Search Results (20)

The present study was designed to establish the distribution pattern and immunohistochemical characteristics of phoenixin-immunoreactive (PNX-IR) urinary bladder afferent neurons (UB-ANs) of dorsal root ganglia (DRG) in female pigs. The sensory neurons investigated were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile(s) were identified using double-labelling immunohistochemistry with antibodies against PNX, calcitonin gene-related peptide (CGRP), calretinin (CRT), galanin (GAL), neuronal nitric oxide synthase (nNOS), pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin (SOM) and substance P (SP). Nearly half of UB-ANs contained PNX (45%), and the majority of such encoded sensory neurons were small in size (66%). The most numerous subpopulation of FB/PNX-positive neurons were those containing SP (71%). CGRP, GAL or PACAP were observed in a smaller number of PNX-containing UB-ANs (50%, 30% or 25%, respectively), while PNX-positive sensory neurons simultaneously immunostained with nNOS, CRT or SOM constituted a small fraction of all retrogradely-traced DRG neurons (DRGs; 15%, 6.5% or 1.6%, respectively). Furthermore, the numerical analysis of neurons expressing individual antigens, performed on 10 μm-thick consecutive sections, allows us to state that studied sensory neurons can be classified as neurons “coded” either by the simultaneous presence of SP/CGRP/PACAP/GAL, SP/CGRP/PACAP/NOS, SP/CGRP/PACAP/NOS/CRT and/or SP/CGRP/GAL/PACAP, or, as a separate population, those capable of SOM synthesis (SP/CGRP/SOM/PACAP/GAL-positive neurons). The present study reveals the extensive expression of PNX in the DRGs supplying to the urinary bladder, indicating an important regulatory role of this neuropeptide in the control of physiological function(s) of this organ. Full article

Background/Objectives: Endometriosis is a painful chronic condition in which the endometrium grows outside the uterus. The epithelial–mesenchymal transition (EMT) is critical to endometriosis progression, where cells lose epithelial traits and gain invasiveness. Methods: This study investigates the effects of phoenixin-14 (PNX-14), a neuropeptide found at reduced levels in endometriosis patients, on the expression of two molecular EMT markers, CDH1 (E-cadherin) and THBS2 (thrombospondin 2), as well as cell viability in the endometriosis-derived 12Z cell line. Cells were treated with physiological (0.2 nM) and endometriosis-relevant (0.05 nM) concentrations of PNX-14. Gene expression was analyzed using RT-qPCR, while protein localization was assessed by immunocytochemistry. Cell viability was measured using an XTT assay. Results: THBS2 gene expression was significantly decreased, and CDH1 remained unchanged in cells stimulated by 0.05 nM PNX-14. Immunolocalization indicates a weaker THBS2 and CDH1 protein immunosignal reaction for 0.05 nM PNX-14. PNX-14 treatment also exhibited a biphasic effect on cell viability. Lower concentration initially decreased viability at 48 h but then significantly increased it at 72 h. This increase coincided with the decrease in THBS2 expression, suggesting a potential link between PNX-14, THBS2, and cell viability. Conclusions: A negative correlation between cell viability and the expression of both EMT markers further highlights their possible involvement in the survival and adaptability of ectopic epithelial cells. Our findings suggest a complex interplay between PNX-14, EMT markers, and cell viability in ectopic epithelial cells. PNX-14’s ability to modulate these factors warrants further investigation to elucidate its role in endometriosis. Full article

This review article comprehensively explores the role of orexigenic and anorexigenic peptides in the management of obesity in companion animals, with a focus on clinical applications. Obesity in domestic animals, particularly dogs and cats, is prevalent, with significant implications for their health and well-being. Factors contributing to obesity include overfeeding, poor-quality diet, lack of physical activity, and genetic predispositions. Despite the seriousness of this condition, it is often underestimated, with societal perceptions sometimes reinforcing unhealthy behaviors. Understanding the regulation of food intake and identifying factors affecting the function of food intake-related proteins are crucial in combating obesity. Dysregulations in these proteins, whether due to genetic mutations, enzymatic dysfunctions, or receptor abnormalities, can have profound health consequences. Molecular biology techniques play a pivotal role in elucidating these mechanisms, offering insights into potential therapeutic interventions. The review categorizes food intake-related proteins into anorexigenic peptides (inhibitors of food intake) and orexigenic peptides (enhancers of food intake). It thoroughly examines current research on regulating energy balance in companion animals, emphasizing the clinical application of various peptides, including ghrelin, phoenixin (PNX), asprosin, glucagon-like peptide 1 (GLP-1), leptin, and nesfatin-1, in veterinary obesity management. This comprehensive review aims to provide valuable insights into the complex interplay between peptides, energy balance regulation, and obesity in companion animals. It underscores the importance of targeted interventions and highlights the potential of peptide-based therapies in improving the health outcomes of obese pets. Full article

The onset of puberty, which is under the control of the hypothalamic–pituitary–gonadal (HPG) axis, is influenced by various factors, including obesity, which has been associated with the earlier onset of puberty. Obesity-induced hypothalamic inflammation may cause premature activation of gonadotropin-releasing hormone (GnRH) neurons, resulting in the development of precocious or early puberty. Mechanisms involving phoenixin action and hypothalamic microglial cells are implicated. Furthermore, obesity induces structural and cellular brain alterations, disrupting metabolic regulation. Imaging studies reveal neuroinflammatory changes in obese individuals, impacting pubertal timing. Magnetic resonance spectroscopy enables the assessment of the brain’s neurochemical composition by measuring key metabolites, highlighting potential pathways involved in neurological changes associated with obesity. In this article, we present evidence indicating a potential association among obesity, hypothalamic inflammation, and precocious puberty. Full article

The regulation of food intake occurs at multiple levels, and two of the components of this process are orexigenic and anorexigenic peptides, which stimulate or inhibit appetite, respectively. The study of the function of these compounds in domestic cattle is essential for production efficiency, animal welfare, and health, as well as for economic benefits, environmental protection, and the contribution to a better understanding of physiological aspects that can be applied to other species. In this study, the real-time PCR method was utilized to determine the expression levels of GHRL, GHSR, SMIM20, GPR173, LEP, LEPR, and NUCB2 (which encode ghrelin, its receptor, phoenixin-14, its receptor, leptin, its receptor, and nesfatin-1, respectively) in the gastrointestinal tract (GIT) of Polish Holstein–Friesian breed cattle. In all analyzed GIT segments, mRNA for all the genes was present in both age groups, confirming their significance in these tissues. Gene expression levels varied distinctly across different GIT segments and between young and mature subjects. The differences between calves and adults were particularly pronounced in areas such as the forestomachs, ileum, and jejunum, indicating potential changes in peptides regulating food intake based on the developmental phase. In mature individuals, the forestomachs predominantly displayed an increase in GHRL expression, while the intestines had elevated levels of GHSR, GPR173, LEP, and NUCB2. In contrast, the forestomachs in calves showed upregulated expressions of LEP, LEPR, and NUCB2, highlighting the potential importance of peptides from these genes in bovine forestomach development. Full article

There are some initial suggestions in the literature that phoenixin, spexin, nesfatin-1 and kisspeptin may play a role in the pathogenesis of affective disorders. Therefore, they may also be cautiously considered as potential diagnostic or predictive biomarkers of BD. This study aimed to evaluate the levels of the aforementioned neuropeptides in the peripheral blood of children and adolescents with bipolar. This study included 122 individuals: 67 persons with diagnosed bipolar disorder types I and II constituted the study group, and 55 healthy persons were included in the control group. Statistically significant differences in the concentrations of neuropeptides between the control and study groups were noted in relation to nesfatin-1 and spexin (although spexin lost statistical significance after introducing the Bonferroni correction). In a logistic regression analysis, an increased risk of bipolar disorder was noted for a decrease in nesfatin-1 concentration. Lower levels of nesfatin-1 seemed to be a significant risk factor for the development of bipolar disorder types I and II. Furthermore, the occurrence of bipolar disorder was associated with significantly elevated levels of spexin. None of the analyzed neuropeptides was significantly correlated with the number of symptoms of bipolar disorder. Full article

Phoenixin-14 (PNX), initially discovered in the rat hypothalamus, was also detected in dorsal root ganglion (DRG) cells, where its involvement in the regulation of pain and/or itch sensation was suggested. However, there is a lack of data not only on its distribution in DRGs along individual segments of the spinal cord, but also on the pattern(s) of its co-occurrence with other sensory neurotransmitters. To fill the above-mentioned gap and expand our knowledge about the occurrence of PNX in mammalian species other than rodents, this study examined (i) the pattern(s) of PNX occurrence in DRG neurons of subsequent neuromeres along the porcine spinal cord, (ii) their intraganglionic distribution and (iii) the pattern(s) of PNX co-occurrence with other biologically active agents. PNX was found in approximately 20% of all nerve cells of each DRG examined; the largest subpopulation of PNX-positive (PNX⁺) cells were small-diameter neurons, accounting for 74% of all PNX-positive neurons found. PNX⁺ neurons also co-contained calcitonin gene-related peptide (CGRP; 96.1%), substance P (SP; 88.5%), nitric oxide synthase (nNOS; 52.1%), galanin (GAL; 20.7%), calretinin (CRT; 10%), pituitary adenylate cyclase-activating polypeptide (PACAP; 7.4%), cocaine and amphetamine related transcript (CART; 5.1%) or somatostatin (SOM; 4.7%). Although the exact function of PNX in DRGs is not yet known, the high degree of co-localization of this peptide with the main nociceptive transmitters SP and CGRP may suggests its function in modulation of pain transmission. Full article

Background: We study the relationship between phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA) and oxytocin (OT) levels together with pregnancy rates in women after ovarian stimulation (OS). Methods: In a prospective case–control study, 56 infertile women were enrolled from the Department of Gynecological Endocrinology University Hospital. Infertile women age < 40 years old, with polycystic ovary syndrome (PCOS), confirmed tubal patency and suitable sperm quality were included. Blood samples were drawn twice—before the initiation of OS and before the human chorionic gonadotropin (hCG) administration. Assessments of PNX-14, NES-1, DA and OT serum levels were performed. Pregnancy rates after OS were observed. Results: Pregnant women showed higher baseline NES-1 and OT levels (+29.2% and +44%) but not PNX-14 and DA levels when compared to non-pregnant ones. In pregnant women, positive correlations between OT and prolactin, PRL (r = 0.47, p = 0.04), as well as between OT and NES-1 (r = 0.55, p = 0.02), were observed at baseline. At baseline, an OT level increase was associated with a positive pregnancy rate (per 100 pg/mL, OR = 1.39, 95% CI 1.04–1.74), while after OS, higher PNX-14 was a predictor of pregnancy (by 10 pg/mL, OR = 1.23, 95%CI 1.07–1.39). Post-stimulation PNX-14, NES-1 and DA concentrations were higher in pregnant women compared to non-pregnant ones (+17.4%, +26.1%, and +45.5%, respectively; all p < 0.05). In the pregnant group, OT levels were 2.7-times lower than in the remainder (p = 0.03). Moreover, in pregnant participants, a negative association between NES-1 and PNX (r = −0.53, p = 0.024) was observed. Conclusion: Elevated PNX-14, NES-1 and DA along with decreased OT levels were observed in women who achieved pregnancy. Full article

Purpose: Acute central serous chorioretinopathy (ACSCR) is a condition characterized by decreased visual acuity, macular thickening, and edema under the retinal layer. Although the underlying mechanisms of the disease are not fully understood, oxidative stress is considered to be a critical risk factor. The aim of this study was to shed light on the pathophysiology of ACSCR by investigating the levels of circulating trimethylamine N-oxide (TMAO), phoenixin (PNX), alarin (ALA), and spexin (SPX) molecules in ACSCR patients. Methods: The study included 30 ACSCR patients and 30 healthy individuals as controls. ACSCR was diagnosed using optical coherence tomography (OCT) imaging. Five mL blood samples were collected from all participants following overnight fasting. The levels of TMAO, PNX, ALA, and SPX in the blood samples were measured using the ELISA method. Results: Visual acuity was found to be significantly reduced in ACSCR patients compared to the control group (<0.05), while macular thickness was increased (<0.05). Furthermore, TMAO, PNX, and ALA levels were significantly higher in ACSCR patients (<0.05), while SPX levels were significantly lower compared to the control group (<0.05). In ACSCR patients, there was a positive correlation between macular thickness and TMAO, PNX, and ALA; there was, however, a negative correlation with SPX. Additionally, visual acuity was negatively correlated with TMAO, PNX, and ALA, while SPX levels decreased as visual acuity decreased. Conclusions: These results demonstrate a correlation between the TMAO, PNX, ALA, and SPX levels of ACSCR patients and their visual acuity and macular thickness. Given the role of these molecules in ACSCR’s pathophysiology, they hold promise as potential diagnostic, therapeutic, and follow-up markers in the future. Full article

Phoenixin-14 is a recently discovered peptide regulating appetite. Interestingly, it is expressed in the gastrointestinal tract; however, its supposed receptor, GPR173, is predominantly found in hypothalamic areas. To date, it is unknown how peripherally secreted phoenixin-14 is able to reach its centrally located receptor. To investigate whether phoenixin is able to pass the blood–brain barrier, we used an in vitro mono-culture blood–brain barrier (BBB) model consisting of brain capillary-like endothelial cells derived from human induced-pluripotent stem cells (hiPSC-BCECs). The passage of 1 nMol and 10 nMol of phoenixin-14 via the mono-culture was measured after 30, 60, 90, 120, 150, 180, 210, and 240 min using a commercial ELISA kit. The permeability coefficients (PC) of 1 nMol and 10 nMol phoenixin-14 were 0.021 ± 0.003 and 0.044 ± 0.013 µm/min, respectively. In comparison with the PC of solutes known to cross the BBB in vivo, those of phoenixin-14 in both concentrations are very low. Here, we show that phoenixin-14 alone is not able to cross the BBB, suggesting that the effects of peripherally secreted phoenixin-14 depend on a co-transport mechanism at the BBB in vivo. The mechanisms responsible for phoenixin-14′s orexigenic property along the gut–brain axis warrant further research. Full article

The corpus luteum is a small gland of great importance because its proper functioning determines not only the appropriate course of the estrous/menstrual cycle and embryo implantation, but also the subsequent maintenance of pregnancy. Among the well-known regulators of luteal tissue functions, increasing attention is focused on the role of neuropeptides and adipose tissue hormones—adipokines. Growing evidence points to the expression of these factors in the corpus luteum of women and different animal species, and their involvement in corpus luteum formation, endocrine function, angiogenesis, cells proliferation, apoptosis, and finally, regression. In the present review, we summarize the current knowledge about the expression and role of adipokines, such as adiponectin, leptin, apelin, vaspin, visfatin, chemerin, and neuropeptides like ghrelin, orexins, kisspeptin, and phoenixin in the physiological regulation of the corpus luteum function, as well as their potential involvement in pathologies affecting the luteal cells that disrupt the estrous cycle. Full article

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women and a major cause of anovulatory infertility. A diagnosis of PCOS is established based the presence of two out of three clinical symptoms, which are criteria accepted by the ESHRE/ASRM (European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine). Gonadotropin-releasing hormone (GnRH) is responsible for the release of luteinizing hormone, and follicle stimulating hormone from the pituitary and contributes a leading role in controlling reproductive function in humans. The goal of this review is to present the current knowledge on neuroendocrine determinations of PCOS. The role of such neurohormones as GnRH, and neuropeptides kisspeptin, neurokinin B, phoenixin-14, and galanin is discussed in this aspect. Additionally, different neurotransmitters (gamma-aminobutyric acid (GABA), glutamate, serotonin, dopamine, and acetylcholine) can also be involved in neuroendocrine etiopathogenesis of PCOS. Studies have shown a persistent rapid GnRH pulse frequency in women with PCOS present during the whole ovulatory cycle. Other studies have proved that patients with PCOS are characterized by higher serum kisspeptin levels. The observations of elevated serum kisspeptin levels in PCOS correspond with the hypothesis that overactivity in the kisspeptin system is responsible for hypothalamic-pituitary-gonadal axis overactivity. In turn, this causes menstrual disorders, hyperandrogenemia and hyperandrogenism. Moreover, abnormal regulation of Neurokinin B (NKB) is also suspected of contributing to PCOS development, while NKB antagonists are used in the treatment of PCOS leading to reduction in Luteinizing hormone (LH) concentration and total testosterone concentration. GnRH secretion is regulated not only by kisspeptin and neurokinin B, but also by other neurohormones, such as phoenixin-14, galanin, and Glucagon-like peptide-1 (GLP-1), that have favorable effects in counteracting the progress of PCOS. A similar process is associated with the neurotransmitters such as GABA, glutamate, serotonin, dopamine, and acetylcholine, as well as the opioid system, which may interfere with secretion of GnRH, and therefore, influence the development and severity of symptoms in PCOS patients. Additional studies are required to explain entire, real mechanisms responsible for PCOS neuroendocrine background. Full article

Due to phoenixin’s role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide (LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (n = 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (p < 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold, p < 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (p < 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress. Full article

Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic–pituitary–gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17β-estradiol association in women with endometriosis, and the expression of SMIM20/PNX signaling via GPR173. Serum PNX, FSH, LH, and 17β-estradiol concentrations were measured by enzyme and electrochemiluminescence immunoassay. SMIM20/PNX and GPR173 expression in the eutopic and ectopic endometrium was assessed by qPCR and immunohistochemistry. Reduced PNX level, increased LH/FSH ratio and elevated 17β-estradiol concentration were found in patients with endometriosis. No differences in SMIM20 expression were observed between the studied endometria. GPR173 expression was lower in ectopic than in eutopic endometria. SMIM20 expression was mainly restricted to stroma. GPR173 was detected in some eutopic and ectopic stromal cells and in eutopic glandular epithelial cells. Discriminant analysis indicates the diagnostic relevance of PNX and LH/FSH ratio in patients with endometriosis. In women with endometriosis, reduced PNX levels and GPR173 expression may be responsible for HPG axis dysregulation. These new insights may contribute to a better understanding of the pathophysiology of endometriosis and provide the basis for a new strategy for diagnosis and treatment of endometriosis. Full article

Recent studies have shown a rise in precocious puberty, especially in girls. At the same time, childhood obesity due to overnutrition and energy imbalance is rising too. Nutrition and fertility are currently facing major challenges in our societies, and are interconnected. Studies have shown that high-fat and/or high-glycaemic-index diet can cause hypothalamic inflammation and microglial activation. Molecular and animal studies reveal that microglial activation seems to produce and activate prostaglandins, neurotrophic factors activating GnRH (gonadotropin-releasing hormone expressing neurons), thus initiating precocious puberty. GnRH neurons’ mechanisms of excitability are not well understood. In this review, we study the phenomenon of the rise of precocious puberty, we examine the physiology of GnRH neurons, and we review the recent literature regarding the pathophysiological mechanisms that connect diet-induced hypothalamic inflammation and diet-induced phoenixin regulation with precocious puberty. Full article