Neuroendocrinology最新文献

{"title":"Survivin as a Therapeutic Target for Neuroendocrine Neoplasms.","authors":"Yuma Hane, Takahiro Tsuchikawa, Toru Nakamura, Kanako C Hatanaka, Katsunori Sasaki, Noriko Kawai, Shintaro Takeuchi, Kimitaka Tanaka, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Toshiaki Shichinohe, Yutaka Hatanaka, Yoshihiko Hirohshi, Toshihiko Torigoe, Satoshi Hirano","doi":"10.1159/000543270","DOIUrl":"10.1159/000543270","url":null,"abstract":"<p><strong>Introduction: </strong>Although neuroendocrine neoplasms (NENs) have a good prognosis, distant metastasis remains a crucial prognostic factor. Survivin, a tumor-associated antigen, is overexpressed in several solid tumors, indicating poor prognosis. We aimed to evaluate the clinical significance and role of survivin as a therapeutic target for NEN.</p><p><strong>Methods: </strong>We assessed the cytotoxicity of Survivin-2B (a splicing variant of survivin) 80-88 specific CTL clone with HLA-A24 restriction against NEN cell lines using intracellular staining for interferon-γ and assessed the frequency of Survivin-2B 80-88 CTL precursors in nine HLA-A24-positive patients with NEN using tetramer staining and compared it before and after resection. Finally, we evaluated the association between survivin expression and prognosis in 74 patients with pancreatic NEN using immunohistochemistry.</p><p><strong>Results: </strong>Survivin-2B 80-88 CTL clone showed high cytotoxicity against QGP-1 (HLA-A24 positive) cocultured with the Survivin-2B 80-88 peptide. Only three patients were positive for tetramer staining; two showed decreased Survivin-2B 80-88 CTL precursor following resection. The nuclear survivin-low group had a significantly better prognosis than the nuclear survivin-high group.</p><p><strong>Conclusion: </strong>Survivin in NEN is antigenic and may induce cellular immunity via the Survivin-2B CTL precursor. Survivin-targeting immunotherapy can be used to treat NEN with highly expressed Survivin-2B.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-13"},"PeriodicalIF":3.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142922375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Novel SSTR3 Full Agonist ITF2984 Shows Antitumor Properties against Pancreatic Neuroendocrine Tumors.","authors":"Margarita Bistika, Alessandro Marangelo, Francesco Ascione, Nicole Valentini, Francesco Fedeli, Jörg Schrader, Daniela Modena, Christian Steinkühler, Natalia S Pellegata","doi":"10.1159/000543136","DOIUrl":"10.1159/000543136","url":null,"abstract":"<p><strong>Background: </strong>Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide) or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptom control and antiproliferative effects in subsets of NET patients and this was associated with the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2, and SSTR3 and thus should respond to agonists targeting SSTR3.</p><p><strong>Summary: </strong>We evaluated the efficacy of ITF2984, a novel multireceptor agonist with specificity for SSTR3, against Pan-NET cells representative of well-differentiated, functioning tumors, and expressing high levels of SSTR3. The effect of ITF2984 on cell proliferation/viability and on its ability to promote apoptosis and suppress hormone secretion was evaluated in 2D and 3D organotypic culture systems. Pasireotide was tested in parallel for comparative purposes.</p><p><strong>Key message: </strong>We found that ITF2984 is as effective as pasireotide at inhibiting both proliferation/viability and hormone secretion, as well as at inducing apoptosis of Pan-NET cells grown as both 2D monolayers and 3D spheroids. High-dose ITF2984 elicits structural alterations in Pan-NET 3D spheroids compatible with cell death more effectively than pasireotide. Altogether, ITF2984 may represent a useful alternative to pasireotide for the medical treatment of Pan-NETs and other tumors with elevated SSTR3 expression.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Levels of Organic Acids Associated with the Gut Microbiome Display Significant Alterations in Neuroendocrine Tumor Patients.","authors":"Silje Udjus Johansen, Rasmus Goll, Anna Nordborg, Kai Vernstad, Einar Paul Helge Jensen, Jon Ragnar Florholmen, Terkel Hansen","doi":"10.1159/000543247","DOIUrl":"10.1159/000543247","url":null,"abstract":"<p><strong>Introduction: </strong>The gut microbiome, allegedly involved in both healthy homeostasis and development of disease, is found to be associated with several types of cancer. Short-chain fatty acids (SCFAs), important metabolites derived from the gut microbiota, are described to carry both protective and promoting features in cancer development. Limited research exists on neuroendocrine tumors (NETs) and their association with microbiota-derived SCFAs. The aim of this study was to investigate possible alterations in plasma SCFAs/organic acids in NET patients compared to healthy controls.</p><p><strong>Methods: </strong>We quantified 11 organic acids, including SCFAs, in plasma from 109 NET patients (49 curatively operated patients and 60 patients with distant metastasis) as well as 20 healthy controls. Acids were quantified using liquid chromatography tandem mass spectrometry.</p><p><strong>Results: </strong>We found that levels of 3OH-propionic acid, 3OH-butyric acid, lactic acid, formic acid, acetic acid, glyoxylic acid, and glycolic acid were significantly altered in NET patients with metastatic disease, as well as curatively operated NET patients, compared to healthy controls (p < 0.05). In addition, a trend displaying increased acid level alterations from healthy controls in curatively operated patients with future recurrence, compared to patients with no documented recurrent disease, was detected.</p><p><strong>Conclusion: </strong>Our results demonstrating significantly altered levels of multiple organic acids in NET patients represents a novel finding implicating further research on their role in NET pathophysiology.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Identification of Sensory Neuropeptides Calcitonin Gene-Related Peptide, Substance P, and Pituitary Adenylate Cyclase-Activating Polypeptide in Efferent Vestibular Nucleus Neurons.","authors":"David Lorincz, Hannah Rose Drury, Rebecca Lim, Alan Martin Brichta","doi":"10.1159/000542984","DOIUrl":"10.1159/000542984","url":null,"abstract":"<p><strong>Introduction: </strong>The efferent vestibular system (EVS) originates in brainstem efferent vestibular nuclei (EVN) and modifies afferent vestibular signals at their source, in peripheral vestibular organs. Recent evidence suggests that EVS is also involved in the development of motion sickness symptoms, including vertigo and nausea, but the underlying mechanism is unknown. One possible link between EVN and motion sickness symptoms is through the neuropeptide calcitonin gene-related peptide (CGRP). CGRP often co-exists with substance P and pituitary adenylate cyclase-activating polypeptide (PACAP), two neuropeptides with similar vasodilatory effects. Collectively, these sensory neuropeptides have been associated with vestibular migraine pathophysiology and motion sickness. While CGRP and the fast EVS neurotransmitter, acetylcholine (ACh), have previously been identified in EVN neurons and their peripheral terminals, the presence of substance P and PACAP in the EVN has not yet been described.</p><p><strong>Methods: </strong>We used fluorescent immunohistochemistry combined with confocal microscopy to examine the distribution of these three neuropeptides in the mouse EVN. In transgenic choline acetyltransferase (ChAT)-gCaMP6f mice, EVN neurons were positively identified using the fluorescent expression of gCaMP6f. In wild-type C57/BL6 mice, EVN neurons were confirmed using ChAT immunolabelling.</p><p><strong>Results: </strong>Consistent with previous studies, CGRP was labelled in a subset of cholinergic EVN neurons. Additionally, we also show evidence for substance P and PACAP expression in EVN of transgenic and wild-type mice.</p><p><strong>Conclusion: </strong>The presence of CGRP, substance P, and PACAP in EVN neurons suggests a complex peptidergic modulation of cholinergic signalling, whose release into local blood vessels may contribute to motion sickness symptoms.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Function and Brain Structure: Insight from a Mendelian Randomization Study.","authors":"Ping Li, Xiao Liu, Liming Wu, Liming Dong, Jianbo Zhou, Zhihui Song","doi":"10.1159/000542955","DOIUrl":"10.1159/000542955","url":null,"abstract":"<p><strong>Introduction: </strong>Thyroid hormones play a critical role in brain development. However, the precise causal associations between thyroid function and structural changes in specific brain regions remain uncertain.</p><p><strong>Methods: </strong>We applied the univariate Mendelian randomization (UVMR) method to assess the causal effects of thyroid function on brain structure. Genome-wide association study (GWAS) data on thyroid-related traits from the ThyroidOmics Consortium including free thyroxine (FT4), free tri-iodothyronine (FT3), thyroid-stimulating hormone (TSH), FT3/FT4 ratio, as well as dichotomized high and low TSH levels were used as exposures. GWAS data on cortical thickness, surface area, and volume of subcortical structures served as outcomes. Inverse variance weighted was the main estimate method. Subsequently, multivariable MR (MVMR) was conducted to validate significant causal associations identified in UVMR.</p><p><strong>Results: </strong>UVMR analysis demonstrated a statistically significant inverse association between genetically predicted FT4 and putamen volume (β = -71.91 mm3, 95% confidence interval: -112.11 mm3 to -31.71 mm3, p = 4.54 × 10-4). The findings were robust in sensitivity analysis. MVMR analysis further confirmed a persistent causal relationship between FT4 and putamen volume after adjusting for FT3, TSH, and neuropsychiatric disorders. Functional enrichment analyses indicated the pathways by which FT4 influences putamen volume may be related to the thyroid hormone signaling pathway, sodium-independent organic anion transport, and Rap1 signaling pathway.</p><p><strong>Conclusion: </strong>MR analysis provides evidence for causal relationships between thyroid function and brain structural alterations, particularly highlighting the impact of FT4 on putamen volume. Further research is warranted to elucidate the underlying mechanisms by which thyroid hormones modulate brain structure.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypothyroidism Promotes Microglia M1 Polarization by Inhibiting BDNF-Promoted PI3K-Akt Signaling Pathway.","authors":"Yuan Zhan, Lang Lang, Fen Wang, Xian Wu, Haiwang Zhang, Yuelin Dong, Hao Yang, Defa Zhu","doi":"10.1159/000542858","DOIUrl":"10.1159/000542858","url":null,"abstract":"<p><strong>Introduction: </strong>Hypothyroidism and its induced neurological-associated disorders greatly affect the health-related quality of patients' life. Meanwhile, microglia in brain have essential regulatory functions on neurodegeneration, but the underlying link between hypothyroidism and microglia function is largely ambiguous.</p><p><strong>Methods: </strong>We deciphered how hypothyroidism modulates the polarization of microglia by constructing methimazole-induced mice model and checking the expression pattern of biomarkers of microglia M1 polarization. Then, we used lipopolysaccharide (LPS)-treated BV2 cells to explore the effecting factors on microglia M1 polarization. Finally, global transcriptome sequencing (RNA-seq) was utilized to identify the underlying regulatory mechanisms.</p><p><strong>Results: </strong>We detected that biomarkers of microglia M1 polarization and pro-inflammatory cytokines were significantly increased in hypothyroidism mice brain; hypothyroidism could also repress the expression of BDNF and TrkB, and the anti-inflammatory cytokine such as IL-10. In BV2 cells, LPS treatment decreased expression of BDNF, IL-10, and Arg1, while BDNF overexpression (BDNF-OE) significantly reversed the inflammation induced by LPS. BDNF-OE significantly repressed expression of iNOS and TNF-α, but increased expression of IL-10 and Arg1. For mechanism, RNA-seq analysis demonstrated that BDNF-OE could globally regulate transcriptome profile by affecting gene expression. In LPS-treated BV2 cells, BDNF-OE significantly altered expression pattern of genes involved in PI3K-Akt signaling pathway, including Thbs3, Myc, Gdnf, Thbs1, and Ccnd1 as upregulated genes, and Gnb4, Fgf22, Pik3r3, Pgf, Cdkn1a, and Pdgfra as downregulated genes. Myc, Gdnf, Thbs1, and Ccnd1 showed much higher expression levels than other genes in PI3K-Akt signaling pathway and could be promising targets of BDNF in reversing microglia M1 polarization.</p><p><strong>Conclusion: </strong>Our study demonstrated a sound conclusion that hypothyroidism promotes microglia M1 polarization by inhibiting BDNF expression in brain; BDNF could inhibit the M1 polarization of microglia by activating PI3K-Akt signaling pathway, which could serve as a promising therapeutic target for microglia-induced neurodegenerative or emotional disorders in future.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-14"},"PeriodicalIF":3.2,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Variation of Hypothalamic-Pituitary-Adrenal Axis Activity in Farm Animals and Beyond.","authors":"Elena Mormede, Pierre Mormede","doi":"10.1159/000542831","DOIUrl":"10.1159/000542831","url":null,"abstract":"<p><strong>Background: </strong>Many experimental data in several species clearly demonstrate the important genetic contribution to variations in HPA axis activity. The influence of corticosteroid hormones on adaptive processes and on production traits such as growth rate, feed efficiency, carcass composition, and meat quality is a strong impetus to the search for the molecular bases of these differences for efficient genetic selection.</p><p><strong>Summary: </strong>Three main sources of genetic variability have been documented so far in farm animal species, the adrenal cortex sensitivity to ACTH-regulating corticosteroid hormone production, the bioavailability of corticosteroid hormones and especially corticosteroid-binding globulin capacity, and glucocorticoid receptor function. The effect of single mutations may be dependent on the genetic background, and genetic variation of cortisol levels may have different functional consequences depending on the molecular mechanisms responsible for this change.</p><p><strong>Key messages: </strong>Understanding the genetic basis of HPA axis activity allows the development of genomic tools and breeding technologies aimed at improving adaptive capacity and stress tolerance in farm animals and their use as valuable models for the genetic study of the HPA axis and the correlation with adaptation, metabolism, and other functions regulated by adrenal hormones, and associated pathologies (obesity, cardiovascular, etc.). The next step will be to explore HPA axis variability from a system genetics perspective including the multiple sources of variation and their interactions. This multifactorial approach is a prerequisite to the use of the HPA axis phenotypes in the genetic selection for more productive and robust animals, with a high level of production of quality products.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of thyroid status modulation on pituitary and peripheral hormone concentrations in healthy older subjects.","authors":"Evie van der Spoel, Saskia Cornet, Ana Zutinic, Bart Ballieux, P Eline Slagboom, Hanno Pijl, Diana van Heemst","doi":"10.1159/000542832","DOIUrl":"https://doi.org/10.1159/000542832","url":null,"abstract":"<p><strong>Introduction: </strong>Depending on age, sex, and familial longevity, alterations in thyroid status occur frequently, and often co-occur with differences in other hormonal axes. However, studies that explore the effects of thyroid status modulation on other hormonal axes remain scarce. We aim to determine the effects of thyroid status modulation on prolactin, IGF-1, cortisol, LH, testosterone, and SHBG levels. We also explored whether effects differed depending on type of challenge, sex, and familial longevity.</p><p><strong>Methods: </strong>Data was gathered from two single-arm challenge studies comprising an intramuscular injection of 0.1 mg recombinant human (rh)TSH (N=29) or 100 µg T3 orally (N=27) in healthy older individuals. Changes in hormone concentration profiles relative to baseline were determined for 4 and 5 days respectively.</p><p><strong>Results: </strong>IGF-1 increased with a maximum of 6.3% (SEM=1.6%, P=0.002) in the rhTSH challenge and 8.8% (SEM=1.6%, P<0.001) in the T3 challenge, while LH (19.3% (SEM=6.6%, P=0.048)), testosterone (13.8% (SEM=4.7%, P=0.048)), and SHBG (11.8% (SEM=3.5%, P=0.02)) increased significantly in the T3 challenge only. Moreover, prolactin significantly decreased in both rhTSH and T3 challenges (-8.8% (SEM=3.4%, P=0.048) and -12.0% (3.3%, P=0.004) respectively) as did cortisol (-14.8% (SEM=3.6%, P<0.001) and -15.6% (SEM=3.5%, P<0.001)). There was no significant interaction with type of challenge, sex, or familial longevity, except for prolactin in the rhTSH challenge (P=0.004) which decreased significantly in men only.</p><p><strong>Conclusions: </strong>Upon modulation of thyroid status, changes were observed in IGF-1, prolactin, and cortisol. In the T3 challenge, LH, testosterone, and SHBG increased in men. Observed changes are hypothesized to be driven by (f)T3.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-22"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic Cancer Hallmarks as Novel Markers Associated with Progression-free Survival in Gastroenteropancreatic Neuroendocrine Tumor Patients Undergoing PRRT.","authors":"Mahesh Kumar Padwal, Rahul Vithalrao Parghane, Avik Chakraborty, Aman Kumar Ujaoney, Narasimha Anaganti, Sandip Basu, Bhakti Basu","doi":"10.1159/000542918","DOIUrl":"https://doi.org/10.1159/000542918","url":null,"abstract":"<p><strong>Introduction: </strong>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors often detected at the metastatic stage. The aim of this study was to profile the peripheral blood transcriptome through RNA-Seq and investigate the association of the systemic cancer hallmarks with progression-free survival in PRRT-treated GEP-NET patients.</p><p><strong>Methods: </strong>The cohorts were: discovery cohort [PRRT-naïve well-differentiated GEP-NETs, n=59; age- and sex-matched healthy individuals, n=38], and independent evaluation cohort [GEP-NETs, n=66]. Peripheral blood transcriptomes were profiled through RNA sequencing and cancer hallmarks were identified via Gene Set Enrichment Analysis (GSEA). Activities of cancer hallmarks in each sample were calculated using Gene Set Variation Analysis (GSVA). Differentially expressed genes were identified with DESeq2. Progression-free survival was used as a primary endpoint and prognostic association was evaluated using univariate and multivariate COXPH analyses.</p><p><strong>Results: </strong>RNA-Seq captured global changes in the peripheral blood transcriptome of GEP-NET patients. Peripheral blood transcriptome of NET patients showed differential enrichment of 30 systemic cancer hallmarks viz., TNF-α signaling via NF-κB, IL2/STAT5 signaling, TNF-α response, TNF-γ response, IL6/JAK/STAT signaling, TGF-β signaling, heme metabolism. etc. In the univariate analyses, two cancer hallmarks were prognostically significant (p<0.05) in GEP-NETs. Heme metabolism and IL2/STAT5 signaling were statistically significant in the Discovery cohort (n=58) and independent evaluation cohort (n=66). In multivariate COXPH analyses, heme metabolism and IL2/STAT5 signaling were independently associated with PFS in GEP-NET patients undergoing PRRT.</p><p><strong>Conclusions: </strong>This study provides comprehensive coverage of the peripheral blood transcriptome of GEP-NET patients via RNA-Seq and identifies systemic cancer hallmarks as independent prognostic factors in NETs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-18"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obesogens and Energy Homeostasis: Definition, Mechanisms of Action, Exposure and Adverse Effects on Human Health.","authors":"Bayram Yilmaz, Cihan Suleyman Erdogan, Suleyman Sandal, Fahrettin Kelestimur, David O Carpenter","doi":"10.1159/000542901","DOIUrl":"https://doi.org/10.1159/000542901","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a major risk factor for noncommunicable diseases and is associated with a reduced life expectancy of up to 20 years, as well as with other consequences such unemployment and increased economic burden for society. It is a multifactorial disease and physiopathology of obesity involves dysregulated calorie utilization and energy balance, disrupted homeostasis of appetite and satiety, lifestyle factors including sedentary lifestyle, lower socio-economic status, genetic predisposition, epigenetics and environmental factors. Some endocrine-disrupting chemicals (EDCs) have been proposed as \"obesogens\" that stimulate adipogenesis leading to obesity. In this review, definition of obesogens, their adverse effects, underlying mechanisms and metabolic implications will be updated and discussed.</p><p><strong>Summary: </strong>Disruption of lipid homeostasis by EDCs involves multiple mechanisms including increase in the number and size of adipocytes, disruption of endocrine-regulated adiposity and metabolism, alteration of hypothalamic regulation of appetite, satiety, food preference and energy balance, and modification of insulin sensitivity in the liver, skeletal muscle, pancreas, gastrointestinal system and the brain. At a cellular level, obesogens can exert their endocrine disruptive effects by interfering with peroxisome proliferator-activated receptors and steroid receptors. Human exposure to chemical obesogens mainly occurs by ingestion and, to some extent, by inhalation and dermal uptake, usually in an unconscious manner. Persistent pollutants are lipophilic features; thus, they bio-accumulate in adipose tissue.</p><p><strong>Key messages: </strong>Although there is an increasing number of reports studying the effects of obesogens, their mechanisms of action remain to be elucidated. In addition, epidemiological studies are needed in order to evaluate human exposure to obesogens.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-40"},"PeriodicalIF":3.2,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}