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 methodsA 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.ResultsSerum 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.ConclusionEGCG 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

Pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation

Enhancing Faba Bean Yields in Alpine Agricultural Regions: The Impact of Plastic Film Mulching and Phosphorus Fertilization on Soil Dynamics

Plastic film mulching is widely used in water and temperature-limited regions to enhance crop yields. Phosphorus (P) fertilization can address deficiencies in soil P availability. In this four-year field experiment conducted in an alpine agricultural area, we explored the effects of nitrogen (N) and P supply imbalance on faba bean cultivation, particularly examining intensified N competition between soil microbes and plants. The randomized block design comprised three film mulching treatments—no film mulching with flat planting (NMF), double ridges and furrows mulched with one plastic film (DRM), and three ridges and furrows mulched with one plastic film (TRM)—and three P levels—P0 (0 kg P ha−1), P1 (9.10 kg P ha−1), and P2 (18.2 kg P ha−1). The results indicated that NMF enhanced soil available N and microbial biomass N (MBN) during early growth stages, consequently improving faba bean yield, nodule weight, total N, and microbial biomass carbon (MBC) compared to DRM and TRM. DRM and TRM exhibited higher soil available N and MBN during later growth stages and higher soil temperature and water content, soil water storage (SWS), soil organic C (SOC), and soil C/N ratio than NMF. In NMF and DRM, P fertilization increased grain yield, nodule weight, SOC, total N, soil C/N ratio, soil available N, and MBC but decreased MBN during early growth stages, and decreased soil water content and SWS. TRM exhibited the opposite trend. P fertilization increased soil total P and available P. Overall, NMF combined with P fertilization (~18.2 kg P ha−1) significantly improved faba bean yield. However, it may also accelerate SOC decomposition, highlighting the need to consider N fertilizer application in this alpine agricultural region

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

Abstract 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

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 [β=-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

Soil, Plant, and Microorganism Interactions Drive Secondary Succession in Alpine Grassland Restoration

Plant secondary succession has been explored extensively in restoring degraded grasslands in semiarid or dry environments. However, the dynamics of soil microbial communities and their interactions with plant succession following restoration efforts remain understudied, particularly in alpine ecosystems. This study investigates the interplay between soil properties, plant communities, and microbial populations across a chronosequence of grassland restoration on the Qinghai–Tibet Plateau in China. We examined five succession stages representing artificial grasslands of varying recovery durations from 0 to 19. We characterized soil microbial compositions using high-throughput sequencing, enzymatic activity assessments, and biomass analyses. Our findings reveal distinct plant and microbial secondary succession patterns, marked by increased soil organic carbon, total phosphorus, and NH4+-N contents. Soil microbial biomass, enzymatic activities, and microbial community diversity increased as recovery time progressed, attributed to increased plant aboveground biomass, cover, and diversity. The observed patterns in biomass and diversity dynamics of plant, bacterial, and fungal communities suggest parallel plant and fungal succession occurrences. Indicators of bacterial and fungal communities, including biomass, enzymatic activities, and community composition, exhibited sensitivity to variations in plant biomass and diversity. Fungal succession, in particular, exhibited susceptibility to changes in the soil C: N ratio. Our results underscore the significant roles of plant biomass, cover, and diversity in shaping microbial community composition attributed to vegetation-induced alterations in soil nutrients and soil microclimates. This study contributes valuable insights into the intricate relationships driving secondary succession in alpine grassland restoration

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 (β = 2.932, 95% CI: 0.214 to 5.650), serum UA (β = 52.601, 95% CI: 2.520 to 102.681), and ovarian volumes (right: β = 1.881, 95% CI: 0.062 to 3.699, left: β = 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]