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1.
Front Microbiol ; 13: 1041338, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466668

RESUMO

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the full-length and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development.

3.
Acta Pharmacol Sin ; 38(12): 1589-1600, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28748915

RESUMO

Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 µmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.


Assuntos
Autofagia/efeitos dos fármacos , Cardiomiopatia Hipertrófica/induzido quimicamente , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Animais , Cardiomiopatia Hipertrófica/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Ratos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
4.
Acta Pharmacol Sin ; 37(4): 425-43, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26838072

RESUMO

Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.


Assuntos
Doenças Cardiovasculares/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Resposta a Proteínas não Dobradas/fisiologia , Animais , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Chaperonas Moleculares/metabolismo
5.
Chemosphere ; 71(7): 1276-83, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18262587

RESUMO

The southern French (Ganges) ecotype of Thlaspi caerulescens J & C Presl is able to hyperaccumulate several thousand mg Cd kg(-1) shoot dry weight without suffering from phytotoxicity. We investigated the effect of Cd on growth and the activity of carbonic anhydrase (CA), a typical Zn-requiring enzyme, of T. caerulescens in soil and hydroponic experiments. In one of the hydroponic experiments, T. caerulescens was compared to the non-accumulator Thlaspi ferganense N. Busch. In the soil experiment, additions of Cd at 5-500 mg kg(-1) soil increased the growth of T. caerulescens significantly. In the hydroponic experiments, exposure to Cd at 1-50 microM for three weeks had no significant effect on the growth of T. caerulescens, but decreased the growth of T. ferganense markedly even at the lowest concentration of Cd (1muM). Cadmium exposure significantly increased the CA activity in T. caerulescens, but decreased it in T. ferganense. The CA activity in T. caerulescens correlated positively with the Cd concentration in the shoots up to 6000 mg kg(-1), even though shoot Zn concentration was decreased by the Cd treatments. For comparison, Cd treatments had no consistent effect on the activity of superoxide dismutase in T. caerulescens. The results suggest that Cd may play a physiological role in the Cd-hyperaccumulating ecotype of T. caerulescens by enhancing the activities of some enzymes such as CA. Further research is needed to establish whether a Cd-requiring CA exists in T. caerulescens.


Assuntos
Cádmio/farmacologia , Fenômenos Fisiológicos Vegetais/efeitos dos fármacos , Thlaspi/enzimologia , Thlaspi/crescimento & desenvolvimento , Anidrases Carbônicas/metabolismo , Relação Dose-Resposta a Droga , Brotos de Planta/enzimologia , Brotos de Planta/crescimento & desenvolvimento , Superóxido Dismutase/metabolismo
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