Aim To study the inhibitory activities of potential new anti-influenza virus agents,3-O-β-chaco-triosyl pentacyclic triterpenoids against the entry of H5N1influenza viruses.Methods Three target com-pounds were designed and synthesized structurally re-lated to the lead compound 3-O-β-chacotriosyl dioscin derivative (1 )with inhibitory activities against H5N1 influenza viruses.The inhibitory activities of these tar-get compounds were tested at a cellular level pseudo vi-rus system targeting H5N1 influenza viruse entry.Re-sults All the compounds 1 a,1 b and 1 c showed po-tent inhibitory activities against the entry of A/Thai-land/Kan353/2004 pseudo virus into the target cells, of which compound 1 b showed the best inhibitory activ-ity with an IC50 value of (1.25 ±0.22)μmol·L-1. Conclusion The SARs analysis of these compounds indicated that replacement of the aglycone moiety of compound 1 with pentacyclic triterpenoids could in-crease antiviral activity.Different types of pentacyclic triterpen as aglycone residue had the significant influ-ence on the inhibitory activity (1 b >1 c >1 a),sug-gesting ursane type of triterpenes was superior to the two other kinds of triterpenes as aglycone residue.

OBJECTIVETo study the inhibitory activities of 3-O-β-chacotriosyl benzyl ursolate and its derivatives as potential new anti-influenza virus agents against the entry of H5N1 influenza viruses into the target cells.

METHODSFour target compounds were designed and synthesized, which were structurally related to the lead compound 3-O-β-chacotriosyl methyl ursolate (1). The inhibitory activities of these compounds were tested at a cellular level psuedovirus system targeting H5N1 influenza viruse entry.

RESULTS AND CONCLUSIONThe compounds 1b, 1c and 1d showed potent inhibitory activities against the entry of A/Thailand/Kan353/2004 pseudovirus into the target cells, and among them compound 1d showed the strongest inhibitory activity with an IC50 value of 0.96 ± 0.10 µmol/L. The structure-activity relationship analysis of these compounds indicated that when 17-COOH of ursolic acid was esterified, introduction of Me groups rather than aryl groups more strongly enhanced the inhibitory activity. Changing 17-COOH of ursolic acid into amide could increase the antiviral activity and decrease the cytotoxicity of the compounds in MDCK cells.

Animals ; Antiviral Agents ; chemistry ; Dogs ; Influenza A Virus, H5N1 Subtype ; drug effects ; physiology ; Madin Darby Canine Kidney Cells ; Structure-Activity Relationship ; Triterpenes ; chemistry ; Virus Internalization ; drug effects

Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.

This study explored the feasibility of mineral element content and ratios of nitrogen isotopes to discriminate the cultivation mode of Dendrobium nobile in order to provide theoretical support for the discrimination of the cultivation mode of D. nobile. The content of 11 mineral elements(N, K, Ca, P, Mg, Na, Fe, Cu, Zn, Mn, and B) and nitrogen isotope ratios in D. nobile and its substrate samples in three cultivation methods(greenhouse cultivation, tree-attached cultivation, and stone-attached cultivation) were determined. According to the analysis of variance, principal component analysis, and stepwise discriminant analysis, the samples of different cultivation types were classified. The results showed that the nitrogen isotope ratios and the content of elements except for Zn were significantly different among different cultivation types of D. nobile(P<0.05). The results of correlation analysis showed that the nitrogen isotope ratios, mineral element content, and effective component content in D. nobile were correlated with the nitrogen isotope ratio and mineral element content in the corresponding substrate samples to varying degrees. Principal component analysis can preliminarily classify the samples of D. nobile, but some samples overlapped. Through stepwise discriminant analysis, six indicators, including δ~(15)N, K, Cu, P, Na, and Ca, were screened out, which could be used to establish the discriminant model of D. nobile cultivation methods, and the overall correct discrimination rates after back-substitution test, cross-check, and external validation were all 100%. Therefore, nitrogen isotope ratios and mineral element fingerprints combined with multivariate statistical analysis could effectively discriminate the cultivation types of D. nobile. The results of this study provide a new method for the identification of the cultivation type and production area of D. nobile and an experimental basis for the quality evaluation and quality control of D. nobile.
Dendrobium ; Minerals ; Discriminant Analysis ; Multivariate Analysis ; Nitrogen Isotopes

Objective: To evaluate the feasibility, efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs) for neoadjuvant therapy. Methods: Eighty-six patients with stage ⅢA EGFR-mutant lung adenocarcinoma were assigned to 2 groups (n=43 in each group) according to the random number table method: neoadjuvant targeted therapy group (single oral dose of erlotinib 150 mg per day, for 9 weeks) and neoadjuvant chemotherapy group (2 cycles of pemetrexed combined with cisplatin chemotherapy followed by 3- week discontinuation). Surgical treatment was underwent after imaging efficacy evaluation. Results: In neoadjuvant targeted therapy group, 4 achieved complete response (CR), 25 achieved partial response (PR), giving an objective response rate (ORR) of 67.4%. In pathological response, 8 patients had grade Ⅰ, 20 patients had grade Ⅱ, giving a pathological response rate of 65.1%. The most frequent adverse events (AEs) were rash and diarrhea. In neoadjuvant chemotherapy group, 2 had CR and 17 had PR, giving an ORR of 44.2%. In pathological response, 3 patients had grade Ⅰ, 15 patients had grade Ⅱ, giving a pathological response rate of 41.9%. The main AEs were hematologic toxic effects. The ORR, histological efficacy and hematologic toxicity showed statistical significance between the two groups (P<0.05). The neoadjuvant targeted therapy group had 90.7% resection rate, (299.8±23.4) ml of hemorrhage volume during operation, (5.2±0.4) days of extubation time and 9.3% postoperative complication rate. Corresponding results were 83.7%, (308.9±22.7) ml, (5.4±0.6) days and 11.6% in neoadjuvant chemotherapy group, which showed no statistical significance (P>0.05). Conclusions Neoadjuvant targeted treatment for stage ⅢA lung adenocarcinoma harboring EGFR mutations. The regimen could be considered as a choice of neoadjuvant treatment for patients with stage ⅢA EGFR-mutant lung adenocarcinoma.