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Front Med ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34515940


Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

Signal Transduct Target Ther ; 6(1): 300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381015


Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.

COVID-19/genética , Diabetes Mellitus/genética , MicroRNAs/genética , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Fatores Etários , Idoso , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , China , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Exercício Físico , Exossomos/genética , Exossomos/metabolismo , Exossomos/virologia , Feminino , Regulação da Expressão Gênica , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Replicação Viral
Sci Adv ; 7(7)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33568480


Evidence that offspring traits can be shaped by parental life experiences in an epigenetically inherited manner paves a way for understanding the etiology of depression. Here, we show that F1 offspring born to F0 males of depression-like model are susceptible to depression-like symptoms at the molecular, neuronal, and behavioral levels. Sperm small RNAs, and microRNAs (miRNAs) in particular, exhibit distinct expression profiles in F0 males of depression-like model and recapitulate paternal depressive-like phenotypes in F1 offspring. Neutralization of the abnormal miRNAs in zygotes by antisense strands rescues the acquired depressive-like phenotypes in F1 offspring born to F0 males of depression-like model. Mechanistically, sperm miRNAs reshape early embryonic transcriptional profiles in the core neuronal circuits toward depression-like phenotypes. Overall, the findings reveal a causal role of sperm miRNAs in the inheritance of depression and provide insight into the mechanism underlying susceptibility to depression.

Proc Natl Acad Sci U S A ; 116(13): 6162-6171, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30867286


Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underlying mechanism is not fully elucidated. Here we identify hepatic miR-122 as a mediator of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in an exosome-independent manner into the circulation compared with normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds Toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting miR-122 in mouse liver or plasma largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding GU-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.

Doença Hepática Induzida por Substâncias e Drogas/complicações , Macrófagos Alveolares/metabolismo , MicroRNAs/metabolismo , Pneumonia/etiologia , Transdução de Sinais , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Pneumonia/metabolismo , Receptor 7 Toll-Like
Sensors (Basel) ; 18(3)2018 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-29522458


RFID (Radio Frequency Identification) offers a way to identify objects without any contact. However, positioning accuracy is limited since RFID neither provides distance nor bearing information about the tag. This paper proposes a new and innovative approach for the localization of moving object using a particle filter by incorporating RFID phase and laser-based clustering from 2d laser range data. First of all, we calculate phase-based velocity of the moving object based on RFID phase difference. Meanwhile, we separate laser range data into different clusters, and compute the distance-based velocity and moving direction of these clusters. We then compute and analyze the similarity between two velocities, and select K clusters having the best similarity score. We predict the particles according to the velocity and moving direction of laser clusters. Finally, we update the weights of the particles based on K clusters and achieve the localization of moving objects. The feasibility of this approach is validated on a Scitos G5 service robot and the results prove that we have successfully achieved a localization accuracy up to 0.25 m.