Motta GA, Halmenschlager G, Pinto Dornelles Dutra R
… +7 more, Ramos Rhoden C, Maria Vicente Tavares Â, de Castro AL, Sander da Rosa Araujo A, Belló-Klein A, Breitenbach da Silva K, Luis Rhoden E
Horm Metab Res
· 2025 May · PMID 40389212
·
Publisher ↗
Motta GA, Halmenschlager G, Pinto Dornelles Dutra R
… +7 more, Ramos Rhoden C, Maria Vicente Tavares Â, de Castro AL, Sander da Rosa Araujo A, Belló-Klein A, Breitenbach da Silva K, Luis Rhoden E
Horm Metab Res
· 2025 May · PMID 40262765
·
Publisher ↗
Several studies have linked low levels of testosterone with increased symptoms of cardiac disease and cardiovascular mortality; however, the effects of testosterone deficiency on cardiac systolic function and morphology...Several studies have linked low levels of testosterone with increased symptoms of cardiac disease and cardiovascular mortality; however, the effects of testosterone deficiency on cardiac systolic function and morphology are still not completely elucidated. The present study aims to evaluate the influence of testosterone deprivation on cardiac systolic function and morphology. Male Wistar rats were divided into two groups: Sham operation group (Sham): animals underwent sham operation and Orchiectomized group (Orchiec): animals underwent bilateral orchiectomy. The experimental protocol lasted 60 days after the surgery. All animals were weighted and blood samples collected to serum testosterone analysis, determined by chemiluminescence, on first (before orchiectomy) and on 60th days. One day before euthanasia (on the 59th day) echocardiographic parameters were assessed to evaluate left ventricle (LV) systolic function and morphology. Statistical significant difference was set at≤0.05. Orchiec rats presented reduced LV fractional shortening (p=0.032), increased myocardial performance index (MPI) (p=0.043), prolonged mitral valve closure time (p=0.013) and decreased heart rate (p=0.049) when compared to Sham. No statistically significant difference was found in the ejection fraction (p=0.666) between groups. Besides that, heart weight was lower in Orchiec group (p=0.035) when compared to Sham group. Testosterone deprivation reduced cardiac systolic function, changing contraction and relaxation parameters. Testosterone deficiency also changed heart rate and heart weight. The present study demonstrated for the first time that castrated levels of testosterone could alter parameters such as mitral valve closing time and MPI.
Walther R, Singh B, Yin X
… +6 more, Mavberg P, Mücke A, Rodionov R, Babir M, Mayr M, Bornstein SR
Horm Metab Res
· 2025 Nov · PMID 40233791
·
Publisher ↗
Lipoprotein apheresis (LA) is often the last option to adequately reduce lipoproteins in patients with familial hypercholesterolemia and lipoprotein (a) hyperlipidemia. Characterized by mild side effects, it is now the m...Lipoprotein apheresis (LA) is often the last option to adequately reduce lipoproteins in patients with familial hypercholesterolemia and lipoprotein (a) hyperlipidemia. Characterized by mild side effects, it is now the most effective method of preventing major cardiovascular events (CVEs). This benefit is due not only to the lowering of lipoprotein levels, but probably also to many other pleiotropic effects that have been extensively described in the literature. These include the reduction of inflammatory signaling substances, fibrinogen, plasminogen or components of the oxidative stress response. Here, we performed a proteomic analysis of 12 patients treated with therapeutic apheresis using two different pore size filters to quantify the effect on age-related plasma proteins. This study showed that important proteins such as α-2-macroglobulin, apolipoprotein C-III, complement C1s subcomponent, C4b-binding protein alpha chain, CD5 antigen-like and pregnancy zone protein, whose role in numerous aging processes has been well described, were significantly reduced by apheresis treatment. We conclude that therapeutic apheresis may be a promising approach to reduce these age-related proteins and that these treatments may become an essential part of managing cardiovascular risk in an aging population.
Prostate cancer (PCa) ranks among the most prevalent cancers in men, noted for its high mortality rate and unfavorable prognosis. Estrogen-related genes (ERGs) are significantly associated with the progression of PCa. Th...Prostate cancer (PCa) ranks among the most prevalent cancers in men, noted for its high mortality rate and unfavorable prognosis. Estrogen-related genes (ERGs) are significantly associated with the progression of PCa. This investigation aims to comprehensively assess the prognosis of PCa based on ERGs and explore its underlying biological mechanisms. Univariate, multivariate, and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were conducted to identify prognostic signature genes and build a prognostic model. The model's predictive performance was assessed using Receiver Operating Characteristic (ROC) curve analysis. Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were employed to investigate the underlying molecular mechanisms of PCa. Antitumor drugs with high sensitivity were predicted using the CellMiner database and the pRRophitic package. Additionally, miRNAs targeting the identified signature genes were predicted using the miRNet database. This study identified six ERGs as prognostic biomarkers for PCa: POU4F1, BMP2, PGF, GAS1, GNAZ, and FGF11. The findings indicated that individuals in the low-risk category exhibited improved prognostic results. Notably, PCa progression may be closely linked to the cell adhesion molecule pathway and epigenetic regulation. Additionally, hsa-let-7a-5p and hsa-miR-34a-5p were identified as potential therapeutic regulators for PCa treatment. In conclusion, this research offers novel perspectives into the progression of PCa, providing robust scientific support for the development of personalized treatment strategies for PCa patients.
Breast cancer (BC) threatens women's health, and the prognosis is dismal. Folic acid metabolism affects cancer prognosis, but research on folic acid metabolism-related genes (FMRs) in BC is scarce. We used TCGA-BRCA as t...Breast cancer (BC) threatens women's health, and the prognosis is dismal. Folic acid metabolism affects cancer prognosis, but research on folic acid metabolism-related genes (FMRs) in BC is scarce. We used TCGA-BRCA as the training set and GSE21653 as the validation set. Five FMRs (PLAT, SERPINA3, IFNG, SLC19A1, NFKB2) were screened via univariate and LASSO Cox regression analyses, and a prognostic model was built based on multivariate Cox regression analysis. The model showed excellent predictive performance. Differentially expressed genes in high- and low-risk groups were enriched in steroid hormone biosynthesis and neuroactive ligand-receptor interaction pathways. The low-risk group exhibited higher immune cell infiltration and better immunotherapy response. AM-5992 and 5-fluorodeoxyuridine 10mer may be potential BC drugs. This FMR-based model can accurately predict BC prognosis, offering a clinical reference.
The triglyceride glucose (TyG) index is used to assess insulin resistance, which is associated with the occurrence and development of cardiovascular diseases, but the risk of carotid plaques is controversial in Asia. We...The triglyceride glucose (TyG) index is used to assess insulin resistance, which is associated with the occurrence and development of cardiovascular diseases, but the risk of carotid plaques is controversial in Asia. We searched PubMed, Embase, Scopus, and Cochrane Library for articles published up to October 15, 2023, to assess the association and dose-response association of the TyG index with the risk of carotid plaques in Asia. The random effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). A total of 534 articles were retrieved, and eleven studies were selected, involving 145 218 Asian participants. When the TyG index was analyzed as a categorical variable, compared with the low TyG index, the high TyG index increased the risk of carotid plaques (OR=1.38, 95% CI: 1.20, 1.60, p<0.001). As continuous variables were analyzed, similar results were observed (OR=1.33, 95% CI: 1.22, 1.45, p<0.001). Meanwhile, dose-response analysis showed that the risk of carotid plaque increased by 1.03 times for every unit increase in the TyG index (RR=1.03, 95% CI: 1.02, 1.03, p<0.001). Our meta-analysis indicates an association between the TyG index and the risk of carotid plaques in Asia. Further studies are required to substantiate these findings.
We aimed to examine if serum lipoprotein(a) [Lp(a)] values could be used to predict the risk of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). English-language observational studies available as full-texts...We aimed to examine if serum lipoprotein(a) [Lp(a)] values could be used to predict the risk of diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM). English-language observational studies available as full-texts on PubMed, Embase, Scopus, and Web of Science databases up to 28th November 2024 were included in the review. Studies were to assess the association between Lp(a) and DN and report adjusted effect size. Random-effects meta-analysis was conducted. Five cross-sectional, two case-control, and eight studies prospective cohort were included. Six studies used Lp(a) as a continuous variable while eight used it as a categorical variable. Two studies used Lp(a) as both. Meta-analysis showed that an incremental increase in Lp(a) was associated with a small increase in the risk of DN (OR: 1.03 95% CI: 1.01, 1.04 I=86%). Meta-analysis also showed that high levels of Lp(a) were associated with a significant increase in the risk of DN (OR: 1.64 95% CI: 1.24, 2.17 I=67%). Subgroup analysis based on study design, location, sample size, T2DM duration, baseline HbA1c, and definition of DN yielded mixed results. Lp(a) could be a potential marker for DN in T2DM. Further investigations may provide better evidence.
Cushing's syndrome (CS) is associated with high morbidity and mortality triggered by increased risk for cardiovascular events. Nevertheless, no screening tool to predict the individual risk for these events in patients w...Cushing's syndrome (CS) is associated with high morbidity and mortality triggered by increased risk for cardiovascular events. Nevertheless, no screening tool to predict the individual risk for these events in patients with Cushing's syndrome has been established. Nonenhanced electron-beam computed tomography scans with calculation of the Coronary Artery Calcium (CAC) score may offer a non-invasive method. Hence, we evaluated the diagnostic accuracy of Agatston score to predict the risk of a cardiac event in patients with Cushing's syndrome. Single center prospective study of 34 patients with endogenous CS Multidetector computer tomography and calculation of CAC score was performed at diagnosis of CS. Prevalence of cardiovascular events was documented with median follow-up over 5 years and results were compared with data from the Heinz Nixdorf Recall (HNR) Study. In addition, correlations of CAC score with parameters of cortisol excess were evaluated. CAC score was significantly higher in CS patients with a cardiovascular event than in patients without an event (117 vs. 90; p=<0.01). An odds ratio of 31.7 (p=0.03, 95% CI: 1.3-773.0) for a cardiovascular event could be shown in Cushing's syndrome patients with a CAC score>75th risk factor-specific reference percentile, while the odds ratio in the HNR study was 4.5 (p<0.01, 95% CI: 3.0-6.9). No correlation between the degree of cortisol excess and CAC score was evident. The CAC score>75th risk factor-specific reference percentile could offer a useful screening tool to precise the cardiovascular risk in patients with Cushing's syndrome.
Controversial results exist regarding the influence of exemestane on serum lipids in women affected with breast cancer. Since CVD remains the predominate cause of demise in women with breast cancer and considering the lo...Controversial results exist regarding the influence of exemestane on serum lipids in women affected with breast cancer. Since CVD remains the predominate cause of demise in women with breast cancer and considering the long-term use of exemestane in women with breast cancer, this meta-analysis holds significant value. Hence, we carried out the current meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of exemestane treatment on lipid parameters in women with breast cancer. PubMed/Medline, Web of Science, EMBASE, and Scopus databases were explored for articles published from inception till December 3, 2024. A random effect analysis was employed for result generation as weighted mean differences (WMD) with 95% confidence intervals (CI). Six eligible and relevant RCTs were incorporated in this meta-analysis. The comprehensive findings from random effect analysis indicated a reduction in TC (WMD: -8.13 mg/dl, 95% CI: -14.48 to -1.79, p=0.012), HDL-C (WMD: -6.60 mg/dl; 95% CI: -8.17 to -5.01, p<0.001) and an increase in LDL-C (WMD: 4.66 mg/dl; 95% CI: 0.26 to 9.06, p=0.038) after exemestane intervention. Additionally, a noteworthy decline in the levels of TG was noted in studies lasting less than 12 months duration (WMD: -16.18 mg/dl; 95% CI: -25.99 to -6.37, p=0.001). Exemestane influences the lipid parameters in women with breast cancer. It elevates LDL-C levels while decreasing TC, TG, and HDL-C concentrations.
Horm Metab Res
· 2025 May · PMID 40073909
·
Publisher ↗
The study explores the vital role of gut microbiota in regulating neurotransmitters and its subsequent effects on brain function and mental health. It aims to unravel the mechanisms by which microbial metabolites influen...The study explores the vital role of gut microbiota in regulating neurotransmitters and its subsequent effects on brain function and mental health. It aims to unravel the mechanisms by which microbial metabolites influence neurotransmitter synthesis and signaling. The ultimate goal is to identify potential therapeutic strategies targeting gut microbiota for the management and treatment of neurological disorders, such as depression, autism spectrum disorder (ASD), anxiety, and Parkinson's disease. The review synthesizes current research on the gut-brain axis, focusing on the influence of gut microbial metabolites on key neurotransmitters, including dopamine, serotonin, and gamma-aminobutyric acid (GABA). It incorporates a multidisciplinary approach, linking microbiology, neurobiology, and clinical research. Each section presents an in-depth review of scientific studies, clinical trials, and emerging therapeutic strategies. The findings highlight the intricate interplay between gut microbiota and the central nervous system. Gut microbes significantly impact the synthesis and signaling of crucial neurotransmitters, which play a pivotal role in neurological health. Evidence supports the hypothesis that modulating gut microbiota can alter neurotransmitter output and alleviate symptoms associated with neurological disorders. Notable therapeutic potentials include microbiota-targeted interventions for managing depression, ASD, anxiety, and Parkinson's disease. This comprehensive analysis underscores the critical connection between gut microbiota and neurological health. By bridging gaps between microbiology, neurobiology, and clinical practice, the study opens avenues for innovative therapeutic approaches. It provides a valuable resource for researchers, clinicians, and students, emphasizing the need for continued investigation into gut microbiota's role in neurological disorders and its therapeutic potential.
Song Y, Wang X, Pan J
… +6 more, Wang T, Wu Y, Pang Q, Zhang Y, Wang Y, Yang J
Horm Metab Res
· 2025 Mar · PMID 40049227
·
Publisher ↗
The relationship between serum circCSPP1, circNIPSNAP3A, or circRFX8 and the occurrence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be fully elucidated. A total of 494 participants were divided i...The relationship between serum circCSPP1, circNIPSNAP3A, or circRFX8 and the occurrence and severity of non-alcoholic fatty liver disease (NAFLD) has yet to be fully elucidated. A total of 494 participants were divided into NAFLD and control groups, and clinical data, including demographic, physiological and biochemical parameters, were collected. Serum levels of circCSPP1, circNIPSNAP3A, and circRFX8 were measured using quantitative real-time PCR, and the severity of NAFLD was assessed by ultrasonography and quantitative computed tomography. The NAFLD group exhibited significantly higher levels of serum circCSPP1 compared to the control group (p=0.04). CircCSPP1 is significantly and independently associated with NAFLD. Participants with high serum circCSPP1 levels (>66th percentile) had a greater prevalence of mild and advanced NAFLD, as well as higher triglyceride levels, compared to those with low circCSPP1 levels (<33rd percentile) (p<0.05 for all). No significant correlations were observed between circNIPSNAP3A or circRFX8 and the occurrence or severity of NAFLD. These findings suggest that serum circCSPP1 is associated with the occurrence and severity of NAFLD, potentially mediated by hypertriglyceridemia.
Horm Metab Res
· 2025 Mar · PMID 40049226
·
Publisher ↗
We conducted this meta-analysis of randomized controlled trials (RCTs) with the aim of assessing the effect of 17β-estradiol plus norethisterone acetate on estradiol, testosterone, IGF-1, and SHBG in postmenopausal women...We conducted this meta-analysis of randomized controlled trials (RCTs) with the aim of assessing the effect of 17β-estradiol plus norethisterone acetate on estradiol, testosterone, IGF-1, and SHBG in postmenopausal women. To our knowledge, this is the first meta-analysis of RCTs to assess these effects. Databases including the Web of Science, PubMed/Medline, Scopus, and EMBASE were searched to identify publications up to July 2024. The results were reported as weighted mean difference (WMD) and 95% confidence intervals (CI) generated by using a random-effects model according to the Der-Simonian-Laird model. Fifteen publications were included in current meta-analysis. Overall results from the random-effects model manifested a significant increase in estradiol (WMD: 55.30 pg/ml, 95% CI: 39.32, 7128, p<0.001) and SHBG (WMD: 18.48 nmol/l, 95% CI: 3.64, 33.33, p=0.015) levels, a significant decrease in FSH (WMD: -41.55 IU/l, 95% CI: -53.17, -29.92, p<0.001) and testosterone (WMD: -4.29 ng/dl, 95% CI: -5.38, -3.21, p=0.000) levels, and a non-significant decrease in IGF-1 levels (WMD: -9.70 μg/l, 95% CI: -34.21, 14.80, p=0.438) after treatment with 17β-estradiol plus norethisterone acetate on postmenopausal women. In conclusion, 17β-estradiol plus norethisterone acetate in postmenopausal women increases estradiol and SHBG concentrations and decreases FSH and testosterone concentrations, with no statistically significant effect on IGF-1.
Uysal S, Sulu C, Muradov I
… +12 more, Sahin S, Gul N, Soyluk Selcukbiricik O, Kubat Uzum A, Unal Kocabas G, Sarer Yurekli B, Hacioglu A, Karaca Z, Barburoglu M, Korkmazer B, Kizilkilic O, Kadioglu P
Horm Metab Res
· 2025 Mar · PMID 40049225
·
Publisher ↗
We aimed to characterize the clinical features and remission rates of patients with Cushing's Disease (CD) without magnetic resonance imaging (MRI) detectable pituitary adenoma compared to CD patients with MRI-detectable...We aimed to characterize the clinical features and remission rates of patients with Cushing's Disease (CD) without magnetic resonance imaging (MRI) detectable pituitary adenoma compared to CD patients with MRI-detectable pituitary adenoma.All patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) without MRI-detectable pituitary adenoma underwent high-dose dexamethasone suppression test, corticotropin-releasing hormone stimulation test, and/or bilateral inferior petrosal sinus sampling (BIPSS). The diagnosis of CD in patients without MRI-detectable adenoma was confirmed when the results of dynamic testing and sampling concordantly indicated ACTH-producing adenoma.These patients were included in MRI-undetectable group. Patients with ACTH-dependent CS had pituitary adenoma≥6 mm and those with pituitary adenoma<6 mm but BIPSS findings indicative of CD were included in MRI-detectable adenoma group. The study included 60 patients without MRI-detectable adenoma and 74 patients with MRI-detectable adenoma. At presentation, patients without MRI-detectable adenoma were older [47 years (30.25-58) vs. 40.5 years (29-49), p=0.036]. Hypertension (65% vs. 47.3%), diabetes mellitus (58.3% vs. 39.2%), and cardiovascular disease (13.3% vs. 2.7%) were more common in patients without MRI-detectable adenoma (p=0.040, p=0.027, p=0.020; respectively). The transsphenoidal surgery as initial treatment was higher in the patients with MRI-detectable adenoma group (97.3% vs. 80%, p=0.001). Third-month remission (60.4% vs. 63.8%, p=0.700) after surgery, and remission rates in the last visit (65.3% vs. 79.7%, p=0.077) were similar between the two groups. Inconclusion, the absence of an MRI-detectable adenoma underscores the necessity for comprehensive management.
Grindskar C, Andreassen M, Feltoft CL
… +6 more, Eldrup E, Ugleholdt RK, Jørgensen NR, Mørup S, Voss N, Krogh J
Horm Metab Res
· 2025 Mar · PMID 40049224
·
Publisher ↗
A proportion of patients with primary aldosteronism (PA) have a paradox increasein plasma-Aldosterone (P-Aldosterone) concentration (PAC) during the Captopril Challenge Test (CCT). This study aimed to investigate if a pa...A proportion of patients with primary aldosteronism (PA) have a paradox increasein plasma-Aldosterone (P-Aldosterone) concentration (PAC) during the Captopril Challenge Test (CCT). This study aimed to investigate if a paradoxical rise in PAC during CCT, was associated with clinical characteristics or outcomes inpatients with PA. We hypothesized that a paradoxical response to CCT is ameasure of disease severity, reflected by a higher baseline aldosterone/renin-ratio (ARR). A retrospective study of patients with PA,confirmed by CCT, who were referred for adrenal venous sampling between May 2011and August 2021 were eligible. Patients with an increase in PAC>10% frombaseline during CCT were classified as cases, while patients with 10 to 30% suppression were classified as controls. Of 167 patients referred, 116 (70%) were eligible for this study. Based on the CCT, 61/116 (53%) were classified as cases while 55/116 (47%) were classified as controls. The baseline ARR was 122 pmol/mIU (IQR: 65 to 223) for cases and 137 pmol/mIU (IQR: 65 to 223) for controls (p=0.66). Cases had lower systolic blood pressure (p=0.02) and higherpotassium levels (p=0.05) compared to controls. Complete clinical remission was obtained in 22 of 31 (71%) of the cases and 13 of 27 (48%) of the controls (p=0.03) after adrenalectomy. In conclusion, a paradoxical response to CCT wasnot associated with ARR. By contrast, patients with a paradoxical response did have lower systolic blood pressure, higher potassium levels, and markedly higher odds of full clinical remission after adrenalectomy.
Horm Metab Res
· 2025 Mar · PMID 40049223
·
Publisher ↗
Heightened aldosterone levels are associated with increased risk of renal sequelae, cardiovascular morbidity and mortality. Historically, primary aldosteronism is linked to hypertension. However, growing evidence reveals...Heightened aldosterone levels are associated with increased risk of renal sequelae, cardiovascular morbidity and mortality. Historically, primary aldosteronism is linked to hypertension. However, growing evidence reveals its presence even in normotensive individuals. This review consolidates data from diverse sources, delves into clinical studies of this underexplored condition, discusses the potential mechanisms, and provides a comprehensive and an up-to-date overview of the current state of knowledge. It highlights the evidence and understanding of normotensive primary aldosteronism, summarizes findings, and identifies opportunities for future research in this area. By addressing the clinical evidence, risk of hypertension development and possible mechanisms involved, this review aims to advance the understanding of this distinct form of primary aldosteronism and inspire further research in this emerging field.
Congenital adrenal hyperplasia (CAH) is a rare disorder with autosomal recessive inheritance; it was historically known as adrenogenital syndrome. Patients with virilizing forms of CAH and a 46,XX karyotype present with...Congenital adrenal hyperplasia (CAH) is a rare disorder with autosomal recessive inheritance; it was historically known as adrenogenital syndrome. Patients with virilizing forms of CAH and a 46,XX karyotype present with varied degrees of hyperandrogenism due to different genetic defects in the adrenal steroidogenesis pathway. This comprehensive review describes a simplified diagnostic approach for patients with atypical genitalia and 46, XX DSD. It highlights the importance of a detailed history and clinical examination, with specific pointers toward the etiological diagnosis. There is a need for utilizing standardized liquid chromatography/tandem mass spectrometry (LC-MS/MS) assays to accurately diagnose these disorders of steroidogenesis. Choosing appropriate molecular testing methods has significant implications for establishing the diagnosis and providing genetic counseling.
Shift work causes a disruption between the circadian system and the external light-dark cycle, but also a misalignment between various levels of the circadian system. There is no information on patients with adrenal insu...Shift work causes a disruption between the circadian system and the external light-dark cycle, but also a misalignment between various levels of the circadian system. There is no information on patients with adrenal insufficiency (AI) who are working shifts. The objective of the study was to analyze the hormone replacement therapy with hydrocortisone (HC) and the adaptation scheme in patients with AI on shifts. Patients working on shifts (n=15) from two German endocrine centers received a questionnaire regarding their therapy scheme, dose adaptations, working shifts, dose adaptations during working shifts, and occurrence of adrenal crisis. We observed that 20% of patients stated that they experience difficulties taking glucocorticoid replacement on time, 40% of patients reported these difficulties to occur only occasionally. Consequently, nearly half of the patients had forgotten to take their replacement therapy at some point. More than 50% of patients reported an adrenal crisis during the last two years. The timely adaptation of HC or of modified-release HC during shifts was very inhomogeneous. In conclusion, the adaptation schemes for HC dosing during shift work are currently not evidence-based but opinion-driven. Our findings highlight the need for further investigations of shift workers with AI.
Potassium channel-related genes (PCRGs) play an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to develop a new prognostic model associated with PCRGs that...Potassium channel-related genes (PCRGs) play an important role in hepatocellular carcinoma (HCC) development, recurrence, and immunotherapy tolerance. We aimed to develop a new prognostic model associated with PCRGs that can be used for prognosis and immunotherapy prediction in HCC patients. The transcriptional profiles and clinical data related to HCC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed PCRGs were identified using the "edgeR" package. Prognostic model associated with PCRGs were constructed using univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariate regression analysis. The prognostic value of the model was evaluated through Kaplan-Meier (K-M) survival analysis and receiver operating characteristic (ROC) curves. Additionally, the tumor immune microenvironment was assessed using single sample gene set enrichment analysis (ssGSEA) and the CIBERSORT algorithm. Finally, potential drugs targeting signature genes were predicted. We successfully constructed a prognostic signature based on PCRGs, and the prognostic results were superior in the low-risk group. The nomogram demonstrated satisfactory predictive performance in estimating overall survival (OS) in HCC patients. The results of immune cell infiltration and predictions of immunotherapy response revealed that the low-risk group exhibited a more favorable response to immunotherapy. In addition, signature gene expression was significantly correlated with antitumor drug sensitivity. In conclusion, the characteristics of PCRGs serve as valuable tools for accurately assessing the prognosis and tumor microenvironment of HCC patients. Additionally, PCRGs markers can facilitate precision therapy in HCC management.
Liu J, Lu X, Zhu X
… +5 more, Song J, Zheng X, Xu C, Tong H, Wang M
Horm Metab Res
· 2025 Feb · PMID 39929172
·
Publisher ↗
Blood urea nitrogen (BUN) is a key metric when evaluating the renal function of a given patient. Individuals with chronic kidney disease also often present with abnormal thyroid functionality. The specific association be...Blood urea nitrogen (BUN) is a key metric when evaluating the renal function of a given patient. Individuals with chronic kidney disease also often present with abnormal thyroid functionality. The specific association between BUN and thyroid function, however, is not well understood. This study was thus developed to explore how BUN levels within the normal range are related to thyroid activity among adults in the USA. The National Health and Nutrition Examination Survey (NHANES) dataset was leveraged for these analyses. Linear regression and smoothed curve fitting approaches were employed to examine the association between BUN levels and measures of thyroid function, with appropriate weighted and subgroup analyses. The 2007-2012 NHANEs cycles included 6231 eligible adults with BUN levels from 2.5-8.0 mmol/l. Under adjusted models, a higher BUN level was associated with reductions in FT3 (β=-0.01; p=0.047), TT3 (β=-1.08; p=0.003), and TT4 (β=-0.10; p=0.003) levels. In subgroup analyses, BUN levels were respectively found to be negatively correlated with FT3 and TT4 levels in subjects who were inactive and active. These findings are consistent with reduced FT3, TT4, and TT4 levels being correlated with higher BUN levels within the normal range among American adults. In non-physically active subjects, FT3 levels were more closely related to increasing BUN levels, whereas TT4 levels were more closely related to BUN levels among physically active subjects. However, additional research will be vital to clarify the mechanisms that underlie these results.