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000277773 1001_ $$0P:(DE-He78)396821e874b632341e4bcabd27bcad3f$$aDragomir, Mihnea-Paul$$b0$$udkfz
000277773 245__ $$aAnti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response.
000277773 260__ $$aAnn Arbor, Mich.$$bASCJ$$c2023
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000277773 520__ $$aSepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA targets for sepsis therapeutics, we used samples for miRNA array analysis of PBMCs from patients with sepsis and control individuals, blood samples from 2 cohorts of patients with sepsis, and multiple animal models: mouse cecum ligation puncture-induced (CLP-induced) sepsis, mouse viral miRNA challenge, and baboon Gram+ and Gram- sepsis models. miR-93-5p met the criteria for a therapeutic target, as it was overexpressed in baboons that died early after induction of sepsis, was downregulated in patients who survived after sepsis, and correlated with negative clinical prognosticators for sepsis. Therapeutically, inhibition of miR-93-5p prolonged the overall survival of mice with CLP-induced sepsis, with a stronger effect in older mice. Mechanistically, anti-miR-93-5p therapy reduced inflammatory monocytes and increased circulating effector memory T cells, especially the CD4+ subset. AGO2 IP in miR-93-KO T cells identified important regulatory receptors, such as CD28, as direct miR-93-5p target genes. In conclusion, miR-93-5p is a potential therapeutic target in sepsis through the regulation of both innate and adaptive immunity, with possibly a greater benefit for elderly patients than for young patients.
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000277773 650_7 $$2Other$$aAdaptive immunity
000277773 650_7 $$2Other$$aImmunology
000277773 650_7 $$2Other$$aInfectious disease
000277773 650_7 $$2Other$$aInnate immunity
000277773 650_7 $$2Other$$aNoncoding RNAs
000277773 650_7 $$2NLM Chemicals$$aAntagomirs
000277773 650_7 $$2NLM Chemicals$$aMicroRNAs
000277773 650_7 $$2NLM Chemicals$$aMIRN93 microRNA, human
000277773 650_2 $$2MeSH$$aHumans
000277773 650_2 $$2MeSH$$aMice
000277773 650_2 $$2MeSH$$aAnimals
000277773 650_2 $$2MeSH$$aAged
000277773 650_2 $$2MeSH$$aAntagomirs
000277773 650_2 $$2MeSH$$aMicroRNAs: genetics
000277773 650_2 $$2MeSH$$aAdaptive Immunity
000277773 650_2 $$2MeSH$$aSepsis: pathology
000277773 7001_ $$aFuentes-Mattei, Enrique$$b1
000277773 7001_ $$aWinkle, Melanie$$b2
000277773 7001_ $$aOkubo, Keishi$$b3
000277773 7001_ $$aBayraktar, Recep$$b4
000277773 7001_ $$aKnutsen, Erik$$b5
000277773 7001_ $$aQdaisat, Aiham$$b6
000277773 7001_ $$aChen, Meng$$b7
000277773 7001_ $$aLi, Yongfeng$$b8
000277773 7001_ $$aShimizu, Masayoshi$$b9
000277773 7001_ $$aPang, Lan$$b10
000277773 7001_ $$aLiu, Kevin$$b11
000277773 7001_ $$aLiu, Xiuping$$b12
000277773 7001_ $$aAnfossi, Simone$$b13
000277773 7001_ $$aZhang, Huanyu$$b14
000277773 7001_ $$aKoch, Ines$$b15
000277773 7001_ $$aTran, Anh M$$b16
000277773 7001_ $$aMohapatra, Swati$$b17
000277773 7001_ $$aTon, Anh$$b18
000277773 7001_ $$aKaplan, Mecit$$b19
000277773 7001_ $$aAnderson, Matthew W$$b20
000277773 7001_ $$aRothfuss, Spencer J$$b21
000277773 7001_ $$aSilasi, Robert$$b22
000277773 7001_ $$aKeshari, Ravi S$$b23
000277773 7001_ $$aFerracin, Manuela$$b24
000277773 7001_ $$aIvan, Cristina$$b25
000277773 7001_ $$aRodriguez-Aguayo, Cristian$$b26
000277773 7001_ $$aLopez-Berestein, Gabriel$$b27
000277773 7001_ $$aGeorgescu, Constantin$$b28
000277773 7001_ $$aBanerjee, Pinaki P$$b29
000277773 7001_ $$aBasar, Rafet$$b30
000277773 7001_ $$aLi, Ziyi$$b31
000277773 7001_ $$0P:(DE-HGF)0$$aHorst, David$$b32
000277773 7001_ $$aVasilescu, Catalin$$b33
000277773 7001_ $$aBertilaccio, Maria Teresa S$$b34
000277773 7001_ $$aRezvani, Katayoun$$b35
000277773 7001_ $$aLupu, Florea$$b36
000277773 7001_ $$aYeung, Sai-Ching$$b37
000277773 7001_ $$aCalin, George A$$b38
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