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Combination therapy of phytonanomedicine and post-biotic for the management of Parkinson's disease. 植物药物与生物后疗法联合治疗帕金森病。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-10-10 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7770
Bushra Bashir, Sukriti Vishwas, Monica Gulati, Gaurav Gupta, Sachin Kumar Singh
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引用次数: 0
Unveiling the anticancer potential of platycodin D. 揭示桔梗素D的抗癌潜力。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-10-10 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7724
Tae Kyung Hyun
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引用次数: 0
AI is revolutionizing biomedical research, but are there any negatives? 人工智能正在彻底改变生物医学研究,但它有什么负面影响吗?
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-10-08 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7761
Bor Luen Tang
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引用次数: 0
Ultrastructural alterations and mitochondrial dysfunction in skeletal muscle of peripheral artery disease patients: implications for early therapeutic interventions. 外周动脉疾病患者骨骼肌的超微结构改变和线粒体功能障碍:对早期治疗干预的影响。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-10-07 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7592
Dylan Wilburn, Emma Fletcher, Evlampia Papoutsi, William T Bohannon, Gleb Haynatzki, Bernd Zechmann, Yuqian Tian, Iraklis I Pipinos, Dimitrios Miserlis, Panagiotis Koutakis
<p><p>Peripheral artery disease (PAD) is an atherosclerotic condition that impairs blood flow to the lower extremities, resulting in myopathy in affected skeletal muscles. Improving our understanding of PAD and developing novel treatment strategies necessitates a comprehensive examination of cellular structural alterations that occur in the muscles with disease progression. Here we aimed to employ electron microscopy to quantify skeletal muscle ultrastructural alterations responsible for the myopathy of PAD. Fifty-two participants (22 controls, 10 PAD Stage II, and 20 PAD Stage IV) were enrolled. Gastrocnemius biopsies were obtained to determine mitochondrial respiration and oxidative stress. Skeletal muscle sarcomere, mitochondria, lipid droplets, and sarcoplasm were assessed using transmission electron microscopy and focused ion beam scanning electron microscopy. Controls and PAD Stage II patients underwent walking performance tests: 6-minute walking test, 4-minute walking velocity, and maximum graded treadmill test. We identified several prominent ultrastructural modifications in PAD gastrocnemius, including reduced sarcomere dimensions, alterations in mitochondria number and localization, myofibrillar disorientation, changes in lipid droplets, and modifications in mitochondria-lipid droplet contact area. These changes correlated with impaired mitochondrial respiration and increased ROS production. We observed progressive deterioration in mitochondrial parameters across PAD stages. Stage II PAD showed impaired mitochondrial function and structure, while stage IV exhibited further deterioration, more pronounced structural alterations, and a decrease in mitochondrial content. The walking performance of Stage II PAD patients was significantly reduced. Our findings suggest that pathological mitochondria play a key role in the skeletal muscle dysfunction of PAD patients and represent an important target for therapeutic interventions aimed at improving clinical and functional outcomes in this patient population. Our data indicate that treatments should be implemented early and may include therapies designed to preserve and enhance mitochondrial biogenesis and respiration, optimize mitochondrial-lipid droplet interactions, or mitigate oxidative stress. <b>Translational Perspective</b>: Peripheral artery disease (PAD) is characterized by skeletal muscle and mitochondrial dysfunction. Ultrastructural changes in skeletal muscle myofibers and mitochondria morphology can provide significant information on the PAD pathophysiology. Here, we investigated skeletal muscle and mitochondria morphological and functional changes at the sarcomere level and across the disease progression and have found that sarcomere lengths and mitochondria count and function are associated with disease progression, indicating loss of skeletal muscle contractile and metabolic function. Ultrastructural changes in the PAD skeletal muscle can provide significant information in the dev
外周动脉疾病(PAD)是一种动脉粥样硬化性疾病,会损害下肢血流,导致受影响的骨骼肌发生肌病。要加深我们对 PAD 的了解并制定新的治疗策略,就必须全面检查随着病情发展肌肉中发生的细胞结构变化。在此,我们旨在利用电子显微镜量化导致 PAD 肌肉病变的骨骼肌超微结构改变。我们共招募了 52 名参与者(22 名对照组、10 名 PAD II 期患者和 20 名 PAD IV 期患者)。采集腓肠肌活组织样本以确定线粒体呼吸和氧化应激。使用透射电子显微镜和聚焦离子束扫描电子显微镜评估骨骼肌肌节、线粒体、脂滴和肌浆。对照组和 PAD II 期患者接受了步行能力测试:6分钟步行测试、4分钟步行速度和最大分级跑步机测试。我们在 PAD 腓肠肌中发现了几种明显的超微结构改变,包括肌节尺寸减小、线粒体数量和定位改变、肌纤维失调、脂滴改变以及线粒体-脂滴接触面积改变。这些变化与线粒体呼吸受损和 ROS 生成增加有关。我们观察到线粒体参数在不同的 PAD 阶段逐渐恶化。二期 PAD 显示线粒体功能和结构受损,而四期则表现出进一步恶化、更明显的结构改变和线粒体含量下降。二期 PAD 患者的行走能力明显下降。我们的研究结果表明,病理性线粒体在 PAD 患者骨骼肌功能障碍中起着关键作用,是治疗干预的重要目标,旨在改善该患者群体的临床和功能预后。我们的数据表明,治疗应尽早实施,其中可能包括旨在保护和增强线粒体生物生成和呼吸、优化线粒体-脂滴相互作用或减轻氧化应激的疗法。转化视角:外周动脉疾病(PAD)的特点是骨骼肌和线粒体功能障碍。骨骼肌肌纤维和线粒体形态的超微结构变化可提供有关 PAD 病理生理学的重要信息。在此,我们研究了骨骼肌和线粒体在肌节水平和疾病进展过程中的形态和功能变化,发现肌节长度、线粒体数量和功能与疾病进展相关,表明骨骼肌收缩和代谢功能丧失。PAD 骨骼肌的超微结构变化可为开发新的治疗方法提供重要信息。
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引用次数: 0
Optimized therapeutic potential of Sijunzi-similar formulae for chronic atrophic gastritis via Bayesian network meta-analysis. 通过贝叶斯网络荟萃分析优化四君子汤治疗慢性萎缩性胃炎的潜力
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-09-06 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7618
Meilan Huang, Shiman Luo, Jiayue Yang, Huiling Xiong, Xiaohua Lu, Xiao Ma, Jinhao Zeng, Thomas Efferth

Chronic atrophic gastritis (CAG) is considered as a significant risk factor for triggering gastric cancer incidence, if not effectively treated. Sijunzi decoction (SD) is a well-known classic formula for treating gastric disorders, and Sijunzi-similar formulae (SF) derived from SD have also been highly regarded by Chinese clinical practitioners for their effectiveness in treating chronic atrophic gastritis. Currently, there is a lack of meta-analysis for these formulae, leaving unclear which exhibits optimal efficacy. Therefore, we employed Bayesian network meta-analysis (BNMA) to evaluate the efficacy and safety of SF as an intervention for CAG and to establish a scientific foundation for the clinical utilization of SF. The result of meta-analysis demonstrated that the combination of SF and basic therapy outperformed basic therapy alone in terms of clinical efficacy rate, eradication rate of H. pylori, and incidence of adverse events. As indicated by the SUCRA value, Chaishao Liujunzi decoction (CLD) demonstrated superior efficacy in enhancing clinical effectiveness and ameliorating H. pylori infection, and it also showed remarkable effectiveness in minimizing the occurrence of adverse events. Comprehensive analysis of therapeutic efficacy suggests that CLD is most likely the optimal choice among these six formulations, holding potential value for optimizing clinical treatment strategies. See also the graphical abstract(Fig. 1).

慢性萎缩性胃炎(CAG)如果得不到有效治疗,被认为是诱发胃癌的重要危险因素。四君子汤(SD)是治疗胃病的著名经典方剂,由四君子汤衍生出的四君子汤类似方剂(SF)也因其治疗慢性萎缩性胃炎的疗效而备受中国临床医师的推崇。目前,对这些方剂缺乏荟萃分析,因此尚不清楚哪种方剂具有最佳疗效。因此,我们采用贝叶斯网络荟萃分析法(BNMA)来评价顺和丸干预慢性萎缩性胃炎的有效性和安全性,为顺和丸的临床应用奠定科学基础。荟萃分析结果表明,SF与基础治疗联合应用在临床有效率、幽门螺杆菌根除率、不良反应发生率等方面均优于单纯基础治疗。从 SUCRA 值来看,柴芍六君子汤(CLD)在提高临床疗效和改善幽门螺杆菌感染方面表现出卓越的疗效,在减少不良反应发生方面也有显著效果。对疗效的综合分析表明,CLD 很可能是这六种制剂中的最佳选择,具有优化临床治疗策略的潜在价值。另请参阅图表摘要(图 1)。
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引用次数: 0
Pitfalls in the use of sex chromosome sequence markers for internal quality control of next-generation sequencing. 将性染色体序列标记用于下一代测序内部质量控制的陷阱。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-09-05 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7387
Danielle Patchell, Stephen E Langabeer
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引用次数: 0
AI illuminates paths in oral cancer: transformative insights, diagnostic precision, and personalized strategies. 人工智能照亮口腔癌治疗之路:变革性见解、精准诊断和个性化策略。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7253
Devesh U Kapoor, Pushpendra Kumar Saini, Narendra Sharma, Ankul Singh, Bhupendra G Prajapati, Gehan M Elossaily, Summya Rashid

Oral cancer retains one of the lowest survival rates worldwide, despite recent therapeutic advancements signifying a tenacious challenge in healthcare. Artificial intelligence exhibits noteworthy potential in escalating diagnostic and treatment procedures, offering promising advancements in healthcare. This review entails the traditional imaging techniques for the oral cancer treatment. The role of artificial intelligence in prognosis of oral cancer including predictive modeling, identification of prognostic factors and risk stratification also discussed significantly in this review. The review also encompasses the utilization of artificial intelligence such as automated image analysis, computer-aided detection and diagnosis integration of machine learning algorithms for oral cancer diagnosis and treatment. The customizing treatment approaches for oral cancer through artificial intelligence based personalized medicine is also part of this review. See also the graphical abstract(Fig. 1).

口腔癌是全球存活率最低的癌症之一,尽管最近在治疗方面取得了进展,但这仍是医疗保健领域面临的一项严峻挑战。人工智能在升级诊断和治疗程序方面表现出了值得关注的潜力,为医疗保健领域带来了可喜的进步。本综述介绍了用于口腔癌治疗的传统成像技术。人工智能在口腔癌预后中的作用,包括预测建模、预后因素识别和风险分层,在本综述中也有重要讨论。综述还包括人工智能的利用,如自动图像分析、计算机辅助检测和诊断,以及将机器学习算法整合到口腔癌诊断和治疗中。通过基于人工智能的个性化医疗定制口腔癌治疗方法也是本综述的一部分。另请参见图表摘要(图 1)。
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引用次数: 0
In silico approaches supporting drug repurposing for Leishmaniasis: a scoping review. 支持利什曼病药物再设计的硅学方法:范围综述。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7552
Gustavo Scheiffer, Karime Zeraik Abdalla Domingues, Daniela Gorski, Alexandre de Fátima Cobre, Raul Edison Luna Lazo, Helena Hiemisch Lobo Borba, Luana Mota Ferreira, Roberto Pontarolo

The shortage of treatment options for leishmaniasis, especially those easy to administer and viable for deployment in the world's poorest regions, highlights the importance of employing these strategies to cost-effectively investigate repurposing candidates. This scoping review aims to map the studies using in silico methodologies for drug repurposing against leishmaniasis. This study followed JBI recommendations for scoping reviews. Articles were searched on PubMed, Scopus, and Web of Science databases using keywords related to leishmaniasis and in silico methods for drug discovery, without publication date restrictions. The selection was based on primary studies involving computational methods for antileishmanial drug repurposing. Information about methodologies, obtained data, and outcomes were extracted. After the full-text appraisal, 34 studies were included in this review. Molecular docking was the preferred method for evaluating repurposing candidates (n=25). Studies reported 154 unique ligands and 72 different targets, sterol 14-alpha demethylase and trypanothione reductase being the most frequently reported. In silico screening was able to correctly pinpoint some known active pharmaceutical classes and propose previously untested drugs. Fifteen drugs investigated in silico exhibited low micromolar inhibition (IC50 < 10 µM) of Leishmania spp. in vitro. In conclusion, several in silico repurposing candidates are yet to be investigated in vitro and in vivo. Future research could expand the number of targets screened and employ advanced methods to optimize drug selection, offering new starting points for treatment development. See also the graphical abstract(Fig. 1).

利什曼病治疗方案的短缺,尤其是那些易于施用且可用于世界最贫困地区的治疗方案的短缺,凸显了采用这些策略对候选药物进行具有成本效益的再利用研究的重要性。本范围综述旨在对使用硅学方法对利什曼病进行药物再利用的研究进行梳理。本研究遵循了 JBI 关于范围界定综述的建议。在 PubMed、Scopus 和 Web of Science 数据库中使用与利什曼病和药物发现的硅学方法相关的关键词对文章进行了检索,没有出版日期限制。选择的依据是涉及抗利什曼病药物再利用计算方法的主要研究。提取了有关方法、获得的数据和结果的信息。经过全文评估,34 项研究被纳入本综述。分子对接是评估再利用候选药物的首选方法(n=25)。研究报告了154种独特的配体和72个不同的靶点,其中甾醇14-α去甲基化酶和胰硫蛋白还原酶是最常见的靶点。硅学筛选能够正确确定一些已知的活性药物类别,并提出以前未曾测试过的药物。硅学研究的 15 种药物在体外对利什曼原虫属的抑制作用较低(IC50 < 10 µM)。总之,有几种硅学再利用候选药物还有待在体外和体内进行研究。未来的研究可以扩大筛选靶点的数量,并采用先进的方法优化药物选择,为治疗开发提供新的起点。另见图表摘要(图 1)。
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引用次数: 0
Advances in cartilage tissue regeneration: a review of stem cell therapies, tissue engineering, biomaterials, and clinical trials. 软骨组织再生的进展:干细胞疗法、组织工程、生物材料和临床试验综述。
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-09-03 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7088
Julia Skoracka, Kaja Bajewska, Maciej Kulawik, Wiktoria Suchorska, Katarzyna Kulcenty

Cartilage tissue, characterized by its limited regenerative capacity, presents significant challenges in clinical therapy. Recent advancements in cartilage regeneration have focused on integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to overcome existing limitations. Stem cells, particularly Mesenchymal Stem Cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise for cartilage repair due to their ability to differentiate into chondrocytes, the key cells responsible for cartilage formation. Tissue engineering approaches, including 3D models, organ-on-a-chip systems, and organoids, offer innovative methods to mimic natural tissue microenvironments and evaluate potential treatments. MSC-based techniques, such as cell sheet tissue engineering, address challenges associated with traditional therapies, including cell availability and culture difficulties. Furthermore, advancements in 3D bioprinting enable the fabrication of complex tissue structures, while organ-on-a-chip systems provide microfluidic platforms for disease modeling and physiological mimicry. Organoids serve as simplified models of organs, capturing some complexity and enabling the monitoring of pathophysiological aspects of cartilage diseases. This comprehensive review underscores the transformative potential of integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to improve cartilage regeneration and pave the way for more effective clinical treatments.

软骨组织的再生能力有限,给临床治疗带来了巨大挑战。软骨再生的最新进展主要集中在整合干细胞疗法、组织工程策略和先进的建模技术,以克服现有的局限性。干细胞,尤其是间充质干细胞(MSCs)和诱导多能干细胞(iPSCs),由于能够分化为软骨细胞(负责软骨形成的关键细胞),因此在软骨修复方面大有可为。组织工程方法,包括三维模型、片上器官系统和类器官,提供了模拟天然组织微环境和评估潜在治疗方法的创新方法。基于间充质干细胞的技术,如细胞片组织工程,解决了与传统疗法相关的挑战,包括细胞可用性和培养困难。此外,三维生物打印技术的进步使复杂组织结构的制造成为可能,而片上器官系统则为疾病建模和生理模拟提供了微流控平台。有机体可作为器官的简化模型,捕捉某些复杂性,监测软骨疾病的病理生理方面。这篇综述强调了干细胞疗法、组织工程策略和先进建模技术相结合的变革潜力,以改善软骨再生,为更有效的临床治疗铺平道路。
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引用次数: 0
The role of miR-134-5p in 7-ketocholesterol-induced human aortic endothelial dysfunction. miR-134-5p 在 7 酮胆固醇诱导的人体主动脉内皮功能障碍中的作用
IF 3.8 3区 生物学 Q1 BIOLOGY Pub Date : 2024-08-29 eCollection Date: 2024-01-01 DOI: 10.17179/excli2024-7342
Kind-Leng Tong, Ahmad Syadi Mahmood Zuhdi, Pooi-Fong Wong

Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. In our previous study, a panel of miRNA including miR-134-5p was deregulated in young acute coronary syndrome (ACS) patients. However, the roles of these ACS-associated miRNAs in endothelial dysfunction, an early event preceding atherosclerosis, remain to be investigated. In the present study, human aortic endothelial cells (HAECs) were treated with 7-ketocholesterol (7-KC) to induce endothelial dysfunction. Following treatment with 20 μg/ml 7-KC, miR-134-5p was significantly up-regulated and endothelial nitric oxide synthase (eNOS) expression was suppressed. Endothelial barrier disruption was evidenced by the deregulation of adhesion molecules including the activation of focal adhesion kinase (FAK), down-regulation of VE-cadherin, up-regulation of adhesion molecules (E-selectin and ICAM-1), increased expression of inflammatory genes (IL1B, IL6 and COX2) and AKT activation. Knockdown of miR-134-5p in 7-KC-treated HAECs attenuated the suppression of eNOS, the activation of AKT, the down-regulation of VE-cadherin and the up-regulation of E-selectin. In addition, the interaction between miR-134-5p and FOXM1 mRNA was confirmed by the enrichment of FOXM1 transcripts in the pull-down miRNA-mRNA complex. Knockdown of miR-134-5p increased FOXM1 expression whereas transfection with mimic miR-134-5p decreased FOXM1 protein expression. In summary, the involvement of an ACS-associated miRNA, miR-134-5p in endothelial dysfunction was demonstrated. Findings from this study could pave future investigations into utilizing miRNAs as a supplementary tool in ACS diagnosis or as targets for the development of therapeutics.

动脉粥样硬化性心血管疾病是全球发病率和死亡率的主要原因。在我们之前的研究中,包括 miR-134-5p 在内的一组 miRNA 在年轻的急性冠状动脉综合征(ACS)患者中出现了失调。然而,这些与急性冠状动脉综合征相关的 miRNA 在动脉粥样硬化前的早期事件--内皮功能障碍中的作用仍有待研究。在本研究中,用 7-酮胆固醇(7-KC)处理人主动脉内皮细胞(HAECs)以诱导内皮功能障碍。用 20 μg/ml 7-KC 处理后,miR-134-5p 明显上调,内皮一氧化氮合酶(eNOS)的表达受到抑制。内皮屏障的破坏表现为粘附分子的失调,包括局灶粘附激酶(FAK)的激活、VE-cadherin 的下调、粘附分子(E-选择素和 ICAM-1)的上调、炎症基因(IL1B、IL6 和 COX2)表达的增加以及 AKT 的激活。在 7-KC 处理的 HAECs 中敲除 miR-134-5p 可减轻 eNOS 的抑制、AKT 的激活、VE-cadherin 的下调和 E-selectin 的上调。此外,miR-134-5p 与 FOXM1 mRNA 之间的相互作用通过 FOXM1 转录物在拉取 miRNA-mRNA 复合物中的富集得到了证实。敲除 miR-134-5p 增加了 FOXM1 的表达,而转染模拟 miR-134-5p 则降低了 FOXM1 蛋白的表达。总之,研究证实了一种与 ACS 相关的 miRNA(miR-134-5p)参与了内皮功能障碍。这项研究的结果可为今后研究利用 miRNA 作为 ACS 诊断的辅助工具或作为开发治疗药物的靶点铺平道路。
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引用次数: 0
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