The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Simultaneous determination of cortisone and cortisol in serum by HPLC-DAD and application for pharmacokinetics

To develop a high performance liquid chromatography method for the simultaneous determination of cortisone and cortisol in rat serum and apply it for pharmacokinetics. After addition of pirfenidone as internal standard (IS), a liquid-liquid extraction with ethylacetate was employed for the sample preparation. Samples were separated on Zorbax SB-C18 column at 25 ºC using mobile phase consisting of acetonitrile-water-0.1 % trifluoroacetic acid with flow rate of 0.9 mL/min, utilizing DAD detection at 246 nm. Excellent liner relationships of the cortisone and cortisol concentrations were obtained from 50 to 6000 ng/mL, with r = 0.9997, 0.9999 respectively, and the lower limit of quantitation (LLOQ) were both 50 ng/mL. The developed method was successfully applied to pharmacokinetic studies of cortisone and cortisol in rats following single dose of 20 mg/kg via intraperitoneal injection.Colegio de Farmacéuticos de la Provincia de Buenos Aire

The effects of (+)-Gossypol on 11β-HSD and the concentration of corticosterone and dehydrocorticosterone in mice serum and tissues

11β-hydroxysteroid dehydrogenase (11β-HSD) plays an important part in mediating glucocorticoid action, catalyzing the interconversion of corticosterone (B) and dehydrocorticosterone (A) in rodents. The aim of our study is to investigate the effects of (+)-gossypol (G+) on 11β-HSD. Adult ICR mice were given B and B + (G+) by intraperitoneal injection. The activity of 11β-HSD was evaluated by measuring the ratio of A and B, meanwhile the effects of (+)-gossypol on the conversion rate of B to A was determined with HPLC. Serum A/B levels of the B+(G+) group decreased by 2.42, 7.32, 17.85, 31.39, and 40.02 % compared to the B group at each measured time interval. A/B levels at 1 h for the B + (G+) group decreased by 43.78, 21.29 and 34.47% in liver, kidney and adrenal glands, respectively, in comparison to the B group. However, (+)-gossypol had no effect on brain and testis. (+)-Gossypol was an inhibitor of 11β-HSD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates

Influence of Built Environment on Street Vitality: A Case Study of West Nanjing Road in Shanghai Based on Mobile Location Data

A successful built environment is assumed to encourage street vitality in the time and space dimensions. The availability of mobile location data has made it possible to measure street vitality from a large-scale and multiperiod perspective. We used the mobile location data recorded in West Nanjing Road and the surrounding streets in Shanghai as a proxy for street activity, and introduced intensity and instability as indicators of street vitality to test whether there is still a correlation between street vitality and built environment in high-density cities, and whether there are applicable conditions. The results show that for spatial units with higher intensity, the street activities tend to be more unstable. It is more effective to promote street vitality by increasing the diversity of commercial formats. For the streets in high-intensity areas, increasing the mix degree of building functions and the development intensity of the surrounding blocks may not necessarily enhance the street vitality. The design of the external spaces is always an effective measure to maintain continuous vitality. Subway stations play a significant role in promoting street vitality

Association of metformin exposure with low risks of frailty and adverse outcomes in patients with diabetes

Abstract Background Diabetes is an independent risk factor of frailty, which increases adverse outcomes in patients with diabetes. Metformin is a common antidiabetic drug in clinical practice. Insulin resistance and chronic inflammation are the two common mechanisms of diabetes and frailty, as well as the main targets of metformin. Research suggested that metformin has anti-aging potential. However, few studies focus on the relationship between metformin and frailty. Thus, we aimed to explore whether metformin was associated with a low risk of frailty and other adverse outcomes in diabetic patients. Methods A total of 422 patients (≥ 40 years old) with type 2 diabetes were recruited. Frailty was defined by the Fried phenotype. General information and metformin exposure data were collected, and comprehensive geriatric assessment and laboratory tests were performed. Follow-up was conducted after 4.5 years. The primary outcome was the combined endpoint of cardiovascular events, cerebrovascular events, readmission, and death. Binary logistic regression analysis was used to analyze the association of metformin with frailty. Survival analysis was performed using Cox proportional hazards models. Results The total prevalence of frailty was 19.4% among the participants with diabetes. 13.1% of patients in the metformin group and 28.2% in the non-metformin group had frailty. Metformin was inversely associated with frailty after adjusting for age, sex, duration, blood glucose levels, target organ damage, comorbidities, and polypharmacy. Further longitudinal analysis showed that metformin was also independently associated with a low risk of combined primary outcomes after adjusting for multiple covariables, while frailty was related to an increased risk of the combined primary outcomes. In the non-frail group, metformin was associated with a decreased risk of combined primary outcomes after adjustment for age and sex. However, the protective effect of metformin on adverse outcomes was not found in frail participants with diabetes. Conclusions Metformin use is associated with a reduced risk of frailty. In addition, frailty may attenuate the protective effects of metformin on adverse outcomes in diabetic patients. The early identification and prevention of frailty progression may help enhance the benefits of metformin in patients with diabetes

The pulmonary sequalae in discharged patients with COVID-19: a short-term observational study

BACKGROUND: A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia were discharged from hospitals in Wuhan, China. We aimed to determine the cumulative percentage of complete radiological resolution at each time point, to explore the relevant affecting factors, and to describe the chest CT findings at different time points after hospital discharge. METHODS: Patients with COVID-19 pneumonia confirmed by RT-PCR who were discharged consecutively from the hospital between 5 February 2020 and 10 March 2020 and who underwent serial chest CT scans on schedule were enrolled. The radiological characteristics of all patients were collected and analysed. The total CT score was the sum of non-GGO involvement determined at discharge. Afterwards, all patients underwent chest CT scans during the 1st, 2nd, and 3rd weeks after discharge. Imaging features and distributions were analysed across different time points. RESULTS: A total of 149 patients who completed all CT scans were evaluated; there were 67 (45.0%) men and 82 (55.0%) women, with a median age of 43 years old (IQR 36–56). The cumulative percentage of complete radiological resolution was 8.1% (12 patients), 41.6% (62), 50.3% (75), and 53.0% (79) at discharge and during the 1st, 2nd, and 3rd weeks after discharge, respectively. Patients ≤44 years old showed a significantly higher cumulative percentage of complete radiological resolution than patients > 44 years old at the 3-week follow-up. The predominant patterns of abnormalities observed at discharge were ground-glass opacity (GGO) (125 [83.9%]), fibrous stripe (81 [54.4%]), and thickening of the adjacent pleura (33 [22.1%]). The positive count of GGO, fibrous stripe and thickening of the adjacent pleura gradually decreased, while GGO and fibrous stripe showed obvious resolution during the first week and the third week after discharge, respectively. “Tinted” sign and bronchovascular bundle distortion as two special features were discovered during the evolution. CONCLUSION: Lung lesions in COVID-19 pneumonia patients can be absorbed completely during short-term follow-up with no sequelae. Two weeks after discharge might be the optimal time point for early radiological estimation

Influences of Anlotinib on Cytochrome P450 Enzymes in Rats Using a Cocktail Method

The present study aimed to investigate the effect of anlotinib (AL3818) on pharmacokinetics of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C6, CYP2D1, CYP2D2, and CYP3A1/2) by using five cocktail probe drugs in vivo. After pretreatment for 7 days with anlotinib (treatment group) or saline (control group) by oral administration, probe drugs phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam were administered to rats by oral administration. Blood samples were obtained at a series of time-points and the concentrations of five probe drugs in plasma were determined by a UHPLC-MS/MS method. The results showed that treatment with anlotinib had no significant effect on rat CYP1A2, CYP2D2, and CYP2C6. However, anlotinib had a significant inductive effect on CYP2D1 and CYP3A1/2. Therefore, caution is needed during the concomitant use of anlotinib with other drugs metabolized by CYP2D1 and CYP3A1/2 because of potential drug-anlotinib interactions

Influences of Corydalis decumbens on the Activities of CYP450 Enzymes in Rats with a Cocktail Approach

Corydalis decumbens, a Traditional Chinese Medicine, has been widely used for the alternative and/or complementary therapy of hypertension, arrhythmias rheumatoid arthritis, sciatica, stroke, hemiplegia, paraplegia, and vascular embolism. The aim of this study was to determinate the potential effects of Corydalis decumbens on the five cytochrome P450 (CYP) enzyme activities (CYP1A2, CYP3A4, CYP2C9, CYP2C19, and CYP2D6) by cocktail approach. To evaluate whether concurrent use of Corydalis decumbens interferes with the effect of several prescription drugs, saline (control group) or Corydalis decumbens (XTW group) were administrated via gavage for 7 successive days. A probe cocktail solution (phenacetin, omeprazole, metoprolol, tolbutamide, and midazolam) was given 24 h after the last dose of saline or Corydalis decumbens. A specific and sensitive UHPLC–MS/MS method was validated for the determination of five substrates and their metabolites in control group and XTW group. Our results indicated that Corydalis decumbens could have inductive effects of CYP2C19 and inhibit the activities of CYP1A2 and CYP3A4. However, Corydalis decumbens had no significant influence on CYP2C9 and CYP2D6. The herb-drug interaction should require more attention by careful monitoring and appropriate drug dosing adjustments to the concurrent use of western medications which were metabolized by CYP1A2, CYP2C19, and CYP3A4 in human—Corydalis decumbens, Cytochrome P450, Cocktail, Pharmacokinetics, herb–drug interactions