Unraveling paraquat-induced toxicity on mouse neural stem cells: Dose-response metabolomics insights and identification of sensitive biomarkers for risk assessment.

Exposure to pesticide could contribute to neurodevelopmental and neurodegenerative disorders. Notably, research suggests that prenatal or early postnatal exposure to paraquat (PQ), an herbicide, might trigger neurodevelopmental toxicity in neural stem cells (NSCs) via oxidative stress. However, the molecular mechanisms of PQ-induced perturbations in NSCs, particularly at the metabolite level, are not fully understood. Using a dose-response metabolomics approach, we examined metabolic changes in murine NSCs exposed to different PQ doses (0, 10, 20, 40 µM) for 24h. At 20 µM, PQ treatment led to significant metabolic alterations, highlighting unique toxic mechanisms. Metabolic perturbations, mainly affecting amino acid metabolism pathways (e.g., phenylalanine, tyrosine, arginine, tryptophan, and pyrimidine metabolism), were associated with oxidative stress, mitochondrial dysfunction, and cell cycle dysregulation. Dose-response models were used to identify potential biomarkers (e.g., Putrescine, L-arginine, ornithine, L-histidine, N-acetyl-L-phenylalanine, thymidine) reflecting early damage from low-dose PQ exposure. These biomarkers could be used as points of departure (PoD) for characterizing PQ exposure hazard in risk assessment. Our study offers insights into mechanisms and risk assessment related to PQ-induced neurotoxicity in NSCs.

Dietary pattern and precocious puberty risk in Chinese girls: a case-control study.

BACKGROUND: The role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chinese girls. METHODS: In this case-control study, we enrolled 185 precocious puberty girls and 185 age-matched controls. Their dietary intake was assessed through a semi-quantitative food frequency questionnaire. Their sociodemographic and lifestyle data were collected. The associations between dietary intake and risk of precocious puberty were assessed by conditional logistic regression models. RESULTS: After multivariate adjustment, consuming a higher amount of red meat was associated with higher precocious puberty risk (OR = 2.74, 95% CI: 1.25-6.02), while a higher frequency of fruit ( P for trend = 0.024) and amount of vegetable intake was associated with a lower risk of precocious puberty (P for trend = 0.002). The high vegetable and protein dietary pattern was significantly negatively associated with precocious puberty (OR = 0.78, 95% CI: 0.63-0.97), whereas the high animal food and fruits dietary pattern was remarkably positively associated with precocious puberty (OR = 1.36, 95% CI: 1.09-1.69), after adjusting for age and body mass index. CONCLUSIONS: High vegetable and protein dietary pattern is a protective factor against precocious puberty, while high animal food and fruits dietary pattern is a risk factor for precocious puberty in Chinese girls. Attentions should be paid to a reasonable intake of red meat, eggs, and fruits in children's daily diet, increase their intake of vegetables, in order to reduce the risk of precocious puberty.

The therapeutic role and potential mechanism of EGCG in obesity-related precocious puberty as determined by integrated metabolomics and network pharmacology.

Objective: (-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study was to integrate metabolomics and network pharmacology to reveal the mechanism of EGCG in the prevention of obesity-related precocious puberty. Materials and methods: A high-performance liquid chromatography-electrospray ionization ion-trap tandem mass spectrometry (LC-ESI-MS/MS) was used to analyze the impact of EGCG on serum metabolomics and associated metabolic pathways in a randomized controlled trial. Twelve weeks of EGCG capsules were given to obese girls in this trail. Additionally, the targets and pathways of EGCG in preventing obesity-related precocious puberty network pharmacology were predicted using network pharmacology. Finally, the mechanism of EGCG prevention of obesity-related precocious puberty was elucidated through integrated metabolomics and network pharmacology. Results: Serum metabolomics screened 234 endogenous differential metabolites, and network pharmacology identified a total of 153 common targets. These metabolites and targets mainly enrichment pathways involving endocrine-related pathways (estrogen signaling pathway, insulin resistance, and insulin secretion), and signal transduction (PI3K-Akt, MAPK, and Jak-STAT signaling pathways). The integrated metabolomics and network pharmacology indicated that AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 may be key targets for EGCG in preventing obesity-related precocious puberty. Conclusion: EGCG may contribute to preventing obesity-related precocious puberty through targets such as AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 and multiple signaling pathways, including the estrogen, PI3K-Akt, MAPK, and Jak-STAT pathways. This study provided a theoretical foundation for future research.

Green tea catechin EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway.

This study aimed to explore the potential regulatory pathways of (-)-epigallocatechin-3-gallate (EGCG) in preventing obesity-related precocious puberty. A retrospective analysis on the impact of EGCG on puberty onset in obese girls was conducted on plasma samples collected from a human randomized controlled trial. In the trial, participants consumed EGCG capsules for 12 weeks. In the animal experiment, rats were divided into four groups: normal diet control (NC) group, high-fat diet (HFD) group, NC+EGCG group, and HFD+EGCG group. Blood samples were collected on postnatal days 27, 33, and 36 to detect sexual development indicators. The hypothalamic expressions of kisspeptin/Kiss1R and neurokinin B (NKB)/NK3R signaling were measured by RT-qPCR and Western blot assay. The ovary NKB protein expression was assessed by immunohistochemical assays. Serum NKB level in the EGCG group was lower than the placebo group by 0.599 ng/mL [ß=-0.599, 95% CI: (-1.005, -0.193)], at the end of intervention and after adjusting for confounders (clinical study). In the animal experiment, EGCG intervention could significantly delay the vaginal opening (VO) time of rats fed with HFD. On day 33, EGCG intervention could significantly reduce serum NKB, luteinizing hormone (LH) levels, ovarian NKB protein expression, and endometrial thickness of HFD-fed rats, while EGCG intervention could remarkably increase mRNA and protein expression of NKB/NK3R. EGCG could prevent obesity-related precocious puberty through NKB/NK3R signaling pathway, which may provide a novel insight into the role of EGCG in preventing precocious puberty in obese girls.

Effect of Decaffeinated Green Tea Polyphenols on Body Fat and Precocious Puberty in Obese Girls: A Randomized Controlled Trial.

Background: Obesity has been reported to be an important contributing factor for precocious puberty, especially in girls. The effect of green tea polyphenols on weight reduction in adult population has been shown, but few related studies have been conducted in children. This study was performed to examine the effectiveness and safety of decaffeinated green tea polyphenols (DGTP) on ameliorating obesity and early sexual development in girls with obesity. Design: This is a double-blinded randomized controlled trial. Girls with obesity aged 6-10 years old were randomly assigned to receive 400 mg/day DGTP or isodose placebo orally for 12 weeks. During this period, all participants received the same instruction on diet and exercise from trained dietitians. Anthropometric measurements, secondary sexual characteristics, B-scan ultrasonography of uterus, ovaries and breast tissues, and related biochemical parameters were examined and assessed pre- and post-treatment. Results: Between August 2018 and January 2020, 62 girls with obesity (DGTP group n = 31, control group n = 31) completed the intervention and were included in analysis. After the intervention, body mass index, waist circumference, and waist-to-hip ratio significantly decreased in both groups, but the percentage of body fat (PBF), serum uric acid (UA), and the volumes of ovaries decreased significantly only within the DGTP group. After controlling confounders, DGTP showed a significantly decreased effect on the change of PBF (ß = 2.932, 95% CI: 0.214 to 5.650), serum UA (ß = 52.601, 95% CI: 2.520 to 102.681), and ovarian volumes (right: ß = 1.881, 95% CI: 0.062 to 3.699, left: ß = 0.971, 95% CI: 0.019 to 1.923) in girls with obesity. No side effect was reported in both groups during the whole period. Conclusion: DGTP have shown beneficial effects of ameliorated obesity and postponed early sexual development in girls with obesity without any adverse effects. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT03628937], identifier [NCT03628937].

Higher poultry consumption was associated with an earlier age at menarche.

AIM: To examine the association between meat consumption and earlier age of menarche among schoolgirls in Shanghai. METHODS: The study randomly selected 1981 schoolgirls aged 6-18 years in Shanghai using a two-stage random sampling design. Information on meat intake was collected using a semi-quantitative food frequency questionnaire. Menarche age, household income, physical activity and other covariates were obtained by standardised questionnaires. Logistic regression was used to analyse the association between intake of meat and earlier age of menarche. Earlier age of menarche was defined as first menstruation before 12 years of age. RESULTS: Among the 986 girls who had experienced menarche, 518/986 (52.5%) had earlier age of menarche. After adjusting for body mass index, age, physical activity, sleep, household income and parental education, consumption of poultry was positively associated with risk of earlier age of menarche (P-trend = .03). Girls who never consumed poultry had a lower risk of earlier age of menarche (odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.39-0.96). Neither the consumption of pork, beef, lamb, processed meat nor total meat consumption was associated with menarche age. CONCLUSION: Higher consumption of poultry was associated with an earlier age at menarche.

Higher toenail selenium is associated with increased insulin resistance risk in omnivores, but not in vegetarians.

BACKGROUND: The relationship between selenium (Se) and insulin resistance remains unclear. We aim to explore the association between toenail Se levels and insulin resistance through a cross-sectional study comprising Chinese vegetarians and matched omnivores. METHODS: In this study, we enrolled 220 vegetarians and 220 omnivores matched by age and sex from Shanghai. The inductively coupled plasma mass spectrometry method was used to measure toenail Se levels. Dietary Se intakes were assessed by the 24-h dietary recall method. Blood samples were collected to measure fasting blood glucose level and fasting insulin concentrations. Insulin resistance index (HOMA-IR) and insulin secretion index (HOMA-B) were calculated to evaluate insulin resistance. Multi-linear regression analysis was performed to determine the association between toenail Se levels and insulin resistance, after adjusting for confounders. RESULTS: The mean ages of vegetarians (76 vegans, 144 lacto-ovo-vegetarians) and omnivores were 35.96 ± 8.73 years and 35.23 ± 8.93 years, respectively. Of these, 180 (81.8%) were female and 40 (18.2%) were male. No association was found between toenail Se levels and insulin resistance in vegetarians. However, the concentration of Se in toenails was positively correlated with fasting insulin levels (ß = 1.030, 95%CI: 0.393 to 1.667) and HOMA-IR (ß = 0.245, 95%CI: 0.098 to 0.392) in omnivores, after multivariate adjustment for age, sex, BMI, alcohol consumption, income, and daily dietary intakes (energy, protein, fat, carbohydrate, and fiber). This positive relationship persisted only in omnivores whose dietary Se intake was above 60 µg/d. CONCLUSIONS: Higher toenail Se levels were associated with increased insulin resistance risk in Chinese omnivores whose dietary Se intake was above 60 µg/d, but not in vegetarians. These findings create awareness on the association of dietary Se intake above 60 µg/d with the risk of insulin resistance.

COMPARATIVE EFFICACY AND SAFETY OF THREE CURRENT CLINICAL TREATMENTS FOR GIRLS WITH CENTRAL PRECOCIOUS PUBERTY: A NETWORK META-ANALYSIS.

Objective: The optimal treatment for girls with central precocious puberty (CPP) is unknown. We conducted a network meta-analysis to evaluate the efficacy and safety of existing treatments to provide credible clinical guidelines. Methods: We compared gonadotropin-releasing hormone analogue (GnRHa) therapy, GnRHa plus growth hormone (GH) combination therapy, and no-treatment therapy for girls with CPP by performing an electronic search for studies in PubMed, Embase, Chinese National Knowledge Infrastructure databases, and Wanfang Data from their inception until September 30, 2018. Six outcomes, including bone maturation ratio, final height, final height compared with target height, growth velocity, height gain, and gain in predicted adult height (ΔPAH), were expressed as the mean difference with 95% confidence interval. The surface under the cumulative ranking curve (SUCRA) value illustrated the rank probability of each treatment under different outcomes. Results: Twenty-two studies with 1,268 patients were included. GnRHa plus GH had the best performance on final height, final height compared with target height, growth velocity, height gain, and ΔPAH, with the highest SUCRA values of 0.919, 0.975, 0.909, 0.999, and 0.957, respectively. For bone maturation ratio, GnRHa ranked the highest, with a SUCRA value of 0.663. No severe adverse effects were reported. Conclusion: For girls with CPP, GnRHa plus GH had the highest probability of being the optimal therapy for improving final height, and no severe adverse effects were reported. Abbreviations: BMI = body mass index; CI = confidence interval; CPP = central precocious puberty; GH = growth hormone; GnRHa = gonadotropin-releasing hormone analogue; HPG = hypothalamic-pituitary-gonadal; LH = luteinizing hormone; NMA = network meta-analysis; PAH = predicted adult height; PCOS = polycystic ovary syndrome; RCT = randomized controlled trial; SUCRA = surface under the cumulative ranking curve.

Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods.

BACKGROUND: Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. MAIN BODY: Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. CONCLUSIONS: In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.

Children's Caregivers and Public Playgrounds: Potential Reservoirs of Infection of Hand-foot-and-mouth Disease.

Hand-foot-and-mouth disease (HFMD) is a common infectious disease, which has led to millions of clinical cases and hundreds of deaths every year in China. This study aimed to exploring the effects on HFMD transmission of children's caregivers and public area, as well as trying to locate the potential reservoirs of infections in primary cases. Total children's 257 samples (98 children's caregivers and 159 environmental samples) were tested for the presence of universal enterovirus, enterovirus 71, coxsackie virus A6 and A16 by real-time fluorescence quantitative polymerase chain reaction (qPCR). 5.84% (15/257, 95% confidence interval [CI]: 2.98%, 8.70%) of total samples had positive results of enterovirus. The enterovirus positive rates of children's caregiver samples and environmental samples were respectively 7.14% (7/98, 95% CI: 2.04%, 12.24%), and 5.03% (8/159, 95% CI: 1.63%, 8.43%); 7.61% (7/92, 95% CI: 2.21%, 13.01%) of wiping samples from playgrounds and 1.49% (1/67, 95% CI: 0, 7.00%) of air samples in indoor market places had positive result of enterovirus. High positive rates of enterovirus in children's caregivers and from playgrounds indicated that they would be potential reservoirs of HFMD infection, as children might be infected via contacting with asymptomatic-infected individuals or exposure of contaminated surface of public facilities.