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Nutrients May 2024Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations... (Review)
Review
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome caused by inactivating mutations in the MEN1 tumor suppressor gene. The three main clinical manifestations of MEN1 are primary hyperparathyroidism (PHPT), duodenal-pancreatic neuroendocrine tumors (DP-NETs) and anterior pituitary tumors. Endocrine tumors in patients with MEN1 differ from sporadic tumors because of their younger age at onset, common multiple presentations and the different clinical course. MEN1 is characterized by a complex clinical phenotype; thus, patients should be followed by a multidisciplinary team of experts that includes an endocrinologist, a surgeon, a oncologist, a radiotherapist, and not least, a nutritionist. It is important to remember the fundamental role that diet plays as a primary prevention tool, together with a healthy and active lifestyle in preventing osteoporosis/osteopenia and reducing the risk of developing kidney stones due to hypercalciuria, two frequent clinical complications in MEN1 patients. Is very important for MEN1 patients to have an adequate intake of calcium, vitamin D, magnesium and phosphate to maintain good bone health. The intake of foods containing oxalates must also be kept under control because in combination with calcium they concur to form calcium oxalate crystals, increasing the risk of nephrolithiasis. Another aspect to consider is the management of patients with pancreatic neuroendocrine tumors undergoing major surgical resections of the pancreas that can lead to alterations in digestion and absorption mechanisms due to partial or total reduction in pancreatic enzymes such as amylase, lipase, and protease, resulting in malabsorption and malnutrition. Therefore, the nutritionist's aim should be to devise a dietary plan that takes into consideration each single patient, educating them about a healthy and active lifestyle, and accompanying them through various life stages by implementing strategies that can enhance their quality of life.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Nutritional Status
PubMed: 38892509
DOI: 10.3390/nu16111576 -
International Journal of Molecular... May 2024Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model,...
Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of and in the hypothalamus does not change, except for and , while at the pituitary level the , and genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated and expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.
Topics: Animals; Encephalomyelitis, Autoimmune, Experimental; Female; Rats; Growth Hormone; Insulin-Like Growth Factor I; Hypothalamus; Pituitary Gland; Receptors, Somatotropin; Receptors, Pituitary Hormone-Regulating Hormone; Multiple Sclerosis; Growth Hormone-Releasing Hormone; Liver; Disease Models, Animal
PubMed: 38892024
DOI: 10.3390/ijms25115837 -
International Journal of Molecular... May 2024The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and... (Review)
Review
The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.
Topics: Humans; Male; Testis; Animals; Spermatogenesis; Follicle Stimulating Hormone; Hypothalamo-Hypophyseal System; Androgens; Testosterone
PubMed: 38891991
DOI: 10.3390/ijms25115805 -
BMC Genomics Jun 2024Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the...
BACKGROUND
Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes.
METHODS AND RESULTS
A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets.
CONCLUSIONS
Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.
Topics: Humans; Genetic Predisposition to Disease; Genome-Wide Association Study; Blood Pressure; Gene Expression Profiling; Hypertension; Transcriptome; Polymorphism, Single Nucleotide; Male; Risk Assessment; Female; Sodium Chloride, Dietary
PubMed: 38890564
DOI: 10.1186/s12864-024-10409-9 -
Acta Neurochirurgica Jun 2024Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective...
BACKGROUND
Invasion of the CS is one of the limiting factors for total resection for PitNet tumors with cure rates less than 30%. Extended approaches may be considered in selective and well-studied cases of secreting adenomas.
METHOD
We describe the key steps of the endoscopic transcavernous approach for functional pituitary adenomas with a video illustration. The surgical anatomy is described along with the advantages and limitations of this approach.
CONCLUSION
A detailed knowledge of CS anatomy and familiarity with this surgical approach acquired in the laboratory is essential. Proper instrumentation is critical to decrease the risks of vascular injury.
Topics: Humans; Pituitary Neoplasms; Adenoma; Neuroendoscopy; Cavernous Sinus; Endoscopy; Neurosurgical Procedures
PubMed: 38890156
DOI: 10.1007/s00701-024-06168-x -
Psychoneuroendocrinology Jun 2024Non-suicidal self-injury (NSSI) is a highly prevalent phenomenon during adolescence. Nonetheless, research on predictors of the clinical course of NSSI over time is...
AIM
Non-suicidal self-injury (NSSI) is a highly prevalent phenomenon during adolescence. Nonetheless, research on predictors of the clinical course of NSSI over time is still scarce. The present study aimed at investigating the impact of adverse childhood experiences (ACE) and hypothalamus-pituitary-adrenal (HPA) axis functioning on the longitudinal course of NSSI.
METHODS
In a sample of n = 51 help-seeking adolescents engaging in NSSI, diurnal cortisol secretion (CAR, cortisol awakening response; DSL, diurnal slope), hair cortisol concentrations and ACE were assessed at baseline. Clinical outcome was defined by change in the frequency of NSSI in the past 6 months measured 12 and 24 months after the baseline assessments. Mixed-effects linear regression models were used to test for effects of ACE and HPA axis functioning on the course of NSSI.
RESULTS
ACE and HPA axis functioning did not show main but interaction effects in the prediction of NSSI frequency over time: Adolescents with a low severity of ACE and either an increased CAR or a flattened DSL showed a steep decline of NSSI frequency in the first year followed by a subsequent increase of NSSI frequency in the second year.
CONCLUSIONS
Our findings could be interpreted in the sense of high diurnal cortisol concentrations in the absence of ACE being favorable for clinical improvement on the short-term but bearing a risk of allostatic load and subsequent increase of NSSI frequency. In contrast, adolescents with severe ACE may benefit from elevated cortisol concentrations leading to slower but lasting decreases of NSSI frequency.
PubMed: 38889567
DOI: 10.1016/j.psyneuen.2024.107093 -
Annals of Clinical and Translational... Jun 2024Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those... (Review)
Review
OBJECTIVE
Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those targeting calcitonin gene-related peptide (CGRP). However, there remains a substantial need for further treatments for those unresponsive to current therapies. Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) as a possible therapeutic strategy in the primary headache disorders has gained interest over recent years.
METHODS
This review will summarize what we know about PACAP to date: its expression, receptors, roles in migraine and cluster headache biology, insights gained from preclinical and clinical models of migraine, and therapeutic scope.
RESULTS
PACAP shares homology with vasoactive intestinal polypeptide (VIP) and is one of several vasoactive neuropeptides along with CGRP and VIP, which has been implicated in migraine neurobiology. PACAP is widely expressed in areas of interest in migraine pathophysiology, such as the thalamus, trigeminal nucleus caudalis, and sphenopalatine ganglion. Preclinical evidence suggests a role for PACAP in trigeminovascular sensitization, while clinical evidence shows ictal release of PACAP in migraine and intravenous infusion of PACAP triggering attacks in susceptible individuals. PACAP leads to dural vasodilatation and secondary central phenomena via its binding to different G-protein-coupled receptors, and intracellular downstream effects through cyclic adenosine monophosphate (cAMP) and phosphokinase C (PKC). Targeting PACAP as a therapeutic strategy in headache has been explored using monoclonal antibodies developed against PACAP and against the PAC1 receptor, with initial positive results.
INTERPRETATION
Future clinical trials hold considerable promise for a new therapeutic approach using PACAP-targeted therapies in both migraine and cluster headache.
PubMed: 38887982
DOI: 10.1002/acn3.52119 -
Acta Neuropathologica Communications Jun 2024A link between chronic stress and Parkinson's disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein...
A link between chronic stress and Parkinson's disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.
Topics: alpha-Synuclein; Animals; Parkinson Disease; Humans; Rats, Transgenic; Rats; Stress, Psychological; Male; Corticosterone; Brain; Hypothalamo-Hypophyseal System; Female; Pituitary-Adrenal System
PubMed: 38886854
DOI: 10.1186/s40478-024-01797-w -
Middle ear neuroendocrine tumor with multiple brain metastases: a case report and literature review.Frontiers in Oncology 2024Middle ear neuroendocrine tumor (MeNET) is a low-grade tumor with rare recurrence or metastasis. Here, we describe the case of a 29-year-old man who suffered from MeNET... (Review)
Review
Middle ear neuroendocrine tumor (MeNET) is a low-grade tumor with rare recurrence or metastasis. Here, we describe the case of a 29-year-old man who suffered from MeNET that recurred 3 times over 10 years and eventually metastasized to the brain. The patient was treated with surgical resection, radiotherapy, and chemotherapy. However, the tumor was not entirely removed as the brain metastatic tumor adhered tightly to the brainstem. Due to tumor rupture and bleeding after multiple brain tumor removal, profound coma developed. Finally, the patient died 10 months after the last surgery. To our knowledge, this is the first report of a MeNET case with multiple brain metastases. Characteristics of the present case indicate that CK, SYN, increased Ki67 index, and ATRX may be potential biomarkers of invasive MeNET. The survival of patients with brain metastatic MeNET may be extended by surgical resection, radiotherapy, and chemotherapy. Close follow-up of distinctive metastases and biomarkers related to recurrence is also suggested.
PubMed: 38884081
DOI: 10.3389/fonc.2024.1392610 -
Clinical Case Reports Jun 2024Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment...
KEY CLINICAL MESSAGE
Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN.
ABSTRACT
Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.
PubMed: 38883224
DOI: 10.1002/ccr3.9031