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1.
Clin Exp Pharmacol Physiol ; 47(11): 1783-1790, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32621522

RESUMO

Myocardial ischaemia reperfusion (I/R) injury is one of the leading causes of coronary artery disease-associated morbidity and mortality. While different strategies have been used to limit I/R injuries, cardiac functions often do not recover to the normal level as anticipated. Recent studies have pointed to important roles of long noncoding RNAs (lncRNAs) in the development of myocardial I/R injury. LncRNA is a class of RNA molecules of more than 200 nucleotides in length which are not translated into proteins. I/R causes dysregulation of lncRNA expression in cardiomyocytes, thereby affecting multiple cellular functions including mitochondrial homeostasis, apoptosis, necrosis and autophagy, suggesting that manipulating lncRNAs may be of great potential in counteracting I/R injury-induced myocardial dysfunctions. In this review, we provide an updated summary on our knowledge about contributions of lncRNAs to the development of I/R injury, with an emphasis on the functional links between several well established cardiac lncRNAs and regulation of cellular outcomes post I/R.


Assuntos
Terapia de Alvo Molecular , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Humanos , Mitocôndrias/metabolismo , Transdução de Sinais/genética
2.
Biosci Biotechnol Biochem ; 84(4): 815-823, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31791197

RESUMO

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe-/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe-/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.


Assuntos
Aterosclerose/prevenção & controle , Diabetes Mellitus Experimental/complicações , Endotélio Vascular/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Floretina/farmacologia , Animais , Aterosclerose/complicações , Aterosclerose/metabolismo , Glicemia/análise , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperglicemia/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/metabolismo , Floretina/administração & dosagem , Transdução Genética
3.
Fa Yi Xue Za Zhi ; 31(3): 200-3, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26442372

RESUMO

OBJECTIVE: To establish the method to analyze γ-hydroxybutyric acid (GHB) and its precursors 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL) in urine through LC-MS/MS and provide evidence for related cases. METHODS: GHB-d6 and MOR-d3 were used as the internal standard. The urine sample was separated by LC after protein precipitation with methanol. The electrospray ion source was for ionization. Each compound was detected through multiple-reaction monitoring (MRM) mode. RESULTS: The limits of detection of GHB and its precursors 1,4-BD and GBL were 0.1, 0.1 and 2 µg/mL. The accuracy was 87.6%-98.1%. The intra-day and inter-day precisions were less than 15% and matrix effects were higher than 80%. CONCLUSION: The method is high sensitive, simple, rapid, specific and with high reliability. This study has provided technical support and basic data for forensic cases involving GHB.


Assuntos
4-Butirolactona/urina , Butileno Glicóis/urina , Hidroxibutiratos/urina , Cromatografia Líquida , Ciências Forenses , Humanos , Espectrometria de Massas , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
4.
Heart Vessels ; 28(1): 101-13, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22241736

RESUMO

The aim of this work is to study cytoskeletal impairment during the development of ouabain-induced ventricular hypertrophy. Male Sprague-Dawley rats were treated with either ouabain or saline. Systolic blood pressure (SBP) was recorded weekly. At the end of the 3rd and 6th week, the rats were killed and cardiac mass index were measured. Hematoxylin-eosin and Sirius red staining were carried out and cardiac ultrastructure were studied using transmission electron microscopy. The mRNA level of Profilin-1, Desmin, PCNA, TGF-ß(1) and ET-1 in the left ventricle were measured using real-time quantitative PCR while their protein levels were examined by Western blot or immunohistochemistry. After 3 weeks, there was no significant difference in the mean SBP, cardiac mass index, mRNA and protein expression of PCNA, TGF-ß(1) and ET-1 between the two groups. However, ouabain-treated rats showed disorganized cardiac cytoskeleton with abnormal expression of Profilin-1 and Desmin. After 6 weeks, the cardiac mass index remained the same in the two groups while PCNA, TGF-ß(1), and ET-1 have been upregulated in ouabain-treated rats. The cardiac cytoskeletal impairment was more severe in ouabain-treated rats with further changes of Profilin-1 and Desmin. Cytoskeletal abnormality is an ultra-early change during ouabain-induced ventricular hypertrophy, before the release of hypertrophic factors. Therapy for prevention of ouabain-induced hypertrophy should start at the early stage by preventing the cytoskeleton from disorganization.


Assuntos
Citoesqueleto/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/patologia , Miocárdio/ultraestrutura , Ouabaína/toxicidade , Animais , Pressão Sanguínea , Citoesqueleto/ultraestrutura , Desmina/biossíntese , Desmina/genética , Modelos Animais de Doenças , Progressão da Doença , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Microscopia Eletrônica de Transmissão , Miocárdio/metabolismo , Profilinas/biossíntese , Profilinas/genética , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
6.
J Nutr Sci Vitaminol (Tokyo) ; 54(4): 321-8, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18797155

RESUMO

Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. The aim of this study was to clarify whether grape seed proanthocyanidins extracts (GSPE) are therapeutic agents against DPN. In this study, we used streptozocin (STZ) to induce diabetic rats. GSPEs (250 mg/kg body weight/d) were administrated to diabetic rats for 24 wk. Motor nerve conductive velocity (MNCV) and mechanical hyperalgesia were determined in the rats. Serum glucose, glycated hemoglobin, advanced glycation end products (AGEs), and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. Light and electron microscopy were used to observe the changes of nerval ultrastructure.GSPE significantly increased the MNCV, mechanical hyperalgesia and SOD of diabetic rats (p<0.05) and reduced the AGEs and MDA of diabetic rats (p<0.05). After being treated by GSPE, the severe segmental demyelination was decreased and Schwann cells were improved. In conclusion, GSPE plays an important role against DPN. With the decreasing of AGEs and MDA, it can ameliorate oxidation-associated nerval damage. This study may provide a new recognition of natural medicine for the treatment of DPN.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Nervo Isquiático/efeitos dos fármacos , Vitis , Animais , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/patologia , Extrato de Sementes de Uva , Masculino , Estresse Oxidativo/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Nervo Isquiático/patologia
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