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Background: Asthma and chronic obstructive pulmonary disease (COPD) are heterogenetic diseases and exhibit many similarities. Dutch hypothesis proposed that these two diseases may have common genetic origins. This study aims to investigate whether asthma and COPD share a common genetic background in Chinese patients. Methods: In this case-control study, single nucleotide polymorphisms (SNPs) were genotyped using SNaPshot. Haplotype disease analysis and haplotype phenotype analysis were applied to assess the relationship between three polymorphisms of the FCER2 gene and the risk of COPD/asthma. Additionally, associations between polymorphisms of the FCER2 gene and phenotypes were analyzed. Results: We detected ten SNPs of seven genes (FCER1A, FCGR2A, FCGR2B, CHI3L1, ADRB2, STAT6, and FCER2) expressed by airway epithelial cells. We detected genotypes and allele distributions in 251 COPD patients, 597 asthma patients, and 632 healthy controls. A significant difference was found in the FCER2 gene (rs28364072) between COPD patients and controls (P=0.009). Significant differences were observed in the genotype and allele distributions of rs1801274 (FCGR2A), rs12368672 (STAT6), and rs2228137 (FCER2) between asthma patients and controls (P=0.004, 0.007 and 0.010, respectively). Notably, polymorphisms of FCER2 gene were associated with the risk of both COPD (P=0.009 for rs28364072) and asthma (P=0.01 for rs2228137). Haplotype analysis revealed that haplotype T-G-T (alleles of rs28364072, rs2228137, and rs3760687, respectively) was significantly associated with a higher risk of asthma [odds ratios (OR) =2.25, 95% confidence interval (CI): 1.26-4.01, P=0.006]. Further analysis showed that the C-A-C haplotype and C-G-T haplotype were associated with increased blood eosinophils in either COPD or asthma patients (P=0.034, and P<0.001, respectively). Moreover, haplotypes C-A-C, C-G-C, and T-G-C showed significant associations with serum IgE levels in asthma patients (P=0.002, 0.041, and 0.004, respectively). Conclusions: Our data suggest that the FCER2 gene might associate with predisposition to asthma and COPD, while FCER2 haplotypes were associated with pulmonary function measurements and blood eosinophils counts in both diseases. Our findings support the common genetic basis for asthma and COPD, suggesting a potential therapeutic target for the two diseases.
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Background: To evaluate risk factors and further develop prediction models for intraocular pressure elevation (IOP) after vitreoretinal surgery with silicone oil tamponade to support clinical management. Methods: A retrospective study analyzed 1,061 eyes of 1,061 consecutive patients that presented to the Jiangsu Province Hospital between December 2015 and December 2020, the IOP was measured from the preoperative visit and at the 1-week, 1-month, 3-month, and 6-month visits, and the final postoperative visit before silicone oil removal. Four machine learning methods were used to carried out the prediction of IOP elevation: Decision Tree, Logistic Regression, Random Forest, and Gradient-Boosted Decision Trees (GBDT) based on features including demographic and clinical characteristics, preoperative factors and surgical factors. Predictors were selected based on the p-value of the univariate analysis. Results: Elevated intraocular pressure developed in 26.01% of the eyes postoperatively. Elevated intraocular pressure primarily occurred within 1-2 weeks after surgery. Additionally, the majority of IOP values were distributed around 25-40 mmHg. GBDT utilizing features with p-values less than 0.5 from the hypothesis testing demonstrated the best predictive performance for 0.7944 in accuracy. The analysis revealed that age, sex, hypertension, diabetes, myopia, retinal detachment, lens status and biological parameters have predictive value. Conclusion: Age, sex, hypertension, diabetes, myopia, retinal detachment, lens status and biological parameters have influence on postoperative intraocular pressure elevation for patients with silicone oil tamponade after pars plana vitrectomy. The prediction model showed promising accuracy for the occurrence of IOP elevation. This may have some reference significance for reducing the incidence of high intraocular pressure after pars plana vitrectomy combined with silicone oil filling.
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In this work, twenty-eight novel 17a-aza-D-homo-androster-17-one derivatives, which divided into two categories, were synthesized with commercial available starting material (dehydroepiandrosterone) via oximation reaction, Beckmann rearrangement, hydroxyl protection, N-alkylation and deprotection. All compounds were characterized by 1H NMR, 13C NMR and HRMS. The structure of 14 g was also identified by X-ray single crystal diffraction. The bioactivities, brine shrimp toxicity and cytotoxicity, of all derivatives were tested. The results indicated that compounds 11 h, 11i, 11 m, 11 s, 14 b and 14 g exhibited excellent toxicity against brine shrimp with LC50 values ranging from 5.34 to 16.89 µg/mL, and compounds 11 s and 14 g displayed significant cytotoxicity against HT29 cells and A549 cells with IC50 values of 9.70 µM and 8.85 µM, respectively. Structure-activity relationships are discussed based on the results obtained from our research, and some important determinants for further modification of steroids towards the development of novel drug candidates are identified.
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Artemia , Esteroides , Animais , Células HT29 , Humanos , Relação Estrutura-AtividadeRESUMO
The exopolysaccharides were extracted and separated from the broth of the liquid fermentation of P. umbellatus, and the antioxidant activities and other relative bioactivities were investigated, aiming to find clues for a wider use in the future. Three novel exopolysaccharides of PPS1, PPS2 and PPS3 with molecular weight of 3.7×104-6.9×104Da were obtained. Monosaccharide analysis showed that they were mainly composed of mannose, along with galactose and glucose with different molar ratio, and their structural features were also investigated by FT-IR, NMR and SEM. The antioxidant activity assay in vitro showed these exopolysaccharides exhibited a significant scavenging effect on DPPH· and other free radicals in a dose-dependent manner. Significantly, the stimulate nitric oxide production and phagocytic activity implied that the polysaccharides could enhance the immunity of RAW 264.7 macrophages. Other assays revealed that they have obvious cellular aging delaying activity and the DNA damage protecting activity. In conclusion, these three exopolysaccharides might have potential applications in the fields of pharmaceuticals, cosmetics, and food products.
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Fermentação , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polyporus/química , Polyporus/metabolismo , Animais , Senescência Celular/efeitos dos fármacos , Dano ao DNA , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Monossacarídeos/análise , Óxido Nítrico/biossíntese , Fagocitose/efeitos dos fármacos , Células RAW 264.7RESUMO
Great variations have been found in composition and content of the essential oil of Zanthoxylum bungeanum Maxim. (Rutaceae), resulting from various factors such as harvest time, drying and extraction methods (Huang et al., 2006; Shao et al., 2013), solvent and herbal parts used (Zhang, 1996; Cao and Zhang, 2010; Wang et al., 2011). However, in terms of artificial introduction and cultivation, there is little research on the chemical composition of essential oil extracted from Z. bungeanum Maxim. cultivars, which have been introduced from different origins. In this study, the composition and content of essential oil from six cultivars (I-VI) have been investigated. They were introduced and cultivated for 11 years in the same cultivation conditions. Cultivars were as followings: Qin'an (I) cultivar originally introduced from Qin'an City in Gansu Province; Dahongpao A (II) from She County in Hebei Province; Dahongpao B (III) from Fuping County; Dahongpao C (IV) from Tongchuan City; Meifengjiao (V) from Feng County; and, Shizitou (VI) from Hancheng City, in Shaanxi Province, China. This research is expected to provide a theoretical basis for further introduction, cultivation, and commercial development of Z. bungeanum Maxim.