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1.
Mol Med Rep ; 24(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34328196

RESUMO

Inflammation and oxidative stress have indispensable roles in the development of acute lung injury (ALI). MicroRNA (miRNA/miR)­351­5p was initially identified as a myogenesis­associated miRNA; however, its role in lipopolysaccharide (LPS)­induced ALI remains unclear. The aim of the present study was to investigate the role and potential mechanisms of miR­351­5p in ALI. ALI was induced through a single intratracheal injection of LPS for 12 h, and miR­351­5p agomir, antagomir or their corresponding negative controls were injected into the tail vein before LPS stimulation. Compound C, 2',5'­dideoxyadenosine and H89 were used to inhibit AMP­activated protein kinase (AMPK), adenylate cyclase and protein kinase A (PKA), respectively. miR­351­5p levels in the lungs were significantly increased in response to LPS injection. miR­351­5p antagomir alleviated, while miR­351­5p agomir aggravated LPS­induced oxidative stress and inflammation in the lungs. The present results also demonstrated that miR­351­5p antagomir attenuated LPS­induced ALI via activating AMPK, and that the cAMP/PKA axis was required for the activation of AMPK by the miR­351­5p antagomir. In conclusion, the present study indicated that miR­351­5p aggravated LPS­induced ALI via inhibiting AMPK, suggesting that targeting miR­351­5p may help to develop efficient therapeutic approaches for treating ALI.


Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Inflamação/genética , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/genética
2.
Immunopharmacol Immunotoxicol ; 43(4): 431-442, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34157933

RESUMO

OBJECTIVES: Acute lung injury (ALI) is a devastating lung disease characterized by uncontrolled pulmonary inflammation and oxidative stress. Currently, no effective therapeutic strategies are available for ALI and its prognosis remains poor. The present study aims to investigate the role and potential mechanism of microRNA-30d-5p (miR-30d-5p) in the progression of ALI. METHODS: Mice were intravenously treated with miR-30d-5p agomir, antagomir or their respective controls for 3 consecutive days and then were exposed to a single intratracheal injection of lipopolysaccharide (LPS) for 12 h at a dosage of 5 mg/kg to induce ALI. To inhibit adenosine monophosphate-activated protein kinase α (AMPKα) or phosphodiesterase 4 D (PDE4D), compound C (CpC) and rolipram were used. RESULTS: miR-30d-5p expression in the lungs was significantly inhibited by LPS treatment. miR-30d-5p agomir significantly alleviated, while miR-30d-5p antagomir aggravated pulmonary inflammation, oxidative damage, and dysfunction in ALI mice. Besides, we found that miR-30d-5p agomir ameliorated LPS-induced ALI via activating AMPKα and that the inhibition of AMPKα by CpC completely abolished these beneficial effects of miR-30d-5p agomir. Further findings validated that PDE4D downregulation was required for the activation of AMPKα by miR-30d-5p agomir. CONCLUSION: miR-30d-5p ameliorates LPS-induced ALI via activating AMPKα and it is a valuable therapeutic candidate in the treatment of ALI.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Lipopolissacarídeos/toxicidade , MicroRNAs/biossíntese , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Camundongos , MicroRNAs/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia
3.
Ann Transl Med ; 8(10): 653, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32566590

RESUMO

Primary neuroendocrine tumors (NETs) in the heart are exceptionally rare. Here, we report a case found at our hospital of a 51-year-old woman with a primary left ventricular NET. The patient presented with non-causal recurrent diarrhea for 2 years, abdominal pain, and vomiting. Endoscopy revealed chronic proctitis and duodenal ulcer but found no explanation for the clinical symptoms. Comprehensive cardiovascular tests were conducted, and a mass measuring 26 mm × 41 mm × 30 mm was detected in the left ventricle. The patient underwent complete surgical resection to remove the tumor. Postoperative pathological results indicated a NET. No recurrence or other signs of metastasis were experienced during a 13-month follow-up observation period. Herein, we report this case and describe the imaging manifestations and clinical diagnosis strategy of this rare tumor. A diagnosis of NET of the heart may be considered when there are unexplained abdominal symptoms and without an abdominal or pelvic mass.

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