Journal of King Saud University - Science最新文献_第7页

Reno-protective potential of poncirin against polyethylene microplastics instigated kidney damage in rats via regulating Nrf-2/Keap-1 pathway 枸橘苷通过调节 Nrf-2/Keap-1 通路对聚乙烯微塑料引发的大鼠肾损伤具有保护潜力

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-11 DOI: 10.1016/j.jksus.2024.103486

Muhammad Faisal Hayat , Maryam Javed , Rahat Andleeb , Asma Ashraf , Huma Naz , Mohammad Z. Ahmed , Ayesha Ishtiaq

Polyethylene microplastics (PEMPs) are noxious environmental pollutants that are documented to cause organ damage including the kidneys. Poncirin (PON) is a naturally occurring flavonoid which demonstrates a wide range of pharmacological properties. This experiment was conducted to evaluate the palliative potential of PON against PEMPs induced renal toxicity by examining a range of biochemical and physiological parameters. Twenty-four male albino rats were randomly apportioned into four distinct groups including the control, PEMPs (1.5 mgkg⁻¹), PEMPs (1.5 mgkg⁻¹) + PON (20 mgkg⁻¹) and only PON (20 mgkg⁻¹). Our results displayed that PEMPs intoxication escalated the levels of urea, KIM-1, creatinine and NGAL while reducing the creatinine clearance level. Besides reduction in the activities of GPx, GST, HO-1, CAT, GSR & upsurge in the levels of MDA and ROS were detected in PEMPs group. Conversely, the levels of inflammatory markers including COX-2, IL-6, IL-1β, NF-kB and TNF-α were augmented following the PEMPs intoxication. Besides, the results of the current research demonstrated that the expressions of Bax and caspase-3 were esclated whereas the Bcl-2 expression was lowered from its standard value due to PEMPs provision. However, PON treatment significantly restored the PEMPs-induced aforementioned impairments. Therefore, PON could be used as a therapeutic compound to ameliorate PEMPs-induced kidney impairments in rats, possibly due to its tremendous pharmacotherapeutic potential.

聚乙烯微塑料（PEMPs）是一种有害的环境污染物，据记载会对包括肾脏在内的器官造成损害。枸橘苷（PON）是一种天然黄酮类化合物，具有广泛的药理特性。本实验通过检测一系列生化和生理参数，评估 PON 对 PEMPs 引起的肾毒性的缓解潜力。二十四只雄性白化大鼠被随机分为四组，包括对照组、PEMPs（1.5 毫克/公斤-1）组、PEMPs（1.5 毫克/公斤-1）+ PON（20 毫克/公斤-1）组和仅 PON（20 毫克/公斤-1）组。我们的结果显示，PEMPs 中毒会使尿素、KIM-1、肌酐和 NGAL 水平升高，同时降低肌酐清除水平。除了 GPx、GST、HO-1、CAT、GSR & 活性降低外，在 PEMPs 组中还检测到 MDA 和 ROS 水平升高。相反，COX-2、IL-6、IL-1β、NF-kB 和 TNF-α 等炎症标志物的水平在 PEMPs 中毒后有所增加。此外，目前的研究结果表明，PEMPs 中毒导致 Bax 和 caspase-3 的表达量下降，而 Bcl-2 的表达量则低于标准值。然而，PON 治疗可明显恢复 PEMPs 引起的上述损伤。因此，PON 可作为一种治疗化合物来改善 PEMPs 诱导的大鼠肾功能损伤，这可能是由于其巨大的药物治疗潜力。

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引用次数: 0

Influence of phosphorous fertilizer on mineral nutrition and yield attributes of wheat: Acquisition with PSTOL1 gene for arid environment 磷肥对小麦矿质营养和产量属性的影响干旱环境下 PSTOL1 基因的获取

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-11 DOI: 10.1016/j.jksus.2024.103485

Muhammad Iqbal Makhdum , Muhammad Abid , Rashida Hameed , Sidra Balooch , Sibgha Noreen , Muhammad Salim Akhter , Ummar Iqbal , Adeel Abbas , Mohammad Abul Farah , Rattandeep Singh

To boost agricultural yields, understanding mineral nutrition’s reliance on fertilizers is crucial, underscoring the need to evaluate nutrient-use efficiency for optimal fertilization. In this regard, a field study was conducted to elaborate the role of phosphorus fertilizer in enhancing growth, yield and marginal rate of return in four wheat varieties; two Zn-biofortified (Zincol-2016 and Akbar-2019) and two standard types (Anaj-2017 and FSD-2008). The study revealed that application of phosphorus significantly enhanced the uptake of nitrogen (N), phosphorous (P) and potassium (K) contents in straw (13 %, 59 % and 79 %) and grains (63 %, 92 % and 28 %) respectively. Similarly, the contents of Zinc (Zn) and iron (Fe) were reduced in straw (23 % and 19 %) and grains (19 % and 18 %) respectively after application of 80 and 120 kg P₂O₅, however at 40 kg P₂O₅ the contents of Zn and Fe were slightly enhanced. The grain yield (21 %) and harvest index (11 %) was maximum at 80 kg P₂O₅ as compared to 40 and 120 kg P₂O₅. The Marginal rate of return over investment (MRR) in P₂O₅ was maximum (241 %) in Akbar-2019 when P-fertilizer was applied at the rate of 80 kg P₂O₅ per ha⁻¹. Regression analysis showed a positive correlation between grain yield and its determinants. Biofortified wheat varieties responded better to 80 kg P₂O₅, outperforming standard varieties in yield. Additionally, our findings demonstrate a significant upregulation of PSTOL1 gene expression at 80 kg P₂O₅ level. Concludingly the application of P-fertilizer at the rate of 80 kg P₂O₅ per ha⁻¹ enhanced growth, yield and rate of return of testing wheat varieties especially the biofortified ones; Zincol-2016 and Akbar-2019.

为了提高农业产量，了解矿物质营养对肥料的依赖至关重要，这就强调了评估养分利用效率以优化施肥的必要性。为此，我们进行了一项田间研究，以阐述磷肥在提高四个小麦品种（两个锌生物强化品种（Zincol-2016 和 Akbar-2019）和两个标准品种（Anaj-2017 和 FSD-2008）的生长、产量和边际收益率方面的作用。研究表明，施磷能显著提高秸秆（13 %、59 % 和 79 %）和谷物（63 %、92 % 和 28 %）中氮（N）、磷（P）和钾（K）的吸收率。同样，施用 80 和 120 千克 P2O5 后，秸秆（23 % 和 19 %）和谷物（19 % 和 18 %）中的锌（Zn）和铁（Fe）含量分别减少，但施用 40 千克 P2O5 时，锌和铁的含量略有增加。与 40 和 120 公斤 P2O5 相比，80 公斤 P2O5 的谷物产量（21%）和收获指数（11%）最高。在 Akbar-2019 中，当每公顷施用 80 千克 P2O5 时，P2O5 的边际投资回报率（MRR）最高（241%）。回归分析表明，谷物产量与其决定因素之间存在正相关。生物强化小麦品种对 80 千克 P2O5 的反应更好，产量优于标准品种。此外，我们的研究结果表明，在 80 千克 P2O5 水平下，PSTOL1 基因表达显著上调。总之，以每公顷-1 80 千克 P2O5 的比率施用磷肥可提高试验小麦品种（尤其是生物强化品种 Zincol-2016 和 Akbar-2019）的生长、产量和收益率。

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引用次数: 0

Effectiveness and safety of chemical inhibitors against mammalian target of rapamycin (mTOR) for primary immunosuppression in recipients of kidney transplant: A systematic review and meta-analysis 针对哺乳动物雷帕霉素靶标（mTOR）的化学抑制剂用于肾移植受者初级免疫抑制的有效性和安全性：系统综述与荟萃分析

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-10 DOI: 10.1016/j.jksus.2024.103481

Ahmad Alsulimani , Ayman K. Johargy , Hani Faidah , Ahmad O. Babalghith , Abdullah F. Aldairi , Farkad Bantun , Faraz Ahmad , Darin Mansor Mathkor , Shafiul Haque

The current systematic review and meta-analysis was undertaken to assess the efficaciousness of mammalian target of rapamycin (mTOR) inhibitors in transplant subjects with regards to kidney functions and survival, with special reference to co-administration (or absence of) calcineurin inhibitors (CNIs). The analysis was done through searching and retrieving information from online scholarly databases. The collected data represented outcomes after at least twelve months following transplantation of kidney. It was observed that parameters such as glomerular filtration rate (GFR) was improved in subjects administered with mTOR inhibitors, however some studies indicated that acute rejection following biopsy was dominant in subjects administered with mTOR inhibitors. Owing to their complementary mechanisms of action as well as beneficial effects on mitigating nephrotoxicity, concomitantly with favorable outcomes on parameters such as serum creatinine and GFR leading to increased survival, this meta-analysis proposes early utilization of mTOR inhibitors and CNI minimization in subjects with kidney transplantation.

本系统综述和荟萃分析旨在评估雷帕霉素哺乳动物靶标（mTOR）抑制剂在移植受试者肾功能和存活率方面的疗效，并特别参考了联合使用（或不使用）钙调磷酸酶抑制剂（CNIs）的情况。分析是通过搜索和检索在线学术数据库中的信息完成的。所收集的数据代表了肾移植后至少十二个月后的结果。据观察，使用mTOR抑制剂的受试者肾小球滤过率（GFR）等参数有所改善，但一些研究表明，使用mTOR抑制剂的受试者活检后出现急性排斥反应的情况居多。由于mTOR抑制剂和氯化萘抑制剂的作用机制互补，而且对减轻肾毒性有好处，同时对血清肌酐和肾小球滤过率等参数也有好处，从而提高了存活率，因此本荟萃分析建议肾移植患者尽早使用mTOR抑制剂和氯化萘抑制剂。

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引用次数: 0

Review of toxic metals in tobacco cigarette brands and risk assessment 烟草卷烟品牌中有毒金属的审查和风险评估

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-10 DOI: 10.1016/j.jksus.2024.103484

Anastazia Tarimo Felix, Amos Vincent Ntarisa

The act of tobacco smoking cigarettes is linked to the development of lung cancer, which accounts for around 90 % of lung cancers in the world. This paper reviewed 76 articles on harmful heavy metals in tobacco cigarette brands and associated health risk assessment. This comprehensive examination involved searching targeted databases across multiple search engines, such as Scopus, Web of Science, Google Scholar, Science Direct, PubMed and Research Gate, published in English from 2000 to September 2024. The mean heavy metals concentrations are 2.9, 10.5, 4.5, 7.9 and 3.5 mg/kg for Cd, Pb, Cr, As and Hg, respectively. Related mean hazard quotient (HQ

)

for non-carcinogenic ingestion and inhalation were determined. HQ for ingestion and inhalation were < 1 and > 1, respectively. HQ

> 1

for all metal inhalation, which signifies considerable health risk. The risk of cancer for ingestion of all metals is in the acceptable limit below 1E-04, while the risk of cancer for inhalation of all metals is in the unacceptable range. Additional research on toxic heavy metals in tobacco cigarette brands from diverse countries is necessary to arrive at conclusive mean risks for each specific toxic heavy metal.

吸烟行为与肺癌的发病有关，肺癌约占全球肺癌发病率的 90%。本文综述了 76 篇关于烟草卷烟品牌中有害重金属及相关健康风险评估的文章。这项全面审查涉及在 Scopus、Web of Science、Google Scholar、Science Direct、PubMed 和 Research Gate 等多个搜索引擎上搜索 2000 年至 2024 年 9 月期间以英文发表的目标数据库。镉、铅、铬、砷和汞的重金属平均浓度分别为 2.9、10.5、4.5、7.9 和 3.5 毫克/千克。确定了非致癌的摄入和吸入的相关平均危害商数（HQ）。摄入和吸入的 HQ 分别为 1 和 1。所有金属吸入的 HQ 均为 1，这意味着相当大的健康风险。摄入所有金属的致癌风险都在 1E-04 以下的可接受范围内，而吸入所有金属的致癌风险都在不可接受的范围内。有必要对不同国家烟草卷烟品牌中的有毒重金属进行更多的研究，以确定每种特定有毒重金属的平均风险。

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引用次数: 0

Comprehensive in silico characterization of Arabidopsis thaliana RecQl helicases through structure prediction and molecular dynamics simulations 通过结构预测和分子动力学模拟对拟南芥 RecQl 螺旋酶进行全面的硅学鉴定

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-10 DOI: 10.1016/j.jksus.2024.103479

Amit Kumar Dutta , Md Ekhtiar Rahman

Helicases are ubiquitous enzymes with specific functions that contribute to almost all nucleic acid metabolic processes. The RecQ helicase family is essential for integrity in all organisms through DNA replication, repair, and recombination. This study investigated five RecQ-like helicases in Arabidopsis thaliana (AtRecQl) that exhibit diverse structural and physiochemical attributes and functions. Cis-regulatory element analysis identified stress, hormone, cell cycle, and development-responsive modules involved in various events in plant growth and development. Gene ontology analysis revealed that the five AtRecQl were associated with various cellular components, molecular functions, and biological processes. Protein-protein interaction analysis also implicated some in various abiotic stress processes. Structural analysis and molecular dynamics (MD) simulations were performed to examine conformational stability through root means square deviation and radius of gyration, showing stable AtRecQl protein structures. Free energy landscape analysis validated thermodynamically stable structures throughout the MD simulation. Principle component analysis and probability density functions from MD simulations provided satisfactory structural variational data for the complexes and limited coordinate movements. These insights might greatly benefit future studies.

螺旋酶是一种无处不在的酶，具有特殊功能，几乎参与了所有核酸代谢过程。RecQ 螺旋酶家族通过 DNA 复制、修复和重组对所有生物的完整性至关重要。本研究调查了拟南芥（AtRecQl）中的五种类似 RecQ 的螺旋酶，它们表现出不同的结构和理化属性及功能。顺式调控元件分析确定了参与植物生长和发育过程中各种事件的胁迫、激素、细胞周期和发育响应模块。基因本体分析表明，五种 AtRecQl 与各种细胞成分、分子功能和生物过程有关。蛋白质-蛋白质相互作用分析还表明，其中一些与各种非生物胁迫过程有关。通过均方根偏差和回转半径进行结构分析和分子动力学（MD）模拟，研究了构象稳定性，结果显示 AtRecQl 蛋白结构稳定。自由能谱分析验证了整个 MD 模拟过程中的热力学稳定结构。来自 MD 模拟的主成分分析和概率密度函数为复合物和有限的坐标移动提供了令人满意的结构变异数据。这些见解对今后的研究大有裨益。

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引用次数: 0

Mechanistic analysis for identifying the anti-diabetic effects of Cholic acid-loaded chitosan nanoparticles: An in vitro approach 鉴定壳聚糖纳米颗粒抗糖尿病作用的机制分析：体外方法

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-10 DOI: 10.1016/j.jksus.2024.103480

Vijay Kumar Deenadayalan , Divya Sunder Raj , ArulJothi Kandasamy Nagarajan , Judith Nivedha Baskar , David Prince , Rajakrishnan Rajagopal , Ahmed Alfarhan , Rajasekhara Reddy Iska , Vijaya Bhaskar Reddy Iska , Yijun Shi , Joe Antony Jacob

The identification of novel therapeutic agents using nanomedicine is critical in the fight against diabetes mellitus (DM). Cholic acid (CA) has shown potential in diabetes management, but its effectiveness is limited by poor solubility and stability. To overcome these challenges, CA was encapsulated in chitosan nanoparticles (CACNPs). The CACNPs had a negative zeta potential (ZP) of −13.6 ± 5.81 mV, which is an indication of good stability and potential for enhanced uptake by diseased cells. The average particle size (PS) measured by dynamic light scattering (DLS) was 169.8 ± 84.3 nm. The polydispersity index (PDI) was 0.220, indicating uniform particle size distribution. The drug loading capacity (DL%) of the CACNPs was 60.96 ± 0.9 %, whereas, the entrapment efficiency (EE%) was 69.19 ± 1.02 %. The MTT assay on 3 T3-L1 cells revealed a concentration-dependent effect on cell viability, with an IC₅₀ value of 766.0 ± 0.09 µg/ml. Furthermore, CACNPs demonstrated dose-dependent enhancement of glucose uptake in differentiated adipocytes, while at 500 µg/ml, they inhibited adipocyte differentiation, suggesting a potential role in adipogenesis inhibition. Quantitative PCR (qPCR) indicated positive modulation of glucose metabolism-related genes (PI3K, GLUT4, PPARg) upon treatment with CACNPs. These findings suggest that CACNPs could serve as a novel inhibitor of adipocyte differentiation and may influence key pathways in glucose metabolism, making them promising candidates for the management of DM.

利用纳米医学鉴定新型治疗药物对于防治糖尿病（DM）至关重要。胆酸（CA）已显示出治疗糖尿病的潜力，但其有效性受到溶解性和稳定性差的限制。为了克服这些挑战，人们将胆酸封装在壳聚糖纳米颗粒（CACNPs）中。CACNPs的负Zeta电位（ZP）为-13.6 ± 5.81 mV，这表明其具有良好的稳定性和被病变细胞吸收的潜力。用动态光散射（DLS）法测定的平均粒径（PS）为 169.8 ± 84.3 nm。多分散指数（PDI）为 0.220，表明粒度分布均匀。CACNPs 的载药量（DL%）为 60.96 ± 0.9 %，而夹带效率（EE%）为 69.19 ± 1.02 %。对 3 个 T3-L1 细胞进行的 MTT 检测显示，CACNPs 对细胞活力的影响与浓度有关，IC50 值为 766.0 ± 0.09 µg/ml。此外，CACNPs 还能剂量依赖性地增强分化脂肪细胞对葡萄糖的摄取，而当浓度为 500 µg/ml 时，CACNPs 则会抑制脂肪细胞的分化，这表明它在抑制脂肪生成方面具有潜在作用。定量 PCR（qPCR）表明，使用 CACNPs 处理后，葡萄糖代谢相关基因（PI3K、GLUT4、PPARg）会发生正向调节。这些研究结果表明，CACNPs 可作为一种新型的脂肪细胞分化抑制剂，并可能影响葡萄糖代谢的关键通路，因此有望成为治疗 DM 的候选药物。

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引用次数: 0

Cloud spot instance price forecasting multi-headed models tuned using modified PSO 使用改进的 PSO 调整云现货实例价格预测多头模型

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-09 DOI: 10.1016/j.jksus.2024.103473

Mohamed Salb , Luka Jovanovic , Ali Elsadai , Nebojsa Bacanin , Vladimir Simic , Dragan Pamucar , Miodrag Zivkovic

The increasing dependence and demands on cloud infrastructure have brought to light challenges associated with cloud instance pricing. The often unpredictable nature of demand as well as changing costs of supplying a reliable instance can leave companies struggling to appropriately budget to support a healthy cash flow while maintaining operating costs. This work explores the potential of multi-headed recurrent architectures to forecast cloud instance prices based on historical and instance data. Two architectures are explored, long short-term memory (LSTM) and gated recurrent unit (GRU) networks. A modified optimizer is introduced and tested on a publicly available Amazon elastic compute cloud dataset. The GRU model, enhanced by the proposed modified approach, had the most impressive outcomes with an MAE score of 0.000801. Results have undergone meticulous statistical validation with the best-performing models further analyzed using explainable artificial intelligence techniques to provide further insight into model reasoning and information on feature importance.

对云基础设施的依赖和需求日益增加，这也带来了与云实例定价相关的挑战。需求的不可预测性以及提供可靠实例的成本变化，往往会让企业在维持运营成本的同时，难以适当地编制预算以支持健康的现金流。这项研究探索了多头循环架构的潜力，以根据历史数据和实例数据预测云实例价格。本文探讨了两种架构：长短期记忆（LSTM）和门控递归单元（GRU）网络。在公开的亚马逊弹性计算云数据集上引入并测试了修改后的优化器。经过改进的 GRU 模型的 MAE 值为 0.000801，取得了最令人瞩目的成果。结果经过了细致的统计验证，并使用可解释人工智能技术对表现最佳的模型进行了进一步分析，以进一步深入了解模型推理和特征重要性信息。

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引用次数: 0

The discovery and simulation analysis of a novel mutation c.40 G < T (V14F) in the NRAS gene in patients with colorectal cancer in Saudi Arabia 沙特阿拉伯结直肠癌患者 NRAS 基因中 c.40 G < T (V14F) 新型突变的发现与模拟分析

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-05 DOI: 10.1016/j.jksus.2024.103477

Mahmood Rasool , Absarul Haque , Mohammed Alharthi , Abdulrahman Sibiany , Mohammed Saad Alamri , Samer Mohammed Hassan Alqarni , Irfan A. Rather , Adeel Gulzar Chaudhary , Peter Natesan Pushparaj , Sajjad Karim

Background

Colorectal cancer (CRC) is the most diagnosed cancer in men and the second most common cancer in women and remains associated with high morbidity and mortality in Saudi Arabia. The current understanding of genetic heterogeneity of CRC biology encourages the identification of the genetic causes of CRC in the Saudi population.

Methods

In this study, we obtained 89 CRC patients’ tumor samples from Saudi Arabia and investigated the molecular alterations of the NRAS proto-oncogene, GTPase (NRAS) gene in the collected CRC tumor tissue samples to identify gene mutations using DNA sequencing using an automated DNA sequencer ABI 3730xl. The impact of mutations was analyzed using different bioinformatics tools including SwissModel, Missense3D, molecular dynamics simulations using YASARA DYNAMICS and Protein Variation Effect Analyzer (PROVEAN) tool.

Results

We identified a novel mutation c.40 G > T, in one patient in whom valine was replaced by phenylalanine (V14F). Notably, we also identified another mutation in the same codon c.40 G > A where valine is replaced by isoleucine (V14I). Our in-silico analysis revealed that this novel mutation alters the binding affinity of the NRAS gene substantially, and as a result, could have lethal consequences on the downstream signaling genes and pathways including MAPK and PI3K involved in regulating CRC growth and progression.

Conclusions

These findings provide insights into the molecular etiology of CRC in general and particularly in the Saudi population. Thus, these findings in NRAS mutation testing may also guide further treatment modalities, and more personalized therapy may be optimized.

背景在沙特阿拉伯，结直肠癌（CRC）是男性诊断率最高的癌症，也是女性诊断率第二高的癌症，而且发病率和死亡率居高不下。方法在这项研究中，我们从沙特阿拉伯获得了 89 例 CRC 患者的肿瘤样本，并使用 ABI 3730xl 自动 DNA 测序仪进行 DNA 测序，调查了所收集的 CRC 肿瘤组织样本中 NRAS 原癌基因 GTPase（NRAS）基因的分子改变，以确定基因突变。我们使用不同的生物信息学工具分析了基因突变的影响，包括 SwissModel、Missense3D、YASARA DYNAMICS 分子动力学模拟和 Protein Variation Effect Analyzer (PROVEAN) 工具。值得注意的是，我们还在同一密码子 c.40 G > A 中发现了另一个突变，其中缬氨酸被异亮氨酸取代（V14I）。我们进行的室内分析表明，这种新型突变大大改变了 NRAS 基因的结合亲和力，因此可能对参与调控 CRC 生长和进展的下游信号基因和通路（包括 MAPK 和 PI3K）产生致命影响。因此，这些 NRAS 基因突变检测结果还可指导进一步的治疗方法，并优化更多的个性化疗法。

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引用次数: 0

Internalization of macromolecules into filarial parasites – Possible operation of host’s anti-fecundity immunity inside adult filarial nematodes 丝虫寄生虫体内大分子的内化--丝虫成虫体内宿主抗繁殖免疫的可能作用

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-05 DOI: 10.1016/j.jksus.2024.103476

Bikash Ranjan Sahu , Nityananda Mandal , Ahmad O. Babalghith , Noha E. Abdel-razik , Abdullah F. Aldairi , Farkad Bantun , Raju K. Mandal , Shafiul Haque , Aditya K. Panda

Objectives

Immune effector mechanisms operating against large extracellular systemic pathogens, such as adult stages of filarial nematodes, are not clearly understood. The only immune effect on the adult worms appears to be directed towards embryos in adult worms. The role of IL-4 or TLR-4 in immune responses that inhibit embryogenesis in adult filarial worms has been well-documented. This host’s immune responses that control embryogenesis (anti-fecundity immunity) are considered critical and were addressed in the current study. The current investigation demonstrated the possible operation of anti-adult immunity that could be functional against large stage adults.

Methods

Adult filaria worms were pulsed with macromolecules such as Concanavalin A, Human immunoglobulins, and Rabbit immunoglobulins for 6 hrs, and entry of these molecules was demonstrated using flow cytometry. Filaria worms were also preincubated with Latrunculin A, an endocytic inhibitor, to explain if macromolecules enter by endocytosis.

Results

Using the flow cytometry approach, we could show the entry of immunoglobulins into the uterine cavity of female Setaria digitata, a cattle-dwelling filarial parasite. Immunoglobulins were observed to bind to the surface of intrauterine stages of female worms. We also demonstrated the presence of bovine immunoglobulins in different embryonic stages in situ.

Conclusions

Overall, experimental evidence demonstrates the existence of the host’s immune molecules inside large-stage adult parasites. However, future studies are directed to understand the functional aspect of the presence of these effector molecules inside the adults.

目的针对大型细胞外系统性病原体（如丝虫的成虫阶段）的免疫效应机制尚不清楚。对成虫的唯一免疫效应似乎是针对成虫体内的胚胎。IL-4 或 TLR-4 在抑制丝虫成虫胚胎发生的免疫反应中的作用已得到充分证实。这种控制胚胎发生的宿主免疫反应（抗繁殖免疫）被认为是至关重要的，也是本次研究的主题。目前的研究表明，抗成虫免疫可能对大阶段成虫起作用。方法用大分子如康卡纳伐林 A、人免疫球蛋白和兔免疫球蛋白对成丝虫脉冲 6 小时，并用流式细胞术证明这些分子的进入。我们还用内吞抑制剂 Latrunculin A 预孵化丝虫，以解释大分子是否通过内吞作用进入。我们观察到免疫球蛋白与雌虫宫内阶段的表面结合。我们还在原位证明了牛免疫球蛋白存在于不同的胚胎阶段。总之，实验证据表明寄生虫大阶段成虫体内存在宿主免疫分子，但未来的研究方向是了解成虫体内存在这些效应分子的功能方面。

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引用次数: 0

Antiproliferative and antioxidant potential of Tridax procumbens extracts against various human cancer cell lines: An insight for medicines from weeds 踯躅草提取物对多种人类癌细胞株的抗增殖和抗氧化潜力：从杂草中提取药物的启示

IF 3.7 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Journal of King Saud University - Science

Pub Date : 2024-10-01 DOI: 10.1016/j.jksus.2024.103474

Rida Sagheer , Annie Gupta , Suaib Luqman , Harshpreet Kaur , Kajal Srivastava , S.M. Kawish , Sunil Kumar Panda , Muzaffar Iqbal

This study aimed to evaluate the anticancer and antioxidant potential of Tridax potential and to identify its main phenolic compounds using reverse-phase HPLC. The crude extract of T. procumbens was separated into different fractions using the liquid–liquid partition method. T. procumbens crude extracts and fractions were tested on human cancer cell lines (PC-3, COLO-205, A549, A431, MDA-MB-231, MDA-MB-468, and K562) as well as a control cell line (HEK-293). The antioxidant activities of the extracts and fractions were also assessed. The majority of the extracts appeared to inhibit the progression of human cancer cell lines based on IC₅₀ values that varied from 23.41 to 90.76 µg/mL. However, the chloroform fraction of the stem (7) displays strong activity against A431 and MDA-MB-231, with IC₅₀ values of 23.41 g/mL and 29.45 µg/mL, respectively. The antioxidant result shows that extracts and their fractions scavenge free radicals with an IC₅₀ value between 14.70 and 93.80 µg/mL. However, 7 showed more efficacies with an IC₅₀ of 14.70 µg/mL in the DPPH assay and 29.90 µg/mL in the nitric oxide assay. HPLC analysis revealed that the flower part of T. procumbens contains high levels pf ferulic acid (0.55 to 2.65 mg/g) and kaempferol (1.1 to 4.95 mg/g). A strong antioxidant activity observed in DPPH and NO assay which helps to measure the extract’s effectiveness in scavenging NO free radical, neutralizing other reactive oxygen species (ROS), often correlate with significant antiproliferative effects in various cancer cell lines. This study highlights the potential of plant-based compounds in cancer treatment.

本研究旨在评估砗磲的抗癌和抗氧化潜力，并采用反相高效液相色谱法鉴定其主要酚类化合物。研究采用液-液分配法将普鲁卡因的粗提取物分离成不同的馏分。在人类癌症细胞系（PC-3、COLO-205、A549、A431、MDA-MB-231、MDA-MB-468 和 K562）以及对照细胞系（HEK-293）上测试了 T. procumbens 的粗提取物和馏分。此外，还评估了提取物和馏分的抗氧化活性。根据从 23.41 微克/毫升到 90.76 微克/毫升不等的 IC50 值，大多数提取物似乎都能抑制人类癌细胞系的发展。不过，茎（7）的氯仿馏分对 A431 和 MDA-MB-231 具有很强的活性，IC50 值分别为 23.41 克/毫升和 29.45 微克/毫升。抗氧化结果显示，提取物及其馏分清除自由基的 IC50 值介于 14.70 和 93.80 µg/mL 之间。不过，7 号提取物的功效更高，在 DPPH 试验中的 IC50 值为 14.70 µg/mL ，在一氧化氮试验中的 IC50 值为 29.90 µg/mL。高效液相色谱分析显示，T. procumbens 的花朵部分含有大量阿魏酸（0.55-2.65 毫克/克）和山柰酚（1.1-4.95 毫克/克）。在 DPPH 和 NO 检测中观察到的强抗氧化活性有助于衡量提取物在清除 NO 自由基、中和其他活性氧（ROS）方面的有效性。这项研究凸显了植物化合物在癌症治疗中的潜力。

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