PBPK/PD Modeling of Nifedipine for Precision Medicine in Pregnant Women: Enhancing Clinical Decision-Making for Optimal Drug Therapy.

OBJECTIVE: This study aims to develop physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) predictive models for nifedipine in pregnant women, enhancing precision medicine and reducing adverse reactions for both mothers and infants. METHODS: A PBPK/PD model was constructed using PK-Sim, MoBi, and MATLAB software, integrating literature and pregnancy-specific physiological information. The process involved: (1) establishing and validating a PBPK model for serum clearance after intravenous administration in non-pregnant individuals, (2) establishing and validating a PBPK model for serum clearance after oral administration in non-pregnant individuals, (3) constructing and validating a PBPK model for enzyme clearance after oral administration in non-pregnant individuals, and (4) adjusting the PBPK model structure and enzyme parameters according to pregnant women and validating it in oral administration. (5) PK/PD model was explored through MATLAB, and the PBPK and PK/PD models were integrated to form the PBPK/PD model. RESULTS: The Nifedipine PBPK model's predictive accuracy was confirmed by non-pregnant and pregnant validation studies. The developed PBPK/PD model accurately predicted maximum antihypertensive effects for clinical doses of 5, 10, and 20 mg. The model suggested peak effect at 0.86 h post-administration, achieving blood pressure reductions of 5.4 mmHg, 14.3 mmHg, and 21.3 mmHg, respectively. This model provides guidance for tailored dosing in pregnancy-induced hypertension based on targeted blood pressure reduction. CONCLUSION: Based on available literature data, the PBPK/PD model of Nifedipine in pregnancy demonstrated good predictive performance. It will help optimize individualized dosing of Nifedipine, improve treatment outcomes, and minimize the risk of adverse reactions in mothers and infants.

BDE-209 inhibits pluripotent genes expression and induces apoptosis in human embryonic stem cells.

Decabromodiphenyl ether (BDE-209) has been detected in human serum, semen, placenta, cord blood and milk worldwide. However, little is known regarding the potential effects on the early human embryonic development of BDE-209. In this study, human embryonic stem cell lines FY-hES-10 and FY-hES-26 were used to evaluate the potential effects and explore the toxification mechanisms using low-level BDE-209 exposure. Our data showed that BDE-209 exposure (1, 10 and 100 nM) reduced the expression of pluripotent genes such as OCT4, SOX2 and NANOG and induced human embryonic stem cells (hESCs) apoptosis. The downregulation of BIRC5/BCL2 and upregulation of BAX were related to apoptosis of hESCs induced by BDE-209 exposure. A mechanism study showed that OCT4 down-regulation accompanied by OCT4 promoter hypermethylation and increasing miR-145/miR-335 levels, OCT4 inhibitors. Moreover, BDE-209 could increase the generation of intracellular reactive oxygen species (ROS) and decrease SOD2 expression. The ROS increase and OCT4 downregulation after BDE-209 exposure could be reversed partly by antioxidant N-acetylcysteine supplement. These findings showed that BDE-209 exposure could decrease pluripotent genes expression via epigenetic regulation and induce apoptosis through ROS generation in human embryonic stem cells in vitro.

Effects of acupuncture on preeclampsia in Chinese women: a pilot prospective cohort study.

OBJECTIVE: To investigate the acceptability and feasibility of acupuncture treatment as an adjunct to usual care in Chinese women with preeclampsia. METHODS: This was a pilot prospective cohort study. Pregnant women with a diagnosis of preeclampsia were offered acupuncture and allocated into groups based on their choice: the acupuncture group (n=11) comprised women electing to receive treatment (up to 10 sessions over 2 weeks). The control group (n=11) was made up of women who declined and was matched for age, gestation at diagnosis, and parity. All women received usual care and underwent measurement of blood pressure (BP) at four time points: at baseline, at the end of the intervention, immediately before delivery, and postpartum (within 24 h). RESULTS: Patients in the acupuncture group had significantly lower BP at time of delivery, and postpartum, than patients in the control group (p<0.05). The individual change in BP between baseline and the end of treatment was significantly greater in the acupuncture group versus the control group for both systolic BP (median (IQR) -8 (-3 to -14) vs +1 (-7 to +9) mm Hg, p=0.007) and diastolic BP (-3 (-1 to -3) vs +2 (-2 to +7) mm Hg, p=0.013). There were no significant differences between the groups in perinatal outcomes and no adverse effects of treatment. CONCLUSIONS: Acupuncture plus usual care was associated with a greater reduction in BP than usual care alone. Further studies are needed to clarify the role of acupuncture in the treatment of preeclampsia.

[Effects of danshen on NO and ET-1 secreted by endothelial cells induced by the serum of pre-eclampsia patients].

OBJECTIVE: To explore the protective effects of danshen (Salvia Miltiorrhiza) on vascular endothelial cells in hypertension patients in the gestation period. METHODS: The umbilical vein endothelial cells pre-incubated with Danshen solution at different concentrations (0, 100, 200, and 300 mg/L) were randomly divided into 3 groups, i.e., the blank control group (8 cases), the normal control group (14 cases, cultured in the serum from 14 normal pregnant women), and the observation group (14 cases, cultured in the serum from 14 pregnant women with severe pre-eclampsia). The levels of nitric oxide (NO) and endothelin-1 (ET-1) in each culture supernatant were detected respectively. RESULTS: The ET-1 level was higher in 300 mg/L Danshen solution group than in 0 mg/L and 100 mg/L Danshen solution groups (P <0.05). The NO level was lower in the observation group than in the blank control group and the normal control group (P <0. 05). The NO level was higher in 200 mg/L Danshen solution group than in 0 mg/L Danshen solution group (P <0.05). The NO level was higher in 300 mg/L Danshen solution group than in 0 mg/L, 100 mg/L, and 200 mg/L Danshen solution groups (P <0.05). CONCLUSION: Danshen could increase the secretion of NO from in vitro umbilical vein endothelial cells cultured in the serum from patients with pre-eclampsia, and reduce the secretion of ET-1.