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Insulin Resistance, Anti-inflammatory, and Antioxidant In vitro Activity of Heterologously Expressed Arenin from Dryophytes arenicolor 槟榔草异源表达槟榔素的胰岛素抵抗、抗炎和抗氧化活性研究
Q1 Immunology and Microbiology Pub Date : 2026-01-14 DOI: 10.1016/j.btre.2026.e00947
Enrique Hidalgo-Vázquez , Marilena Antunes-Ricardo , Jesús Hernández-Pérez , Jorge Benavides
Amphibian-derived peptides are promising therapeutics for metabolic dysfunction, oxidative stress, and immune imbalance. We investigated arenin, a Kunitz-type peptide from Dryophytes arenicolor, produced heterologously in E. coli, for anti-metabolic, antioxidant, and immunomodulatory activities. In insulin-resistant hepatocytes, arenin increased glucose uptake from 23.97 ± 2.79% (IR control) to 51.38 ± 2.95% at 250 µg/mL. Arenin also reduced intracellular reactive oxygen species (ROS) in a time-dependent manner. The most significant early effect (20 min) occurred at higher doses (500–1000 µg/mL), whereas at 24 h the effect shifted to lower–intermediate concentrations (15.62–250 µg/mL), with 15.62 µg/mL yielding the lowest ROS levels (15.78 ± 1.66%). In macrophages, nitric oxide (NO) production showed a concentration-dependent, multi-layered response, indicating immunomodulation. These data position arenin as a multifunctional bioactive capable of improving metabolic homeostasis, strengthening antioxidant defenses, and tuning innate immune responses, laying groundwork for peptide-based interventions against metabolic disturbances.
两栖动物衍生的肽是治疗代谢功能障碍、氧化应激和免疫失衡的有希望的药物。我们研究了arenin,一种在大肠杆菌中异源产生的来自arenicolor干植物的kunitz型肽,其抗代谢、抗氧化和免疫调节活性。在胰岛素抵抗型肝细胞中,当剂量为250µg/mL时,arenin使葡萄糖摄取从23.97±2.79% (IR对照)增加到51.38±2.95%。Arenin还以时间依赖性的方式减少细胞内活性氧(ROS)。高剂量(500-1000µg/mL)的早期效应最显著(20 min),而在24 h时,效应转移到中低浓度(15.62 - 250µg/mL), 15.62µg/mL产生最低的ROS水平(15.78±1.66%)。在巨噬细胞中,一氧化氮(NO)的产生表现出浓度依赖的多层反应,表明免疫调节。这些数据表明,arenin是一种多功能生物活性物质,能够改善代谢稳态,增强抗氧化防御,调节先天免疫反应,为基于肽的代谢紊乱干预奠定了基础。
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引用次数: 0
Bacillus altitudinis GG-22: A novel plant growth-promoting bacterium with beneficial agronomic properties 高海拔芽孢杆菌GG-22:一种具有有益农艺特性的植物生长促进菌
Q1 Immunology and Microbiology Pub Date : 2026-01-13 DOI: 10.1016/j.btre.2026.e00945
Ana Falcón-Piñeiro , Alberto Baños , Eva M. Molin , Elías González-Gragera , Annalisa Giampetruzzi , Raied Abou Kubaa , Livio Antonielli , Adrian Wallner , Günter Brader , Satish K. Verma , Antonio M. Martin-Platero , Manuel Martínez-Bueno , Stéphane Compant , Pasquale Saldarelli
Bacillus altitudinis GG-22, isolated from the phyllosphere of agricultural crops, has been identified as a promising biocontrol agent and plant growth-promoting bacterium with substantial potential in sustainable agriculture. In this study, whole-genome sequencing using Illumina technology, combined with ANI analysis, confirmed the strain's classification as B. altitudinis. The genome revealed a rich set of genes involved in biocontrol mechanisms, including the capacity of synthesis of siderophores (schizokinen and bacillibactin-like compounds), the lipopeptide pumilacidin, the bacteriocin pumilarin, alkylpyrones and Bacillus volatiles. In vitro antagonism assays demonstrated significant inhibitory effects against phytopathogenic fungi and oomycetes, such as Verticillium dahliae and Pythium sp., and B. altitudinis GG-22 also showed limited efficacy against bacterial phytopathogens, including Xylella fastidiosa. Transcriptomic profiling of olive trees treated with GG-22 indicated early activation of auxin transport and systemic acquired resistance (SAR) pathways, alongside substantial downregulation of cell wall remodelling genes. These findings suggest that B. altitudinis GG-22 primes plant defence responses and modulates hormonal pathways critical for growth and stress resilience. Future research should prioritize optimizing application strategies and exploring synergies with other microbial agents to fully harness the biocontrol and growth-promoting potential of B. altitudinis GG-22. This strain holds promise for sustainable agricultural practices, particularly in controlling fungal diseases and improving plant performance under stress conditions.
高海拔芽孢杆菌GG-22是一种分离自农作物根层的生物防治菌和植物生长促进菌,在可持续农业中具有很大的应用潜力。在本研究中,利用Illumina技术进行全基因组测序,结合ANI分析,证实了该菌株的分类为B. altiudinis。基因组揭示了一组丰富的与生物防治机制有关的基因,包括合成铁载体(分裂素和杆菌杆菌素样化合物)、脂肽彪马酸苷、细菌素彪马酸苷、烷基吡啶酮和芽孢杆菌挥发物的能力。体外拮抗实验表明,g -22对植物病原真菌和卵菌(如大丽花黄萎病菌和毕氏霉)有显著的抑制作用,而B. altiudinis GG-22对植物病原菌(包括木杆菌)也有有限的抑制作用。GG-22处理的橄榄树转录组学分析表明,生长素运输和系统性获得性抗性(SAR)途径的早期激活,以及细胞壁重塑基因的大幅下调。这些发现表明,B. aludinis GG-22启动植物防御反应并调节对生长和应激恢复至关重要的激素通路。未来的研究应优先优化应用策略,探索与其他微生物制剂的协同作用,以充分发挥高海拔双歧杆菌GG-22的生物防治和促生潜力。该菌株有望用于可持续农业实践,特别是在控制真菌疾病和改善逆境条件下的植物性能方面。
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引用次数: 0
Production and characterization of rNGFSP: a recombinant fusion immunogen eliciting dual anti-NGF and anti-Substance P therapeutic antibodies for Degenerative Joint Disease rNGFSP的制备和表征:一种重组融合免疫原,可引发抗ngf和抗P物质治疗性退行性关节疾病的双重抗体
Q1 Immunology and Microbiology Pub Date : 2026-01-12 DOI: 10.1016/j.btre.2026.e00946
Valentina Varela , Monique Costa , Cecilia Maciel , Joaquín Barbeito , Exequiel E. Barrera , Erica Gutierre , Agustín Correa , Melania Elgue , Sebastián Carrasco , Magdalena Domínguez Larrosa , María Pereira , Josefina Correa , Nadia Crosignani , Joseph S. Beckman , Luis Barbeito , Emiliano Trias
Anti-NGF monoclonal antibodies have recently been approved for treating degenerative joint disease, including osteoarthritis pain, in dogs and cats. However, their widespread use is limited by high cost and the requirement for repeated injections. Nerve Growth Factor and Substance P play central roles in the initiation and maintenance of inflammation and chronic pain in OA. There is a pressing need for new, safe, cost-effective therapies that target the underlying mechanisms of OA chronic pain. Here, we designed and produced a novel recombinant fusion protein, termed rNGFSP, which functions as an immunogen due to its unique molecular structure combining amino acid sequences from NGF and SP in a non-native conformation. When formulated and administered as a vaccine, rNGFSP elicits dual anti-NGF and anti-SP therapeutic antibodies in the host. rNGFSP was produced in E. coli and purified from inclusion bodies using metal affinity chromatography under denaturing conditions. Mass spectrometry confirmed the expected molecular weight (17.5 kDa) and preserved amino acid sequence. Structural prediction using Alphafold2 revealed rNGFSP presented a non-natural folding, but a preserved NGF core and a flexible SP tail, supporting antigenic presentation. Vaccination of mice, rabbits, horses, and dogs, showed that rNGFSP elicited cross-reactive IgG antibodies against the native conformations of NGF and SP. Furthermore, immunoglobulins elicited in vaccinated dogs neutralized the biological activity of NGF and SP in cell cultures, suggesting a therapeutic potential. These findings support rNGFSP as a promising vaccine candidate simultaneously targeting endogenous NGF and SP species, providing a cost-effective alternative to monoclonal antibodies.
抗ngf单克隆抗体最近已被批准用于治疗退行性关节疾病,包括狗和猫的骨关节炎疼痛。然而,它们的广泛使用受到高成本和需要反复注射的限制。神经生长因子和P物质在OA炎症和慢性疼痛的发生和维持中起核心作用。迫切需要针对OA慢性疼痛潜在机制的新的、安全的、具有成本效益的治疗方法。在这里,我们设计并生产了一种新的重组融合蛋白,称为rNGFSP,由于其独特的分子结构将NGF和SP的氨基酸序列以非天然构象组合而成,因此具有免疫原的功能。当rNGFSP作为疫苗配制和使用时,可在宿主体内引发双重抗ngf和抗sp治疗抗体。rNGFSP由大肠杆菌产生,在变性条件下用金属亲和层析法从包涵体中纯化。质谱分析证实了预期的分子量(17.5 kDa)和保存的氨基酸序列。利用Alphafold2进行结构预测,发现rNGFSP呈非自然折叠,但保留了NGF核心和灵活的SP尾部,支持抗原呈递。对小鼠、兔子、马和狗接种rNGFSP后,研究人员发现rNGFSP可诱导抗NGF和SP天然构象的交叉反应性IgG抗体。此外,接种犬的免疫球蛋白可中和细胞培养中NGF和SP的生物活性,这表明rNGFSP具有治疗潜力。这些发现支持rNGFSP作为一种有希望的候选疫苗,同时靶向内源性NGF和SP物种,提供了单克隆抗体的经济替代方案。
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引用次数: 0
Neural Latent Filtering for Gene Discovery in Breast Cancer Subtypes 乳腺癌亚型基因发现的神经潜伏过滤
Q1 Immunology and Microbiology Pub Date : 2025-12-31 DOI: 10.1016/j.btre.2025.e00942
Danilo Menegatti , Giulia Fiscon , Alessandro Giuseppi , Paola Paci , Antonio Pietrabissa
Gene selection from expression data represents a challenging task, primarily due to the high data dimensionality and the vast number of genes that would be identified, many of which may be unrelated to cancer-relevant biological processes. To tackle this issue, filtering methods constitute an effective solution to identify the most informative genes, which can serve as potential biomarkers to tailor cancer therapies. This work proposes a novel neural-based filtering approach which aims to identify genes by means of their latent representation extracted from RNA Sequencing expression data. This approach has been applied to study breast invasive carcinoma dataset, aiming to identify the most relevant genes of two breast cancer subtypes, Luminal-A and Basal-like, to better investigate their molecular landscape.
从表达数据中选择基因是一项具有挑战性的任务,主要是由于高数据维度和大量的基因将被识别,其中许多可能与癌症相关的生物学过程无关。为了解决这个问题,过滤方法构成了一种有效的解决方案,可以识别最具信息量的基因,这些基因可以作为潜在的生物标志物来定制癌症治疗。这项工作提出了一种新的基于神经的过滤方法,旨在通过从RNA测序表达数据中提取的潜在表示来识别基因。该方法已被应用于研究乳腺浸润性癌数据集,旨在识别两种乳腺癌亚型(Luminal-A和Basal-like)最相关的基因,以更好地研究它们的分子景观。
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引用次数: 0
Plant-produced monoclonal antibodies recognize the native circumsporozoite protein on Plasmodium falciparum sporozoites 植物产生的单克隆抗体识别恶性疟原虫孢子体上的天然环孢子子蛋白
Q1 Immunology and Microbiology Pub Date : 2025-12-30 DOI: 10.1016/j.btre.2025.e00944
Kanokporn Thiganta , Kaewta Rattanapisit , Pipob Suwanchaikasem , Wanlapa Roobsoong , Christine Joy I. Bulaon , Waranyoo Phoolcharoen
Malaria is primarily caused by Plasmodium parasites and remains a major global health threat due to drug resistance and limited vaccine efficacy. Monoclonal antibodies (mAbs) targeting the conserved NANP repeat region of the circumsporozoite protein (PfCSP), such as MS-1797, represent a promising prophylactic strategy. Here, we demonstrate the plant-based production of MS-1797 in glycoengineered Nicotiana benthamiana ΔXF. Two variants were generated: MS-01 (original MS-1797) and MS-02 (MS-1797-SEKDEL), which yielded up to 457.3 µg/g fresh weight and 415.7 µg/g FW at 6 days post-infiltration. The plant-derived mAbs were obtained in high purity (>90%) and displayed either human core glycans or high mannose structures. Notably, both MS-01 and MS-02 retained antigen specificity in vitro and bound native PfCSP on sporozoites by immunofluorescence assay. These results establish the feasibility of producing functional anti-malarial mAbs in plants and highlight their potential use as affordable reagents for malaria research, diagnostics, and future prophylactic interventions.
疟疾主要由疟原虫引起,由于耐药性和疫苗效力有限,它仍然是一个主要的全球健康威胁。针对环孢子子蛋白(PfCSP)保守的NANP重复区域的单克隆抗体(mab),如MS-1797,是一种很有前途的预防策略。在这里,我们展示了糖工程的benthamiana ΔXF中MS-1797的植物性生产。产生了MS-01(原MS-1797)和MS-02 (MS-1797- sekdel)两个变体,在浸润后6天产生高达457.3µg/g鲜重和415.7µg/g FW。获得的植物源单抗具有高纯度(>90%),并显示人源核心聚糖或高甘露糖结构。值得注意的是,MS-01和MS-02在体外都保留了抗原特异性,并通过免疫荧光法在孢子体上结合了天然PfCSP。这些结果确定了在植物中生产功能性抗疟疾单克隆抗体的可行性,并强调了它们作为疟疾研究、诊断和未来预防干预的廉价试剂的潜力。
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引用次数: 0
Cyanobacterium-Penicillium co-flocculation under erythromycin treatment: increased CO2 capture and biomass production in an organic compound-free co-cultivation 红霉素处理下的蓝藻-青霉共絮凝:在无有机化合物共培养中增加CO2捕获和生物量生产
Q1 Immunology and Microbiology Pub Date : 2025-12-29 DOI: 10.1016/j.btre.2025.e00943
Jidapa Leksingto , Panutchaya Pichaiyotinkul , Kobkul Boorachokwiwat , Janine Kaewbai-ngam , Nichaphat Kanoksinwuttipong , Nannaphat Sukkasam , Tanakarn Monshupanee
Photoautotrophic cyanobacteria convert CO₂ into bioproducts. However, efficient cell harvesting remains a major obstacle. Auto-bioflocculation offers a promising solution. In cultures of Synechocystis sp. PCC 6803, Synechocystis co-flocculated with natural fungal contaminant (identified as Penicillium sp.) into spherical clusters with internal hollow spaces—but only in the presence of erythromycin (EM), and not without EM. Optimized co-cultivation of Synechocystis and Penicillium for five days in BG11 medium (lacking organic compounds) supplemented with 5 µM EM resulted in complete biomass co-flocculation, yielding up to 2.0 g/L. This corresponds to atmospheric CO₂ capture rate of 0.50 g/L/day, representing a 7.9-fold increase in biomass and a 7.0-fold enhancement in CO₂ capture compared to axenic Synechocystis culture. Protein was the major component of the flocculated biomass, accounting for 39–61 % of dry weight. Increasing EM concentrations (from 0.3 to 10 µM) led to an increase in floc diameter from 0.5 to 1.9 mm. Scaling the culture volume from 100 to 200–1000 mL changed the surface texture of the co-flocculates from relatively smooth to rough with thorn-like structures. Transcriptomic analysis indicated that co-flocculation was associated with upregulation of genes involved in S-layer protein synthesis, molecular chaperones, exopolysaccharide polymerization, and pilin regulation. Genes related to minor pilin proteins, pili function, and capsular polysaccharide synthesis were downregulated. Differentially expressed genes between smooth-surfaced and rough-surfaced co-flocs were reported. This bio-flocculation demonstrates low-energy, organic-free strategy that boosts CO₂ capture, highlighting strong potential for carbon-negative bioprocesses. The protein-rich co-flocs offer opportunities for downstream use in animal feed or biorefinery.
光自养蓝藻将二氧化碳转化为生物产物。然而,高效的细胞收集仍然是一个主要障碍。自动生物定位提供了一个很有前途的解决方案。在Synechocystis sp. PCC 6803的培养中,Synechocystis与天然真菌污染物(鉴定为青霉菌sp.)共絮凝成球状团簇,内部有中空空间,但只有在红霉素(EM)存在的情况下,而不是在没有EM的情况下。优化Synechocystis和青霉菌在添加5µM EM的BG11培养基(缺乏有机化合物)中共培养5天,生物量共絮凝完全实现,产量高达2.0 g/L。这相当于大气CO₂捕获率为0.50 g/L/天,与无氧共生藻培养相比,生物量增加了7.9倍,CO₂捕获率提高了7.0倍。蛋白质是絮凝生物量的主要成分,占干重的39 ~ 61%。随着EM浓度的增加(从0.3µM增加到10µM),絮凝体直径从0.5µM增加到1.9µM。当培养量从100到200-1000 mL时,共絮凝体的表面纹理从相对光滑变为粗糙,具有刺状结构。转录组学分析表明,共絮凝与参与s层蛋白合成、分子伴侣、胞外多糖聚合和pilin调控的基因上调有关。与次要毛蛋白、毛功能和荚膜多糖合成相关的基因下调。报道了表面光滑和表面粗糙的共絮凝体之间差异表达的基因。这种生物絮凝展示了低能量、无有机的策略,可以促进CO 2的捕获,突出了碳负性生物过程的强大潜力。富含蛋白质的共絮凝体为下游动物饲料或生物炼制提供了机会。
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引用次数: 0
Pathogenesis and advances in immunotherapy for type 1 diabetes treatment 免疫疗法治疗1型糖尿病的发病机制及进展
Q1 Immunology and Microbiology Pub Date : 2025-12-02 DOI: 10.1016/j.btre.2025.e00940
Tran Chi Linh , Nguyen Khanh Dung
Type 1 diabetes (T1D) is an autoimmune disease marked by selective destruction of pancreatic β-cells, resulting in absolute insulin deficiency. Although insulin replacement remains the standard therapy, it does not address the underlying autoimmune process or prevent long-term complications. Advances in understanding the pathogenesis have highlighted the interaction of genetic susceptibility, environmental triggers, and immune dysregulation, paving the way for innovative immunotherapies. Current strategies include nonspecific immunosuppressants, monoclonal antibodies (e.g., teplizumab, rituximab), peptide vaccines, and cell-based therapies such as regulatory T cells and stem cells. Among these, teplizumab has gained FDA approval to delay disease onset in high-risk individuals, representing a milestone in preventive intervention. Nevertheless, limited durability, high costs, and safety concerns restrict broader clinical application. Looking forward, personalized treatment strategies, rational drug combinations, and early preclinical interventions are expected to optimize outcomes, offering new hope for improving prognosis and quality of life in T1D patients.
1型糖尿病(T1D)是一种以胰腺β细胞选择性破坏为特征的自身免疫性疾病,导致绝对胰岛素缺乏。虽然胰岛素替代仍然是标准的治疗方法,但它不能解决潜在的自身免疫过程或预防长期并发症。在了解其发病机制方面的进展突出了遗传易感性、环境触发因素和免疫失调之间的相互作用,为创新免疫疗法铺平了道路。目前的策略包括非特异性免疫抑制剂、单克隆抗体(例如,teplizumab、rituximab)、肽疫苗和基于细胞的疗法,如调节性T细胞和干细胞。其中,teplizumab已获得FDA批准,用于延迟高风险人群的疾病发病,这是预防性干预的一个里程碑。然而,有限的耐用性、高成本和安全问题限制了其广泛的临床应用。展望未来,个性化的治疗策略、合理的药物组合、早期的临床前干预有望优化预后,为改善T1D患者的预后和生活质量带来新的希望。
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引用次数: 0
EIOFX-DT: Leveraging graph centrality metrics for feature extraction and classification of viral genetic sequences EIOFX-DT:利用图中心性度量进行特征提取和病毒基因序列分类
Q1 Immunology and Microbiology Pub Date : 2025-11-27 DOI: 10.1016/j.btre.2025.e00939
Amin Khodaei , Zahra Pourabbas , Fatemeh Hashem-zadehdizajyekan , Erfan Esmaeili
Many diseases have a genetic origin, and analyzing intracellular structures through genetic data yields specific features for the diagnosis and classification of viral disease samples. In this study, 30 types of viruses were analyzed using a graph-based approach on genetic data. Genetic data has been modeled in the form of genomic sequences at the nucleotide scale using the graph theory of complex networks concepts. Degree and eigenvector centrality metrics were employed to extract features. The decision tree was utilized as a machine learning classifier algorithm on the resulting feature space. The results, presented in the form of interpretable rules, enable the classification and identification of virus types from both a binary and multi-class perspective. The model achieved high accuracy and f1 score, which exceeded 99 % on >173,000 samples. Additionally, the feature extraction algorithm demonstrated robust performance across all datasets and classifiers.
许多疾病具有遗传起源,通过遗传数据分析细胞内结构可为病毒性疾病样本的诊断和分类提供特定特征。在这项研究中,使用基于图的方法分析了30种病毒的遗传数据。利用复杂网络概念的图论,遗传数据以基因组序列的形式在核苷酸尺度上建模。采用度度量和特征向量中心性度量提取特征。在得到的特征空间上,将决策树作为机器学习分类器算法。结果以可解释规则的形式呈现,能够从二进制和多类的角度对病毒类型进行分类和识别。该模型在17.3万个样本上取得了很高的准确率和f1分数,超过99%。此外,特征提取算法在所有数据集和分类器上都表现出鲁棒性。
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引用次数: 0
Integrating multi-omics data: Methods and applications in human complex diseases 整合多组学数据:人类复杂疾病的方法与应用
Q1 Immunology and Microbiology Pub Date : 2025-11-15 DOI: 10.1016/j.btre.2025.e00938
Pasquale Sibilio , Enrico De Smaele , Paola Paci , Federica Conte
Over the past few decades, technological advancements and declining costs of high-throughput data generation have revolutionized biomedical research, enabling the collection of large-scale datasets across multiple omics layers—including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. The analysis and integration of these datasets provides global insights into biological processes and holds great promise in elucidating the myriad molecular interactions associated with human diseases, particularly multifactorial ones such as cancer, cardiovascular, and neurodegenerative disorders. However, integrating multi-omics data presents significant challenges due to high dimensionality and heterogeneity. This review explores computational methods for integrating multi-omics data, with a particular focus on network-based approaches that offer a holistic view of relationships among biological components in health and disease. Furthermore, this review showcases a selection of recent, successful applications of multi-omics data integration, moving beyond theoretical methods to demonstrate their transformative potential in biomarker discovery, patient stratification, and guiding therapeutic interventions in specific human diseases.
在过去的几十年里,技术的进步和高通量数据生成成本的下降已经彻底改变了生物医学研究,使跨多个组学层的大规模数据集的收集成为可能,包括基因组学、转录组学、蛋白质组学、代谢组学和表观基因组学。这些数据集的分析和整合提供了对生物过程的全局见解,并在阐明与人类疾病相关的无数分子相互作用方面具有很大的希望,特别是多因素疾病,如癌症、心血管和神经退行性疾病。然而,由于多组学数据的高维度和异质性,集成多组学数据面临着巨大的挑战。这篇综述探讨了整合多组学数据的计算方法,特别关注基于网络的方法,这些方法提供了健康和疾病中生物成分之间关系的整体视图。此外,本综述还展示了多组学数据集成的一些近期成功应用,这些应用超越了理论方法,展示了它们在生物标志物发现、患者分层和指导特定人类疾病治疗干预方面的变革潜力。
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引用次数: 0
Indole-alkaloid–rich fraction of Ervatamia coronaria leaf extract regresses breast cancer by inducing apoptotic cell death 莪术叶提取物富含吲哚生物碱部分通过诱导凋亡细胞死亡来治疗乳腺癌
Q1 Immunology and Microbiology Pub Date : 2025-11-15 DOI: 10.1016/j.btre.2025.e00937
Chirantan Majumder , Anirban Manna , Satyajit Halder , Somesh Roy , Subhash C Mandal , Kuladip Jana , Mahadeb Pal
Current anti-breast cancer therapies often cause severe toxicity to normal cells and promote chemoresistance, while their exorbitant costs limit their accessibility to many patients. This underscores the need for safer, effective, and affordable alternative treatment strategies. In this study, we evaluated the anti-breast cancer potential of an alkaloid-rich dichloromethane fraction of Ervatamia coronaria (DFE) leaf extract, identified by LC-MS to contain eight indole-alkaloids as its major constituents. Using 4T1 cell-induced tumour allografts in BALB/c mice, alongside cell-based assays including cell viability, scratch assay, immunoblotting, immunohistochemistry, and scanning electron microscopy, we investigated its mechanisms of action. DFE treatment induced cell cycle arrest in the sub-G1 phase, triggering apoptosis, with little effect on normal cells. Mechanistically, elevated mitochondrial ROS were identified as the primary driver of toxicity, as pre-treatment with NAC reversed DFE’s effects. Additionally, DFE downregulated AKT signalling in breast cancer cells. Importantly, DFE significantly reduced 4T1 tumour growth in vivo, both alone and in combination with doxorubicin, without exerting significant toxicity on healthy mice. These findings support further evaluation of DFE in clinical models.
目前的抗乳腺癌疗法通常会对正常细胞造成严重的毒性,并促进化疗耐药性,而其高昂的费用限制了许多患者的可及性。这强调需要更安全、有效和负担得起的替代治疗策略。在这项研究中,我们评估了富含生物碱的Ervatamia coronaria (DFE)叶提取物二氯甲烷部分的抗乳腺癌潜力,通过LC-MS鉴定其主要成分含有8种吲哚类生物碱。利用4T1细胞诱导的BALB/c小鼠肿瘤同种异体移植物,结合细胞活力、划痕实验、免疫印迹、免疫组织化学和扫描电镜等细胞基础实验,研究了其作用机制。DFE处理诱导细胞周期阻滞于亚g1期,引发细胞凋亡,对正常细胞影响不大。机制上,线粒体ROS升高被认为是毒性的主要驱动因素,因为NAC预处理逆转了DFE的作用。此外,DFE下调乳腺癌细胞中AKT信号。重要的是,无论是单独使用还是与阿霉素联合使用,DFE都能显著降低体内4T1肿瘤的生长,而对健康小鼠没有明显的毒性。这些发现支持在临床模型中进一步评估DFE。
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