Exosomal microRNA (miRNA) exerts potential roles in non-small-cell lung cancer (NSCLC). The current study elucidated the role of miR-30b-5p shuttled by bone marrow mesenchymal stem cells (BMSCs)-derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC-related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR-30b-5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs-derived exosomes overexpressing miR-30b-5p were used to establish subcutaneous tumorigenesis models to study the effects of miR-30b-5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC-exo-miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC-exo-miR-30b-5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR-30b-5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC-exo-miR-30b-5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC-derived exosomes-loaded miR-30b-5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis. 相似文献
In this work, binding interactions of artemisinin (ART) and dihydroartemisinin (DHA) with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated thoroughly to illustrate the conformational variation of serum albumin. Experimental results indicated that ART and DHA bound strongly with the site I of serum albumins via hydrogen bond (H-bond) and van der Waals force and subsequently statically quenched the intrinsic fluorescence of serum albumins through concentration-dependent manner. The quenching abilities of two drugs on the intrinsic fluorescence of HSA were much higher than the quenching abilities of two drugs on the intrinsic fluorescence of BSA. Both ART and DHA, especially DHA, caused the conformational variation of serum albumins and reduced the α-helix structure content of serum albumins. DHA with hydrophilic hydroxyl group bound with HSA more strongly, suggesting the important roles of the chemical polarity and the hydrophilicity during the binding interactions of two drugs with serum albumins. These results reveal the molecular understanding of binding interactions between ART derivatives and serum albumins, providing vital information for the future application of ART derivatives in biological and clinical areas. 相似文献
OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs. DESIGN: Comparison of drug-resistant and non-drug-resistant cases of tuberculosis. SETTING: Manitoba. PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989. MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described. RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem. CONCLUSION: Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease. 相似文献
Rhizosphere effect of nanoscale zero-valent iron (nZVI) is crucial but little reported. Maize seeds were dressed with four nZVI concentrations (0, 1.0, 1.5, 2 g kg−1) and inoculated with arbuscular mycorrhizal fungus (AMF) (Funneliformis mosseae). The SEM images illuminated that excessive nZVI particles (2 g kg−1) were agglomerated on the surface of hyphae and spore, causing severe deformation and inactivation of AMF symbionts and thereafter inhibiting water uptake in maize seedlings. This restrained the scavenging effects of enzymatic (superoxide dismutase, peroxidase) and non-enzymatic compounds (proline & malondialdehyde) on ROS, and leaf photoreduction activity and gas exchange ability (p < 0.05). Interestingly, the inoculation with AMF effectively alleviated above negative effects. In contrast, appropriate dose of nZVI, that is, ≤1.5 g kg−1, can be evenly distributed on the hyphae surface and form the ordered symbionts with AMF. This help massively to enhance hyphae growth and water and nutrient uptake. The enhanced mycorrhizal infection turned to promote rhizosphere symbiont activity and leaf Rubisco and Rubisco activase activity. Light compensation point was massively lowered, which increased photosynthetic carbon supply for AMF symbionts. Particularly, such priming effects were evidently enhanced by drought stress. Our findings provided a novel insight into functional role of nZVI in agriculture and AMF-led green production. 相似文献
Journal of Plant Growth Regulation - 1,2,4-trichlorobenzene (1,2,4-TCB) pollution in fields has become a potential threat to rice growth, yet little is known about the different response of many... 相似文献
Compared with the standard method of manual fertilizer broadcasting (MFB), mechanized hill-drilling direct-seeding with deep application of slow-release nitrogen fertilizer (MHDDF) is an efficient method to integrate both fertilization and seeding. However, there are few studies that combine the use of slow-release fertilizer with MHDDF. We sought to explore the combined effect of MHDDF with slow-release fertilizer on rice yield and nitrogen, phosphorus, and potassium utilization, compared to MFB. We compared three different MHDDF methods (D30: 450 kg ha?1, D40: 600 kg ha?1, D50: 750 kg ha?1), with one MFB method (B50: 750 kg ha?1), and one control (CK: 0 kg ha?1). We found that the yield of all MHDDF method was higher than that of both the MFB method. Yield was the highest in the D50 treatment and was 14.14–46.03% higher than that in B50 treatment. Biomass accumulation, nutrient accumulation, and nutrient use efficiency were similarly higher in MHDDF method than both MFB and CK. Compared to B50, the D50 treatment increased nitrogen recovery efficiency by 170.53–231.50%, phosphorus recovery efficiency by 480.00–724.25%, and potassium recovery efficiency by 201.55–169.59%. Overall, we found that combining MHDDF with slow-release fertilizer was an effective method to increase rice yield and nutrient use efficiency compared with MFB.
As one of the common and serious chronic complications of diabetes mellitus (DM), the related mechanism of diabetic retinopathy (DR) has not been fully understood. Müller cell reactive gliosis is one of the early pathophysiological features of DR. Therefore, exploring the manner to reduce diabetes-induced Müller cell damage is essential to delay DR. Thioredoxin 1 (Trx1), one of the ubiquitous redox enzymes, plays a vital role in redox homeostasis via protein–protein interactions, including apoptosis signal-regulating kinase 1 (ASK1). Previous studies have shown that upregulation of Trx by some drugs can attenuate endoplasmic reticulum stress (ERS) in DR, but the related mechanism was unclear. In this study, we used DM mouse and high glucose (HG)-cultured human Müller cells as models to clarify the effect of Trx1 on ERS and the underlying mechanism. The data showed that the diabetes-induced Müller cell damage was increased significantly. Moreover, the expression of ERS and reactive gliosis was also upregulated in diabetes in vivo and in vitro. However, it was reversed after Trx1 overexpression. Besides, ERS-related protein expression, reactive gliosis, and apoptosis were decreased after transfection with ASK1 small-interfering RNA in stable Trx1 overexpression Müller cells after HG treatment. Taken together, Trx1 could protect Müller cells from diabetes-induced damage, and the underlying mechanism was related to inhibited ERS via ASK1. 相似文献