GreenMedInfo

REFRESHED: August 18, 2017 | 23:17:20

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PMID:  Bratisl Lek Listy. 2017 ;118(2):123-128. PMID: 28814095 Abstract Title:  Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells. Abstract:  OBJECTIVE: This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism.BACKGROUND: Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms.METHODS: MCF-7cells were treated by 50µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis.RESULTS: MTT and clonogenicity assays revealed that the Que induced a significant increase in cell viability and proliferation in presence of Nec-1 in comparison to the presence of ZVAD (p

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PMID:  Bratisl Lek Listy. 2017 ;118(2):123-128. PMID: 28814095 Abstract Title:  Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells. Abstract:  OBJECTIVE: This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism.BACKGROUND: Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms.METHODS: MCF-7cells were treated by 50µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis.RESULTS: MTT and clonogenicity assays revealed that the Que induced a significant increase in cell viability and proliferation in presence of Nec-1 in comparison to the presence of ZVAD (p

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Nutrients. 2017 May 25 ;9(6). Epub 2017 May 25. PMID: 28587078 Abstract Title:  Morinda citrifolia Linn. (Noni) and Its Potential in Obesity-Related Metabolic Dysfunction. Abstract:  Cultural and economic shifts in the early 19th century led to the rapid development of companies that made good profits from technologically-produced commodities. In this way, some habits changed in society, such as the overconsumption of processed and micronutrient-poor foods and devices that gave rise to a sedentary lifestyle. These factors influenced host-microbiome interactions which, in turn, mediated the etiopathogenesis of"new-era"disorders and diseases, which are closely related, such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, hypertension, and inflammatory bowel disease, which are characterized by chronic dysregulation of metabolic and immune processes. These pathological conditions require novel and effective therapeutic approaches. Morindacitrifolia (noni) is well known as a traditional healing plant due to its medicinal properties. Thus, many studies have been conducted to understand its bioactive compounds and their mechanisms of action. However, in obesity and obesity-related metabolic (dysfunction) syndrome, other studies are necessary to better elucidate noni's mechanisms of action, mainly due to the complexity of the pathophysiology of obesity and its metabolic dysfunction. In this review, we summarize not only the clinical effects, but also important cell signaling pathways in in vivo and in vitro assays of potent bioactive compounds present in the noni plant which have been reported in studies of obesity and obesity-associated metabolic dysfunction.

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PMID:  Nutrients. 2017 May 25 ;9(6). Epub 2017 May 25. PMID: 28587078 Abstract Title:  Morinda citrifolia Linn. (Noni) and Its Potential in Obesity-Related Metabolic Dysfunction. Abstract:  Cultural and economic shifts in the early 19th century led to the rapid development of companies that made good profits from technologically-produced commodities. In this way, some habits changed in society, such as the overconsumption of processed and micronutrient-poor foods and devices that gave rise to a sedentary lifestyle. These factors influenced host-microbiome interactions which, in turn, mediated the etiopathogenesis of"new-era"disorders and diseases, which are closely related, such as obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease, hypertension, and inflammatory bowel disease, which are characterized by chronic dysregulation of metabolic and immune processes. These pathological conditions require novel and effective therapeutic approaches. Morindacitrifolia (noni) is well known as a traditional healing plant due to its medicinal properties. Thus, many studies have been conducted to understand its bioactive compounds and their mechanisms of action. However, in obesity and obesity-related metabolic (dysfunction) syndrome, other studies are necessary to better elucidate noni's mechanisms of action, mainly due to the complexity of the pathophysiology of obesity and its metabolic dysfunction. In this review, we summarize not only the clinical effects, but also important cell signaling pathways in in vivo and in vitro assays of potent bioactive compounds present in the noni plant which have been reported in studies of obesity and obesity-associated metabolic dysfunction.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Food Nutr Res. 2017 ;61(1):1338919. Epub 2017 Jul 27. PMID: 28814950 Abstract Title:  Morinda citrifolia L. leaf extract prevent weight gain in Sprague-Dawley rats fed a high fat diet. Abstract:  Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain. Plasma leptin, insulin, adiponectin, and ghrelin of all groups were determined. (1)H NMR and LCMS methods were employed for phytochemical profiling of MLE60. Results: The supplementation of MLE60 did not affect food intake indicating that appetite suppression might not be the main anti-obesity mechanism involved. In the treated groups, MLE60 prevented weight gain, most likely through an inhibition of pancreatic and lipoprotein activity with a positive influence on the lipid profiles and a reduction in LDL levels . MLE60 also attenuated visceral fat deposition in treated subjects with improvement in the plasma levels of obesity-linked factors . (1)Spectral analysis showed the presence of several bioactive compounds with rutin being more predominant. Conclusion: MLE60 shows promise as an anti-obesity agents and warrants further research.

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PMID:  Food Nutr Res. 2017 ;61(1):1338919. Epub 2017 Jul 27. PMID: 28814950 Abstract Title:  Morinda citrifolia L. leaf extract prevent weight gain in Sprague-Dawley rats fed a high fat diet. Abstract:  Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain. Plasma leptin, insulin, adiponectin, and ghrelin of all groups were determined. (1)H NMR and LCMS methods were employed for phytochemical profiling of MLE60. Results: The supplementation of MLE60 did not affect food intake indicating that appetite suppression might not be the main anti-obesity mechanism involved. In the treated groups, MLE60 prevented weight gain, most likely through an inhibition of pancreatic and lipoprotein activity with a positive influence on the lipid profiles and a reduction in LDL levels . MLE60 also attenuated visceral fat deposition in treated subjects with improvement in the plasma levels of obesity-linked factors . (1)Spectral analysis showed the presence of several bioactive compounds with rutin being more predominant. Conclusion: MLE60 shows promise as an anti-obesity agents and warrants further research.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Postepy Hig Med Dosw (Online). 2017 Jun 8 ;71(0):446-453. Epub 2017 Jun 8. PMID: 28665275 Abstract Title:  Immune disorders induced by exposure to pyrethroid insecticides. Abstract:  Pyrethroids are biocides, which belong to the third generation of insecticides. They are used as biocides, insecticides and medicines. These agents react selectively, because they are less harmful to birds and mammals (due to poor intestinal absorption and rapid detoxification in the body of homeothermic organisms) and they are poisonous for fish and insects. The aim of the article is to present the current state of knowledge on the effects of pyrethroids on the immune system based on the latest scientific research. The mechanism of action of pyrethroids include the delaying closure of voltage- sensitive sodium and chloride channels (including GABA- dependent channels). These compounds are neurotoxic. Studies have shown that they cause numerous immune disorders contributing to lowering of immunity in humans and animals. Exposure to pyrethroids can cause inhibition of proliferation of peripheral blood leukocytes and reducing the concentration of IgG immunolgobulines. They also cause reduced macrophages and decrease in interleukin 2 (IL-2), interleukin 8 (IL-8), interleukin 12p70 (IL-12p70), and interferonγ (IFN-γ). Some of these compounds cause increase of liver weight and increase of bone marrow cellularity, and may induce apoptosis of the thymus. Pyrethroids can cause allergies and asthma. Their immunosuppressive effects can impair host resistance against infections. Exposure to these compoundscan also contribute to induction of the cancer, especially in patients with impaired immune function.

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PMID:  Postepy Hig Med Dosw (Online). 2017 Jun 8 ;71(0):446-453. Epub 2017 Jun 8. PMID: 28665275 Abstract Title:  Immune disorders induced by exposure to pyrethroid insecticides. Abstract:  Pyrethroids are biocides, which belong to the third generation of insecticides. They are used as biocides, insecticides and medicines. These agents react selectively, because they are less harmful to birds and mammals (due to poor intestinal absorption and rapid detoxification in the body of homeothermic organisms) and they are poisonous for fish and insects. The aim of the article is to present the current state of knowledge on the effects of pyrethroids on the immune system based on the latest scientific research. The mechanism of action of pyrethroids include the delaying closure of voltage- sensitive sodium and chloride channels (including GABA- dependent channels). These compounds are neurotoxic. Studies have shown that they cause numerous immune disorders contributing to lowering of immunity in humans and animals. Exposure to pyrethroids can cause inhibition of proliferation of peripheral blood leukocytes and reducing the concentration of IgG immunolgobulines. They also cause reduced macrophages and decrease in interleukin 2 (IL-2), interleukin 8 (IL-8), interleukin 12p70 (IL-12p70), and interferonγ (IFN-γ). Some of these compounds cause increase of liver weight and increase of bone marrow cellularity, and may induce apoptosis of the thymus. Pyrethroids can cause allergies and asthma. Their immunosuppressive effects can impair host resistance against infections. Exposure to these compoundscan also contribute to induction of the cancer, especially in patients with impaired immune function.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Arch Toxicol. 2017 02 ;91(2):603-604. Epub 2016 Dec 28. PMID: 28032145 Abstract Title:  Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience. Abstract:  Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.

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PMID:  Arch Toxicol. 2017 02 ;91(2):603-604. Epub 2016 Dec 28. PMID: 28032145 Abstract Title:  Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience. Abstract:  Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Environ Sci Technol. 2017 Aug 8. Epub 2017 Aug 8. PMID: 28731686 Abstract Title:  Pyrethroid Insecticide Cypermethrin Accelerates Pubertal Onset in Male Mice via Disrupting Hypothalamic-Pituitary-Gonadal Axis. Abstract:  Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models. Early postnatal exposure to CP at environmentally relevant doses (0.5, 5, and 50μg/kg CP) significantly accelerated the age of puberty onset in male mice. Administration of CP induced a dose-dependent increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in male mice. CP did not affect gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus, but CP at higher concentrations stimulated GnRH pulse frequency. CP could induce the secretion of LH and FSH, as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ, and FSHβ] in pituitary gonadotropes. CP stimulated testosterone production and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in testicular Leydig cells. The interference with hypothalamic sodium channels as well as calcium channels in pituitarygonadotropes and testicular Leydig cells was responsible for CP-induced HPG axis maturation. Our findings established in animal models provide further evidence for the biological plausibility of pyrethroid exposure as a potentially environmental contributor to earlier puberty in males.

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PMID:  Environ Sci Technol. 2017 Aug 8. Epub 2017 Aug 8. PMID: 28731686 Abstract Title:  Pyrethroid Insecticide Cypermethrin Accelerates Pubertal Onset in Male Mice via Disrupting Hypothalamic-Pituitary-Gonadal Axis. Abstract:  Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models. Early postnatal exposure to CP at environmentally relevant doses (0.5, 5, and 50μg/kg CP) significantly accelerated the age of puberty onset in male mice. Administration of CP induced a dose-dependent increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in male mice. CP did not affect gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus, but CP at higher concentrations stimulated GnRH pulse frequency. CP could induce the secretion of LH and FSH, as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ, and FSHβ] in pituitary gonadotropes. CP stimulated testosterone production and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in testicular Leydig cells. The interference with hypothalamic sodium channels as well as calcium channels in pituitarygonadotropes and testicular Leydig cells was responsible for CP-induced HPG axis maturation. Our findings established in animal models provide further evidence for the biological plausibility of pyrethroid exposure as a potentially environmental contributor to earlier puberty in males.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Occup Environ Med. 2017 Mar ;74(4):275-281. Epub 2017 Mar 1. PMID: 28250046 Abstract Title:  Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort. Abstract:  OBJECTIVE: The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds.METHODS: The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.RESULTS: Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03).CONCLUSIONS: The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.

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PMID:  Occup Environ Med. 2017 Mar ;74(4):275-281. Epub 2017 Mar 1. PMID: 28250046 Abstract Title:  Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort. Abstract:  OBJECTIVE: The potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention despite their widespread use. We investigated the associations between prenatal and childhood exposure to pyrethroid insecticides and behavioural skills in 6-year-olds.METHODS: The PELAGIE cohort enrolled 3421 pregnant women from Brittany, France between 2002 and 2006. 428 mothers were randomly selected for the study when their children turned 6, and 287 (67%) agreed to participate. Children's behaviour was assessed using the Strengths and Difficulties Questionnaire (SDQ). Three subscales (prosocial behaviour, internalising disorders and externalising disorders) were considered. Five pyrethroid metabolites were measured in maternal and child urine samples collected between 6 and 19 gestational weeks and at 6 years of age, respectively. Logistic regression and reverse-scale Cox regression models were used to estimate the associations between SDQ scores and urinary pyrethroid metabolite concentrations, adjusting for organophosphate metabolite concentrations and potential confounders.RESULTS: Increased prenatal cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) concentrations were associated with internalising difficulties (Cox p value=0.05). For childhood 3-phenoxybenzoic acid (PBA) concentrations, a positive association was observed with externalising difficulties (Cox p value=0.04) and high ORs were found for abnormal or borderline social behaviour (OR 2.93, 95% CI 1.27 to 6.78, and OR 1.91, 95% CI 0.80 to 4.57, for the intermediate and highest metabolite categories, respectively). High childhood trans-DCCA concentrations were associated with reduced externalising disorders (Cox p value=0.03).CONCLUSIONS: The present study suggests that exposure to certain pyrethroids, at environmental levels, may negatively affect neurobehavioral development by 6 years of age.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Environ Res. 2017 Jul ;156:597-604. Epub 2017 Apr 26. PMID: 28448812 Abstract Title:  Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area. Abstract:  BACKGROUND: Dichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy.OBJECTIVE: To evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy.MATERIALS AND METHODS: We analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models.RESULTS: Thirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH>2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (β=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis.CONCLUSIONS: Our findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.

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PMID:  Environ Res. 2017 Jul ;156:597-604. Epub 2017 Apr 26. PMID: 28448812 Abstract Title:  Effect of exposure to p,p´-DDE during the first half of pregnancy in the maternal thyroid profile of female residents in a Mexican floriculture area. Abstract:  BACKGROUND: Dichlorodiphenyldichloroethene (p,p´-DDE), the main metabolite of dichlorodiphenyltrichloroethane (DDT), has been associated with changes in human thyroid hormone levels. Maternal thyroid hormones are essential for adequate fetal neurodevelopment during the first half of pregnancy.OBJECTIVE: To evaluate the association between maternal p,p´-DDE concentration and the maternal thyroid profile during the first half of pregnancy.MATERIALS AND METHODS: We analyzed the information of 430 pregnant women from a Mexican floriculture area, with a gestational age≤16 weeks. By questionnaire, we obtained sociodemographic, reproductive, and life-style, information. Serum concentrations of thyroid stimulating hormone (TSH), and total and free T3 and T4 were determined by means of Enzyme-Linked ImmunoSorbent Assay (ELISA). p,p´-DDE was analyzed by Gas Chromatography. The association between p,p´-DDE and thyroid profile was assessed through linear and logistic regression models.RESULTS: Thirty eight percent of women had p,p´-DDE levels below the Limit of Detection and 12.3% below the Limit of Quantification. Within the quantifiable range, median was 53.03ng/g. TSH>2.5 mIU/L was present in 9.3% of women; 47.7% had isolated hypothyroxinemia; 3.5% had subclinical hypothyroidism, and 5.8% had overt hypothyroidism. We observed a significant positive association between quantifiable p,p´-DDE and total T3 serum levels in comparison with those with concentrations below the Limit of Detection (β=0.19; 95% CI=0.06, 0.34). There were no significant associations with other hormones of the thyroid profile or with clinical diagnosis.CONCLUSIONS: Our findings suggest that p,p´-DDE exposure, even at low concentrations, could disrupt thyroid homeostasis during pregnancy.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Int J Environ Res Public Health. 2017 May 27 ;14(6). Epub 2017 May 27. PMID: 28554999 Abstract Title:  The Impact of Prenatal Organophosphate Pesticide Exposures on Thai Infant Neurodevelopment. Abstract:  A birth cohort was begun to investigate the levels and sources of pesticide exposure in pregnant women living in Thailand, and to examine the effects of pesticide exposure on infant neurodevelopment at five months of age. Subjects were interviewed using questionnaires regarding their demographic characteristics, educational background, and work and home activities related to pesticide exposures. Spot urine samples were collected at 28 weeks gestation and analyzed by gas chromatography-mass spectrometry to determine maternal metabolite levels of organophosphate pesticides including dimethyl phosphate (DMP); total DEP (diethyl phosphate (DEP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP), and total DAP (the sum of all metabolite levels). At five months of age, infant development was evaluated using the Bayley Scales of Infant and Toddler Development-III (Bayley-III). Higher total DEP and total DAP metabolite levels from the mother at 28 weeks' gestation were significantly associated with reduced motor composite scores on the Bayley-III at five months of age. The total DEP levels were also significantly associated with reduced cognitive composite scores. Prenatal concentrations of maternal urinary metabolites were associated with infant cognitive and motor development. The results of several studies now suggest the need for public health intervention to reduce prenatal pesticide exposures from both agricultural and domestic use.

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PMID:  Int J Environ Res Public Health. 2017 May 27 ;14(6). Epub 2017 May 27. PMID: 28554999 Abstract Title:  The Impact of Prenatal Organophosphate Pesticide Exposures on Thai Infant Neurodevelopment. Abstract:  A birth cohort was begun to investigate the levels and sources of pesticide exposure in pregnant women living in Thailand, and to examine the effects of pesticide exposure on infant neurodevelopment at five months of age. Subjects were interviewed using questionnaires regarding their demographic characteristics, educational background, and work and home activities related to pesticide exposures. Spot urine samples were collected at 28 weeks gestation and analyzed by gas chromatography-mass spectrometry to determine maternal metabolite levels of organophosphate pesticides including dimethyl phosphate (DMP); total DEP (diethyl phosphate (DEP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP), and total DAP (the sum of all metabolite levels). At five months of age, infant development was evaluated using the Bayley Scales of Infant and Toddler Development-III (Bayley-III). Higher total DEP and total DAP metabolite levels from the mother at 28 weeks' gestation were significantly associated with reduced motor composite scores on the Bayley-III at five months of age. The total DEP levels were also significantly associated with reduced cognitive composite scores. Prenatal concentrations of maternal urinary metabolites were associated with infant cognitive and motor development. The results of several studies now suggest the need for public health intervention to reduce prenatal pesticide exposures from both agricultural and domestic use.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Front Pediatr. 2017 ;5:116. Epub 2017 May 24. PMID: 28596952 Abstract Title:  Neurodevelopmental Delay Diagnosis Rates Are Increased in a Region with Aerial Pesticide Application. Abstract:  A number of studies have implicated pesticides in childhood developmental delay (DD) and autism spectrum disorder (ASD). The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06-1.78, p = 0.02). A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight,and birth rates) identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities developplans for Zika virus control.

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PMID:  Front Pediatr. 2017 ;5:116. Epub 2017 May 24. PMID: 28596952 Abstract Title:  Neurodevelopmental Delay Diagnosis Rates Are Increased in a Region with Aerial Pesticide Application. Abstract:  A number of studies have implicated pesticides in childhood developmental delay (DD) and autism spectrum disorder (ASD). The influence of the route of pesticide exposure on neurodevelopmental delay is not well defined. To study this factor, we examined ASD/DD diagnoses rates in an area near our regional medical center that employs yearly aerial pyrethroid pesticide applications to combat mosquito-borne encephalitis. The aim of this study was to determine if areas with aerial pesticide exposure had higher rates of ASD/DD diagnoses. This regional study identified higher rates of ASD/DD diagnoses in an area with aerial pesticides application. Zip codes with aerial pyrethroid exposure were 37% more likely to have higher rates of ASD/DD (adjusted RR = 1.37, 95% CI = 1.06-1.78, p = 0.02). A Poisson regression model controlling for regional characteristics (poverty, pesticide use, population density, and distance to medical center), subject characteristics (race and sex), and local birth characteristics (prematurity, low birthweight,and birth rates) identified a significant relationship between aerial pesticide use and ASD/DD rates. The relationship between pesticide application and human neurodevelopment deserves additional study to develop safe and effective methods of mosquito prevention, particularly as communities developplans for Zika virus control.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Neurotoxicology. 2017 Aug 12. Epub 2017 Aug 12. PMID: 28811173 Abstract Title:  Prenatal Exposure to Pyrethroid Pesticides and Childhood Behavior and Executive Functioning. Abstract:  Several previous studies of pyrethroid biomarkers and behavior have reported associations between concurrent pyrethroid levels and adverse behavioral problems in children. One geospatial study reported associations between prenatal exposure to pyrethroids and autism. However, the association between prenatal pyrethroid biomarkers and childhood behavior is unknown. The Mount Sinai Children's Environmental Health Center is a prospective birth cohort with urinary pyrethroid biomarkers during pregnancy and behavioral measurements at 4, 6, and 7-9 years of age. Primiparous women were enrolled between 1998-2002. 162 mother/child pairs with complete exposure and behavioral outcomes data were used to investigate associations between detectable levels of prenatal pyrethroid metabolites and scores on the Behavioral Assessment System for Children and the Behavior Rating Inventory of Executive Function. Overall, detection frequencies of pyrethroid metabolites were low (

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PMID:  Neurotoxicology. 2017 Aug 12. Epub 2017 Aug 12. PMID: 28811173 Abstract Title:  Prenatal Exposure to Pyrethroid Pesticides and Childhood Behavior and Executive Functioning. Abstract:  Several previous studies of pyrethroid biomarkers and behavior have reported associations between concurrent pyrethroid levels and adverse behavioral problems in children. One geospatial study reported associations between prenatal exposure to pyrethroids and autism. However, the association between prenatal pyrethroid biomarkers and childhood behavior is unknown. The Mount Sinai Children's Environmental Health Center is a prospective birth cohort with urinary pyrethroid biomarkers during pregnancy and behavioral measurements at 4, 6, and 7-9 years of age. Primiparous women were enrolled between 1998-2002. 162 mother/child pairs with complete exposure and behavioral outcomes data were used to investigate associations between detectable levels of prenatal pyrethroid metabolites and scores on the Behavioral Assessment System for Children and the Behavior Rating Inventory of Executive Function. Overall, detection frequencies of pyrethroid metabolites were low (

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Environ Int. 2017 Sep ;106:248-256. Epub 2017 Jun 8. PMID: 28602489 Abstract Title:  Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants. Abstract:  BACKGROUND: Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development.METHODS: 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n=199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ).RESULTS: Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in≥10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1ng/mL increase in log-naled, for V-M (p=0.04), FM (p=0.04), and FMQ (p=0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p=0.04), locomotion (p=0.02), grasping (p=0.05), V-M (p

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PMID:  Environ Int. 2017 Sep ;106:248-256. Epub 2017 Jun 8. PMID: 28602489 Abstract Title:  Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants. Abstract:  BACKGROUND: Organophosphate insecticides (OPs) are used worldwide, yet despite nearly ubiquitous exposure in the general population, few have been studied outside the laboratory. Fetal brains undergo rapid growth and development, leaving them susceptible to long-term effects of neurotoxic OPs. The objective here was to investigate the extent to which prenatal exposure to OPs affects infant motor development.METHODS: 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Motor function was assessed at 6-weeks and 9-months using Peabody Developmental Motor Scales 2nd edition (PDMS-2) (n=199). Outcomes included subtest scores: reflexes, stationary, locomotion, grasping, visual-motor integration (V-M), composite scores: gross (GM), fine (FM), total motor (TM), and standardized motor quotients: gross (GMQ), fine (FMQ), total motor (TMQ).RESULTS: Naled, methamidophos, trichlorfon, chlorpyrifos, and phorate were detected in≥10% of samples. Prenatal naled and chlorpyrifos were associated with decreased 9-month motor function. Scores were 0.55, 0.85, and 0.90 points lower per 1ng/mL increase in log-naled, for V-M (p=0.04), FM (p=0.04), and FMQ (p=0.08), respectively. For chlorpyrifos, scores were 0.50, 1.98, 0.80, 1.91, 3.49, 2.71, 6.29, 2.56, 2.04, and 2.59 points lower for exposed versus unexposed infants, for reflexes (p=0.04), locomotion (p=0.02), grasping (p=0.05), V-M (p

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Neurotoxicology. 2017 Jun 12 ;62:111-123. Epub 2017 Jun 12. PMID: 28600141 Abstract Title:  Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons. Abstract:  Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide that has recently come under increasing scrutiny due to environmental health concerns particularly its association with neurodevelopmental defects. While the insecticidal actions and acute toxicity of CPF are attributed to its oxon metabolite (CPO) which potently inhibits the cholinergic enzyme acetylcholinesterase (AChE), there is significant evidence that CPF, CPO, and other organophosphates may affect a variety of neuronal targets and processes that are not directly related to AChE. Previously, in adult rat sciatic nerves ex vivo and postnatal neurons from rats in vitro we observed that CPF and CPO impaired the movements of vesicles and mitochondria in axons. Here, in embryonic neurons from rats in culture, we evaluated 24h exposures to CPF and CPO across picomolar to micromolar concentrations for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). The most notable observations of this study were concentration-dependent decreases in the velocity and percentage of MBOs moving in the anterograde direction, an increase in the number of stationary MBOs, and an increased frequency of pauses associated with both CPF and CPO. These effects occurred at concentrations that did not significantly inhibit AChE activity, they were not blocked by cholinergic receptor antagonists, and they were not associated with compromised cell viability. These effects of CPF and CPO may be significant given the importance of axonal transport to neuronal development as well the function of fully developed neurons.

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PMID:  Neurotoxicology. 2017 Jun 12 ;62:111-123. Epub 2017 Jun 12. PMID: 28600141 Abstract Title:  Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons. Abstract:  Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide that has recently come under increasing scrutiny due to environmental health concerns particularly its association with neurodevelopmental defects. While the insecticidal actions and acute toxicity of CPF are attributed to its oxon metabolite (CPO) which potently inhibits the cholinergic enzyme acetylcholinesterase (AChE), there is significant evidence that CPF, CPO, and other organophosphates may affect a variety of neuronal targets and processes that are not directly related to AChE. Previously, in adult rat sciatic nerves ex vivo and postnatal neurons from rats in vitro we observed that CPF and CPO impaired the movements of vesicles and mitochondria in axons. Here, in embryonic neurons from rats in culture, we evaluated 24h exposures to CPF and CPO across picomolar to micromolar concentrations for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). The most notable observations of this study were concentration-dependent decreases in the velocity and percentage of MBOs moving in the anterograde direction, an increase in the number of stationary MBOs, and an increased frequency of pauses associated with both CPF and CPO. These effects occurred at concentrations that did not significantly inhibit AChE activity, they were not blocked by cholinergic receptor antagonists, and they were not associated with compromised cell viability. These effects of CPF and CPO may be significant given the importance of axonal transport to neuronal development as well the function of fully developed neurons.

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  Environ Sci Pollut Res Int. 2017 Jul 18. Epub 2017 Jul 18. PMID: 28721614 Abstract Title:  Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones. Abstract:  Use of pesticides results in indirect effects on human health. We aimed to evaluate implications of toxicological effects of subchronic chlorpyrifos exposure on reproductive function in male rats. A total of 48 adult Wistar male rats were separated into four groups (n = 12). Animals were gavaged with 2.5 mg/kg (T1), 5 mg/kg (T2), or 10 mg/kg (T3) body weight of chlorpyrifos (CPF) or distilled water (control) daily for 30 days. Organ weights, epididymal sperm parameters, DNA integrity, sex hormonal (FHS and LH) levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and creatinine concentrations were determined on day 31. Another two sets of (four groups/set; n = 10) animals were orally treated with the same doses of CPF, control animal groups were treated with distilled water only for 30 days, and fertility indices and blood plasma acetylcholine esterase (AchE) were determined on day 31. Exposure to CPF resulted in a significant (p 

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PMID:  Environ Sci Pollut Res Int. 2017 Jul 18. Epub 2017 Jul 18. PMID: 28721614 Abstract Title:  Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones. Abstract:  Use of pesticides results in indirect effects on human health. We aimed to evaluate implications of toxicological effects of subchronic chlorpyrifos exposure on reproductive function in male rats. A total of 48 adult Wistar male rats were separated into four groups (n = 12). Animals were gavaged with 2.5 mg/kg (T1), 5 mg/kg (T2), or 10 mg/kg (T3) body weight of chlorpyrifos (CPF) or distilled water (control) daily for 30 days. Organ weights, epididymal sperm parameters, DNA integrity, sex hormonal (FHS and LH) levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and creatinine concentrations were determined on day 31. Another two sets of (four groups/set; n = 10) animals were orally treated with the same doses of CPF, control animal groups were treated with distilled water only for 30 days, and fertility indices and blood plasma acetylcholine esterase (AchE) were determined on day 31. Exposure to CPF resulted in a significant (p 

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Author: greenmedinfo
Posted: 18-08-2017
PMID:  J Matern Fetal Neonatal Med. 2017 Aug 14:1-15. Epub 2017 Aug 14. PMID: 28805116 Abstract Title:  Bisphenol A and adverse pregnancy outcomes: a systematic review of the literature. Abstract:  PURPOSE: Bisphenol A is a chemical compound related to adverse maternal and neonatal outcomes. The purpose of the present systematic review is to summarize current knowledge in the field.MATERIALS AND METHODS: We systematically searched the Medline (1966-2017), Scopus (2004-2017), Clinicaltrials.gov (2008-2017), Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases.RESULTS: Thirty-five studies were included in the present systematic review. According to our findings BPA has a direct negative impact on maternal, fetal and neonatal outcomes, including birthweight, rates of preterm birth, developmental defects and recurrent miscarriage. Data in the field of preeclampsia and gestational diabetes mellitus remain inconclusive because current research is very limited.CONCLUSION: BPA exposure during pregnancy can result in significant antenatal pathology; hence, occupational exposure should be at least discouraged during this period. However, cross-sectional studies in the field that would assess the levels of exposure at timely intervals are still lacking, therefore the actual impact of BPA remains unclear.

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PMID:  J Matern Fetal Neonatal Med. 2017 Aug 14:1-15. Epub 2017 Aug 14. PMID: 28805116 Abstract Title:  Bisphenol A and adverse pregnancy outcomes: a systematic review of the literature. Abstract:  PURPOSE: Bisphenol A is a chemical compound related to adverse maternal and neonatal outcomes. The purpose of the present systematic review is to summarize current knowledge in the field.MATERIALS AND METHODS: We systematically searched the Medline (1966-2017), Scopus (2004-2017), Clinicaltrials.gov (2008-2017), Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases.RESULTS: Thirty-five studies were included in the present systematic review. According to our findings BPA has a direct negative impact on maternal, fetal and neonatal outcomes, including birthweight, rates of preterm birth, developmental defects and recurrent miscarriage. Data in the field of preeclampsia and gestational diabetes mellitus remain inconclusive because current research is very limited.CONCLUSION: BPA exposure during pregnancy can result in significant antenatal pathology; hence, occupational exposure should be at least discouraged during this period. However, cross-sectional studies in the field that would assess the levels of exposure at timely intervals are still lacking, therefore the actual impact of BPA remains unclear.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Sci Total Environ. 2017 Aug 11 ;610-611:291-297. Epub 2017 Aug 11. PMID: 28806546 Abstract Title:  Parental exposure to bisphenol A and its analogs influences zebrafish offspring immunity. Abstract:  Transgenerational effects of environmental pollutants on humans and animals are complex. Thus, we used zebrafish to evaluate the effects of parental whole-life cycle exposure to bisphenol A and its analogs (bisphenol S and F) on offspring innate immunity. At adulthood, offspring were examined with/without continued chemicals treatment until 72h post-fertilization (hpf). To measure offspring immune function, larvae at 72 hpf were expose for 24h with/without the viral mimic polyinosinic-cytidylic acid (Poly I:C) or the bacterial mimic Pam3Cys-Ser-Lys4 (PAM3CSK4). Data show modified immunity in offspring. Specifically, lysozyme activity was significantly induced in F1 larvae and respiratory burst response and oxidative defense genes were inhibited. Genes of the innate immune system including Toll-like receptors and their downstream molecules and inflammatory cytokines were significantly down-regulated, whereas matrix metalloproteinases were up-regulated in larvae. In addition, recombination-activating genes in the immature adaptive immune system were significantly reduced. Thus, immune defense is diminished by exposing parental generations of zebrafish to environmentally relevant concentration of bisphenols and this suggests that fish chronically exposed to bisphenols in the wild may be vulnerable to pathogens.

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PMID:  Sci Total Environ. 2017 Aug 11 ;610-611:291-297. Epub 2017 Aug 11. PMID: 28806546 Abstract Title:  Parental exposure to bisphenol A and its analogs influences zebrafish offspring immunity. Abstract:  Transgenerational effects of environmental pollutants on humans and animals are complex. Thus, we used zebrafish to evaluate the effects of parental whole-life cycle exposure to bisphenol A and its analogs (bisphenol S and F) on offspring innate immunity. At adulthood, offspring were examined with/without continued chemicals treatment until 72h post-fertilization (hpf). To measure offspring immune function, larvae at 72 hpf were expose for 24h with/without the viral mimic polyinosinic-cytidylic acid (Poly I:C) or the bacterial mimic Pam3Cys-Ser-Lys4 (PAM3CSK4). Data show modified immunity in offspring. Specifically, lysozyme activity was significantly induced in F1 larvae and respiratory burst response and oxidative defense genes were inhibited. Genes of the innate immune system including Toll-like receptors and their downstream molecules and inflammatory cytokines were significantly down-regulated, whereas matrix metalloproteinases were up-regulated in larvae. In addition, recombination-activating genes in the immature adaptive immune system were significantly reduced. Thus, immune defense is diminished by exposing parental generations of zebrafish to environmentally relevant concentration of bisphenols and this suggests that fish chronically exposed to bisphenols in the wild may be vulnerable to pathogens.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  PLoS One. 2017 ;12(5):e0176927. Epub 2017 May 3. PMID: 28467477 Abstract Title:  Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae. Abstract:  Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS,the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSHconcentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.

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PMID:  PLoS One. 2017 ;12(5):e0176927. Epub 2017 May 3. PMID: 28467477 Abstract Title:  Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae. Abstract:  Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS,the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSHconcentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  J Biomed Res. 2017 Jul 13 ;31(4):358-369. PMID: 28808208 Abstract Title:  Effects of bisphenol compounds on the growth and epithelial mesenchymal transition of MCF-7 CV human breast cancer cells. Abstract:  Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical (EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-dependent cancer has been reported rarely compared with the numerous cases of BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors (ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased proliferation of MCF-7 CV cells compared to control (DMSO) as did 17β-estradiol (E2). In Western blotting assay, BPA, BPS, and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1. In addition, MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA, BPS, or BPF for 24 hours.In cell migration assay, BPA, BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2. In relation with the EMT process, BPA, BPS, and BPF increased the protein expression ofN-cadherin, while they decreased the protein expression of E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER antagonist, proliferation effects were reversed, the expression of cyclin D1 and cyclin E1 was downregulated, and the altered cell migration and expression ofN-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control level. Thus, these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markersvia the ER-dependent pathway.

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PMID:  J Biomed Res. 2017 Jul 13 ;31(4):358-369. PMID: 28808208 Abstract Title:  Effects of bisphenol compounds on the growth and epithelial mesenchymal transition of MCF-7 CV human breast cancer cells. Abstract:  Bisphenol-A (BPA) has been considered as an endocrine disrupting chemical (EDC) because it can exert estrogenic properties. For bisphenol-S (BPS) and bisphenol-F (BPF) that are BPA analogs and substitutes, their risk to estrogen-dependent cancer has been reported rarely compared with the numerous cases of BPA. In this study, we examined whether BPA, BPS, and BPF can lead to the proliferation, migration, and epithelial mesenchymal transition (EMT) of MCF-7 clonal variant (MCF-7 CV) breast cancer cells expressing estrogen receptors (ERs). In a cell viability assay, BPA, BPS, and BPF significantly increased proliferation of MCF-7 CV cells compared to control (DMSO) as did 17β-estradiol (E2). In Western blotting assay, BPA, BPS, and BPF enhanced the protein expression of cell cycle progression genes such as cyclin D1 and E1. In addition, MCF-7 CV cells lost cell to cell contacts and acquired fibroblast-like morphology by the treatment of BPA, BPS, or BPF for 24 hours.In cell migration assay, BPA, BPS, and BPF accelerated the migration capability of MCF-7 CV cells as did E2. In relation with the EMT process, BPA, BPS, and BPF increased the protein expression ofN-cadherin, while they decreased the protein expression of E-cadherin. When BPA, BPS, and BPF were co-treated with ICI 182,780, an ER antagonist, proliferation effects were reversed, the expression of cyclin D1 and cyclin E1 was downregulated, and the altered cell migration and expression ofN-cadherin and E-cadherin by BPA, BPS, and BPF were restored to the control level. Thus, these results imply that BPS and BPF also have the risk of breast cancer progression as much as BPA in the induction of proliferation and migration of MCF-7 CV cells by regulating the protein expression of cell cycle-related genes and EMT markersvia the ER-dependent pathway.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Tumour Biol. 2017 Mar ;39(3):1010428317694536. PMID: 28351329 Abstract Title:  Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy. Abstract:  The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

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PMID:  Tumour Biol. 2017 Mar ;39(3):1010428317694536. PMID: 28351329 Abstract Title:  Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy. Abstract:  The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  J Agric Food Chem. 2017 Jul 19 ;65(28):5639-5649. Epub 2017 Jul 7. PMID: 28643510 Abstract Title:  Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer. Abstract:  Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9± 4.7 μM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114.0 ± 8.0 and 113.0 ± 11.1 μM, respectively). The results described in this article suggest that saffron may be a helpful alimentary component in the prevention of cancer that potentially contributes to the efficacy of approved cancer therapies.

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PMID:  J Agric Food Chem. 2017 Jul 19 ;65(28):5639-5649. Epub 2017 Jul 7. PMID: 28643510 Abstract Title:  Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer. Abstract:  Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9± 4.7 μM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114.0 ± 8.0 and 113.0 ± 11.1 μM, respectively). The results described in this article suggest that saffron may be a helpful alimentary component in the prevention of cancer that potentially contributes to the efficacy of approved cancer therapies.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Neurosci Bull. 2017 Aug 2. Epub 2017 Aug 2. PMID: 28770439 Abstract Title:  Crocetin Potentiates Neurite Growth in Hippocampal Neurons and Facilitates Functional Recovery in Rats with Spinal Cord Injury. Abstract:  Crocetin is an ingredient of traditional Chinese medicine and has therapeutic potential in various diseases due to its pharmacological properties, such as neuroprotection, anti-oxidative stress, and anti-inflammation. These properties might benefit the treatment of spinal cord injury. In the present study, we tested the effect of crocetin on neurite growth and sensorimotor dysfunction in a rat model of spinal cord injury. We evaluated the viability of cultured hippocampal neurons with tetrazolium dye and lactate dehydrogenase assays, visualized neurites and axons with antibody staining, and monitored motor and sensorimotor functions in rats with spinal cord injury using the Basso, Beattie, and Bresnahan assay and the contact plantar placement test, respectively, and measured cytokine expression using enzyme-linked immuno-absorbent assays. We found that crocetin (1) did not alter the viability of cultured hippocampal neurons; (2) accelerated neurite growth with preference for the longest process in individual hippocampal neurons; (3) reversed the inhibition of neurite growth by chondroitin sulfate proteoglycan and NogoA; (4) facilitated the recovery of motor and sensorimotor functions after spinal cord injury; and (5) did not inhibit pro-inflammatory responses, but restored the innervation of the descending 5-HT system in injured spinal cord. Crocetin promotes neurite growth and facilitates the recovery of motor and sensorimotor functions after spinal cord injury, likely through repairing neuronal connections.

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PMID:  Neurosci Bull. 2017 Aug 2. Epub 2017 Aug 2. PMID: 28770439 Abstract Title:  Crocetin Potentiates Neurite Growth in Hippocampal Neurons and Facilitates Functional Recovery in Rats with Spinal Cord Injury. Abstract:  Crocetin is an ingredient of traditional Chinese medicine and has therapeutic potential in various diseases due to its pharmacological properties, such as neuroprotection, anti-oxidative stress, and anti-inflammation. These properties might benefit the treatment of spinal cord injury. In the present study, we tested the effect of crocetin on neurite growth and sensorimotor dysfunction in a rat model of spinal cord injury. We evaluated the viability of cultured hippocampal neurons with tetrazolium dye and lactate dehydrogenase assays, visualized neurites and axons with antibody staining, and monitored motor and sensorimotor functions in rats with spinal cord injury using the Basso, Beattie, and Bresnahan assay and the contact plantar placement test, respectively, and measured cytokine expression using enzyme-linked immuno-absorbent assays. We found that crocetin (1) did not alter the viability of cultured hippocampal neurons; (2) accelerated neurite growth with preference for the longest process in individual hippocampal neurons; (3) reversed the inhibition of neurite growth by chondroitin sulfate proteoglycan and NogoA; (4) facilitated the recovery of motor and sensorimotor functions after spinal cord injury; and (5) did not inhibit pro-inflammatory responses, but restored the innervation of the descending 5-HT system in injured spinal cord. Crocetin promotes neurite growth and facilitates the recovery of motor and sensorimotor functions after spinal cord injury, likely through repairing neuronal connections.

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Author: greenmedinfo
Posted: 17-08-2017

Citizen groups say Clean Water Act lawsuit needed now more than ever

Citizen groups say Clean Water Act lawsuit needed now more than ever

Author: cleanenergy
Posted: 17-08-2017
PMID:  Nutr Cancer. 2017 Jul 18:1-9. Epub 2017 Jul 18. PMID: 28718677 Abstract Title:  Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line). Abstract:  Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05-4 mM) and safranal (0.2-3.2 mM) significantly inhibited thegrowth of KB cells (the inhibitory growth effects of all concentrations for both were>50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC50 values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects inKB cell line.

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PMID:  Nutr Cancer. 2017 Jul 18:1-9. Epub 2017 Jul 18. PMID: 28718677 Abstract Title:  Evaluation of the Cytotoxic Activity of Crocin and Safranal, Constituents of Saffron, in Oral Squamous Cell Carcinoma (KB Cell Line). Abstract:  Crocin and safranal are active ingredients in the saffron. Some studies have demonstrated antitumor activities of saffron ingredients. The aim of this study was to evaluate cytotoxic effects of crocin and safranal in oral squamous cell carcinoma (KB cells) and NIH 3T3 cell line as nonmalignant cells. The cells were incubated with crocin and safranal at 37°C for 24, 48, and 72 h, and cell viability was quantitated by MTT assay. Apoptotic cells, cell cycle distribution, and sub-G1 fraction were determined using propidium iodide staining of DNA fragmentation by flow cytometry. Crocin (0.05-4 mM) and safranal (0.2-3.2 mM) significantly inhibited thegrowth of KB cells (the inhibitory growth effects of all concentrations for both were>50% after 72 h), while they had less inhibitory effects on NIH 3T3 cells viability. The IC50 values of crocin and safranal against NIH 3T3 cells after 72 h were determined as 2.8 and 0.3 mM, respectively. Crocin and safranal induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in the toxicity of crocin and safranal. Apoptotic effects of crocin and safranal in tumor cells were more than normal cells. Neither crocin nor safranal affected the cell cycle progression. Crocin and safranal exerted apoptotic effects inKB cell line.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Cell Physiol Biochem. 2017 Jul 18 ;42(4):1481-1492. Epub 2017 Jul 18. PMID: 28719912 Abstract Title:  Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB. Abstract:  BACKGROUND/AIMS: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB.METHODS: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria. Cells were incubated with 15 or 25 mM D-glucose to mimic diabetic conditions. The expression of Wilms tumor 1 (WT-1) and synaptopodin was evaluated to identify differentiated podocytes, and the expression of nephrin, podocin, and CD2ap was measured as markers of slit diaphragms, the main structures within the glomerular filtration barrier.RESULTS: The high-glucose conditions led to reduced nephrin, podocin, and CD2ap expression, which was prevented by pretreatment with crocin. The oxidative stress and pro-inflammatory response of podocytes associated with DN induced by high glucose were also reduced by crocin pretreatment. Phosphorylated IκBα (p-IκBα) expression induced by high glucose was also significantly decreased by crocin pretreatment. Moreover, pyrrolidine dithiocarbamate, a NF-κB inhibitor, pyrrolidine dithio carbamate, augmented the protective effects of crocin.CONCLUSION: Our results demonstrate a protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB. This study presents a potential therapy for DN and contributes to the understanding of the mechanism underlying DN.

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PMID:  Cell Physiol Biochem. 2017 Jul 18 ;42(4):1481-1492. Epub 2017 Jul 18. PMID: 28719912 Abstract Title:  Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB. Abstract:  BACKGROUND/AIMS: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB.METHODS: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria. Cells were incubated with 15 or 25 mM D-glucose to mimic diabetic conditions. The expression of Wilms tumor 1 (WT-1) and synaptopodin was evaluated to identify differentiated podocytes, and the expression of nephrin, podocin, and CD2ap was measured as markers of slit diaphragms, the main structures within the glomerular filtration barrier.RESULTS: The high-glucose conditions led to reduced nephrin, podocin, and CD2ap expression, which was prevented by pretreatment with crocin. The oxidative stress and pro-inflammatory response of podocytes associated with DN induced by high glucose were also reduced by crocin pretreatment. Phosphorylated IκBα (p-IκBα) expression induced by high glucose was also significantly decreased by crocin pretreatment. Moreover, pyrrolidine dithiocarbamate, a NF-κB inhibitor, pyrrolidine dithio carbamate, augmented the protective effects of crocin.CONCLUSION: Our results demonstrate a protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB. This study presents a potential therapy for DN and contributes to the understanding of the mechanism underlying DN.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Int Immunopharmacol. 2017 Sep ;50:305-312. Epub 2017 Jul 21. PMID: 28738246 Abstract Title:  Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Abstract:  Allergic asthma is a chronic respiratory disease with a prevalent T helper (Th2)-mediated immune reaction. Crocin, the major bioactive constituent of saffron, has been reported in multiple studies to have numerous pharmacological activities, including prominent anti-oxidant activities. In the current study, the anti-asthmatic potential of crocin was evaluated. Adult male Swiss Albino mice were administered 10mg of ovalbumin (OVA) mixed with 1mg of aluminum hydroxide intraperitoneally on days 0 and 7 and were administered crocin (25mg/kg) orally daily for 16days. Asthma progression was associated with significant increase in the lung/body weight index, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung total protein content, and serious index of lung permeability, indicating pulmonary edema with accumulation of serous fluids within the lungs. Serum lactate dehydrogenase (LDH) activity and lung malondialdehyde (MDA) content were significantly increased, while lung superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and serum and lung catalase activities were significantly decreased. These changes reflect significant pulmonary inflammation with concomitant disturbance of oxidant/antioxidant homeostasis. Moreover, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-13 contents in the lung were also significantly high after OVA sensitization. Crocin treatment significantly alleviated the OVA-induced allergic asthma-associated alterations in inflammatory and oxidative stress biomarkers. Crocin enhanced anti-oxidant defenses, reduced the incidence of oxidative stress, and restored pro-inflammatory cytokines to normal levels. Histopathological analysis showed significant lung improvement in crocin-treated mice. In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associatedwith down-regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis.

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PMID:  Int Immunopharmacol. 2017 Sep ;50:305-312. Epub 2017 Jul 21. PMID: 28738246 Abstract Title:  Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Abstract:  Allergic asthma is a chronic respiratory disease with a prevalent T helper (Th2)-mediated immune reaction. Crocin, the major bioactive constituent of saffron, has been reported in multiple studies to have numerous pharmacological activities, including prominent anti-oxidant activities. In the current study, the anti-asthmatic potential of crocin was evaluated. Adult male Swiss Albino mice were administered 10mg of ovalbumin (OVA) mixed with 1mg of aluminum hydroxide intraperitoneally on days 0 and 7 and were administered crocin (25mg/kg) orally daily for 16days. Asthma progression was associated with significant increase in the lung/body weight index, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), lung total protein content, and serious index of lung permeability, indicating pulmonary edema with accumulation of serous fluids within the lungs. Serum lactate dehydrogenase (LDH) activity and lung malondialdehyde (MDA) content were significantly increased, while lung superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels, and serum and lung catalase activities were significantly decreased. These changes reflect significant pulmonary inflammation with concomitant disturbance of oxidant/antioxidant homeostasis. Moreover, tumor necrosis factor (TNF)-α, interleukin (IL)-4, and IL-13 contents in the lung were also significantly high after OVA sensitization. Crocin treatment significantly alleviated the OVA-induced allergic asthma-associated alterations in inflammatory and oxidative stress biomarkers. Crocin enhanced anti-oxidant defenses, reduced the incidence of oxidative stress, and restored pro-inflammatory cytokines to normal levels. Histopathological analysis showed significant lung improvement in crocin-treated mice. In conclusion, crocin showed a significant protective effect against allergic asthma progression, which was associatedwith down-regulation of inflammatory cytokine expression and restoration of oxidant/antioxidant homeostasis.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Biomed Pharmacother. 2017 Jul 29 ;94:307-316. Epub 2017 Jul 29. PMID: 28763753 Abstract Title:  The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells. Abstract:  Cervical cancer is the fourth cause of cancer-related mortality among females worldwide. Although current therapies reduce disease symptoms, resistance of tumor cells to chemotherapy agents after a while is a serious problem. Therefore, utilization of novel adjuvant agents to increase efficiency of chemotherapy is essential. In the last two decades, botanicals with effective anticancer activities have been studied. Among them, the anticancer properties of crocin have been more attended. In this study, the molecular mechanism of crocin action was investigated in sensitive human cervical cancer cell line (OV2008) in comparison with the resistant one (C13). A 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay showed that crocin inhibits proliferation of sensitive cells (OV2008) at a time- and dose-dependent manner at 48 and 72h. Also, this inhibitory effect has been shown on resistant cells (C13) at 72h. Hoechst staining and flow cytometry assay also confirmed these results and revealed that antiproliferative effect of crocin might be due to the induction of apoptosis. Moreover, the genetic mechanism of crocin-induced apoptosis was accomplished by studying the relative expressions of P53, Bax, Bcl2 and miR-365, an upstream regulator of the last two ones. Real-time PCR analysis indicated that 1.5 and 3mg/ml crocin led to up-regulation of Bax and P53 and down-regulation of Bcl2 and miR-365 at all time intervals in both two cell lines. However, OV2008 cell line was more sensitive to crocin, and alternation of gene expretion was more obvious in this cell line. In this regard, the present study demonstrated the anti-proliferative and apoptotic activities of crocin against both sensitive and resistant cervical cancer cells that may benefit cervical cancer treatment as an adjuvant agent to decrease chemoresistance and increase the efficiency of therapy.

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PMID:  Biomed Pharmacother. 2017 Jul 29 ;94:307-316. Epub 2017 Jul 29. PMID: 28763753 Abstract Title:  The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells. Abstract:  Cervical cancer is the fourth cause of cancer-related mortality among females worldwide. Although current therapies reduce disease symptoms, resistance of tumor cells to chemotherapy agents after a while is a serious problem. Therefore, utilization of novel adjuvant agents to increase efficiency of chemotherapy is essential. In the last two decades, botanicals with effective anticancer activities have been studied. Among them, the anticancer properties of crocin have been more attended. In this study, the molecular mechanism of crocin action was investigated in sensitive human cervical cancer cell line (OV2008) in comparison with the resistant one (C13). A 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay showed that crocin inhibits proliferation of sensitive cells (OV2008) at a time- and dose-dependent manner at 48 and 72h. Also, this inhibitory effect has been shown on resistant cells (C13) at 72h. Hoechst staining and flow cytometry assay also confirmed these results and revealed that antiproliferative effect of crocin might be due to the induction of apoptosis. Moreover, the genetic mechanism of crocin-induced apoptosis was accomplished by studying the relative expressions of P53, Bax, Bcl2 and miR-365, an upstream regulator of the last two ones. Real-time PCR analysis indicated that 1.5 and 3mg/ml crocin led to up-regulation of Bax and P53 and down-regulation of Bcl2 and miR-365 at all time intervals in both two cell lines. However, OV2008 cell line was more sensitive to crocin, and alternation of gene expretion was more obvious in this cell line. In this regard, the present study demonstrated the anti-proliferative and apoptotic activities of crocin against both sensitive and resistant cervical cancer cells that may benefit cervical cancer treatment as an adjuvant agent to decrease chemoresistance and increase the efficiency of therapy.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Inflammation. 2017 Aug 7. Epub 2017 Aug 7. PMID: 28785878 Abstract Title:  Crocin Attenuates Joint Pain and Muscle Dysfunction in Osteoarthritis Rat. Abstract:  Osteoarthritis is the most prevalent form of arthritis, affecting a large part of population. It has been reported that muscle weakness and inflammation contribute to osteoarthritis development and progression. Oxidative stress plays important roles in muscle dysfunction and inflammation induction. Crocin, a component of saffron, has excellent antioxidative property. However, it is unclear if crocin can be a potential medicine for osteoarthritis therapy. Osteoarthritis in rats was induced by meniscectomy (MNX) surgery. Then, rats were given with 30 mg/kg of crocin daily for 10 days after osteoarthritis induction. The parameters were determined 7 days after crocin administration. MNX surgery induced osteoarthritis in rats. Crocin treatment significantly decreased osteoarthritis-associated joint pain, decreased muscular interleukin-6 (IL-6)level, and increased citrate synthase (CS) activity, as well as myosin heavy chain (MHC) IIα expression. In addition, crocin reduced muscular lipid peroxidation (LPO) and Nrf2 expression and increased glutathione production and glutathione peroxidase activity. Finally, crocin inhibited the activityof JNK, but not ERK, to repress NF-κB activation and inflammation induction. Crocin attenuates osteoarthritis symptoms through alleviating oxidative stress and inflammation, suggesting that crocin is a potential medicine for osteoarthritis therapy.

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PMID:  Inflammation. 2017 Aug 7. Epub 2017 Aug 7. PMID: 28785878 Abstract Title:  Crocin Attenuates Joint Pain and Muscle Dysfunction in Osteoarthritis Rat. Abstract:  Osteoarthritis is the most prevalent form of arthritis, affecting a large part of population. It has been reported that muscle weakness and inflammation contribute to osteoarthritis development and progression. Oxidative stress plays important roles in muscle dysfunction and inflammation induction. Crocin, a component of saffron, has excellent antioxidative property. However, it is unclear if crocin can be a potential medicine for osteoarthritis therapy. Osteoarthritis in rats was induced by meniscectomy (MNX) surgery. Then, rats were given with 30 mg/kg of crocin daily for 10 days after osteoarthritis induction. The parameters were determined 7 days after crocin administration. MNX surgery induced osteoarthritis in rats. Crocin treatment significantly decreased osteoarthritis-associated joint pain, decreased muscular interleukin-6 (IL-6)level, and increased citrate synthase (CS) activity, as well as myosin heavy chain (MHC) IIα expression. In addition, crocin reduced muscular lipid peroxidation (LPO) and Nrf2 expression and increased glutathione production and glutathione peroxidase activity. Finally, crocin inhibited the activityof JNK, but not ERK, to repress NF-κB activation and inflammation induction. Crocin attenuates osteoarthritis symptoms through alleviating oxidative stress and inflammation, suggesting that crocin is a potential medicine for osteoarthritis therapy.

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  J Cell Biochem. 2017 Aug 8. Epub 2017 Aug 8. PMID: 28786504 Abstract Title:  Crocin reduces A. fumigatus-induced airway inflammation and NF-κB signal activation. Abstract:  Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammation and its exacerbation is often accompanied by A. Aspergillus infection. Increasing evidences demonstrated the potent antioxidant and anti-inflammatory effects of crocin. However, the role of crocin in A. Aspergillus-induced inflammation is still unknown. We aimed to evaluate the role of crocin in inflammation response induced by A. Aspergillus in human bronchial epithelial cells and the possible mechanisms. BEAS-2B and NHBE cells were pre-treated with crocin for 24 h, and then A. fumigatus conidia were added for 24 h. A. Aspergillus treatment exhibited a significant higher TNF-α, IL-8, IL-6 and IL-1β level (P 

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PMID:  J Cell Biochem. 2017 Aug 8. Epub 2017 Aug 8. PMID: 28786504 Abstract Title:  Crocin reduces A. fumigatus-induced airway inflammation and NF-κB signal activation. Abstract:  Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammation and its exacerbation is often accompanied by A. Aspergillus infection. Increasing evidences demonstrated the potent antioxidant and anti-inflammatory effects of crocin. However, the role of crocin in A. Aspergillus-induced inflammation is still unknown. We aimed to evaluate the role of crocin in inflammation response induced by A. Aspergillus in human bronchial epithelial cells and the possible mechanisms. BEAS-2B and NHBE cells were pre-treated with crocin for 24 h, and then A. fumigatus conidia were added for 24 h. A. Aspergillus treatment exhibited a significant higher TNF-α, IL-8, IL-6 and IL-1β level (P 

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  Toxicol Mech Methods. 2017 Aug 16:1-34. Epub 2017 Aug 16. PMID: 28812436 Abstract Title:  The Mechanism of Protective Effect of Crocin against Liver Mitochondrial Toxicity Caused by Arsenic III. Abstract:  In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25µg/ml significantly (P 

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PMID:  Toxicol Mech Methods. 2017 Aug 16:1-34. Epub 2017 Aug 16. PMID: 28812436 Abstract Title:  The Mechanism of Protective Effect of Crocin against Liver Mitochondrial Toxicity Caused by Arsenic III. Abstract:  In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25µg/ml significantly (P 

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Author: greenmedinfo
Posted: 17-08-2017
PMID:  J Pharmacol Exp Ther. 2017 Aug 7. Epub 2017 Aug 7. PMID: 28784820 Abstract Title:  Urolithin A mitigates cisplatin-induced nephrotoxicity by inhibiting renal inflammation and apoptosis in an experimental rat model. Abstract:  Cumulative kidney toxicity associated with cisplatin is severe and there is no clear consensus on the therapeutic management of the same. The pathogenesis involves activation of inflammatory and apoptotic pathways, therefore regulating these pathways offers protection. Given the anti-inflammatory and antioxidant effects of urolithin A, a gut microbial metabolite of ellagic acid, our aim was to explore the potential of urolithin A for prevention of cisplatin-induced nephrotoxicity in an experimental rat model. For this purpose, animals received a single intraperitoneal dose of cisplatin (5 mg/kg body weight). Six hours prior to cisplatin administration, rats were orally treated with either ellagic acid or urolithin A (50 mg/kg body weight), followed by a daily dose of these compounds during the next 5 days. At the end, plasma and kidneys were collected for analysis. Cisplatin-induced kidney damage was revealed by a significant rise in the plasma creatinine levels accompanied by significant morphological changes in tubules, T cell Ig and mucin domain-containing protein-1, ionized calcium-binding adapter molecule 1, as well as a marked increase in the number of apoptotic cells localized in tubules. Cisplatin also reduced nitric oxide synthase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells resulting in regulation of various inflammatory cytokines. Urolithin A effectively attenuated cisplatin-induced kidney damage and showed significantly greater effect than its precursor ellagic acid on preserving the normal kidney architecture by downregulating the pro-inflammatory cytokines. In summary, urolithin A mitigates cisplatin-induced nephrotoxicity in rats by modulation of the inflammatory cascade and inhibition of the pro-apoptotic pathway.

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PMID:  J Pharmacol Exp Ther. 2017 Aug 7. Epub 2017 Aug 7. PMID: 28784820 Abstract Title:  Urolithin A mitigates cisplatin-induced nephrotoxicity by inhibiting renal inflammation and apoptosis in an experimental rat model. Abstract:  Cumulative kidney toxicity associated with cisplatin is severe and there is no clear consensus on the therapeutic management of the same. The pathogenesis involves activation of inflammatory and apoptotic pathways, therefore regulating these pathways offers protection. Given the anti-inflammatory and antioxidant effects of urolithin A, a gut microbial metabolite of ellagic acid, our aim was to explore the potential of urolithin A for prevention of cisplatin-induced nephrotoxicity in an experimental rat model. For this purpose, animals received a single intraperitoneal dose of cisplatin (5 mg/kg body weight). Six hours prior to cisplatin administration, rats were orally treated with either ellagic acid or urolithin A (50 mg/kg body weight), followed by a daily dose of these compounds during the next 5 days. At the end, plasma and kidneys were collected for analysis. Cisplatin-induced kidney damage was revealed by a significant rise in the plasma creatinine levels accompanied by significant morphological changes in tubules, T cell Ig and mucin domain-containing protein-1, ionized calcium-binding adapter molecule 1, as well as a marked increase in the number of apoptotic cells localized in tubules. Cisplatin also reduced nitric oxide synthase 3 and nuclear factor kappa-light-chain-enhancer of activated B cells resulting in regulation of various inflammatory cytokines. Urolithin A effectively attenuated cisplatin-induced kidney damage and showed significantly greater effect than its precursor ellagic acid on preserving the normal kidney architecture by downregulating the pro-inflammatory cytokines. In summary, urolithin A mitigates cisplatin-induced nephrotoxicity in rats by modulation of the inflammatory cascade and inhibition of the pro-apoptotic pathway.

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Author: greenmedinfo
Posted: 17-08-2017