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Biomarkers in Disease Diagnosis and Monitoring: Insights into Clinical Applications and Mass Spectrometry-based Detection. 生物标志物在疾病诊断和监测:洞察临床应用和基于质谱的检测。
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05549-x
Shibam Das, Ankit Awasthi, Ravindra Kumar Rawal, Rohit Bhatia
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引用次数: 0
Adiponectin Promotes SHBG Expression in Trophoblast Cells and Improves Insulin Signaling in Streptozotocin-Induced Gestational Diabetes Mellitus Rats. 脂联素促进滋养细胞SHBG表达并改善妊娠期糖尿病大鼠胰岛素信号转导
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05505-9
Yijie Cheng, Shangling Lv, Ronghui Liu

Objective This study aimed to explore the possible mechanism of adiponectin on the insulin signaling in streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) rats. Methods The GDM rats were induced by injection of 40 mg/kg STZ, and then orally treated with adiponectin (5, 10, 20 mg/kg) every day from gestation day (GD)7 to GD20. The body weight and fasting blood glucose (FBG) were observed every 3 days from GD9 to GD18. Meanwhile, the insulin tolerance test (ITT), homeostasis model assessment insulin resistance (HOMA-IR), and adiponectin expression were observed in rats. Moreover, the insulin signaling-related factors, sex hormone-binding globulin (SHBG), PPAR-α, phospho-AMPK alpha, glucose transporter-3 (GLUT3), and phospho-insulin receptor substrate-1 (p-IRS1) in placental tissues were measured in rats. In vitro, HTR-8-Svneo cells were induced by 30 mM glucose and then treated with adiponectin (50, 100, 200 ng/mL) to observe the changes in cell viability, SHBG expression, and the insulin signaling-related factors. Moreover, silencing or overexpression of SHBG was achieved via transfection with siRNA or pEX-4 SHBG, respectively. The effects of SHBG on the insulin signaling-related factors were observed in cells. Results Adiponectin treatment significantly improved the STZ-induced decrease in body weight, increase in the FBG, ITT, and HOMA-IR with increasing doses. Specifically, adiponectin treatment upregulated the SHBG expression and the insulin signaling-related factors (PPAR-α, p-AMPK, GLUT3, and p-IRS1) in the placental tissues of GDM rats with increasing doses. In line with the results of animal experiments, adiponectin treatment alleviated the high glucose-induced decrease in cell viability, SHBG expression, and the levels of GLUT3 and p-IRS1 in HTR-8-Svneo cells with increasing doses. Moreover, the levels of GLUT3 and p-IRS1 were regulated by the SHBG expression. SHBG silencing weakened the effect of adiponectin in improving the levels of GLUT3 and p-IRS in the high-glucose-induced cells. Conclusion The study showed that adiponectin upregulated the SHBG expression and improved the insulin signaling in STZ-induced GDM rats, as well as adiponectin upregulated the insulin signaling-related factors via SHBG in high-glucose-induced trophoblast cells. This study suggests that adiponectin may be a potential therapeutic target in GDM.

目的探讨脂联素对链脲佐菌素(STZ)诱导的妊娠期糖尿病(GDM)大鼠胰岛素信号通路的影响机制。方法从妊娠第7天至妊娠第20天,先注射STZ 40 mg/kg诱导GDM大鼠,然后每天口服脂联素(5、10、20 mg/kg)。在GD9 ~ GD18期间,每3 d观察一次体重和空腹血糖(FBG)。同时观察大鼠胰岛素耐量试验(ITT)、胰岛素抵抗稳态模型评估(HOMA-IR)及脂联素表达。测定大鼠胎盘组织中胰岛素信号相关因子、性激素结合球蛋白(SHBG)、PPAR-α、磷酸化- ampk α、葡萄糖转运蛋白-3 (GLUT3)和磷酸化-胰岛素受体底物-1 (p-IRS1)的含量。在体外,先用30 mM葡萄糖诱导HTR-8-Svneo细胞,然后用脂联素(50、100、200 ng/mL)处理HTR-8-Svneo细胞,观察细胞活力、SHBG表达及胰岛素信号相关因子的变化。此外,分别通过转染siRNA或pEX-4 SHBG来实现SHBG的沉默或过表达。在细胞中观察SHBG对胰岛素信号相关因子的影响。结果脂联素治疗显著改善了stz诱导的体重下降、FBG、ITT和HOMA-IR随剂量增加而升高。具体而言,脂联素处理可上调GDM大鼠胎盘组织SHBG表达和胰岛素信号相关因子(PPAR-α、p-AMPK、GLUT3和p-IRS1)的表达。与动物实验结果一致,脂联素处理随着剂量的增加,可以缓解高糖诱导的HTR-8-Svneo细胞活力、SHBG表达以及GLUT3和p-IRS1水平的下降。此外,GLUT3和p-IRS1水平受SHBG表达的调控。SHBG沉默减弱了脂联素提高高糖诱导细胞中GLUT3和p-IRS水平的作用。结论脂联素上调stz诱导的GDM大鼠SHBG表达,改善胰岛素信号通路,脂联素通过高糖诱导的滋养细胞SHBG上调胰岛素信号通路相关因子。本研究提示脂联素可能是GDM的潜在治疗靶点。
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引用次数: 0
Rational Enzyme Modification and Expression Enhancement Strategies for 1,8-cineole Production in Serratia marcescens Cell Factories. 粘质沙雷氏菌细胞工厂生产1,8-桉树脑的酶修饰及表达增强策略
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05544-2
Cong Wang, Linbo Gou, Di Liu, Shengfang Wu, Xiuwen Zhou, Tai-Ping Fan, Long Wang, Yujie Cai

1,8-cineole, a bicyclic monoterpenoid compound with significant application value, is widely used in the fields of flavoring, pharmaceuticals, and biofuels. Although recent advances have enabled its biosynthesis in model microorganisms (Escherichia coli and Saccharomyces cerevisiae), the inherent cytotoxicity of terpenoids and the low catalytic efficiency of terpene synthases remain major bottlenecks limiting further improvement in biosynthetic efficiency. To address these limitations, we employed Serratia marcescens HBQA7-a non-model microorganism with high terpene tolerance, previously isolated in our lab-as a chassis for constructing an efficient 1,8-cineole biosynthetic system. Heterologous expression and functional screening of six 1,8-cineole synthase (CinS) genes from different sources were performed, among which SoCinS from Salvia officinalis exhibited the highest catalytic activity. Rational enzyme engineering through site-directed mutagenesis further improved SoCinS activity. In addition, fusion with high-expression tag proteins significantly improved enzyme expression levels, leading to increased 1,8-cineole titers. Under 72-hour shake flask fermentation conditions, the 1,8-cineole concentration reached 2.1 g/L. Finally, fed-batch fermentation in a 5-L bioreactor yielded a final 1,8-cineole titer of 10.2 g/L, demonstrating a higher productivity and greater industrial application potential than current model microbial systems. This work highlights the promising potential of non-model microorganisms in the efficient biosynthesis of terpenoid natural products.

1,8-桉树脑是一种具有重要应用价值的双环单萜类化合物,广泛应用于香料、制药和生物燃料等领域。尽管近年来的进展使其能够在模式微生物(大肠杆菌和酿酒酵母)中进行生物合成,但萜类化合物固有的细胞毒性和萜类合成酶的低催化效率仍然是限制生物合成效率进一步提高的主要瓶颈。为了解决这些限制,我们采用粘质沙雷氏菌hbqa7 -一种具有高萜烯耐受性的非模式微生物,先前在我们的实验室中分离出来-作为构建高效的1,8-桉树脑生物合成体系的基础。对来自不同来源的6个1,8-桉树油脑合成酶(CinS)基因进行了异源表达和功能筛选,其中来自鼠尾草的CinS表现出最高的催化活性。通过定点诱变进行合理的酶工程进一步提高了SoCinS的活性。此外,与高表达标签蛋白的融合显著提高了酶的表达水平,导致1,8-桉树脑滴度增加。在摇瓶发酵72小时的条件下,1,8-桉叶油脑浓度达到2.1 g/L。最后,在5-L的生物反应器中分批补料发酵产生了10.2 g/L的1,8桉叶脑滴度,显示出比当前模型微生物系统更高的生产率和更大的工业应用潜力。这项工作强调了非模式微生物在萜类天然产物的有效生物合成中的巨大潜力。
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引用次数: 0
Impacts of the Herbal Antimicrobial Compounds on the Antimicrobial Potency of Green Synthesized Copper Nanoparticles. 中药抗菌化合物对绿色合成纳米铜抗菌效能的影响。
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05520-w
Alireza Ebrahiminezhad, Susan Sohrabi, Mohammad Kargar, Aydin Berenjian

Plant-mediated synthesis is a most recent approach toward green synthesis of copper-based nanoparticles. In this approach nanoparticles are capped with phytochemicals, suggesting that plants with unique biological properties might transfer these benefits to the nanoparticles. However, there is no experimental evidences to directly corelate bioactivities of nanoparticles to their capping phytochemicals. This study aims to assess the impacts of herbal antimicrobial compounds on the antimicrobial potency of resulted nanoparticles. Cu(OH)2 nanoparticles (CuNPs) were synthesized by leaf extracts of eucalyptus and tobacco. Resulted particles were characterized to exhibit similar physicochemical properties which are determinative for antimicrobial activity. Antimicrobial effects of the leaf extracts and CuNPs were tested against Staphylococcus aureus and Escherichia coli. Eucalyptus leaf extract was found effective against S. aureus with growth inhibition zone of 13.1 ± 0.6 mm. CuNPs exhibited efficacy against both bacterial strains with inhibition zones exceeding 15 mm. Notably, no significant difference in antimicrobial effectiveness of CuNPs was observed, suggesting that the antimicrobial superiority of eucalyptus extract was not transferred to nanoparticles. These results could reshape our understanding about the impacts of herbal bioactive molecules on the bioactivity of plant-mediated synthesized nanoparticles.

植物介导合成是一种绿色合成铜基纳米颗粒的最新方法。在这种方法中,纳米颗粒被植物化学物质覆盖,这表明具有独特生物特性的植物可能将这些好处转移到纳米颗粒上。然而,没有实验证据表明纳米颗粒的生物活性与其覆盖的植物化学物质直接相关。本研究旨在评估草药抗菌化合物对所得纳米颗粒抗菌效力的影响。以桉树叶提取物和烟草叶提取物为原料合成了Cu(OH)2纳米颗粒。所得到的颗粒具有相似的物理化学性质,这是抗菌活性的决定性因素。研究了其对金黄色葡萄球菌和大肠杆菌的抑菌作用。桉树叶提取物对金黄色葡萄球菌的生长抑制区为13.1±0.6 mm。CuNPs对两种细菌均有抑制作用,抑制区均超过15 mm。值得注意的是,CuNPs的抗菌效果没有显著差异,这表明桉树提取物的抗菌优势并未转移到纳米颗粒上。这些结果可以重塑我们对草药生物活性分子对植物介导合成纳米颗粒生物活性影响的认识。
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引用次数: 0
ENPP2 Protects Mouse Myocardium from Ischemia-Reperfusion-Induced Ferroptosis Injury Via the SIRT1/PGC-1α/NRF1 Pathway. ENPP2通过SIRT1/PGC-1α/NRF1通路保护小鼠心肌缺血-再灌注诱导的上铁损伤
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05494-9
Dongshan Liao, Zhisheng Wang, Gengyan Tian, Honghao Wang, Guanhua Fang

Ferroptosis is a critical contributor to ischemia-reperfusion (I/R) injury and subsequent organ failure. While ENPP2 has been implicated in regulating ferroptosis in cardiomyocytes, its specific role in myocardial I/R injury remains unclear. This study aims to elucidate the function of ENPP2-mediated ferroptosis in myocardial ischemia-reperfusion injury (MI/RI), to provide novel insights into potential therapeutic strategies. A mouse model of MI/RI was established and subjected to interventions with ENPP2 overexpression and/or SIRT1 knockdown. In vitro, cardiomyocytes were treated with palmitate and subjected to hypoxia/reoxygenation (H/R) to simulate I/R injury. These cells received treatments with ENPP2 overexpression (oe-ENPP2), SIRT1 overexpression (oe-SIRT1), PGC-1α silencing (si-PGC-1α), and/or SIRT1 knockdown (sh-SIRT1). Additionally, Erastin-induced ferroptosis in cardiomyocytes was used to assess the protective effects of oe-ENPP2. Ferroptosis was assessed through the lipid peroxidation (MDA, 4-HNE), iron and Fe2+ assays, GPx4 and SLC7A11 expression, and transmission electron microscope. Overexpression of ENPP2 significantly alleviated myocardial infarction in MI/RI mice, as indicated by the upregulation of GPx4 and SLC7A11 protein levels. In cardiomyocytes subjected to hypoxia/reoxygenation (H/R) or erastin-induced ferroptosis, oe-ENPP2 reduced apoptosis rates, preserved Fe2+ content, and restored GPx4 and SLC7A11 expression. Silencing PGC-1α blocked the protective effect of oe-ENPP2 against H/R-induced ferroptosis in HL-1 cells. Additionally, SIRT1 overexpression inhibited PGC-1α acetylation, whereas SIRT1 knockdown similarly reversed the anti-ferroptotic effects of oe-ENPP2 in H/R-treated HL-1 cells. SIRT1 silencing blocked the protective effects of oe-ENPP2 against myocardial infarction and fibrosis in MI/RI mice via the PGC-1α/NRF1 pathway. ENPP2 overexpression protects the mouse myocardium from I/R-induced ferroptosis injury via the SIRT1/PGC-1α/NRF1 pathway. These findings suggest a novel gene therapy strategy for mitigating myocardial I/R injury.

铁下垂是缺血再灌注(I/R)损伤和随后的器官衰竭的关键因素。虽然ENPP2参与调节心肌细胞的铁下沉,但其在心肌I/R损伤中的具体作用尚不清楚。本研究旨在阐明enpp2介导的铁上落在心肌缺血再灌注损伤(MI/RI)中的功能,为潜在的治疗策略提供新的见解。建立小鼠MI/RI模型,并进行ENPP2过表达和/或SIRT1敲低干预。在体外,用棕榈酸盐处理心肌细胞,并进行缺氧/再氧化(H/R)模拟I/R损伤。这些细胞接受ENPP2过表达(e-ENPP2)、SIRT1过表达(e-SIRT1)、PGC-1α沉默(si-PGC-1α)和/或SIRT1敲低(sh-SIRT1)的处理。此外,erastin诱导的心肌细胞铁下垂被用来评估e- enpp2的保护作用。通过脂质过氧化(MDA, 4-HNE),铁和Fe2+测定,GPx4和SLC7A11表达,透射电镜评估铁下垂。过表达ENPP2可通过上调GPx4和SLC7A11蛋白水平,显著缓解MI/RI小鼠心肌梗死。在缺氧/再氧化(H/R)或erastin诱导的铁凋亡心肌细胞中,e- enpp2降低了凋亡率,保留了Fe2+含量,恢复了GPx4和SLC7A11的表达。沉默PGC-1α可阻断e- enpp2对H/ r诱导的HL-1细胞铁凋亡的保护作用。此外,SIRT1过表达抑制PGC-1α乙酰化,而SIRT1敲低类似地逆转了H/ r处理的HL-1细胞中e- enpp2的抗铁沉作用。SIRT1沉默可通过PGC-1α/NRF1途径阻断e- enpp2对MI/RI小鼠心肌梗死和纤维化的保护作用。ENPP2过表达通过SIRT1/PGC-1α/NRF1途径保护小鼠心肌免受I/ r诱导的铁下垂损伤。这些发现为减轻心肌I/R损伤提供了一种新的基因治疗策略。
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引用次数: 0
Identification of Cuproptosis-Associated Biomarker Candidates in Hypertrophic Cardiomyopathy via Machine Learning and Multi-Omics Integration. 通过机器学习和多组学整合鉴定肥厚性心肌病中铜腐病相关生物标志物候选物。
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05533-5
Weidong Wang, Ye Tian, Chunyu Wang, Xiuhua Yang

Hypertrophic cardiomyopathy (HCM) is a complex genetic disorder characterized by left ventricular hypertrophy and impaired cardiac function. Although progress has been made in understanding its genetic basis, the discovery of novel biomarker candidates and therapeutic targets remains crucial for improving diagnosis and treatment. Recent studies have demonstrated that copper metabolism plays an important role in various diseases, suggesting that copper-related genes (CRGs) may be of significant importance in HCM. In this study, we analyzed bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data from healthy controls (HC) and HCM patients. Differentially expressed genes (DEGs) were identified through differential expression analysis, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify associated pathways. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify gene modules related to the HCM phenotype, and a diagnostic model was constructed based on these modules. Additionally, cell type-specific expression patterns were explored through single-cell analysis, and Gene Set Enrichment Analysis (GSEA) and MR analyses were conducted to evaluate the causal relationships between genes and HCM risk. The study found that DEGs associated with HCM were significantly enriched in pathways related to immune responses. WGCNA identified gene modules highly correlated with HCM, among which the blue module exhibited the strongest correlation with HCM. The diagnostic model constructed based on DEGs and WGCNA module genes demonstrated good diagnostic performance, with FCN3, TIPARP, and PROM1 emerging as potential diagnostic biomarker candidates for HCM. Additionally, single-cell analysis revealed the expression characteristics of different cell types in HCM, and causal relationships between key genes and HCM risk were confirmed through GSEA and MR analyses. This study identified FCN3, TIPARP, and PROM1 as cuproptosis-associated biomarker candidates that showed reproducible expression patterns across cohorts and experimental validation. These findings are associative and hypothesis-generating; they suggest potential diagnostic utility that warrants prospective clinical evaluation and mechanistic studies (e.g., perturbation of copper homeostasis and gene manipulation) before any therapeutic inference can be made.

肥厚性心肌病(HCM)是一种复杂的遗传性疾病,以左心室肥厚和心功能受损为特征。尽管在了解其遗传基础方面取得了进展,但发现新的生物标志物候选物和治疗靶点对于改善诊断和治疗仍然至关重要。最近的研究表明,铜代谢在多种疾病中起重要作用,提示铜相关基因(copper-related genes, CRGs)可能在HCM中起重要作用。在这项研究中,我们分析了健康对照(HC)和HCM患者的大量RNA-seq和单细胞RNA-seq (scRNA-seq)数据。通过差异表达分析鉴定差异表达基因(DEGs),并通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析鉴定相关途径。采用加权基因共表达网络分析(Weighted Gene Co-expression Network Analysis, WGCNA)识别与HCM表型相关的基因模块,并基于这些模块构建诊断模型。此外,通过单细胞分析探索细胞类型特异性表达模式,并进行基因集富集分析(GSEA)和MR分析来评估基因与HCM风险之间的因果关系。研究发现,与HCM相关的deg在与免疫反应相关的途径中显著富集。WGCNA鉴定出与HCM高度相关的基因模块,其中蓝色模块与HCM相关性最强。基于deg和WGCNA模块基因构建的诊断模型显示出良好的诊断性能,FCN3、TIPARP和PROM1成为HCM潜在的诊断生物标志物候选物。单细胞分析揭示了HCM中不同细胞类型的表达特征,并通过GSEA和MR分析证实了关键基因与HCM风险之间的因果关系。该研究确定了FCN3、TIPARP和PROM1作为铜腐病相关的生物标志物候选物,在队列和实验验证中显示出可重复的表达模式。这些发现是相互关联的,可以产生假设;他们认为,在做出任何治疗推断之前,潜在的诊断效用需要进行前瞻性临床评估和机制研究(例如,铜稳态的扰动和基因操纵)。
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引用次数: 0
DUSP7 Overexpression Suppresses Lung Adenocarcinoma Cell Proliferation, Invasion, and M2 Macrophage Polarization Through JAK2/STAT3 Pathway Inhibition. DUSP7过表达通过抑制JAK2/STAT3通路抑制肺腺癌细胞增殖、侵袭和M2巨噬细胞极化
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-03 DOI: 10.1007/s12010-025-05483-y
Hui Tian, Shanshan Li, Xiuping Gu, Gaofeng Liang, Jinxian He
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引用次数: 0
Biogenic ZnO Nanoparticles from Allium Cepa and Tagetes erecta: Synthesis, Characterization and its Antidiabetic, Antioxidant Evaluation and Cytotoxic Studies against Mouse Insulinoma (MIN6) Cell Line. 大蒜和万寿菊生物源氧化锌纳米颗粒的合成、表征及其抗糖尿病、抗氧化评价和对小鼠胰岛素瘤(MIN6)细胞系的细胞毒性研究
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-29 DOI: 10.1007/s12010-025-05500-0
Rachana S Bhimanwar, Animesh Sanap, Sohan Chitlange, Chetan Bhoite, Shubhangi Sutar

Plant-based nanoparticles have potential uses and advantages over traditional physico-chemical techniques. In this study, zinc oxide nanoparticles (ZnO-NPs) were biosynthesized from Tagetes erecta flower extract and Allium cepa peel extract, characterized and evaluated their antioxidant, and antidiabetic activities. UV-visible absorption spectroscopy (UV-Vis) revealed a characteristic absorption peak at 355 nm, while X-ray diffraction (XRD) confirmed the presence of crystalline ZnO-NPs having an average size of 35.14 nm. Fourier transform infrared (FTIR) spectroscopy provided evidence for presence of functional groups that stabilizes nanoparticles, elemental composition was confirmed by energy-dispersive X-ray spectroscopy (EDX). Scanning electron microscopy (SEM) provided evidence of the rod-like morphology of nanoparticles, and dynamic light scattering determined the particle size distribution and polydispersity index. The biosynthesized ZnO-NPs presented a range of biological activities that included key antioxidant properties and strong inhibition of α-glucosidase activity (IC₅₀ = 35.9 ± 2.49 µg/mL). The MTT assay was performed for cytotoxicity screening MIN6 pancreatic β-cells that confirmed high viability from 99.4% at 10 µg/mL to 85.6% at 100 µg/mL, indicating non-toxic behaviour. Furthermore, the biosynthesized ZnO-NPs also induce dose-dependent stimulation of insulin secretion, with fold-increases ranging from 2.29 to 7.64 (p ≤ 0.0001) compared to controls. The ZnO-NPs derived from peel of Allium cepa and the floral extracts of Tagetes erecta shown strong antioxidant and antidiabetic characteristics, suggesting that they have the potential to be effective therapeutic agents with minimal side effects for advanced biomedical applications.

基于植物的纳米颗粒比传统的物理化学技术具有潜在的用途和优势。以万寿菊花提取物和葱皮提取物为原料合成氧化锌纳米颗粒(ZnO-NPs),对其抗氧化和抗糖尿病活性进行了表征和评价。紫外可见吸收光谱(UV-Vis)在355nm处发现了一个特征吸收峰,x射线衍射(XRD)证实了ZnO-NPs晶体的存在,平均尺寸为35.14 nm。傅里叶变换红外光谱(FTIR)提供了稳定纳米颗粒的官能团存在的证据,元素组成由能量色散x射线光谱(EDX)证实。扫描电子显微镜(SEM)提供了纳米颗粒棒状形貌的证据,动态光散射确定了纳米颗粒的尺寸分布和多分散性指数。生物合成的ZnO-NPs具有一系列生物活性,包括关键的抗氧化性能和对α-葡萄糖苷酶活性的强抑制作用(IC₅₀= 35.9±2.49µg/mL)。MTT法对MIN6胰腺β细胞进行细胞毒性筛选,证实在10µg/mL时存活率为99.4%,在100µg/mL时存活率为85.6%,表明无毒行为。此外,生物合成的ZnO-NPs还诱导胰岛素分泌的剂量依赖性刺激,与对照组相比,增加了2.29至7.64倍(p≤0.0001)。从葱皮和万寿菊花提取物中分离得到的ZnO-NPs具有较强的抗氧化和降糖作用,提示其有潜力成为一种副作用小的治疗药物,可用于先进的生物医学应用。
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引用次数: 0
Beta Carboline Alkaloid Harmine as Biofilm Inhibitor: In vitro, in Silico and in Vivo Studies Suppressing Growth and Virulence-Related Factors Against Resistant Staphylococcus Aureus. 作为生物膜抑制剂的-碳碱生物碱碱碱:体外、硅和体内抑制耐药金黄色葡萄球菌生长和毒力相关因子的研究
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-27 DOI: 10.1007/s12010-025-05508-6
Paromita Sarkar, Sharmistha Das, Shrabasti Bandyopadhyay, Priyanka Gopi, Samik Biswas, Prosun Tribedi, Prateek Pandya, Supratim Mandal, Kakali Bhadra

Screening plant-based alkaloids is one of the alternate therapeutic approaches to control antibiotic-resistant micro-pathogens. Our research highlighted beta carboline alkaloids as one of the most promising small molecules to established anti-virulent and anti-biofilm efficacy to regulate resistant bacterial infection. In vitro, in vivo assay and molecular docking were employed. Result Among six different bacterial strains, harmine showed 160 ± 2.07 µg/ml as the minimum inhibitory concentrations (MIC), followed by harmalol (190 ± 2.46) and harmaline (270 ± 3.04) against Staphylococcus aureus 96 (SA 96). Methicillin-resistant Staphylococcus aureus MRSA strain also showed inhibition of growth (MIC) by harmine, harmalol and harmaline at 250 ± 3.10, 320 ± 3.39 and 390 ± 4.90 µg/ml, respectively. MRSA is a prominent source of nosocomial infections, forming biofilms. The growth of biofilm got decreased with exposure to the sub-MIC concentrations (60, 80 and 100 µg/mL) of harmine, suppressing protein, targeting EPS and inhibiting extracellular protease. Harmine promote biofilm cell detachment by targeting cell surface hydrophobicity. Harmine causes depolarization of bacteria's cell membrane. Bacterial cell viability was further studied by propidium iodide (PI), DNA leakage and Acridine Orange (A/O)-Ethidium Bromide (EtBr) assay. Harmine treatment leads to increased reactive oxygen species (ROS) levels in biofilm cells. The binding affinities by molecular docking and dynamics indicated highest affinity with AgrC (-6.17 kcal/mol). Harmine treatment (32.0 mg/ kg bw, IP for five days) further recovered MRSA infected lungs in BALB/c mice. The findings revealed that among the three beta carboline alkaloids, harmine might be employed as a potential antibiofilm and antimicrobial agent for successful control of clinical S. aureus infection.

筛选植物生物碱是控制耐药微病原体的替代治疗方法之一。我们的研究强调了-碳碱生物碱是最有希望建立抗毒和抗生物膜功效的小分子之一,以调节耐药细菌感染。体外、体内实验和分子对接。结果在6种不同的菌株中,毒芹碱对金黄色葡萄球菌96 (SA 96)的最低抑制浓度为160±2.07µg/ml,其次是哈玛洛尔(190±2.46)和哈玛洛林(270±3.04)。耐甲氧西林金黄色葡萄球菌MRSA菌株的生长抑制浓度分别为250±3.10µg/ml、320±3.39µg/ml和390±4.90µg/ml。MRSA是医院感染的主要来源,形成生物膜。暴露于亚mic浓度(60、80和100µg/mL)下,生物膜的生长受到抑制,抑制蛋白,靶向EPS,抑制胞外蛋白酶。毒碱通过靶向细胞表面疏水性促进生物膜细胞脱离。毒碱导致细菌细胞膜去极化。采用碘化丙啶(PI)、DNA泄漏和吖啶橙(A/O)-溴化乙啶(EtBr)试验进一步研究细菌的细胞活力。毒碱处理导致生物膜细胞活性氧(ROS)水平增加。分子对接和动力学结果表明,与AgrC的亲和力最高(-6.17 kcal/mol)。毒碱治疗(32.0 mg/ kg bw,连续5天)进一步恢复了感染MRSA的BALB/c小鼠的肺部。结果表明,在3种β -碳碱类生物碱中,伤害碱可能作为一种潜在的抗生物膜和抗菌药物,成功控制临床金黄色葡萄球菌感染。
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引用次数: 0
DNMT3A-mediated Methylation of IRF4 Alleviates Inflammatory Response in Allergic Rhinitis Mice. dnmt3a介导的IRF4甲基化减轻变应性鼻炎小鼠的炎症反应
IF 3.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-12-27 DOI: 10.1007/s12010-025-05490-z
Dan Shan, Simin Gao, Lin Li, Shuyi Huang, Mengru Yao

This study explores the mechanism of DNMT3A in inflammatory response in allergic rhinitis (AR) mice. A mouse model of AR was established by ovalbumin induction, followed by injection of DNMT3A overexpression vector. The times of nose rubbing and sneezing within 15 min were recorded. The nasal mucosa tissues were observed by H&E staining. The serum histamine, IgE, IL-1β, IL-10, IFN-γ, and TNF-α were detected by ELISA. The proportion of Th17/Treg cells in lymphocytes was detected by flow cytometry. DNMT3A, IRF4, and CD44 expressions were tested by qRT-PCR or Western blot. ChIP evaluated the DNMT3A enrichment on IRF4 promoter and IRF4 enrichment on CD44 promoter. Methylation-specific PCR determined the methylation level of IRF4 promoter. The binding of IRF4 to CD44 was verified by dual-luciferase assay. DNMT3A was poorly expressed in AR mice. DNMT3A overexpression reduced the times of nose rubbing and sneezing in AR mice, alleviated nasal mucosal tissue injury, reduced the proportion of Th17/Treg cells, and diminished serum inflammatory factors. DNMT3A was enriched on IRF4 promoter and repressed IRF4 expression by enhancing IRF4 methylation level. IRF4 bound to CD44 promoter to elevate CD44 expression. In conclusion, DNMT3A-mediated methylation of IRF4 reduces AR inflammatory response by elevating CD44 expression.

本研究探讨DNMT3A在变应性鼻炎(AR)小鼠炎症反应中的作用机制。通过卵清蛋白诱导建立小鼠AR模型,然后注射DNMT3A过表达载体。记录15分钟内揉鼻、打喷嚏次数。H&E染色观察大鼠鼻黏膜组织。ELISA法检测血清组胺、IgE、IL-1β、IL-10、IFN-γ、TNF-α。流式细胞术检测淋巴细胞中Th17/Treg细胞的比例。采用qRT-PCR或Western blot检测DNMT3A、IRF4、CD44的表达。ChIP检测了DNMT3A在IRF4启动子上的富集和IRF4在CD44启动子上的富集。甲基化特异性PCR检测IRF4启动子的甲基化水平。双荧光素酶实验证实了IRF4与CD44的结合。DNMT3A在AR小鼠中表达不良。DNMT3A过表达可减少AR小鼠擦鼻和打喷嚏次数,减轻鼻黏膜组织损伤,降低Th17/Treg细胞比例,降低血清炎症因子。DNMT3A富集于IRF4启动子上,通过提高IRF4甲基化水平抑制IRF4表达。IRF4结合CD44启动子提升CD44表达。综上所述,dnmt3a介导的IRF4甲基化通过提高CD44的表达来降低AR炎症反应。
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Applied Biochemistry and Biotechnology
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