Neuroendocrinology最新文献

{"title":"Acute Optogenetic Activation of the Subfornical Organ Produces Sympathetically Mediated Increases in Blood Pressure.","authors":"Monique L Van Acquoy, Teodora Nedelkoska, Simon McMullan, Peter G R Burke, Cara M Hildreth","doi":"10.1159/000545849","DOIUrl":"10.1159/000545849","url":null,"abstract":"<p><strong>Introduction: </strong>The subfornical organ (SFO) is a vital blood pressure-controlling region that elicits blood pressure changes likely via an excitatory (or glutamatergic) projection to the paraventricular nucleus of the hypothalamus (PVN). However, the role of this SFO-PVN pathway in blood pressure control has been poorly defined in the literature. As such, the present study aimed to examine the functional connectivity between the SFO neurons and the PVN and how they intersect to control blood pressure.</p><p><strong>Methods: </strong>In Lewis rats (n = 10), glutamatergic SFO neurons (SFOglut) were transduced with channelrhodopsin via a CaMKIIa-promotor vector (pAAV9-CaMKIIa-hChR2(H134R)-EYFP). Under urethane anaesthesia, changes in blood pressure and renal and splanchnic nerve activities were recorded in response to photostimulation of SFOglut neurons before and after administration of an intravenous ganglionic blocker and V1a receptor antagonism and inhibition of the PVN via muscimol microinjection. Immunohistochemistry was used to examine the projections between the SFO and PVN.</p><p><strong>Results: </strong>Photostimulation of SFOglut neurons produced a frequency-dependent pressor response that was abolished by sympathetic ganglionic blockade but not by inhibiting the vasoactive hormone vasopressin. This pressor response depends on ongoing neuronal transmission within the PVN as it is abolished by bilateral PVN inhibition. Confirming this, we found dense projections from SFOglut neurons to magnocellular and parvocellular PVN neurons. Finally, photostimulation of SFOglut neurons elicited a peak increase in sympathetic nerve activity that was reversibly abolished by phenylephrine administration and abolished by inhibition of the PVN, suggesting that the neuronal circuitry underpinning this response is barosensitive.</p><p><strong>Conclusion: </strong>The pressor response elicited by SFOglut neurons is largely mediated by barosensitive sympathetic nerve activity and dependent on the PVN.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"564-575"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Existence of Coexpressive Role of Kisspeptin and Insulin-2 in the Regulation of Luteinizing Hormone in Chronic Stress-Induced Polycystic Ovarian Syndrome-Like Phenotype in Rattus norvegicus.","authors":"Nitin K Rajashekara, Bindu Jayashankaraswamy, Raghu Nataraj, Raghu Nataraj","doi":"10.1159/000546126","DOIUrl":"10.1159/000546126","url":null,"abstract":"<p><strong>Background: </strong>Polycystic ovary syndrome (PCOS) is an ill manifestation of the normal ovarian function that obstructs folliculogenesis. Clinically, patients diagnosed with PCOS possess chronic psychological distress with the downregulated hypothalamus-pituitary-gonadal (HPG) axis under the influence of cortisol, but, in contrast, studies done elsewhere have demonstrated an increased hypothalamus-pituitary activity under the PCOS condition. This contradiction has led to several independent research studies assessing the role of metastatic suppressor genes Kisspeptin (KiSS1) and Insulin (INS2) in regulating LH by acting upon GnRH. The current study demonstrates the coexpressive role of KiSS1 and INS2 in regulating LH and monitoring ovarian health.</p><p><strong>Methodology: </strong>PCOS-like features were induced in the rats by a chronic stress regime, and the parameters were established. Another stress group of animals was dosed with 60 mg/kg body weight of ketoconazole before the stress exposure, and the parameters of the study were estimated and established.</p><p><strong>Results: </strong>The current study has observed that upon chronic stress exposure, the animals have exhibited all the features of PCOS, like hyperandrogenism, cystic follicles with dysregulated estrous cyclicity, an elevated LH, and decreased plasma insulin levels. As hypothesized, a 7-fold increase of KiSS1 expression and a 2-fold increase of INS-2 expressions have been observed in the stress group animals, unlike the corticosterone inhibitor group of animals which have exhibited a controlled phenotype.</p><p><strong>Conclusion: </strong>The obtained relative fold changes in the gene expression level of both KiSS1 and INS2 reveal the association of stress with the pathology of PCOS via neuroendocrine regulation. The study has demonstrated the existence of a putative temporal coupling activity of KiSS1-INS2 expression-driven elevated LH in preclinical Rattus norvegicus models.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"589-603"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid Profile Differences in Monomeric Hyperprolactinemia, Macroprolactinemia, and Healthy Controls: A Comparative Analysis.","authors":"Sami Bahçebaşı, Ferhat Gökay, Yasin Şimşek","doi":"10.1159/000547540","DOIUrl":"10.1159/000547540","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to investigate the effects of different prolactin isoforms - specifically macroprolactin and monomeric prolactin - on lipid metabolism across various subtypes of hyperprolactinemia.</p><p><strong>Methods: </strong>A total of 166 adults were retrospectively analyzed and categorized into macroprolactinemia, gray zone, and monomeric hyperprolactinemia (further subdivided into prolactinoma and idiopathic groups), along with a healthy control group. Lipid parameters, including total cholesterol, lipoprotein cholesterol (LDL), HDL, triglycerides, and non-HDL cholesterol, were compared among groups. Statistical analyses were adjusted for age and body mass index (BMI).</p><p><strong>Results: </strong>Patients with prolactinoma, idiopathic hyperprolactinemia, and those in the gray zone exhibited significantly elevated total cholesterol, LDL, and non-HDL cholesterol levels compared to healthy controls (p < 0.05). There were no significant differences in lipid profiles between the macroprolactinemia group and either the healthy controls or the monomeric hyperprolactinemia groups. Serum prolactin concentrations positively correlated with LDL, triglycerides, and non-HDL cholesterol, whereas macroprolactin recovery rates showed no such associations.</p><p><strong>Conclusion: </strong>Monomeric hyperprolactinemia - particularly in prolactinoma - is associated with dyslipidemia and potentially increased cardiovascular risk. In contrast, macroprolactinemia appears metabolically inactive or may represent an intermediate metabolic state. Differentiating prolactin isoforms are crucial for accurate clinical evaluation and appropriate metabolic risk assessment in patients with hyperprolactinemia.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"719-729"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962555","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":"Recent Advances in the Understanding of Gonadotrope Lineage Differentiation in the Developing Pituitary.","authors":"Charles Le Ciclé, Joëlle Cohen-Tannoudji, David L'Hôte","doi":"10.1159/000542513","DOIUrl":"10.1159/000542513","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/strong&gt;Overall, this review aimed to provide new insights into three aspects of the gonadotrope differentiation process by reconsidering pioneering studies in the light of data gained from latest technological developments. Firstly, we re-investigated the long debated developmental trajectory of pituitary gonadotrope cells. Secondly, we reported new regulatory mechanisms of Nr5a1 expression, focusing on the involvement of ERα. Finally, we highlighted the molecular and cellular mechanisms driving gonadotrope network formation during embryogenesis, a process that seems essential for regulation of gonadotrope activity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The pituitary gland is a vital endocrine organ regulating body homoeostasis through six hormone-secreting cell types. Among these, pituitary gonadotrope cells are essential for reproductive function. Throughout pituitary ontogenesis, gonadotrope cells differentiate in a stepwise process, involving both morphogenic cues and transcription factors, which drives specification of progenitor cells into specialised endocrine cells. It is crucial to understand the mechanisms underlying gonadotrope differentiation, as developmental defects and abnormalities in this process can lead to many reproductive pathologies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary: &lt;/strong&gt;This review offers a detailed overview of the latest advances in gonadotrope cell differentiation. We addressed this question with a specific focus on three important aspects of gonadotrope differentiation: the identification of the progenitor population giving rise to gonadotrope cells, the early mechanisms that initiate Nr5a1 expression and thus gonadotrope fate commitment, and finally, the mechanisms driving the formation of physical and functional gonadotrope networks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key messages: &lt;/s","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"195-210"},"PeriodicalIF":2.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11924211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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><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 t","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"34-47"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854979/pdf/","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":"OA","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":"128-137"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","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":"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":"283-294"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","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":"Genetic Associations between Obesity and Brain Cortical Thickness: Combined Genetic Correlation, Multi-Trait Meta-Analysis, and Mendelian Randomization.","authors":"Jiankun Chen, Simin Pan, Yingfei Tan, Yuan Wu, Taoliang Huang, Bin Huang, Shiheng Wu, Changcai Xie, Shubin Cai, Jiqiang Li, Yue Lu, Yu Chen","doi":"10.1159/000543574","DOIUrl":"10.1159/000543574","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity may lead to cognitive impairment and neuropsychiatric disorders, which are associated with changes in the brain cortical structure, particularly in cortical thickness. However, the exact genetic association between obesity and brain cortical thickness remains inconclusive. We aimed to identify the relationship between obesity-related traits (body mass index [BMI], waist-hip ratio [WHR], and waist-hip ratio adjusted for BMI [WHRadjBMI]) and brain cortical thickness.</p><p><strong>Methods: </strong>Leveraging summary statistics of large-scale GWAS(s) conducted in European-ancestry populations on BMI (N = 806,834), WHR (N = 697,734), WHRadjBMI (N = 694,649), and brain cortex thickness (N = 33,709), we performed GWAS combining genetic correlation, multi-trait meta-analysis, and Mendelian randomization analysis.</p><p><strong>Results: </strong>Our findings revealed a strong genetic correlation between BMI and brain cortical thickness (rg = -0.0542, p = 0.0435), and a significant result was also observed for WHR and brain thickness (rg = -0.0744, p = 0.009). In addition, we identified three loci between obesity-related traits. Mendelian randomization analysis supported the causal role of BMI (inverse-variance-weighted [IVW] beta = -0.006, 95% CI = -0.011 to -3.85E-04; weighted median beta = -0.006, 95% CI = -0.013 to -0.002), WHR (IVW beta = -0.011, 95% CI = -0.018 to -0.005; weighted median beta = -0.008, 95% CI = -0.018 to -0.003), and WHRadjBMI (IVW beta = 0.011, 95% CI = -0.018 to -0.005; weighted median beta = -0.008, 95% CI = -0.018 to -0.002) in brain cortical thickness.</p><p><strong>Conclusion: </strong>This study has shown that genetically predicted obesity-related traits have a causal relationship with reduced cortical thickness. These findings provide genetic evidence for a link between obesity and structural changes in the brain and suggest that obesity may be associated with neuropsychiatric disorders by affecting brain structure, particularly cortical thickness.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"308-314"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007660","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":"Cabozantinib in the Treatment of Neuroendocrine Neoplasms: Insights across Different Tumor Origins.","authors":"Giovanni Vitale, Ilona Rybinska, Giulia Arrivi, Vincenzo Marotta, Gianfranco Di Iasi, Alessia Filice, Christopher Nardi, Annamaria Colao, Antongiulio Faggiano","doi":"10.1159/000543953","DOIUrl":"10.1159/000543953","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors arising from neuroendocrine cells, exhibiting a wide range of behaviors from indolent to highly aggressive forms. Treatment options remain limited, particularly for progressive cases. Cabozantinib, a multitarget tyrosine kinase inhibitor, has demonstrated potential in targeting key pathways related to tumor growth, angiogenesis, and metastasis.</p><p><strong>Summary: </strong>This review provides a comprehensive analysis of cabozantinib's therapeutic role across various NEN subtypes, including gastroenteropancreatic NENs, lung NENs, pheochromocytomas/paragangliomas, Merkel cell carcinoma, presacral NENs, pituitary neuroendocrine tumors, and neuroendocrine prostate cancer.</p><p><strong>Key messages: </strong>The paper discusses several preclinical and clinical studies that demonstrate the efficacy of cabozantinib in slowing tumor progression and improving progression-free survival, particularly in patients with progressive, well-differentiated NENs. However, cabozantinib's complex toxicity profile limits its broad application, necessitating further research to optimize dosing, particularly in syndromic NENs. Ongoing trials are investigating cabozantinib in combination with somatostatin analogs, peptide receptor radionuclide therapy, temozolomide, and immunotherapies in order to overcome treatment resistance and expanding therapeutic strategies for advanced NENs.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"460-479"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188884","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":"Role of Melatonin in Intestinal Mucosal Injury Induced by Chronic Restraint Stress in Mice.","authors":"Sun Zhongxin, Chai Lulu, Li Dandan, Yang Yao, Yao Wenqian, Li Hui, Shan Chunlan, Wen Xin, Lin Rutao","doi":"10.1159/000547254","DOIUrl":"10.1159/000547254","url":null,"abstract":"<p><strong>Introduction: </strong>A growing body of evidence demonstrates that gastrointestinal motility disorder (GIMD) and gastric stress ulcers can be induced by chronic stress, whereas melatonin (MT) elicits anti-inflammatory and antioxidant effects. The present study investigated the mechanisms of MT-mediated protection against chronic restraint stress-induced GIMD.</p><p><strong>Methods: </strong>Sixty 8-week-old male Institute of Cancer Research mice were divided into four groups: control, restraint stress, restraint stress + MT, and MT (positive control). MT (20 mg/kg) or vehicle was administered intraperitoneally 60 min before chronic restraint stress (5 h/day) once daily for 30 days. Biochemical parameters, intestinal mucosal integrity, tissue antioxidant ability, and autophagic protein levels were determined.</p><p><strong>Results: </strong>Mice subjected to restraint stress presented elevated CORT and NE levels of 141.41% and 151.24%, respectively, and a decreased plasma MT content of 37.12%. Consistent with the decrease in MT levels, we observed a reduction in antioxidant ability and autophagic proteins and increased apoptotic protein levels in the gut, resulting in injury to the intestinal mucosa, which manifested as reductions in the villus height and the V/C ratio; the number of goblets; the number of mast and PCNA-positive cells; and the expression of tight junction proteins (ZO-1, occludin and claudin-1). In contrast, MT reversed these changes caused by chronic restraint stress and improved intestinal mucosal injury. However, there was no significant difference between the MT (positive control) and control groups.</p><p><strong>Conclusion: </strong>Our results suggest that MT effectively mitigates chronic psychological stress-induced intestinal mucosa injury, providing evidence demonstrating the potential for the use of MT as a therapy for intestinal impairment associated with chronic psychological stress.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"741-756"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575923","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}