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1.
Naunyn Schmiedebergs Arch Pharmacol ; 396(5): 983-1000, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36576506

RESUMO

Ulcerative colitis (UC) is a chronic nonspecific intestinal inflammatory disease, which belongs to a subtype of inflammatory bowel disease, but still lacks effective drug treatment. Bletilla striata (B. striata) is one of the most valuable traditional Chinese medicines (TCMs) in China, can stop bleeding, can promote wound healing, and can regulate immunity. Based on data mining, B. striata was found to be a common TCM for the treatment of UC, but the exact therapeutic mechanism is not yet known. This study aims to explore the potential mechanisms of B. striata in the treatment of UC using network pharmacology, molecular docking techniques, and in vivo experimental research. We extracted the active ingredients and targets of B. striata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. We retrieved and screened the corresponding UC-related target genes in multiple databases. Subsequently, we constructed an herb-ingredient-target-disease-network, generated a protein-protein interaction network, performed Gene Ontology enrichment analysis, and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify potential treatment mechanisms. After screening for key active ingredients and target genes, we performed molecular docking using AutoDock Vina software to select the best binding target for molecular docking and validate the binding activity. The UC model was established in mice, and the results of network pharmacology and molecular docking were verified by in vivo experiments. In all, 5 compounds were obtained from the TCMSP database, and 74 UC-related pathogenic genes were obtained from GeneCards, DisGeNET, OMIM, TTD, and DrugBank. After KEGG enrichment analysis, pathways in cancer, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, and metabolic pathways were identified as the top three signalling pathways associated with UC treatment. The results of molecular docking showed that the active components of B. striata have good binding activities to the pivotal targets epidermal growth factor receptor (EGFR) and PIK3CA. In a dextran sulphate sodium-induced colitis model, we found that B. striata can alleviate the symptoms of UC, decrease the secretion of the inflammatory cytokines interleukin-6 and tumour necrosis factor-α, and downregulate the expression levels of EGFR, PIK3CA, and p-AKT. In conclusion, the treatment of UC with B. striata may alleviate the inflammatory response of the colon, and B. striata mainly inhibits the EGFR/PI3K/AKT signalling pathways.


Assuntos
Colite Ulcerativa , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Receptores ErbB , Classe I de Fosfatidilinositol 3-Quinases
2.
Medicine (Baltimore) ; 100(14): e25287, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832097

RESUMO

ABSTRACT: It is important for patients to maintain a good nutritional status as a health promotion strategy to improve the immune function and thus the prognosis of coronavirus disease 2019 (COVID-19).The objective of this retrospective study is to analyze the relationships of nutritional status with inflammation levels, protein reserves, baseline immune status, severity, length of hospital stay, and prognosis of COVID-19 patients.A total of 63 COVID-19 patients hospitalized in the People's Hospital and the Traditional Chinese Medicine Hospital of the Xinzhou District, Wuhan, China, from January 29, 2020 to March 17, 2020. Sixty-three patients were divided into 3 groups according to the guidelines, moderate (n = 22), severe (n = 14), and critical (n = 25), respectively. The differences in the total nutrition risk screening (NRS) score, inflammation level, protein reserve, baseline immune status, length of hospital stay, and prognosis were compared among patients with moderate, severe, and critical COVID-19.Patients with higher NRS scores tend to have more severe COVID-19, higher C-reactive protein and serum procalcitonin levels, higher white blood cell counts, lower lymphocyte counts, and higher mortality rates (P < .05).Nutritional status may be an indirect factor of the severity and prognosis of COVID-19.


Assuntos
COVID-19/fisiopatologia , Estado Nutricional/fisiologia , Adulto , Idoso , Proteínas Sanguíneas , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Globulinas/análise , Humanos , Tempo de Internação/estatística & dados numéricos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Proteínas , Estudos Retrospectivos , SARS-CoV-2 , Albumina Sérica/análise , Índice de Gravidade de Doença
3.
Front Genet ; 11: 621871, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33552136

RESUMO

High-temperature stress can cause serious abiotic damage that limits the yield and quality of rice. Heat tolerance (HT) during the flowering stage of rice is a key trait that can guarantee a high and stable yield under heat stress. HT is a complex trait that is regulated by multiple quantitative trait loci (QTLs); however, few underlying genes have been fine mapped and cloned. In this study, the F2:3 population derived from a cross between Huanghuazhan (HHZ), a heat-tolerant cultivar, and 9311, a heat-sensitive variety, was used to map HT QTLs during the flowering stage in rice. A new major QTL, qHTT8, controlling HT was identified on chromosome 8 using the bulked-segregant analysis (BSA)-seq method. The QTL qHTT8 was mapped into the 3,555,000-4,520,000 bp, which had a size of 0.965 Mb. The candidate region of qHTT8 on chromosome 8 contained 65 predicted genes, and 10 putative predicted genes were found to be associated with abiotic stress tolerance. Furthermore, qRT-PCR was performed to analyze the differential expression of these 10 genes between HHZ and 9311 under high temperature conditions. LOC_Os08g07010 and LOC_Os08g07440 were highly induced in HHZ compared with 9311 under heat stress. Orthologous genes of LOC_Os08g07010 and LOC_Os08g07440 in plants played a role in abiotic stress, suggesting that they may be the candidate genes of qHTT8. Generally, the results of this study will prove useful for future efforts to clone qHTT8 and breed heat-tolerant varieties of rice using marker-assisted selection.

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