Neuropeptide Levels Research Articles

ХАРАКТЕРИСТИКА ЗУДА И НЕКОТОРЫХ НЕЙРОПЕПТИДОВ ПРИ ПСОРИАЗЕ, АССОЦИИРОВАННОМ С ПСИХИЧЕСКИМИ РАССТРОЙСТВАМИ

Background. Pruritus is one of the most common symptoms accompanying psoriasis. Patients with pruritus report decreased quality of life, depression, anxiety, and body dysmorphic concerns, as well as reduced effectiveness of treatment. Objective. To study the intensity of skin pruritus and the level of neuropeptides in the blood serum in patients with psoriasis associated with mental disorders. Material and methods. The main methods of examination of 110 patients with psoriasis were clinical and anamnestic method as well as clinical laboratory and clinical psychopathological ones. Results. In patients with a combined variant of psoriasis and mental disorders, a significantly higher incidence of skin pruritus (p <0.001), pain (p <0.01), elevated serum levels of substance P (p˂0.001) was established; significantly more often scratching increased pruritus (p<0.05), pruritus led to depression (p<0.01), pruritus was prolonged (p<0.05) with a significant decrease in quality of life (p<0.05), mood swings were characterized as “severe"(p<0.05) and "unbearable" (p<0.001). Conclusion. Pruritus is one of the most common and bothersome symptoms of psoriasis and is often associated with psychosomatic and psychiatric comorbidities, as well as elevated blood serum levels of certain neuropeptides. This fact may indicate the role of the latter in the pathogenesis of this combined pathology. Considering the possibility of therapeutic potential on the neuropeptides production level, the obtained data on their role in the pathogenesis of psoriasis and its comorbid pathology will allow us to develop a personalized approach to therapy, taking into account the severity of the disease and concomitant pathology.

Frequency and impact of post-traumatic stress disorder and traumatic life events in patients with migraine

IntroductionPost-traumatic stress disorder (PTSD) has been proposed as a risk factor for chronification of migraine. The aim of this study was to investigate the frequency of PTSD and traumatic life events (TE) in patients with episodic (EM) and chronic migraine (CM) and their impact on clinical parameters, other comorbidities, and migraine biomarkers. Material and methodsPatients with EM and CM according to the International Classification of Headache Disorders (third edition; beta version) were recruited at a headache unit and a primary care centre. We used questionnaires validated for research on PTSD, TEs, cranial autonomic symptoms, comorbidities (depression, anxiety, and fatigue), disability, migraine impact, and quality of life. Baseline serum levels of CGRP, VIP, and PACAP were determined by ELISA. ResultsThe study included 116 patients: 35 with EM and 81 with CM. Nineteen presented refractory migraine. PTSD was detected in 23 patients (19.8%): 20 with CM and 3 with EM (chi-square: P = .046; Fisher T: P = .073). No significant differences were identified between the EM and CM groups for frequency of any TE nor the number of TEs per patient. A total of 5/19 patients with refractory migraine had experienced sexual violence (vs 2/97 with non-refractory migraine; P = .002). PTSD was associated with more autonomic symptoms; higher scores on anxiety, depression, and fatigue scales; and poorer quality of life; it did not change neuropeptide levels. ConclusionsOur results suggest that PTSD is frequent in patients with migraine, and especially CM, in our setting; history of sexual violence is particularly frequent in patients with refractory migraine. PTSD has a negative impact on migraine, with higher numbers of comorbidities and poorer quality of life; therefore, further research is needed in this patient group.

Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches

BackgroundIn addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors.MethodsIn a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague–Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration.ResultsBoth doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP.ConclusionsThe findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine.

Comparison of orexigenic and anorexigenic neuropeptide levels in hyperemesis gravidarum patients with normal pregnant women: A prospective cohort study.

The aim of this study was to determine whether orexigenic neuropeptides, orexin and galanin, and anorexigenic neuropeptides, alpha-melanocyte-stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcript (CART), are implicated in hyperemesis gravidarum (HG). Fifty pregnant women who had been diagnosed with HG between April 2022 and February 2023 at the Siirt University Faculty of Medicine Training and Research Hospital (tertiary center) were recruited for this study. An equal number of pregnant women without an HG diagnosis were included in the study as the control group. Participants' age, pregnancy history, medical history, thyroid function test results, complete blood count results, and electrolyte levels were recorded, and their orexin, galanin, α-MSH, and CART serum levels were analyzed using an enzyme-linked immunosorbent assay. No statistically significant differences in orexigenic neuropeptides (orexin and galanin) were observed between the HG and control groups. A statistical difference was found between an anorexigenic neuropeptide (α-MSH) and the control group (P = .012). Based on a receiver operating characteristic analysis, the α-MSH parameter was statistically significant for distinguishing between participants with an HG diagnosis and those without, with a sensitivity of 63.6%, specificity of 65.9%, and cutoff value of 11769.3 pg/mL (P = .012, area under curve: 0.655). Based on the severity classification of ketonuria (ketonuria levels of +1 or +2 were classified as mild, whereas levels of +3 or +4 were classified as moderate to severe), the anorexigenic CART neuropeptide was found to be a statistically significant diagnostic indicator of severe ketonuria (P = .020). α-MSH and CART levels were found to be related in HG patients and in HG patients with severe ketonuria.

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity

BackgroundSrc family kinases (SFKs) contribute to migraine pathogenesis, yet its role in regulating photophobia behaviour, one of the most common forms of migraine, remains unknown. Here, we addressed whether SFKs antagonism alleviates photophobia behavior and explored the underlying mechanism involving hypothalamus and trigeminal ganglion activity, as measured by the alteration of neuropeptide levels and transcriptome respectively.MethodsA rapid-onset and injury-free mouse model of photophobia was developed following intranasal injection of the TRPA1 activator, umbellulone. The role of SFKs antagonism on light aversion was assessed by the total time the mouse stays in the light and transition times between the dark and light compartments. To gain insight to the preventive mechanism of SFKs antagonism, hypothalamic neuropeptides levels were assessed using enzyme linked immunofluorescent assay and trigeminal ganglion activity were assessed using RNA-sequencing and qPCR analysis.ResultsSFKs antagonism by a clinically relevant SFKs inhibitor saracatinib reduced the total time in light and transition times in male mice, but not in females, suggesting SFKs play a crucial role in photophobia progressing and exhibit a male-only effect. SFKs antagonism had no effect on hypothalamic calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide levels of all mice investigated, suggesting the gender-different effect of saracatinib on light aversion appears to be independent of these hypothalamic neuropeptide levels. In trigeminal ganglion of male mice, photophobia is associated with profound alteration of differentially expressed genes, part of which were reversed by SFKs antagonism. Subsequent qPCR analysis showed SFKs antagonism displayed gender-different modulation of expression in some candidate genes, particularly noteworthy those encoding ion channels (trpm3, Scn8a), ATPase signaling (crebbp, Atp5α1) and kinase receptors (Zmynd8, Akt1).ConclusionsIn conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine.

Correlation between the neuroendocrine axis, microbial species, inflammatory response, and gastrointestinal symptoms in irritable bowel syndrome.

This study examines the complex relationships among the neuroendocrine axis, gut microbiome, inflammatory responses, and gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes. To investigate the interactions between the neuroendocrine axis, gut microbiome, inflammation, and gastrointestinal symptoms in patients with IBS. Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study. Healthy individuals undergoing routine check-ups during the same period served as the control group. Data were collected on neuroendocrine hormone levels, gut microbiome profiles, inflammatory biomarkers, and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis. IBS patients exhibited significant dysregulation of the neuroendocrine axis, with altered levels of cortisol, serotonin, and neuropeptides compared to healthy controls. The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera, including Bifidobacterium, Lactobacillus, and Faecalibacterium, which were associated with neuroendocrine disturbances. Additionally, elevated levels of inflammatory markers, such as C-reactive protein, interleukin-6, and tumor necrosis factor-α, were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain, bloating, and altered bowel habits. The findings suggest that targeting the neuroendocrine axis, gut microbiome, and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.

Effects of replacing soybean meal with enzymolysis-fermentation compound protein feed on growth performance, apparent digestibility of nutrients, carcass traits, and meat quality in growing-finishing pigs

BackgroundAddressing the shortage of high-quality protein resources, this study was conducted to investigate the effects of replacing soybean meal (SBM) with different levels of enzymolysis-fermentation compound protein feed (EFCP) in the diets of growing-finishing pigs, focusing on growth performance, nutrients digestibility, carcass traits, and meat quality.MethodsSixty DLY (Duroc × Landrace × Yorkshire) pigs with an initial body weight of 42.76 ± 2.05 kg were assigned to 5 dietary treatments in a 2 × 2 + 1 factorial design. These dietary treatments included a corn-soybean meal diet (CON), untreated compound protein feed (UCP) substitution 50% (U50) and 100% SBM (U100) diets, and EFCP substitution 50% (EF50) and 100% SBM (EF100) diets. Each treatment had 6 pens (replicates) with 2 pigs per pen, and the experiment lasted 58 d, divided into phase I (1–28 d) and phase II (29–58 d). Following phase I, only the CON, U50, and EF50 groups were continued for phase II, each with 5 replicate pens. On d 59, a total of 15 pigs (1 pig/pen, 5 pens/treatment) were euthanized.ResultsDuring phase I, the EF50 group had a higher average daily gain (ADG) in pigs (P < 0.05) compared to the CON group, whereas the U50 group did not have a significant difference. As the substitution ratio of UCP and EFCP increased in phase I, there was a noticeable reduction in the final body weight and ADG (P < 0.05), along with an increase in the feed-to-gain ratio (F/G) (P < 0.05). In phase II, there were no significant differences in growth performance among the treatment groups, but EF50 increased the apparent digestibility of several nutrients (including dry matter, crude protein, crude fiber, acid detergent fiber, ash, gross energy) compared to U50. The EF50 group also exhibited significantly higher serum levels of neuropeptide Y and ghrelin compared to the CON and U50 groups (P < 0.05). Moreover, the EF50 group had higher carcass weight and carcass length than those in the CON and U50 groups (P < 0.05), with no significant difference in meat quality.ConclusionsThe study findings suggest that replacing 50% SBM with EFCP during the growing-finishing period can improve the growth performance, nutrient digestibility, and carcass traits of pigs without compromising meat quality. This research offers valuable insights into the modification of unconventional plant protein meals and developing alternatives to SBM.

Analysis of Salivary Neuropeptides in Anxiety and Depression Using the Luminex MAGPIX® System.

Anxiety and depressive disorders are highly prevalent mental health conditions, affecting millions worldwide.Advancements in neurobiology have identified the effects of various neuropeptides in modulating mood and stress responses.Some of the well-researched neuropeptides in plasma are oxytocin (OXT), alpha-melanocyte-stimulating hormone (alpha-MSH), beta-endorphin, neurotensin, and substance P.In this study, we used methods of liquid biopsy to acquire saliva samples to analyze the concentrations of neuropeptides associated with depression. The study was conducted in Bratislava, Slovakia, from January to June 2022. Participants were 20 subjects treated for depression and anxiety without medication; the control group consisted of 20 healthy individuals with no personal history of depression or anxiety. Salivary samples were collected using buccal swabs to measure the concentrations of the examined neuropeptides. Laboratory analysis was based on detecting fluorescent signals performed on the Luminex MAGPIX® System (Luminex Corporation, Austin, Texas).Means and standard deviations were calculated for individual neuropeptide levels.To determine if there are statistically significant differences in neuropeptide levels between individuals with and without depression, independent t-tests and a one-way ANOVA were conducted. Our findings indicate a significant decrease in all studied neuropeptides in subjects compared to healthy controls. Reductions in mean levels were observed for OXT (7.3), alpha-MSH (3.9), beta-endorphin (2.9), neurotensin (15.1), and a 6.9-fold decrease for substance P.Alpha-MSH and beta-endorphin showed higher variability in measured levels within both groups. The results of this study indicate that the levels of the studied salivary neuropeptides, OXT, alpha-MSH, beta-endorphin, neurotensin, and substance P, are statistically significantly reduced in individuals with depression compared to healthy controls.

Is Nasal Dysbiosis a Required Component for Neuroinflammation in Major Depressive Disorder?

Human microbiota is known to influence immune and cerebral responses by direct and/or indirect mechanisms, including hypothalamic-pituitary-adrenal axis signaling, activation of neural afferent circuits to the brain, and by altering the peripheral immune responses (cellular and humoral immune function, circulatory inflammatory cells, and the production of several inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species). The inflammatory responses in the nasal mucosa (rhinitis) or paranasal sinuses (chronic rhinosinusitis) are dual conditions related with a greater risk for developing depression. In the nasal cavity, anatomic components of the olfactive function are in direct contact with the CNS through the olfactory receptors, neurons, and axons that end in the olfactory bulb and the entorhinal cortex. Local microbiome alterations (dysbiosis) are linked to transepithelial translocation of microorganisms and their metabolites, which disrupts the epithelial barrier and favors vascular permeability, increasing the levels of several inflammatory molecules (both cytokines and non-cytokine mediators: extracellular vesicles (exosomes) and neuropeptides), triggering local inflammation (rhinitis) and the spread of these components into the central nervous system (neuroinflammation). In this review, we discuss the role of microbiota-related immunity in conditions affecting the nasal mucosa (chronic rhinosinusitis and allergic rhinitis) and their relevance in major depressive disorders, focusing on the few mechanisms known to be involved and providing some hypothetical proposals on the pathophysiology of depression.

The role of depth of general anesthesia in serum CGRP and SP level in diabetes patients.

Diabetes, which is associated with cardiovascular disease and related microvascular complications, affects life expectancy and decrease quality of life. A trial reports that the risk of patients with diabetes having cardiovascular disease is 2-4 times compared with that in patients without diabetes. This study aims to investigate the relationship between depth of general anesthesia in patients with diabetes mellitus. This clinical study totally includes 40 patients with diabetes mellitus, and these patients are divided into following two groups: diabetes mellitus deep anesthesia group and diabetes mellitus light anesthesia group, and then these patients receive general anesthesia combined with laparoscopic surgery. Preoperative patient general data and intraoperative patient general data are collected and analyzed. Calcitonin gene-related peptide (CGRP) and substance P (SP) level are determined by Enzyme-linked immunosorbent assay (ELISA). This study included a total of 40 patients. There were no significant differences in demographic and preoperative patient general data between the two groups. Measurements were taken for operative time, anesthesia time, recovery time after drug withdrawal, dwell time in the recovery room, intraoperative fluid volume, intraoperative blood loss, and intraoperative urine output between the two groups. Significant differences were observed in the recovery time after drug withdrawal between the two groups. CGRP and SP level in diabetes mellitus deep anesthesia group are evidently more than those in diabetes mellitus light anesthesia group. CGRP and SP level are involved in the diabetes mellitus and up-regulated CGRP and SP can prevent the development of diabetes mellitus. Our study extends the existing literature by addressing a gap in knowledge regarding the impact of anesthesia depth on neuropeptide levels in diabetes mellitus patients. By delineating this relationship, we aim to contribute to the advancement of perioperative care practices and ultimately improve outcomes for individuals with diabetes undergoing surgical procedures. Our study's findings provide valuable insights into the complex interactions between anesthesia, neuropeptides, and diabetes mellitus, offering the potential for personalized perioperative care, enhanced pain management, and improved surgical outcomes. These implications highlight the clinical relevance of our research and its potential to inform future advancements in perioperative care for diabetic patients undergoing surgery.

Effects of Venoactive Drug Therapy and Ovarian Vein Interventions on Vasoactive Neuropeptide and Cytokine Levels in Patients with Pelvic Venous Disorders

To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs). The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n=38) or OVE/OVR (n=32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3months after OVE/OVR. The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7±0.1ng/mL and 0.12±0.02ng/mL before treatment; 0.5±0.12ng/mL and 0.09±0.06ng/mL after treatment, respectively; all P<0.05). No changes in cytokine levels were revealed. Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.

Nape seven needles combined with pressing moxibustion for cervical vertigo: a randomized controlled trial

To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV). A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups. After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05). Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.

Secretory factors released from high dose radiation-activated osteoclasts increase the expression level of pain-associated neuropeptides in sensory neuronal cultures.

Stereotactic Body Radiation Therapy for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients' quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated the potential crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using the murine pre-osteoclast cell line Raw264.7, we induced differentiation with RANKL, followed by 10Gy gamma-irradiation. Conditioned media from these irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also directly exposed to 10Gy radiation, with and without osteoclast co-culture. Analysis of osteoclast markers and pain-associated neuropeptides was conducted using RT-qPCR and histochemical staining. Osteoclast differentiation and activity were inhibited using Osteoprotegerin and risedronate. Results showed that high-dose radiation significantly increased osteoclast size, resorption pit size, and activity biomarkers. Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain.

The role of body composition and appetite-regulating hormones in idiopathic central precocious puberty and their changes during GnRH analog therapy.

It was aimed to compare circulating levels of ghrelin, leptin, peptide YY (PYY), and neuropeptide (NPY) between girls with idiopathic central precocious puberty (ICPP) and prepubertal girls, as well as to evaluate alterations in these hormone levels and body composition during leuprolide acetate treatment in girls with ICPP. This prospective study was conducted on girls with isolated premature thelarche (IPT), girls with ICPP, and age-matched prepubertal controls. Anthropometric measurements, body composition analysis and appetite-regulating hormone level measurements were performed in each group and also at the 6th and 12th months of the leuprolide acetate treatment for the girls with ICPP. Seventy-three girls participated in the study (24 girls with ICPP, 28 with IPT, and 21 prepubertal controls). No significant differences were observed in ghrelin, leptin, PYY, and NPY levels among the three groups. Leuprolide acetate treatment resulted in increased leptin, decreased PYY and NPY levels, and no significant changes in ghrelin. Despite no significant change in body mass index standard deviation score (BMI SDS), body fat percentage increased during treatment. While appetite-regulating hormones do not seem to directly contribute to precocious puberty pathogenesis, puberty blockade was shown to lead to altered levels of these hormones along with changes in body composition.

Chronic unpredictable stress (CUS) reduced phoenixin expression, induced abnormal sperm and testis morphology in male rats

Chronic stress caused by prolonged emotional pressure can lead to various physiological issues, including reproductive dysfunction. Although reproductive problems can also induce chronic stress, the impact of chronic stress-induced reproductive dysfunction remains contentious. This study investigates the effects of chronic unpredictable stress (CUS) on reproductive neuropeptides, sperm quality, and testicular morphology. Sixteen twelve-week-old Sprague Dawley rats were divided into two groups: a non-stress control group and a CUS-induced group. The CUS regimen involved various stressors over 28 days, with both groups undergoing behavioural assessments through sucrose-preference and forced-swim tests. Hypothalamic gene expression levels of CRH, PNX, GPR173, kisspeptin, GnRH, GnIH, and spexin neuropeptides were measured via qPCR, while plasma cortisol, luteinizing hormone (LH), and testosterone concentrations were quantified using ELISA. Seminal fluid and testis samples were collected for sperm analysis and histopathological evaluation, respectively. Results showed altered behaviours in CUS-induced rats, reflecting stress impacts. Hypothalamic corticotropin-releasing hormone (CRH) expression and plasma cortisol levels were significantly higher in CUS-induced rats compared to controls (p < 0.05). Conversely, phoenixin (PNX) expression decreased in the CUS group (p < 0.05), while kisspeptin, spexin, and gonadotropin-inhibitory hormone (GnIH) levels showed no significant differences between groups. Despite a significant increase in GnRH expression (p < 0.05), plasma LH and testosterone concentrations were significantly lower (p < 0.05) in CUS-induced rats. Histopathological analysis revealed abnormal testis morphology in CUS-induced rats, including disrupted architecture, visible interstitial spaces between seminiferous tubules, and absence of spermatogenesis. In conclusion, CUS affects reproductive function by modulating PNX and GnRH expression, influencing cortisol levels, and subsequently reducing plasma LH and testosterone concentrations. This study highlights the complex interplay between chronic stress and reproductive health, emphasizing the significant impact of stress on reproductive functions.

Specific Salivary Neuropeptides Shift Synchronously during Acute Stress in Fire Recruits.

Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting.

Gene Expression and Ultrastructural Evidence for Metabolic Derangement in the Primary Mitral Regurgitation Heart

Abstract Aims Chronic neurohormonal activation and hemodynamic load cause derangement in myocardial substrate utilization. We test the hypothesis that the primary mitral regurgitation heart (PMR) heart shows altered metabolic gene profile and cardiac ultrastructure consistent with decreased fatty acid and glucose metabolism despite LVEF &amp;gt; 60%. Methods and Results Metabolic gene expression in right atrial (RA), left atrial (LA), and left ventricular (LV) biopsies from donor hearts (n = 10) and from patients with moderate to severe PMR (n = 11) at surgery showed decreased mRNA glucose transporter type 4 (GLUT-4), GLUT-1 and insulin receptor substrate 2 and increased mRNA hexokinase 2, O-linked N-acetylglucosamine transferase and O-GlcNAcase, rate-limiting steps in the hexosamine biosynthetic pathway. Pericardial fluid levels of Neuropeptide Y were 4-fold higher than simultaneous plasma indicative of increased sympathetic drive. Quantitative TEM shows glycogen accumulation, glycophagy, increased lipid droplets, and mitochondrial cristae lysis. These findings are associated with increased mRNA for glycogen synthase kinase 3β, decreased carnitine palmitoyl transferase 2, and fatty acid synthase in PMR vs. normals. Cardiac magnetic resonance/positron emission tomography for 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake showed decreased LV [18F]FDG uptake and increased plasma HbA1c, free fatty acids, mtDAMPs in a separate cohort of stable moderate PMR patients with LVEF &amp;gt; 60% (n = 8) vs. normal controls (n = 8). Conclusions The PMR heart has a global ultrastructural and metabolic gene expression pattern of decreased glucose uptake along with increased glycogen and lipid droplets. Further studies must determine whether this presentation is an adaptation or maladaptation in the PMR heart in the clinical evaluation of PMR.

Effects on peripheral and central nervous system of key inflammatory intercellular signalling peptides and proteins in psoriasis.

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.

CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study

Background and objectiveEndometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients.Materials and methodsThe Visual Analog Scale (VAS) assessed pain in diagnosed EM. individuals. Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels.ResultsIn the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05).ConclusionDNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.

Insulin eye drops improve corneal wound healing in STZ-induced diabetic mice by regulating corneal inflammation and neuropeptide release

IntroductionIn recent years, insulin eye drops have attracted increasing attention from researchers and ophthalmologists. The aim of this study was to investigate the efficacy and possible mechanism of action of insulin eye drops in diabetic mice with corneal wounds.MethodsA type 1 diabetes model was induced, and a corneal epithelial injury model of 2.5 mm was established. We used corneal fluorescein staining, hematoxylin-eosin (H-E) staining and the Cochet-Bonnet esthesiometer to examine the process of wound healing. Subsequently, the expression levels of Ki-67, IL-1β, β3-tubulin and neuropeptides, including substance P (SP) and calcitonin gene-related peptide (CGRP), were examined at 72 h after corneal injury.ResultsFluorescein staining demonstrated an acceleration of the recovery of corneal epithelial injury in diabetic mice compared with the saline treatment, which was further evidenced by the overexpression of Ki-67. Moreover, 72 h of insulin application attenuated the expression of inflammatory cytokines and neutrophil infiltration. Remarkably, the results demonstrated that topical insulin treatment enhanced the density of corneal epithelial nerves, as well as neuropeptide SP and CGRP release, in the healing cornea via immunofluorescence staining.ConclusionsOur results indicated that insulin eye drops may accelerate corneal wound healing and decrease inflammatory responses in diabetic mice by promoting nerve regeneration and increasing levels of neuropeptides SP and CGRP.