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Advancements and challenges in the epidemiology, diagnosis, treatment, and management of multiple sclerosis: a comprehensive review 多发性硬化症的流行病学、诊断、治疗和管理方面的进展和挑战:全面回顾
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-23 DOI: 10.1186/s43088-025-00702-1
Taha Saeed, Hanan Afzal, Aiman Aijaz, Aqsa Ashfaq, Amna Rehman, Zoraiz Ahmad, Farzeen Abid, Memoona Suleman, Salman Waris, Ali Afzal, Muhammad Babar Khawar

Background

Multiple sclerosis is a chronic autoimmune disease that damages the central nervous system through inflammation, loss of myelin, and progressive neurodegeneration. Its prevalence has been increasing worldwide, with variations that reflect genetic predisposition, environmental influences, and immune system dysregulation.

Main Body

Advances in high-resolution magnetic resonance imaging and the use of cerebrospinal fluid biomarkers have enhanced the ability to detect early disease activity, monitor progression, and evaluate therapeutic response. Despite these improvements, challenges remain in understanding the mechanisms driving disease progression, particularly in progressive forms of multiple sclerosis where treatment options are limited. Barriers such as unequal access to therapies, variable long-term efficacy, and incomplete knowledge of disease pathways continue to hinder effective management. Current research emphasizes the need for personalized approaches that incorporate genetic, immunological, and environmental factors. Efforts are also being directed toward identifying neuroprotective and remyelinating agents, alongside integrating biomarkers into treatment strategies, in order to better tailor therapies and improve monitoring of disease activity.

Conclusion

Future directions in multiple sclerosis research should focus on precision medicine, the discovery of novel therapeutic targets, and the integration of biomarkers into clinical care. These strategies hold the potential to improve long-term outcomes, reduce disease burden, and enhance the quality of life for affected individuals. This review explores global epidemiological patterns, recent diagnostic innovations, and the effectiveness of emerging treatment strategies in multiple sclerosis.

多发性硬化症是一种慢性自身免疫性疾病,通过炎症、髓磷脂丢失和进行性神经退行性变损害中枢神经系统。其患病率在全球范围内呈上升趋势,其变化反映了遗传易感性、环境影响和免疫系统失调。高分辨率磁共振成像技术的进步和脑脊液生物标志物的使用提高了检测早期疾病活动、监测进展和评估治疗反应的能力。尽管取得了这些进展,但在理解驱动疾病进展的机制方面仍然存在挑战,特别是在治疗选择有限的进行性多发性硬化症中。诸如获得治疗机会不平等、长期疗效不一以及对疾病途径了解不全等障碍继续阻碍有效管理。目前的研究强调需要结合遗传、免疫和环境因素的个性化方法。研究人员还致力于识别神经保护和髓鞘再生药物,同时将生物标志物整合到治疗策略中,以便更好地定制治疗方法并改善疾病活动的监测。结论未来多发性硬化症的研究方向应集中在精准医学、新靶点的发现、生物标志物与临床护理的结合等方面。这些策略具有改善长期结果、减轻疾病负担和提高受影响个体生活质量的潜力。这篇综述探讨了多发性硬化症的全球流行病学模式、最新的诊断创新和新兴治疗策略的有效性。
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引用次数: 0
Guanine and β-aminobutyric acid as novel elicitors enhance barley defence against net blotch disease through oxidative stress and enzymatic defence mechanisms 鸟嘌呤和β-氨基丁酸作为新的激发子,通过氧化应激和酶防御机制增强大麦对网斑病的防御
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-23 DOI: 10.1186/s43088-025-00697-9
Marian Thabet, Hala Badr Khalil, Mervat Sh Sadak, Sherin Mikhail

Background

Net blotch disease, caused by Pyrenophora teres, poses a growing threat to global barley production, highlighting the need for sustainable disease management strategies. Traditional control relies heavily on chemical fungicides, which raise concerns about environmental safety and resistance development. There is growing interest in sustainable, eco-friendly alternatives to enhance plant immunity. Elicitors like guanine and β-aminobutyric acid (βABA) offer promising potential for boosting resistance in barley against fungal pathogens.

Methods

This study investigated the effectiveness of guanine and βABA as elicitors in boosting systemic resistance in a susceptible barley cultivar (Hordeum vulgare cv. Giza 2000) against P. teres, compared to the conventional fungicide epoxiconazole, under both greenhouse and field conditions. Barley leaves were analysed for reactive oxygen species (ROS) using 3,3'-diaminobenzidine (DAB) and nitro blue tetrazolium (NBT) staining, for physiological parameters measurements, including chlorophyll, carotenoids, hydrogen peroxide (H₂O₂), and superoxide anion (O₂•⁻). Enzymatic activities of key antioxidant and defence-related enzymes were spectrophotometrically assessed.

Results

All epoxiconazole, guanine, and βABA significantly reduced disease severity and infection response with epoxiconazole being the most effective, followed by guanine and βABA. Notably, guanine and βABA induced an early oxidative burst, characterised by increased endogenous production of ROS, H₂O₂, and O₂•⁻, detected in guard and mesophyll cells within 24 h post-inoculation (hpi). This response was inversely correlated with fungal colonisation. Further analyses at 3 and 15 days post-inoculation (dpi) revealed that both elicitors enhanced antioxidant enzyme activity and promoted the accumulation of osmoprotectants and non-enzymatic antioxidants, crucial for countering oxidative stress. Additionally, foliar application of guanine and βABA mitigated oxidative damage by reducing excessive ROS, lipoxygenase activity, and malondialdehyde levels.

Conclusions

The findings underscore the potential of guanine and βABA as key immune signalling molecules in plant–microbe interactions, playing a pivotal role in plant defence. To our knowledge, this is the first study to elucidate the mechanisms behind guanine- and βABA-mediated defence activation in barley against net blotch disease, positioning them as sustainable alternatives to synthetic fungicides for integrated disease management in barley cultivation.

由白斑孢菌引起的斑点病对全球大麦生产构成越来越大的威胁,这突出表明需要可持续的疾病管理战略。传统的防治严重依赖化学杀菌剂,这引起了对环境安全和耐药性发展的担忧。人们对可持续的、生态友好的替代品越来越感兴趣,以增强植物的免疫力。鸟嘌呤和β-氨基丁酸(βABA)等激发子在提高大麦对真菌病原体的抗性方面具有很大的潜力。方法研究了鸟嘌呤和βABA作为诱导子对大麦(Hordeum vulgare cv)系统抗性的增强作用。在温室和田间条件下,与传统的杀菌剂环氧康唑相比,Giza 2000)对圆线虫的杀伤效果更好。使用3,3'-二氨基苯胺(DAB)和硝基蓝四氮唑(NBT)染色分析大麦叶片的活性氧(ROS),并测量生理参数,包括叶绿素,类胡萝卜素,过氧化氢(H₂O₂)和超氧阴离子(O₂•毒血症)。用分光光度法测定了关键抗氧化酶和防御相关酶的酶活性。结果环氧康唑、鸟嘌呤和βABA均能显著降低疾病严重程度和感染反应,其中以环氧康唑效果最好,鸟嘌呤和βABA次之。值得注意的是,鸟嘌呤和βABA诱导了早期氧化爆发,其特征是内源性ROS, H₂O₂和O₂•毒血症,在接种后24小时内在保护细胞和叶肉细胞中检测到。这种反应与真菌定植呈负相关。接种后3天和15天的进一步分析显示,两种激发子都增强了抗氧化酶活性,促进了渗透保护剂和非酶抗氧化剂的积累,这对对抗氧化应激至关重要。此外,叶面施用鸟嘌呤和βABA通过降低过量的活性氧、脂氧合酶活性和丙二醛水平来减轻氧化损伤。结论鸟嘌呤和βABA可能是植物与微生物相互作用的关键免疫信号分子,在植物防御中发挥关键作用。据我们所知,这是第一个阐明鸟嘌呤和β aba介导的大麦抗网斑病防御激活机制的研究,将它们定位为大麦种植综合病害管理中合成杀菌剂的可持续替代品。
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引用次数: 0
Lipid nanocosmeceuticals: a novel approach to skin therapy for anti-aging and skin disorders 脂质纳米药妆:一种抗衰老和皮肤疾病的新方法
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-23 DOI: 10.1186/s43088-025-00695-x
Krithiga Venkatesan, Gouranga Dutta, Reechik Bandyopadhyay, Nilayan Guha, Biplab Debnath, Sivakumar Manickam, Abimanyu Sugumaran

Background

Psoriasis, eczema, fungal infections, and skin aging are prevalent dermatological conditions characterized by chronic inflammation, impaired skin barrier function, and a reduced quality of life. Conventional topical cosmetic treatments, however, are constrained by limited suboptimal efficacy, instability of active compounds, and inadequate skin penetration. The application of nanotechnology in cosmetics, known as nanocosmeceuticals, has emerged as a promising strategy to overcome these drawbacks. Lipid-based nanocarriers, including liposomes, phytosomes, niosomes, and solid lipid nanoparticles, facilitate site-specific delivery, enhance transdermal permeation, and protect bioactive constituents from degradation, improving therapeutic effectiveness.

Main body

This study aims to provide a comprehensive evaluation of lipid-based nanocosmeceuticals for the prevention and treatment of skin aging and related dermatological disorders, with particular emphasis on formulation strategies, therapeutic efficacy, and safety considerations. This work presents a comprehensive review of peer-reviewed studies addressing the physicochemical properties, delivery strategies, and both in vitro and in vivo performance of lipid-based nanocarriers in dermatological applications. Studies show lipid-based nanocarriers exhibit minimal toxicity, enhanced stability, and controlled, sustained release profiles, with the added ability to deliver active compounds to targeted skin sites. Reported benefits include improved skin hydration, reduced wrinkles, and more effective management of psoriasis, eczema, and microbial infections. Their high entrapment efficiency and capacity for co-delivery of multiple drugs further strengthen their potential as versatile platforms for dermatological therapy.

Conclusion

Lipid-based nanocosmeceuticals represent novel and versatile platforms that provide both cosmetic and therapeutic benefits. They hold strong potential to transform dermatological care through enhanced efficacy and improved safety; however, large-scale clinical trials and regulatory harmonization remain essential to enable their successful translation into clinical practice.

Graphical abstract

背景银屑病、湿疹、真菌感染和皮肤老化是常见的皮肤病,其特征是慢性炎症、皮肤屏障功能受损和生活质量下降。然而,传统的局部美容治疗受到有限的次优疗效、活性化合物的不稳定性和皮肤渗透不足的限制。纳米技术在化妆品中的应用,被称为纳米药妆品,已经成为克服这些缺点的一种有希望的策略。脂基纳米载体,包括脂质体、磷脂质体、乳质体和固体脂质纳米颗粒,促进部位特异性递送,增强透皮渗透,保护生物活性成分免受降解,提高治疗效果。本研究旨在对脂质纳米药妆预防和治疗皮肤老化及相关皮肤病的效果进行综合评价,特别强调配方策略、治疗效果和安全性考虑。这项工作提出了一个全面的审查同行评审的研究解决物理化学性质,传递策略,体外和体内性能的脂基纳米载体在皮肤病学应用。研究表明,基于脂质的纳米载体具有最小的毒性,增强的稳定性和可控的持续释放特性,并具有将活性化合物输送到目标皮肤部位的附加能力。报告的好处包括改善皮肤水合作用,减少皱纹,更有效地管理牛皮癣,湿疹和微生物感染。它们的高捕获效率和多种药物的共同递送能力进一步增强了它们作为皮肤病治疗的多功能平台的潜力。结论脂质纳米药妆是一种兼具美容和治疗双重功效的新型、多功能平台。它们具有通过增强疗效和提高安全性来改变皮肤科护理的强大潜力;然而,大规模临床试验和监管协调仍然是使其成功转化为临床实践的关键。图形抽象
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引用次数: 0
Fractional-order model for marburg virus transmission: assessing the impact of awareness, burial and cremation practices 马尔堡病毒传播的分数阶模型:评估认识、埋葬和火化做法的影响
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-23 DOI: 10.1186/s43088-025-00691-1
Kaushal Soni, Shyamsunder Kumawat, Arvind Kumar Sinha

The highly infectious Marburg virus (MARV) spreads rapidly through contact with infected individuals and improperly handled deceased bodies. Although burial and cremation practices have been examined for other pathogens, their role in MARV transmission remains largely unquantified. This study introduces a novel fractional-order compartmental model that explicitly incorporates burial, cremation, and awareness-based interventions to assess their combined impact on MARV control. The model employs the Caputo fractional derivative to capture memory effects in disease progression, offering a more realistic representation of transmission dynamics compared to traditional integer-order models. The basic reproduction number is derived via the next-generation matrix (NGM) approach, and the local asymptotic stability of the Marburg-free equilibrium is established. The Marburg present equilibrium point is obtained, and its global stability is rigorously proved using a Lyapunov function framework. Furthermore, bifurcation analysis is conducted to explore qualitative changes in system dynamics and confirm the occurrence of a forward bifurcation at (textrm{R}_0=1). Global sensitivity analysis identifies the most influential parameters affecting disease spread, highlighting that increasing awareness and reducing contact with infectious or deceased individuals markedly suppress transmission. Theoretical contributions include proofs of positivity, boundedness, existence, and uniqueness of solutions, and Ulam–Hyers stability. To validate the proposed approach, results from the generalized Euler method (GEM) are compared with those obtained using Runge–Kutta methods for integer-order models and the Adams-Bashforth-Moulton (ABM) scheme for fractional-order models, showing strong agreement. The findings underscore the novel application of fractional-order modeling to MARV, demonstrating its superior capability to capture long-term effects and guide culturally sensitive, evidence-based public health strategies for outbreak mitigation.

传染性极强的马尔堡病毒(MARV)通过与受感染者和处理不当的尸体接触而迅速传播。虽然已经检查了埋葬和火葬的做法是否存在其他病原体,但它们在MARV传播中的作用在很大程度上仍然无法量化。本研究引入了一个新的分数阶隔间模型,该模型明确地结合了埋葬、火化和基于意识的干预措施,以评估它们对MARV控制的综合影响。该模型采用卡普托分数阶导数来捕捉疾病进展中的记忆效应,与传统的整阶模型相比,提供了更真实的传播动力学表示。利用新一代矩阵(NGM)方法导出了基本再现数,并建立了无马尔堡平衡的局部渐近稳定性。得到了马尔堡平衡点,并利用Lyapunov函数框架严格证明了其全局稳定性。进一步进行分岔分析,探索系统动力学的质变,确认在(textrm{R}_0=1)处存在前向分岔。全球敏感性分析确定了影响疾病传播的最具影响力的参数,强调提高认识和减少与感染者或死者的接触可显著抑制传播。理论贡献包括证明解的正性、有界性、存在性和唯一性,以及Ulam-Hyers稳定性。为了验证所提出的方法,将广义欧拉方法(GEM)的结果与整阶模型的龙格-库塔方法和分数阶模型的Adams-Bashforth-Moulton (ABM)格式的结果进行了比较,结果显示出很强的一致性。这些发现强调了分数阶模型在MARV中的新应用,证明了其在捕捉长期影响和指导具有文化敏感性、基于证据的公共卫生战略以缓解疫情方面的卓越能力。
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引用次数: 0
Advances in research on palliative care and family meeting: a bibliometric study from 2004 to 2024 姑息治疗与家庭会议研究进展:2004 - 2024年文献计量学研究
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-11 DOI: 10.1186/s43088-025-00698-8
Jing Zhang, Yuan Li, Huan Yu, Shanshan Gong, Yuchang Fei

Background

The study conducted a comprehensive literature search from 2004 to 2024 to delve into the strong relationship between palliative care and family meetings.

Methods

We conducted a comprehensive search of the literature in the Web of Science Core Collection, published “English” papers, and the paper types were limited to “Article” and “Review”. The bibliometric tools CiteSpace, VOSviewer, SCImago Graphica, and COOC tools were used to process and visualize the data.

Results

The results show that the number of publications in this field has grown continuously for more than 20 years. The USA was the largest contributor, followed by Australia and China. Although China ranks high in the number of publications, the average number of citations is still low, indicating that suggesting a need for more high-quality research. In the field of research institutions, the University of Washington and the University of Pittsburgh have a high level of productivity, but the potential for inter-institutional collaboration remains to be exploited, which provides a path for future collaborative development. In terms of authors, Curtis Jr. is by far the leading author in both the number of publications and citations and establishing him as a pioneering scholar in the field who has made remarkable contributions to the development of the discipline.

Conclusions

The development of family meetings is of great significance for critically ill patients and their families in palliative care. Bibliometrics aims to provide more powerful evidence for the future development of this field through visual statistical analysis.

本研究从2004年到2024年进行了全面的文献检索,以深入研究姑息治疗与家庭会议之间的紧密关系。方法全面检索Web of Science Core Collection的文献,发表“英文”论文,论文类型限于“Article”和“Review”。使用文献计量工具CiteSpace、VOSviewer、SCImago Graphica和COOC工具对数据进行处理和可视化。结果20多年来,该领域的出版物数量持续增长。美国是最大的贡献者,其次是澳大利亚和中国。尽管中国在发表论文数量上排名靠前,但平均被引次数仍然很低,这表明需要更多高质量的研究。在研究机构领域,华盛顿大学和匹兹堡大学的生产力水平较高,但机构间合作的潜力仍有待挖掘,这为未来的合作发展提供了一条路径。就作者而言,Curtis Jr.在发表论文数量和被引用次数方面都是迄今为止的第一作者,这使他成为该领域的先驱学者,为该学科的发展做出了卓越的贡献。结论开展家属会议对危重病人及其家属开展姑息治疗具有重要意义。文献计量学旨在通过可视化的统计分析,为这一领域的未来发展提供更有力的证据。
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引用次数: 0
Insights into North African endemic plants and their applications in the food industry with particular emphasis on their quality and safety assessment 深入了解北非特有植物及其在食品工业中的应用,特别强调其质量和安全评估
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-10 DOI: 10.1186/s43088-025-00690-2
Hesham R. El-Seedi, Hanen Najjaa, Rim Gatran, Malak Harabi, Doaa M. Abo‑Atya, Shaden A. M. Khalifa, Abdelkarim Ben Arfa, Zhiming Guo, Mohamed Neffati

Background

The exploration of alternative food sources has gained significant attention mainly to secure the food supply, maintain sustainability and face the environmental, climate and human challenges. North Africa hosts a plethora of endemic plants that have remained largely untapped in terms of their potential for human consumption.

Materials and methods

A comprehensive literature survey was conducted using several search engines, including Google Scholar, Scopus, BASE, CORE, MDPI, Wiley publications, Web of Science, Springer Link, Microsoft Academia, and PubMed. Relevant studies available up to 2025 were included without time restrictions.

Results

Through an extensive literature review, we identified several native plants that exhibit promising nutritional profiles, with potential health benefits especially for the food industry. The integration of these endemic plants into the food industry has the potential to diversify diets, promote sustainable agriculture harvesting and cultivation practices, support regional food security, and to safeguard local ecosystems and maintain ecological balance.

Conclusion

This review underscores the significance of collaborative efforts between researchers, policymakers, and the private sector to fully unlock the benefits of North African endemic plants as alternative food sources and foster a more resilient and sustainable food future for the region and beyond. Furthermore, the review highlights their adaptability to various culinary uses, encompassing traditional dishes, modern recipes, and potential industrial applications.

对替代食物来源的探索已经引起了人们的极大关注,主要是为了确保食物供应,保持可持续性,面对环境、气候和人类的挑战。北非拥有大量的地方植物,就其供人类消费的潜力而言,这些植物在很大程度上尚未开发。材料与方法使用谷歌Scholar、Scopus、BASE、CORE、MDPI、Wiley publications、Web of Science、施普林格Link、Microsoft Academia、PubMed等多个搜索引擎进行了全面的文献调查。纳入截至2025年的相关研究,没有时间限制。结果通过广泛的文献回顾,我们确定了几种具有良好营养价值的本土植物,特别是对食品工业具有潜在的健康益处。将这些特有植物纳入食品工业有可能使饮食多样化,促进可持续农业收获和种植方法,支持区域粮食安全,并保护当地生态系统和维持生态平衡。本综述强调了研究人员、政策制定者和私营部门之间合作努力的重要性,以充分释放北非特有植物作为替代食物来源的好处,并为该地区和其他地区建立一个更具弹性和可持续的粮食未来。此外,综述还强调了它们对各种烹饪用途的适应性,包括传统菜肴、现代食谱和潜在的工业应用。
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引用次数: 0
Comparative neurobehavioral and histopathological toxicity induced by chronic exposure to metallic oxide nanoparticles and perovskite nanomembrane 慢性暴露于金属氧化物纳米颗粒和钙钛矿纳米膜诱导的神经行为和组织病理学毒性比较
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-09 DOI: 10.1186/s43088-025-00696-w
Bashir Jararr, Mansour Almansour, Amin Al-Doaiss, Qais Jarrar, Edi Syams Zainudin, Su-Jun Lee, Amal Sewelam

Background

Nanoparticles (NPs) are increasingly used in medicine, industry, agriculture, cosmetics, drug delivery, and energy storage. Despite their widespread use, their potential toxicity, particularly their effects on behavior, remains poorly understood. This study aimed to investigate behavioral and neuronal changes following chronic exposure to four types of NPs: silicon dioxide, nickel oxide, cobalt oxide, and perovskite nanomembrane.

Methods

Eighty adult male BALB/c mice were divided into four treatment groups and four control groups. Treated mice received daily intraperitoneal injections of silicon dioxide, nickel oxide, cobalt oxide, or perovskite for 35 days, while controls received the corresponding vehicle. All mice underwent eight neurobehavioral tests. Brain tissues were collected for histological and immunohistochemical analysis.

Results

NPs-exposed mice exhibited anxiety- and depression-like behaviors, increased stress, thigmotaxis, reduced locomotion, and impaired exploratory activity. Spatial learning and both reference and working memory were also compromised. Histological analysis revealed neuronal shrinkage and pyknosis in the prefrontal cortex, hippocampus, and cerebellum, along with gliosis, vascular changes, perivascular edema, neuronophagia, and spongiosis. Moreover, a positive inducible nitric oxide synthase (iNOS) immunoreactivity has been increased by the exposure to different types of NPs indicating nitrosative stress with subsequent oxidative stress.

Conclusions

Chronic exposure to NPs induces nitrosative and subsequent oxidative stresses-related neuronal damage and behavioral alterations, potentially disrupting brain function. Among the tested NPs, perovskite nanomembranes displayed the most severe effects, followed by Co3O4, NiO, and SiO2 NPs. Further studies are needed to elucidate the relationship between behavioral outcomes and neuronal pathology caused by long-term NP exposure.

纳米粒子(NPs)在医药、工业、农业、化妆品、药物输送和能源储存等领域的应用越来越广泛。尽管它们被广泛使用,但它们的潜在毒性,特别是对行为的影响,仍然知之甚少。本研究旨在探讨慢性暴露于四种NPs(二氧化硅、氧化镍、氧化钴和钙钛矿纳米膜)后的行为和神经元变化。方法80只成年雄性BALB/c小鼠分为4个治疗组和4个对照组。实验组小鼠每天腹腔注射二氧化硅、氧化镍、氧化钴或钙钛矿,持续35天,对照组小鼠接受相应的载药。所有小鼠都进行了八次神经行为测试。采集脑组织进行组织学和免疫组织化学分析。结果暴露于snp的小鼠表现出焦虑和抑郁样行为、应激增加、趋动、运动减少和探索活动受损。空间学习、参考记忆和工作记忆也受到损害。组织学分析显示,前额皮质、海马和小脑的神经元萎缩和固缩,并伴有胶质瘤、血管改变、血管周围水肿、神经元吞噬和海绵状病变。此外,诱导型一氧化氮合酶(iNOS)的阳性免疫反应性通过暴露于不同类型的一氧化氮合酶而增加,表明亚硝化应激伴随着随后的氧化应激。结论长期暴露于NPs可引起亚硝化和随后的氧化应激相关的神经元损伤和行为改变,潜在地破坏脑功能。在测试的NPs中,钙钛矿纳米膜的影响最严重,其次是Co3O4、NiO和SiO2 NPs。行为结果与长期NP暴露引起的神经病理之间的关系有待进一步研究。
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引用次数: 0
PCSK9 molecular bridge between hyperlipidemia and vascular inflammation: novel insights into PCSK9-centered pathways in atherosclerosis: a comprehensive review 高脂血症和血管炎症之间的PCSK9分子桥:对动脉粥样硬化中PCSK9中心通路的新见解:一项全面的综述
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-07 DOI: 10.1186/s43088-025-00694-y
Muhammad A. Desouky, Mohammed A. El-Magd, Mohamed Abdelmeguid Mousa, Abbas Hayat Mallick, Delwar Khan, Dina A. Desouky

Background

Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality despite advances in lipid-lowering therapy. The proprotein convertase subtilisin/kexin type 9 protein (PCSK9) was originally characterized for promoting degradation of the low-density lipoprotein receptor and raising circulating low-density lipoprotein cholesterol, but growing evidence shows that PCSK9 also participates directly in vascular inflammation and oxidative stress, bridging lipid dysregulation and immune activation.

Main body

PCSK9 amplifies vascular inflammation through several linked mechanisms. PCSK9 augments toll-like receptor 4/nuclear factor kappa B signaling, raising transcription and release of cytokines such as tumor necrosis factor alpha, and increasing adhesion molecule expression that promotes leukocyte recruitment. PCSK9 upregulates scavenger receptors, notably lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and CD36, which enhances uptake of oxidized lipoprotein, foam cell formation and activation of the NLRP3 inflammasome. PCSK9 also promotes reactive oxygen species generation via NADPH oxidase and impairs nitric oxide biology, worsening endothelial dysfunction. Together these pathways form a self-amplifying loop in which oxidized lipoprotein and cytokines further increase PCSK9 expression. Clinical and preclinical data indicate that PCSK9 inhibitors markedly lower low-density lipoprotein cholesterol and can reduce some markers of plaque inflammation and oxidative stress, but its full therapeutic potential remains a subject of ongoing investigation.

Conclusion

PCSK9 functions as a molecular bridge between dyslipidemia and vascular inflammation; defining the precise molecular interactions and how different modes of PCSK9 inhibition affect these pathways may enable targeted anti-inflammatory strategies to complement lipid lowering and reduce residual cardiovascular risk.

背景:尽管降脂疗法取得了进展,动脉硬化仍然是心血管疾病发病和死亡的主要原因。蛋白转化酶枯草杆菌素/ keexin 9型蛋白(PCSK9)最初被认为是促进低密度脂蛋白受体降解和提高循环低密度脂蛋白胆固醇,但越来越多的证据表明PCSK9还直接参与血管炎症和氧化应激,桥接脂质失调和免疫激活。pypcsk9通过几种相关机制放大血管炎症。PCSK9增强toll样受体4/核因子κ B信号,提高肿瘤坏死因子α等细胞因子的转录和释放,并增加促进白细胞募集的粘附分子表达。PCSK9上调清扫剂受体,特别是凝集素样氧化低密度脂蛋白受体1 (LOX-1)和CD36,从而增强氧化脂蛋白的摄取、泡沫细胞的形成和NLRP3炎性体的激活。PCSK9还通过NADPH氧化酶促进活性氧的产生,损害一氧化氮生物学,加重内皮功能障碍。这些途径共同形成一个自我放大的循环,其中氧化脂蛋白和细胞因子进一步增加PCSK9的表达。临床和临床前数据表明,PCSK9抑制剂可显著降低低密度脂蛋白胆固醇,并可降低斑块炎症和氧化应激的一些标志物,但其全部治疗潜力仍有待进一步研究。结论pcsk9在血脂异常与血管炎症之间起着分子桥梁作用;确定精确的分子相互作用以及PCSK9抑制的不同模式如何影响这些途径可能使靶向抗炎策略能够补充降脂和降低剩余心血管风险。
{"title":"PCSK9 molecular bridge between hyperlipidemia and vascular inflammation: novel insights into PCSK9-centered pathways in atherosclerosis: a comprehensive review","authors":"Muhammad A. Desouky,&nbsp;Mohammed A. El-Magd,&nbsp;Mohamed Abdelmeguid Mousa,&nbsp;Abbas Hayat Mallick,&nbsp;Delwar Khan,&nbsp;Dina A. Desouky","doi":"10.1186/s43088-025-00694-y","DOIUrl":"10.1186/s43088-025-00694-y","url":null,"abstract":"<div><h3>Background</h3><p>Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality despite advances in lipid-lowering therapy. The proprotein convertase subtilisin/kexin type 9 protein (PCSK9) was originally characterized for promoting degradation of the low-density lipoprotein receptor and raising circulating low-density lipoprotein cholesterol, but growing evidence shows that PCSK9 also participates directly in vascular inflammation and oxidative stress, bridging lipid dysregulation and immune activation.</p><h3>Main body</h3><p>PCSK9 amplifies vascular inflammation through several linked mechanisms. PCSK9 augments toll-like receptor 4/nuclear factor kappa B signaling, raising transcription and release of cytokines such as tumor necrosis factor alpha, and increasing adhesion molecule expression that promotes leukocyte recruitment. PCSK9 upregulates scavenger receptors, notably lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and CD36, which enhances uptake of oxidized lipoprotein, foam cell formation and activation of the NLRP3 inflammasome. PCSK9 also promotes reactive oxygen species generation via NADPH oxidase and impairs nitric oxide biology, worsening endothelial dysfunction. Together these pathways form a self-amplifying loop in which oxidized lipoprotein and cytokines further increase PCSK9 expression. Clinical and preclinical data indicate that PCSK9 inhibitors markedly lower low-density lipoprotein cholesterol and can reduce some markers of plaque inflammation and oxidative stress, but its full therapeutic potential remains a subject of ongoing investigation.</p><h3>Conclusion</h3><p>PCSK9 functions as a molecular bridge between dyslipidemia and vascular inflammation; defining the precise molecular interactions and how different modes of PCSK9 inhibition affect these pathways may enable targeted anti-inflammatory strategies to complement lipid lowering and reduce residual cardiovascular risk.</p></div>","PeriodicalId":481,"journal":{"name":"Beni-Suef University Journal of Basic and Applied Sciences","volume":"14 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bjbas.springeropen.com/counter/pdf/10.1186/s43088-025-00694-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel topical delivery of biphasic Janus nanoparticles loaded with miconazole nitrate and berberine hydrochloride for antifungal therapy against Candida albicans 一种新的局部递送的双相Janus纳米颗粒装载硝酸咪康唑和盐酸小檗碱抗真菌治疗白色念珠菌
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-10-04 DOI: 10.1186/s43088-025-00692-0
Mohan Prasad Arunmahalingam, Radhakrishnan Nithya

Background

This study develops and characterizes biphasic Janus nanoparticles (JNPs) for the co-delivery of miconazole nitrate (MCN) and berberine hydrochloride (BER), aiming to enhance antifungal efficacy through combinatorial therapy against superficial fungal infections.

Methods

JNPs were synthesized using single-phase emulsion (O/W-S) and double-phase emulsion (W/O/W) methods, and their physicochemical properties were characterized, including size distribution, polydispersity, surface charge, and encapsulation efficiency. In vitro drug release profiles of MCN and BER from JNPs were evaluated, along with a hydrogel (HG) formulation incorporating optimized JNPs for topical application. Solubility assessments, Fourier transform infrared (FT-IR) spectroscopy for compatibility analysis, and antifungal activity testing against Candida albicans using the agar well diffusion method were also performed.

Results

JNPs exhibited a unique dumbbell-shaped morphology, achieving encapsulation efficiencies of 90.32% for MCN and 71.13% for BER in the W/O/W method. In vitro drug release studies showed cumulative releases of 97.52% for MCN and 90.23% for BER over 24 h in the JNP-HG formulation. The hydrogel, with a pH of 6.75 ± 0.13 and exhibiting non-Newtonian pseudoplastic behaviour, demonstrated excellent spreadability. Antifungal tests revealed significant efficacy of the co-loaded JNPs in the hydrogel, showing larger inhibition zones compared to individual drugs due to synergism.

Conclusion

This research introduces a novel platform employing JNPs for the combinatorial delivery of hydrophilic and hydrophobic drugs, facilitating sustained release and offering promising therapeutic potential for antifungal agents. Future studies should evaluate its in vivo performance and explore diverse combinatorial therapies.

本研究开发并表征了双相Janus纳米颗粒(JNPs),用于共同递送硝酸咪康唑(MCN)和盐酸小檗碱(BER),旨在通过联合治疗表面真菌感染来提高抗真菌效果。方法采用单相乳状液(O/W- s)和双相乳状液(W/O/W)法制备sjnps,并对其粒径分布、多分散性、表面电荷和包封效率等理化性质进行表征。评估了JNPs中MCN和BER的体外药物释放谱,以及含有优化JNPs的水凝胶(HG)配方。溶解度评估,傅里叶变换红外(FT-IR)光谱分析的相容性分析,以及琼脂孔扩散法对白色念珠菌的抗真菌活性测试。结果jnps呈现出独特的哑铃状形态,在W/O/W法下,MCN的包封率为90.32%,BER的包封率为71.13%。体外释药研究表明,JNP-HG制剂24 h内MCN和BER的累积释药量分别为97.52%和90.23%。该水凝胶的pH值为6.75±0.13,具有非牛顿假塑性行为,具有良好的涂抹性。抗真菌试验显示水凝胶中共负载JNPs的显著功效,由于协同作用,与单个药物相比,显示出更大的抑制区。结论本研究提出了一种利用JNPs联合递送亲疏水药物的新平台,促进了抗真菌药物的缓释,为抗真菌药物的治疗提供了广阔的前景。未来的研究应评估其在体内的表现,并探索多种联合治疗方法。
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引用次数: 0
DDN gene downregulation in endometrium: a potential immune-mediated link between bipolar disorder and spontaneous abortion revealed by Mendelian randomization and bioinformatics 子宫内膜DDN基因下调:孟德尔随机化和生物信息学揭示的双相情感障碍与自然流产之间潜在的免疫介导联系
IF 2.6 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-09-27 DOI: 10.1186/s43088-025-00674-2
Jian Tang, Zhixin Xu, Lingling Yang, Qiong Zou

Background

Spontaneous abortion, affecting over 20% of pregnancies, presents significant physical and psychological burdens. While chromosomal aneuploidy and environmental factors contribute to its etiology, the role of maternal genetic and psychiatric factors remains underexplored. Emerging evidence links psychiatric disorders, particularly bipolar disorder, to increased spontaneous abortion risk, potentially via immune or neuroendocrine dysregulation. This research examines the causal link between bipolar disorder and spontaneous abortion using mendelian randomization (MR) and delves into molecular mechanisms via bioinformatics analysis.

Results

Initial MR analysis revealed no direct causal association between bipolar disorder and spontaneous abortion (odds ratio (OR) = 1.05, 95% Confidence Interval (CI): 0.99–1.12). However, single-nucleotide-polymorphism-level analysis identified rs1054442 as a potential mediator, linked to reduced expression of DDN, a gene implicated in neurodevelopment and immune modulation. Microarray data demonstrated significant downregulation of DDN in endometrial tissue from spontaneous abortion patients (logFold Change (logFC) = − 1.21, p = 0.004). Concurrently, immune checkpoint genes—CTLA4, IGSF8, ITPRIPL1, and TIGIT—exhibited altered expression patterns, suggesting disrupted immune tolerance at the maternal–fetal interface.

Conclusions

Although bipolar disorder does not directly elevate spontaneous abortion risk, genetic variants associated with the disorder may contribute to immune dysfunction via DDN dysregulation, indirectly predisposing to spontaneous abortion. These discoveries point to the potential influence of maternal immune modulation in the origins of spontaneous abortion and indicate therapeutic targets for those at risk. Further studies are needed to validate these mechanisms and explore clinical interventions targeting immune checkpoint pathways.

自然流产影响了超过20%的妊娠,造成了严重的生理和心理负担。虽然染色体非整倍体和环境因素有助于其病因,但母体遗传和精神因素的作用仍未得到充分探讨。新出现的证据表明,精神疾病,特别是双相情感障碍,可能通过免疫或神经内分泌失调导致自然流产风险增加。本研究利用孟德尔随机化(MR)研究了双相情感障碍与自然流产之间的因果关系,并通过生物信息学分析深入研究了分子机制。结果初步MR分析显示双相情感障碍与自然流产之间无直接因果关系(优势比(OR) = 1.05, 95%可信区间(CI): 0.99-1.12)。然而,单核苷酸多态性水平分析发现rs1054442是一个潜在的中介,与DDN(一种与神经发育和免疫调节有关的基因)的表达减少有关。微阵列数据显示,自然流产患者子宫内膜DDN显著下调(logFold Change (logFC) = - 1.21, p = 0.004)。同时,免疫检查点基因ctla4、IGSF8、ITPRIPL1和tigit表现出表达模式的改变,表明母胎界面的免疫耐受被破坏。结论双相情感障碍不直接增加自然流产风险,但其相关基因变异可能通过DDN失调导致免疫功能障碍,间接导致自然流产。这些发现指出了母体免疫调节在自然流产起源中的潜在影响,并指出了高危人群的治疗靶点。需要进一步的研究来验证这些机制,并探索针对免疫检查点途径的临床干预措施。
{"title":"DDN gene downregulation in endometrium: a potential immune-mediated link between bipolar disorder and spontaneous abortion revealed by Mendelian randomization and bioinformatics","authors":"Jian Tang,&nbsp;Zhixin Xu,&nbsp;Lingling Yang,&nbsp;Qiong Zou","doi":"10.1186/s43088-025-00674-2","DOIUrl":"10.1186/s43088-025-00674-2","url":null,"abstract":"<div><h3>Background</h3><p>Spontaneous abortion, affecting over 20% of pregnancies, presents significant physical and psychological burdens. While chromosomal aneuploidy and environmental factors contribute to its etiology, the role of maternal genetic and psychiatric factors remains underexplored. Emerging evidence links psychiatric disorders, particularly bipolar disorder, to increased spontaneous abortion risk, potentially via immune or neuroendocrine dysregulation. This research examines the causal link between bipolar disorder and spontaneous abortion using mendelian randomization (MR) and delves into molecular mechanisms via bioinformatics analysis.</p><h3>Results</h3><p>Initial MR analysis revealed no direct causal association between bipolar disorder and spontaneous abortion (<i>odds ratio (OR)</i> = <i>1.05, 95% Confidence Interval (CI): 0.99–1.12</i>). However, single-nucleotide-polymorphism-level analysis identified rs1054442 as a potential mediator, linked to reduced expression of <i>DDN</i>, a gene implicated in neurodevelopment and immune modulation. Microarray data demonstrated significant downregulation of <i>DDN</i> in endometrial tissue from spontaneous abortion patients (<i>logFold Change</i> (<i>logFC)</i> = <i>− 1.21</i>, <i>p</i> = <i>0.004</i>). Concurrently, immune checkpoint genes—<i>CTLA4</i>, <i>IGSF8</i>, <i>ITPRIPL1</i>, and <i>TIGIT</i>—exhibited altered expression patterns, suggesting disrupted immune tolerance at the maternal–fetal interface.</p><h3>Conclusions</h3><p>Although bipolar disorder does not directly elevate spontaneous abortion risk, genetic variants associated with the disorder may contribute to immune dysfunction via <i>DDN</i> dysregulation, indirectly predisposing to spontaneous abortion. These discoveries point to the potential influence of maternal immune modulation in the origins of spontaneous abortion and indicate therapeutic targets for those at risk. Further studies are needed to validate these mechanisms and explore clinical interventions targeting immune checkpoint pathways.</p></div>","PeriodicalId":481,"journal":{"name":"Beni-Suef University Journal of Basic and Applied Sciences","volume":"14 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bjbas.springeropen.com/counter/pdf/10.1186/s43088-025-00674-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145210292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Beni-Suef University Journal of Basic and Applied Sciences
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