PMID: 

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug ;27(4):1111-1117. PMID: 31418365

Abstract Title: 

[Apoptosis-Inducing Effect of Ginsenoside Rh2 on Human Acute T Lymphoblastic Leukemia Jurkat Cells and Its Mechanism].

Abstract: 

OBJECTIVE: To investigate the apoptosis-inducing effect of Ginsenoside (Rh2) on human acute T lymphoblastic leukemia Jurkat cells and it mechamism.METHODS: The effects of different concentration of Rh2 (0, 10 , 20, 40 and 80µg/ml) on the proliferation activity of Jurkat cells were detected by methyl thiazolyl tetrazolium (MTT) method, and the semi-inhibitory concentration (IC) of Rh2 on Jurkat cells at 48 h was calculated. Microscopy and Hoechst 33258 fluorescence staining were used to observe the apoptosis of Jurkat cells treated with ICRh2 for 48 h. And then, the cell experiment was divided into 4 groups: control, Rh2 (IC), PI3K inhibitor LY294002 (50µmol/l) and Rh2 (IC) + LY294002 (50µmol/l). After synchronous culture for 48 h, the apoptosis and cycle changes of Jurkat cells were detected by using PI single staining and Annexin V-FITC/PI double staining, respectively. Western blot was used to detect the expression level of apoptosis-related protein BAX, BCL-2, Cleaved-Caspasase3, cell cycle-related protein Cyclin D1 and PI3K/AKT signaling pathway-related protein AKT and p-AKT.RESULTS: Rh2 (10-80µg/ml) inhibited the Jurkat cell proliferation in a dose-time dependent manner (r= 0.999, P＜0.01; r= 0.991; P＞0.05), accompanied by obvious morphological changes of apoptosis cells. Flow cytometry showed that compared with the control group, the cell apoptosis rate in Rh2 or LY294002 group significantly increased, and the cell cycle was mostly blocked in G0/G1 phase. However, the cell apoptosis and cellcycle block in Rh2+LY294002 group were more significant than that in Rh2 and LY294002 group. Western blot showed that compared with the control group, Rh2 significantly promoted the expression of BAX and Cleaved-Caspasase 3, inhibited the expression of BCL-2, Cyclin D1 and p-AKT, furthermore LY294002 significantly promoted this effect.CONCLUSION: Rh2 can induce the apoptosis of Jurkat cells in time-dose dependent manner, moreover, Rh2 also can result in an obvious block of Jurkat cells at G0/G1, that may be closely related to a series of apoptotic signaling cascades mediated by Rh2 inhibiting PI3K/AKT pathway.

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PMID: 

J Agric Food Chem. 2019 Aug 27. Epub 2019 Aug 27. PMID: 31422666

Abstract Title: 

Ginsenoside Rg3 Prevents Cognitive Impairment by Improving Mitochondrial Dysfunction in the Rat Model of Alzheimer's Disease.

Abstract: 

Ginseng, the roots and rhizomes ofC. A. Meyer, is used not only as a herbal medicine but also as a functional food to support body functions. Ginsenoside Rg3 (GRg3) is a major bioactive component in ginseng. In this study, the beneficial effects of GRg3 on rats with Alzheimer's disease (AD) were evaluated via the behavioral experiment and antioxidant capacity. Moreover, metabolomic analysis based on UPLC-QTOF-MS/MS and apoptosis analysis was used to obtain the change between AD and GRg3-administrated rats to assess the underlying mechanisms on improving mitochondrial dysfunction. Results showed that GRg3 could prevent the cognitive impairment of AD rats by improving the mitochondrial dysfunction. The potential mechanisms were related to regulate the abnormality of energy metabolism, electron transport chain, amino acid metabolism, purine metabolism, and antiapoptosis. These findings support the exploitation of GRg3 as an effective complementary and functional food to prevent and delay AD.

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PMID: 

J Cell Mol Med. 2019 Aug 19. Epub 2019 Aug 19. PMID: 31423730

Abstract Title: 

Ginsenoside Rb1 ameliorates CKD-associated vascular calcification by inhibiting the Wnt/β-catenin pathway.

Abstract: 

Vascular calcification (VC) is a pathological process underpinning major cardiovascular conditions and has attracted public attention due to its high morbidity and mortality. Chronic kidney disease (CKD) is a common disease related to VC. Ginsenoside Rb1 (Rb1) has been reported to protect the cardiovascular system against vascular diseases, yet its role in VC and the underlying mechanisms remain unclear. In this study, we established a CKD-associated VC rat model and aβ-glycerophosphate (β-GP)-induced vascular smooth muscle cell (VSMC) calcification model to investigate the effects of Rb1 on VC. Our results demonstrated that Rb1 ameliorated calcium deposition and VSMC osteogenic transdifferentiation both in vivo and in vitro. Rb1 treatment inhibited the Wnt/β-catenin pathway by activating peroxisome proliferator-activated receptor-γ (PPAR-γ), and confocal microscopy was used to show that Rb1 inhibited β-catenin nuclear translocation in VSMCs. Furthermore, SKL2001, an agonist of the Wnt/β-catenin pathway, compromised the vascular protective effect ofRb1. GW9662, a PPAR-γ antagonist, reversed Rb1's inhibitory effect on β-catenin. These results indicate that Rb1 exerted anticalcific properties through PPAR-γ/Wnt/β-catenin axis, which provides new insights into the potential theraputics of VC.

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PMID: 

Molecules. 2019 Aug 17 ;24(16). Epub 2019 Aug 17. PMID: 31426477

Abstract Title: 

Inhibitory Effects of Ginsenoside Ro on the Growth of B16F10 Melanoma via Its Metabolites.

Abstract: 

Ginsenoside Ro (Ro), a major saponin derived and isolated fromC.A. Meyer, exerts multiple biological activities. However, the anti-tumour efficacy of Ro remains unclear because of its poor in vitro effects. In this study, we confirmed that Ro has no anti-tumour activity in vitro. We explored the anti-tumour activity of Ro in vivo in B16F10 tumour-bearing mice. The results revealed that Ro considerably suppressed tumour growth with no significant side effects on immune organs and body weight. Zingibroside R1, chikusetsusaponin IVa, and calenduloside E, three metabolites of Ro, were detected in the plasma of Ro-treated tumour-bearing mice and showed excellent anti-tumour effects as well as anti-angiogenic activity. The results suggest that the metabolites play important roles in the anti-tumour efficacy of Ro in vivo. Additionally, the haemolysis test demonstrated that Ro has good biocompatibility. Taken together, the findings of this study demonstrate that Ro markedly suppresses the tumour growth of B16F10-transplanted tumours in vivo, and its anti-tumour effects are based on the biological activity of its metabolites. The anti-tumour efficacy of these metabolites is due, at least in part, to its anti-angiogenic activity.

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PMID: 

Environ Sci Pollut Res Int. 2019 Aug 6. Epub 2019 Aug 6. PMID: 31388950

Abstract Title: 

Maternal exposure to environmentally relevant doses of bisphenol A causes reproductive dysfunction in F1 adult male rats: protective role of melatonin.

Abstract: 

This study investigated the protective effects of melatonin (MLT), a potent antioxidant, in male Wistar rats exposed to environmentally relevant doses of bisphenol A (BPA) in utero. Pregnant Wistar rats were randomly assigned into five groups. Group 1 (control) received 0.2 mL 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group 2 received BPA at 25μg/kg/day; group 3 received BPA at 250 μg/kg/day; group 4 received BPA at 25 μg/kg/day with concurrent MLT 1 mg/kg/day while group 5 received BPA at 250 μg/kg/day with concurrent MLT 1 mg/kg/day. Treatments were by gavage from gestational day (GD) 10-21. The BPA-treated rats showed dose-dependent significant reduction in body weight, gonosomatic index, sperm motility, livability and count. Also, BPA caused significant reduction in the levels of serum testosterone and luteinizing hormone while it caused significant increases in the levels of follicle stimulating hormone as well as estradiol. Furthermore, BPA induced testicular oxidative stress including significant decreases in the activities of testicular SOD, GSH and GPx as well as GST, increasing the levels of testicular MDA and HO. It further induced interstitial necrosis and germinal cell degeneration in the testis with a subsequent diminution of the tubular and luminal diameter. However, co-treatment with MLT offered protection against testicular damage induced by BPA. Melatonin is likely to protect against alterations of the male reproductive system caused by BPA through a direct action on the mechanism of anti-oxidants as well as through the inhibition of necrosis.

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PMID: 

Ecotoxicol Environ Saf. 2019 Aug 5 ;183:109502. Epub 2019 Aug 5. PMID: 31394373

Abstract Title: 

Organophosphate flame retardants and bisphenol A in children's urine in Hong Kong: has the burden been underestimated?

Abstract: 

The urine levels of organophosphate flame retardants (PFRs) and bisphenol A (BPA) in kindergarten children (n = 31, 4-6 years old, sampling performed in 2016) in Hong Kong were measured. The detection frequency of the target PFRs, tri(2-chloroethyl)phosphate (TCEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), tris(chloroisopropyl)phosphate (TCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl diphenyl phosphate (EHDPP) ranged from 52% to 84%. The 95th percentile urinary concentrations of TPHP, TDCIPP, TCIPP, EHDPP and TCEP were 1.70, 0.24, 0.03, 0.05, 0.68 and 0.03 ng/mL, respectively. The median urine level of BPA was 1.69 ng/mL, with a detection frequency of 77%. Due to the lack of metabolism information, two scenarios were used to calculate the estimated daily intake (EDI) of these compounds. Back-calculated EDIs of PFRs using the urinary excretion rates from in vivo animal data (scenario 2) were up to 2.97 μg/kg/d (TDCIPP), which was only a little less than that observed in asample of American infants, and the reference dose (RfD), meaning that the potential health risk of TDCIPP cannot be ignored. Dust ingestion was suggested to be the major pathway of exposure to PFRs, but when the levels in dust and air particles in kindergartens in Hong Kong were used to predict EDIs, these values were nearly half as much as those predicted from urinary TDCIPP in this study. This suggested that children's PFRs burden may be underestimated when considering only PFR levels in dust or air. There is thus a need for further studies with large-scale surveys and investigation of exposure routes.

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PMID: 

Reprod Toxicol. 2019 Aug 21. Epub 2019 Aug 21. PMID: 31445078

Abstract Title: 

Male exposure to bisphenol A (BPA) and semen quality in the Home Observation of Periconceptional Exposures (HOPE) cohort.

Abstract: 

BACKGROUND: Exposure to bis-phenol A (BPA) has been associated with reduced semen quality. The objective of this study was to examine associations between BPA measured in serial daily first-morning urine samples and semen quality parameters among men trying to conceive.METHODS: This prospective, preconception cohort included 161 men ages 18-40 without known subfertility. Men collected daily, first morning urine during their female partner's fertile window. Semen samples were collected through intercourse after the fertile window.RESULTS: Samples from 161 men were analyzed. Higher geometric mean (GM) BPA exposures (ng/mL) were found among men with abnormal sperm tail morphology (GM = 3.12, 95% CI = 2.43, 4.01) compared to men with normal morphologic findings (GM = 2.39, 95% CI = 2.17, 2.74). There was no association with sperm count.CONCLUSION: Higher exposure to BPA was associated with abnormal sperm tail morphology in this prospective, pre-conception cohort.

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PMID: 

Birth Defects Res. 2019 Aug 9. Epub 2019 Aug 9. PMID: 31400084

Abstract Title: 

Developmental toxicity of e-cigarette aerosols.

Abstract: 

Maternal smoking during pregnancy represents a major public health concern increasing the risk for low birth weight, congenital anomalies, preterm birth, fetal mortality, and morbidity. In an effort to diminish adverse developmental effects of exposure to cigarette smoking, pregnant women, and women of reproductive age, are increasingly turning to electronic nicotine delivery systems (ENDS), such as e-cigarettes, as an alternative. Given that health risks associated with ENDS use during pregnancy are largely unknown, there is an acute need to determine risks vs. benefits of e-cigarette use by pregnant women. While the most recent Surgeon General's Report on the"Health Consequences of Smoking"states that"the evidence is sufficient to infer that nicotine adversely affects maternal and fetal health during pregnancy, contributing to multiple adverse outcomes,"it remains unclear whether use of ENDS represents a"safer alternative"to tobacco smoking during pregnancy. This is due, in part, to the lack of sufficient and conclusive evidence concerning whether or not maternal e-cigarette use adversely affects embryonic/fetal development. While several recent developmental studies have challenged the safety of nicotine inhalation via ENDS, the true risks of smoking e-cigarettes during the first trimester of pregnancy-the period of organogenesis-are largely unknown. Moreover, evidence is emerging that even nicotine-free e-cigarette aerosols may harm the developing conceptus, suggesting that components of e-cigarette liquid, including flavorings, may be developmentally toxicity. Focused human epidemiological analyses, and carefully designed animal studies are critically needed to address the question of the safety of ENDS use during pregnancy.

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PMID: 

J Adolesc. 2019 Aug 20 ;76:48-54. Epub 2019 Aug 20. PMID: 31442814

Abstract Title: 

E-cigarette use and sleep-related complaints among youth.

Abstract: 

INTRODUCTION: E-cigarette use is highly prevalent among adolescents. However, little research has examined the relationship between e-cigarette use and sleep-related complaints in this population. The objective of this study was to assess whether exclusive e-cigarette, exclusive combusted cigarette, and dual-product use are associated with sleep-related complaints among adolescents.METHODS: Participants were 9,588 U.S. adolescents from the Population Assessment of Tobacco and Health Study, a nationally representative cohort, followed from 2013 through 2015. Using logistic regression, we examined the cross-sectional association between past-year e-cigarette, combusted cigarette, or dual-product use and past-year sleep-related complaints (bad dreams, sleeping restlessly, or falling asleep during the day), both measured at Wave 2. We controlled for Wave 1 demographic characteristics, emotional and behavioral health, and prior history of e-cigarette use, combusted cigarette use, and sleep-related complaints.RESULTS: In unadjusted analyses, e-cigarette, combusted cigarette, and dual-product use were significantly associated with greater odds of sleep-related complaints, compared to use of neither product (e-cigarettes: OR = 1.61, 95% CI 1.34-1.94; combusted cigarettes: OR = 1.62, 95% CI 1.26-2.09; dual-product use: OR = 2.00, 95% CI 1.63-2.46). Associations between e-cigarette and dual-product use and sleep-related complaints remained significant in fully adjusted analyses (e-cigarettes: aOR = 1.29,95% CI 1.05-1.59; dual-product use: aOR = 1.57, 95% CI 1.24-1.99), whereas associations with combusted cigarette use were significant in all models except the fully adjusted model (aOR = 1.30, 95% CI 0.98-1.71).CONCLUSIONS: E-cigarette and dual-product use are significantly associated with greater odds of reporting sleep-related complaints among adolescents. Future research should evaluate whether this association may be causal.

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PMID: 

Radiology. 2019 Aug 20:190562. Epub 2019 Aug 20. PMID: 31429679

Abstract Title: 

Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI.

Abstract: 

Background Previous studies showed that nicotinized electronic cigarettes (hereafter, e-cigarettes) elicit systemic oxidative stress and inflammation. However, the effect of the aerosol alone on endothelial function is not fully understood. Purpose To quantify surrogate markers of endothelial function in nonsmokers after inhalation of aerosol from nicotine-free e-cigarettes. Materials and Methods In this prospective study (from May to September 2018), nonsmokers underwent 3.0-T MRI before and after inhaling nicotine-free e-cigarette aerosol. Peripheral vascular reactivity to cuff-induced ischemia was quantified by temporally resolving blood flow velocity and oxygenation (SvO) in superficial femoral artery and vein, respectively, along with artery luminal flow-mediated dilation. Precuff occlusion, resistivity index, baseline blood flow velocity, and SvOwere evaluated. During reactive hyperemia, blood flow velocity yielded peak velocity, time to peak, and acceleration rate (hyperemic index); SvOyielded washout time of oxygen-depleted blood, rate of resaturation, and maximum SvOincrease (overshoot). Cerebrovascular reactivity was assessed in the superior sagittal sinus, evaluating the breath-hold index. Central arterial stiffness was measured via aortic pulse wave velocity. Differences before versus after e-cigarette vaping were tested with Hotellingtest. Results Thirty-one healthy never-smokers (mean age, 24.3 years± 4.3; 14 women) were evaluated. After e-cigarette vaping, resistivity index was higher (0.03 of 1.30 [2.3%];

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