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1.
Eur Heart J ; 44(19): 1732-1744, 2023 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-36861348

RESUMEN

AIMS: Members of the chromogranin family play a role in angiogenesis. One such biologically active peptide, generated through the processing of chromogranin A, is vasostatin-2. This study aimed at assessing the association of serum vasostatin-2 levels with coronary collateral vessels (CCV) in diabetic patients with chronic total occlusions (CTO) and the effects of vasostatin-2 on angiogenesis in diabetic mice with hindlimb or myocardial ischemia. METHODS AND RESULTS: Serum levels of vasostatin-2 in 452 diabetic CTO patients were evaluated. The status of CCV was categorized according to the Rentrop score. Vasostatin-2 recombinant protein or phosphate-buffered saline were then injected intraperitoneally in diabetic mouse models of hindlimb or myocardial ischemia, followed by laser Doppler imaging and molecular biology examinations. The effects of vasostatin-2 were also ascertained in endothelial cells and macrophages, with mechanisms clarified using ribonucleic acid (RNA) sequencing. Serum levels of vasostatin-2 were significantly different and progressively higher across Rentrop score 0, 1, 2, and 3 groups (P < .001), with significantly lower levels in patients with poor CCV (Rentrop score 0 and 1) than in those with good CCV (Rentrop score 2 and 3) (P < .05). Vasostatin-2 significantly promoted angiogenesis in diabetic mice with hindlimb or myocardial ischemia. RNA-seq analyzes verified an angiotensin-converting enzyme 2 (ACE2)-mediated vasostatin-2-induction of angiogenesis in ischemic tissues. CONCLUSION: Lower serum levels of vasostatin-2 are associated with poor CCV in diabetic CTO patients compared with patients with good CCV. Vasostatin-2 significantly promotes angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Such effects are mediated by ACE2.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Experimental , Isquemia Miocárdica , Ratones , Animales , Cromogranina A/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Células Endoteliales/metabolismo , Diabetes Mellitus Experimental/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Circulación Colateral
2.
Bioorg Chem ; 101: 104042, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32650179

RESUMEN

A series of new fluoro-substituted benzimidazole derivatives were designed, synthesized and pharmacologically evaluated. All the target compounds were characterized by 1HNMR, 13CNMR, mass spectra and elemental analysis. The biological evaluation showed that most of the synthesized compounds displayed nanomolar affinity to the angiotensin II type 1 (AT1) receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. The maximal response of mean blood pressure (MBP) lowered 74.5 ± 3.5 mmHg (1g) and 69.2 ± 0.9 mmHg (2a) at 10 g/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than both losartan and telmisartan. So, compounds 1g and 2a may be considered as potential antihypertension drug candidates.


Asunto(s)
Antihipertensivos/uso terapéutico , Bencimidazoles/síntesis química , Bencimidazoles/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Animales , Antihipertensivos/farmacología , Diseño de Fármacos , Estructura Molecular , Relación Estructura-Actividad
3.
Front Public Health ; 11: 1139786, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36908426

RESUMEN

Objective: This study aimed to examine the associations among mental health related eHealth literacy (eHL), mental health-seeking attitude, and wellbeing among Chinese young electronic media users during the COVID-19 pandemic. Methods: A web-based cross-sectional survey was conducted in Guangzhou, China. The modified eHealth literacy Scale, Mental Help-Seeking Attitudes Scale, and Short Warwick-Edinburgh Mental Wellbeing Scale were used. Structural equation modeling (SEM) examined the associations between them and was adjusted by several controlled variables. Results: Totally, 1,008 participants completed the questionnaire and provided valid responses. The eHL showed a statistically significant and direct effect on mental wellbeing in this sample. The higher the level of eHL, the better wellbeing of the participants. The mental health-seeking attitude is also positively correlated with mental wellbeing, indicating that the more positive attitude toward seeking mental health services, the better the wellbeing participants reported. The higher level of eHL is significantly associated with a more positive attitude toward seeking mental health services. Conclusion: Training to improve eHL may optimize young electronic media users' mental health outcomes. Development and use of a mental health specific eHL instrument in future studies should be encouraged.


Asunto(s)
COVID-19 , Telemedicina , Humanos , Salud Mental , Estudios Transversales , Pandemias , China
4.
ACS Med Chem Lett ; 10(1): 40-43, 2019 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-30655944

RESUMEN

A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.

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