Neuroendocrinology最新文献

Introduction: Among neuroendocrine lung cancers, lung carcinoids (LCs, further divided into typical [TC] and atypical [AC]) are rare, representing only the 2% of all bronchopulmonary malignancies, and lack prognostic classification and stratification.

Methods: We audited 2 international cohorts of patients with a confirmed diagnosis of LC for prognostic analysis. We used data from the Christie Hospital (Manchester, UK, N = 282) and validated our findings using the cohort of Vall d'Hebron Hospital patients (Barcelona, Spain, N = 80). We analysed patient data to identify a prognostic model for metastasis-free survival (MFS) and stage IV overall survival (OS).

Results: Serum lactate dehydrogenase concentration, stage, gender, and tumour Ki-67% were significant at multivariable analysis (stratified for stage) for MFS after surgery (C-index = 0.76, p < 0.001), while histological subtype (TC vs. AC) and other clinical variables were not. Independent prognostic factors for OS from onset of metastases included smoking history, along with known factors (patient age, proliferation index, FDG-PET maximum SUV). The model C-index was 0.77 (p < 0.001), with good concordance when applied to the external validation from Vall d'Hebron (C-index = 0.94). Previously undescribed, patients with smoking history lived shorter (median OS = 34 months vs. not reached, p < 0.0001), and the median OS could be shorter in current smokers (26.2 months) compared to ex-smokers (35.3 months).

Conclusion: We provide a novel prognostic tool to estimate patient risk, clinical trial stratification and assist clinical decisions in the rarest lung tumours. We also describe for the first time that smoking history is an independent prognostic factor for OS in stage IV.

Background: Autoimmune thyroid disease is an autoimmune disease. Observational studies have shown that individuals with thyroid dysfunction have dyslipidaemia. However, it is uncertain whether there is a causal relationship between the two. Therefore, the purpose of this study was to evaluate the causal relationship between plasma liposomes and autoimmune thyroid disease, thereby providing new insights into disease mechanisms and potential therapeutic targets.

Method: We used two-sample Mendelian randomization (MR) to elucidate the causal relationship between plasma liposomes and autoimmune thyroid disease. We divide autoimmune thyroid disease into three types: autoimmune hyperthyroidism, autoimmune hypothyroidism, and autoimmune thyroiditis. The IVW method is the main analysis method, and Cochran Q test is used. MR-Egger intercept, leave-one-out test, and other tests are used to explore whether there are heterogeneity and pleiotropy in MR results.

Result: MR analysis revealed causal relationships between eight plasma lipoproteins and autoimmune hyperthyroidism. Eleven causal relationships were identified between plasma lipoproteins and autoimmune hypothyroidism, including cholesterol ester (27:1/16:0) and cholesterol ester (27:1/18:2). Sixteen plasma lipoproteins have been confirmed to have causal relationships with autoimmune thyroiditis, including cholesterol ester (27:1/20:3) and sphingosine (d40:2) levels, which are associated with an increased risk of autoimmune thyroiditis, while phosphatidylethanolamine (18:2:0:0) levels are associated with a reduced risk of autoimmune thyroiditis. A series of sensitivity tests also confirmed the reliability of the results.

Conclusion: According to this MR study, an established study, there is a causal relationship between plasma liposomes and autoimmune thyroid disease, which provides fresh insights into the potential mechanisms of autoimmune thyroid disease that may contribute to the development, prevention, and treatment of autoimmune thyroid disease.

The caudal neurosecretory system (CNSS) is a neuroendocrine complex, whose existence is specific to fishes. In teleosts, it consists of neurosecretory cells (Dahlgren cells) whose fibers are associated with a neurohemal terminal tissue (urophysis). In other actinopterygians as well as in chondrichthyes, the system is devoid of urophysis, so that Dahlgren cells end in a diffuse neurohemal region. Structurally, it has many similarities with the hypothalamic-neurohypophysial system. However, it differs regarding its position at the caudal end of the spinal cord and the nature of the hormones it secretes, the most notable ones being urotensins. The CNSS was first described more than 60 years ago, but its embryological origin is still hypothetical, and its role is poorly understood. Observations and experimental data gave some evidences of a possible involvement in osmoregulation, stress, and reproduction. But one may question the benefit for fish to possess this second neurosecretory system, while the central hypothalamic-pituitary complex already controls such functions. As an introduction of our review, a brief report on the discovery of the CNSS is given. A description of its organization follows, and our review then focuses on the neuroendocrinology of the CNSS with the different factors it produces and secretes. The current knowledge on the ontogenesis and developmental origin of the CNSS is also reported, as well as its evolution. A special focus is finally given on what is known on its potential physiological roles.

Introduction: Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare gynecologic malignant tumor, which has lack of systematic research. In order to investigate its molecular characteristics, origin, and pathogenesis, single-cell transcriptome sequencing (scRNA-Seq) of SCNECC was performed for the first time, the cellular and molecular landscape was revealed, and the key genes for clinical prognosis were screened.

Methods: This article initially performed the scRNA-Seq on a tumor tissue sample from an SCNECC patient, combined with scRNA-Seq data from a healthy cervical tissue sample downloaded from a public database; the single-cell transcriptome landscape was constructed. Then, we investigated the cell types, intratumoral heterogeneity, characteristics of tumor microenvironment, and potential predictive markers of SCNECC.

Results: We identified two malignant cell populations, tumor stem cells and malignant carcinoma cells, and revealed two tumor progression pathways of SCNECC. By analyzing gene expression levels in the pathophysiology of SCNECC, we found that the expression levels of ERBB4 and NRG1, as well as the expression profile of mTOR signaling pathway mediated by them, were significantly upregulated in malignant carcinoma cells. In addition, we also found that carcinoma cells were able to stimulate malignant cell proliferation through the FN1 signaling pathway. The immune cells were in a stress state, with T-cell depletion, macrophage polarization, and mast cell glycolysis. These results suggested that carcinoma cells could interfere with immune response and promote tumor escape through MIF, TGFb, and other immunosuppressive-related signaling pathways.

Conclusion: This study revealed the mechanism of genesis and progression in SCNECC and the related important signaling pathways, such as mTOR, and provided new insights into the treatment of SCNECC.

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: The pressor response elicited by SFOglut neurons is largely mediated by barosensitive sympathetic nerve activity and dependent on the PVN.

Background: 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.

Methodology: 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.

Results: 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.

Conclusion: 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.

Introduction: This study aimed to investigate the effects of different prolactin isoforms - specifically macroprolactin and monomeric prolactin - on lipid metabolism across various subtypes of hyperprolactinemia.

Methods: 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).

Results: 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.

Conclusion: 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.

Introduction: Peptide receptor radionuclide therapy (PRRT) is a highly effective, targeted treatment option in advanced neuroendocrine tumours (NETs). However, NET patients expressing low levels of Somatostatin receptor type (SSTR) 2 do not benefit from this powerful tool. Recently, several preclinical studies have revealed that histone deacetylase (HDAC) inhibitors can upregulate the expression of SSTR2 and enhance somatostatin ligand binding to tumour cells. In this preclinical study, we explored the effects of single and combined treatment of NET cells with the class I HDAC inhibitor entinostat and the lysine-specific demethylase 1 (LSD1) inhibitor CC-90011, on cell viability, SSTR2 expression and radioligand binding.

Methods: The human NET cell lines BON1, NCI-H727, and QGP1 were treated with entinostat, CC-90011 or a combination of both. Cell viability was measured with a cell viability assay. SSTR2 expression was assessed by quantitative PCR, Western blot analysis, and immunohistochemistry. [18F]SiTATE uptake was investigated by a radioligand binding assay.

Results: Treatment of NET cells with entinostat, CC-90011, and especially the combination of both reduced tumour cell viability and strongly induced SSTR2 expression resulting in potently enhanced radioligand binding of [18F]SiTATE.

Conclusion: Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.