RESUMEN
Seven undescribed polyketide compounds (1-4, 9-11) and six known polyketide compounds (5-8,12, 13) were isolated from Rhodiola tibetica endophytic Penicillium sp. HJT-A-10. The structural of seven undescribed polyketides metabolites were established on the basis of spectroscopic methods. The results of anti-inflammatory activity showed that compounds 1-8ï¼10-13 had significant inhibitory effects on LPS-induced NO production in RAW 264.7 cells.
Asunto(s)
Penicillium , Policétidos , Rhodiola , Penicillium/química , Estructura Molecular , Antiinflamatorios/químicaRESUMEN
Background: CircFBXW7 has been determined to be involved in various cancers; however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. Methods: The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. Results: The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. Conclusion: CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.
RESUMEN
Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.
Asunto(s)
Alternaria/química , Antivirales/aislamiento & purificación , Antivirales/farmacología , Cetonas/aislamiento & purificación , Cetonas/farmacología , Polímeros/aislamiento & purificación , Polímeros/farmacología , SARS-CoV-2/efectos de los fármacos , Antivirales/química , Humanos , Cetonas/química , Estructura Molecular , Polímeros/químicaRESUMEN
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating researches have highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the significance of mesenchymal stem cells (MSCs)-derived exosomal miR-204 in the invasion, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Initially, the expression of miR-204 in human NSCLC tissues and cells was determined by RT-qPCR, which demonstrated that miR-204 was downregulated in NSCLC tissues and cells. Next, Krüppel-like factor 7 (KLF7) was predicted and validated to be a target of miR-204 using dual-luciferase reporter gene assay. NSCLC A549 cells were treated with MSCs-derived exosomes, after which the migration and invasion of A549 cells were detected and expression of EMT-related proteins (E-cadherin, N-cadherin, and Vimentin), KLF7, p-AKT/AKT, and HIF-1α were measured. The results of gain- and loss-of-function assays revealed that miR-204 overexpression in MSCs-derived exosomes inhibited KLF7 expression and the AKT/HIF-1α pathway activity, resulting in impaired cell migration, invasion, as well as EMT. In conclusion, the key findings of the current study demonstrate that exosomal miR-204 from MSCs possesses anticarcinogenic properties against NSCLC via the KLF7/AKT/HIF-1α axis.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exosomas , Neoplasias Pulmonares , Células Madre Mesenquimatosas , MicroARNs , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Transición Epitelial-Mesenquimal/genética , Exosomas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Pulmonares/genética , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
OBJECTIVE: To explore whether or not CD8(+)CD28(-)T cell play a pathogenic role in asthma and detect the effects of dexamethasone (DXM). METHODS: A total of 30 mice were randomly divided into 3 groups: asthmatic group, DXM group and control group (n = 10 each). The asthmatic and DXM groups were sensitized twice and inhaled ovalbumin. The DXM Group received an intraperitoneal injection of DXM 1mg/kg before inhaling ovalbumin. After successful modeling, 3 mice were selected randomly from each group to measure the airway responsiveness. Also a bronchoalveolar lavage cytological study was performed and lung tissue sections were prepared for histopathologic examination to evaluate the airway inflammation. The content of IgE in bronchoalveolar lavage fluid (BALF) was detected with a murine IgE ELISA kit. And the fractions of CD8(+)CD28(-)T cell of peripheral blood and BALF were tested by flow cytometry to analyze the correlation between IgE, eosinophils (EOS) of BALF and CD8(+)CD28(-)T cell of blood. RESULTS: The airway hyperresponsiveness in asthmatic and DXM groups were significantly higher than that in the control group. The number of total cells and EOS of BALF in the asthmatic group [(5.56 ± 4.06) × 10(2)/L; (3.29 ± 2.23) × 10(2)/L] were significantly higher than that in control group [(0.91 ± 0.65) × 10(2)/L, P = 0.003; (0.43 ± 0.37) × 10(2)/L, P = 0.001] and DXM group [(2.59 ± 1.69) × 10(2)/L, P = 0.044; (1.11 ± 0.73) × 10(2)/L, P = 0.008]; while the DXM group was insignificantly higher than the control group (P = 0.234, P = 0.363). There were significant differences in the contents of IgE of BALF for the asthmatic, DXM and control groups [(23.85 ± 5.97) g/L, (13.15 ± 2.22) g/L, (6.54 ± 1.03) g/L, F = 38.558, P = 0.000]. The percentages of CD8(+)CD28(-)T cell in peripheral blood in asthmatic and DXM groups [(18.68 ± 4.12)% and (13.43 ± 2.91)%] were significantly higher than those in control mice [(8.43 ± 4.60)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of BALF in asthmatic group and DXM group [(1.25 ± 0.40)% and (0.66 ± 0.49)%] were also significantly higher than those in control mice [(0.21 ± 0.19)%, both P < 0.05]. The percentages of CD8(+)CD28(-)T cell of blood and BALF in the DXM mice were significantly lower than those in asthmatic group. The correlations between IgE (r = 0.864, P = 0.012), EOS (r = 0.804, P = 0.029) and CD8(+)CD28(-)T cell were significant. CONCLUSION: The fraction of CD8(+)CD28(-)T cell is closely correlated with the inflammation of asthmatic airway. The airway hyperresponsiveness and inflammation in asthmatic mice may be relieved by DXM through its effect of inhibiting the expression of CD8(+)CD28(-) T cell.