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1.
Sci Rep ; 11(1): 19454, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593840

RESUMO

We examined the association between maternal air purifier use during pregnancy and neurodevelopmental delay in toddlers by analysing data from 82,457 mother-toddler pairs. Air purifier use was measured using a simple yes/no question. Developmental delays at 1.5, 2.0, 2.5, and 3.0 years were assessed using the Ages and Stages Questionnaire, Third Edition. Generalized additive mixed model analysis with 21 covariates revealed that air purifier use was associated with lower prevalence of developmental delay in all five areas-communication, gross motor, fine motor, problem solving, and personal-social-at all four time points (adjusted risk ratios ranged from 0.827 to 0.927, and only one 95% confidence interval crossed the reference). These findings suggest a negative association between air purifier use during pregnancy and neurodevelopmental delay in toddlers.Trial registration: UMIN000030786 (15/01/2018).

2.
BMC Pediatr ; 21(1): 419, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556067

RESUMO

BACKGROUND: The association between delivery mode and subsequent development of diseases is a growing area of research. Cesarean delivery affects the diversity of the microbiota in the infant gut, which may be associated with gastrointestinal disorders, including functional constipation, in infants. In this study, we investigated the association between delivery mode and prevalence of functional constipation in 3-year-old Japanese toddlers. METHODS: This study used data from the Japan Environment and Children's Study, an ongoing nationwide birth cohort study. We analyzed 71,878 toddler-mother pairs. The presence of functional constipation was determined according to the Rome III diagnostic criteria. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The prevalence of functional constipation in 3-year-old Japanese toddlers was estimated to be 12.3%. Logistic regression analysis revealed that the prevalence of functional constipation was higher in toddlers born by cesarean delivery (13.1%) compared with those born by vaginal delivery (12.1%), independent of 22 confounders (adjusted odds ratios = 1.064, 95% confidence interval = 1.004-1.128). CONCLUSIONS: We determined the prevalence of functional constipation in 3-year-old Japanese toddlers and found that delivery mode was associated with the prevalence of functional constipation in Japanese toddlers.

3.
Eur J Nutr ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34505173

RESUMO

PURPOSE: N-3 polyunsaturated fatty acids (n-3 PUFAs), which are an important nutrient for humans, are particularly essential to the growth and development of the central nervous system (CNS) in fetuses and infants. Consequently, sufficient n-3 PUFA intake by mothers during pregnancy is considered to contribute to CNS development in their infants. CNS development is known to be associated with sleep, but no large epidemiological studies have yet confirmed that n-3 PUFA intake during pregnancy is associated with infants' sleep. METHODS: After exclusion and multiple imputation from a dataset comprising 104 065 records from the Japan Environment and Children's Study (JECS), we examined 87 337 mother-child pairs for the association between mothers' fish and n-3 PUFA intakes and risk of their infants sleeping less than 11 h at 1 year of age. RESULTS: Multiple logistic regression analysis with the lowest quintile used as a reference revealed odds ratios for the second through fifth quintiles of 0.81 (95% confidence interval [95% CI] 0.76-0.87), 0.81 (95% CI 0.76-0.87), 0.78 (95% CI 0.72-0.84), and 0.82 (95% CI 0.76-0.88) for fish intake (p for trend < 0.001) and 0.90 (95% CI 0.84-0.97), 0.88 (95% CI 0.81-0.94), 0.88 (95% CI 0.82-0.95), and 0.93 (95% CI 0.86-0.998) for n-3 PUFA intake (p for trend = 0.04). CONCLUSIONS: Low fish intake during pregnancy may increase the risk of infants sleeping less than 11 h at 1 year of age. This relationship may have been mediated by maternal n-3 PUFA intake and infant neurodevelopment, but further evidence from interventional and other studies is needed to determine the appropriate level of fish intake during pregnancy. TRIAL REGISTRATION: The Japan Environment and Children's Study, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035091 (Registration no. UMIN000030786).

4.
J Epidemiol ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34373419

RESUMO

BACKGROUND: Many epidemiological studies have reported the association between various social factors and health status in mothers during and after pregnancy. However, little is known about their joint and longitudinal impact. We therefore examined the association of lack of social support and trust during pregnancy and at 2.5 years postpartum with health status in mothers. METHODS: To adequately address time-varying exposure, marginal structural models were fitted to a pseudopopulation constructed by inverse probability weighting. The model included records of 90,071 mothers participating in the Japan Environment and Children's Study. Social support and trust were measured using a 9-item questionnaire (Q1-9). Mental and physical health were measured using Mental and Physical Component Summary scores from the 8-item Short-Form Health Survey. RESULTS: For the Mental Component Summary, the magnitude of the effect estimate was largest when participants lacked close friends/neighbors (Q4) at only 2.5 years postpartum (= -6.23), followed by a lack in emotional support (Q2) at the same time point (= -4.94). For the Physical Component Summary, effect estimates were negligible. The magnitude of the effect estimates of lack of social support and trust tended to be larger when there was a lack at only 2.5 years postpartum than at both time points. CONCLUSIONS: These findings suggest that, after childbirth, a loss in social support, particularly in a concrete or instrumental aspect, carries high risk, especially for mental health. Our results highlight the importance of supporting mothers for more than a few years after pregnancy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34416000

RESUMO

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in mid-pregnancy are associated with small- (SGA) or large- (LGA) for-gestational-age independent of pre-pregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: To prospectively investigate the association between maternal TC in mid-pregnancy and SGA or LGA. DESIGN AND SETTING: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. PARTICIPANTS: A total of 37,449 non-diabetic, non-hypertensive mothers with singleton birth at term without congenital abnormalities. OUTCOME MEASURES: Birth weight for the gestational age <10 percentile and ≥90 percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7±4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, pre-pregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and Study Areas, one standard deviation decrement of maternal TC was linearly associated with SGA [odds ratio (OR): 95% confidence intervals (CI) = 1.20: 1.15-1.25]. In contrast, one standard deviation increment of maternal TC was linearly associated with LGA [OR: 95% CI = 1.13: 1.09-1.16]. Associations did not differ according to pre-pregnancy BMI and gestational weight gain (p for interaction>0.20). CONCLUSION: Maternal TC levels in mid-pregnancy were associated with SGA or LGA in Japanese. Maternal TC in mid-pregnancy may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

6.
Sci Total Environ ; 794: 148643, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34198080

RESUMO

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Orgânicos Voláteis , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Japão , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Compostos Orgânicos Voláteis/toxicidade
7.
BMJ Open ; 11(7): e047226, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226223

RESUMO

OBJECTIVE: To compare the incidence of atopic dermatitis in children aged from 6 months to 3 years across birth seasons and climate conditions. DESIGN: Cohort study. SETTING: Fifteen regional centres across Japan. PARTICIPANTS: A total of 100 304 children born from 2011 to 2014. EXPOSURE: Birth month, and mean sunshine duration (short/long) and humidity (high/low) in the first 6 months of life. PRIMARY OUTCOME MEASURE: Incidence of atopic dermatitis. RESULTS: The highest incidence of atopic dermatitis was in children born in the months of October to December. The lowest incidence of atopic dermatitis was in the months of April to June and in periods with a long duration of sunshine and high humidity. Low humidity was significantly associated with a higher incidence of atopic dermatitis. However, this significant difference disappeared when the birth season and parental history of allergic disease were considered in multivariate analysis. CONCLUSIONS: In Japan, being born in the late autumn to early winter months is associated with a risk of developing atopic dermatitis until the age of 3 years. Sunshine duration and humidity from birth to 6 months of age are not associated with the incidence of atopic dermatitis.


Assuntos
Dermatite Atópica , Criança , Pré-Escolar , Estudos de Coortes , Dermatite Atópica/epidemiologia , Humanos , Umidade , Incidência , Lactente , Japão/epidemiologia
8.
Allergol Int ; 70(4): 445-451, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34140239

RESUMO

BACKGROUND: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. METHODS: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. RESULTS: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1-10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270-1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341-2.078; asthma: 1-10 cigarettes/day: aOR 1.389, 95% CI 1.087-1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045-2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083-1.256; asthma: aOR 1.258, 95% CI 1.075-1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739-2.317; asthma: aOR 1.995, 95% CI 1.528-2.605). CONCLUSIONS: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

9.
Psychol Med ; : 1-10, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34176535

RESUMO

BACKGROUND: Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. METHODS: Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. RESULTS: Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of 'hitting' decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77-1.13), 0.79 (95% CI 0.64-0.97), 0.78 (95% CI 0.64-0.96), and 0.72 (95% CI 0.59-0.89), respectively. Adjusted ORs (95% CIs) for 'shaking very hard' at 6 months were 0.87 (0.73-1.04), 0.81 (0.67-0.97), 0.73 (0.61-0.89), and 0.78 (0.65-0.94), respectively. Adjusted ORs for 'leaving alone at home' for the second to fifth quintiles were 0.92 (0.87-0.98), 0.91 (0.86-0.97), 0.94 (0.88-0.99), and 0.85 (0.80-0.90), respectively. CONCLUSIONS: Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment.

10.
Mol Med Rep ; 24(1)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34080650

RESUMO

Diet and exercise are the most effective approaches used to induce weight loss. D­psicose is a low­calorie sweetener that has been shown to reduce weight in obese individuals. However, the effect of D­psicose on muscle cells under oxidative stress, which is produced during exercise, requires further investigation. The present study aimed to determine the effects of D­psicose on C2C12 myogenic cells in vitro. Hydrogen peroxide (H2O2) was used to stimulate the generation of intracellular reactive oxygen species (ROS) in muscle cells to mimic exercise conditions. Cell viability was analyzed using a MTT assay and flow cytometry was used to analyze the levels of apoptosis, mitochondrial membrane potential (MMP), the generation of ROS and the cell cycle distribution following treatment. Furthermore, protein expression levels were analyzed using western blotting and cell proliferation was determined using a colony formation assay. The results of the present study revealed that D­psicose alone exerted no toxicity on C2C12 mouse myogenic cells. However, in the presence of low­dose (100 µM) H2O2­induced ROS, D­psicose induced C2C12 cell injury and significantly decreased C2C12 cell viability in a dose­dependent manner. In addition, the levels of apoptosis and the generation of ROS increased, while the MMP decreased. MAPK family molecules were also activated in a dose­dependent manner following treatment. Notably, the combined treatment induced G2/M phase arrest and reduced the proliferation of C2C12 cells. In conclusion, the findings of the present study suggested that D­psicose may induce toxic effects on muscle cells in a simulated exercise situation by increasing ROS levels, activating the MAPK signaling pathway and disrupting the MMP.

11.
Eur Psychiatry ; 64(1): e38, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34106043

RESUMO

BACKGROUND: Paternal childcare is reported to benefit maternal mental health, but specific childcare behaviors have not been comprehensively determined. This study sought to identify paternal childcare behaviors associated with maternal mental health by adjusting for other covariates associated with maternal mental health and examining childcare behaviors. METHODS: This study investigated whether seven types of paternal childcare behaviors at 6 months after delivery were associated with maternal psychological distress at 1 year after delivery, which was assessed using the Kessler Psychological Distress Scale (K6). After exclusions from a dataset of 103,062 pregnancies obtained in the Japan Environment and Children's Study, we evaluated data from 75,607 mothers. RESULTS: More than 70% of fathers were always or sometimes involved in "playing at home," "playing outdoors," "changing diapers," and "bathing," 60%-70% in "helping with feeding" and "dressing," and 45.9% in "putting the child to bed." All paternal childcare behaviors showed some beneficial association with less maternal psychological distress, both moderate (K6 score 5-12) and severe (K6 score ≥ 13) distress. Playing at home was the most beneficial association identified (adjusted odds ratio [aOR] 0.66, 95% confidence interval [CI] 0.56-0.76 for moderate psychological distress; aOR 0.36, 95% CI 0.28-0.48 for severe psychological distress). CONCLUSIONS: These seven types of paternal childcare behaviors may help lessen maternal psychological distress. Emphasis should be given to building education systems and working environments that promote paternal childcare.

13.
Congenit Anom (Kyoto) ; 61(5): 159-168, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34041797

RESUMO

We investigated the relationship between maternal smoking history and congenital anomalies in children. Drawing on data from the Japan Environment and Children's Study collected between January 2011 and March 2014, the smoking habits of pregnant women were categorized as "never smoked," "quit before pregnancy, "quit after pregnancy," and "full smoking." Of the 91 626 participants examined, a total of 2199 (2.4%) infants were born with any congenital anomalies. Logistic regression analysis was used to determine the odds ratio for congenital anomalies in each group based on maternal smoking history. No significant difference was seen between the full-smoking and never smoked groups in the odds ratios for congenital anomalies of the nervous system; the eyes, ears, face, and neck; the cardiovascular system; or the musculoskeletal system. However, in the full-smoking group, the odds ratios for trisomy (adjusted odds ratio, 2.14; 95% confidence interval, 1.15-3.97) and any congenital anomalies (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.67) were significantly higher compared with the never smoked group. Our results indicate that continuing to smoke during pregnancy is associated with increased risk of trisomy and any congenital anomalies in the general Japanese population.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33920677

RESUMO

House dust, well known for causing allergy, contains chemicals that are harmful to fetal neurodevelopment. However, whether countermeasures for house dust allergy, such as frequent use of vacuum cleaners, frequent airing of futons, and the usage of anti-mite covers during pregnancy, are related to subsequent reduced risk of infant developmental delay remains unknown. Therefore, we examined this association by analyzing 81,106 mother-infant pairs who participated in a nationwide birth cohort in Japan. Infant developmental delays at 6 and 12 months postpartum were assessed using the Ages and Stages Questionnaire, Third Edition. A generalized linear model analysis was used to derive adjusted odds ratios (AORs) with the lowest care frequency as reference, while controlling 22 covariates. Our analysis showed that the above-mentioned cleaning measures were overall associated with a reduced risk of developmental delays, both at 6 and 12 months postpartum (AOR varied from 0.73 to 0.95, median: 0.84). Additionally, risks tended to decrease with an increase in the cleaning frequency. In conclusion, a negative dose-response association existed between these measures during pregnancy and infant developmental delay. Our results identify a potential role of frequent vacuum cleaning, airing bedding, and usage of anti-mite bedding covers in promoting intact infant development.


Assuntos
Hipersensibilidade , Ácaros , Alérgenos , Animais , Criança , Poeira , Feminino , Humanos , Lactente , Japão , Gravidez
15.
Sci Rep ; 11(1): 6841, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767216

RESUMO

This research aimed to examine the efficacy of the early initiation of breastfeeding within 1 h of birth, early skin-to-skin contact, and rooming-in for the continuation of exclusive breastfeeding until 6 months postpartum. The research used data from the Japan Environment and Children's Study (JECS), a nationwide government-funded birth cohort study. A total of 80,491 mothers in Japan between January 2011 and March 2014 who succeeded or failed to exclusively breastfeed to 6 months were surveyed in JECS. Multiple logistic regression model was used to analyse the data. The percentage of mothers who succeeded in exclusively breastfeeding to 6 months is 37.4%. Adjusted odds ratios were analysed for all 35 variables. Early initiation of breastfeeding (adjusted odds ratio [AOR]: 1.455 [1.401-1.512]), early skin-to-skin contact (AOR: 1.233 [1.165-1.304]), and rooming-in (AOR: 1.567 [1.454-1.690]) affected continuation of exclusive breastfeeding. Regional social capital (AOR: 1.133 [1.061-1.210]) was also discovered to support the continuation of breastfeeding. In contrast, the most influential inhibiting factors were starting childcare (AOR: 0.126 [0.113-0.141]), smoking during pregnancy (AOR: 0.557 [0.496-0.627]), and obese body type during early pregnancy (AOR: 0.667 [0.627-0.710]).

16.
Apoptosis ; 26(3-4): 219-231, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33738673

RESUMO

Acute myeloid leukemia (AML) is a malignant cancer of the hematopoietic system. Although the effectiveness of arsenic compounds has been recognized and applied clinically, some patients are still found resistant to this chemotherapy. In this study, we investigated that a synthetic thyroid hormone analog (TA), 2-iodo-4-nitro-1-(o-tolyloxy) benzene, had a strong apoptosis effect on U937 cells. U937 cells were treated with TA, and examinted the generation of reactive oxygen species (ROS), dysfunction of mitochondria, expression of pro-apoptosis and anti-apoptosis, and cleavage of caspase-3 and Poly (ADP-ribose) polymerase (PARP). Further, it is also evaluated that insight molecular mechanism and signaling pathways involved in the study. It is found that TA significantly induced apoptosis in U937 cells through production of ROS, dysfunction of mitochondria, and activation of caspase cascade. It was also observed that MAPK signaling pathway including ERK, JNK, and P38 signals are involved in the induction of apoptosis. Moreover, marked activation of autophagy and ER stress markers such as LC3, P62, Beclin1 and GRP78, CHOP were observed, respectively. Pretreatment with ER stress inhibitor tauroursodeoxycholic acid (TUDCA) and autophagy inhibitor 3-Methyladenine (3-MA) have successfully attenuated and aggravated TA-induced apoptosis, respectively. We further confirmed the active involvement of ER stress and autophagy signals. In conclusion, TA induced apoptosis through ER stress and activation of autophagy, and the latter is not conducive to TA-induced cell death. Our results may provide a new insight into the strategic development of novel therapy for the treatment of AML.

17.
J Affect Disord ; 285: 152-159, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667755

RESUMO

BACKGROUND: Breastfeeding is increasingly being promoted worldwide. Although several studies have examined breastfeeding and postpartum depression, contradictory results concerning their relationship have been found. This study investigated the influence of the feeding patterns of 1- to 6-month-old infants on maternal postpartum depression, as well as the influence of activities performed by mothers during feeding on postpartum depression. METHODS: We used data from parents and children who participated in the Japan Environment and Children's Study (JECS). The data were from 71,448 mothers who did not show depressive symptoms at 1 month postpartum. RESULTS: The group that continued exclusive breastfeeding for 6 months postpartum had a lower risk of postpartum depression compared with those who adopted other feeding patterns. Regardless of the pattern or duration of feeding, the group that maintained eye contact or talked to their baby during feeding had a lower risk of postpartum depression compared with the group that performed other activities. Furthermore, the group that continued both exclusive breastfeeding for 6 months and maintained eye contact or talked to their babies during feeding had an odds ratio of 0.69 for postpartum depression (95% confidence interval: 0.61-0.79), the lowest of any group. LIMITATIONS: All variables were measured using a self-administered questionnaire. CONCLUSIONS: It may be possible to control the onset of postpartum depression by recommending breastfeeding to new mothers, providing them with appropriate information on how to interact with their babies, and offering them support. TRIAL REGISTRATION: UMIN000030786.


Assuntos
Depressão Pós-Parto , Adulto , Aleitamento Materno , Criança , Depressão Pós-Parto/epidemiologia , Comportamento Alimentar , Feminino , Humanos , Lactente , Japão/epidemiologia , Mães
18.
Redox Biol ; 36: 101632, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32863233

RESUMO

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.


Assuntos
Melatonina , Neoplasias , Sirtuína 3 , Apoptose , Morte Celular , Células HeLa , Humanos , Melatonina/farmacologia , Naftoquinonas , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio , Sirtuína 3/genética , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo
19.
BMC Pregnancy Childbirth ; 20(1): 450, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762739

RESUMO

BACKGROUND: Previous studies revealed positive, negative, and no influence of social capital on the health outcomes of pregnant women. It was considered that such differences were caused by the disparities of outcome measures and sample sizes between studies. Our chief aim was to verify the positive influence of social capital on the health condition of pregnant women using established health outcome measures and large-scale nationwide survey data. METHODS: We employed questionnaire survey data from 79,210 respondents to the Japan Environment and Children's Study, and physical and mental component summary scores from the 8-Item Short-Form Health Survey as outcome measures. We estimated the effect of individual and neighborhood social capitals on physical and mental component summary scores. To consider the property that the richness of social capital would be generally determined by individual characteristics, and to estimate the causal influence of social capital on health without bias caused by said property, we adopted average treatment effect estimation with inverse probability weighting. Generally, average treatment effects are based on the difference of average outcomes between treated and untreated groups in an intervention. In this research, we reckoned individuals' different levels of social capital as a kind of non-randomized treatment for respective individuals, and we applied average treatment effect estimation. The analysis regarded pregnant women with the lowest level of social capital as untreated samples and women with other levels of social capitals as treated samples. RESULTS: For mental component summary score, the maximum average treatment effects in the comparison between the lowest and highest levels of social capital were approximately 4.4 and 1.6 for individual and neighborhood social capital, respectively. The average treatment effects for the physical component summary score were negligible for both social capital types. CONCLUSIONS: Social capital particularly contributes to improving mental component summary score in pregnant women. The likelihood of a mentally healthy pregnancy may be increased by enhancing social capital.


Assuntos
Saúde Mental , Características de Residência , Capital Social , Saúde da Mulher , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Japão , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
20.
Am J Clin Nutr ; 112(5): 1295-1303, 2020 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-32766751

RESUMO

BACKGROUND: Although emerging evidence indicates a relation between maternal intake of fish and improved child neurodevelopment, the results are inconsistent. OBJECTIVES: This study investigated whether dietary consumption of fish during pregnancy is associated with offspring neurodevelopment at age 6 mo and 1 y. As exploratory research, we also examined the association between consumption of PUFAs and neurodevelopment at the same time points. METHODS: After exclusion and multiple imputation from a dataset comprising 104,065 records from the Japan Environment and Children's Study, we evaluated 81,697 and 77,751 mother-child pairs at age 6 mo and 1 y, respectively. RESULTS: Maternal fish intake during pregnancy was independently associated with reduced risk of delay in problem-solving at age 6 mo (lowest compared with highest quintile OR = 0.88; 95% CI: 0.79, 0.99; P-trend = 0.01) and in fine motor skills (highest quintile OR = 0.90; 95% CI: 0.81, 0.99; P-trend = 0.02) and problem-solving (fourth quintile OR = 0.89; 95% CI: 0.81, 0.98; and highest quintile OR = 0.90; 95% CI: 0.81, 0.99; P-trend = 0.005) at age 1 y. Dietary intake of total n-3 PUFAs was associated with reduced risk of delay in fine motor skills at 6 mo, and in fine motor skills and problem-solving at 1 y. Dietary intake of total n-6 PUFAs was associated with reduced risk of delay in communication and fine motor skills at 6 mo, and in gross motor skills, fine motor skills, and problem-solving at 1 y. In contrast, the dietary n-6/n-3 ratio was positively associated with increased risk of delay in problem-solving at 1 y. CONCLUSIONS: The results of this study suggest there might be beneficial effects of fish intake during pregnancy on some domains of child psychomotor development and this effect might be partially explained by PUFA intake from fish. Trial registration: UMIN000030786.


Assuntos
Desenvolvimento Infantil , Dieta , Ácidos Graxos Insaturados/administração & dosagem , Peixes , Fenômenos Fisiológicos da Nutrição Materna , Animais , Estudos de Coortes , Feminino , Humanos , Lactente , Japão
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