Multiscale pore contained carbon nanofiber-based field-effect transistor biosensors for nesfatin-1 detection.

Nesfatin-1 (NES1) is a potential biomarker found in serum and saliva that indicates hyperpolarization and depolarization in the hypothalamic ventricle nucleus as well as an increase in epileptic conditions. However, real-time investigations have not been carried out to detect changes in the concentration of NES1. In this study, we develop a multiscale pore contained carbon nanofiber-based field-effect transistor (FET) biosensor to detect NES1. The activated multiscale pore contained carbon nanofiber (a-MPCNF) is generated using a single-nozzle co-electrospinning method and a subsequent steam-activation process to obtain a signal transducer and template for immobilization of bioreceptors. The prepared biosensor exhibits a high sensitivity to NES1. It can detect levels as low as 0.1 fM of NES1, even in the presence of other interfering biomolecules. Furthermore, the a-MPCNF-based FET sensor has significant potential for practical applications in non-invasive real-time diagnosis, as indicated by its sensing performance in artificial saliva.

Colocalized neurotransmitters in the hindbrain cooperate in adaptation to chronic hypernatremia.

Chronic hypernatremia activates the central osmoregulatory mechanisms and inhibits the function of the hypothalamic-pituitary-adrenal (HPA) axis. Noradrenaline (NE) release into the periventricular anteroventral third ventricle region (AV3V), the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN) from efferents of the caudal ventrolateral (cVLM) and dorsomedial (cDMM) medulla has been shown to be essential for the hypernatremia-evoked responses and for the HPA response to acute restraint. Notably, the medullary NE cell groups highly coexpress prolactin-releasing peptide (PrRP) and nesfatin-1/NUCB2 (nesfatin), therefore, we assumed they contributed to the reactions to chronic hypernatremia. To investigate this, we compared two models: homozygous Brattleboro rats with hereditary diabetes insipidus (DI) and Wistar rats subjected to chronic high salt solution (HS) intake. HS rats had higher plasma osmolality than DI rats. PrRP and nesfatin mRNA levels were higher in both models, in both medullary regions compared to controls. Elevated basal tyrosine hydroxylase (TH) expression and impaired restraint-induced TH, PrRP and nesfatin expression elevations in the cVLM were, however, detected only in HS, but not in DI rats. Simultaneously, only HS rats exhibited classical signs of chronic stress and severely blunted hormonal reactions to acute restraint. Data suggest that HPA axis responsiveness to restraint depends on the type of hypernatremia, and on NE capacity in the cVLM. Additionally, NE and PrRP signalization primarily of medullary origin is increased in the SON, PVN and AV3V in HS rats. This suggests a cooperative action in the adaptation responses and designates the AV3V as a new site for PrRP's action in hypernatremia.

The role of nesfatin and selected molecular factors in various types of endometrial cancer.

OBJECTIVES: Endometrial cancers (ECs) are the most common gynaecological cancers in well developed countries. Diabetes and metabolic syndrome are among the biggest risk factors. Nesfatin-1, the adipokine derivative of NUCB2 (nucleobindin derivative 2) is linked to the clinical course of EC. Molecular factors, including mutations in MLH1 and MHS2 genes, c-MET and ARID1A are also related to prognosis in endometrial cancer. MATERIAL AND METHODS: Using sections of paraffin-embedded preparations and immunohistochemistry, the expression of NESF1, MLH1, MSH2,c-MET and ARID1A were examined. RESULTS: In this study on protein expression, EC tissues manifested (although insignificantly) an elevated expression of NESF-1 in type II EC. In type I EC, NESF-1 expression was significantly higher in G1 in comparison to G2 and G3 together. A significantly lower expression of MLH1 was demonstrated in type I EC. CONCLUSIONS: The most pronounced expression involved c-MET in all EC I and EC II tissues (in over 80% of cases). A tendency was detected for a high expression of NESF-1 in patients with type II EC, who also exhibited a high expression of MSH2.

Nucleobindins and encoded peptides: From cell signaling to physiology.

Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two NUCBs, nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2), were discovered during the 1990s. These two peptides are shown to have diverse functions, including the regulation of inflammation and bone formation, among others. In 2006, Oh-I and colleagues discovered that three peptides encoded within the NUCB2 could be processed by prohormone convertases. These peptides were named nesfatin-1, 2 and 3, mainly due to the satiety and fat influencing properties of nesfatin-1. However, it was found that nesfatin-2 and -3 have no such effects. Nesfatin-1, especially its mid-segment, is very highly conserved across vertebrates. Although the receptor(s) that mediate nesfatin-1 effects are currently unknown, it is now considered an endogenous peptide with multiple functions, affecting central and peripheral tissues to regulate metabolism, reproduction, endocrine and other functions. We recently identified a nesfatin-1-like peptide (NLP) encoded within the NUCB1. Like nesfatin-1, NLP suppressed feed intake in mice and fish, and stimulated insulin secretion from pancreatic beta cells. There is considerable evidence available to indicate that nucleobindins and its encoded peptides are multifunctional regulators of cell biology and whole animal physiology. This review aims to briefly discuss the structure, distribution, functions and mechanism of action nucleobindins and encoded peptides.

Ghrelin and NUCB2/Nesfatin-1 Co-Localization With Digestive Enzymes in the Intestine of Pejerrey (Odontesthes bonariensis).

Ghrelin (orexigenic) and nesfatin-1 (anorexigenic) are two peptides with opposing actions on food intake regulation and are mainly expressed in the hypothalamus and gut of mammals and fish. Both are involved in the regulation of a wide range of physiological processes in vertebrates, including metabolism, growth, and reproduction. However, the anatomical relationship between these peptides and the nutrient assimilation processes are not well understood. Thus, the aim of this work was to determine the localization of ghrelin, nesfatin-1, and several enzymes involved in the digestive process (lipoprotein lipase, aminopeptidase A, trypsin, and sucrase-isomaltase) in the intestine of pejerrey (Odontesthes bonariensis), a species with commercial importance in South America. We observed co-localization of ghrelin and nesfatin-1 in enteroendocrine cells, absorptive cells, and in cells of the lamina propia. Approximately half of the cells displaying ghrelin-like immunoreactivity co-localized the NUCB2/nesfatin-1-like signal. In addition, both peptides showed co-localization with lipoprotein lipase, aminopeptidase A, trypsin, or sucrase-isomaltase. All digestive enzymes except for aminopeptidase A and trypsin, showed high co-localization (68-88%) with both ghrelin-like and NUCB2/nesfatin-1-like signals in absorptive, enteroendocrine, and lamina propria cells. Together, our results provide immunohistochemical evidence supporting a role for both ghrelin and NUCB2/nesfatin-1 in the regulation of nutrient assimilation in fish. Anat Rec, 302:973-982, 2019. © 2018 Wiley Periodicals, Inc.