PMID: 

JBRA Assist Reprod. 2020 Mar 23. Epub 2020 Mar 23. PMID: 32202744

Abstract Title: 

Coenzyme Q10 improves the in vitro maturation of oocytes exposed to the intrafollicular environment of patients on fertility treatment.

Abstract: 

OBJECTIVE: To evaluate the impact of patient follicular environment with oxidative stress on oocyte quality.METHODS: Patients on fertility treatment with either advanced maternal age or endometriosis were asked to donate follicular fluid collected during ovum pick-up. Follicular fluid (FF) was added (20%, 10% and 5%; %V/V) to in vitro maturation (IVM) medium with mouse oocytes. Following maturation culture, the oocytes were assessed for meiosis reinitiation. In a second setup, coenzyme Q10 was added to culture medium with FF. In addition to assessing meiotic maturation, a subset of oocytes was assessed for spindle structure and chromosome alignment.RESULTS: Supplementation of IVM medium with FF of patients of advanced maternal age (with or without antioxidants) did not have an effect on the maturation capacity of mouse oocytes. However, the addition of FF of individuals with endometriosis (without antioxidants) in the two highest concentrations affected oocyte maturation (61.5%&57.0% maturation) compared with the lowest concentration (89.2% maturation) (p

read more

PMID: 

Food Sci Nutr. 2020 Feb ;8(2):1093-1103. Epub 2020 Jan 14. PMID: 32148818

Abstract Title: 

Honokiol, an active compound ofis involved in restoring normal baroreflex sensitivity in hypercholesterolemic rabbits.

Abstract: 

This study investigated the effects of methanol extract(MEMO) on baroreceptor reflex sensitivity (BRS) in the hypercholesterolemic rabbits and the involved molecular mechanisms. Male New Zealand white rabbits were randomly divided into Control (normal diet), Cholesterol (0.5% w/w cholesterol diet), and Magnolia groups (0.5% w/w cholesterol diet plus 1% w/w MEMO). The animals were treated with the designated diet for 4 or 8 weeks. BRS in the control of heart rate was assessed by linear regression method. After 8 weeks of treatments, plasma total cholesterol (TC) was significantly elevated in the Cholesterol/Magnolia groups. The arterial blood pressure (aBP) was increased in the Cholesterol and Magnolia groups. The depression of BRS observed in the Cholesterol group was significantly ameliorated in the Magnolia group. After L-NAME (-nitro-Larginine methyl ester, 20 mg/kg,), the BRS of the Cholesterol group was significantly improved. Results from our in vitro study further indicated that honokiol, the principle component of MEMO, would protect human umbilical vein endothelial cells (HUVECs) from HO-induced damages and inhibit HO-induced vascular smooth muscles cells (VSMCs) proliferation, which was evident by the decreased expression of pFAK, and p-Erk1/2. The results of the present study suggested that the improvement of BRS by MEMO in the hypercholesterolemic rabbits might be mediated by the antioxidant property of MEMO as indicated by the results from the L-NAME and in vitro honokiol studies.

read more

PMID: 

Anim Cells Syst (Seoul). 2020 ;24(1):60-68. Epub 2019 Dec 28. PMID: 32158617

Abstract Title: 

Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway.

Abstract: 

Honokiol is one of the main active components of, and has been demonstrated to have multiple pharmacological activities against a variety of diseases. Recently, this phenolic compound is known to have antioxidant activity, but its mechanism of action remains unclear. The purpose of the current study was to evaluate the preventive effects of honokiol against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts. The present study found that honokiol inhibited hydrogen peroxide (HO)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation. The inhibitory effect of honokiol on HO-induced apoptosis was associated with the up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio that in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose) polymerase cleavage, which was associated with the blocking of cytochromerelease to the cytoplasm. Collectively, these results demonstrate that honokiol defends C2C12 myoblasts against HO-induced DNA damage and apoptosis, at least in part, by preventing mitochondrial-dependent pathway through scavenging excessive ROS.

read more

PMID: 

Food Sci Nutr. 2020 Mar ;8(3):1534-1545. Epub 2020 Feb 6. PMID: 32180962

Abstract Title: 

Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6-mediated matrix metalloproteinase 9.

Abstract: 

Metastasis is the crucial mechanism to cause high mortality in lung cancer. Degradation of extracellular matrix (ECM) by proteolytic enzymes, especially matrix metalloproteinases (MMPs), is a key process for promoting cancer cell migration and invasion. Therefore, targeting MMPs might be a strategy for lung cancer metastasis suppression. Honokiol, a biological active component of, has been indicated to suppress lung cancer tumorigenesis through epigenetic regulation. However, the regulation of MMPs-mediated migration and invasion by honokiol through epigenetic regulation in lung cancer is still a mystery. In the present study, the migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment. The proteolytic activity of MMP-9, rather than MMP-2, was inhibited in honokiol-treated H1299 cells. Honokiol-inhibited MMP-9 expression was through promoting MMP-9 protein degradation rather than suppressing transcription mechanism. Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl-α-tubulin, was accumulated after honokiol incubation. The disassociation of MMP-9 with hyper-acetylated heat shock protein 90 (Hsp90) was observed resulting in MMP-9 degradation after honokiol treatment. Meanwhile, honokiol-suppressed MMP-9 expression and invasion ability of H1299 lung cancer cellswas rescued by HDAC6 overexpression. Accordingly, the results suggested that the suppression of migration and invasion activities by honokiol was through inhibiting HDAC6-mediated Hsp90/MMP-9 interaction and followed by MMP-9 degradation in lung cancer.

read more

PMID: 

Brain Res Bull. 2020 Apr ;157:1-9. Epub 2020 Jan 23. PMID: 31982453

Abstract Title: 

Bisphenol A exposure inhibits contrast sensitivity in cats involving increased response noise and inhibitory synaptic transmission.

Abstract: 

Contrast sensitivity (CS) is one of the primary fundamental factors determining how well we can see, and it directly influences object recognition. Whether bisphenol-A (BPA, an environmental xenoestrogen) can perturb contrast detection in the visual system has yet to be elucidated. In the present study, we analyzed CS of single neurons in the primary visual cortex (area 17, A17) of cats before and after BPA exposure using a multiple-channel recording technique. The results showed that CS of A17 neurons was markedly depressed with an increased contrast threshold after two hour of intravenous BPA administration, which had a positive correlation with decreased firing rates of A17 neurons. Additionally, responses of these neurons presented an overt increase in the trial-to-trail response variability (a kind of neuronal noise), which could disturb the information-filtering function of single neurons. We also found that neuronal CS in the visual relay station was not disturbed after BPA administration, which rules out the contribution of CS alteration in the optical pathway. Importantly, acute BPA treatment obviously increased the inhibitory innervation to the visual pyramidal neurons. This implies that alteration of intracortical inhibitory regulation contributes to the compromised contrast detection in the visual system after BPA treatment.

read more

PMID: 

Environ Pollut. 2020 Jan 25 ;261:114060. Epub 2020 Jan 25. PMID: 32045791

Abstract Title: 

Chronic exposure to environmentally relevant concentrations of bisphenol S differentially affects cognitive behaviors in adult female zebrafish.

Abstract: 

Evidence is emerging that environmental exposure to bisphenol S (BPS), a substitute for bisphenol A (BPA), to humans and wildlife is on the rise. However, research on the neurobehavioral effects of this endocrine disruptive chemical is still in its infancy. In this study, we aimed to investigate the effects of long-term exposure to environmentally relevant concentrations of BPS on recognition memory and its mechanism(s) of action, especially focusing on the glutamatergic/ERK/CREB pathway in the brain. Adult female zebrafish were exposed to the vehicle, 17β-estradiol (E2, 1 μg/L), or BPS (1, 10 and 30 μg/L) for 120 days. Fish were then tested in the object recognition (OR), object placement (OP), and social recognition tasks (SR). Chronic exposure to E2 and 1 μg/L of BPS improved fish performance in OP task. This was associated with an up-regulation in the mRNA expression of several subtypes of metabotropic and ionotropic glutamate receptors, an increase in the phosphorylation levels of ERK1/2 and CREB, and an elevated transcript abundance of several immediate early genes involved in synaptic plasticity and memory formation. In contrast,the exposure to 10 and 30 μg/L of BPS attenuated fish performance in all recognition memory tasks. The impairment of these memory functions was associated with a marked down-regulation in the expression and activity of genes and proteins involved in glutamatergic/ERK/CREB signaling cascade. Collectively, our study demonstrated that the long-term exposure to BPS elicits hermetic effects on the recognition memory in zebrafish. Furthermore, the effect of BPS on the recognition memory seems to be mediated by the glutamatergic/ERK/CREB signaling pathway.

read more

PMID: 

J Toxicol Environ Health A. 2020 Feb 1 ;83(3):95-112. Epub 2020 Feb 20. PMID: 32075523

Abstract Title: 

Effects of Bisphenol A ongene expression and DNA damage in adult viviparous fish.

Abstract: 

Bisphenol A (BPA) is an emerging pollutant of global concern. Viviparous fishis endemic to the Central Mexican Plateau where BPA was detected; however, few studies examined the influence of this chemical on native viviparous fish. The effects of BPA (sublethal dose) were determined on DNA integrity andexpression ingonads, and interactions of BPA with FOXL2 protein. Genotoxicity analysis revealed that % comets, at 14 and 28 days and comet tail length (at 14 days) were significantly higher in exposed compared to controls. In general, the % DNA tail was not markedly higher in BPA-treated fish; however, tail moment related to tail length exhibited significant increases in DNA damage. RT-qPCR assays showedoverexpression after 14 and 28 days of exposure in females; while in males,was overexpressed after 28 days.analysis demonstrated that BPA interacted with seven residues located in FOXL2 homeodomain. In summary, sublethal BPA doses induced DNA damage and changes inexpression in gonadal cells of, which may adversely affect reproduction in BPA-exposed wild populations.overexpression and BPA-FOXL2 interaction suggested alterations in processes involving. Viviparous fish may thus serve as potential non-conventional models for assessing pollutants effects.

read more

PMID: 

J Toxicol Environ Health A. 2020 Jan 17 ;83(2):66-81. Epub 2020 Feb 20. PMID: 32077375

Abstract Title: 

A suggested bisphenol A metabolite (MBP) interfered with reproductive organ development in the chicken embryo while a human-relevant mixture of phthalate monoesters had no such effects.

Abstract: 

Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While these compounds have been reported as reproductive toxicants, their effects may partially be attributed to metabolites. The aim of this study was to examine reproductive organ development in chicken embryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP; 100 µg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 µg/g egg). The mixture was designed within the EU project EDC-MixRisk based upon a negative association with anogenital distance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryos were exposedfrom an initial stage of gonad differentiation (embryonic day 4) and dissected two days prior to anticipated hatching (embryonic day 19). No discernible effects were noted on reproductive organs in embryos exposed to the mixture. MBP-treated males exhibited retention of Müllerian ducts and feminization of the left testicle, while MBP-administered females displayed a diminished the left ovary. In the left testicle of MBP-treated males, mRNA expression of female-associated genes was upregulated while the testicular marker gene SOX9 was downregulated, corroborating afeminizing effect by MBP. Our results demonstrate that MBP, but not the phthalate monoester mixture, disrupts both male and female reproductive organ development in an avian embryo model.

read more

PMID: 

Chemosphere. 2020 Feb 27 ;251:126340. Epub 2020 Feb 27. PMID: 32135373

Abstract Title: 

Urinary bisphenol A concentrations and adiposity measures at age 7 years in a prospective birth cohort.

Abstract: 

Bisphenol A (BPA) exposure during early life may increase risk of childhood obesity, however, prospective evidence of birth cohort is limited and inconclusive. We aimed to explore the associations of maternal and childhood BPA exposure with child adiposity measures, including body mass index, waist circumference and skinfold thickness and waist to height ratio of children at 7 years. 430 mother-child pairs were examined from a population-based prospective cohort in a rural area of East China. BPA concentrations of spot urine samples were quantified in mothers and their children aged 3 and 7 years. Maternal urinary BPA concentration was significantly positively associated with waist circumference in children aged 7 years (β = 0.508 cm, 95% CI: 0.067, 0.950). These significant associations were not modified by child sex, but they were only observed among girls in sex-stratified analyses. Risk of central obesity related to prenatal BPA exposure was significantly higher in the second and the third tertile than thosein the first tertile (odds ratio, OR = 2.510, 95% CI = 1.146, 5.499; OR = 2.584, 95% CI = 1.186, 5.631, respectively; p for trend = 0.022). The present findings suggested that prenatal exposure to BPA may enhance waist circumference of children and thereby increase risk of central obesityin school-age girls.

read more

PMID: 

Food Chem Toxicol. 2020 Apr ;138:111235. Epub 2020 Mar 3. PMID: 32142877

Abstract Title: 

Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring.

Abstract: 

Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treateddams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice.

read more