INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Miao Tang,Xiao Zhang,Dongli Sun,Yao Yao,Yunchun Zhao,Weidong Fei,Caihong Zheng
The great challenge in developing safe medications for placenta-derived diseases is to reduce or eliminate fetal drug exposure while still providing the necessary therapeutic effect. Rapid advances in nanotechnology have brought opportunities for the therapy of placenta-derived disease through accumulating the drug in the placenta while reducing its placental penetration. Among various nanocarriers, liposomes are regarded as an ideal type of carrier for placental drug delivery due to their biosafety and biodegradability. However, their placental retention effect with different particle sizes has not been studied. This research aimed to explore a suitable size of liposomes for placenta drug delivery. Cy 5 dye was chosen as a model molecule for tracing the distribution of three different-sized liposomes (∼80 nm , 200 nm, and 500 nm) in ICR pregnant mice. The stability, cytotoxicity, and cellular uptake study of Cy 5-loaded liposomes were performed. The in vivo fluorescence studies on ICR pregnant mice suggested that the particle size of liposomes was positively correlated with the degree of liposome aggregation in the placenta. The ratio of fluorescence in the placenta and fetus section (P/F value) was proposed to evaluate the placental retention effect of different-sized liposomes. The results showed that the liposomes with 500 nm had the highest P/F value and thus exhibited the strongest placental retention effect and the weakest placental penetration ability. Moreover, liquid chromatography-mass spectrometry analysis confirmed the reliability of the fluorescence section analysis in exploring the placental retention effect of nanovehicles. In general, this study introduced a simple and intuitive method to evaluate the placental retention effect of nanoplatforms and defined a suitable size of liposomes for placenta-derived disease drug delivery.
研究领域:
药剂学
·
纳米医学
·
妇产科学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Chaochao Gong,Zhuoqi Chen,Yunbing Tang,Han Lu,Sailing Chen,Yang Zhu,Ren-shan Ge,Junzhao Zhao
Aromatase (CYP19A1), a pivotal enzyme in the biosynthesis of estradiol from testosterone, is predominantly expressed in reproductive tissues including placentas. This study investigated the effects of paraben acid and nine parabens on the activity of human and rat CYP19A1 using microsomes derived from human and rat placentas and on estradiol secretion in human choriocarcinoma BeWo cells. The results showed that propyl, butyl, hexyl, heptyl, and nonyl parabens significantly inhibited human CYP19A1 activity, with IC 50 values of 66.37, 61.08, 55.65, 48.26, and 27.24 μM, respectively. In BeWo cells, these parabens notably diminished estradiol secretion at concentrations of 100 μM. Similarly, rat CYP19A1 was inhibited by these parabens, with IC 50 values of 98.07, 70.10, 41.30, 27.93, and 6.33 μM for propyl, butyl, hexyl, heptyl, and nonyl parabens, respectively. Kinetic analysis identified these compounds as mixed inhibitors. Bivariate correlation analysis revealed a negative correlation between the partition coefficient value, molecular weight, the number of carbon atoms in the alcohol moiety, as well as heavy atom number and IC 50 values. Three-dimensional quantitative structure-activity relationship analysis highlighted the critical role of hydrophobic regions in determining inhibitory potency. Docking studies suggested that parabens interact with the heme-iron binding site of both human and rat CYP19A1. This study elucidates the inhibitory effects of various parabens on CYP19A1 and their binding mechanisms, thereby providing a deeper understanding of their potential impact on estrogen biosynthesis.
研究领域:
药理学
·
毒理学
·
生殖生物学
·
分子生物学
·
计算化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2022
·
IF 3.318
Xuan Guo,Lei Zhang,Zihan Lei,Zhe Hou,Hui Li,Xiaodong Li,Jing Dong,Ling Song,Dingding Chen,Dongyang Liu
Objective The aim of this study is to develop a LC-MS/MS method for the quantitation of seven cytochrome P450 (CYP450) enzymes. Methods A high-performance liquid chromatography-tandem mass spectrometry method was developed using multiple reaction monitoring mode with positive electrospray ionization. The method was validated with selectivity, linearity, stability, accuracy and precious. In addition, the abundance of seven CYP450 enzymes in human liver microsomes and CYP3A4 in placenta were determined using the current method. Results The linear range for CYP1A2, CYP2B6 and CYP2C8 was 0.036–3.6 nM and for CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was 0.090–9.0 nM. No interference was found between the blank matrix and each specific peptides. The accuracy and precious results were in accord with the requirement of analytical methods for biological samples in Chinese Pharmacopoeia. In addition, the peptides were stable under current stability conditions. The content of CYP3A4 in placenta and the seven CYP450 enzymes in human liver microsomes were accurately quantified. Conclusion The developed method is sensitive and specific and can be applied to the quantification of enzymes abundance in different human derived samples like placenta and liver microsomes.
研究领域:
药理学
·
分析化学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
·
2016
·
IF 2.85
Hua Wang,Ying Wang,Qing-Li Bo,Yan-Li Ji,Lu Liu,Yong-Fang Hu,Yuan-Hua Chen,Jun Zhang,Ling-Li Zhao,De-Xiang Xu
Cadmium (Cd) is linked with increased risk of fetal growth restriction (FGR). Nevertheless, the mechanism remains unknown. This study established a mouse model of Cd-induced FGR through two exposure methods. Pregnant mice were either administered with CdCl 2 (5, 50 and 250 ppm) throughout pregnancy through drinking water or intraperitoneally injected with CdCl 2 (4.5 mg/kg) on GD9. As expected, fetal weight and crown-rump length were reduced in a gender-independent manner. Interestingly, Mt1 and Mt2, two metallothionein genes, were up-regulated in maternal liver. Correspondingly, Cd accumulated mainly in maternal liver and kidney, and only trace amounts of Cd could pass from dam to placentas and fetuses. Further analysis showed that placental Zn concentration was elevated. Conversely, embryonic Zn concentration was reduced. Moreover, placental Znt1 and Znt2 , two zinc transporters, were down-regulated in Cd-exposed mice. These results suggest that maternal Cd exposure during pregnancy reduces placental Zn transport and induces fetal growth restriction.
研究领域:
毒理学
·
生殖生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Veterinary Medicine and Science
·
2021
·Vol. 7
·期 6
·2260-2267
·
IF 1.95
Jie Peng,Menglin Yang,Guoli Li,Xiu Zhang,Yanhua Huang,Yimei Tang
Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in placental lipid deposition, subsequently inhibiting placental angiogenesis and fetal development. However, the effect of different types of fatty acids on placental angiogenesis is still unclear. Trophoblast cells and vascular endothelial cells constitute two important types of placental tissue. In this study, we used palmitic acid (C16:0) and eicosapentaenoic acid (C20:5, n -3), respectively, to treat porcine trophectoderm cells (pTr2) and porcine iliac artery endothelial cells (PIEC) to study the effects of saturated fatty acids and n -3 polyunsaturated fatty acids (PUFAs) on placental angiogenesis in vitro. We found that C16:0 caused significant cytotoxicity in pTr2 and PIEC ( p < 0.01) and inhibited the proliferation and migration of PIEC ( p < 0.01), whereas C20:5 treatment exhibited very low cytotoxicity and minimal inhibition of cellular proliferation. Meanwhile, a low concentration of C16:0 had no effect on the tube formation in PIEC, whereas C20:5 significantly promoted tube formation of PIEC ( p < 0.01). These results suggested that saturated fatty acids and n -3 PUFAs had different effects on placental angiogenesis. As essential functional fatty acid, n -3 PUFA might be effective measure in alleviating the placental lipotoxicity caused by sow obesity during pregnancy.
研究领域:
生殖生物学
·
营养学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Jing Li,Xiaojie Quan,Saifei Lei,Gang Chen,Jiawei Hong,Zhenyao Huang,Qi Wang,Weiyi Song,Xinxin Yang
Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10 −1 , 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3 /miR-770/ PTX3 axis.
研究领域:
毒理学
·
分子生物学
·
生殖健康
✓ 已验证
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2016
·Vol. 182
·期 2
·482-494
·
IF 1.606
Bai Yin,Zhou Wen-Di,Mu Xian-Min,Zhang Qian,Yu Chen,Di Bin,Su Meng-Xiang
Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), a potential target in breast cancer prevention and therapy, was extracted from human placenta and immobilized on nonporous silica (∼5 μm) with a covalent method for the first time. The optimum initial enzyme concentration and immobilization time during the immobilization process were 0.42 mg mL −1 and 12 h, repectively. The binding was confirmed by scanning electron microscope (SEM) and infrared spectroscopy (FT-IR). It could improve the pH, thermal and storage stability compared to free enzyme. Moreover, the immobilized enzyme could be reused at least four times. A screening method based on it coupled with liquid chromatography–time-of-flight mass spectrometer (LC-TOF/MS) was established, and the half-maximal inhibitory concentration (IC 50) of apigenin for the immobilized enzyme was 291 nM. Subsequently, 10 natural products were evaluated leading to inhibition of the activity of 17β-HSD1 at the concentration of 25 μM, and six of them inhibit the activity over 50%.
研究领域:
生物化学
·
药物开发
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 11
·2332
·
IF 6.706
Meng-Ling Zhang,Qian Yang,Yan-Di Zhu,Ya-Di Zhang,Rui Zhang,Jian Liu,Xiao-Yan Zhao,Qin-Yu Dang,Dong-Xu Huang,Ming-Yuan Zhang,Yu-Chen Wei,Zhuo Hu,Xia-Xia Cai,Li-Fang Gao,Yang Shan,Huan-Ling Yu
In this study, we aimed to evaluate the effect of Nobiletin (NOB) on the placenta of Sprague–Dawley (SD) rats that had undergone reduced uterine perfusion pressure (RUPP) surgery and to evaluate the safety of NOB intervention during pregnancy. The results showed that NOB alleviated placental hypoxia, attenuated placental cell apoptosis, and inhibited placental damage in RUPP rats. No side effect of NOB intervention during pregnancy was observed. BeWo cell lines with P53 knockdown were then constructed using lentiviral transfection, and the P53 signaling pathway was found to be essential for NOB to reduce hypoxia-induced apoptosis of the BeWo cell lines. In summary, NOB attenuated hypoxia-induced placental damage by regulating the P53 signaling pathway, and those findings may contribute some insights into the role of NOB in placental development and the prevention of placental-related diseases.Keywords:Nobiletin;placenta;hypoxia;RUPP;P53 signaling pathway
研究领域:
药理学
·
妇产科学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Environmental Science-Nano
·
2025
·
IF 5.1
Yao Li,Zhaomin Dong,Xiangrui Wang,Ying Wang,Wenhong Fan
Limited research on the toxicokinetics of nanoparticles (NPs) in pregnant rats hinders our understanding of the potential risks they pose to the pregnant population. This study examined how exposure dose and size of NPs impacted their specific distribution in pregnant rats under repeated dosing. Results revealed that Au NPs mainly accumulated in the spleen and liver, followed by the uterus, while the heart, placenta, and fetus showed the least accumulation. The decrease of exposure size induced faster elimination of Au NPs in serum and organs. The increase of exposure dose induced faster elimination in serum but slower elimination in organs, higher accumulation, and larger size of Au NPs in vivo. The accumulation and biodistribution of Au NPs varied across different organs depending on the exposure size. Particularly, Au NPs with an in vivo size of 40 nm were shown to transfer the placenta and accumulate in the fetus, regardless of the exposure dose and size. Such effect was closely related to the transport routes of Au NPs across the placenta, possibly via vesicular transport and the uptake of trophoblast cells. Our study illustrating the specific distribution of NPs in vivo provides important evidence for assessing the health risk of NPs.
研究领域:
毒理学
·
纳米医学
·
生殖健康
✓ 已验证
产品关联
DOI
高影响因子
BIOLOGY OF REPRODUCTION
·
2025
·
IF 3
Zhang Yingying,Zhang Eryun,Li Ling,Ren Yongwei,Zhang Jinqiu,Zheng Qiutong,Sun Minya,Zhao Shaojie,Cui Yugui,Gu Ying,Xu Zhice
The risk of multiple placental thrombosis is significantly elevated in preeclampsia, and the vascular endothelium plays a vital role in coagulation processes through the secretion of Integrin alpha 2b, von Willebrand factor, and tissue factor. However, the underlying pathological mechanisms remain unclear. In this study, placental blood vessels were collected from both preeclampsia and normal pregnancies. Protein levels of Integrin alpha 2b were found to be up-regulated in preeclampsia samples compared to controls, indicating enhanced coagulation function in preeclampsia placental tissue. Additionally, higher cholesterol levels of plasma and lower AlkB homolog 1 expression in placental blood vessels of preeclampsia were found, overall DNA N6-methyldeoxyadenosine levels were up-regulated. Interestingly, the DNA N6-methyldeoxyadenosine level at the Integrin alpha 2b promoter was decreased. Cholesterol overload experiments in human umbilical vein endothelial cells demonstrated that cholesterol regulates the protein expression of AlkB homolog 1 and Integrin alpha 2b in a concentration-dependent manner. Furthermore, Integrin alpha 2b protein expression was increased following AlkB homolog 1 knockout, but no changes were observed when cholesterol was incubated with AlkB homolog 1 knockout cells. These findings provide critical insights into the roles of cholesterol levels, AlkB homolog 1, and Integrin alpha 2b in coagulation function within placental blood vessels. This information may contribute to further investigations of potential therapeutic targets and early prevention strategies for placental thrombosis in preeclampsia.
研究领域:
医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Animals
·
2020
·Vol. 10
·期 2
·251
·
IF 2.323
Jie Peng,Mao Xia,Jia Xiong,Chenbin Cui,Ningning Huang,Yuanfei Zhou,Hongkui Wei,Jian Peng
Simple SummaryHydrogen sulfide (H2S) is an important second messenger, which has been implicated in regulating placental angiogenesis. Our findings revealed that gestational dietary methionine could affect maternal and placental H2S concentrations. With the increase of dietary methionine, maternal plasma and placental H2S concentrations changed quadratically, which was consistent with placental vascular density and reproductive performance. The decrease in H2S production caused by an increase in dietary methionine was likely to be the cause for the increase in the rate of low birth weight piglets and needs further study.AbstractThe placenta is a unique bond between the mother and the fetus during pregnancy, and a proper placental angiogenesis is vital for fetal development. H2S is an endogenous stimulator of angiogenesis that is mainly produced by the methionine transsulfurationpathway. The goal of this study was to evaluate the effect of gestational dietary methionine on maternal and placental H2S production in sows. Multiparous sows (Large×White; third parity;n= 65) were randomly allocated into five groups, with feed diets comprisingstandardized ileal digestible methionine/lysine (Met/Lys) ratios of 0.27 (nutrient requirements of swine (NRC); 2012 level), 0.32, 0.37, 0.42, and 0.47, respectively. The litter size and weight at birth were measured and recorded. Maternal blood samples were obtained at embryonic day (E) E40 d, E90 d, and E114 d of gestation. The placental samples were collected at parturition. The results showed that maternal plasma H2S concentration was not affected at E40 d. However, the maternal plasma H2S concentration changed quadratically with the dietary Met/Lys ratio at E90 d (p< 0.01) and E114 d (p= 0.03). The maximum maternal plasma H2S concentration was at the dietary Met/Lys ratio of 0.37. Meanwhile, maternal plasma H2S concentration was positively correlated with piglets born alive (p< 0.01) and litter weight (p< 0.01). Consistent with the maternal plasma, the placental H2S concentration also changed quadratically with the dietary Met/Lys ratio (p= 0.03); the Met/Lys ratio of 0.37 showed the maximum H2S concentration. In conclusion, our findings revealed that the gestational dietary Met/Lys ratio could affect maternal and placental H2S concentrations, which may be an important molecular mechanism affecting placental angiogenesis and piglet development.Keywords:hydrogen sulfide;reproductive performance;pregnant sows;methionine;placental angiogenesis
研究领域:
动物营养学
·
生殖生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Yuxue Pan,Danhui Hu,Honglei Chen,Mengyuan Wang,Xiaocong Dong,Guoyun Wan,Hongbo Tang,Haijiao Wang,Hongli Chen
This study focuses on the preparation and characterization of platelet membrane biomimetic nanocarriers (P-PLGA NPs) and investigates their interactions with the transplacental barrier. Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were coated with platelet membrane (PLTM) to construct P-PLGA NPs. Additionally, fluorinated polyethylenimine (F-PEI) was grafted onto PLGA NPs to prepare F-PEI-PLGA NPs, which were compared with PLGA NPs. In vitro placental barrier cell models using human choriocarcinoma cells (BeWo b30) and in vivo pregnancy animal models using ICR mice were utilized to evaluate the transplacental barrier efficiency of the PLGA NPs with different surface modifications. The results demonstrated that all three types of nanoparticles could accumulate in the uterus and placenta. The transplacental barrier efficiency of F-PEI-PLGA NPs was found to be the highest at 4 h, while P-PLGA NPs exhibited the highest transplacental barrier efficiency at 12 and 24 h. Furthermore, there were no significant effects on the main organs, structure, and quantity of uterine spiral arteries, indicating the safety of the nanoparticles (NPs). P-PLGA NPs are expected to be a safe and effective nano-delivery system for perinatal drug delivery. This study provides insights into the transplacental barrier mechanism of NPs with different surface characteristics.
研究领域:
药学
·
生物医学工程
·
妇产科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）