Epidemiological research advances on antibiotic exposure in early life and child health / 环境与职业医学

Early life is a critical window period that determines the growth and development of children, but this delicate and complex period is highly susceptible to the disturbance of various exogenous chemicals, which in consequence may lead to short-term or long-term adverse health effects in human beings. The massive use of antibiotics has contributed to widespread exposure in early life, along with the potentially adverse effects on child health, and has caused great concern in public health. This review summarized recent epidemiological studies on the population with early-life antibiotic exposure and associated health outcomes such as growth and development, allergies, and psycho-behavioral problems in children, as well as potential biological mechanisms underlying these associations. Current findings suggested that antibiotic exposure early in life, including pregnancy and infancy, is strongly associated with childhood allergic diseases (e.g., atopic dermatitis and asthma), growth and development (e.g., obesity and birth length), and childhood psycho-behavioral problems (e.g., autism and anxiety). It also suggested that antibiotic exposure may affect individual health through gut microbiota, thyroid function, inflammation factors, mitochondrial function, and epigenetic mechanisms. In the future, more large prospective birth cohorts should be established to determine the levels of internal exposure to different types of antibiotics at multiple time points in early life and to explore their associations with child health outcomes, as well as to further validate relevant mechanisms, aiming to provide high-quality scientific evidence for research on child health associated with environmental exposure in early life.

Life expectancy of premature death caused by cardiovascular and cerebrovascular diseases in Suzhou in 2011-2020 / 公共卫生与预防医学

Objective To understand the death prevalence of cardiovascular and cerebrovascular diseases and the life expectancy of premature death caused by them in Suzhou, and to provide data basis for the health administrative department to formulate the prevention and control policies of cardiovascular and cerebrovascular diseases. Methods Based on the death data of ischemic heart disease and stroke of residents in Suzhou from 2011 to 2020, the death prevalence of cardiovascular and cerebrovascular diseases during the past decade was calculated. The years of life lost (YLLs), years of life lost per thousand (YLL rate) and annual percentage of change (APC) caused by ischemic heart disease and stroke were calculated. The YLLs and YLL rates of different age groups and different genders were also calculated. Results From 2011 to 2020, the average annual mortality rate of ischemic heart disease in Suzhou was 45.61/100 000, and the mortality rate showed an upward trend in the past decade. The average annual mortality rate of stroke was 174.23/100 000, with a trend of decreasing first and then increasing in the past decade. From 2011 to 2020, the disease burden caused by ischemic heart disease in Suzhou totaled 359,153.97 YLLs, with a YLL rate of 6.77 person years per 1000 people, and an APC of 2.05%. The YLLs caused by stroke death were 1 269,193.8 person years, the YLL rate was 23.91 person years per thousand, and the APC was 1.35%. Conclusion From 2011 to 2020, the prevention and treatment of cardiovascular and cerebrovascular diseases in Suzhou has achieved certain results, but ischemic heart disease and stroke are still important causes affecting the health of people and causing death and life loss of the elderly in Suzhou. The prevention and treatment of cardiovascular and cerebrovascular diseases still has a long way to go, and it is necessary to continue strengthening the screening, monitoring and intervention work.

Research progress on the correlation between early life adversity and the puberty initiation / 中华实用儿科临床杂志

Earlier onset of puberty has become a worldwide trend.A large number of epidemiologic and animal experiment evidences have indicated that environmental changes in the early life may influence development plasticity and cause structural and functional changes, which are correlated with adult chronic diseases.The impact of fluctuations in environmental factors on the reproductive phenotype of offspring has been well concerned in recent years.This review summarizes the influences of nutritional state, endocrine disrupting chemicals, hormonal perturbation and stressful events during the prenatal and early childhood on the puberty initiation, especially neuroendocrine changes in puberty, thus providing a new idea for the prevention and control of pubertal disorders.

The Nucleus Accumbens CRH-CRHR1 System Mediates Early-Life Stress-Induced Sleep Disturbance and Dendritic Atrophy in the Adult Mouse / 神经科学通报·英文版

Adverse experiences in early life have long-lasting negative impacts on behavior and the brain in adulthood, one of which is sleep disturbance. As the corticotropin-releasing hormone (CRH)-corticotropin-releasing hormone receptor 1 (CRHR1) system and nucleus accumbens (NAc) play important roles in both stress responses and sleep-wake regulation, in this study we investigated whether the NAc CRH-CRHR1 system mediates early-life stress-induced abnormalities in sleep-wake behavior in adult mice. Using the limited nesting and bedding material paradigm from postnatal days 2 to 9, we found that early-life stress disrupted sleep-wake behaviors during adulthood, including increased wakefulness and decreased non-rapid eye movement (NREM) sleep time during the dark period and increased rapid eye movement (REM) sleep time during the light period. The stress-induced sleep disturbances were accompanied by dendritic atrophy in the NAc and both were largely reversed by daily systemic administration of the CRHR1 antagonist antalarmin during stress exposure. Importantly, Crh overexpression in the NAc reproduced the effects of early-life stress on sleep-wake behavior and NAc morphology, whereas NAc Crhr1 knockdown reversed these effects (including increased wakefulness and reduced NREM sleep in the dark period and NAc dendritic atrophy). Together, our findings demonstrate the negative influence of early-life stress on sleep architecture and the structural plasticity of the NAc, and highlight the critical role of the NAc CRH-CRHR1 system in modulating these negative outcomes evoked by early-life stress.

Research progress on shortened telomere length in newborns and impaired cardiovascular metabolic health in children caused by exposure to cadmium during pregnancy / 环境与职业医学

Cadmium exposure during pregnancy is a non-negligible public health problem which may increase the risk of shortened telomere length in newborns and cardiovascular metabolic health damage in children, and has attracted attention from many researchers in recent years. This article reviewed recent studies both domestically and internationally on the associations among cadmium exposure during pregnancy, shortened telomere length in newborns, and cardiovascular metabolic abnormalities in children, and briefly outlined possible mechanisms of shortened telomere length in newborns by cadmium exposure during pregnancy. Current research results showed that cadmium exposure during pregnancy is related to shortened telomere length in newborns and cardiovascular metabolic abnormalities in children, and shortened telomere length in newborns is also related to cardiovascular metabolic abnormalities in children. It suggested that telomere length in newborns may be a biomarker reflecting cardiovascular metabolic abnormalities in children caused by cadmium exposure during pregnancy. In addition, the current potential mechanisms of cadmium exposure during pregnancy accelerating neonatal telomere length shortening include inflammatory reaction, mitochondrial dysfunction, antioxidant consumption/antioxidant enzyme inactivation, and DNA methylation, and these biological mechanisms are associated with cardiovascular metabolic abnormalities through certain factors, such as obesity, elevated blood pressure, impaired fasting blood glucose, and dyslipidemia in children, suggesting that cardiovascular metabolic abnormalities in children may be programmed in early life, but there are still few relevant studies. In the future, research should be conducted on the association among cadmium exposure during pregnancy, telomere length, and offspring cardiovascular metabolism, as well as possible mediating efficacy and related biological mechanisms of telomere length, aiming to provide early-life biological information for the prevention of cardiovascular and metabolic diseases.

Role of an enriched environment in ameliorating early life stress-induced changes in structure and functions of hippocampus and amygdala in rats

Objectives: This study aimed to understand whether an enriched environment (EE) in adulthood benefits in mitigating the early life stress-induced changes in the structure and functions of the hippocampus and amygdala. Materials and Methods: Male Wistar rats were exposed daily for 6 h to early maternal separation and isolation (MS) stress from postnatal days (PND) 4–14 and later at PND 60–70 days subjected to EE, while, the normal control (NC) rats were not subjected to stress but reared with the mother under standard housing conditions. The effects of MS and EE on adulthood behaviour were not subjected to stress but assessed by measuring the ambulatory, repetitive and anxiety-like behaviour. The study has also done the plasma corticosterone concentrations. The dendritic remodelling in the amygdala and hippocampus was assessed using the Golgi cox staining approach. Finally, the present study compared the reactive oxygen species-induced lipid peroxidation and total antioxidant capacity in MS rats as an indirect measure of oxidative stress to study the impact of MS stress on the limbic circuit and peripheral organs. Results: MS rats showed increased anxiety and lower plasma corticosterone levels. The pyramidal neurons’ dendritic plasticity displayed a different pattern, with shrinkage in the CA1 hippocampal neurons and hypertrophy in the amygdala’s primary neurons. Variations in antioxidant activity and peroxidation observed in NC to MS across tissues indicate the occurrence and management of oxidative stress in MS. The 10 days of EE in young adulthood helped to reduce MS stress-induced structural abnormalities in hippocampal and amygdala pyramidal neurons, as well as anxiety and plasma corticosterone levels. Conclusion: These findings together indicate that exposure to adverse experiences may cause harmful effects on brain plasticity and behaviour in young adulthood. Exposure to EE may be beneficial in reducing the early life stress-induced pathophysiology later in life.

Early life adversity and depression / 中华行为医学与脑科学杂志

The onset of depression is related to many factors such as biological, psychological and social environment, and more and more studies have shown that early life adversity is a risk factor for depression. Patients with depression who have early life adversity have different clinical characteristics, such as greater cognitive impairment and higher risk of suicide, which may be related to changes in cognitive patterns. In addition, early life adversity can cause endocrine, immune and nervous system specific changes in depressed patients. This article reviews the relationship and mechanism between various types of early life adverse and depression, explores the onset of depression and provides theory evidence for early intervention.

Effect of early-life maternal deprivation on depressive-like behavior and neurogenesis in hippocampal granular layer of adolescent rat / 中华行为医学与脑科学杂志

Objective:To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats (6-7 weeks old).Methods:Neonatal rats were randomly divided into maternal deprivation group and control group, with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old, the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution, and then t-test was carried out. Results:There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group, rats in the maternal deprivation group had lower body weight growth ((20.57±2.19) g, (30.57±1.25) g, t=3.96, P<0.01)) and lower sucrose preference rate((58.38±53.14)%, (73.88±3.67)%, t=3.21, P<0.01). The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group ((5.13±0.31), (7.60±0.38), t=5.09, P<0.01), and the number of Nestin immunofluorescence positive cells was more than that in the control group ((16.65±0.79), (7.64±0.70), t=8.51, P<0.01). The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches, and the morphology was similar to astrocytes, while the immunofluorescence positive cells in the control group had fewer protrusions, and the cell body was oval. Conclusions:Early-life maternal deprivation leads to depressive-like behavior in adolescent rats, which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.

Embryonic and larval development is conditioned by water temperature and maternal origin of eggs in the sea urchin Arbacia dufresnii (Echinodermata: Echinoidea) / El desarrollo embrionario y larvario está condicionado por la temperatura del agua y el origen materno de los huevos en el erizo de mar Arbacia dufresnii (Echinodermata: Echinoidea)

Introduction: Embryonic and larval development in sea urchins is highly dependent on maternal nutritional status and on the environmental conditions of the seawater. Objective: To compare the development of Arbacia dufresnii in two different water temperatures and in progeny with varying maternal origins. Methods: We induced A. dufresnii females and males from Nuevo Gulf to spawn, collected the eggs of each female individually (progeny), separated them into two seawater temperatures (12 and 17 °C), and fertilized them. We recorded the percentage of fertilized eggs and embryos per developmental stage according to time, temperature and progeny. We measured larval growth by total length (TL) and midline body length (M) according to time post fecundation (DPF), temperature, and progeny. Results: Temperature did not affect fertilization, but embryo development was faster and more synchronized in the high temperature treatment. The generalized linear models indicate that embryo development depends on a quadruple interaction between the embryonic stage, time (h), seawater temperature and progeny. Larval growth was faster, producing larger larvae at the highest temperature. Larval growth depends on a triple interaction between time (DPF), seawater temperature and progeny. Conclusions: We found a temperature and progeny impact during embryonic and larval development and, in both cases, these factors generate a synergistic effect on developmental timing and larval size. This probably provides a survival advantage as a more rapid speed of development implies a decrease in the time spent in the water column, where the sea urchins are vulnerable to biotic and abiotic stressors.

Introducción: El desarrollo embrionario y larvario de los erizos de mar depende en gran medida del estado nutricional materno y de las condiciones ambientales del agua de mar. Objetivo: Comparar el desarrollo de Arbacia dufresnii en dos temperaturas de agua diferentes y en progenies con diferentes orígenes maternos. Métodos: Indujimos a las hembras y machos de A. dufresnii del Golfo Nuevo a desovar, recolectamos los huevos de cada hembra individualmente (progenie), los separamos en dos temperaturas de agua de mar (12 y 17 ° C) y los fertilizamos. Registramos el porcentaje de óvulos fecundados y el porcentaje de embriones por etapa de desarrollo según tiempo, temperatura y descendencia. Medimos el crecimiento larvario según la longitud total (TL) y la longitud corporal de la línea media (M) de acuerdo con el tiempo en días post fecundación, la temperatura y la progenie. Resultados: La temperatura no afectó la fertilización, pero el desarrollo del embrión fue más rápido y más sincronizado en el tratamiento de alta temperatura. Los modelos lineales generalizados indican que el desarrollo del embrión depende una interacción cuádruple entre el estadio embrionario, el tiempo (h), la temperatura del agua de mar y la progenie. El crecimiento larvario fue más rápido, produciendo larvas más grandes a la temperatura más alta. El crecimiento de las larvas depende de una triple interacción entre el tiempo (DPF), la temperatura del agua de mar y la progenie. Conclusiones: Encontramos un impacto en la temperatura y en la progenie durante el desarrollo embrionario y larvario y, en ambos casos, estos factores generaron un efecto sinérgico sobre el tiempo de desarrollo y el tamaño de las larvas. Esto probablemente proporciona una ventaja de supervivencia, ya que una velocidad de desarrollo más rápida implica una disminución en el tiempo que pasan en la columna de agua, donde los erizos de mar son vulnerables a los factores estresantes bióticos y abióticos.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021

BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Research progress on factors affecting the establishment and development of oral microbiota in early life / 口腔疾病防治

@#The oral microbiota has been proven to play an essential role in local and systemic health. Hence, it is essential to understand how the oral microbiota and further microbial ecosystems are established and the associated development process to understand the physiologic and pathologic events related to the oral microbiota and management of the whole lifecycle oral and systemic health. The present review summarizes recent studies of the establishment and development of oral microbial communities in early life with related factors and briefly describes their prospects. By investigating the characteristics and development of the oral microbiota, current studies have shown that health status during pregnancy, mode of delivery, diet, environment, antibiotics and genetic factors are related to oral microbiota development, which is helpful in clinical practice. Nevertheless, current studies are mostly cross-sectional. Prospective cohort studies with larger sample sizes using metagenomics or metatranscriptomics and studies on molecular mechanisms are needed to further elucidate the influences and mechanisms of the related factors on the establishment and development of microbiota in early life and their impact on local or systemic health.

Relationship between early factors life stress and college students’ risk-taking behaviors: gender difference and situational influence / 中华行为医学与脑科学杂志

Objective:To explore the differences in risk-taking behaviors of individuals with early life stress between different genders under the control of social situation.Methods:A total of 160 college students including 78 males and 82 females were selected by the child psychological abuse and neglect scale.Then the subjects were divided into the early life stress group ( n=80) and the non-early life stress group ( n=80) according to the scores of the above scales.According to the presence or absence of peers, the subjects in the two groups were randomly assigned to peer presence group ( n=80) or no peer presence group ( n=80). The study adopted an experimental design of 2 (early life stress, non-early life stress) ×2 (peer presence, no peer presence) ×2 (male, female) among the subjects.All subjects performed the task of simulating risky behavior, and the number of times they chose "forward" and did not crash in the task was used as the measurement index of risky behavior.Three-factor ANOVA and Bonferroni simple effect test were carried out using SPSS 22.0 software under various conditions. Results:There were significant differences in the main effects of early life stress ( F(1, 152)=162.06, P<0.01, η2=0.52). In the simulated risk behavior task, the risk behavior of the early life stressed individuals was higher than that of the non-early life stressed individuals (no peer presence: (59.11±11.48) vs (34.91±7.42), P<0.01); peer presence: (59.24±8.59) vs (55.08±10.32), P<0.01). The interaction between early life stress and the presence of peers was statistically significant ( F(1, 152)=65.35, P<0.01, η2=0.30), for non-early life stressed individuals, the risk-taking behaviors in the peer presence group was significantly higher than that in the no peer presence group ((55.08±10.32) vs (34.91±7.42), P<0.01, but the difference was not significant for early life stressed individuals ((59.24±8.59) vs (59.11±11.48), P>0.05). The interaction of early life stress, peer presence and gender was statistically significant ( F(1, 152) =5.92, P=0.016, η2=0.04). In the presence of companions, female early-life stressed individuals exhibited higher risk behaviors than non-early life stressed individuals ((53.91±5.12) vs (46.30±4.57), P<0.01), while the difference between male early life stressed individuals and non-early life stressed individuals was not statistically significant ((65.75±7.42) vs (62.27±7.78), P>0.05). Conclusion:The influence of early life stress on individual risk-taking behavior is related with presence and gender.

Early childhood abuse: adult impulsivity and risky behavior / Abuso na infância: impulsividade no adulto e comportamentos de risco

We review the role of childhood abuse (CA) in the practice of impulsive, risk-taking behaviors during adulthood. CA deregulates the adult response to stress, which in turn disrupts the prefrontal-striatal systems that provide executive control over reward-related behavior. The result is impulsivity and risk-taking, including self-medication with drugs and alcohol and the practice of unsafe sex. These behaviors decrease quality of life and impair the attainment of long-term goals. Risky sexual behavior, in particular, increases the chance of HIV infection and perpetuates the epidemic.

Revisamos o papel do abuso na infância na prática de comportamentos impulsivos e de risco durante a vida adulta. O abuso na infância desregula a resposta do adulto ao estresse, o que, por sua vez, impede os circuitos frontoestriatais de fornecerem o adequado controle executivo sobre comportamentos associados à recompensa. O resultado é a impulsividade e escolhas de risco, incluindo automedicação com drogas e álcool e a prática de sexo inseguro, reduzindo a qualidade de vida e prejudicando o alcance de metas de longo prazo. O comportamento sexual de risco, em particular, aumenta a chance de infecção pelo Vírus de Imunodeficiência Humana e perpetua a sua epidemia.

Early maladaptive schemas and harm avoidance as mediating factors between early life stress and psychiatric symptoms in adults

Objective: This study investigated how factors of temperament and early maladaptive schemas predict psychiatric symptoms, as well as how they mediate the relation between early life stress and psychiatric symptoms in adults. Methods: A cross-sectional study was conducted with a sample of 200 university students. Data was collected through a sociodemographic questionnaire, the Adult Self-Report Inventory, the Childhood Trauma Questionnaire, the Young Schema Questionnaire, and the Temperament and Character Inventory-Revised. Results: A model including early maladaptive schemas, harm avoidance (temperament factor), and early life stress explained 69% of the variation of the psychiatric symptoms; among the predictors, early maladaptive schemas explained 31% of psychiatric symptoms, while harm avoidance explained 25%. Most of the predictive power associated with early life stress can be better explained by early maladaptive schemas and, to a lesser extent, harm avoidance. Conclusion: By managing these processes therapeutically, deleterious effects associated with early life stress can be minimized.

Research progress on correlation between antibiotic exposure in early life and childhood obesity / 中华实用儿科临床杂志

Childhood obesity continues to be a public health concern worldwide, which seriously affects children′s health.In recent years, children have been generally exposed to low doses of antibiotics, and antibiotic problem has drawn international attention.Domestic and foreign researches show that antibiotic exposure in the early life of children is associated with childhood obesity risk, while its specific mechanism has not been completely clear.It is possible that antibiotics may lead to changes in the normal intestinal flora colonization of infants and young children and damage the early intestinal microflora, thus increasing the risk of childhood obesity, but further research is needed to confirm this causal mechanism.

Research progress on correlation between antibiotic exposure in early life and childhood obesity / 中华实用儿科临床杂志

Childhood obesity continues to be a public health concern worldwide,which seriously affects children's health.In recent years,children have been generally exposed to low doses of antibiotics,and antibiotic problem has drawn international attention.Domestic and foreign researches show that antibiotic exposure in the early life of children is associated with childhood obesity risk,while its specific mechanism has not been completely clear.It is possible that antibiotics may lead to changes in the normal intestinal flora colonization of infants and young children and damage the early intestinal microflora,thus increasing the risk of childhood obesity,but further research is needed to confirm this causal mechanism.

The effects of maternal obesity during gestation and lactation and orange juice intake on the metabolic profile of male offspring exposed to control and obesogenic diets and breast cancer risk of female offspring / A obesidade materna durante a gestação e lactação e o consumo do suco de laranja: efeitos nos parâmetros metabólicos da prole masculina exposta a dieta controle e obesogênica e programação do risco do câncer de mama da prole feminina de camundongos

Obesity is a worldwide public health problem and the main risk factor for a number of chronic diseases. Breast cancer is another worrisome disease: it is the leading cause of cancer amongst women and has an elevated mortality rate. Approximately 30 years ago, Barker and Trichopoulos suggested that cardiovascular disease and breast cancer, respectively, may be originated in utero. In subsequent years, studies proved both hypotheses correct. Understanding how in-utero environment can affect development of obesity and breast cancer in adulthood is key for preventing these diseases. Nutrition during gestation and lactation is considered a modifiable factor to impact in-utero environment. Orange juice (OJ) is an excellent source of bioactive compounds, including vitamin C and flavonoids, and reports suggests that intake of orange juice minimizes damaging effects of obesity. The objective of this thesis was to evaluate the effects of maternal obesity during gestation and lactation and OJ intake on (a) metabolic profile of male offspring exposed to control and obesogenic diets and (b) breast cancer risk of female offspring. Four-week-old C57BL/6 female mice were assigned into three groups: control- fed a control diet and water ad libitum, obese- fed obesogenic diet and water ad libitum and obese+OJ- fed obesogenic diet and OJ. After three weeks on the diet, females were mated to control males. Male offspring from each group were weaned into control or obesogenic diets for 21 weeks. Female offspring was either euthanized for evaluation of mammary gland development or submitted to a chemically induced breast carcinogenesis protocol. Parameters to assess metabolism (as body composition and adipose tissue expression of obesity-related genes), breast cancer risk (as epithelial elongation and number of terminal end buds) and tumorigenesis (incidence, latency and multiplicity of mammary tumors) were collected. ANOVA followed by Tukey or Fischer´s LSD test were used to investigate differences between groups and a p<0.05 was considered significant. Male offspring of obese mothers fed control diet presented increased glucose concentrations and expression of F4/80 and interleukin-6 compared to control offspring. Male offspring of obese+OJ mothers fed a control diet presented expression of F4/80 and interleukin-6 similar to control offspring. Male offspring to control mothers fed obesogenic diet presented increased glucose concentrations and epidydimal fat tissue compared to offspring of obese mothers. Offspring to obese+OJ mothers presented increased expression of leptin and tumor necrosis factor-α. Female offspring of obese mothers had decreased terminal end buds and increased latency of first tumor and OJ intake decreased epithelial elongation compared to offspring of control/obese mothers. Maternal obesity had greater impact in offspring exposed to control than obesogenic environment. OJ intake by mothers helped with harmful effects induced by maternal obesity on male offspring fed control diet. Control offspring exposed to obesogenic diet presented worse metabolic profile than offspring from obese mothers. In this particular case, OJ was not beneficial to male offspring. Whereas obesity induced by a high-fat high-sugar diet presented a somewhat protective effect on breast cancer risk, OJ further protected offspring of obese mothers

A obesidade é um problema de saúde pública e o principal fator de risco para uma série de doenças crônicas. O câncer de mama é outra doença preocupante: é a principal causa de câncer entre as mulheres e tem elevada taxa de mortalidade. Há 30 anos, Barker e Trichopoulos sugeriram que a doença cardiovascular e o câncer de mama, respectivamente, podem ser originados no útero. Nos anos seguintes essas hipóteses foram confirmadas. Compreender como o ambiente intrauterino pode afetar o desenvolvimento da obesidade e o câncer de mama na idade adulta, portanto, é fundamental para prevenir essas doenças. O estado nutricional e a nutrição durante a gestação e lactação são considerados fatores modificáveis e que pode influenciar o ambiente intrauterino. O suco de laranja (SL) é uma excelente fonte de compostos bioativos, incluindo vitamina C e flavonoides, e estudos sugerem que a ingestão de suco de laranja pode minimizar os efeitos deletérios da obesidade. O objetivo dessa tese foi de avaliar os efeitos da obesidade materna durante a gestação e lactação e a ingestão de SL no (a) perfil metabólico da prole masculinas expostos à dietas controle e obesogênica e (b) risco de câncer de mama da prole feminina. Camundongos fêmeas C57BL/6, com quatro semanas de idade, foram distribuídos em três grupos: controle - alimentados com uma dieta de controle e água ad libitum, obesosalimentados com dieta obesogênica e água ad libitum e obesos+SL- alimentados com dieta obesogênica e SL. Após três semanas na dieta, as fêmeas foram acasaladas com machos controle. A prole masculina de cada grupo foi desmamada e alimentadas com dieta obesogênica ou controle por 21 semanas. A prole feminina foi eutanasiada para a avaliação do desenvolvimento da glândula mamária ou submetida a um protocolo de carcinogênese mamária quimicamente induzida. Parâmetros para avaliar o metabolismo (como a composição corporal e expressão de genes relacionados à obesidade do tecido adiposo), risco de câncer de mama (como desenvolvimento epitelial e número de terminal end buds) e tumorigênese (incidência, latência e multiplicidade dos tumores mamários) foram coletados. Para investigar diferença estatística entre os grupos foi realizada ANOVA, seguida pelo teste de Tukey ou LSD de Fischer e um p<0,05 foi considerado significante. A prole masculina de mães obesas alimentadas com dieta de controle apresentou aumento das concentrações de glicose e aumento das expressões de F4/80 e interleucina-6 em relação a prole controle. A prole masculina de mães obesas+SL alimentadas com dieta controle apresentou expressão de F4/80 e interleucina-6 similar à da prole de controle. A prole masculina de mães controle e alimentada com dieta obesogênica apresentou aumento das concentrações de glicose e aumento do tecido adiposo epididimal em comparação à prole de mães obesas. A prole de mães obesas+SL apresentou maior expressão de leptina e TNF-α. A prole feminina de mães obesas apresentou redução do número de terminal end buds e aumento da latência para o aparecimento do primeiro tumor. O consumo de SL diminuiu o desenvolvimento epitelial comparado as proles de mães controles e obesas. A obesidade materna teve maior impacto na prole masculina exposta a dieta controle do que na obesogênica. A ingestão materna de SL ajudou com efeitos danosos induzidos pela obesidade materna na prole masculina alimentada com dieta controle. A prole de fêmeas controles e alimentada com dieta obesogênica apresentou perfil metabólico pior que a prole das mães obesas. Neste caso, o SL não foi benéfico para a prole masculina. A obesidade materna induzida por uma dieta rica em banha e açúcares apresentou discreto efeito protetor no risco de câncer de mama, o SL acentuou esta proteção

Relationship between early life respiratory infections and childhood asthma / 国际儿科学杂志

Viral infections in early life,especially respiratory syncytial virus and human rhinovirus,are closely related to childhood asthma.An initial wheezing of the lower respiratory tract infection of human rhinovirus can serve as a marker of asthma predisposition,whereas respiratory syncytial virus bronchiolitis (particularly severe infection) in early life can have a causative role in asthma attacks.The interaction of viral infections with the bacterial microbiological environment of respiratory tract is an important determinant of childhood asthma.

Protection effect of Lactobacillus rhamnosus GG supplied in early life on intestinal barrier in offspring / 中华临床营养杂志

Objective To investigate the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on intestinal barrier and intestinal development in offspring mice and its possible mechanism.Methods Six C57BL/6 pregnant mice with the same conception time of 6 weeks were selected and randomly divided into experiment group given 108 cfu/ml LGG live bacteria and control group given LGG inactivated bacteria by gavage from the 18th day of pregnancy until natural birth.The progeny mice in the two groups were continued to be gavaged with 107 cfu/ml of LGG live bacteria or LGG inactivated bacteria on days 1-5 of birth.The body weight changes of 3 week'progeny mice were recorded.The colonization of LGG bacteria in offspring mice was detected at 2nd and 3rd weeks.The mRNA of intestinal proinflammatory cytokines and tight junction molecules were evaluated by real-time PCR method.HE,immunohistochemistry,immunofluorescence staining and enzyme-linked immunosorbent assay were used to evaluate the intestinal barrier of 3-week old off spring mice.Results Compared with the control group,the progeny mice of the experiment group showed no significant difference in body weight at the first week,and the body weight increased at the second week and the third week [2ndweek:(3.790±0.240) g vs.(4.326±0.140) g,t=3.707,P=0.006;3rd week:(7.295±0.326) g vs.(8.040±0.370) g,t=3.130,P=0.011].LGG colonization can be detected only in the feces of progeny mice in the experiment group.Intestinal colonization can promote the growth of small intestine villi and colon crypt depth [jejunum:(320.000±22.514) μm vs.(265.100±15.611) μm,t=8.258,P＜0.001;ileum:(150.500±13.099) μm vs.(111.000±11.308) μm,t=9.958,P＜0.001;colon:(295.000±15.209) μm vs.(233.100±6.678) μm,t=9.129,P＜0.001].Compared with the control group,the number of goblet cells in the colonic crypt of the experiment group increased (11.62 ± 0.780 vs.35.24 ±1.370,t=15.000,P＜0.001),and the relative mRNA expression levels of pro-inflammatory factors as IFN-γ (1.280±0.232 vs.0.512±0.206,t=4.970,P=0.001),IL-6 (1.364±0.271 vs.0.941±0.215,t=2.452,P=0.040),IL-10 (1.341±0.320vs.0.744±0.294,t=2.762,P=0.025)andTNF-α (3.702±0.150 vs.2.581±0.500,t=2.553,P=0.034) in the experiment group decreased;the expression levels of the intimate tight junction molecules (Claudin3) (1.283±0.152 vs.1.881±0.172,t=4.932,P=0.001) and the atresia protein molecule (Occludin) (1.164±0.342 vs.0.812±0.224,t=3.67,P=0.016) significantly increased.Conclusion Early life LGG colonization protects the intestinal barrier by inhibiting lowgrade intestinal inflammation.This study will lay the experimental foundation for the supplementation of probiotics in early life so as to prevent intestinal diseases.

Early-life stress alters sleep structure and the excitatory-inhibitory balance in the nucleus accumbens in aged mice / 中华医学杂志(英文版)

Background@#Exposure to adverse experiences in early life may profoundly reshape the neurodevelopmental trajectories of the brain and lead to long-lasting behavioral and neural alterations. One deleterious effect of early-life stress that manifests in later life is sleep disturbance, but this has not been examined in aged mice and the underlying neural mechanisms remain unknown. Considering the important role of the nucleus accumbens (NAc) in the sleep-wake regulation, this study aimed to assess the effects of early-life stress on the sleep behaviors in aged mice and the potential involvement of the NAc in stress-induced sleep abnormalities.@*Methods@#Twenty aged male C57BL/6 mice (>16 months, n = 10 per group) were used in this study. During post-natal days 2 to 9, dams were provided with either sufficient (control) or a limited nesting and bedding materials (stressed). When the mice were 16 to 17 months old, their sleep-wake behaviors were recorded over 24 h using electroencephalogram and electromyelogram. The amount of each sleep-wake stage, mean duration, and stage transition was analyzed. Then, five animals were randomly chosen from each group and were used to measure the expression levels of vesicular glutamate transporter-1 (VGluT1) and vesicular transporters of γ-aminobutyric acid (VGAT) in the NAc using immunohistochemistry. Group comparisons were carried out using Student t test or analysis of variances when appropriate.@*Results@#Compared with the control mice, the early-life stressed aged mice spent less time awake over 24 h (697.97 ± 77.47 min vs. 631.33 ± 34.73 min, t17 = 2.376, P = 0.030), accordingly, non-rapid eye movement sleep time was increased (667.37 ± 62.07 min vs. 723.54 ± 39.21 min, t17 = 2.326, P = 0.033) and mean duration of rapid eye movement sleep was prolonged (73.00 ± 8.98 min vs. 89.39 ± 12.69 min, t17 = 3.277, P = 0.004). Meanwhile, we observed decreased VGluT1/VGAT ratios in the NAc in the stressed group (F(1, 16) = 81.04, P < 0.001).@*Conclusion@#Early adverse experiences disrupt sleep behaviors in aged mice, which might be associated with the excitatory-inhibitory imbalance in the NAc.