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Gut–kidney axis disruption by antibiotics: Dysbiosis, renal dysfunction and biomarker insights 抗生素对肠肾轴的破坏:生态失调、肾功能障碍和生物标志物的见解
Pub Date : 2025-12-17 DOI: 10.1016/j.abst.2025.12.007
Zhao Han , Bo Yang , Nanmei Liu , Cheng Xue
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引用次数: 0
Protective effects of nutritional and polyphenolic supplementation in polycystic ovarian syndromes 营养和多酚补充对多囊卵巢综合征的保护作用
Pub Date : 2025-12-16 DOI: 10.1016/j.abst.2025.12.005
Shaifali Joshi, Kavita Munjal, Gautam Saxena, Havagiray R. Chitme
Hormonal abnormalities, insulin resistance, and chronic inflammation are the hallmarks of Polycystic Ovary Syndrome (PCOS), a prevalent endocrine condition affecting women of reproductive age. Oxidative stress is a key factor in the pathophysiology of PCOS, spurring interest in antioxidant-based treatment approaches. Many reproductive processes, including ovulation, endometrial decidualization, menstruation, oocyte fertilization, and the growth and implantation of an embryo, depend on oxidative stress (OS). Physiological quantities of reactive oxygen and nitrogen species, which function as redox signaling molecules to start and stop each phase, govern the menstrual cycle. Given that an excess of OS in comparison to antioxidants can result in gynecological illnesses, infertility, and reproductive problems, it is thought that a pathological rise in OS plays a role in the loss in female fertility. Antioxidants are therefore necessary for the best possible reproductive function in females. They aid in the hormonal control of vascular processes, support endometrial maturation by activating antioxidant signaling pathways such as Nrf2 and NF-κB, and contribute to oocyte metabolism. Free radicals can be directly neutralized by antioxidants, they can act as cofactors for enzymes essential to cell formation and differentiation, or they can improve the activity of already-existing antioxidant enzymes. Fertility may be increased by taking antioxidant supplements to address deficits. The functions of certain vitamins and flavonoids with antioxidant qualities in the processes of female reproduction are examined in this review.
激素异常、胰岛素抵抗和慢性炎症是多囊卵巢综合征(PCOS)的特征,多囊卵巢综合征是一种影响育龄妇女的普遍内分泌疾病。氧化应激是多囊卵巢综合征病理生理的一个关键因素,激发了对基于抗氧化剂的治疗方法的兴趣。许多生殖过程,包括排卵、子宫内膜脱卵、月经、卵母细胞受精以及胚胎的生长和着床,都依赖于氧化应激(OS)。生理数量的活性氧和活性氮作为氧化还原信号分子,控制着月经周期的开始和结束。考虑到与抗氧化剂相比,过量的OS会导致妇科疾病、不孕症和生殖问题,人们认为OS的病理性上升在女性生育能力的丧失中起着重要作用。因此,抗氧化剂对于女性最好的生殖功能是必要的。它们有助于血管过程的激素控制,通过激活抗氧化信号通路如Nrf2和NF-κB来支持子宫内膜成熟,并促进卵母细胞代谢。自由基可以被抗氧化剂直接中和,它们可以作为细胞形成和分化所必需的酶的辅助因子,或者它们可以提高已经存在的抗氧化酶的活性。通过服用抗氧化剂补充剂来解决缺陷,可以提高生育能力。本文综述了几种具有抗氧化作用的维生素和类黄酮在雌性生殖过程中的作用。
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引用次数: 0
Multi-omics integration and machine learning reveal biomarker networks and therapeutic targets in Alzheimer's disease 多组学整合和机器学习揭示阿尔茨海默病的生物标志物网络和治疗靶点
Pub Date : 2025-12-12 DOI: 10.1016/j.abst.2025.12.004
Shreya Satyanarayan Bhat , Vidya Niranjan , Trilok Chandran , Spoorthi R. Kulkarni , Samridhi Makkar , Vishwam Dixit , Cherishma K. Subhasa , Adarsh Vishal
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited early diagnostic options and no curative therapy. This study presents a multi-region transcriptomic and systems biology framework for the identification of robust biomarker genes and pharmacologically actionable targets in AD. Differential gene expression profiles from the entorhinal cortex, hippocampus, and frontal cortex were analyzed using three supervised machine learning algorithms: LASSO regression, Random Forest, and SVM-RFE to prioritize predictive biomarkers. Consensus genes demonstrated region-specific differential expression and moderate diagnostic accuracy (AUC up to 0.70). Functional enrichment revealed their roles in synaptic transmission, translational regulation, lysosomal acidification, and extracellular matrix remodeling, hallmarks of AD pathology. Protein–protein interaction networks and hub gene analyses further underscore the role of translational regulators, such as EIF3C and FAU. Transcription factor mapping (e.g., MEF2C, ZBTB18), miRNA targeting (e.g., miR-107, miR-195–5p), and drug–gene interaction analysis identified GABBR2 and COL5A2 as translationally relevant targets linked to approved or investigational drugs. This integrative study proposes a reproducible pipeline combining machine learning, regulatory network modeling, and pharmacogenomic mining to inform biomarker-driven drug repurposing in Alzheimer's disease.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,早期诊断选择有限,无治愈治疗。本研究提出了一个多区域转录组学和系统生物学框架,用于识别AD中强大的生物标志物基因和药理学上可操作的靶点。使用LASSO回归、随机森林和SVM-RFE三种监督机器学习算法对内嗅皮层、海马体和额叶皮层的差异基因表达谱进行分析,以优先考虑预测性生物标志物。共识基因表现出区域特异性差异表达和中等诊断准确性(AUC高达0.70)。功能富集揭示了它们在突触传递、翻译调节、溶酶体酸化和细胞外基质重塑等AD病理特征中的作用。蛋白-蛋白相互作用网络和枢纽基因分析进一步强调了翻译调节因子的作用,如EIF3C和FAU。转录因子定位(如MEF2C, ZBTB18), miRNA靶向(如miR-107, miR-195-5p)和药物-基因相互作用分析确定GABBR2和COL5A2是与已批准或正在研究的药物相关的翻译相关靶点。这项综合研究提出了一个可重复的管道,结合机器学习、监管网络建模和药物基因组学挖掘,为阿尔茨海默病的生物标志物驱动药物再利用提供信息。
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引用次数: 0
Mapping autophagy-lncRNA co-expression networks in early ovarian carcinoma by stage-resolved transcriptomic modelling 通过分期分解转录组学模型绘制早期卵巢癌自噬- lncrna共表达网络
Pub Date : 2025-12-03 DOI: 10.1016/j.abst.2025.12.003
A. Shriraksha, V.R. Devaraj
Early-stage ovarian carcinoma exhibits heterogeneous molecular programming that influences tumor progression and therapeutic vulnerability. Using RNA-seq data from 96 tumors (GSE101108), we developed an integrative bioinformatics workflow that combines DESeq2, ssGSEA, and weighted gene co-expression network analysis (WGCNA) to identify autophagy-associated biomarkers and long non-coding RNA (lncRNA)- driven co-expression networks across FIGO stage I-II ovarian tumors. Differential expression analysis (DESeq2) identified 140 stage-dependent genes, with the lncRNA LOC105374020 emerging as the most upregulated transcript in FIGO II tumors. ssGSEA revealed elevated autophagy activity in FIGO II tumors, coinciding with the enrichment of MHC class I antigen-processing pathways, suggesting adaptive remodeling of immune surveillance. WGCNA uncovered a lncRNA-enriched module strongly correlating with autophagy intensity (r = 0.78, FDR = 1.8 × 10−19). Within this module, LOC105374020 displayed high intramodular connectivity, making it a potential regulator of early tumor adaptation. These results suggest lncRNAs embedded within autophagy-linked modules as candidate biomarkers of early progression and immune modulation. Collectively, this study outlines a systems-level framework integrating autophagy, immunity, and lncRNA regulation in early ovarian carcinoma. While the findings highlight promising biomarker candidates, additional external validation and functional assays will be essential to translate these signatures for prognostic or therapeutic use.
早期卵巢癌表现出影响肿瘤进展和治疗脆弱性的异质性分子程序设计。利用来自96个肿瘤(GSE101108)的RNA-seq数据,我们开发了一个综合生物信息学工作流,该工作流结合了DESeq2、ssGSEA和加权基因共表达网络分析(WGCNA),以鉴定FIGO I-II期卵巢肿瘤中自噬相关的生物标志物和长链非编码RNA (lncRNA)驱动的共表达网络。差异表达分析(DESeq2)鉴定了140个阶段依赖基因,其中lncRNA LOC105374020是FIGO II肿瘤中表达上调最多的转录物。ssGSEA显示FIGO II肿瘤中自噬活性升高,与MHC I类抗原加工途径的富集一致,提示免疫监视的适应性重塑。WGCNA发现lncrna富集模块与自噬强度密切相关(r = 0.78, FDR = 1.8 × 10−19)。在该模块中,LOC105374020显示出较高的胞内连通性,使其成为早期肿瘤适应的潜在调节因子。这些结果表明,嵌入自噬相关模块中的lncrna是早期进展和免疫调节的候选生物标志物。总的来说,本研究概述了早期卵巢癌中自噬、免疫和lncRNA调控的系统水平框架。虽然这些发现突出了有希望的生物标志物候选物,但额外的外部验证和功能分析对于将这些特征转化为预后或治疗用途至关重要。
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引用次数: 0
Exploring the potential of IP-10 and sCD14 as inflammatory biomarkers in HIV–TB co-infection: a systematic review 探索IP-10和sCD14作为HIV-TB合并感染炎症生物标志物的潜力:一项系统综述
Pub Date : 2025-12-02 DOI: 10.1016/j.abst.2025.12.001
Tolutope Adebimpe Oso , Olalekan John Okesanya , Uthman Okikiola Adebayo , Khalifat Boluwatife Obadeyi , Oluwatobi Babajide Ayelaagbe , Mohamed Mustaf Ahmed , Clement Ngele Chukwu , Olaoluwa Joseph Oso , Don Eliseo Lucero-Prisno III

Background

Human Immunodeficiency Virus (HIV) and tuberculosis (TB) are major global health challenges, especially in sub-Saharan Africa and Southeast Asia, where their co-infection greatly increases illness and death. People living with HIV are far more likely to develop TB, and the interaction between the two infections worsens immune dysfunction and complicates management.

Methods

This systematic review followed PRISMA 2020 guidelines to assess the roles of Interferon-γ–induced Protein 10 (IP-10) and Soluble Cluster of Differentiation 14 (sCD14) as inflammatory biomarkers in HIV-TB co-infection. A comprehensive search of PubMed, Scopus, and Google Scholar was conducted for studies published between 2014 and 2024. Eligible interventional and observational studies involving adults with HIV-TB co-infection were included based on predefined inclusion criteria. Data extraction covered study characteristics, biomarker levels, and their associations with inflammation, disease progression, and clinical outcomes.

Results

Six studies met the inclusion criteria, all assessing IP-10, while only one measured sCD14. Most studies reported significantly elevated IP-10 levels in HIV–TB co-infected individuals, linking it to systemic inflammation, disease progression, and poor clinical outcomes, highlighting its potential as a predictive and prognostic biomarker. The single study evaluating sCD14 found increased levels indicating generalized immune activation but limited specificity for distinguishing Tuberculosis-Immune Reconstitution Inflammatory Syndrome , suggesting its broader role as a nonspecific marker of inflammation.

Conclusion

Although the current evidence base is limited, IP-10 shows promise as a diagnostic and prognostic biomarker, and sCD14 may complement its use as a marker of immune activation. Further large-scale, standardized studies are needed to validate these biomarkers in HIV–TB co-infection.
人类免疫缺陷病毒(HIV)和结核病(TB)是主要的全球卫生挑战,特别是在撒哈拉以南非洲和东南亚,它们的合并感染大大增加了疾病和死亡。艾滋病毒感染者患结核病的可能性要大得多,而且这两种感染之间的相互作用加剧了免疫功能障碍并使治疗复杂化。方法本系统综述遵循PRISMA 2020指南,评估干扰素-γ诱导蛋白10 (IP-10)和可溶性分化簇14 (sCD14)作为炎症生物标志物在HIV-TB合并感染中的作用。对2014年至2024年间发表的研究进行了PubMed, Scopus和b谷歌Scholar的综合搜索。根据预先确定的纳入标准纳入了涉及成人HIV-TB合并感染的符合条件的干预性和观察性研究。数据提取包括研究特征、生物标志物水平及其与炎症、疾病进展和临床结果的关联。结果6项研究符合纳入标准,均评估IP-10,而只有1项研究评估sCD14。大多数研究报告了HIV-TB合并感染个体中IP-10水平显著升高,将其与全身性炎症、疾病进展和不良临床结果联系起来,突出了其作为预测和预后生物标志物的潜力。评估sCD14的单一研究发现,sCD14水平升高表明普遍的免疫激活,但在区分结核-免疫重建炎症综合征方面的特异性有限,这表明它作为炎症的非特异性标志物具有更广泛的作用。尽管目前的证据基础有限,但IP-10有望作为一种诊断和预后的生物标志物,而sCD14可能补充其作为免疫激活标志物的用途。需要进一步的大规模标准化研究来验证这些生物标志物在HIV-TB合并感染中的作用。
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引用次数: 0
Methanol extract of Smritisagara Rasa attenuates neurobehavior, neurochemical and stress indicators in rotenone-induced Drosophila model of Parkinson's disease 鱼藤酮诱导的帕金森病果蝇模型的神经行为、神经化学和应激指标减弱
Pub Date : 2025-11-28 DOI: 10.1016/j.abst.2025.11.003
Gopinath G , Ramesha Hanumanthappa , Raifa Abdul Aziz , P.C. Kiran , Hemalatha Nanjaiah , Iranna B. Kotturshetty , Shamprasad Varija Raghu , Manjunath Ajanal , Devaraju Kuramkote Shivanna
Smritisagara Rasa (SSR), a traditional Ayurvedic herbo-mineral formulation, has long been prescribed for the treatment of Parkinson's disease (PD) since ancient times. Nevertheless, the underlying molecular mechanisms and treatment strategies remain unclear due to a lack of adequate experimental data. This study focused on formulating SSR and extracting its components using different solvent systems, including water and methanol. SSR, along with its water extract (SSR-WEX) and methanol extract (SSR-MEX), was tested for efficacy in mitigating PD phenotypes using a Rotenone (ROT)-induced Drosophila melanogaster PD model. SSR was prepared according to the Ayurvedic Formulary of India and subsequently characterized, followed by solvent extraction and phytoconstituent profiling. Different concentrations of SSR, SSR-WEX, and SSR-MEX were administered to control flies to evaluate their potential toxicity. Flies were then co-exposed to 500 μM ROT and 75 mg/kg diet of SSR, SSR-WEX, and SSR-MEX for seven days. Behavioral, neurochemical, and oxidative stress parameters were assessed, with pramipexole (PPX) used as a positive control. ROT exposure markedly impaired climbing ability, reduced dopamine and acetylcholinesterase (AChE) activity, and elevated oxidative stress markers, including malondialdehyde (MDA), protein carbonyl content (PCC), hydrogen peroxide, and nitric oxide. Co-treatment with SSR and its extracts significantly restored locomotor function, dopamine, and AChE levels, while enhancing antioxidant enzymes (glutathione-S-transferase and catalase) and reducing oxidative damage indices. Among the formulations, SSR-MEX demonstrated superior neuroprotective and antioxidative efficacy, comparable to the standard drug pramipexole. This effect is likely due to its enriched profile of flavonoids, coumarins, and phenolic acids. These findings substantiate traditional claims regarding SSR's role in mitigating neurodegenerative symptoms and highlight SSR-MEX as a promising phytopharmaceutical candidate for managing PD-like pathologies through attenuation of oxidative stress and restoration of dopaminergic and cholinergic systems.
Smritisagara Rasa (SSR)是一种传统的阿育吠陀草药矿物配方,自古以来就被用于治疗帕金森病(PD)。然而,由于缺乏足够的实验数据,潜在的分子机制和治疗策略仍不清楚。本研究的重点是制备SSR,并利用不同的溶剂体系,包括水和甲醇提取其成分。利用鱼藤酮(ROT)诱导的果蝇PD模型,研究了SSR及其水提取物(SSR- wex)和甲醇提取物(SSR- mex)对PD表型的缓解效果。根据印度阿育吠陀处方制备了SSR,并对其进行了表征,随后进行了溶剂提取和植物成分分析。用不同浓度的SSR、SSR- wex和SSR- mex对照蝇,评价其潜在毒性。然后将果蝇分别暴露于500 μM ROT和75 mg/kg的SSR、SSR- wex和SSR- mex中7天。以普拉克索(PPX)作为阳性对照,评估行为、神经化学和氧化应激参数。暴露于ROT环境中会显著损害攀爬能力,降低多巴胺和乙酰胆碱酯酶(AChE)活性,并升高氧化应激标志物,包括丙二醛(MDA)、蛋白质羰基含量(PCC)、过氧化氢和一氧化氮。与SSR及其提取物共处理可显著恢复运动功能、多巴胺和AChE水平,同时增强抗氧化酶(谷胱甘肽- s -转移酶和过氧化氢酶),降低氧化损伤指标。在这些制剂中,SSR-MEX表现出与标准药物普拉克索相当的优越的神经保护和抗氧化功效。这种效果可能是由于其富含类黄酮、香豆素和酚酸。这些发现证实了SSR在缓解神经退行性症状方面的作用,并强调了SSR- mex作为一种有前途的植物药物候选物,可以通过降低氧化应激和恢复多巴胺能和胆碱能系统来治疗pd样病理。
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引用次数: 0
In silico screening of tripeptide inhibitors reveals potential lead compounds for targeting zika virus NS2B-NS3 protease 三肽抑制剂的计算机筛选揭示了针对寨卡病毒NS2B-NS3蛋白酶的潜在先导化合物
Pub Date : 2025-11-19 DOI: 10.1016/j.abst.2025.11.001
Farhan Ullah , Wajeeha Rahman , Anees Ullah , Shahid Ullah , Sheng Wang
ZIKV is a public health threat causing neurological complications such as microcephaly and Guillain-Barre syndrome, with the additional risk of sexual transmission. The absence of FDA-approved drugs or vaccines for ZIKV, highlight the immediate requirement for potential therapeutics. A potential target for antiviral drug development is the NS2B-NS3 protease which is a critical enzyme in the replication and maturation of ZIKV. Here, we report the inhibitory activity of tripeptide compounds for this protease via molecular docking and molecular dynamics (MD) study. The docking studies were further followed by a 200 ns MD simulation to investigate the stability and binding mode of the inhibitor within the active site of protease. The simulation revealed that, the complex remains stable with lower root mean square deviation RMSD and higher root mean square fluctuation (RMSF) values and showed strong ligand-protein interaction. Further investigation of torsion angles in the ligand and secondary structural changes in the protease support to the viability of these tripeptide inhibitors as anti-viral agents. The results obtained in this study suggest that tripeptide-derived inhibitors of ZIKV may be applied as potential leads for developing novel therapies against the ZIKV, indicating a potential direction for future drug discovery and clinical treatments.
寨卡病毒是一种公共卫生威胁,会导致小头症和格林-巴利综合征等神经系统并发症,并伴有性传播的额外风险。缺乏fda批准的针对寨卡病毒的药物或疫苗,突出了对潜在治疗方法的迫切需求。抗病毒药物开发的潜在靶点是NS2B-NS3蛋白酶,它是ZIKV复制和成熟的关键酶。本文通过分子对接和分子动力学(MD)研究,报道了三肽化合物对该蛋白酶的抑制活性。对接研究之后,进一步进行了200 ns MD模拟,以研究抑制剂在蛋白酶活性位点的稳定性和结合方式。模拟结果表明,该配合物具有较低的均方根偏差RMSD和较高的均方根波动(RMSF)值,并表现出较强的配体-蛋白相互作用。进一步研究配体的扭转角和蛋白酶的二级结构变化支持这些三肽抑制剂作为抗病毒药物的可行性。本研究结果提示,三肽衍生的ZIKV抑制剂可能作为开发新的治疗方法的潜在先导,为未来的药物发现和临床治疗指明了潜在的方向。
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引用次数: 0
An in-depth exploration of CNN-based deep learning models in cervical carcinoma analysis 基于cnn的深度学习模型在宫颈癌分析中的深入探索
Pub Date : 2025-11-17 DOI: 10.1016/j.abst.2025.11.007
P. Karthika , M. Premkumar
Cervical cancer has an extreme effect on women's health worldwide, recognized as the 4th most significant contributor to cancer fatalities among female. World Health Organization (WHO) states that there was on 660,000 new reports and 350,000 death occurred. Detecting the disease early can lead to a significant decrease in the death rate up to 80 %. Currently, doctors diagnose cervical cancer by examining cervical biopsies through Pap smears and colposcopy images. However this techniques is time-intensive, taking up to several hours per case and susceptible to misdiagnosis and diagnostic error between 10 and 30 %.Deep learning has illustrated significant potential for addressing biomedical challenges such as analysis of medical images, disease forecasting, and image partitioning. AI-powered diagnostic methods utilizing deep learning models–such as CNNs, DenseNets, and U-Nets—have achieved classification accuracies exceeding 95 % on datasets like Herlev and SIPaKMeD. This paper surveys diverse deep learning strategies that were implemented for the identification and analysis of cervical carcinoma, emphasizing their performance metrics, datasets and clinical applicability.
宫颈癌对全世界妇女的健康影响极大,被公认为导致女性癌症死亡的第四大因素。世界卫生组织(世卫组织)指出,有66万份新报告,35万人死亡。及早发现该病可使死亡率显著降低,最高可达80%。目前,医生通过子宫颈抹片检查和阴道镜检查来诊断宫颈癌。然而,这种技术是耗时的,每个病例需要花费几个小时,并且容易误诊和诊断错误率在10%到30%之间。深度学习在解决医学图像分析、疾病预测和图像分割等生物医学挑战方面显示了巨大的潜力。利用深度学习模型(如cnn、DenseNets和u - nets)的人工智能诊断方法在Herlev和SIPaKMeD等数据集上的分类准确率超过95%。本文调查了用于宫颈癌识别和分析的各种深度学习策略,强调了它们的性能指标、数据集和临床适用性。
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引用次数: 0
Amoxicillin and cotrimoxazole-driven dysbiosis disrupted blood cell levels, cytokine balance and induced oxido-nitrosative stress in young mice 阿莫西林和复方新恶唑引起的生态失调破坏了年轻小鼠的血细胞水平、细胞因子平衡和诱导氧化-亚硝化应激
Pub Date : 2025-11-15 DOI: 10.1016/j.abst.2025.11.002
Kiptoo K. Cosmas , Silas Kiruki , Olivia A. Njiri , Grace K. Nyambati , John Mokua Mose , Omwenga Isaac , Alfred Orina Isaac , James Nyabuga Nyariki
Amoxicillin and cotrimoxazole are among the most frequently prescribed antibiotics, yet their impact on gut microbiota and systemic physiology, particularly during early life, remains a critical concern. This study investigated the effects of these antibiotics on the gut microbiome and associated physiological and biochemical responses in young male Swiss mice (5 weeks old), serving as a model for infant exposure. Five experimental groups were employed: control, amoxicillin (9.62 mg/kg), cotrimoxazole (15 mg/kg), cotrimoxazole + amoxicillin, and cotrimoxazole + amoxicillin followed by probiotic administration. Parameters assessed included gut microbial composition, hematological indices, organ weights, liver and kidney function, cytokine profiles, oxidative stress markers, and histopathological alterations. Both antibiotics induced marked gut dysbiosis. Cotrimoxazole significantly increased leukocyte, neutrophil, lymphocyte, and monocyte counts, while amoxicillin caused thrombocytosis and cotrimoxazole induced thrombocytopenia; probiotic treatment normalized these effects. Amoxicillin reduced brain glutathione (GSH) levels, whereas cotrimoxazole decreased GSH in both liver and brain. Combined antibiotic exposure exacerbated GSH depletion and elevated nitric oxide (NO) and malondialdehyde (MDA) levels, effects mitigated by probiotics exposure. Co-exposure to cotrimoxazole and amoxicillin upregulated pro-inflammatory cytokines TNF-α and IFN-γ and increased serum markers of hepatic and renal injury (alanine-transaminases, alkaline phosphatases, Aspartate transaminases, creatinine, urea, uric acid). Histopathological analysis confirmed aggravated hepatic and renal damage under combined antibiotic exposure, which was markedly alleviated by probiotics. These findings demonstrate that amoxicillin and cotrimoxazole disrupt gut microbial balance, eliciting systemic oxidative, organ damage and inflammatory responses. Probiotic intervention confers significant protection, underscoring the need for cautious antibiotic use and microbiota-restorative strategies.
阿莫西林和复方新诺明是最常用的抗生素,但它们对肠道微生物群和全身生理的影响,特别是在生命早期,仍然是一个关键问题。本研究调查了这些抗生素对年轻雄性瑞士小鼠(5周龄)肠道微生物组和相关生理生化反应的影响,作为婴儿暴露的模型。5个试验组:对照组、阿莫西林(9.62 mg/kg)、复方新诺明(15 mg/kg)、复方新诺明+阿莫西林、复方新诺明+阿莫西林加益生菌。评估的参数包括肠道微生物组成、血液学指标、器官重量、肝肾功能、细胞因子谱、氧化应激标志物和组织病理学改变。两种抗生素均引起明显的肠道失调。复方新诺明显著增加白细胞、中性粒细胞、淋巴细胞和单核细胞计数,而阿莫西林引起血小板增多,复方新诺明引起血小板减少;益生菌治疗使这些效果正常化。阿莫西林降低脑谷胱甘肽(GSH)水平,而复方新诺明降低肝和脑谷胱甘肽水平。联合抗生素暴露加剧了谷胱甘肽的消耗和一氧化氮(NO)和丙二醛(MDA)水平的升高,益生菌暴露减轻了这种影响。共暴露于复方新诺明和阿莫西林可上调促炎细胞因子TNF-α和IFN-γ,并增加肝脏和肾脏损伤的血清标志物(丙氨酸转氨酶、碱性磷酸酶、天冬氨酸转氨酶、肌酐、尿素、尿酸)。组织病理学分析证实,抗生素联合暴露加重了肝脏和肾脏的损害,而益生菌明显减轻了这种损害。这些发现表明阿莫西林和复方新诺明破坏肠道微生物平衡,引起全身氧化、器官损伤和炎症反应。益生菌干预具有重要的保护作用,强调了谨慎使用抗生素和微生物群恢复策略的必要性。
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引用次数: 0
Mechanistic insights on effective ratio of Linoelaidic and Docosapentaenoic acid by modulating adipogenic and inflammatory biomarkers in 3T3-L1 preadipocytes 通过调节3T3-L1前脂肪细胞中的脂肪生成和炎症生物标志物,亚油酸和二十碳五烯酸有效比例的机制见解
Pub Date : 2025-11-14 DOI: 10.1016/j.abst.2025.11.005
Pipika Das , Riya Kar , Titli Panchali , Ananya Dutta , Manisha Phoujdar , Kuntal Ghosh , Shrabani Pradhan
Obesity is a condition of energy balance in which nutrient intake consistently exceeds energy expenditure, increasing the risk of various potentially fatal disorders. Docosapentaenoic acid (DPA) is an omega-3 fatty acid that has been reported to provide a number of health benefits. However, the effects of DPA on adipocyte differentiation are poorly understood. Linoelaidic acid (LA) is an isomer of linoleic acid that remains underexplored. The main aim of this investigation is to explore the role of linoelaidic acid and DPA ratio on lipid accumulation and AMPK pathway activation in 3T3-L1 cells. Differentiated adipocyte were treated with different ratio of fatty acids and performed cell viability assay, Oil Red O staining, gene expression and immunoblotting analysis. The fatty acids did not cause cytotoxicity in preadipocytes. Notably, DPA reduced lipid accumulation, suggesting its anti-adipogenic potential. Moreover, LA/DPA ratio also markedly increased the mRNA expression of genes associated with lipolysis, including peroxisome proliferator-activated receptor-α, carnitine palmitoyl transferase-1, adiponectin, and lipoprotein lipase, while inhibiting those involved in lipogenesis, such as leptin, sterol regulatory element binding protein-1c and fatty acid synthase. In addition, LA/DPA mixture strongly suppressed inflammation induced by TNF-α, IL-6, IL-1β. On mechanistic levels, LA/DPA in ratio of 1:1 and 4:1 regulates the AMPK signaling by reducing phosphorylation levels of PPAR-γ, C/EBP-α, acetyl-CoA carboxylase, and stearoyl-CoA desaturase. These findings demonstrated that LA and DPA in combination can prevent 3T3-L1 preadipocytes from differentiating, which implies it may be used therapeutically to prevent obesity.
肥胖是一种能量平衡的状态,在这种状态下,营养摄入持续超过能量消耗,增加了各种潜在致命疾病的风险。二十二碳五烯酸(DPA)是一种omega-3脂肪酸,据报道对健康有益。然而,DPA对脂肪细胞分化的影响尚不清楚。亚油酸(LA)是亚油酸的一种异构体,尚未得到充分的研究。本研究的主要目的是探讨亚油酸和DPA比值对3T3-L1细胞脂质积累和AMPK通路激活的作用。用不同比例的脂肪酸处理分化后的脂肪细胞,进行细胞活力测定、油红O染色、基因表达和免疫印迹分析。脂肪酸不引起前脂肪细胞的细胞毒性。值得注意的是,DPA减少脂质积累,表明其抗脂肪生成潜力。此外,LA/DPA比值还显著增加了脂肪分解相关基因的mRNA表达,包括过氧化物酶体增殖物激活受体-α、肉毒碱棕榈酰转移酶-1、脂联素和脂蛋白脂肪酶,而抑制了参与脂肪生成的基因,如瘦素、固醇调节元件结合蛋白-1c和脂肪酸合成酶。此外,LA/DPA混合物对TNF-α、IL-6、IL-1β诱导的炎症有较强的抑制作用。在机制水平上,LA/DPA以1:1和4:1的比例通过降低PPAR-γ、C/EBP-α、乙酰辅酶a羧化酶和硬脂酰辅酶a去饱和酶的磷酸化水平来调节AMPK信号传导。这些发现表明,LA和DPA联合使用可以阻止3T3-L1前脂肪细胞的分化,这意味着它可能用于治疗预防肥胖。
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Advances in biomarker sciences and technology
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