels of VEGF, NRG1β1, neuropilin-1, S100B, and S100A8 were measured using the Luminex liquid suspension chip technology in 31 TRS patients, 47 CMS patients, and 47 healthy controls. Psychiatric symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).</div></div><div><h3>Results</h3><div>VEGF levels were significantly lower in TRS versus controls (<em>P</em> &lt; 0.001), with no significant difference between TRS-CMS (<em>P</em> = 0.053) or CMS-controls (<em>P</em> = 0.051). NRG1β1 was significantly reduced in both TRS (<em>P</em> = 0.003) and CMS (P &lt; 0.001) groups compared to controls. Neuropilin-1 decreased significantly only in the TRS group versus controls (<em>P</em> = 0.029). No significant difference was observed in S100B and S100A8 levels across all groups (all <em>P</em> &gt; 0.05). Correlation analysis revealed a negative association between NRG1β1 levels and positive scores (<em>r</em> = −0.355, <em>P</em> = 0.014), and a significant positive correlation between VEGF levels and language function (<em>r</em> = 0.313, <em>P</em> = 0.032) in CMS patients. Additionally, VEGF demonstrated potential protective properties in TRS patients (B = -1.098, RR = 0.333, 95 %CI: 0.131–0.849, <em>P</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>VEGF may serve as a protective factor against TRS, with its reduction possibly contributing to treatment resistance. The positive correlation between VEGF and language function suggests its role in cognitive processes, highlighting its potential as a biomarker in schizophrenia treatment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157056"},"PeriodicalIF":3.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnostic potential of immune serum proteins in Osteosaropenia identified via proximity extension assay 通过邻近扩展试验确定免疫血清蛋白在骨质减少症中的诊断潜力。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-13 DOI: 10.1016/j.cyto.2025.157054
Seok Woo Hong , Jeong-Hwa Baek , Kyung Jae Yoon , Jeong-Hyun Kang

Background

Osteosarcopenia, characterized by coexistence of osteoporosis and sarcopenia, is influenced by immunological dysfunction and systemic inflammation, however their specific roles remain unclear. This study aimed to investigate inflammation-related serum profiles in osteosarcopenia using the Proximity Extension Assay (PEA).

Methods

Overall, 50 participants with a history of falls and fractures were recruited and classified into three groups, controls, sarcopenia, and osteosarcopenia. Oseteosarcopenia was diagnosed in individuals with both functional sarcopenia and osteoporosis. Functional sarcopenia was diagnosed according to the Korean Working Group on Sarcopenia guidelines. Osteoporosis was defined as a T-score of the areal bone mineral density (aBMD) of the femoral neck ≤ −2.5. Serum inflammatory protein levels were quantified using the Olink® PEA inflammation panel, targeting 92 proteins.

Results

Twenty inflammation-related proteins were identified as differentially expressed proteins (DEPs), and 33 proteins showed significant correlations with clinical measures of muscle function or aBMD of the total hip, femoral neck or lumbar spine. Weighted Gene Co-Expression Network Analysis (WGCNA) identified 27 proteins with significant module membership and contribution to group separation. Notably, four proteins, including SLAMF1, OPG, FGF-23, and CSF-1 were DEPs, significant in WGCNA, and correlated with clinical variables. Principal component analysis and heatmap analyses revealed osteosacropenia as a distinct entity, differing from sarcopenia and controls. Bioinformatics suggested that T cell modulation and tumor necrosis factor binding capacity play significant roles in osteosarcopenia development.

Conclusions

Osteosarcopenia exhibited unique immune-related profiles distinct from those of sarcopenia and controls, emphasizing the potential role of inflammation and adaptive immunity in its pathogenesis.
背景:骨骼肌减少症以骨质疏松和骨骼肌减少并存为特征,受免疫功能障碍和全身性炎症的影响,但其具体作用尚不清楚。本研究旨在利用邻近扩展试验(PEA)研究骨骼肌减少症的炎症相关血清谱。方法:总共招募了50名有跌倒和骨折史的参与者,并将其分为三组,对照组,肌肉减少组和骨肌肉减少组。骨骼肌减少症在功能性骨骼肌减少症和骨质疏松症患者中诊断。功能性肌肉减少症是根据韩国肌肉减少症工作组的指南诊断的。骨质疏松定义为股骨颈面骨矿物质密度(aBMD) t评分≤-2.5。使用Olink®PEA炎症面板定量血清炎症蛋白水平,针对92种蛋白。结果:20种炎症相关蛋白被鉴定为差异表达蛋白(DEPs), 33种蛋白与全髋关节、股骨颈或腰椎的肌肉功能或aBMD的临床指标有显著相关性。加权基因共表达网络分析(Weighted Gene Co-Expression Network Analysis, WGCNA)鉴定出27个具有显著模块隶属关系和对组分离有贡献的蛋白。值得注意的是,包括SLAMF1、OPG、FGF-23和CSF-1在内的4种蛋白是dep,在WGCNA中具有显著意义,并与临床变量相关。主成分分析和热图分析显示,骨骼肌减少症是一个不同的实体,不同于肌肉减少症和对照组。生物信息学提示T细胞调节和肿瘤坏死因子结合能力在骨骼肌减少症的发生发展中起重要作用。结论:骨骼肌减少症表现出不同于骨骼肌减少症和对照组的独特免疫相关特征,强调炎症和适应性免疫在其发病机制中的潜在作用。
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引用次数: 0
Unveiling the role of trace elements in modulating inflammatory and oxidative pathways in CAG repeat–driven spinocerebellar ataxia 揭示微量元素在CAG重复驱动的脊髓小脑性共济失调中调节炎症和氧化途径的作用。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-11 DOI: 10.1016/j.cyto.2025.157050
Surbhi Singh , Deepika Joshi , Abhay Kumar Yadav , Shani Vishwakarma , Janki Makani , Janhavi Yadav , Anil Kumar Maurya , Gulabi Yadav , Chandmayee Mohanty , Anand Kumar , Royana Singh
Spinocerebellar ataxias are genetically inherited neurodegenerative disorders, primarily caused by CAG trinucleotide repeat expansions in genes. While these genetic mutations initiate disease onset, increasing evidence suggests that systemic factors, particularly trace element imbalance, oxidative stress, and immune dysregulation, play critical roles in disease progression. In this study, peripheral blood samples from genetically confirmed SCA patients (n = 15) and age- and sex-matched healthy controls (n = 18) were analyzed. Atomic Absorption Spectroscopy revealed significant alterations in plasma concentrations of both essential and toxic trace elements, suggesting their involvement in neurotoxicity, redox imbalance, and inflammation. To explore these links, oxidative stress markers, including malondialdehyde, superoxide dismutase, and glutathione peroxidase, as well as cytokines such as interleukin-6, interleukin-4, and interleukin-10, were quantified using ELISA. Receiver operating characteristic analysis demonstrated high diagnostic accuracy of these markers, particularly GPx and IL-10. A strong interconnection was observed among trace element dysregulation, oxidative stress, and inflammatory responses, indicating a synergistic role in exacerbating neurodegeneration. Molecular docking revealed that abnormal trace element levels may impair antioxidant enzyme function by disrupting metal-binding interactions, offering mechanistic insight into enzymatic dysfunction. Bioinformatics analyses, including functional enrichment and protein–protein interaction mapping, identified significant associations with mitochondrial dysfunction, reactive oxygen species metabolism, and cytokine signaling pathways. These findings suggest that SCA pathogenesis is not driven by genetic mutation alone. The combined effects of trace element imbalance, oxidative stress, and inflammation contribute to a complex pathogenic network, reinforcing the importance of targeting both genetic and systemic factors in therapeutic strategies.
脊髓小脑共济失调是一种遗传性神经退行性疾病,主要由CAG三核苷酸重复扩增引起。虽然这些基因突变引发了疾病的发生,但越来越多的证据表明,系统性因素,特别是微量元素失衡、氧化应激和免疫失调,在疾病进展中起着关键作用。在这项研究中,我们分析了基因证实的SCA患者(n = 15)和年龄和性别匹配的健康对照(n = 18)的外周血样本。原子吸收光谱显示血浆中必需和有毒微量元素浓度的显著变化,表明它们参与神经毒性、氧化还原失衡和炎症。为了探索这些联系,氧化应激标志物,包括丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶,以及细胞因子,如白细胞介素-6、白细胞介素-4和白细胞介素-10,使用ELISA进行定量。受试者工作特征分析表明,这些标记具有较高的诊断准确性,特别是GPx和IL-10。微量元素失调、氧化应激和炎症反应之间存在密切联系,表明它们在加剧神经变性方面具有协同作用。分子对接揭示了异常微量元素水平可能通过破坏金属结合相互作用而损害抗氧化酶的功能,为酶功能障碍提供了机制见解。生物信息学分析,包括功能富集和蛋白-蛋白相互作用定位,确定了与线粒体功能障碍、活性氧代谢和细胞因子信号通路的显著关联。这些发现表明SCA的发病机制并非仅由基因突变驱动。微量元素失衡、氧化应激和炎症的综合作用形成了一个复杂的致病网络,这加强了在治疗策略中针对遗传和全身因素的重要性。
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引用次数: 0
Anakinra ameliorates insulin resistance and inflammation in a murine model of gestational diabetes through downregulation of Th17 responses Anakinra for the treatment of GDM in mice 阿那白素通过下调Th17反应改善妊娠糖尿病小鼠模型中的胰岛素抵抗和炎症
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-10 DOI: 10.1016/j.cyto.2025.157039
Lingyan Zhang , Fudan Huang , Shaik Althaf Hussain , Yi Tian
Gestational diabetes mellitus (GDM) is associated with low-grade inflammation which can contribute to insulin resistance and dysregulated glucose metabolism. Anakinra is a recombinant form of IL-1 receptor antagonist (IL-1Ra) that has shown promise in the control of several inflammatory diseases. The present study aimed to evaluate the potential of Anakinra in the control of inflammation and glucose metabolism in a genetic model of GDM.
Pregnant C57BL/KsJdb/+ (db/+) mice were used as the murine model of GDM and the glucose metabolism, insulin resistance as well as levels of inflammatory mediators were evaluated. The populations of Th17 and Treg cells were also analyzed in spleens of mice. Some GDM-associated parameters were studied in offspring along with an evaluation of oxidative stress in the liver and placenta.
Anakinra improved the glucose tolerance and insulin sensitivity of GDM mice and controlled the weight gain of the pregnant mice. The population of Th17 cells as key mediators of inflammatory processes declined in the Anakinra-received mice and the serum levels of pro-inflammatory cytokines as well as the activation of the NF-κB pathway declined accordingly. Besides, the infiltration of T-cells into the placenta was diminished in Anakinra-treated mice.
Anakinra demonstrated a potential for control of GDM by targeting low-grade inflammation and improving glucose metabolism. Regarding the fair properties of small molecules that render them suitable therapeutic tools, Anakinra might be a candidate therapeutic for the control of GDM more efficiently.
妊娠期糖尿病(GDM)与低度炎症相关,可导致胰岛素抵抗和糖代谢失调。Anakinra是IL-1受体拮抗剂(IL-1Ra)的重组形式,在控制几种炎症性疾病方面显示出希望。本研究旨在评估阿那白在GDM遗传模型中控制炎症和糖代谢的潜力。以妊娠C57BL/KsJdb/+ (db/+)小鼠为GDM小鼠模型,观察其糖代谢、胰岛素抵抗及炎症介质水平。同时还分析了小鼠脾脏中Th17和Treg细胞的数量。在后代中研究了一些gdm相关参数,并对肝脏和胎盘的氧化应激进行了评估。阿那白改善了GDM小鼠的葡萄糖耐量和胰岛素敏感性,控制了妊娠小鼠的体重增加。在anakinra小鼠中,作为炎症过程关键介质的Th17细胞数量下降,血清中促炎细胞因子水平以及NF-κB通路的激活也相应下降。此外,在anakinra处理的小鼠中,t细胞向胎盘的浸润减少。Anakinra通过靶向低度炎症和改善葡萄糖代谢,证明了控制GDM的潜力。考虑到小分子的公平性质使其成为合适的治疗工具,Anakinra可能是更有效控制GDM的候选治疗药物。
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引用次数: 0
Sepsis-induced cardiac dysfunction: Gender bias role of allograft inflammatory factor-1 败血症引起的心功能障碍:异体移植物炎症因子-1的性别偏见作用
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-09 DOI: 10.1016/j.cyto.2025.157040
B.C. Wang , S. Chaki , H. Taufiq , K. Sikder , S.K. Shukla , K. Rafiq
Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (-/-) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation.
Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges.
These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.
脓毒症引起的心功能障碍是导致脓毒症患者高发病率和高死亡率的主要原因,并发心功能障碍的患者死亡率高达90%。本研究通过野生型(WT)和AIF-1敲除(-/-)C57BL/6小鼠的盲肠结扎穿刺(CLP)模型,阐明了同种异体移植物炎症因子-1 (AIF-1)在败血症诱导的心功能障碍中的作用。我们专门研究了AIF-1在性别中的表达及其对心功能和炎症的影响。结果表明,在感染性休克期间,雌性小鼠心脏中AIF-1有显著的性别特异性上调,表明该分子在减轻心功能障碍方面具有保护作用。相比之下,与野生型小鼠相比,AIF-1敲除的雌性小鼠表现出更严重的心功能障碍,这可以通过射血分数和分数缩短降低、促炎细胞因子(TNF-α、IL-6)表达增加和心脏炎症加剧来证明。此外,AIF-1缺失减少了心脏中巨噬细胞的浸润,强调了其在脓毒性挑战中调节免疫反应的作用。这些发现强调了AIF-1对雌性小鼠的保护作用,并提示其可能作为脓毒症引起的心功能障碍的治疗靶点。了解AIF-1的机制可以促进性别特异性治疗的发展,以改善败血症的预后,特别是通过利用其在增强心脏恢复力和调节炎症中的作用。
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引用次数: 0
Quercetin enhances amphotericin B activity and regulates ROS and cytokine production in human monocytes infected by Leishmania infantum 槲皮素增强两性霉素B活性,调节感染婴儿利什曼原虫的人单核细胞ROS和细胞因子的产生。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-08 DOI: 10.1016/j.cyto.2025.157047
Leonardo Lima Cardoso, Delva Fonseca Lamec Thyares, Ana Letícia Monteiro Fernandes, Rosália Santos Ferreira, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Fernanda Silva Almeida, Tatjana de Souza Lima Keesen
Leishmania infantum, the main causative agent of zoonotic visceral leishmaniasis, persists and proliferates within host monocytes and macrophages. Numerous studies have focused on developing innovative therapies, as conventional treatments are hampered by high toxicity, drug resistance, and relapse. In recent decades, anti-leishmanial immunotherapy — aimed at triggering or modulating the host's immune response — has gained momentum, with various immunomodulators being tested in experimental and clinical settings. However, achieving effective immunotherapy remains challenging, as it requires a delicate balance between enhancing protective, parasite-specific immune responses and avoiding harmful hyperinflammation. In this context, we evaluated quercetin, a natural flavonoid with reported immunomodulatory properties, alone and in combination with Amphotericin B (AmB), against Leishmania infantum promastigotes and during human monocyte infection. Infected and non-infected PBMCs were assessed for parasite viability and cytotoxicity; monocyte infection rates, reactive oxygen species (ROS), nitric oxide (NO) production, and cytokine profiles. Quercetin showed significant anti-promastigote activity and, in combination with AmB, enhanced parasite death, indicating synergistic effects. It also reduced monocyte infection rates, enhanced ROS production, and downregulated levels of IL-6, IL-10, and IL-17, without altering NO production. These findings support the concept of quercetin as a dual-action agent, exerting direct anti-leishmanial effects while fine-tuning the host immune response. By promoting beneficial immunological pathways and dampening potentially deleterious cytokines, quercetin exemplifies the “trapeze act” of immunotherapy, suggesting its potential as an adjuvant to conventional chemotherapy in visceral leishmaniasis.
婴儿利什曼原虫是人畜共患内脏利什曼病的主要病原体,在宿主单核细胞和巨噬细胞中持续存在并增殖。许多研究都集中在开发创新疗法上,因为传统疗法受到高毒性、耐药性和复发的阻碍。近几十年来,旨在触发或调节宿主免疫反应的抗利什曼免疫疗法获得了发展势头,各种免疫调节剂正在实验和临床环境中进行测试。然而,实现有效的免疫治疗仍然具有挑战性,因为它需要在增强保护性、寄生虫特异性免疫反应和避免有害的过度炎症之间取得微妙的平衡。在这种情况下,我们评估了槲皮素,一种具有免疫调节特性的天然类黄酮,单独使用和与两性霉素B (AmB)联合使用,对婴儿利什曼原虫和人类单核细胞感染的影响。评估感染和未感染的pbmc的寄生虫活力和细胞毒性;单核细胞感染率、活性氧(ROS)、一氧化氮(NO)的产生和细胞因子谱。槲皮素显示出显著的抗promastigote活性,并与AmB联合,促进寄生虫死亡,表明协同作用。它还降低了单核细胞感染率,增强了ROS的产生,下调了IL-6、IL-10和IL-17的水平,而没有改变NO的产生。这些发现支持槲皮素作为一种双作用剂的概念,在微调宿主免疫反应的同时发挥直接的抗利什曼效应。通过促进有益的免疫途径和抑制潜在的有害细胞因子,槲皮素体现了免疫治疗的“空中飞人行为”,表明它有可能作为内脏利什曼病常规化疗的辅助药物。
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引用次数: 0
Long-term storage stability of plasma TNF-α and IL-6 concentrations of psychiatric emergency patients: The Signature Biobank 精神急症患者血浆TNF-α和IL-6浓度的长期储存稳定性:特征生物库。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-10-07 DOI: 10.1016/j.cyto.2025.157033
Enzo Cipriani , Charles-Édouard Giguère , Cécile Le Page , Helen Findlay , Janick Boissoneault , Stéphane Potvin , Robert-Paul Juster
Cytokines are increasingly incorporated in psychiatric research. While biobanking provides advantages for different study designs, long-term storage could degrade cytokine quality and introduce bias. To date, reports on cytokine stability are based on small sample sizes (n < 20) and do not address long-term (4+ years) storage effects. This article reports two studies evaluating IL-6 and TNF-α measurements in human plasma samples biobanked for long periods. In the first study, with samples stored between 5 and 139 months (11.6 years), IL-6 concentrations were not significantly correlated with storage length in all available baseline data of the Signature Biobank (n[IL-6] = 1206, n[TNF-α] = 1223). TNF-α correlated negatively with storage length (r = −0.217; p < 0.001) indicating a decrease of concentrations with longer storage. In the second study, IL-6 and TNF-α concentrations were measured twice in the same plasma samples of 50 psychiatric participants from the Signature Biobank stored between analyses from 32 to 45 months. We assessed if storage effects differed between analytes. In IL-6, we observe a relatively good stability in samples stored up to 6 years. For TNF-α, we observed only a moderate stability of measurements (rTNF-α = 0.59; rIL-6 = 0.71) with linear decrease over time. As a potential solution, a corrective equation extracted from Study 1 was applied to TNF-α in the Study 2 sample; however, this did not improve correlation coefficients but might be useful in other settings. Integrating samples' age in statistical analyses and/or more systematic quality controls could mitigate degradation process.
细胞因子越来越多地被纳入精神病学研究。虽然生物银行为不同的研究设计提供了优势,但长期储存可能会降低细胞因子的质量并引入偏差。迄今为止,关于细胞因子稳定性的报告都是基于小样本量(n
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引用次数: 0
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Cytokine
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