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Nutritional and Metabolic Control of Ferroptosis. 铁下垂的营养与代谢控制。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2022-06-01 DOI: 10.1146/annurev-nutr-062320-114541
Eikan Mishima, M. Conrad
Ferroptosis is a type of regulated cell death characterized by an excessive lipid peroxidation of cellular membranes caused by the disruption of the antioxidant defense system and/or an imbalanced cellular metabolism. Ferroptosis differentiates from other forms of regulated cell death in that several metabolic pathways and nutritional aspects, including endogenous antioxidants (such as coenzyme Q10, vitamin E, and di/tetrahydrobiopterin), iron handling, energy sensing, selenium utilization, amino acids, and fatty acids, directly regulate the cells' sensitivity to lipid peroxidation and ferroptosis. As hallmarks of ferroptosis have been documented in a variety of diseases, including neurodegeneration, acute organ injury, and therapy-resistant tumors, the modulation of ferroptosis using pharmacological tools or by metabolic reprogramming holds great potential for the treatment of ferroptosis-associated diseases and cancer therapy. Hence, this review focuses on the regulation of ferroptosis by metabolic and nutritional cues and discusses the potential of nutritional interventions for therapy by targeting ferroptosis. Expected final online publication date for the Annual Review of Nutrition, Volume 42 is August 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
脱铁症是一种调节性细胞死亡,其特征是抗氧化防御系统破坏和/或细胞代谢失衡导致细胞膜脂质过氧化过度。脱铁症与其他形式的调节性细胞死亡的不同之处在于,几种代谢途径和营养方面,包括内源性抗氧化剂(如辅酶Q10、维生素E和二/四氢生物蝶呤)、铁处理、能量传感、硒利用、氨基酸和脂肪酸,直接调节细胞对脂质过氧化和脱铁症的敏感性。由于脱铁症的特征已被记录在多种疾病中,包括神经退行性变、急性器官损伤和耐治疗肿瘤,使用药理学工具或代谢重编程调节脱铁症在治疗脱铁症相关疾病和癌症治疗中具有巨大潜力。因此,这篇综述的重点是代谢和营养线索对脱铁性贫血的调节,并讨论了通过靶向脱铁性肾病进行营养干预治疗的潜力。《营养年度评论》第42卷预计最终在线出版日期为2022年8月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 21
The Oscillating Gut Microbiome and Its Effects on Host Circadian Biology. 振荡肠道微生物组及其对宿主昼夜生物学的影响。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2022-05-16 DOI: 10.1146/annurev-nutr-062320-111321
Lev Litichevskiy, Christoph A. Thaiss
The microbial community colonizing the gastrointestinal tract, collectively termed the gut microbiota, is an important element of the host organism due to its impact on multiple aspects of health. The digestion of food, secretion of immunostimulatory molecules, performance of chemical reactions in the intestine, and production of metabolites by the microbiota contribute to host homeostasis and disease. Recent discoveries indicate that these major functions are not constantly performed over the course of a day, but rather undergo diurnal fluctuations due to compositional and biogeographical oscillations in the microbiota. Here, we summarize the characteristics and origins of diurnal microbiome rhythms as well as their functional consequences for the circadian biology of the host. We describe the major known pathways of circadian host-microbiome communication and discuss possible implications of altered diurnal microbiome rhythms for human disease. Expected final online publication date for the Annual Review of Nutrition, Volume 42 is August 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
定殖在胃肠道的微生物群落,统称为肠道微生物群,由于其对健康的多个方面的影响,是宿主生物的重要组成部分。食物的消化、免疫刺激分子的分泌、肠道中化学反应的表现以及微生物群产生代谢产物有助于宿主体内平衡和疾病。最近的发现表明,这些主要功能并不是在一天中不断发挥的,而是由于微生物群的组成和生物地理振荡而发生的昼夜波动。在这里,我们总结了昼夜微生物组节律的特征和起源,以及它们对宿主昼夜生物学的功能影响。我们描述了昼夜节律宿主-微生物组交流的主要已知途径,并讨论了昼夜节律改变对人类疾病的可能影响。《营养年度评论》第42卷预计最终在线出版日期为2022年8月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 12
A Female Career in Research. 研究中的女性职业生涯。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2022-04-01 DOI: 10.1146/annurev-nutr-062220-103411
K. Flegal
After a long career at the National Center for Health Statistics, I retired and joined the Stanford Prevention Research Center as an unpaid associate. I was once described by a former US Food and Drug Administration commissioner as "one of the great epidemiologists." The chair of the Harvard nutrition department, speaking on National Public Radio, once described my research as "rubbish." Both may be exaggerations. Here I address some of the events that led to these contrasting descriptions. I also address the extent to which the so-called Matilda effect may have influenced my career. Are women in science on an equal footing with men? The Matilda effect suggests not. Unlike the Matthew effect for scientists, whereby those of higher prestige accrue a disproportionate share of recognition and rewards, the Matilda effect proposes that women scientists are systematically undervalued and underrecognized. I could never get a faculty job and was often treated like an underling. Nonetheless I persevered to publish highly cited research on several high-profile and sometimes controversial topics. Though overt sexism in science and workplaces has diminished over the course of my career, progress toward eliminating unconscious bias has been slower. The Matthew and Matilda effects are still powerful forces that distort incentives and rewards in science. Expected final online publication date for the Annual Review of Nutrition, Volume 42 is August 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
在国家卫生统计中心工作了很长一段时间后,我退休了,加入了斯坦福预防研究中心,成为一名无薪助理。一位前美国食品和药物管理局局长曾将我描述为“伟大的流行病学家之一”。哈佛大学营养系主任曾在国家公共广播电台上称我的研究是“垃圾”。两者都可能是夸大其词。在这里,我讲述了导致这些对比描述的一些事件。我还谈到了所谓的玛蒂尔达效应可能在多大程度上影响了我的职业生涯。女性在科学领域与男性处于平等地位吗?玛蒂尔达效应表明并非如此。与科学家的马太效应不同,在马太效应中,声望较高的科学家获得了不成比例的认可和奖励,而玛蒂尔达效应则认为女性科学家被系统地低估和低估。我永远找不到一份教员的工作,经常被当作下属对待。尽管如此,我还是坚持发表了一些备受关注、有时甚至有争议的主题的高引用研究。尽管在我的职业生涯中,科学和工作场所中公开的性别歧视已经减少,但消除无意识偏见的进展较慢。马太和玛蒂尔达效应仍然是扭曲科学激励和奖励的强大力量。《营养年度评论》第42卷预计最终在线出版日期为2022年8月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。
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引用次数: 0
Designing Relevant Preclinical Rodent Models for Studying Links Between Nutrition, Obesity, Metabolism, and Cancer. 设计相关的临床前啮齿动物模型,以研究营养、肥胖、新陈代谢和癌症之间的联系。
IF 12.6 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2021-10-11 Epub Date: 2021-08-06 DOI: 10.1146/annurev-nutr-120420-032437
Elaine M Glenny, Michael F Coleman, Erin D Giles, Elizabeth A Wellberg, Stephen D Hursting

Diet and nutrition are intricately related to cancer prevention, growth, and treatment response. Preclinical rodent models are a cornerstone to biomedical research and remain instrumental in our understanding of the relationship between cancer and diet and in the development of effective therapeutics. However, the success rate of translating promising findings from the bench to the bedside is suboptimal. Well-designed rodent models will be crucial to improving the impact basic science has on clinical treatment options. This review discusses essential experimental factors to consider when designing a preclinical cancer model with an emphasis on incorporatingthese models into studies interrogating diet, nutrition, and metabolism. The aims of this review are to (a) provide insight into relevant considerations when designing cancer models for obesity, nutrition, and metabolism research; (b) identify common pitfalls when selecting a rodent model; and (c) discuss strengths and limitations of available preclinical models.

饮食和营养与癌症的预防、生长和治疗反应密切相关。临床前啮齿类动物模型是生物医学研究的基石,对于我们了解癌症与饮食之间的关系以及开发有效的治疗方法仍然非常重要。然而,将有前景的研究成果从实验室转化到临床的成功率却不尽如人意。精心设计的啮齿类动物模型对于提高基础科学对临床治疗方案的影响至关重要。本综述讨论了在设计临床前癌症模型时应考虑的基本实验因素,重点是将这些模型纳入有关饮食、营养和新陈代谢的研究中。本综述的目的是:(a) 深入探讨为肥胖、营养和代谢研究设计癌症模型时的相关注意事项;(b) 找出选择啮齿动物模型时的常见误区;(c) 讨论现有临床前模型的优势和局限性。
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引用次数: 0
Vitamin A and Vitamin E: Will the Real Antioxidant Please Stand Up? 维生素A和维生素E:真正的抗氧化剂会站起来吗?
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2021-10-11 Epub Date: 2021-06-11 DOI: 10.1146/annurev-nutr-082018-124228
William S Blaner, Igor O Shmarakov, Maret G Traber

Vitamin A, acting through its metabolite, all-trans-retinoic acid, is a potent transcriptional regulator affecting expression levels of hundreds of genes through retinoic acid response elements present within these genes. However, the literature is replete with claims that consider vitamin A to be an antioxidant vitamin, like vitamins C and E. This apparent contradiction in the understanding of how vitamin A acts mechanistically within the body is a major focus of this review. Vitamin E, which is generally understood to act as a lipophilic antioxidant protecting polyunsaturated fatty acids present in membranes, is often proposed to be a transcriptional regulator. The evaluation of this claim is another focus of the review. We conclude that vitamin A is an indirect antioxidant, whose indirect function is to transcriptionally regulate a number of genes involved in mediating the body's canonical antioxidant responses. Vitamin E, in addition to being a direct antioxidant, prevents the increase of peroxidized lipids that alter both metabolic pathways and gene expression profiles within tissues and cells. However, there is little compelling evidence that vitamin E has a direct transcriptional mechanism like that of vitamin A. Thus, we propose that the term antioxidant not be applied to vitamin A, and we discourage the use of the term transcriptional mediator when discussing vitamin E.

维生素A通过其代谢产物全反式视黄酸发挥作用,是一种有效的转录调节因子,通过这些基因中存在的视黄酸反应元件影响数百个基因的表达水平。然而,文献中充斥着认为维生素A是一种抗氧化维生素的说法,就像维生素C和E一样。对维生素A在体内机制作用的理解存在明显矛盾,这是本综述的主要焦点。维生素E通常被认为是一种亲脂性抗氧化剂,保护膜中存在的多不饱和脂肪酸,经常被认为是转录调节因子。对这一索赔的评估是审查的另一个重点。我们得出结论,维生素A是一种间接抗氧化剂,其间接功能是转录调节许多参与介导身体典型抗氧化反应的基因。维生素E除了是一种直接的抗氧化剂外,还能防止过氧化脂质的增加,从而改变组织和细胞内的代谢途径和基因表达谱。然而,几乎没有令人信服的证据表明维生素E与维生素a一样具有直接的转录机制。因此,我们建议抗氧化剂一词不适用于维生素a,并且在讨论维生素E时,我们不鼓励使用转录介质一词。
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引用次数: 0
Novel Approaches for Omega-3 Fatty Acid Therapeutics: Chronic Versus Acute Administration to Protect Heart, Brain, and Spinal Cord. Omega-3脂肪酸治疗的新方法:慢性与急性给药以保护心脏、大脑和脊髓。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2020-09-23 DOI: 10.1146/annurev-nutr-082018-124539
Hylde Zirpoli, Chuchun L Chang, Yvon A Carpentier, Adina T Michael-Titus, Vadim S Ten, Richard J Deckelbaum

This article reviews novel approaches for omega-3 fatty acid (FA) therapeutics and the linked molecular mechanisms in cardiovascular and central nervous system (CNS) diseases. In vitro and in vivo research studies indicate that omega-3 FAs affect synergic mechanisms that include modulation of cell membrane fluidity, regulation of intracellular signaling pathways, and production of bioactive mediators. We compare how chronic and acute treatments with omega-3 FAs differentially trigger pathways of protection in heart, brain, and spinal cord injuries. We also summarize recent omega-3 FA randomized clinical trials and meta-analyses and discuss possible reasons for controversial results, with suggestions on improving the study design for future clinical trials. Acute treatment with omega-3 FAs offers a novel approach for preserving cardiac and neurological functions, and the combinations of acute treatment with chronic administration of omega-3 FAs might represent an additional therapeutic strategy for ameliorating adverse cardiovascular and CNS outcomes.

本文综述了omega-3脂肪酸(FA)治疗心血管和中枢神经系统疾病的新方法及其相关分子机制。体外和体内研究表明,omega-3脂肪酸影响协同机制,包括细胞膜流动性的调节、细胞内信号通路的调节和生物活性介质的产生。我们比较了omega-3脂肪酸在慢性和急性治疗中触发心脏、大脑和脊髓损伤保护通路的差异。我们还总结了最近的omega-3 FA随机临床试验和荟萃分析,讨论了有争议结果的可能原因,并提出了改进未来临床试验研究设计的建议。omega-3脂肪酸的急性治疗为保护心脏和神经功能提供了一种新的方法,急性治疗与慢性给予omega-3脂肪酸的联合治疗可能是改善心血管和中枢神经系统不良结局的一种额外的治疗策略。
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引用次数: 20
All Children Thrive: Integration of Nutrition and Early Childhood Development. 所有儿童茁壮成长:营养与儿童早期发展的整合。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2020-09-23 DOI: 10.1146/annurev-nutr-120219-023757
Maureen M Black, Angela C B Trude, Chessa K Lutter

Building on the successes of child survival, we review the evidence needed to ensure both that children who survive also thrive and that recommendations promote equity, with no child left behind. To illustrate the critical roles played by nutrition and child development, we revise the Conceptual Framework for the Causes of Malnutrition and Death and the Nurturing Care Framework to create the Conceptual Framework of All Children Surviving and Thriving. The revised framework highlights the goals of child growth and development, supported by health, nutrition, learning, responsive caregiving, and security and safety. We review the challenges posed by undernutrition, stunting, micronutrient deficiencies, overweight, and children not reaching their developmental potential. Although integrated nutrition-childhood development interventions have shown promising effects, most have not been implemented at scale. Implementation science that investigates how and why integrated interventions work in real life, along with the acceptability, feasibility, cost, coverage, and sustainability of the interventions, is needed to ensure equity for all children thriving.

在儿童生存成功的基础上,我们审查了确保生存下来的儿童茁壮成长和各项建议促进公平、不让任何一个儿童掉队所需的证据。为了说明营养和儿童发育所起的关键作用,我们修订了《营养不良和死亡原因概念框架》和《养育照料框架》,以创建《所有儿童生存和茁壮成长概念框架》。修订后的框架强调了在健康、营养、学习、响应性照料以及保障和安全的支持下实现儿童生长和发展的目标。我们回顾了营养不良、发育迟缓、微量营养素缺乏、超重和儿童未达到其发展潜力所带来的挑战。尽管营养-儿童发展综合干预措施已显示出有希望的效果,但大多数尚未大规模实施。为了确保所有儿童都能公平地茁壮成长,需要研究综合干预措施在现实生活中如何以及为何起作用的实施科学,以及干预措施的可接受性、可行性、成本、覆盖范围和可持续性。
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引用次数: 10
Nutrition and the 2020 Pandemic. 营养与2020年大流行。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2020-09-23 DOI: 10.1146/annurev-nu-40-082120-100001
Patrick J Stover, Rudi Balling
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引用次数: 0
Nutrient Control of mRNA Translation. mRNA翻译的营养调控。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2020-09-23 Epub Date: 2020-07-06 DOI: 10.1146/annurev-nutr-120919-041411
Xin Erica Shu, Robert V Swanda, Shu-Bing Qian

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.

研究细胞DNA、RNA和蛋白质含量的全基因组分析的出现,彻底改变了介导细胞稳态的控制网络的研究。mRNA翻译是遗传流动的最后一步,并主要定义蛋白质组。因此,翻译调控对基因表达至关重要,特别是在营养过剩或缺乏的情况下。直到最近,人们还不清楚翻译控制的全球影响是如何通过营养信号传导途径协调的。一个新兴的翻译重编程概念解决了如何通过翻译选择性mrna来维持营养胁迫期间特定蛋白质的表达。在这篇综述中,我们描述了我们对转化控制原则的理解的最新进展;nutrient-sensing机制;以及它们在糖尿病、癌症和衰老等人类疾病中的失调。对不同营养条件下的翻译调控机制的理解可能有助于确定潜在的饮食和治疗靶点,以改善人类健康。
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引用次数: 14
Nutritional Aspects of Spermidine. 亚精胺的营养方面。
IF 8.9 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2020-09-23 Epub Date: 2020-07-07 DOI: 10.1146/annurev-nutr-120419-015419
Frank Madeo, Sebastian J Hofer, Tobias Pendl, Maria A Bauer, Tobias Eisenberg, Didac Carmona-Gutierrez, Guido Kroemer

Natural polyamines (spermidine and spermine) are small, positively charged molecules that are ubiquitously found within organisms and cells. They exert numerous (intra)cellular functions and have been implicated to protect against several age-related diseases. Although polyamine levels decline in a complex age-dependent, tissue-, and cell type-specific manner, they are maintained in healthy nonagenarians and centenarians. Increased polyamine levels, including through enhanced dietary intake, have been consistently linked to improved health and reduced overall mortality. In preclinical models, dietary supplementation with spermidine prolongs life span and health span. In this review, we highlight salient aspects of nutritional polyamine intake and summarize the current knowledge of organismal and cellular uptake and distribution of dietary (and gastrointestinal) polyamines and their impact on human health. We further summarize clinical and epidemiological studies of dietary polyamines.

天然多胺(亚精胺和精胺)是小的,带正电的分子,在生物体和细胞中无处不在。它们发挥许多(细胞内)功能,并涉及预防几种与年龄有关的疾病。尽管多胺水平以复杂的年龄依赖性、组织和细胞类型特异性方式下降,但它们在健康的九十岁和百岁老人中保持不变。增加多胺水平,包括通过增加饮食摄入,一直与改善健康和降低总体死亡率有关。在临床前模型中,膳食补充亚精胺可延长寿命和健康寿命。在这篇综述中,我们强调了营养多胺摄入的突出方面,并总结了目前关于饮食(和胃肠道)多胺的有机和细胞摄取和分布及其对人体健康的影响的知识。我们进一步总结了多胺的临床和流行病学研究。
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引用次数: 44
期刊
Annual review of nutrition
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