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The synergy of 177Lu-FAPI-46 with tyrosine kinase inhibitor in a sarcoma patient-derived xenograft mouse model 肉瘤患者异种移植小鼠模型中 177Lu-FAPI-046 与酪氨酸激酶抑制剂的协同作用
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2024.100744
Jing-Ren Tseng , Cheng-Lung Hsu , Hsin-Hua Hsieh , Kung-Chu Ho , Yi-Hsiu Chung , Chun-Yi Wu

Background

Given the heterogeneity and high mortality associated with metastatic soft tissue sarcoma, this study aims to evaluate the therapeutic efficacy of combining 177Lu-FAPI-46 with Pazopanib against this malignancy.

Methods

Patient-derived xenograft (PDX)-bearing mice were randomly divided into three groups: the control group, the 177Lu-FAPI-46 monotherapy group, and the 177Lu-FAPI-46 combined with Pazopanib therapy group. Therapeutic efficacy was regularly monitored.

Results

The microPET imaging showed a 0.84-fold decrease in the T/M ratio of 68Ga-FAPI-46 on day 7/8 post combination therapy, while the control group exhibited a 1.23-fold increase. Combination therapy significantly inhibited tumor proliferation, as evidenced by reduced Ki-67 and increased caspase 3 expressions. Notably, there was no significant body weight loss observed in any group.

Conclusion

This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of 177Lu-FAPI-46 with Pazopanib.

研究背景鉴于转移性软组织肉瘤的异质性和高死亡率,本研究旨在评估177Lu-FAPI-46与帕唑帕尼联合治疗该恶性肿瘤的疗效:患者异种移植(PDX)小鼠随机分为三组:对照组、177Lu-FAPI-46 单药治疗组和 177Lu-FAPI-46 联合帕唑帕尼治疗组。定期监测疗效:结果:microPET成像显示,联合治疗后第7/8天,68Ga-FAPI-46的T/M比值下降了0.84倍,而对照组则上升了1.23倍。联合疗法明显抑制了肿瘤的增殖,Ki-67的减少和caspase 3的增加都证明了这一点。值得注意的是,各组均未观察到明显的体重下降:本研究成功证明了 177Lu-FAPI-46 与帕唑帕尼联合治疗后,肉瘤 PDX 中 FAP 表达的减少和肿瘤体积的抑制。
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引用次数: 0
The next generation of healthcare ecosystem in the metaverse 元宇宙中的下一代医疗保健生态系统。
IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-01 DOI: 10.1016/j.bj.2023.100679
Yong Li , Dinesh Visva Gunasekeran , Narrendar RaviChandran , Ting Fang Tan , Jasmine Chiat Ling Ong , Arun James Thirunavukarasu , Bryce W. Polascik , Ranya Habash , Khizer Khaderi , Daniel S.W. Ting

The Metaverse has gained wide attention for being the application interface for the next generation of Internet. The potential of the Metaverse is growing, as Web 3·0 development and adoption continues to advance medicine and healthcare. We define the next generation of interoperable healthcare ecosystem in the Metaverse. We examine the existing literature regarding the Metaverse, explain the technology framework to deliver an immersive experience, along with a technical comparison of legacy and novel Metaverse platforms that are publicly released and in active use. The potential applications of different features of the Metaverse, including avatar-based meetings, immersive simulations, and social interactions are examined with different roles from patients to healthcare providers and healthcare organizations. Present challenges in the development of the Metaverse healthcare ecosystem are discussed, along with potential solutions including capabilities requiring technological innovation, use cases requiring regulatory supervision, and sound governance. This proposed concept and framework of the Metaverse could potentially redefine the traditional healthcare system and enhance digital transformation in healthcare. Similar to AI technology at the beginning of this decade, real-world development and implementation of these capabilities are relatively nascent. Further pragmatic research is needed for the development of an interoperable healthcare ecosystem in the Metaverse.

作为下一代Internet的应用程序接口,Metaverse获得了广泛的关注。随着Web 3.0的开发和采用继续推动医学和医疗保健的发展,Metaverse的潜力正在不断增长。我们在Metaverse中定义下一代可互操作的医疗保健生态系统。我们研究了有关Metaverse的现有文献,解释了提供沉浸式体验的技术框架,以及公开发布和积极使用的传统和新型Metaverse平台的技术比较。Metaverse的不同功能的潜在应用,包括基于虚拟化身的会议、沉浸式模拟和社会互动,研究了从患者到医疗保健提供者和医疗保健组织的不同角色。本文讨论了Metaverse医疗保健生态系统开发中的当前挑战,以及潜在的解决方案,包括需要技术创新的功能、需要监管监督的用例和健全的治理。这个提出的概念和框架可能会重新定义传统的医疗保健系统,并加强医疗保健领域的数字化转型。与本世纪初的人工智能技术类似,这些能力在现实世界的开发和实施相对来说还处于起步阶段。在Metaverse中开发可互操作的医疗保健生态系统需要进一步的实用研究。
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引用次数: 0
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 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 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 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。
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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 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 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 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。
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引用次数: 0
"Mpox in MSM: Tackling Stigma, Minimizing Risk Factors, Exploring Pathogenesis, and Treatment Approaches". "男男性行为者中的 Mpox:消除耻辱感、尽量减少风险因素、探索发病机制和治疗方法"。
IF 5.5 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-09 DOI: 10.1016/j.bj.2024.100746
Arpan Acharya, Narendra Kumar, Kamal Singh, Siddappa N Byrareddy

Mpox is a zoonotic disease caused by the monkeypox virus (MPV), primarily found in Central and West African countries. The typical presentation of the disease before the 2022 mpox outbreak includes a febrile prodrome 5-13 days post-exposure, accompanied by lymphadenopathy, malaise, headache, and muscle aches. Unexpectedly, during the 2022 outbreak, several cases of atypical presentations of the disease were reported, such as the absence of prodromal symptoms and the presence of genital skin lesions suggestive of sexual transmission. As per the World Health Organization (WHO), as of March 20, 2024, 94,707 cases of mpox were reported worldwide, resulting in 181 deaths (22 in African endemic regions and 159 in non-endemic countries). The United States Centers for Disease Control and Prevention (CDC) reports a total of 32,063 cases (33.85% of total cases globally), with 58 deaths (32.04% of global deaths) due to mpox. Person-to-person transmission of mpox can occur through respiratory droplets and sustained close contact. However, during the 2022 outbreak of mpox, a high incidence of anal and perianal lesions among MSMs indicated sexual transmission of MPV as a major route of transmission. Since MSMs are disproportionately at risk for HIV transmission, this review discusses the risk factors, transmission patterns, pathogenesis, vaccine, and treatment options for mpox among MSM and people living with HIV (PLWH). Furthermore, we provide a brief perspective on the evolution of the MPV in immunocompromised people like PLWH.

猴痘是一种由猴痘病毒(MPV)引起的人畜共患疾病,主要出现在中非和西非国家。在 2022 年猴痘疫情爆发前,该病的典型表现包括接触后 5-13 天的发热前驱症状,并伴有淋巴结病、乏力、头痛和肌肉酸痛。意想不到的是,在 2022 年疫情爆发期间,报告了几例非典型表现的病例,如无前驱症状和出现生殖器皮损提示性传播。据世界卫生组织(WHO)统计,截至 2024 年 3 月 20 日,全球共报告 94 707 例麻风腮病例,造成 181 人死亡(非洲流行地区 22 人,非流行国家 159 人)。美国疾病控制和预防中心(CDC)报告的天花病例总数为 32063 例(占全球病例总数的 33.85%),死亡 58 例(占全球死亡人数的 32.04%)。天花可通过呼吸道飞沫和持续密切接触进行人际传播。然而,在 2022 年爆发的天花疫情中,男男性行为者肛门和肛周病变的高发病率表明,MPV 的性传播是主要传播途径。由于男男性行为者感染艾滋病毒的风险过高,本综述将讨论男男性行为者和艾滋病毒感染者(PLWH)感染痘病的风险因素、传播模式、发病机制、疫苗和治疗方案。此外,我们还从一个简短的角度探讨了 MPV 在艾滋病毒感染者等免疫力低下人群中的演变。
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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 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
期刊
Biomedical Journal
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