Frontiers in Endocrinology最新文献

Introduction: It is well acknowledged that lipids assume a critical role in oocyte maturation and early embryonic metabolism, this study aimed to evaluate the relationship between the lipid composition of plasma and follicular fluid (FF), and the consequences of embryonic development. This study compared the lipidomic profiles of paired plasma and FF samples obtained from sixty-five Chinese women who underwent assisted reproductive technology (ART) treatments.

Methods: Non-targeted lipidomics analysis.

Result: Results not only indicated similarities in lipid composition between these biofluids, but also revealed a number of unique differences. The biomatrix distinction was found to be primarily driven by lipids belonging to the lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), ether PE, and triglyceride (TG) classes. In addition, specific species from these subclasses were discovered to be correlated with embryo development outcomes during ART. Notably, the composition of the fatty acyl chains appeared to play a crucial role in these associations. Furthermore, thirteen plasma lipid variables were identified, represented by Phosphatidylcholine 18:014:0 and PE P-18:020:1, which correlated with successful blastocyst formation (BF).

Discussion: The present study demonstrated that FF has a distinctive lipid composition, setting it apart from plasma; and the association observed with embryonic development underscored an important role of lipid composition in the healthy development of oocytes.

Background and objective: The incidence of central precocious puberty (CPP) in girls increased significantly during the COVID-19 pandemic. This study aimed to explore the impact of perfluorinated endocrine disruptors on CPP through metabolomics analysis in girls from Hainan Province, China.

Methods: Serum samples from 100 girls with CPP and 100 healthy controls were collected. Untargeted metabolomics profiling was performed using ultra-high performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive-Orbitrap-MS). Differentially expressed metabolites (DEMs) were screened, and pathway enrichment analysis was conducted.

Results: Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) revealed distinct metabolic profiles between the CPP and control groups. A total of 511 metabolites were identified, including 296 up-regulated DEMs and 255 down-regulated DEMs. Three perfluorinated compounds-PFSM-perfluoroalkyl_sulfonamide_Me, PFSM-FSAA, and PFCA-unsaturated-were significantly upregulated in the CPP group. KEGG pathway enrichment analysis suggested the involvement of multiple pathways in the CPP process regulated by these compounds.

Conclusions: Perfluorinated compounds may promote CPP in girls by interfering with various pathways and affecting the hypothalamic-pituitary-gonadal axis function. This study highlighted the need for further research and public health measures to address environmental endocrine disruptors.

Background: Gestational diabetes mellitus (GDM) is a complex metabolic disease that has short-term and long-term adverse effects on mothers and infants. However, the specific pathogenic mechanism has not been elucidated.

Objective: The aim of this study was to confirm the associations between candidate genetic variants (rs4134819, rs720918, rs2034410, rs11109509, and rs12524768) and GDM risk and prediction in a southern Chinese population.

Methods: Candidate variants were genotyped in 538 GDM cases and 626 healthy controls. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated to assess the associations between genotypes and GDM risk. Then, the false-positive report probability (FPRP) analysis was adopted to confirm the significant associations, and bioinformatics tools were used to explore the potential biological function of studied variants. Finally, risk factors of genetic variants and clinical indicators identified by logistics regression were used to construct a nomogram model for GDM prediction.

Results: It was shown that the XAB2 gene rs4134819 was significantly associated with GDM susceptibility (CT vs. CC: adjusted OR = 1.38, 95% CI: 1.01-1.87, p = 0.044; CT/TT vs. CC: crude OR = 1.42, 95% CI: 1.08-1.86, p = 0.013). Functional analysis suggested that rs4134819 can alter the specific transcription factors (CPE bind and GATE-1) binding to the promoter of the XAB2 gene, regulating the transcription of XAB2. The nomogram established with factors such as age, FPG, HbA1c, 1hPG, 2hPG, TG, and rs4134819 showed a good discriminated and calibrated ability with an area under the curve (AUC) = 0.931 and a Hosmer-Lemeshow test p-value > 0.05.

Conclusion: The variant rs4134819 can significantly alter the susceptibility of the Chinese population to GDM possibly by regulating the transcription of functional genes. The nomogram prediction model constructed with genetic variants and clinical factors can help distinguish high-risk GDM individuals.

Type 1 diabetes (T1D) represents a significant health burden worldwide, with associated complications including bone fragility. Current clinical methods and biomarkers for assessing bone health and predicting fracture risk in T1D are limited and lack accuracy. MicroRNAs (miRNAs) have emerged as potential biomarkers for predicting T1D-induced bone loss, although comprehensive profiling studies are lacking. Previous investigations have indicated a link between dysregulated miRNA expression levels and impaired bone health in T1D. Therefore, in this study, we explored differential miRNA expression levels in serum and bone tissue of mice with T1D-induced bone loss using Next Generation Sequencing (NGS). T1D was induced using streptozotocin in male wild-type mice. Serum and bone tissues were analyzed at 14 weeks of age, following the prior characterization of bone loss in this mouse model. MiRNA profiling was conducted using two-independent NGS analyses and validated through quantitative RT-PCR. NGS profiling identified differential expression of miRNAs in serum and bone tissue of T1D mice compared to controls. The first NGS analysis revealed 24 differentially expressed miRNAs in serum and 13 in bone tissue. Especially, miR-136-3p was consistently downregulated in both serum and bone tissue. However, the second NGS analysis presented a distinct set of dysregulated miRNAs, with miR-206-3p overlapping in both tissues but exhibiting differential expression patterns. Surprisingly, miR-144-5p, miR-19a-3p, and miR-21a-5p displayed contrasting regulatory patterns between NGS and qPCR analyses. Finally, gene network analysis identified associations between dysregulated miRNAs and pathways involved in bone physiology, including TGF-beta, PI3-Akt signaling, and osteoclast differentiation in humans. In conclusion, our study offers initial insights into dysregulated miRNAs associated with T1D-induced bone loss, but also highlights the lack of consistency in the results obtained from miRNA sequencing in different cohorts. Thus, further investigation is needed to better understand the complexities of miRNA analyses before they can be established as reproducible biomarkers for predicting bone health in T1D.

Objective: The role of immune cells in type 1 diabetes (T1D) is unclear. The aim of this study was to assess the causal effect of different immune cells on T1D using Mendelian randomization (MR).

Methods: A dataset of immune cell phenotypes (numbered from GCST0001391 to GCST0002121) was obtained from the European Bioinformatics Institute, while a T1D dataset (numbered finngen_R10_T1D) was obtained from FinnGen. Single nucleotide polymorphisms meeting the conditions were screened stepwise according to the assumptions of association, independence, and exclusivity. Inverse variance weighted was used as the main method for the MR analysis. MR-Egger was used to assess the horizontal pleiotropy of the results. Cochran's Q and the leave-one-out method were respectively used for the heterogeneity analysis and the sensitivity analysis of the results.

Results: MR analysis showed that effector memory (EM) double-negative (DN) (CD4^-CD8^-) %T cells [odds ratio (OR) = 1.157, 95% confidence interval (95% CI) = 1.016-1.318, p = 0.028, false discovery rate (FDR) = 0.899], EM CD8^br %T cells (OR = 1.049, 95% CI = 1.003-1.098, p = 0.037, FDR = 0.902), CD28 on CD28⁺CD45RA⁺CD8^br (OR = 1.334, 95% CI = 1.132-1.571, p = 0.001, FDR = 0.044), IgD⁺CD38^dim %lymphocytes (OR = 1.045, 95% CI = 1.002-1.089, p = 0.039, FDR = 0.902), CD80 on monocytes (OR = 1.084, 95% CI = 1.013-1.161, p = 0.020, FDR = 0.834), SSC-A on plasmacytoid dendritic cells (pDCs) (OR = 1.174, 95% CI = 1.004-1.372, p = 0.044, FDR = 0.902), and FSC-A on pDCs (OR = 1.182, 95% CI = 1.011-1.382, p = 0.036, FDR = 0.902) were associated with an increased genetic susceptibility to T1D. Cochran's Q showed that there was heterogeneity for CD28 on the CD28⁺CD45RA⁺CD8^br results (p = 0.043), whereas there was no heterogeneity for the other results (p ≥ 0.05). The sensitivity analysis showed that the MR analysis results were robust.

Conclusion: The MR analysis demonstrated that seven immune cell phenotypes were associated with an increased genetic susceptibility to T1D. These findings provide a new direction for the pathogenesis of and the drug development for T1D.

Diabetes is a significant global health issue, causing extensive morbidity and mortality, and represents a serious threat to human health. Recently, the bioactive lipid molecule Sphingosine-1-Phosphate has garnered considerable attention in the field of diabetes research. The aim of this study is to comprehensively understand the mechanisms by which Sphingosine-1-Phosphate regulates diabetes. Through comprehensive bibliometric analysis and an in-depth review of relevant studies, we investigated and summarized various mechanisms through which Sphingosine-1-Phosphate acts in prediabetes, type 1 diabetes, type 2 diabetes, and their complications (such as diabetic nephropathy, retinopathy, cardiovascular disease, neuropathy, etc.), including but not limited to regulating lipid metabolism, insulin sensitivity, and inflammatory responses. This scholarly work not only unveils new possibilities for using Sphingosine-1-Phosphate in diabetes treatment but also offers fresh insights and recommendations for future research directions to researchers.

Familial hypercholesterolemia (FH) is a genetic disease, usually with onset during childhood, characterized by elevated blood LDL cholesterol levels and potentially associated with severe cardiovascular complications. Concerning mutated genes in FH, such as LDLR, a small subset of FH patients presents a homozygous genotype, resulting in homozygous FH (HoFH) disease with a generally aggressive phenotype. Besides statins, ezetimibe and PCSK9 inhibitors, lomitapide (an anti-ApoB therapy) was also approved in 2012-2013 as an adjunctive treatment for HoFH. Despite its clinical efficacy, lomitapide administration should be done with caution because of the possible occurrence of side effects, such as hepatosteatosis, increased blood transaminase levels and gastrointestinal symptoms, as well as the possible deleterious interactions with other drugs. In this context, we decided to report the main available evidence on the management and monitoring of HoFH patients treated with lomitapide and to accompany this literature review with a description of our clinical experience with a subset of six HoFH patients. In conclusion, this paper aims to address an important topic for HoFH-related clinical practice that, to our knowledge, is not yet formally regulated by proper national and/or international guidelines.

Background: Current evidence regarding the effects of serum Klotho among patients with metabolic syndrome (MetS) is scarce. This study explored the relationship between serum Klotho levels and the odds of chronic kidney disease (CKD) in middle-aged and older populations with MetS.

Materials and methods: This cross-sectional study analyzed data from 4870 adults aged 40-79 years who participated in the National Health and Nutrition Survey (NHANES) from 2007 to 2016. CKD was identified at urinary albumin to creatinine ratio (UACR) of 30 mg/g or higher and/or an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m². Measurement of serum Klotho concentration was determined via enzyme-linked immunosorbent assay (ELISA) and subsequently divided into four quartiles (Q1-Q4). The NHANES criteria were followed in calculating the sampling weights. Multivariable logistic regression models were employed to assess the correlation between Klotho and CKD, while generalized linear models with cubic spline functions and smooth curve fitting were utilized to detect any nonlinear relationship. Additionally, subgroup analysis and a range of sensitivity analyzes were conducted.

Results: Results showed that a nonlinear L-shaped relationship existed between serum Klotho levels and CKD risk, with the lowest prevalence observed at 9.63-9.94 pg/mL Klotho concentrations. With a two-segment linear regression model, an inflection point of 9.88 pg/mL was noted. Hypertension status was identified as an interaction mediator (P _interaction = 0.006). Sensitivity analysis showed stable results.

Conclusions: A nonlinear L-shaped relationship exists between serum Klotho levels and risks of CKD among middle-aged and older adults with MetS, with the lowest prevalence observed at 9.63 to 9.94 pg/mL Klotho concentrations. Our findings, if replicated, underscore the need to estimate the optimal serum Klotho concentrations and the consequential inverse relationship, thus implying the potential of Klotho as both a serum biomarker and a possible preventive or therapeutic intervention.

Metyrapone is commonly used in the initial management of Cushing's syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone. This single-center retrospective observational study included 15 treatment-naïve patients, 7 of whom had Cushing's disease and 8 had adrenal Cushing's syndrome. Serum cortisol levels were measured hourly from the time of administration of 250 mg of metyrapone up to four hours afterward. Parameters analyzed included the nadir of serum cortisol levels (F_nadir), the difference between basal and nadir serum cortisol levels (_ΔF), the time to nadir, and the characteristics of the patients. As a result, cortisol suppression curves showed significant variability among patients, particularly in the time to nadir. While the median time to nadir was 2 hours, 20% of patients required 4 hours or more, and these responses were not associated with patient characteristics. F_nadir was positively correlated with early-morning serum cortisol levels, serum cortisol levels after low-dose dexamethasone suppression test (LDDST), and urinary free cortisol (UFC) levels, whereas _ΔF was positively correlated with late-night serum cortisol levels, serum cortisol levels after LDDST, and UFC levels. In conclusion, the duration of response to metyrapone appeared unpredictable in patients with Cushing's syndrome and did not correlate with patient characteristics at baseline. Tracking the effect of metyrapone following a single low-dose administration may explain this variability and provide insights for optimizing individual dosing regimens. Further studies are required to validate these findings and guide more personalized treatment adjustments.