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In vitro assessment of stearyl triphenyl phosphonium toxicity in drug-resistant tumor cells 硬脂酰三苯磷对耐药肿瘤细胞的体外毒性评价
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022003
Shrey Shah, Miller Ouellette, G. D’souza
Introduction: The triphenyl phosphonium residue is a well-documented mitochondriotropic that has been shown to improve the accumulation of biomolecules in mitochondria. Stearyl triphenyl phosphonium (STPP) modified liposomes have been shown to facilitate the selective accumulation of various biomolecules in mitochondria resulting in improved effect in-vitro and in-vivo. More recently, STPP was reported to have higher toxicity towards a drug resistant ovarian cancer cell line compare to a non-drug resistant cell line. The purpose of this study was to further investigate STPP toxicity using multiple drug resistant and non-drug resistant cell lines. Methods: STPP was incorporated into phosphatidylcholine cholesterol liposomes using the thin film hydration method. Mean particle size and zeta potential was measured using dynamic light scattering. The 5,5,6,6′-tetrachloro-1,1′,3,3′ tetraethylbenzimi-dazoylcarbocyanine iodide (JC-1) dye accumulation assay was used as an indicator of mitochondrial membrane potential in the tested cell lines. Cytotoxicity of the preparations towards different cell lines was determined using light microscopy and the CellTiter 96® AQueous One Solution Cell Proliferation assay. Results: The JC-1 accumulation assay confirmed that the drug-resistant cell lines had significantly higher dye accumulation than the non-drug resistant cell lines. Higher cytotoxicity of STPP towards drug resistant cell line was seen when incorporated into liposomes but not when dissolved in dimethyl sulfoxide (DMSO). STPP showed a comparable toxicity profile to the known oxidative phosphorylation uncoupler carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone (FCCP). Discussion: Taken together, the data suggest that higher STPP toxicity in the drug-resistant cell lines is influenced by the presence of liposomal lipids and that STPP acts in a way similar to an oxidative phosphorylation uncoupler and is therefore more toxic to the drug-resistant cells that rely on a higher mitochondrial membrane potential to maintain their viability.
简介:三苯基磷残基是一种有充分证据的线粒体亲和性物质,已被证明可以改善线粒体中生物分子的积累。硬脂酰三苯磷(STPP)修饰脂质体已被证明可以促进线粒体中各种生物分子的选择性积累,从而提高体外和体内的效果。最近,与非耐药细胞系相比,STPP对耐药卵巢癌细胞系具有更高的毒性。本研究的目的是利用多重耐药和非耐药细胞系进一步研究STPP的毒性。方法:采用薄膜水合法将STPP掺入磷脂酰胆碱胆固醇脂质体中。采用动态光散射法测定了平均粒径和zeta电位。采用5,5,6,6 ' -四氯-1,1 ',3,3 '四乙基苯并咪-dazoylcarbocyanine iodiine (JC-1)染色积累法测定线粒体膜电位。使用光镜和CellTiter 96®水溶液细胞增殖试验测定制剂对不同细胞系的细胞毒性。结果:JC-1积累试验证实,耐药细胞株的染色积累明显高于非耐药细胞株。在脂质体中掺入STPP对耐药细胞系具有更高的细胞毒性,而在二甲亚砜(DMSO)中溶解时则没有。STPP显示出与已知氧化磷酸化解耦剂羰基氰化物对三氟甲氧基苯基腙(FCCP)相当的毒性。讨论:综上所述,数据表明耐药细胞系中较高的STPP毒性受到脂质体脂质存在的影响,并且STPP的作用方式类似于氧化磷酸化解偶联剂,因此对依赖较高线粒体膜电位维持其生存能力的耐药细胞毒性更大。
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引用次数: 0
War against Ukraine: Humanitarian aid and how much morality can science bear 乌克兰战争:人道主义援助和科学能承受多少道德
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022012
Björn BLDM Brücher
An unprovoked war has impacted Ukraine. “Humanity and peace initiatives should have top priority now” [1]. The resulting outrage by the Western world together with a global alliance has imposed economic sanctions on Russia [2]. Though moral, the efficacy of economic sanctions are known to be limited as earlier shown by an empirical cross-national, time-series data analysis of 133 countries during the period from 1970 to 2005 [3]. The TheodorBillroth-Academy with its International Consortium of Research Excellence (INCORE) have so far in solidarity with the Ukraine and with scientists and Board members of 4open realized several projects for active humanitarian aid in a very short time [1]. This included medical transports to the Ukraine which were carried out by pro bono by Veterans from Germany through the Recondo Vets MMC Germany, Military Motorcycle Club (Fig. 1) and from Austria through the Green Knights, Military Motorcycle Club, Chapter 147, Austria as they work closely with the Territorial Defense Forces (of the Ukraine) (Biqcmra nepbnopiakmyoї o,opoyb) and the International Legion of Territorial Defense of Ukraine (Ukrainian Foreign Legion) (Iynepyawioyakmybq keuioy nepbnopiakmyoї o,opoyb Erpaїyb) to ensure that transports arrive where and when needed (Figs. 2–4). Furthermore, medical refugee students from the Kharkiv National Medical University (KNMU) and the Bogomolets National Medical University (NMU) were offered cost-free living along with a German language course, academic lecture and medical internship financed by the Carl-Thiem-Klinikum (CTK) in Cottbus, Germany. The TBA and INCORE continuously encourage (and demand) that European and German-speaking universities to set an example and open their doors to Ukrainian refugee medical students during the war so that they can have the opportunity to continue their studies. Finland on March 9, 2022 provided strong leadership in this regard [4]. So far, only one German University partially opened their doors as suggested, although the primary conditions will only be achievable by a minority of students because students need a valid Test for Medical Studies (TMS) result notification. Soon, Theodor Billroth’ lectures of various themes in science, education, training for students and physicians (independent of their level and stage of career), a project which originally was planned to be realized in 2023, will be realized soon (Fig. 5). This will be cross-linked by the support of 4open and EDP Sciences as increasingly students and physicians should actively be encouraged to publish their thesis also at no cost. Thus, the proposed scientific, humanitarian and peace initiatives of our colleagues provide Ukraine with much-needed assistance. Next to humanitarian aid, it is being demanded to expel Russian culture and science from the fine arts and science. Today’s science (and medicine) is changed from a compassion-based profession into a corporate-greed driven industry why halting and expelling o
一场无端战争影响了乌克兰。“现在应该把人道主义与和平倡议放在首位”[1]。由此引发的西方世界的愤怒和全球联盟对俄罗斯实施了经济制裁[2]。经济制裁虽然具有道德意义,但众所周知,其效果是有限的,正如之前对133个国家1970年至2005年期间的实证跨国时间序列数据分析所表明的那样[3]。到目前为止,西奥多·比尔罗斯学院及其国际卓越研究联盟(INCORE)与乌克兰以及4open的科学家和董事会成员团结一致,在很短的时间内实现了几个积极的人道主义援助项目[1]。这包括由德国退伍军人通过Recondo Vets MMC德国军事摩托车俱乐部(图1)和奥地利退伍军人通过绿色骑士军事摩托车俱乐部(第147章)无偿向乌克兰运送医疗物资。奥地利,因为他们与(乌克兰)领土防卫部队(Biqcmra nepbnopiakmyoturo,opoyb)和乌克兰国际领土防卫军团(乌克兰外籍军团)(Iynepyawioyakmybq keuioy nepbnopiakmyoturo,opoyb Erpaїyb)密切合作,以确保运输到达需要的地点和时间(图2-4)。此外,来自哈尔科夫国立医科大学和波戈莫雷茨国立医科大学的医疗难民学生获得免费生活,并获得德语课程、学术讲座和德国科特布斯卡尔-蒂姆-克里尼库姆资助的医疗实习。TBA和INCORE不断鼓励(并要求)欧洲和讲德语的大学树立榜样,在战争期间向乌克兰难民医科学生敞开大门,使他们有机会继续学习。芬兰于2022年3月9日在这方面发挥了强有力的领导作用[4]。到目前为止,只有一所德国大学按照建议部分开放了他们的大门,尽管只有少数学生才能达到基本条件,因为学生需要有效的医学研究测试(TMS)结果通知。很快,Theodor Billroth的科学、教育、学生和医生培训(与他们的职业水平和阶段无关)等各种主题的讲座将很快实现(图5),这个项目原本计划在2023年实现。这将在4open和EDP Sciences的支持下交叉链接,因为应该积极鼓励越来越多的学生和医生也免费发表他们的论文。因此,我们的同事提出的科学、人道主义和和平倡议为乌克兰提供了急需的援助。除了人道主义援助外,还要求将俄罗斯文化和科学从美术和科学领域驱逐出去。今天的科学(和医学)从一个以同情为基础的职业变成了一个由企业贪婪驱动的行业,为什么停止和驱逐与经济相关的科学被视为人道主义援助的行为。然而,文化和科学需要独立,不应该成为武器。无论是文化[5]还是科学都没有阻止任何暴力或战争,这表明这种要求更多地是与明显的过度自信相对应,而是反映了一种乌托邦理想主义。文化或科学能与政治完全分离吗?不,因为两者都是经济因素。科学有力量,有力量就有责任,在对抗乌克兰的战争中,沉默也不是一种选择[6]。许多各行各业的俄罗斯人都反对这场战争,尽管这意味着被政府视为威胁[7-9]。当然,也有一些俄罗斯科学家支持这场战争[10],这清楚地揭示了民族主义观点滥用了极权主义政权中常见的爱国主义一词。然而,欧洲大学协会(EUA)直接暂停了14所俄罗斯大学的成员资格,这些大学的领导人签署了支持战争的声明[11]。许多国家的政府要求他们的大学停止学术(政府资助的)合作或*通讯作者:b-bruecher@gmx.de
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引用次数: 0
Interconnection of severe obesity, gastric intestinal metaplasia, gastric cancer, bariatric surgery and the necessity of preoperative endoscopy 重度肥胖、胃肠化生、胃癌、减肥手术与术前内镜必要性的联系
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022019
M. Kermansaravi, R. Valizadeh, Behnood Farazmand
Obesity is a growing challenge around the globe accounting for approximately 1.7 billion adults with reduced life expectancy of 5–20 years and these patients are at greater risk for various cancers. Bariatric surgery is one efficient an approved treatment of severe obesity for losing weight and to decrease associated health complications. Besides correct indications and contraindications as well as the various risks of individual bariatric surgical procedures, many more variables influence decision-makings, such as patient’s family history of diseases, as well as individual patient-specific factors, patient and family socioeconomic and nutrition status, and professionalism of a bariatric surgical unit and the presence of intestinal metaplasia that is the replacement of columnar epithelial cells by intestinal architecture and morphology. Patients with severe obesity undergoing esophagogastroduodenoscopy (EGD) and biopsy prior to bariatric surgery may present with gastric IM because regular follow-up to early diagnosis of any subsequent pathological changes is necessary and reveals the importance of addressing interconnections between pre-existing conditions and outcomes. However, there is currently no unified recommendation about preoperative EGD before bariatric surgery. With this short review, we point out the necessary knowledge that undermines why the responsibility for a patient with severe obesity cannot be divided across various disciplines, and why we recommend that EGD always be performed preoperatively.
肥胖在全球范围内是一个日益严峻的挑战,约有17亿成年人的预期寿命缩短了5-20年,这些患者患各种癌症的风险更大。减肥手术是一种有效的治疗严重肥胖的方法,可以减轻体重,减少相关的健康并发症。除了正确的适应症和禁忌症以及个体减肥手术的各种风险外,还有许多变量影响决策,例如患者的家族史,以及个体患者特有的因素,患者和家庭的社会经济和营养状况。以及减肥手术单位的专业性以及肠化生的存在这是肠道结构和形态对柱状上皮细胞的替代。重度肥胖患者在减肥手术前进行食管胃十二指肠镜检查(EGD)和活检可能会出现胃IM,因为有必要定期随访以早期诊断任何后续病理变化,并揭示了解决已有疾病与结果之间相互联系的重要性。然而,对于减肥手术前的术前EGD,目前还没有统一的建议。通过这篇简短的综述,我们指出了必要的知识,这些知识破坏了为什么对严重肥胖患者的责任不能跨学科划分,以及为什么我们建议总是在术前进行EGD。
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引用次数: 0
Membraneless physiology of the living cell. The past and the present 活细胞的无膜生理学过去和现在
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022013
Vladimir Vasilievich Matveev
Since the 1880s, the concept of compartmentalizing through membranes has taken a firm place in cell physiology and has defined the objects, methods, and goals of physiologists’ research for decades. A huge mass of biologists know about the important role of intra-membrane pumps, channels, and lipids, and various hypotheses about the origin of life often begin with explanations about how the lipid membrane occurred, without which it is impossible to imagine the origin of a living cell. Against this background, there was a dissonance of statements that there are membraneless organelles in the cell, the functions of which are rapidly expanding under our eyes. Physically, they are similar to coacervate droplets, which from time to time were used to explain the origin of life, and now the coacervates are being more and more often discussed when describing the physics of the nucleus and cytoplasm of modern cells. However, ideas about the coacervate nature of cytoplasm/protoplasm originated in the first half of the 19th Century, when the contents of cells were likened to jelly, but this approach gradually faded into the shadows. Nevertheless, limited research in this area continued and was completed in the form of a membraneless cell physiology. Now that the focus of attention has turned to membraneless compartmentalization, it’s time to remember the past. The sorption properties of proteins are the physical basis of membraneless cell because of water adsorbed by proteins changes the physical state of any biomolecular system, from supramolecular and subcellular structures to the cell as a whole. A thermodynamic aqueous phase is formed because adsorbed water does not mix with ordinary water and, in this cause, is separated from the surrounding solution in the form of a compartment. This article discusses the fundamental physical properties of such a phase – a biophase. As it turned out, the Meyer–Overton rule, which led to the idea of a lipid membrane, also applies to membraneless condensates.
自19世纪80年代以来,通过膜进行区隔的概念在细胞生理学中占据了稳固的地位,并定义了几十年来生理学家研究的对象、方法和目标。大量的生物学家都知道膜内泵、通道和脂质的重要作用,关于生命起源的各种假设通常都是从解释脂质膜如何发生开始的,没有脂质膜就不可能想象活细胞的起源。在这种背景下,有一种说法是不一致的,即细胞中有无膜细胞器,其功能在我们的眼睛下迅速扩展。在物理上,它们类似于聚簇状液滴,聚簇状液滴有时被用来解释生命的起源,现在聚簇状液滴在描述现代细胞的细胞核和细胞质的物理特性时越来越经常被讨论。然而,关于细胞质/原生质凝聚性的想法起源于19世纪上半叶,当时细胞的内容物被比作果冻,但这种方法逐渐消失在阴影中。然而,这一领域的有限研究仍在继续,并以无膜细胞生理学的形式完成。现在注意力的焦点已经转向无膜区隔化,是时候记住过去了。蛋白质的吸附特性是无膜细胞的物理基础,因为蛋白质吸附的水改变了任何生物分子系统的物理状态,从超分子和亚细胞结构到整个细胞。热力学水相的形成是因为被吸附的水不与普通的水混合,在这个原因中,水以隔室的形式与周围的溶液分离。本文讨论了这种相——生物相的基本物理性质。事实证明,导致脂质膜概念的Meyer-Overton规则也适用于无膜冷凝物。
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引用次数: 2
Biomarker assessment in urgent surgical pathology of the small bowel: case-control analysis of a retrospective database 小肠紧急手术病理中的生物标志物评估:回顾性数据库的病例对照分析
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022014
Kryvoruchko Ia, T. Briukhanova, O. Nakonechna, O. S. Olefir
Background: Small bowel obstruction, mesenteric thrombosis, and strangulated ventral hernia area a challenge in emergency abdominal surgery. This study aimed to evaluate biomarkers of damage to the digestive tract in patients with urgent pathology. Materials and methods: The study involved 71 patients aged 18 to 80 years who were hospitalized in the intensive care unit in the immediate postoperative period. Results: All 71 underwent emergency surgery, 27 with small bowel necrosis. Lactate level area under curve (AUC = 0.964), C-reactive protein (AUC = 0.805) and systolic blood pressure (area under curve, AUC = 0.803) on the context of Sequential Organ Failure Assessment (SOFA) score (AUC = 0.880) showed stratification of patients with complications before surgery. Small bowel necrosis patients revealed an increase in primary thiobarbituric acid (TBA) reactive products (AUC = 0.813) lipid peroxidation products, and a decrease in superoxide dismutase activity (AUC = 0.818) and catalase (AUC = 0.804). Wide variability of intestinal fatty-acid binding protein (I-FABP) from 199.8 to 2189.6 pg/mL were observed in all patients studied, with an AUC = 0.814 in small intestinal necrosis. Conclusion: Surgical pathology of the small intestine due to obstruction of various origina, mesenteric thrombosis, and strangulated ventral hernia pronounced revealed disorders of the antioxidant-prooxidant balance. This was expressed by an increase in lipid peroxidation products, and the level of TBA-reactive products, and the activities of superoxide dismutase (SOD), and catalase. Viewed against the background of an increase in I-FABP above 577 pg/mL, these variables were the most significant indicators of small intestinal necrosis.
背景:小肠梗阻、肠系膜血栓形成和腹部绞窄疝区是急诊腹部手术的一个挑战。本研究旨在评估急性病患者消化道损伤的生物标志物。材料和方法:本研究纳入71例年龄在18 ~ 80岁之间的患者,这些患者在术后立即在重症监护病房住院。结果:71例均行急诊手术,其中27例发生小肠坏死。在顺序器官衰竭评价(SOFA)评分(AUC = 0.880)背景下,乳酸水平曲线下面积(AUC = 0.964)、c反应蛋白(AUC = 0.805)和收缩压(曲线下面积,AUC = 0.803)显示术前并发症患者的分层。小肠坏死患者原发性硫代巴比妥酸(TBA)反应产物(AUC = 0.813)脂质过氧化产物(AUC = 0.813)升高,超氧化物歧化酶(AUC = 0.818)和过氧化氢酶(AUC = 0.804)降低。小肠脂肪酸结合蛋白(I-FABP)在199.8 ~ 2189.6 pg/mL之间变化很大,小肠坏死的AUC = 0.814。结论:小肠各种来源梗阻、肠系膜血栓形成、绞窄性腹疝的手术病理表现为抗氧化-促氧化平衡紊乱。这表现为脂质过氧化产物、tba反应产物水平、超氧化物歧化酶(SOD)和过氧化氢酶活性的增加。在I-FABP高于577 pg/mL的背景下,这些变量是小肠坏死的最重要指标。
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引用次数: 0
Realtime, continuous assessment of complex-mixture protease and protease inhibitor activity 实时,连续评估复杂混合物蛋白酶和蛋白酶抑制剂的活性
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022010
Sarah-Ellen Leonard, P. Kenis, Ray C. Perkins
Recently the treatment PAXLOVID™ (nirmatrelvir co-packaged with ritonavir) was authorized for use as a treatment for COVID-19. The presumed mechanism of action of the treatment, an inhibitor of a Sars-Cov-2 “3CL” protease, continues decades-long interest in viral protease inhibition in the fight against pathogenic viruses (e.g., HIV protease inhibitors). Proteolysis assay methods vary widely, roughly bounded by interrogation of basic biochemistry and high-throughput, early-stage drug screening. Reported here are methods that provide unique and biologically relevant characterization of proteolysis and protease inhibition. A companion report provides evidence that these methods show promise for drug and basic biological discovery, especially for early detection of potential side effects. Electron spin resonance spectroscopy and spin labeling (ESRSL) of whole proteins are leveraged to monitor reactants and products of whole-protein digestion through differentiation of angular mobility of those products and reactants. These proof-of-concept data demonstrate consistency with prior art for all possible combinations of four proteases, two whole-protein substrates and three inhibitors. Thus, ESRSL is shown to uniquely and widely interrogate proteolysis of natural, whole-protein, substrates insuring the biological relevance of results.
最近,PAXLOVID™(nirmatrelvir与利托那韦共包装)被批准用于治疗COVID-19。据推测,该疗法的作用机制是Sars-Cov-2“3CL”蛋白酶抑制剂,这延续了数十年来人们对抑制病毒蛋白酶以对抗致病性病毒(如HIV蛋白酶抑制剂)的兴趣。蛋白水解试验方法差异很大,大致限于基础生物化学的询问和高通量的早期药物筛选。这里报道的方法提供独特的和生物学相关的表征蛋白水解和蛋白酶抑制。一份配套报告提供的证据表明,这些方法有望用于药物和基础生物学发现,特别是早期发现潜在的副作用。利用全蛋白的电子自旋共振光谱和自旋标记(ESRSL)来监测全蛋白消化的反应物和产物,通过区分这些产物和反应物的角迁移率。这些概念验证数据证明了四种蛋白酶、两种全蛋白底物和三种抑制剂的所有可能组合与现有技术的一致性。因此,ESRSL被证明可以独特而广泛地询问天然全蛋白底物的蛋白水解,从而确保结果的生物学相关性。
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引用次数: 1
In memoriam Professor Dr. Philipp A. Schnabel (1953–2021) 纪念Philipp A. Schnabel教授(1953-2021)
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022006
B. Brücher
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引用次数: 0
Logical entropy – special issue 逻辑熵——特殊问题
Pub Date : 2022-01-01 DOI: 10.1051/fopen/2022005
G. Manfredi
Entropy is a fundamental quantity in many areas of knowledge, from physics to information science to biology. Originally put forward in the nineteenth century for very practical purposes (to quantify the reversibility of thermodynamic cycles, hence of thermal engines), entropy was the key concept that allowed Ludwig Boltzmann to bridge the gap between the (time irreversible) macroscopic thermodynamics and the (reversible) microscopic Newtonian physics. As defined by Boltzmann, the entropy SB represents the number of microscopic states that are compatible with a given macroscopic realization:
熵是许多知识领域的基本量,从物理学到信息科学再到生物学。熵最初是在19世纪提出的,用于非常实际的目的(量化热力学循环的可逆性,从而量化热机),它是路德维希·玻尔兹曼(Ludwig Boltzmann)在(时间不可逆的)宏观热力学和(可逆的)微观牛顿物理学之间建立桥梁的关键概念。根据玻尔兹曼的定义,熵SB表示与给定宏观实现相兼容的微观状态的数量:
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引用次数: 2
Quantum logical entropy: fundamentals and general properties 量子逻辑熵:基本原理和一般性质
Pub Date : 2021-08-05 DOI: 10.1051/fopen/2021005
B. Tamir, Ismael Lucas De Paiva, Zohar Schwartzman-Nowik, E. Cohen
Logical entropy gives a measure, in the sense of measure theory, of the distinctions of a given partition of a set, an idea that can be naturally generalized to classical probability distributions. Here, we analyze how this fundamental concept and other related definitions can be applied to the study of quantum systems with the use of quantum logical entropy. Moreover, we prove several properties of this entropy for generic density matrices that may be relevant to various areas of quantum mechanics and quantum information. Furthermore, we extend the notion of quantum logical entropy to post-selected systems.
逻辑熵给出了一个测度,在测度论的意义上,一个集合的给定分区的区别,这个想法可以很自然地推广到经典概率分布。在这里,我们分析了如何使用量子逻辑熵将这个基本概念和其他相关定义应用于量子系统的研究。此外,我们证明了该熵的几个性质,可能与量子力学和量子信息的各个领域有关的一般密度矩阵。此外,我们将量子逻辑熵的概念扩展到后选择系统。
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引用次数: 5
Recent developments in mitochondrial medicine (Part 1) 线粒体医学的最新进展(上)
Pub Date : 2021-01-01 DOI: 10.1051/FOPEN/2021002
V. Weissig, M. Edeas
Research into elucidating structure and function of mitochondria has been quite steady between the time of discovery during the end of the 19th century until towards the late 1980’s. During the 1990s there was talk about a “comeback” of this organelle reflecting a widely revitalized interest into mitochondrial research which was based on two major discoveries made during that time. The first was the etiological association between human diseases and mitochondrial DNA mutations, while the second revealed the crucial function of mitochondria during apoptosis. The March 5th, 1999 issue of Science even featured a textbook image of a mitochondrion on its front cover and was entirely dedicated to this organelle. Whilst the term “comeback” might have been appropriate to describe the general excitement surrounding the new mitochondrial discoveries made during the 1990s, a term for describing the progress made in mitochondrial research during the last two decades is difficult to find. Between 2000 and 2020 the number of publications on mitochondria has skyrocketed. It is now widely accepted that there hardly exists any human disease for which either the etiology or pathogenesis does not seem to be associated with mitochondrial malfunction. In this review we will discuss and follow several lines of mitochondrial research from their early beginnings up to the present. We hope to be able to convince the reader of what we expressed about a decade ago, that the future of medicine will come through mitochondria.
从19世纪末到20世纪80年代末,对线粒体结构和功能的研究一直很稳定。在20世纪90年代,有关于这种细胞器的“回归”的讨论,反映了人们对线粒体研究的广泛兴趣,这是基于当时的两项重大发现。第一个是人类疾病与线粒体DNA突变之间的病因学关联,而第二个揭示了线粒体在细胞凋亡中的关键功能。1999年3月5日出版的《科学》杂志甚至在封面上刊登了一幅教科书式的线粒体图片,并专门介绍了这种细胞器。虽然用“复出”一词来描述20世纪90年代线粒体新发现带来的普遍兴奋可能是合适的,但很难找到一个词来描述过去20年线粒体研究取得的进展。从2000年到2020年,关于线粒体的出版物数量激增。现在人们普遍认为,几乎不存在任何人类疾病,其病因或发病机制似乎与线粒体功能障碍无关。在这篇综述中,我们将讨论并遵循线粒体研究的几个方面,从他们的早期开始到现在。我们希望能够说服读者相信我们十年前表达的观点,即医学的未来将来自线粒体。
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引用次数: 5
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