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1.
Exp Ther Med ; 25(1): 59, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36588818

RESUMO

Colorectal cancer (CRC) is one of the most common cancers worldwide and the consumption of a high-calorie diet is one of its risk factors. Calorie restriction (CR) slows tumor growth in a variety of cancers, including colorectal cancer; however, the mechanism behind this remains unknown. In the present study, CR effectively reduced the tumor volume and weight in a xenograft BALB/c male nude mouse model. In addition, tumor immunohistochemistry revealed that the CR group had significantly higher expression of Bax (P<0.001) and significantly lower levels of Bcl2 (P<0.0001) and Ki67 (P<0.001) compared with control group. Furthermore, data from 16S ribosomal (r)RNA sequencing implied that CR was able to reprogram the microbiota structure, characterized by increased Lactobacillus constituent ratio (P<0.05), with amelioration of microbial dysbiosis caused by CRC. Further receiver operating characteristic curves demonstrated that the bacteria Bacteroides [area under the curve (AUC)=0.800], Lactobacillus (AUC=0.760) and Roseburia (AUC=0.720) served key roles in suppression of CRC in the mouse model. The functional prediction of intestinal flora indicated 'cyanoamino acid metabolism' (P<0.01), 'replication initiation protein REP (rolling circle plasmid replication)' (P<0.01), 'tRNA G10 N-methylase Trm11' (P<0.01) and 'uncharacterized protein with cyclophilin fold, contains DUF369 domain' (P<0.05) were downregulated in CR group. These findings implied that CR suppressed CRC in mice and altered the gut microbiota.

2.
Cell Res ; 29(9): 739-753, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31444469

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV), was listed among the top 10 priority infectious diseases by the World Health Organization due to its high fatality of 12%-50% and possibility of pandemic transmission. Currently, effective anti-SFTSV intervention remains unavailable. Here, by screening a library of FDA-approved drugs, we found that benidipine hydrochloride, a calcium channel blocker (CCB), inhibited SFTSV replication in vitro. Benidipine hydrochloride was revealed to inhibit virus infection through impairing virus internalization and genome replication. Further experiments showed that a broad panel of CCBs, including nifedipine, inhibited SFTSV infection. The anti-SFTSV effect of these two CCBs was further analyzed in a humanized mouse model in which CCB treatment resulted in reduced viral load and decreased fatality rate. Importantly, by performing a retrospective clinical investigation on a large cohort of 2087 SFTS patients, we revealed that nifedipine administration enhanced virus clearance, improved clinical recovery, and remarkably reduced the case fatality rate by >5-fold. These findings are highly valuable for developing potential host-oriented therapeutics for SFTS and other lethal acute viral infections known to be inhibited by CCBs in vitro.


Assuntos
Phlebovirus/fisiologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/química , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo L/metabolismo , Linhagem Celular , Chlorocebus aethiops , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Nifedipino/análogos & derivados , Nifedipino/farmacologia , Nifedipino/uso terapêutico , Febre por Flebótomos/tratamento farmacológico , Febre por Flebótomos/patologia , Febre por Flebótomos/virologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Estudos Retrospectivos , Células Vero , Carga Viral , Replicação Viral/efeitos dos fármacos
3.
Appl Opt ; 57(16): 4649-4658, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877374

RESUMO

Targeting star-like water surface clutter, a clutter suppression method based on infrared polarization information is proposed. First, the clutter is suppressed from a global perspective using infrared polarization imaging technology, and a basic clutter-suppressed image is obtained. Then, using the Reed-Xiaoli anomaly detection algorithm, the remaining clutter positions in the basic image are determined from the polarization intensity image and basic image. Finally, an image filtering algorithm is utilized to further suppress the remaining clutter in the basic image. In experiments, the proposed method can not only improve the signal-to-clutter ratio as much as 152%, but also preserve the target information and background texture features effectively, indicating clear superiority of our method over existing clutter suppression algorithms. Clutter suppression and target detail preservation can enhance observer understanding of a scene significantly, so this method is applied to the detection and recognition of targets on the water surface.

4.
Yi Chuan ; 34(8): 943-9, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-22917899

RESUMO

p53 is an important tumor suppressor gene and one of the key genes in sensing and regulating responses to the environmental stress. Recent study showed that cold winter temperature naturally selected p53 Arg72 in eastern Asian population, suggesting that p53 plays a role in reproduction. It has also been reported that some SNPs of p53, Mdm2(Murine double minute 2), MdmX and Hausp (Herpes virus-associated ubiquitin-specific protease) in p53 pathway are associated with the risk of the women's reproduction disorder. p53 regulates the LIF (leukaemia inhibitory factor) expression level by its DBD domain, and thus contributes to female reproduction by affecting the embryo implantation process. The MDM2, MDMX, and HAUSP proteins regulates the level and activity of p53 protein, which are critical for the appropriate p53 response in the embryo implantation process. The members of p53 family, p63 and p73, also play roles in female reproduction through other pathways. p63 has been implicated as a major regulator of oocyte death following treatment with irradiation and chemotherapeutic drugs, which prevents fetal malformation. p73 regulates the formation of spindle assembly complex(SAC). The dysfunction of SAC results in poor blastocyst quality and defects in kinetochore-microtubule associations, which leads to aneuploidy. This review summarized the function of p53 family and its pathway related proteins in female reproduction, pointed out a new method in improving the success rate in IVF-ET, and provided a new diagnosis idea for unexplained infertile women. It will facilitate personalized strategies in the infertility therapy.


Assuntos
Reprodução/fisiologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Feminino , Fertilização in vitro , Humanos , Infertilidade Feminina , Reprodução/genética , Transdução de Sinais
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