Hormone and Metabolic Research最新文献

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms. Targeting NETs in the elderly as an anti-aging therapy seems to be a very attractive therapeutic approach. Therapeutic apheresis with a specific filter to remove NETs could be a promising strategy worth considering.

The aim of our study is to explore the relationship between remnant cholesterol (RC) levels and visceral adipose tissue (VAT) in the US adult population. This cross-sectional study utilized data from 5301 participants aged 20 to 59 years gathered by the National Health and Nutrition Examination Survey (NHANES). RC was determined by deducting both high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) from total cholesterol (TC), and VAT was measured using dual-energy X-ray absorptiometry. Visceral obesity is defined as a VAT area ≥ 100 cm². With increasing quartiles of RC levels, the prevalence of visceral obesity rises (16.51% vs. 36.11% vs. 55.66% vs. 74.48%, p<0.001). After adjusting for confounders, RC levels positively correlate with visceral obesity risk (OR=1.039, 95% CI 1.031-1.048, p<0.001). Additionally, individuals with low LDL-c/high RC and those with high LDL-c/low RC showed 2.908-fold (95% CI 1.995-4.241) and 1.310-fold (95% CI 1.022-1.680) higher risk of visceral obesity, respectively, compared to those with low LDL-c/low RC. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) show RC's superior predictive ability over other lipid markers. Subgroup analysis showed that the relationship between RC and visceral obesity was more ronounced in those with cardiovascular disease. Smooth curve fitting indicated a nonlinear relationship between RC levels and VAT area. Our study highlights that elevated levels of RC are associated with adverse accumulation of VAT. However, the causal relationship between RC and visceral obesity requires additional investigation.

The aim of the study was to investigate whether the administration of gonadotropins to mimic the physiological development of infants with congenital hypogonadotropic hypogonadism (CHH) after birth can facilitate testicular descent, penile growth, and ultimately preserve fertility. This study included eight infants with CHH who received a gonadotropin-releasing hormone (GnRH) pump or human chorionic gonadotropin (HCG) combined with human menopausal gonadotropin (HMG) therapy at Beijing Children's Hospital from August 2018 to March 2023. The age of the infants ranged from 6 months to 2 years. 2. For literature review, a search was conducted in the PubMed database using the keywords "congenital hypogonadotropic hypogonadism," "infants," and "mini-puberty" up until June 2023. After 1-3 months of treatment, significant increases were observed in PL and TV. The testes descended from the inguinal region to the scrotum. Serum T and INH-B levels increased from being undetectable to 737.1±409.5 ng/dl and from 47.88±23.03 to 168.94±59.34 pg/ml, respectively. In a comparative literature review of 22 infants with CHH, the age at treatment initiation ranged from 0.5 to 7.9 months. Treatment involved various dosages and durations, ranging from 2 to 6 months of subcutaneous injections of LH and FSH. Both therapies successfully improved PL, TV, and testicular descent; reduced the need for surgery; and were safe. This is the first report of the use of a GnRH pump for the treatment of infant CHH.

To predict patient survival prognosis, we aimed to establish a novel set of gene features associated with hypoxia and apoptosis. RNA-seq and clinical data of LUAD were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, while hypoxia and apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB). A 13-gene-prognostic model incorporating hypoxia and apoptosis genes was developed using univariate/multivariate Cox regression, Nonnegative Matrix Factorization (NMF) clustering, and LASSO regression. Patients were divided into high-risk (HR) and low-risk (LR) groups according to the median risk score. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed distinct biological processes between HR and LR groups, including hormone regulation and lipid metabolism pathways. Single sample gene set enrichment analysis (ssGSEA) indicated elevated cell infiltration levels of Neutrophils and T_helper_cells in the LR group, while NK cells and Th1cells were higher in the HR group. Immunophenoscore (IPS) and tumor immune dysfunction and exclusion (TIDE) analyses suggested potential benefits of immunotherapy for LR group patients. In conclusion, this prognostic feature integrating hypoxia- and apoptosis-related genes offers insights into predicting survival, immune status, and treatment response in LUAD patients, paving the way for personalized treatment strategies.

Diabetic nephropathy represents a predominant etiology of end-stage renal disease (ESRD) on a global scale, significantly impacting the morbidity and mortality rates of individuals with diabetes. The primary objective of this analysis is to furnish a comprehensive examination of the etiology, fundamental mechanisms, and treatment modalities for DN. The development of DN stems from a multitude of factors, encompassing a intricate interplay involving metabolic irregularities induced by hyperglycemia, alterations in hemodynamics, inflammatory responses, oxidative stress, and genetic susceptibility. Principal mechanisms encompass the generation of advanced glycation end products (AGEs), activation of protein kinase C (PKC), and overexpression of the renin-angiotensin-aldosterone system (RAAS). These processes precipitate glomerular hyperfiltration, hypertrophy, and eventually, fibrosis and scarring of the renal parenchyma. Initially, hyperglycemia triggers mesangial proliferation and thickening of the glomerular basement membrane in the incipient stages of DN, subsequently leading to progressive glomerular sclerosis and tubulointerstitial fibrosis. Inflammatory cascades, notably involving cytokines like TGF-β and NF-κB, play pivotal roles in the advancement of DN by fostering the accumulation of extracellular matrix and renal fibrosis. Inflammation pathways, particularly those involving cytokines like TGF-β and NF-κB, play essential roles in diabetic nephropathy progression by stimulating extracellular matrix accumulation and renal fibrosis. The presence of oxidative stress, worsened by dysfunctional mitochondria, contributes further to renal injury via lipid peroxidation and DNA damage. Current therapeutic approaches for diabetic nephropathy concentrate on optimizing glycemic control, controlling hypertension, and suppressing the renin-angiotensin-aldosterone system. Among antihypertensive medications, ACE inhibitors and angiotensin II receptor blockers are crucial for decelerating disease advancement.

The high cardiometabolic risk associated with polycystic ovary syndrome (PCOS) may be linked to central fat accumulation. This study compared fat distribution between women with PCOS and controls matched by body mass index. It also sought to determine if insulin resistance (IR), androgens, or inflammatory markers correlate with body composition parameters in PCOS patients. In total, thirty-five women with PCOS and 37 controls, aged 18-40 years, were included. Hormonal/metabolic profiles, inflammatory biomarkers [tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6)], anthropometry (waist circumference, waist-to-hip ratio, lipid accumulation product [LAP], visceral adiposity index [VAI]), and body composition assessed through dual-energy X-ray absorptiometry were assessed. The PCOS group exhibited significantly higher androgen levels and markers of IR. However, levels of TNF-α and IL-6 were comparable between the groups. Despite having similar total body fat mass (FM), the PCOS group had excessive central fat, including increased truncal FM and visceral adipose tissue (VAT). In PCOS, androgens were not associated with body fat or its distribution. IL-6 was positively correlated with total and truncal FM, while insulinemia and the homeostatic model assessment for IR were positively associated with VAT, as well as with total and truncal FM. Although anthropometric measurements and indices were positively associated with DXA-derived central FM parameters, our data suggest that LAP is the most effective tool for assessing central fat deposition and metabolic dysfunction in the PCOS patients studied herein. Furthermore, in this population, IR, rather than androgens or proinflammatory cytokines, is more closely associated with abdominal obesity.

Gestational diabetes mellitus (GDM) is a common metabolic disorder in pregnancy and leads to serious harm to the mother and the fetus. A variety of lncRNAs play a key role in GDM. This meta-analysis was performed to explore the potential value of lncRNAs in GDM diagnosis. Articles correlated with lncRNA and GDM were screened from Embase, Medline, EBSCO, PubMed, Chinese National Knowledge Infrastructure, and WanFang databases. Summary receiver operator characteristic (SROC) was performed to evaluate the pooled area under curve (AUC). Forest plot was conducted to calculate the sensitivity, specificity, diagnostic likelihood ratio (LR), diagnostic score, and diagnostic odds ratio (DOR). Deeks' funnel plot was utilized to evaluate the publication bias. Eleven articles containing 12 tests (1060 GDM patients and 1066 controls) were included in this meta-analysis. AUC (0.89, 95%CI=0.86-0.92), sensitivity (0.84, 95%CI=0.80-0.87), and specificity (0.81, 95%CI=0.77-0.85)of the SROC curve showed a high diagnostic value of lncRNA for GDM. Positive LR (PLR 4.40, 95%CI=3.45-5.60) and negative LR (NLR 0.20, 95%CI=0.15-0.26) results indicated that the diagnosis of lncRNA for GDM had low clinical utility. Diagnostic score (3.09, 95%CI=2.62-3.57) and DOR (22.04, 95%CI=13.68-35.51) results suggested lncRNAs have good discriminative effect on GDM. Heterogeneity was significantly higher, but not induced by the subgroups. LncRNAs had high diagnostic value and good discriminative effect for GDM, but the clinical utility was not high. This meta-analysis study offers a potential target for GDM diagnosis.

Congenital adrenal hyperplasia (CAH) manifests as an autosomal recessive disorder characterized by defects in the enzymes responsible for steroid synthesis. This work aims to perform metabolic profiling of patients with CAH, screen key differential metabolites compared to the control group, and discover the associated metabolic pathways implicated in CAH. Serum samples obtained from 32 pediatric male patients with CAH and 31 healthy control group candidates were subjected to analysis using non-targeted metabolomics strategy using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 278 differential metabolites were identified and annotated in KEGG. Operating characteristic curves (ROC) measurement exhibited 9 metabolites exhibiting high efficacy in differential diagnosis, as evidenced by an area under ROC curve (AUC) exceeding 0.85. Pathway analysis uncovered notable disruptions in steroid hormone biosynthesis (p <0.0001), purine metabolism and irregularities in lipid metabolism and amino acid metabolism, including tyrosine and alanine, in CAH patients. These findings demonstrate that metabolic pathways of purine, amino acid and lipid metabolism, apart from steroid hormone biosynthesis, may be disrupted and associated with CAH. This study helps provide insight into the metabolic profile of CAH patients and offers a new perspective for monitoring and administering follow-up care to CAH patients.

This study aimed to assess the efficacy and safety of a combined recombinant human parathyroid hormone 1-34 [rhPTH (1-34)] and vitamin K2 therapy versus vitamin K2 alone in the treatment of postmenopausal osteoporosis. A total of 77 postmenopausal osteoporosis patients were randomly divided into two groups. Patients in one group received vitamin K2 alone, while patients in the other group received a combination of rhPTH (1-34) and vitamin K2. Bone mineral density (BMD), electrolyte levels, pain scores, bone metabolism levels, and adverse drug reactions were compared pre- and post-treatment. Both two treatments improved BMD, blood calcium concentrations, pain scores, and increased osteocalcin and osteoprotegerin levels. Notably, the combined rhPTH (1-34) and vitamin K2 treatment demonstrated superior efficacy in improving BMD and bone metabolism markers. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups, indicating the safety of the combined treatment. In summary, the combined therapy of rhPTH (1-34) and vitamin K2 exhibited more potent efficacy in the treatment of postmenopausal osteoporosis, more effectively enhancing BMD and bone metabolism markers than vitamin K2 alone, without a significant increase in adverse reactions.