Biomedical Journal最新文献_第10页

The epidemiology of invasive fungal infections in transplant recipients 移植患者真菌感染的流行病学。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2024.100719

Dorra Elhaj Mahmoud , Anaïs Hérivaux , Florent Morio , Benoit Briard , Cécile Vigneau , Guillaume Desoubeaux , Jean-Philippe Bouchara , Jean-Pierre Gangneux , Gilles Nevez , Solène Le Gal , Nicolas Papon

Transplant patients, including solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, are exposed to various types of complications, particularly rejection. To prevent these outcomes, transplant recipients commonly receive long-term immunosuppressive regimens that in turn make them more susceptible to a wide array of infectious diseases, notably those caused by opportunistic pathogens. Among these, invasive fungal infections (IFIs) remain a major cause of mortality and morbidity in both SOT and HSCT recipients. Despite the continuing improvement in early diagnostics and treatments of IFIs, the management of these infections in transplant patients is still complicated. Here, we provide an overview concerning the most recent trends in the epidemiology of IFIs in SOT and HSCT recipients by describing the prominent yeast and mold species involved, the timing of post-transplant IFIs and the risk factors associated with their occurrence in these particularly weak populations. We also give special emphasis into basic research advances in the field that recently suggested a role of the global and long-term prophylactic regimen in orchestrating various biological disturbances in the organism and conditioning the emergence of the most adapted fungal strains to the particular physiological profiles of transplant patients.

移植患者，包括实体器官移植（SOT）和造血干细胞移植（HSCT）受者，会面临各种类型的并发症，尤其是排斥反应。为了预防这些后果，移植受者通常要接受长期的免疫抑制治疗，这反过来又使他们更容易感染各种传染病，尤其是由机会性病原体引起的传染病。其中，侵袭性真菌感染（IFI）仍然是导致SOT和造血干细胞移植受者死亡和发病的主要原因。尽管侵袭性真菌感染的早期诊断和治疗方法不断改进，但移植患者的感染管理仍然十分复杂。在此，我们概述了 SOT 和造血干细胞移植受者 IFI 流行病学的最新趋势，介绍了其中主要涉及的酵母和霉菌种类、移植后 IFI 的发生时间以及在这些特别脆弱的人群中发生 IFI 的相关风险因素。我们还特别强调了该领域的基础研究进展，这些研究最近提出，全面和长期的预防性治疗方案在协调机体内的各种生物紊乱和调节最适应移植患者特殊生理特征的真菌菌株的出现方面发挥了作用。

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引用次数: 0

The role of gut fungi in Clostridioides difficile infection 肠道真菌在艰难梭菌感染中的作用

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2023.100686

Lamei Wang , Yangchun Cao , Eddie Lou , Xuanyin Zhao , Xinhua Chen

Clostridioides difficile, the etiological agent of C. difficile infection (CDI), elicits a spectrum of diarrheal symptoms with varying severity and the potential to result in severe complications such as colonic perforation, pseudomembranous colitis, and toxic megacolon. The perturbation of gut microbiome, often triggered by antibiotic usage, represents the primary factor augmenting the risk of CDI. This underscores the significance of interactions between C. difficile and the microbiome in determining pathogen adaptability. In recent years, researchers have increasingly recognized the pivotal role played by intestinal microbiota in host health and its therapeutic potential as a target for medical interventions. While extensive evidence has been established regarding the involvement of gut bacteria in CDI, our understanding of symbiotic interactions between hosts and fungi within intestinal microbiota remains limited. Herein, we aim to comprehensively elucidate both composition and key characteristics of gut fungal communities that significantly contribute to CDI, thereby enhancing our comprehension from pharmacological and biomarker perspectives while exploring their prospective therapeutic applications for CDI.

难辨梭状芽孢杆菌是难辨梭状芽孢杆菌感染（CDI）的病原体，可引起一系列严重程度不同的腹泻症状，并可能导致结肠穿孔、假膜性结肠炎和中毒性巨结肠等严重并发症。肠道微生物群的紊乱通常由抗生素的使用引发，是增加 CDI 风险的主要因素。这凸显了艰难梭菌与微生物组之间的相互作用在决定病原体适应性方面的重要性。近年来，研究人员越来越认识到肠道微生物群在宿主健康中所起的关键作用及其作为医疗干预目标的治疗潜力。虽然已有大量证据表明肠道细菌参与了 CDI，但我们对宿主与真菌在肠道微生物群中的共生相互作用的了解仍然有限。在此，我们旨在全面阐明对 CDI 有重大影响的肠道真菌群落的组成和关键特征，从而从药理学和生物标志物的角度提高我们的理解能力，同时探索它们在 CDI 治疗中的应用前景。

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引用次数: 0

Unveiling the mycobiota: The fungal frontier of human health 揭开真菌生物群的神秘面纱：人类健康的真菌前沿。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2024.100751

Parvati Iyer , David M. Ojcius

The microbiota and its effect on health has been extensively studied over the past decade. In many studies, the term microbiota has become synonymous with the bacterial component of the microbiota. Other microbes in the microbiota, such as viruses and fungi, have been neglected until recently. This special issue provides some background on the mycobiota and explores the role of gut fungi in human diseases such as cancer, metabolic diseases, and infection by Clostridiodes difficile, and describes the incidence of fungal infections in transplant patients. The mycobiota, once overlooked, now garners increasing attention.

在过去十年中，人们对微生物群及其对健康的影响进行了广泛的研究。在许多研究中，微生物群一词已成为微生物群中细菌成分的同义词。微生物群中的其他微生物，如病毒和真菌，直到最近才被人们所忽视。本特刊介绍了真菌生物群的一些背景情况，探讨了肠道真菌在癌症、代谢性疾病、艰难梭菌感染等人类疾病中的作用，并介绍了移植患者真菌感染的发病率。真菌生物群曾一度被忽视，但现在却受到越来越多的关注。

引用次数: 0

Systemic treatments in pancreatic cancer: Taiwan pancreas society recommendation 胰腺癌的全身治疗：台湾胰脏学会建议

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2023.100696

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Over the past decade, significant therapeutic advancements have improved the survival rates of patients with pancreatic cancer. One of the primary factors contributing to these positive outcomes is the evolution of chemotherapy, from monotherapy to doublet or triplet regimens, and the integration of multimodal approaches. Additionally, targeted agents tailored to patients with specific genetic alterations and the development of cell therapies show promise in benefiting certain subpopulations. This article focuses on examining pivotal studies that explore the role of chemotherapy in neoadjuvant, adjuvant, maintenance, and salvage settings; highlights interesting findings related to cell therapy; and provides an overview of ongoing trials concerning metastatic settings. This review primarily aimed to offer recommendations based on therapeutic evidence, recent advancements in new treatment combinations, and the most innovative approaches. A unique aspect of this review is the inclusion of published papers on clinical trials and real-world data in Taiwan, thus adding a valuable perspective to the overall analysis.

胰腺癌是一种侵袭性很强的恶性肿瘤，预后很差。在过去十年中，治疗方面的重大进展提高了胰腺癌患者的生存率。促成这些积极结果的主要因素之一是化疗的发展，从单一疗法到双联或三联疗法，以及多模式方法的整合。此外，针对具有特定基因改变的患者量身定制的靶向药物以及细胞疗法的发展也为某些亚群患者带来了希望。本文重点探讨了探索化疗在新辅助治疗、辅助治疗、维持治疗和挽救治疗中的作用的关键性研究；重点介绍了与细胞疗法有关的有趣发现；并概述了正在进行的有关转移性治疗的试验。本综述的主要目的是根据治疗证据、新治疗组合的最新进展以及最具创新性的方法提出建议。本综述的一个独特之处在于纳入了台湾已发表的临床试验论文和实际数据，从而为整体分析增添了宝贵的视角。

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引用次数: 0

Intercellular transfer of MHC molecules in T cell alloimmunity and allotransplantation T 细胞异体免疫和同种异体移植中的 MHC 分子细胞间转移。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-05-25 DOI: 10.1016/j.bj.2024.100749

After transplantation of allogeneic tissues and organs, recognition by recipient T cells of donor MHC molecules initiates the pro-inflammatory adaptive immune response leading to allograft rejection. T cell allorecognition has long been known to be mediated via two distinct pathways: the direct pathway in which T cells recognize intact allogeneic MHC molecules displayed on donor cells and the indirect pathway whereby T cells recognize donor MHC peptides processed and presented by recipient antigen-presenting cells (APCs). It is believed that direct allorecognition is the driving force behind early acute allograft rejection while indirect allorecognition is involved in chronic allograft rejection, a progressive condition characterized by graft vasculopathy and tissue fibrosis. Recently, we and others have reported that after transplantation of allogeneic skin and organs, donor MHC molecules are transferred from donor cells to the host's APCs via trogocytosis or extracellular vesicles. Recipient APCs having captured donor MHC molecules can either present them to T cells in their intact form on their surface (semi-direct pathway) or the form of peptides bound to self-MHC molecules (indirect pathway). The present article provides an overview of recent studies evaluating the role of intercellular exchange of MHC molecules in T cell alloimmunity and its contribution to allograft rejection and tolerance.

异体组织和器官移植后，受体 T 细胞对供体 MHC 分子的识别会引发促炎性适应性免疫反应，导致异体移植排斥反应。长期以来，人们一直知道 T 细胞异体识别是通过两种不同的途径介导的：一种是直接途径，即 T 细胞识别供体细胞上显示的完整异体 MHC 分子；另一种是间接途径，即 T 细胞识别由受体抗原递呈细胞（APCs）处理和递呈的供体 MHC 肽。据认为，直接异体识别是早期急性异体移植排斥反应的驱动力，而间接异体识别则参与慢性异体移植排斥反应，这是一种以移植物血管病变和组织纤维化为特征的渐进性疾病。最近，我们和其他人报告说，异体皮肤和器官移植后，供体 MHC 分子会通过逆行细胞吞噬或细胞外囊泡从供体细胞转移到宿主的 APC。俘获了供体 MHC 分子的受体 APC 可将这些分子以完整形式（半直接途径）或与自身 MHC 分子结合的肽形式（间接途径）呈现给 T 细胞。本文概述了最近对细胞间交换 MHC 分子在 T 细胞异体免疫中的作用及其对异体移植物排斥和耐受的贡献进行评估的研究。

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引用次数: 0

Diagnostic Accuracy of Transthoracic Echocardiography for Acute Type A Aortic Syndrome: A Systematic Review and Meta-Analysis. 经胸超声心动图对急性 A 型主动脉综合征的诊断准确性：系统回顾与元分析》。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-05-10 DOI: 10.1016/j.bj.2024.100747

Hsin-Tzu Yeh, Sz-Wei Lu, Tzu-Heng Cheng, Jian-Xun Lu, Chien-Han Hsiao, Chieh-Ching Yen

Background: Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS.

Methods: We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio [1], and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria.

Results: Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38-76%) and 94% (95% CI, 89-97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85-94%) and 74% (95% CI, 61-84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)] in four studies.

Conclusions: Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.

背景：经胸超声心动图（TTE）目前被认为是疑似急性 A 型主动脉综合征（AAAS）患者的潜在一线成像检查。如果两个主动脉管腔之间有内膜瓣分隔，或在升主动脉看到主动脉壁增厚，则检测 AAAS 的直接 TTE 征象为阳性。间接 TTE 征象显示 AAAS 的高风险特征，如主动脉根部扩张、心包积液和主动脉瓣反流。我们的目的是总结有关 TTE 诊断准确性的现有临床证据，并评估其在疑似 AAAS 患者管理中的潜在作用：我们从 PubMed、EMBASE、MEDLINE 和 Cochrane 图书馆等数据库中纳入了以任何语言撰写的前瞻性或回顾性诊断队列研究，这些研究特别关注使用 TTE 诊断 AAAS。我们计算了 TTE 诊断 AAAS 的集合敏感性、特异性、阳性似然比 (PLR)、阴性似然比 (NLR)、诊断几率比 [1] 和分层汇总接收者操作特征曲线 (HSROC)。我们应用了诊断准确性质量评估（QUADAS-2）工具和推荐、评估、发展和评价分级（GRADE）质量评估标准：10项研究（2886名患者）被纳入荟萃分析。直接 TTE 征兆的汇总灵敏度和特异性分别为 58%（95% CI，38-76%）和 94%（95% CI，89-97%）。对于任何 TTE 征象，汇总的敏感性和特异性分别为 91%（95% CI，85-94%）和 74%（95% CI，61-84%）。四项研究的 HSROC 曲线下面积[0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)]显示，直接 TTE 征象的诊断准确性明显高于任何 TTE 征象：我们的研究表明，TTE 可作为疑似 AAAS 患者的初始影像学检查。鉴于其特异性较高，出现直接的 TTE 征象可能预示着 AAAS 的存在，而没有任何 TTE 征象，再加上临床怀疑度较低，则表明 AAAS 的可能性较低。

{"title":"Diagnostic Accuracy of Transthoracic Echocardiography for Acute Type A Aortic Syndrome: A Systematic Review and Meta-Analysis.","authors":"Hsin-Tzu Yeh, Sz-Wei Lu, Tzu-Heng Cheng, Jian-Xun Lu, Chien-Han Hsiao, Chieh-Ching Yen","doi":"10.1016/j.bj.2024.100747","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100747","url":null,"abstract":"<p><strong>Background: </strong>Transthoracic echocardiography (TTE) is currently recognized as the potential first-line imaging test for patients with suspected acute type A aortic syndrome (AAAS). Direct TTE sign for detecting AAAS is positive if there is an intimal flap separating two aortic lumens or aortic wall thickening seen in the ascending aorta. Indirect TTE sign indicates high-risk features of AAAS, such as aortic root dilatation, pericardial effusion, and aortic regurgitation. Our aim is to summarize the existing clinical evidence regarding the diagnostic accuracy of TTE and to evaluate its potential role in the management of patients with suspected AAAS.</p><p><strong>Methods: </strong>We included prospective or retrospective diagnostic cohort studies, written in any language, that specifically focused on using TTE to diagnose AAAS from databases such as PubMed, EMBASE, MEDLINE, and the Cochrane Library. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio [1], and hierarchical summary receiver-operating characteristic (HSROC) curve were calculated for TTE in diagnosing AAAS. We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria.</p><p><strong>Results: </strong>Ten studies (2886 patients) were included in the meta-analysis. The pooled sensitivity and specificity of direct TTE signs were 58% (95% CI, 38-76%) and 94% (95% CI, 89-97%). For any TTE signs, the pooled sensitivity and specificity were 91% (95% CI, 85-94%) and 74% (95% CI, 61-84%). The diagnostic accuracy of direct TTE signs was significantly higher than that of any TTE signs, as measured by the area under the HSROC curve [0.95 (95% CI, 0.92-0.96) vs. 0.87 (95% CI, 0.84-0.90)] in four studies.</p><p><strong>Conclusions: </strong>Our study suggests that TTE could serve as the initial imaging test for patients with suspected AAAS. Given its high specificity, the presence of direct TTE signs may indicate AAAS, whereas the absence of any TTE signs, combined with low clinical suspicion, could suggest a lower likelihood of AAAS.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100747"},"PeriodicalIF":5.5,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Charting new territory: The Plasmodium falciparum tRNA modification landscape. 开拓新领域：恶性疟原虫 tRNA 修饰景观。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-05-09 DOI: 10.1016/j.bj.2024.100745

Benjamin Sian Teck Lee, Ameya Sinha, Peter Dedon, Peter Preiser

Ribonucleoside modifications comprising the epitranscriptome are present in all organisms and all forms of RNA, including mRNA, rRNA and tRNA, the three major RNA components of the translational machinery. Of these, tRNA is the most heavily modified and the tRNA epitranscriptome has the greatest diversity of modifications. In addition to their roles in tRNA biogenesis, quality control, structure, cleavage, and codon recognition, tRNA modifications have been shown to regulate gene expression post-transcriptionally in prokaryotes and eukaryotes, including humans. However, studies investigating the impact of tRNA modifications on gene expression in the malaria parasite Plasmodium falciparum are currently scarce. Current evidence shows that the parasite has a limited capacity for transcriptional control, which points to a heavier reliance on strategies for posttranscriptional regulation such as tRNA epitranscriptome reprogramming. This review addresses the known functions of tRNA modifications in the biology of P. falciparum while highlighting the potential therapeutic opportunities and the value of using P. falciparum as a model organism for addressing several open questions related to the tRNA epitranscriptome.

构成表转录组的核糖核苷修饰存在于所有生物体和所有形式的 RNA 中，包括 mRNA、rRNA 和 tRNA，它们是翻译机制的三大 RNA 组成部分。其中，tRNA 的修饰程度最高，tRNA 表转录组的修饰多样性也最大。除了在 tRNA 的生物发生、质量控制、结构、裂解和密码子识别等方面发挥作用外，tRNA 修饰还被证明可在原核生物和真核生物（包括人类）中转录后调控基因表达。然而，目前很少有研究调查 tRNA 修饰对恶性疟原虫基因表达的影响。目前的证据表明，寄生虫的转录调控能力有限，因此更依赖于转录后调控策略，如 tRNA 表转录组的重编程。本综述探讨了 tRNA 修饰在恶性疟原虫生物学中的已知功能，同时强调了潜在的治疗机会，以及将恶性疟原虫作为模式生物来解决与 tRNA 表转录组相关的几个未决问题的价值。

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引用次数: 0

Antrodia cinnamomea extract alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting the mTOR pathway 蚂蚁肉桂提取物通过抑制mTOR途径减轻博莱霉素诱导的小鼠肺纤维化。

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100720

Background

Pulmonary fibrosis is a progressive diffuse parenchymal lung disorder with a high mortality rate. Studies have indicated that injured lung tissues release various pro-inflammatory factors, and produce a large amount of nitric oxide. There is also accumulation of collagen and oxidative stress-induced injury, collectively leading to pulmonary fibrosis. Antrodia cinnamomea is an endemic fungal growth in Taiwan, and its fermented extracts exert anti-inflammatory effects to alleviate liver damages. Hence, we hypothesized and tested the feasibility of using A. cinnamomea extracts for treatment of pulmonary fibrosis.

Methods

The TGF-β1-induced human lung fibroblast cells (MRC-5) in vitro cell assay were used to evaluate the effects of A. cinnamomea extracts on the collagen production in MRC-5. Eight-week-old ICR mice were intratracheally administered bleomycin and then fed with an A. cinnamomea extract on day 3 post-administration of bleomycin. At day 21 post-bleomycin administration, the pulmonary functional test, the expression level of inflammation- and fibrosis-related genes in the lung tissue, and the histopathological change were examined.

Results

The A. cinnamomea extract significantly attenuated the expression level of collagen in the TGF-β1-induced MRC-5 cells. In the A. cinnamome-treated bleomycin-induced lung fibrotic mice, the bodyweight increased, pulmonary functions improved, the lung tissues expression level of inflammatory factor and the fibrotic indicator were decreased, and the histopathological results showed the reduction of thickening of the inter-alveolar septa.

Conclusions

The Antrodia cinnamomea extract significant protects mice against bleomycin-induced lung injuries through improvement of body weight gain and lung functions, and attenuation of expression of inflammatory and fibrotic indicators.

背景：肺纤维化是一种进行性弥漫性肺实质疾病，死亡率很高。研究表明，损伤的肺组织会释放各种促炎因子，并产生大量一氧化氮。此外，胶原蛋白的积累和氧化应激引起的损伤共同导致了肺纤维化。肉桂蕨是台湾特有的真菌，其发酵提取物具有抗炎作用，可减轻肝损伤。因此，我们假设并测试了使用肉桂提取物治疗肺纤维化的可行性：方法：采用TGF-β1诱导的人肺成纤维细胞（MRC-5）体外细胞试验，评估肉桂提取物对MRC-5胶原蛋白生成的影响。对 8 周大的 ICR 小鼠气管内注射博莱霉素，然后在注射博莱霉素后的第 3 天喂食肉桂萃取物。在使用博莱霉素后第 21 天，检测肺功能测试、肺组织中炎症和纤维化相关基因的表达水平以及组织病理学变化：结果：肉桂提取物能显著降低TGF-β1诱导的MRC-5细胞中胶原蛋白的表达水平。肉桂提取物治疗博莱霉素诱导的肺纤维化小鼠体重增加，肺功能改善，肺组织炎症因子和纤维化指标表达水平降低，组织病理学结果显示肺泡间质增厚减轻：结论：肉桂酸蚂蚁提取物能显著保护小鼠免受博莱霉素诱导的肺损伤，改善小鼠的体重增加和肺功能，减少炎症和纤维化指标的表达。

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引用次数: 0

Pharmaceutical cost savings from the treatment of oncology patients in clinical trials. 临床试验中治疗肿瘤患者节省的医药成本。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-26 DOI: 10.1016/j.bj.2024.100742

Borja Gómez Mediavilla, Paloma Lanza León, Virginia Martínez Callejo, David Cantarero Prieto, María Lanza Postigo, Matilde Salcedo Lambea, Yolanda Blanco Mesonero, María Ochagavia Sufrategui, Ignacio Durán, Carmen María Sarabia Cobo

Objective: The aim of this study was twofold: to assess the annual pharmaceutical savings associated with the treatment of cancer patients at Marqués de Valdecilla University Hospital and to estimate the cost of innovative antineoplastic therapies that patients receive as experimental treatment, both during clinical trials throughout 2020.

Material and methods: An observational and financial analysis of the drug cost related to clinical trials was applied. Direct cost savings to the Regional Health System of Cantabria and the cost of innovative therapies used as an experimental treatment in clinical trials were quantified.

Results: This study includes 38 clinical trials with a sample of 101 patients. The clinical trials analyzed provide a total cost savings of €603,350.21 and an average cost saving of €6,630.22 per patient. Furthermore, the total investment amounts to €789,892.67, with an average investment of €15,488.09 per patient.

Conclusions: Clinical trials are essential for the advancement of science. Furthermore, clinical trials can be a significant source of income for both hospitals and Regional Health Systems, contributing to their financial sustainability.

目的：这项研究有两个目的：评估巴尔德西亚侯爵大学医院每年在治疗癌症患者方面节省的药品费用；估算患者在 2020 年临床试验期间作为试验性治疗接受创新抗肿瘤疗法的费用：对与临床试验相关的药物成本进行了观察和财务分析。对坎塔布里亚地区卫生系统直接节省的费用和临床试验中作为试验性治疗的创新疗法的费用进行了量化：这项研究包括38项临床试验，样本为101名患者。所分析的临床试验共节约成本603,350.21欧元，平均每位患者节约成本6,630.22欧元。此外，总投资额为 789,892.67 欧元，每位患者平均投资额为 15,488.09 欧元：临床试验对科学进步至关重要。此外，临床试验还是医院和地区医疗系统的重要收入来源，有助于其财务可持续性。

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引用次数: 0

m⁶A landscape is more pervasive when Trypanosoma brucei exits the cell cycle. 当布氏锥虫退出细胞周期时，m6A 的分布更为普遍。

IF 5.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomedical Journal

Pub Date : 2024-04-17 DOI: 10.1016/j.bj.2024.100728

Lúcia Serra, Sara Silva Pereira, Idálio J Viegas, Henrique Machado, Lara López-Escobar, Luisa M Figueiredo

N6-methyladenosine (m⁶A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m⁶A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m⁶A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative). We found that 1037 transcripts are methylated in at least one of these three life cycle stages. While 21% of methylated transcripts are common in the three stages of the life cycle, globally each stage has a distinct methylome. Interestingly, 47% of methylated transcripts are detected in the quiescent stumpy form only, suggesting a critical role for m⁶A when parasites exit the cell cycle and prepare for transmission by the Tsetse fly. In this stage, we found that a significant proportion of methylated transcripts encodes for proteins involved in RNA metabolism, which is consistent with their reduced transcription and translation. Moreover, we found that not all major surface proteins are regulated by m⁶A, as procyclins are not methylated, and that, within the VSG repertoire, not all VSG transcripts are demethylated upon parasite differentiation to procyclic form. This study reveals that the m⁶A regulatory landscape is specific to each life cycle stage, becoming more pervasive as T. brucei exits the cell cycle.

N6-甲基腺苷（m6A）是一种在基因表达中起重要作用的 mRNA 修饰。在非洲锥虫中，这种转录后修饰可在数百个转录本中检测到，而且会影响增殖血流形态中变异表面糖蛋白（VSG）转录本的稳定性。然而，m6A 在整个生命周期中的变化情况仍不十分明确。我们使用全长、非碎裂的 RNA，对布氏锥虫三个生命周期阶段--纤细型（增殖型）、粗壮型（静止型）和原环状型（增殖型）--的 m6A 修饰转录本进行了免疫沉淀和测序。我们发现，有 1037 个转录本在这三个生命周期阶段中至少有一个阶段被甲基化。虽然 21% 的甲基化转录本在生命周期的三个阶段中很常见，但总体而言，每个阶段都有一个独特的甲基化组。有趣的是，47%的甲基化转录本仅在静止期的残体中被检测到，这表明当寄生虫退出细胞周期并准备被采采蝇传播时，m6A 起着关键作用。在这一阶段，我们发现相当一部分甲基化转录本编码参与 RNA 代谢的蛋白质，这与它们的转录和翻译减少是一致的。此外，我们还发现并非所有主要的表面蛋白都受 m6A 的调控，因为原环蛋白并没有被甲基化，而且在 VSG 基因库中，并非所有的 VSG 转录本都会在寄生虫分化为原环形态时被去甲基化。这项研究揭示了 m6A 的调控格局是每个生命周期阶段所特有的，随着布氏原虫退出细胞周期而变得更加普遍。

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