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1.
PLoS Pathog ; 17(11): e1010070, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34788350

RESUMO

Nuclear scaffold attachment factor A (SAFA) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS with a high fatality rate of up to 30%. It remains elusive whether and how cytoplasmic SFTSV can be sensed by the RNA sensor SAFA. Here, we demonstrated that SAFA was able to detect SFTSV infection and mediate antiviral interferon and inflammatory responses. Transcription and expression levels of SAFA were strikingly upregulated under SFTSV infection. SAFA was retained in the cytoplasm by interaction with SFTSV nucleocapsid protein (NP). Importantly, SFTSV genomic RNA was recognized by cytoplasmic SAFA, which recruited and promoted activation of the STING-TBK1 signaling axis against SFTSV infection. Of note, the nuclear localization signal (NLS) domain of SAFA was important for interaction with SFTSV NP and recognition of SFTSV RNA in the cytoplasm. In conclusion, our study reveals a novel antiviral mechanism in which SAFA functions as a novel cytoplasmic RNA sensor that directly recognizes RNA virus SFTSV and mediates an antiviral response.


Assuntos
Antivirais/metabolismo , Infecções por Bunyaviridae/imunologia , Citoplasma/imunologia , Imunidade Inata/imunologia , Proteínas Associadas à Matriz Nuclear/metabolismo , Phlebovirus/imunologia , Infecções por Bunyaviridae/metabolismo , Infecções por Bunyaviridae/virologia , Citoplasma/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Proteínas Associadas à Matriz Nuclear/genética
2.
PLoS Negl Trop Dis ; 15(3): e0009113, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33735240

RESUMO

Bats can harbor zoonotic pathogens causing emerging infectious diseases, but their status as hosts for bacteria is limited. We aimed to investigate the distribution, prevalence and genetic diversity of Borrelia in bats and bat ticks in Hubei Province, China, which will give us a better understanding of the risk of Borrelia infection posed by bats and their ticks. During 2018-2020, 403 bats were captured from caves in Hubei Province, China, 2 bats were PCR-positive for Borrelia. Sequence analysis of rrs, flaB and glpQ genes of positive samples showed 99.55%-100% similarity to Candidatus Borrelia fainii, a novel human-pathogenic relapsing fever Borrelia species recently reported in Zambia, Africa and Eastern China, which was clustered together with relapsing fever Borrelia species traditionally reported only in the New World. Multilocus sequence typing (MLST) and pairwise genetic distances further confirmed the Borrelia species in the bats from Central China as Candidatus Borrelia fainii. No Borrelia DNA was detected in ticks collected from bats. The detection of this human-pathogenic relapsing fever Borrelia in bats suggests a wide distribution of this novel relapsing fever Borrelia species in China, which may pose a threat to public health in China.


Assuntos
Borrelia/classificação , Quirópteros/microbiologia , Febre Recorrente/epidemiologia , Carrapatos/microbiologia , Animais , Borrelia/genética , Borrelia/isolamento & purificação , China/epidemiologia , DNA Bacteriano/genética , Vetores de Doenças , Tipagem de Sequências Multilocus , Filogenia , Reação em Cadeia da Polimerase
3.
Am J Transl Res ; 10(12): 3969-3977, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662643

RESUMO

A role of microRNA-4262 (miR-4262) in the carcinogenesis of colon cancer remains undetermined. In this study, we studied the effects and mechanisms of miR-4262 to the colon cancer cell proliferation and apoptosis. We found that the levels of miR-4262 significantly down-regulated in colon cancer tissue, compared to the paired adjacent non-tumor colon tissue. The miR-4262 levels in colon cancer cell lines were significantly lower than those in control normal colon tissues. Transfection with the miR-4262 mimic decreased the cell proliferation and increased cell apoptosis in colon cancer cells, while transfection with the antisense of miR-4262 (as-miR-4262) increased cell proliferation and suppressed cell apoptosis in colon cancer cells. Bioinformatics analyses showed that GALNT4 was a potential target gene of miR-4262. The luciferase activities assay and Western blot verified that miR-4262 targeted GALNT4 mRNA to modulate its protein levels. When we treated cells with miR-4262 and GALN4 siRNA, the cell viability was significantly decreased. Together, our study suggests that aberrantly expressed miR-4262 may affect cell apoptosis and proliferation of human colon cancer cells via GALNT4, which appears to be a promising therapeutic target for colon cancer.

4.
Zhonghua Zheng Xing Wai Ke Za Zhi ; 29(5): 370-5, 2013 Sep.
Artigo em Zh | MEDLINE | ID: mdl-24409781

RESUMO

OBJECTIVE: To observe the effect of zi-hua burn cream on the survival of skin flaps in rats, and its mechanisms. METHODS: 72 Wistar rats, were randomly divided into four groups as zi-hua group(n = 18, external application of alfalfa burn cream), control group (n = 18, external application of heparin sodium cream), model group (n = 18, external application of vaseline) , negative control (n = 18, no operation). 8 cm x 2 cm random skin flaps with pedicle on the side of head were designed on the back of Wistar rats. The drug was applied on the flap surface, 2 times a day. The survival of skin flaps was observed. The change of serum superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), turner necrosis factor-alpha(TNF-alpha)and interleukin-6(IL-6)were compared at 1,2,3,7 d after operation, and histologic examination was performed. RESULTS: The survival rate of zi-hua group (73.58 - 10. 74)% was significantly higher than that of model group (33.40 - 16.05) %, showing a statistical difference (Q = 10.63, P <0.01). There was no significant difference between the zi-hua group and control group (71.65 +/- 11. 92) %. The level of serum SOD, NO in zi-hua group and control group was higher than that in model group, while the level of serum MDA, TNF-alpha and IL-6 was lower than that in model group(P <0.01). On 7 day after operation, skin flaps tissue edema,necrosis and inflammatory cell infiltration in zi-hua group and control group was less obvious than that in model group. There was significant proliferation of granuloma and fibroblast and formation of neonatal capillary in zi-hua group and control group. The vascular density in zi-hua group was obviously higher than that in the model group and control group(P <0. 01). CONCLUSIONS: Zi-hua burn cream could significantly improve the blood supply of skin flaps, increase the survival rate of skin flaps in rats. Its mechanism may be associated with the anti-free-radical-damage action, improve local microcirculation, improve the NO content, reduce the TNF-alpha and IL-6 level, reduce inflammation factor release, improve oxidative stress state, and reduce inflammation reaction.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pele , Retalhos Cirúrgicos , Animais , Interleucina-6/sangue , Masculino , Malondialdeído/sangue , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
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