This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

Objective: To explore the correlation between high-risk human papillomavirus (HPV) infection and bacterial vaginosis in gynecological outpatient department. Methods: From January 2017 to June 2017, 1 563 cases of gynecologic outpatient who underwent vaginal microecological examination and HPV examination in Jiaxing Maternal and Child Health Care Center were selected to analyze the infection rate of high-risk HPV in different age groups.The 1 563 patients were divided into high-risk HPV positive group and negative group.The vaginal microecological indicators and the incidence of bacterial vaginosis in the two groups were analyzed. Results: Among the 1 563 patients, 385 caes were positive for high-risk HPV, the positive rate was 24.63%.The positive rate of high-risk HPV infection increased with age.There wereno statistically significant differences in pH > 4.5, hydrogen peroxide and leukocyte esterase positive rate between high-risk HPV positive group and negative group (40.52% vs.59.48%, 59.74% vs.40.26%, 51.17% vs.48.83%)(χ²=1.625, 0.188, 3.61, all P>0.05), but there was statistically significant difference in sialidase positive rate (12.47% vs.87.53%)(χ²=39.015, P<0.05). The incidence rate of bacterial vaginosis and the positive rate of microecology in the high-risk HPV positive group were significantly higher than those in the negative group (12.73% vs.6.03%, 8.83% vs.3.65%)(χ²=18.377, 16.629, all P<0.05). Conclusion High-risk HPV infection is closely related to female bacterial vaginitis, so it is necessary to pay more attention to the treatment of bacterial vaginosis, restore the balance of vaginal microenvironment, and enhance the vaginal and cervical immunity to further reduce high-risk HPV infection.

Objective To study the correlation between intermedin 1-53 (IMD 1-53) with hypertension and formation of carotid atheromatous plaques.Methods One hundred and thirty-eight patients with 1-2 degree hypertension admitted to our hospital for carotid ultrasonography were divided into atheromatous plaques group (n =98) and atheromatous plaques-free group (n=40) with 30 subjects undergoing physical examination served as a control group in this study.Their serum IMD 1-53 level,blood pressure,and carotid IMT were measured and compared.Results The SBP [(158.57±13.55)mm Hg and (145.16±14.54)mm Hg vs (125.24±10.64)mm Hg,1 mm Hg=0.133 kPa],DBP[(95.23±5.62)mm Hg and (87.15±4.72)mm Hg vs (80.31±4.62)mm Hg] and carotid IMT[(1.26±0.38)mm and (1.05±0.28)mm vs (0.87±0.38)mm] and serum IMD 1-53 level (7.20±1.62 ng/L vs 5.05±1.85 ng/L,P＜0.01) were significantly higher in atheromatous plaques group and atheromatous plaques-free group than in control group and in atheromatous plaques group than in atheromatous plaques-free group.Conclusion IMD 1-53 is involved in the formation of carotid atheromatous plaques and can resist or delay the formation of carotid atheromatous plaques.