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1.
J Gen Virol ; 105(2)2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38299799

RESUMO

Zika virus (ZIKV) is a re-emerging RNA virus and causes major public health events due to its link to severe neurological complications in foetuses and neonates. The cGAS-STING signalling pathway regulates innate immunity and plays an important role in the invasion of DNA and RNA viruses. This study reveals a distinct mechanism by which ZIKV restricts the cGAS-STING signalling to repress IFN-ß expression. ZIKV attenuates IFN-ß expression induced by DNA viruses (herpes simplex virus type 1, HSV-1) or two double-stranded DNAs (dsDNA90 and HSV120) in mouse embryonic fibroblasts (MEFs). Notably, ZIKV NS5, the viral RNA-dependent RNA polymerase, was responsible for the repression of IFN-ß. NS5 interacts with STING in the cytoplasm, suppresses IRF3 phosphorylation and nucleus localization and promotes the cleavage of STING K48-linked polyubiquitination. Furthermore, the NS5 methyltransferase (MTase) domain interacts with STING to restrict STING-induced IFN-ß expression. Interestingly, point mutation analyses of conserved methyltransferase active site residue D146 indicate that it is critical for repressing IFN-ß expression induced by STING stimulation in cGAS-STING signalling.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Camundongos , Domínio Catalítico , DNA , Fibroblastos/metabolismo , Imunidade Inata , Interferons , Metiltransferases/metabolismo , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Zika virus/fisiologia
2.
Arch Dermatol Res ; 314(1): 41-51, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33635414

RESUMO

Androgenic alopecia (AGA) has a high incidence. Excess dihydrotestosterone in blood capillaries, which is converted from testosterone by 5α-reductase, is an AGA causative factor. We identified the inhibitory activity of four Polygonum multiflorum compounds against 5α-reductase via high-performance liquid chromatography, and the results showed that Physcion was a potent 5α-reductase inhibitor. Additionally, we found that through inhibiting 5α-reductase expression, Physcion could shorten the time of dorsal skin darkening and hair growth, improve hair follicle morphology, and significantly increase hair follicle count. Eventually, through molecular docking study, we found the binding energy and molecular interactions between Physcion and 5α-reductase type II. These results suggested that Physcion is a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Alopecia/tratamento farmacológico , Emodina/análogos & derivados , Folículo Piloso/efeitos dos fármacos , Extratos Vegetais/farmacologia , Inibidores de 5-alfa Redutase/química , Animais , Emodina/química , Emodina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
3.
Front Pharmacol ; 12: 632602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967768

RESUMO

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) with a complex aetiology that commonly recurs. Most drugs for UC treatment interfere with metabolism and immune responses, often causing some serious adverse reactions. Therefore, the development of alternative treatments, including nutritional supplements and probiotics, have been one of the main areas of current research due to fewer side effect. As both a Chinese medicine and a food, edible bird's nest (EBN) has high nutritional value. Modern pharmacological studies have shown that it has anti-inflammatory, immunoregulatory, antiviral and neuroprotective effects. In this study, UC was induced with dextran sulfate sodium (DSS) to investigate the protective effect of EBN on colitis mice and the related mechanism. The body weight, faecal morphology and faecal occult blood results of mice were recorded every day from the beginning of the modelling period. After the end of the experiment, the length of the colon was measured, and the colon was collected for histopathological detection, inflammatory factor detection and immunohistochemical detection. Mouse spleens were dissected for flow cytometry. The results showed that in mice with colitis, EBN improved symptoms of colitis, reduced colonic injury, and inhibited the increases in the levels of the pro-inflammatory cytokines IL-1ß and TNF-α. The T helper 17 (Th17)/regulatory T (Treg) cell balance was restored by decreasing the expression of IL-17A and IL-6 in intestinal tissues, increasing the expression of TGF-ß, and decreasing the number of Th17 cells in each EBN dose group. These findings suggest that EBN has a protective effect on DSS-mediated colitis in mice, mainly by restoring the Th17/Treg cell balance.

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