scholarly journals Environmental Pollutant Benzo[a]pyrene Induces Recurrent Pregnancy Loss through Promoting Apoptosis and Suppressing Migration of Extravillous Trophoblast

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yang Ye ◽  
Sushi Jiang ◽  
Chao Zhang ◽  
Yanxiang Cheng ◽  
Huan Zhong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Environmental Pollutant ◽  
Extravillous Trophoblast ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Study Results ◽  
Before And After ◽  
Dose Dependent

Objects. To investigate the effects of environmental pollutant benzo(a)pyrene (BaP) and its metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) on human trophoblasts and on murine miscarriages. Methods. The implantation sites, fetus resorption, and abnormal fetuses were studied in pregnant mice treated with different doses of BaP by oral gavage from day 1 to day 10 of gestation. Additionally, apoptosis and related signaling pathway, and the migration and invasion of trophoblasts, were assessed before and after exposure of BPDE in Swan 71 trophoblast cell. Besides, the migration and invasion, and its related signaling pathway, were assessed in villi obtained from women. Results. We observed a concentration-dependent incidence of abnormal murine fetuses, beginning with 0.1 mg/kg BaP; with a BaP concentration of 2 mg/kg, no fetuses developed. Correspondingly, a BPDE concentration-dependent apoptosis of human trophoblasts. Beginning with 0.5 μM BPDE exposure, Bax/Caspase-3 were increased and Bcl-2 decreased. Furthermore, BPDE also inhibited, in a dose-dependent manner, the migration of villous explants from elective abortion women, consistent with the reduced migration of villous explants from women with recurrent pregnancy loss (RPL), and reduced the cell immigration in Swan 71 trophoblasts, in a dose-dependent manner measured by transwell assays. Conclusions. Our study results provide mechanistic insight to the effect of BPDE on trophoblast dysfunction through enhanced cell apoptosis and inhibited migration, providing further experimental evidence to the causative links between BaP exposure and PRL.

Regulation of Pregnancy: Evidence for Major Roles by the Uterine and Placental Kisspeptin/KISS1R Signaling Systems

2019 ◽  
Vol 37 (04) ◽  
pp. 182-190 ◽  
Author(s):  
Sally Radovick ◽  
Andy V. Babwah
Keyword(s):  
Stromal Cells ◽  
Pregnancy Loss ◽  
Therapeutic Agent ◽  
Recurrent Pregnancy Loss ◽  
Embryo Implantation ◽  
Extravillous Trophoblast ◽  
Migration And Invasion ◽  
Decidual Cell ◽  
Signaling Systems ◽  
Placental Invasion

AbstractSeveral studies provide strong evidence suggesting that in addition to central kisspeptin/KISS1R signaling, the peripheral uterine- and placental-based kisspeptin/KISS1R signaling systems are major regulators of pregnancy. Specifically, the evidence suggests that the uterine-based system regulates embryo implantation and decidualization, while both the uterine- and placental-based systems regulate placentation. Uterine kisspeptin and KISS1R regulate embryo implantation by controlling the availability of endometrial glandular secretions, like leukemia inhibitory factor, which are essential for embryo adhesion to the uterine epithelium. As for decidualization, the data suggest that decidualized stromal cells express KISS1R and secrete kisspeptin-inhibiting decidual cell motility and thereby indirectly regulate embryo and placental invasion of the uterus. Similarly, for placentation, placental kisspeptin and KISS1R negatively regulate extravillous trophoblast migration and invasion and thereby directly control placental invasion of the uterus. Having recognized a significant role for the uterine- and placental-based kisspeptin/KISS1R signaling systems regulating pregnancy, the future looks promising for the development of kisspeptin and KISS1R as prognostic and diagnostic markers of pregnancy disorders and the use of kisspeptin as a therapeutic agent in the prevention and treatment of conditions such as recurring implantation failure, recurrent pregnancy loss, and preeclampsia.

scholarly journals Sulforaphane induces colorectal cancer cell proliferation through Nrf2 activation in a p53-dependent manner

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Yunjeong Gwon ◽  
Jisun Oh ◽  
Jong-Sang Kim
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Related Factor ◽  
Mild Stress ◽  
Dependent Manner ◽  
Cancer Cell Proliferation ◽  
Nrf2 Signaling Pathway ◽  
Dose Dependent

AbstractSulforaphane is a well-known phytochemical that stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant cellular response. In this study, we found that sulforaphane promoted cell proliferation in HCT116 human colon cancer cells expressing a normal p53 gene in a dose-dependent but biphasic manner. Since p53 has been reported to contribute to cell survival by regulating various metabolic pathways to adapt to mild stress, we further examined cellular responses in both p53-wild-type (WT) and p53-knockout (KO) HCT116 cells exposed to sulforaphane in vitro and in vivo. Results demonstrated that sulforaphane treatment activated Nrf2-mediated antioxidant enzymes in both p53-WT and p53-KO cells, decreased apoptotic protein expression in WT cells but increased in KO cells in a dose-dependent manner, and increased the expression of a mitochondrial biogenesis marker PGC1α in WT cells but decreased in KO cells. Moreover, a low dose of sulforaphane promoted tumor growth, upregulated the Nrf2 signaling pathway, and decreased apoptotic cell death in p53-WT HCT116 xenografts compared to that in p53-KO HCT116 xenografts in BALB/c nude mice. These findings suggest that sulforaphane can influence colon cancer cell proliferation and mitochondrial function through a crosstalk between the Nrf2 signaling pathway and p53 axis.

scholarly journals Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: a systematic review and meta-analysis

F&S Reviews ◽  
2021 ◽  
Author(s):  
Nadia A. du Fossé ◽  
Marie-Louise P. van der Hoorn ◽  
Nina H. Buisman ◽  
Jan M.M. van Lith ◽  
S askia le Cessie ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pregnancy Loss ◽  
Meta Analysis ◽  
Dependent Manner ◽  
Increased Risk ◽  
Dose Dependent ◽  
Paternal Smoking

scholarly journals The effect of vitamin C on the gene expression profile of sperm protamines in the male partners of couples with recurrent pregnancy loss: A randomized clinical trial

2020 ◽  
Vol 47 (1) ◽  
pp. 68-76
Author(s):  
Saeideh Hamidian ◽  
Ali Reza Talebi ◽  
Farzaneh Fesahat ◽  
Mohammad Bayat ◽  
Ali Mohammad Mirjalili ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin C ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Sperm Chromatin ◽  
Dna Integrity ◽  
Male Partners ◽  
Expression Levels ◽  
Before And After ◽  
Vitamin C Supplementation

Objective: Since sperm abnormalities are known to be a major reason for recurrent pregnancy loss (RPL), any defects in DNA structure and chromatin condensation can place embryos at risk in the early stage of development and implantation. As antioxidants such as vitamin C may play a protective role against the destruction of protamine genes in sperm chromatin, this study was conducted to evaluate the effects of vitamin C on chromatin and the expression of protamine genes in the male partners of couples with RPL.Methods: Twenty male partners of couples with RPL were selected as the intervention group and received vitamin C supplementation (250 mg daily for 3 months). Healthy fertile men (n=20) were included as controls. Sperm chromatin, DNA integrity, and the expression levels of protamine genes were evaluated before and after treatment.Results: Significant differences were found in sperm morphology, protamine deficiency, and apoptosis between the two groups and before and after vitamin C administration. A significant change was found in mRNA levels of <i>PRM1, PRM2</i>, and the <i>PRM1/PRM2</i> ratio after treatment.Conclusion: Daily oral administration of vitamin C may improve human sperm parameters and DNA integrity by increasing protamine gene expression levels in the male partners of couples with RPL. The beneficial effects of vitamin C supplementation as an antioxidant for the male partners of couples with RPL could lead to improved pregnancy outcomes in these cases.

Calcium dependence of the thrombin-induced increase in endothelial albumin permeability

1989 ◽  
Vol 66 (3) ◽  
pp. 1471-1476 ◽  
Author(s):  
H. Lum ◽  
P. J. Del Vecchio ◽  
A. S. Schneider ◽  
M. S. Goligorsky ◽  
A. B. Malik
Keyword(s):  
Endothelial Cells ◽  
Endothelial Permeability ◽  
Base Line ◽  
Dependent Manner ◽  
Extracellular Medium ◽  
Influx Rate ◽  
Before And After ◽  
Dependent Inhibition ◽  
Permeability Increase ◽  
Dose Dependent

We examined whether the increase in endothelial albumin permeability induced by alpha-thrombin is dependent on extracellular Ca2+ influx. Permeability of 125I-albumin across confluent monolayers of cultured bovine pulmonary artery endothelial cells was measured before and after the addition of 0.1 microM alpha-thrombin. In the presence of normal extracellular Ca2+ concentration ([Ca2+]o, 1000 microM), alpha-thrombin produced a 175 +/- 10% increase in 125I-albumin permeability. At lower [Ca2+]o (100, 10, 1, or less than 1 microM), alpha-thrombin caused a 140% increase in permeability (P less than 0.005). LaCl3 (1 mM), which competes for Ca2+ entry, blunted 38% of the increase in permeability. Preloading endothelial monolayers with quin2 to buffer cytosolic Ca2+ (Cai2+) produced a dose-dependent inhibition of the increase in 125I-albumin permeability. Preincubation with nifedipine or verapamil was ineffective in reducing the thrombin-induced permeability increase. A 60 mM K+ isosmotic solution did not alter base-line endothelial permeability. alpha-Thrombin increased [Ca2+]i in a dose-dependent manner and the 45Ca2+ influx rate. Extracellular medium containing 60 mM K+ did not increase 45Ca2+ influx, and nifedipine did not block the rise in 45Ca2+ influx caused by alpha-thrombin. Ca2+ flux into endothelial cells induced by alpha-thrombin does not occur through voltage-sensitive channels but may involve receptor-operated channels. In conclusion, the increase in endothelial albumin permeability caused by alpha-thrombin is dependent on Ca2+ influx and intracellular Ca2+ mobilization.

Interferon-induced transmembrane protein 1 (IFITM1) is essential for progression of laryngeal squamous cell carcinoma in an Osteopontin/NF-κB-dependent manner

2020 ◽  
Vol 29 (4) ◽  
pp. 521-529
Author(s):  
Yong Yin ◽  
Keke Yang ◽  
Juanjuan Li ◽  
Peng Da ◽  
Zhenxin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Transmembrane Protein ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Normal Tissues

OBJECTIVE: To assess the expression levels of IFITM1 in human tissue samples and laryngeal squamous cell carcinoma (LSCC) cells, and to explore the potential mechanisms of IFITM1 in LSCC progression. METHODS: Quantitative PCR and immunohistochemical (IHC) assays were performed to detect IFITM1 expression in 62 LSCC tissues and corresponding normal tissues. We further detected the effects of IFITM1 on the proliferation, migration and invasion of LSCC cells and NF-κB signaling pathway through colony formation assay, wound healing assay and transwell assay, respectively. RESULTS: We demonstrated the possible involvement of IFITM1 in the progression of LSCC. We found the upregulated expression of IFITM1 in human LSCC tissues and cells, and analyzed the correlations between IFITM1 expression and osteopontin. Our data further confirmed that IFITM1 affected cell proliferation, migration, and invasion of LSCC cells via the regulation of NF-κB signaling pathway. CONCLUSIONS: We investigated the potential involvement of IFITM1 in the progression of LSCC, and therefore confirmed that IFITM1 was a potential therapeutic target for LSCC.

scholarly journals Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3β/Nrf2 Signaling Pathway and Inhibiting the NF-κB Signaling Pathway in 5/6 Nephrectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Hong-feng Zhang ◽  
Jia-hong Wang ◽  
Yan-li Wang ◽  
Cheng Gao ◽  
Yan-ting Gu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Western Blot ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Dependent Manner ◽  
Salvianolic Acid ◽  
Nrf2 Signaling Pathway ◽  
Antioxidative Effects ◽  
Dose Dependent

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Salviae miltiorrhizae Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD). Here, we examined the antioxidative effects and underlying mechanisms of SAA in 5/6Nx rats. The rats were injected with SAA (2.5, 5, and 10 mg·kg-1·d-1, ip) for 28 days. Biochemical, flow cytometry, and Western blot analyses showed that SAA significantly increased the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) and lowered the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and NADPH oxidase 4 (NOX-4) in a dose-dependent manner in 5/6Nx rats and in H2O2-induced HK-2 cells in vitro. Moreover, SAA enhanced the activation of the protein kinase B/glycogen synthase kinase-3β/nuclear factor-erythroid-2-related factor 2 (Akt/GSK-3β/Nrf2) signaling pathway in a dose-dependent manner and subsequently increased the expression of heme oxygenase-1 (HO-1) in the kidney of 5/6Nx rats, which were consistent with those obtained in H2O2-induced HK-2 cells in vitro shown by Western blot analysis. Furthermore, SAA significantly increased the expression of intranuclear Nrf2 and HO-1 proteins compared to HK-2 cells stimulated by LPS on the one hand, which can be enhanced by QNZ to some extent; on the other hand, SAA significantly lowered the expression of p-NF-κB p65 and ICAM-1 proteins compared to HK-2 cells stimulated by H2O2, which can be abrogated by ML385 to some extent. In conclusion, our results demonstrated that SAA effectively protects the kidney against oxidative stress in 5/6Nx rats. One of the pivotal mechanisms for the protective effects of SAA on kidney injury was mainly related with its antioxidative roles by activating the Akt/GSK-3β/Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

scholarly journals NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jianhua Huang ◽  
Li Li ◽  
Weifeng Yuan ◽  
Linxin Zheng ◽  
Zhenhui Guo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Binding Domain ◽  
Dependent Manner ◽  
Protective Effects ◽  
Lps Challenge ◽  
Domain Peptide ◽  
Nemo Binding Domain ◽  
Dose Dependent

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-αand NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-αand IL-1βsecretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

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