E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.
E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition.
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E-系列分解代谢组，生物合成和专业促进分解介体（SPMS）立体化学在炎症分解中的关键作用：为长期Covid-19，人类临床试验和靶向精确营养准备SPMS。
DOI：
10.1016/j.smim.2022.101597
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发表时间：
2022-01
影响因子：
7.8
通讯作者：
Nshimiyimana R
中科院分区：
文献类型：
--
作者：
Serhan CN;Libreros S;Nshimiyimana R
COVID-19大流行提高了国际社会对严格科学证据的重要性以及不受控制的过度炎症造成的严重破坏的认识。在这里，我们考虑的证据是否专门的促消退介质（SPM）准备好迎接这一挑战，以及有针对性的代谢脂质组学的解决炎症代谢。从ω-3必需脂肪酸生物合成SPM的特定立体化学机制产生独特的局部作用脂质介质。SPM具有立体化学定义的有效生物活性结构，其是同源G蛋白偶联表面受体的高亲和力配体，其引起有效解决急性炎症所需的细胞反应。由主要的ω-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）生物合成的SPM被称为Resolvins（消退相相互作用产物; E系列和D系列）、Protectins和Maresins（消退炎症的巨噬细胞介质）。它们的生物合成和立体化学分配被建立和确认（在PubMed.gov中> 1，441篇resolvin出版物）以及它们对先天免疫细胞和适应性免疫细胞（淋巴细胞T细胞亚群和B细胞）的功能作用。保护性急性炎症反应的消退主要由吞噬细胞控制，吞噬细胞主动清除凋亡细胞、碎片、血凝块和病原体。这些急性炎症反应的消退期功能通过SPM增强，SPM一起准备用于稳态的炎症位点并通过激活干细胞和新型cys-SPM（例如MCTR、PCTR和RCTR）的生物合成刺激组织再生。这些cys-SPM还激活再生，是器官保护和刺激局部炎症的解决。本文综述了E-系列消退素的生物合成和功能，即消退素E1（第一个被鉴定的n-3消退素）、消退素E2、消退素E3和消退素E4，以及全有机合成在证实SPM完全立体化学、确定其在炎症消退中的有效功能和新结构方面的关键作用。每种生物衍生SPM的物理性质，即，紫外（UV）吸光度、色谱行为和串联质谱（MS 2）断裂与生物合成的SPM和通过立体特异性全有机合成制备的SPM相匹配。我们简要地回顾了这种方法，也与内源性D-系列resolvins，protectins和maresins一起使用，证实了它们在炎症消退中的有效功能，为它们在人体组织和临床试验中的严格评估铺平了道路。为E和D系列Resolvins、Protectins和Maresins中的每一种分配完整的立体化学是一个关键和必需的步骤，它使人类临床研究成为可能，如在COVID-19感染和实验动物疾病模型中的SPM分析，这也为分辨率生理学、分辨率药理学和靶向精确营养作为监测健康和疾病机制的新领域开辟了前景。
The COVID-19 pandemic has raised international awareness of the importance of rigorous scientific evidence and the havoc caused by uncontrolled excessive inflammation. Here we consider the evidence on whether the specialized pro-resolving mediators (SPMs) are ready to meet this challenge as well as targeted metabololipidomics of the resolution-inflammation metabolomes. Specific stereochemical mechanisms in the biosynthesis of SPMs from omega-3 essential fatty acids give rise to unique local-acting lipid mediators. SPMs possess stereochemically defined potent bioactive structures that are high-affinity ligands for cognate G protein-coupled surface receptors that evoke the cellular responses required for efficient resolution of acute inflammation. The SPMs biosynthesized from the major omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are coined Resolvins (resolution phase interaction products; E series and D-series), Protectins and Maresins (macrophage mediators in resolving inflammation). Their biosynthesis and stereochemical assignments are established and confirmed (>1,441 resolvin publications in PubMed.gov) as well as their functional roles on innate immune cells and adaptive immune cells (both lymphocyte T-cell subsets and B-cells). The resolution of a protective acute inflammatory response is governed mainly by phagocytes that actively clear apoptotic cells, debris, blood clots and pathogens. These resolution phase functions of the acute inflammatory response are enhanced by SPMs, which together prepare the inflammatory loci for homeostasis and stimulate tissue regeneration via activating stem cells and the biosynthesis of novel cys-SPMs (e.g. MCTRs, PCTRs and RCTRs). These cys-SPMs also activate regeneration, are organ protective and stimulate resolution of local inflammation. Herein, we review the biosynthesis and functions of the E-series resolvins, namely resolvin E1 (the first n-3 resolvin identified), resolvin E2, resolvin E3 and resolvin E4 biosynthesized from their precursor eicosapentaenoic acid (EPA), and the critical role of total organic synthesis in confirming SPM complete stereochemistry, establishing their potent functions in resolution of inflammation, and novel structures. The physical properties of each biologically derived SPM, i.e., ultra-violet (UV) absorbance, chromatographic behavior, and tandem mass spectrometry (MS2) fragmentation, were matched to SPMs biosynthesized and prepared by stereospecific total organic synthesis. We briefly review this approach, also used with the endogenous D-series resolvins, protectins and maresins confirming their potent functions in resolution of inflammation, that paves the way for their rigorous evaluation in human tissues and clinical trials. The assignment of complete stereochemistry for each of the E and D series Resolvins, Protectins and Maresins was a critical and required step that enabled human clinical studies as in SPM profiling in COVID-19 infections and experimental animal disease models that also opened the promise of resolution physiology, resolution pharmacology and targeted precision nutrition as new areas for monitoring health and disease mechanisms.
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影响因子：
6.1
作者：
Raatz SK;Golovko MY;Brose SA;Rosenberger TA;Burr GS;Wolters WR;Picklo MJ Sr
通讯作者：
Picklo MJ Sr
影响因子：
20.3
作者：
Chiang N;Sakuma M;Rodriguez AR;Spur BW;Irimia D;Serhan CN
通讯作者：
Serhan CN
DOI：
10.1096/fj.202100540r
发表时间：
2021-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Archambault AS;Zaid Y;Rakotoarivelo V;Turcotte C;Doré É;Dubuc I;Martin C;Flamand O;Amar Y;Cheikh A;Fares H;El Hassani A;Tijani Y;Côté A;Laviolette M;Boilard É;Flamand L;Flamand N
通讯作者：
Flamand N
DOI：
10.1016/j.plefa.2018.04.004
发表时间：
2018-06-01
影响因子：
3
作者：
Barden, Anne;Shinde, Sujata;Mori, Trevor A.
通讯作者：
Mori, Trevor A.
影响因子：
4.4
作者：
Arita, Makoto;Ohira, Taisuke;Serhan, Charles N.
通讯作者：
Serhan, Charles N.