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Neuropeptide Y (NPY) is a 36-amino acid peptide that is widely expressed throughout the limbic system. Recent evidence has highlighted NPY as a marker of resilience to posttraumatic psychopathology, which may be due to its association with neural regions involved with emotion regulation. This study examined whether plasma NPY levels moderated the relationship between emotion regulation and psychopathology in a sample of adult survivors of childhood interpersonal trauma, a population known to be at high risk for psychopathology. Adults exposed to an interpersonal criterion A trauma during childhood (N = 54) were recruited from an urban population at a midwestern medical center and completed a baseline study visit as part of a larger clinical trial. Participants gave a blood sample in order to assess circulating levels of NPY and answered questions related to emotion regulation and mood-related pathology. Results of a moderated multiple regression showed that the overall model was significant R 2  = 0.26, F (5, 48) = 3.46, p < .01. Difficulties in emotion regulation was significantly predictive of psychopathology (unstandardized B = 0.032, p < .01), and this relationship was significantly moderated by levels of NPY (unstandardized B = -0.001, p < .05) such that the relationship between emotion regulation and psychopathology was weaker for those with higher levels of NPY. Results suggest that higher levels of NPY may lessen the association between emotion regulation and posttraumatic psychopathology in survivors of childhood interpersonal trauma. Further investigation of the contribution of NPY to psychopathology in this population is warranted. NCT: 02279290., Competing Interests: Declaration of competing interest The conflicts of interest are noted on the title page of the manuscript for your review. In particular, coauthor Sheila Dowd, PhD is a consultant for WebMD/The Wellness Network. All other coauthors (Sarah K. Stevens, M.A., Randy Boley, B.A., Mark Pollack, M.D., Stevan Hobfall, PhD., Stewart Shankman, PhD., Linzy Pinkerton, Zerbrina Valdespino-Hayden, PhD, Angela C. Glover, Michelle Kaufman, PhD, and Alyson K. Zalta, PhD) have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Acute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI)., Methods: In this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging., Results: Median plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location., Conclusion: High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this analysis, we aimed to investigate the effect of COVID-19 disease on eating behavior. A total of 55 right-handed adults, <50 years of age, without overweight or obesity, from two cross-sectional studies were included. The first one enrolled subjects between September 2018 and December 2019 (non-COVID-19 group). The second one included subjects enrolled between March 2022 and May 2023; for this analysis, 28 with a history of COVID-19 (COVID-19 group) were retained. Hunger, TFEQ-18, plasma ghrelin, neuropeptide Y (NPY) and resting-state fMRI were assessed during fasting. Intraregional neuronal synchronicity and connectivity were assessed by voxel-based regional homogeneity (ReHo) and degree of centrality (DC). Significantly higher ghrelin and NPY levels were observed in the COVID-19 group than in the non-COVID-19 group (ghrelin 197.5 pg/mL vs. 67.1 pg/mL, p < 0.001; NPY 128.0 pg/mL vs. 84.5 pg/mL, p = 0.005). The NPY levels positively correlated with the DC and ReHo in the left lingual (r = 0.67785 and r = 0.73604, respectively). Similar scores were noted for cognitive restraint, uncontrolled eating and emotional eating in both groups according to the TFEQ-18 questionnaire results ( p > 0.05 for all). Our data showed increased levels of appetite-related hormones, correlated with activity in brain regions involved in appetite regulation, persisting long after COVID-19 infection.

Objective: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV)., Methods: 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., Results: 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)., Conclusion: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.

Aim: Neurogenic inflammation has been recognized as an important contributing factor in the pathogenesis of allergic rhinitis. The aim of this study was to investigate the clinical values of substance P, vasoactive intestinal peptide (VIP), and neuropeptide Y as biomarkers of disease severity and treatment outcomes of chronic urticaria complicated with allergic rhinitis., Methods: Our prospective study included 150 patients with chronic urticaria complicated with allergic rhinitis and 80 healthy control patients. Before treatment, the serum samples of all study subjects were collected and analyzed using enzyme-linked immunosorbent analysis. The intervention group received imipramine of 10 mg/day orally for 2 weeks, and the Symptom Score Reduction Index (SSRI) was used to analyze clinical outcomes, which were categorized as effectual and ineffectual., Results: Our data suggested that substance P, VIP, and neuropeptide Y were significantly correlated to each other. Lower levels of substance P, VIP, and neuropeptide Y were associated with better treatment outcomes. A good detection sensitivity (69.49%) and specificity (80.22%) could be achieved using a combination of these markers (area under curve = 0.85)., Conclusions: Our data indicates that substance P, VIP, and neuropeptide Y levels before treatment correlate strongly with the treatment outcomes of the patients, which could potentially serve as a decision support tool in clinical management of chronic urticaria complicated with allergic rhinitis., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: Obesity is a serious public health problem associated with excessive food intake. Regulation of food intake in highly organized organisms is under the control of a large number of orexigenic and anorexigenic molecules. Therefore, the main purpose of this study has been to determine the relationship between obesity and some of the circulating orexigenic and anorexigenic peptides that have a role in appetite control and to determine whether the concentrations of these molecules differ according to blood groups., Patients and Methods: The study included 400 individuals of whom 100 were obese women, 100 obese men, 100 healthy men and 100 healthy women. Obese women and men were divided into 4 groups, according to their blood groups. In the control group, healthy women and healthy men were similarly divided into 4 blood groups. Each blood group within the groups, therefore, had 25 participants., Results: When leptin, nesfatin-1, obestatin and neuropeptide-Y, ghrelin and galanin levels of the control group and obese participants were compared, regardless of blood groups, leptin, nesfatin-1, obestatin and neuropeptide-Y were significantly higher, whereas only the ghrelin levels were significantly lower in obese patients. When the amounts of these hormones were measured according to gender, the situation was similar. When leptin, nesfatin-1, obestatin and neuropeptide-Y values of the control and obese participants' blood groups were compared with each other; these hormones were high in all blood groups; however, leptin levels in A blood group, nesfatin-1 levels in AB and O blood group, obestatin levels in AB blood group, neuropeptide-Y levels in A, B, AB blood groups were significantly higher. When the ghrelin levels of the blood groups in the control group and obese participants were compared, it was only significantly lower in the AB blood group. The ghrelin levels in the other blood groups of the obese individuals were again low, but not significantly so. When the distribution of hormones according to gender was evaluated, a situation parallel to the above results was recorded., Conclusions: Leptin, nesfatin-1, obestatin and neuropeptide-Y and galanin levels of obese individuals were significantly higher than the control values, whereas the ghrelin values were significantly lower regardless of blood groups. Also, these hormones in blood partly varied with ABO blood groups. These different concentrations of hormones in ABO blood groups might be related with stimulation or suppression of appetite in human. However, further studies in other ethnic groups are needed to confirm these results.

Plasma levels of neuropeptide Y (NPY) are elevated in patients with acute myocardial infarction (AMI), but its role in AMI remains unclear, which was examined here in NPY wild-type/knockout (WT/KO) mice treated with/without exogenous NPY and its Y1 receptor antagonist (Y1Ra) BIBP 3226. We found that AMI mice lacking NPY developed more severe AMI than WT mice with worse cardiac dysfunction, progressive cardiac inflammation and fibrosis, and excessive apoptosis but impairing angiogenesis. All of these changes were reversed when the NPY KO mice were treated with exogenous NPY in a dose-dependent manner. Interestingly, treatment with NPY also dose dependently attenuated AMI in WT mice, which was blocked by BIBP 3226. Phenotypically, cardiac NPY was de novo expressed by infiltrating macrophages during the repairing or fibrosing process in heart-failure patients and AMI mice. Mechanistically, NPY was induced by transforming growth factor (TGF)-β1 in bone marrow-derived macrophages and signaled through its Y1R to exert its pathophysiological activities by inhibiting p38/nuclear factor κB (NF-κB)-mediated M1 macrophage activation while promoting the reparative M2 phenotype in vivo and in vitro. In conclusion, NPY can attenuate AMI in mice. Inhibition of cardiac inflammation and fibrosis while enhancing angiogenesis but reducing apoptosis may be the underlying mechanisms through which NPY attenuates cardiac remodeling and deterioration of function following AMI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE)., Methods: The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment., Results: After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups ( P < 0.05). The levels of neuron-specific enolase (NSE), S-100 β protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter ( P < 0.05). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups ( P < 0.05)., Conclusion: Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates., Competing Interests: The authors declare no competing interests., (Copyright © 2021 Jingjing Ge et al.)

Objective: Neuropeptide Y (NPY), a 36-amino acid neuromodulator, is mainly secreted by neurons in the central and peripheral nervous systems, which participate in the regulation of a series of physiological processes. However, there are few studies on its correlation with intracranial hemorrhage (ICH). The purpose of this study is to determine whether the serum NPY level is related to the prognosis of ICH., Methods: 364 patients diagnosed with ICH were included in the current study. The demographics, anthropometrics, medical history, clinical severity, and laboratory data are collected. Enzyme-linked immunoassay (ELISA) was used to detect the serum NPY level of each patient upon admission. Three months after the occurrence of ICH, we used the modified Rankin scale (mRS) to evaluate the prognosis of patients, and mRS > 2 was defined as a poor prognosis., Results: A total of 364 patients with ICH were included in the study, including 140 patients with a good prognosis and 224 patients with a poor prognosis. Compared with patients with a poor prognosis, ICH patients with a good prognosis have a lower baseline National Institutes of Health Stroke Scale (NIHSS) score ( p = 0.036) and smaller hematoma volume ( p = 0.039). The results of ELISA showed that compared with patients with a poor prognosis, ICH patients with a good prognosis had lower serum NPY levels (19.4 ± 3.7 vs. 27.6 ± 3.3 ng/ml, p < 0.001). Linear correlation analysis showed that the serum NPY level of ICH patients was significantly positively correlated with the baseline NIHSS score ( r = 0.413, p = 0.041) and hematoma volume ( r = 0.308, p = 0.026). Receiver operating characteristic (ROC) curve analysis showed that the sensitivity of the serum NPY level to predict the prognosis of ICH was 70.9%, the specificity was 72.6%, and the cut-off value was 24.2 ng/ml., Conclusions: The serum NPY level may be used as a predictor of ICH prognosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Weiming Sun et al.)

We compared the levels of functional activity of cells in each adrenal zone with blood levels of corticosterone, testosterone, and neuropeptide Y in control and hippocampectomized F1(C57BL/6×DBA/2) mice during modeling of metabolic, motivational, and cognitive tension. The morphofunctional state of the adrenal glands was studied using a new morphometric approach. It was found that hippocampectomy changed the testosterone response to neurobiological stimuli; similar changes were observed in the zona reticularis of the adrenal cortex producing dehydroepiandrosterone that is involved in the regulation of testosterone secretion. At the same time, hippocampectomy enhanced the response of the peptide hormone; the index of functional activity of chromaffin cells producing this hormone also increased. These findings allow us to put forward a hypothesis that the hippocampus is involved in the regulation of mutual influences of the studied hormones and that it modulates the sensitivity of testosterone and NPY to metabolic and cognitive factors., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

In vivo receptor targeting with radiolabelled peptide-based probes is an attractive approach for the development of novel radiotracers for molecular imaging. This work presents the development and characterization of two novel neuropeptide Y analogues labelled with a positron emitter 68 Ga, for potential use in breast cancer imaging. Both analogues share the same amino acid sequence and were derivatized with NOTA through either a lysine linker (L1) or an acetylated lysine (L2). In both cases, a single product with radiochemical purity higher than 95% was obtained. The two complexes were hydrophilic, showed remarkable in vitro stability, good cellular uptake, binding affinity in the nanomolar range and high cellular internalization rate. Biodistribution studies revealed low blood uptake and elimination through the urinary tract. The addition of an acetyl group in the spacer increased the lipophilicity of C2 and modified the reactivity of the ε-amino group of the lysine which resulted in lower protein binding and lower percentage of injected dose in bladder and urine. The tumour versus muscle ratio was (3.8 ± 0.4) for 68 Ga-L1 and (4.7 ± 0.4) for 68 Ga-L2. These results encourage performing further studies in order to complete the evaluation of both tracers as potential radiopharmaceutical for breast cancer imaging., (© 2021 John Wiley & Sons A/S.)

Neuropeptide Y (NPY) and peptide YY (PYY) are involved in metabolic regulation. The purpose of the study was to assess the serum levels of NPY and PYY in adolescents with anorexia nervosa (AN) or obesity (OB), as well as in a healthy control group (CG). The effects of potential confounders on their concentrations were also analysed. Eighty-nine adolescents were included in this study (AN = 30, OB = 30, and CG = 29). Anthropometric measurements and psychometric assessment of depressive symptoms, eating behaviours, body attitudes, and fasting serum levels of NPY and PYY were analysed. The AN group presented severe depressive symptoms, while the OB group held different attitudes towards the body. The levels of NPY were lower in the AN and OB groups as compared with the CG. The PYY levels were higher in the OB group than in the AN group and the CG. The severity of eating disorder symptoms predicted fasting serum concentrations of NPY. Lower levels of NPY in AN, as well as in OB suggests the need to look for a common link in the mechanism of this effect. Higher level of PYY in OB may be important in explaining complex etiopathogenesis of the disease. The psychopathological symptoms may have an influence on the neurohormones regulating metabolism.

Background and Purpose: Post-ischemic stroke epilepsy (PISE) is one of the common complications of stroke., Materials and Methods: Methods To determine the risk factors of PISE, in this study, 78 patients with PISE and 86 patients without PISE were recruited. Clinical data and serum neuropeptide Y (NPY) levels were collected and the relative factors including clinical data and serum were analyzed., Results: Logistic regression showed that low serum NPY was significantly associated with PISE. Every 5 ng/ml increment of serum NPY was associated with 62% risk decrease in patients with PISE. The area under curve of serum NPY was 0.910 with a sensitivity of 84.62% and a specificity of 86.05%. The cut-off value of serum NPY was 90 ng/ml. According to cut-off value of serum NPY, the percentage of patients with PISE decreased from 84.6% in low serum NPY group to 14.0% in high serum NPY group. Furthermore, patients were divided into different tertiles according to serum NPY. The percentage of patients with PISE reduced from 90.0% in the lowest tertile (NPY < 85 ng/ml) to 3.5% in the highest tertile (NPY ≥ 105 ng/ml). Compared with patients with normal video-electroencephalogram (VEEG), serum NPY levels significantly decreased in patients with abnormal VEEG; however, serum NPY levels were not associaated with epileptic seizure subtypes., Conclusions: Serum NPY was an independent risk factor for PISE. Targeting serum NPY may be used to the prevention and treatment of PISE., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to investigate the role of leptin, ghrelin, neuropeptide Y, and nesfatin-1 in young children with autism spectrum disorder (ASD). A total of 44 children with ASD and 44 healthy controls aged 18-60 months were included. Plasma levels of hormones were measured using commercial enzyme-linked immunosorbent assay kits. Plasma leptin and ghrelin levels were significantly higher in the ASD group than in the control group. However, no significant difference for plasma neuropeptide Y and nesfatin-1 levels was detected between the groups. No relation was found between the severity of ASD symptoms, severity of eating problems, and plasma levels of hormones. Leptin and ghrelin may play a potential role in the pathogenesis of ASD.

Background: Many risk factors lead to opioid use and drug-related problems. One of the challenges to understand behavioural factors, drug problems and psychopathology is to identify biological markers that are suitable for research on broad substance abuse and dependence involving human participants., Aims: The study has examined the relationships between the self-reported childhood history of trauma, parental bonding, psychopathology, impulsivity, current resiliency, two neuropeptides, possible markers of behaviour and emotion regulation, and severity of drug-related problems., Methods: One hundred and sixty-seven individuals with a history of opioid use completed questionnaires. Serum neuropeptide Y (NPY) and substance P (SP) levels were analysed. Moderating and mediating relationships between variables were examined using structural equation modelling (SEM)., Results: Antisocial features, depression, impulsivity, SP, NPY, emotional neglect and resilience are associated with severity of drug-related problems. SP is associated with antisocial personality traits., Conclusions: The novelty of this study is the proposed possible link between biochemical markers, antisocial features and behavioural and emotional regulation. Serum NPY and SP levels have a potential to be used as a biomarker in opioid users before and in the treatment process to account for interactions between biological vulnerabilities and childhood risk factors in predicting behavioural adjustment and more severe drug-related problems.

Background: Several large clinical trials have confirmed the cardioprotective role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes. However, whether empagliflozin, as an SGLT2i, could alleviate atherosclerosis progression in non-diabetic states remain unknown., Methods: ApoE-/- mice were fed a Western diet for 12 weeks to induce atherosclerosis. On the 7th week, a group of mice were treated with drinking water containing empagliflozin (10 mg/kg/day), while another group was given normal water. At the 12th week, the whole aortas of each group were harvested. Oil Red O, HE and Movat staining were performed for atherosclerotic lesion area and size. Mouse serum lipid profiles (total cholesterol [TC], triglyceride [TG], low-density lipoprotein-c [LDL], and high-density lipoprotein-c [HDL]), systemic inflammation levels (IL-1β, IL-6 and IL-10), renin-angiotensin-aldosterone system (RAAS) components and sympathetic activity (norepinephrine and neuropeptide Y) indicators were measured by ELISA., Results: Empagliflozin reduced the atherosclerotic lesion burden (-8.6 %, P = 0.004) at aortic root in ApoE-/- mice. In addition, empagliflozin decreased body weight (-3.27 g, P = 0.002), lipid profiles (TC: [-15.3 mmol/L, P = 0.011]; TG: [-2.4 mmol/L, P < 0.001]; LDL: [-2.9 mmol/L, P = 0.010]), RAAS (renin [-9.3 ng/L, P = 0.047]; aldosterone [-16.7 ng/L, P < 0.001]) and sympathetic activity (norepinephrine [-8.9 ng/L, P = 0.019]; neuropeptide Y [-8.8 ng/L, P = 0.002]). However, the anti-inflammatory effect of empagliflozin was not significantly evident., Conclusions: The early atherosclerotic lesion size was less visible in empagliflozin-treated mice. Empagliflozin could decrease lipid profiles and sympathetic activity in atherosclerosis.

Objective: The purpose of this observational study was to examine the association of protein and genetic biomarkers with pain and pain-related disability in individuals with axial low back pain undergoing epidural steroid injections., Design: Forty-eight adults with axial low back pain undergoing an epidural steroid injection were recruited from an academic medical center. Blood samples were assayed at baseline and follow-up for plasma proteins and functional single-nucleotide polymorphisms associated with pain. Data regarding pain and function were collected at baseline and follow-up. The characteristics of responders (defined as 50% improvement in pain score) and nonresponders were compared, and the association between response and baseline biomarkers was examined., Results: Thirty-five percent of subjects were responders to injection. Responders had lower baseline plasma levels of chondroitin sulfate 846 and higher neuropeptide Y and serotonin levels than nonresponders, and baseline neuropeptide Y level correlated with change in disability levels. In addition, subjects with the variant allele for the catechol-O-methyltransferase single-nucleotide polymorphism demonstrated increased odds of responding to the injection., Conclusions: These data identify candidates who may have utility for patient selection for spinal procedures and provide support for exploration in prospective studies to assess and validate their predictive ability., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

This study aims to explore the changes in endothelin-1 (ET-1), plasma neuropeptide Y, and calcitonin gene-related peptide (CGRP) in child patients before and after operation. A total of 80 child patients with congenital heart disease (CHD) complicated with pulmonary hypertension (PH) were enrolled and divided into control group (n = 40, conservative treatment for various reasons) and observation group (n = 40, active preoperative preparation and timely operative intervention) according to different treatments. There were positive correlations between systolic pulmonary arterial pressure (sPAP) and ET-1, plasma neuropeptide Y, while negative correlation between sPAP and CGRP. In conclusion, our data demonstrate that the levels of ET-1, plasma neuropeptide Y, and CGRP in PH-CHD were significantly changed after interventions, which provides new leads as alternative biomarkers to assess the efficacy of treatments against PH-CHD.

War veterans are at increased risk of suicide that may be related to deployment and/or post-deployment stressors and to adjustment-related factors. The aim of this study was to examine whether levels of plasma neuropeptide Y (NPY) might distinguish combat veterans who have made a post-deployment suicide attempt from those who have never made a suicide attempt. We focused on NPY because of prior findings linking NPY with the neurobiology of resilience, stress-related and other disorders, and suicidal behavior. Demographic and clinical parameters of suicide attempters and non-attempters were assessed and plasma NPY was determined by radioimmunoassay. NPY levels were higher among attempters in comparison to non-attempters, controlling for sex and body-mass index. Suicide attempters had higher Scale for Suicidal Ideation (SSI) scores than non-attempters. There was a positive correlation between NPY levels and SSI scores among non-attempters but not among attempters. Likewise, NPY levels positively correlated with Brown-Goodwin Aggression Scale scores among suicide attempters but not among non-attempters. This is the first demonstration of altered plasma NPY levels in association with suicide attempt history and suicidal ideation in veterans. Our findings suggest that clinical differences between combat veterans with or without a history of suicide attempt may have a neurobiological origin., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Background: Serum angiopoietin 2 levels have been associated with endothelial dysfunction and diabetic kidney disease. Derangements in autonomous nervous system lead to increased production of vasoconstrictory and angiogenic mediators such as norepinephrine and neuropeptide Y and are associated with increased risk of microvascular complications., Aim: To investigate associations between angiopoietin 2, neuropeptide Y and diabetic kidney disease in patients with type 1 diabetes mellitus., Methods: 289 patients with type 1 diabetes mellitus duration > 1 year were included. Patients were stratified according to presence of diabetic nephropathy (macroalbuminuria, estimated glomerular filtration rate<60 ml/min/1.73 m 2 or end-stage renal disease). Angiopoietin 2 was measured by Luminex technology. Neuropeptide Y was measured by ELISA., Results: Patients with diabetic nephropathy had significantly increased levels of angiopoietin 2 (4020.5 (2172.4-5778.1) pg/ml vs. 2001.0 (1326.7-2862.7) pg/ml) and neuropeptide Y (18.22 (14.85-21.85) ng/ml vs. 12.91 (9.96-17.07) ng/ml). Higher levels of angiopoietin 2 and neuropeptide Y were observed also in patients with arterial hypertension. Angiopoietin 2 and neuropeptide Y correlated significantly (ρ=0.245, p<0.001). Both biomarkers were significant predictors of estimated glomerular filtration rate and diabetic nephropathy in univariate regression models. In the fully adjusted regression models and after application of a stepwise selection regression method, angiopoietin 2 demonstrated a stronger predictive power for diabetic nephropathy compared to neuropeptide Y., Conclusion: Diabetic nephropathy is associated with increased serum concentrations of angiopoietin 2 (marker of endothelial dysfunction) and neuropeptide Y (marker of sympathetic activity) in type 1 diabetes. Angiopoietin 2 is a more potent predictor of diabetic nephropathy compared to neuropeptide Y., Competing Interests: Juris Stefanovics, Gita Gersone, Leonora Pahirko, Janis Valeinis, Sanita Kalva-Vaivode, Vita Rovite, Leons Blumfelds and Peteris Tretjakovs declare no conflict of interest. Jelizaveta Sokolovska received lecture fees and travel expense subsidies from Sandoz, NovoNordisk, Sanofi, AstraZeneca, MSD in the past 3 years. Valdis Pirags received educational subsidies from NovoNordisk and Eli Lilly in the past 3 years., (Thieme. All rights reserved.)

Objective: Neuropeptide Y (NPY), an orexigenic peptide known to cause hyperphagia, has been involved in the occurrence and development of obesity. However, differences in the distribution of serum NPY levels in obese phenotypes (including metabolically unhealthy obesity (MUO) phenotype and metabolically healthy obesity (MHO) phenotype) and the association of NPY with MUO phenotype have not been unequivocally established. We therefore determined associations of serum NPY levels with MUO phenotype in obese Chinese adults., Methods: A cross-sectional study was conducted from 400 obese adults in Hunan province, who underwent a health examination in the Second Xiangya Hospital, and 164 participants were finally enrolled in the study and divided into MHO and MUO groups. Serum NPY levels were examined; univariate and multivariate analyses as well as smooth curve fitting analyses were conducted to measure the association of NPY serum levels with the MUO phenotype., Results: Serum NPY levels were significantly elevated in the MUO group compared with the MHO group ((667.69 ± 292.90) pg/mL vs. (478.89 ± 145.53) pg/mL, p < 0.001). A threshold and nonlinear association between serum NPY levels and MUO was found ( p = 0.001). When serum NPY levels exceeded the turning point (471.5 pg/mL), each 10 pg/mL increment in the NPY serum level was significantly associated with an 18% increased odds ratio of MUO phenotype (OR: 1.18, 95% CI: 1.07-1.29, p = 0.0007) after adjusted for confounders., Conclusions: Higher NPY serum levels were positively correlated with MUO phenotype in obese Chinese adults., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Hao-Neng Tang et al.)

Introduction: Law enforcement and pre-hospital care personnel often confront individuals who must be physically restrained. Many are under the influence of illicit substances, and law enforcement officers may need to use a controlled electrical device (CED) to gain control of the individual and they are often placed into the prone maximum restraint (PMR) position. These techniques have previously been evaluated for their physiologic effects. The purpose of this study was to investigate the psychological effects of anticipating and experiencing a sham CED activation in healthy human subjects who were exercised and restrained compared with no sham activation by assessing the differences in a panel of several known biomarkers of stress., Methods: We performed a randomized, crossover controlled human subject trial to study the stress associated with exercise, physical exhaustion, and restraint with and without an added psychological stress simulating the field use of a CED. Twenty five total subjects; each subject performed two different trials each consisting of a brief period of intense exercise on a treadmill to exhaustion followed by placement in the PMR with and without induced psychological stress. Blood samples were collected for analysis pre and post exercise, as well as 10 min after completion of the exercise. A panel of hormones and stress markers were measured., Results: We found no significant differences in any of the stress biomarkers measured between the two study groups. A trend towards higher levels of copeptin was measured in the sham CED activation arm., Conclusion: During a brief period of intense exercise followed by the psychological stress of anticipated CED application, there did not appear to be statistically significant changes in the stress panel of biomarkers measured, only a trend towards significance for higher copeptin levels in the patients exposed to the psychological stress., (Copyright © 2020 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

The serum hormone concentrations were studied in a group of male F1 (C57BL/6×DBA/2) mice in different states of food activity (satiety, 24-h food deprivation, and cognitive load against the background of food deprivation). The hormonal response depended on food activity: the content of leptin, triiodothyronine, and testosterone decreased in hungry animals, while during cognitive load (learning), we observed a decrease in the concentrations of ghrelin, leptin, thyroxine, and testosterone. The exceptions were neuropeptide Y (its concentration increased in hungry animals) and corticosterone (its level remained unchanged). The use of hierarchical cluster analysis allowed identifying functional organization of the relationships within the hormonal ensemble that underwent plastic changes depending on the state of the organism. It was shown that the hormonal ensemble was system-organized in the form of a "core" that determines stability of the system and the "field", within which functional interactions of the hormones are preserved.

Introduction The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge - NPY admission). Conclusion These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction.

Objective: To investigate the features of neuropeptide Y (NPY), α-melanocyte stimulating hormone (α-MSH), and agouti-related protein (AgRP) in type 2 diabetes mellitus (T2DM) patients with hypertension., Methods: Patients with T2DM (n = 384) and healthy volunteers (n = 80) were enrolled into this study. Serum NPY, α-MSH, and AgRP levels were detected using ELISA., Results: Significantly higher NPY and lower α-MSH and AgRP levels were observed in patients with diabetes compared with those without diabetes, and the mean NPY levels increased, while α-MSH and AgRP levels decreased, with the development of hypertension compared with diabetic patients without hypertension. α-MSH and AgRP levels decreased with an increase in blood pressure in hypertension compared with the non-hypertension patients. Multiple stepwise linear regression analysis showed that NPY, α-MSH, and AgRP levels were closely associated with blood pressure and glucose control. Receiver operating characteristic (ROC) curve analyses indicated that α-MSH may be a better marker compared with NPY and AgRP for regulating glucose and blood pressure and to distinguish between T2DM patients with and without hypertension., Conclusion: NPY, α-MSH, and AgRP might play different roles and be closely related to the occurrence and development of diabetes and hypertension.

Previous studies have suggested that neuropeptide Y (NPY) levels may be altered in patients with major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and chronic stress. We investigated, through systematic review and meta-analysis, whether the mean levels of NPY are significantly different in patients with MDD, PTSD or chronic stress, compared to controls. The main outcome was the pooled standardized mean difference (SMD) with 95% confidence intervals between cases and controls, using the random-effects model. Heterogeneity and publication bias were evaluated. Thirty-five studies met eligibility criteria. Meta-regression determined that medication and sex could explain 27% of the between-study variance. Females and participants currently prescribed psychotropic medications had significantly higher levels of NPY. NPY levels were significantly lower in plasma and cerebrospinal fluid (CSF) in PTSD patients versus controls. Patients with MDD had significantly lower levels of NPY in plasma compared to controls, but not in the CSF. The magnitudes of the decrease in plasma NPY levels were not significantly different between PTSD and MDD. However, chronic stress patients had significantly higher plasma NPY levels compared to controls, PTSD or MDD. Our findings may imply a shared role of NPY in trauma and depression: nevertheless, it is not clear that the association is specific to these disorders. Psychotropic medications may help restore NPY levels. Further controlled studies are needed to better delineate the contribution of confounding variables such as type of depression, body mass index, appetite or sleep architecture., (© 2020 Wiley Periodicals, Inc.)

Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with effects on the regulation of inflammatory cells. The role of NPY on autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is not completely understood. Therefore, we evaluate if NPY levels are markers of disease activity in RA and if there is a correlation between NPY levels and tumor necrosis factor-alpha (TNF- α ), leptin, and interleukin 6 (IL-6) levels., Methods: Cross-sectional design, including 108 women with RA. We assessed disease activity by DAS28-ESR (considering active disease a score of ≥2.6). Serum NPY levels and anti-CCP2 antibody, TNF- α , IL-6, and leptin levels were quantified (ELISA)., Results: Sixty-eight RA had an active disease (RA-active), and 40 were in remission (RA-remission). RA-active patients had higher NPY levels vs. RA-remission (22.8 ± 13.6 vs. 17.8 ± 10.3; p = 0.04). NPY levels correlated with increased TNF- α levels ( r = 0.32, p = 0.001). Leptin or IL-6 did not correlate with NPY levels. In the logistic regression analysis, NPY increased the risk of disease activity (OR: 1.04, 95% CI 1.006-1.09, and p = 0.03)., Conclusion: Higher NPY levels are an independent marker of disease activity in RA. This study encourages the quantification of NPY levels as a surrogate marker for RA-active. Future studies evaluating the role of NPY levels interacting with other proinflammatory cytokines are required., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Melissa Ramirez-Villafaña et al.)

By reducing their metabolism, dipeptidyl peptidase 4 inhibition (DPP4I) enhances the effects of numerous peptides including neuropeptide Y 1-36 (NPY 1-36 ), peptide YY 1-36 (PYY 1-36 ), and SDF-1 α Studies show that separately NPY 1-36 , PYY 1-36 and SDF-1 α stimulate proliferation of, and collagen production by, cardiac fibroblasts (CFs), preglomerular vascular smooth muscle cells (PGVSMCs), and glomerular mesangial cells (GMCs), particularly in cells isolated from genetically hypertensive rats. Whether certain combinations of these factors, in the absence or presence of DPP4I, are more profibrotic than others is unknown. Here we contrasted 24 different combinations of conditions (DPP4I, hypertensive genotype and physiologic levels [3 nM] of NPY 1-36 , PYY 1-36 , or SDF-1 α ) on proliferation of, and [ 3 H]-proline incorporation by, CFs, PGVSMCs, and GMCs. In all three cell types, the various treatment conditions differentially increased proliferation and [ 3 H]-proline incorporation, with a hypertensive genotype + DPP4I + NPY 1-36 + SDF-1 α being the most efficacious combination. Although the effects of this four-way combination were similar in male versus female CFs, physiologic (1 nM) concentrations of 2-methoxyestradiol (2ME; nonestrogenic metabolite of 17 β -estradiol), abolished the effects of this combination in both male and female CFs. In conclusion, this study demonstrates that CFs, PGVSMCs, and GMCs are differentially activated by various combinations of NPY 1-36 , PYY 1-36 , SDF-1 α , a hypertensive genetic background and DPP4I. We hypothesize that as these progrowth conditions accumulate, a tipping point would be reached that manifests in the long term as organ fibrosis and that 2ME would obviate any profibrotic effects of DPP4I, even under the most profibrotic conditions (i.e., hypertensive genotype with high NPY 1-36 + SDF-1 α levels and low 2ME levels). SIGNIFICANCE STATEMENT: This work elucidates combinations of factors that could contribute to long-term profibrotic effects of dipeptidyl peptidase 4 inhibitors and suggests a novel drug combination that could prevent any potential profibrotic effects of dipeptidyl peptidase 4 inhibitors while augmenting the protective effects of this class of antidiabetic agents., (Copyright © 2020 by The Author(s).)

Background: Guillain-Barré syndrome (GBS) is a common acute immune-mediated inflammatory disorder affecting the peripheral nervous system (PNS) of humans. Studies in humans and in animal models revealed that neuropeptide Y (NPY) levels are altered in some neurodegenerative and neuroimmune disorders. Herein, we investigated the levels of NPY and cytokines in the serum of GBS patients and explored the roles of NPY in the disease severity and its short-term prognosis., Methods: Twenty patients with GBS (case group) and twenty healthy individuals (control group) were enrolled in this study. NPY levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The levels of pro- and anti-inflammatory cytokines (including interferon-γ (IFN-γ), interleukin (IL)-4, IL-10, IL-12p70, IL-17A, and tumor necrosis factor-α (TNF-α)) were analyzed using cytometric beads array (CBA). The clinical characteristics, disease severity, and short-term prognosis were compared between the two groups., Results: Compared with the control group, the levels of NPY and cytokines were significantly increased in the serum of patients with GBS. NPY levels in the serum of GBS patients were correlated with the disease severity., Conclusion: Our results suggest that NPY and cytokines are involved in the pathogenesis of GBS. The levels of NPY can help to predict the severity of the disease.

Neuropeptide Y (NPY) is a 36-amino acid peptide circulating at a subpicomolar concentration participating in multiple physiological and pathological processes. NPY is prone to peptidolysis, generating metabolites with modified affinity for the five known receptors of NPY that mediate distinct effects. It is, therefore, crucial to distinguish each metabolite to understand the multiple functions of NPY. Since immunoassays are not able to distinguish NPY from its metabolites, we have validated a microliquid chromatography tandem mass spectrometry (micro-LC-MS/MS) assay for the quantification of endogenous NPY, NPY2-36, NPY3-36, NPY1-35, and NPY3-35 in human plasma. Sample preparation relies on immunoextraction in 96-well plates, followed by solid-phase extraction prior to micro-LC-MS/MS. The LLOQ ranged from 0.03 to 0.16 pM, intra- and inter-assay precision were <27% and trueness <22%. We determined reference intervals in 155 healthy volunteers and 40 hypertensive patients. We found that NPY3-36 is the main circulating peptide in resting conditions and that NPY and catecholamines are simultaneously increased during orthostasis. We also showed that the concentrations of NPY and its metabolites are similar in healthy volunteers and hypertensive patients. NPY is the prototype peptide that circulates in concentrations expected to be beyond instrumental capacities. We have been successful in developing a high-throughput specific and sensitive assay by including a deep knowledge of the physicochemical properties of these peptides to an efficient multistep sample preparation, and a micro-LC chromatography. We believe that our methodological approach opens the possibility to selectively quantify other endogenous peptides cleaved by peptidases whose concentrations are below 1 pM.

Aims: To determine whether renal denervation (RDN) in hypertensive patients affects the platelet activation status., Methods and Results: We investigated the effect of RDN on the platelet activation status in 41 hypertensive patients undergoing RDN. Ambulatory blood pressure (BP), plasma sympathetic neurotransmitter Neuropeptide Y, and platelet activation markers were measured at baseline, at 3 months, and 6 months after RDN. RDN significantly decreased BP at 3 months (150.6 ± 11.3/80.9 ± 11.4 mmHg to 144.7 ± 12.0/77.1 ± 11.1 mmHg; P < 0.01) and at 6 months (144.3 ± 13.8/78.3 ± 11.1 mmHg; P < 0.01). Plasma levels of the sympathetic neurotransmitter Neuropeptide Y, an indicator of sympathetic nerve activity, were significantly decreased at 3 months (0.29 ± 0.11 ng/mL to 0.23 ± 0.11 ng/mL; P < 0.0001) and at 6 months (0.22 ± 0.12 ng/mL; P < 0.001) after RDN. This was associated with a reduction in platelet membrane P-selectin expression (3 months, P < 0.05; 6 months, P < 0.05), soluble P-selectin (6 months, P < 0.05), circulating numbers of platelet-derived extracellular vesicles (EVs) (3 months, P < 0.001; 6 months, P < 0.01), and phosphatidylserine expressing EVs (3 months, P < 0.001; 6 months, P < 0.0001), indicative of a reduction in platelet activation status and procoagulant activity. Only patients who responded to RDN with a BP reduction showed inhibition of P-selectin expression at 3 months (P < 0.05) and 6 months (P < 0.05) as well as reduction of glycoprotein IIb/IIIa activation at 3 months (P < 0.05). Notably, 13 patients who took aspirin did not show significant reduction in platelet P-selectin expression following RDN., Conclusion: Our results imply a connection between the sympathetic nervous system and the platelet activation status and provide a potential mechanistic explanation by which RDN can have favourable effects towards reducing cardiovascular complications., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial., Materials and Methods: Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA., Results: Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes., Conclusions: Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.

Objectives: The biological mechanisms linking diet-related obesity and depression remain unclear. Therefore, we examined the impact of high-fat diet (HFD) on murine behaviour, intestinal microbiome, brain metabolome, neuropeptide Y (NPY) expression, and dipeptidyl peptidase-4 (DPP-4) activity. Methods: Male C57Bl/6J mice were fed an HFD (60 kJ% from fat) or control diet (12 kJ% from fat) for 8 weeks, followed by behavioural phenotyping. Caecal microbiome was analysed by 16S rDNA sequencing, brain metabolome by 1 H nuclear magnetic resonance, NPY expression by PCR and immunoassay, and dipeptidyl peptidase-4 (DPP-4) activity by enzymatic assay. The effect of a 4-week treatment with imipramine (7 mg/kg/day) and the DPP-4 inhibitor sitagliptin (50 mg/kg/day) on HFD-induced behavioural changes was also tested. Results: HFD led to a depression-like phenotype as revealed by reduced sociability and sucrose preference. In the caecum, HFD diminished the relative abundance of Bacteroidetes and increased the relative abundance of Firmicutes and Cyanobacteria. In the brain, HFD modified the metabolome of prefrontal cortex and striatum, changing the relative concentrations of molecules involved in energy metabolism (e.g. lactate) and neuronal signalling (e.g. γ-aminobutyric acid). The expression of NPY in hypothalamus and hippocampus was decreased by HFD, whereas plasma NPY and DPP-4-like activity were increased. The HFD-induced anhedonia remained unaltered by imipramine and sitagliptin. Discussion: The depression-like behaviour induced by prolonged HFD in mice is associated with distinct alterations of intestinal microbiome, brain metabolome, NPY system, and DPP-4-like activity. Importantly, the HFD-evoked behavioural disturbance remains unaltered by DPP-4 inhibition and antidepressant treatment with imipramine.

Background: Acute myocardial infarction (AMI) is considered a major cause of death and disability. Myocardial perfusion scintigraphy (MPS) as a non-invasive diagnostic imaging procedure and certain biomarkers associated with myocardial ischemia (ISCH), such as ischemia-modified albumin (IMA), neuropeptide Y (NPY), N-terminal pro b-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT) could probably aid in the detection of myocardial infarction., Methods: Between December 2011 and June 2012, we prospectively analyzed patients who underwent a MPS study with the clinical question of myocardial ISCH. An exercise test was performed along with a MPS. Blood was drawn from the patients before exercise and the within 3 minutes from achieving maximum load and was analyzed for the aforementioned biomarkers., Results: A total of 71 patients (56 men and 15 women) were enrolled with a mean age of 61 ± 12 years. Twenty-six patients (36.6%) showed reduced uptake on stress MPS images that normalized at rest, a finding consistent with ISCH. Between ISCH and non-ISCH groups, only hsTnT levels showed a significant difference with the highest levels pertaining to the former group both before (0.0075 ng/ml vs 0.0050 ng/ml, P = 0.023) and after stress exercise (0.0085 vs 0.0050, P = 0.015). The most prominent differences were seen in higher stages of the Bruce protocol (stress duration > 9.05 minutes - P < 0.017). None of the IMA, NPY, and NP-pro BNP showed significant differences in time between the two groups., Conclusions: Although IMA, NPY, and NT-pro BNP may not detect minor ischemic myocardial insults, serum hsTnT holds a greater ability of detecting not only myocardial infarction but also less severe ischemia. Further studies with larger cohorts of patients are warranted in order to better define the role of hsTnT as a screening tool for myocardial ischemia.

Background: Neuropeptide Y (NPY) is a multifaceted sympathetic neurotransmitter regulating reflex cardiovascular control, myocardial cell growth, inflammation and innate immunity. Circulating NPY levels predict cardiovascular mortality in patients with end stage kidney disease on dialysis but this relationship has never been tested in predialysis chronic kidney disease (CKD) patients., Methods: We investigated the relationship between circulating NPY and the risk for cardiovascular events (Fine & Gray competing risks model) in a cohort of 753 stages 2-5 CKD patients over a median follow-up of 36 months., Results: Independently of other risk factors, plasma NPY was directly related with the glomerular filtration rate (β = -0.19, P < 0.001) but was independent of systemic inflammation as quantified by serum IL6 and C reactive protein. Over follow-up 112 patients had cardiovascular events and 12 died. In analyses fully adjusted for traditional risk factors and a large series of CKD-specific risk factors and considering death as a competing event (Fine and Gray model) a 0.25 μmol/l increase in NPY robustly predicted the incident risk for cardiovascular events (subdistribution hazard ratio: 1.25; 95% confidence interval: 1.09-1.44; P = 0.002). Furthermore, the fully adjusted NPY - cardiovascular outcomes relationship was modified by age (P = 0.012) being quite strong in young patients but weaker in the old ones., Conclusion: NPY is an independent, robust predictor of cardiovascular events in predialysis CKD patients and the risk for such events is age-dependent being maximal in young patients. These findings suggest that NPY may play a role in the high risk of cardiovascular disease in this population.

Aims: The co-transmitter neuropeptide-Y (NPY) is released during high sympathetic drive, including ST-elevation myocardial infarction (STEMI), and can be a potent vasoconstrictor. We hypothesized that myocardial NPY levels correlate with reperfusion and subsequent recovery following primary percutaneous coronary intervention (PPCI), and sought to determine if and how NPY constricts the coronary microvasculature., Methods and Results: Peripheral venous NPY levels were significantly higher in patients with STEMI (n = 45) compared to acute coronary syndromes/stable angina ( n = 48) or with normal coronary arteries (NC, n = 16). Overall coronary sinus (CS) and peripheral venous NPY levels were significantly positively correlated (r = 0.79). STEMI patients with the highest CS NPY levels had significantly lower coronary flow reserve, and higher index of microvascular resistance measured with a coronary flow wire. After 2 days they also had significantly higher levels of myocardial oedema and microvascular obstruction on cardiac magnetic resonance imaging, and significantly lower ejection fractions and ventricular dilatation 6 months later. NPY (100-250 nM) caused significant vasoconstriction of rat microvascular coronary arteries via increasing vascular smooth muscle calcium waves, and also significantly increased coronary vascular resistance and infarct size in Langendorff hearts. These effects were blocked by the Y1 receptor antagonist BIBO3304 (1 μM). Immunohistochemistry of the human coronary microvasculature demonstrated the presence of vascular smooth muscle Y1 receptors., Conclusion: High CS NPY levels immediately after reperfusion correlate with microvascular dysfunction, greater myocardial injury, and reduced ejection fraction 6 months after STEMI. NPY constricts the coronary microcirculation via the Y1 receptor, and antagonists may be a useful PPCI adjunct therapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Patients with psychogenic non-epileptic seizures (PNES) may present with convulsive events that are not accompanied by epileptiform brain activity. Video-electroencephalography (EEG) monitoring is the gold standard for diagnosis, yet not all patients experience convulsive episodes during video-EEG sessions. Hence, we aimed to construct a predictive model in order to detect PNES from serum hormone levels, detached from an evaluation of patients' convulsive episodes., Methods: Fifteen female patients with PNES and 60 healthy female controls participated in the study, providing blood samples for hormone analysis. A binomial logistic regression model and the leave-one-out cross-validation were employed., Results: We found that levels of neuropeptide Y and adrenocorticotropic hormone were the optimal combination of predictors, with over 90% accuracy (area under the curve=0.980)., Conclusions: The ability to diagnose PNES irrespective of convulsive events would represent an important step considering its feasibility and affordability in daily clinical practice.

The purpose was to investigate changes in neuropeptide Y (NPY) protein and dipeptidyl peptidase IV (DPP-IV) activity in the plasma and saliva in normally cycling women and women after menopause. We recruited 7 cycling women and 7 postmenopausal women for a cross-sectional, prospective pilot study. Blood via venipuncture and saliva samples were taken at each point in the menstrual cycle (premenopausal) or once per week (postmenopausal) for 2 months. Blood and saliva were analyzed for estrogen, NPY using ELISA and DPP-IV activity using a fluorometric assay. Plasma β-estradiol was an average of 96.45 ± 57.04 pg/mL over 2 cycles in the premenopausal group and 1.72 ± 0.35 pg/mL over 2 months in the postmenopausal group (P < .05). In the cycling group, there were no significant differences in saliva or plasma NPY or DPP-IV over the cycle. For the postmenopausal group, salivary NPY and DPP-IV did not change over 2 months. Plasma NPY was lowest in the middle 2 weeks (average: 0.52 ± 0.10 ng/mL) compared to the first and fourth weeks (average of week 1 and 4: 0.60 ± 0.14 ng/mL; P < .05). Plasma NPY in postmenopausal women was higher overall (0.56 ± 0.13 ng/mL) compared to cycling women (0.30 ± 0.11 ng/mL; P < .05). Plasma DPP-IV activity was unchanged by time in the postmenopausal group. Saliva DPP-IV and saliva NPY in the cycling group had a significant negative correlation (R = -0.95; P < .05). We found that saliva measures of NPY and DPP-IV activity appear to be poor estimates of plasma concentrations and activities, but a larger sample size is required to conform this. Differences in plasma NPY concentrations between the groups and the relationship between salivary NPY and DPP-IV suggests that there may be some unique differences between these groups.

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and characterized by inattention, hyperactivity, and impulsivity. ADHD is a neurodevelopmental disorder, and its etiology has not yet been determined precisely. Orexin A is thought to play an important role in different forms of learning, memory, and attention. Despite its importance in attention and learning, no study has investigated serum orexin levels in patients with ADHD. In the present study, we aimed to compare serum orexigenic neuropeptides such as orexin A and orexin B, neuropeptide Y, and ghrelin between drug naive children with ADHD and healthy children. Fifty-six drug-naive children with ADHD and 40 healthy controls were enrolled in the study. After comparison of serum orexin A and orexin B, neuropeptide Y, and ghrelin, we found that serum orexin A levels were significantly lower in the ADHD group (p = 0.001). Furthermore, serum orexin A levels were compared between ADHD subgroups. Orexin A levels were significantly lower in the inattentive subtype compared with the hyperactive subtype and combined subtype (p = 0.009). Our results indicate that orexin A might be a neurobiological etiological factor in ADHD, particularly associated with attention symptoms. The present study is the first to demonstrate decreased serum orexin A levels in drug-naive children with ADHD. Further studies are needed to confirm our results and to show the effects of treatments involving orexin A in patients with ADHD.

Objective: Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)-Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides., Methods: One hundred and twenty-seven participants (36 ALS, 26 ALS- cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration., Results: Compared to controls, ALS and ALS-cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression., Interpretation: ALS-FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments., Competing Interests: No author reports a conflict of interest.

Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases., Methods: We investigated the relationship between circulating NPY and the progression of the glomerular filtration rate (GFR) and proteinuria and the risk for a combined renal endpoint (>30% GFR loss, dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts including follow-up of 753 and 576 patients for 36 and 57 months, respectively., Results: Average plasma NPY was 104 ± 32 pmol/L in the first CKD cohort and 119 ± 41 pmol/L in the second one. In separate analyses of the two cohorts, NPY associated with the progression of the estimated GFR (eGFR) and proteinuria over time in both unadjusted and adjusted {eGFR: -3.60 mL/min/1.73 m2 [95% confidence interval (CI): -4.46 to - 2.74] P < 0.001 and -0.83 mL/min/1.73 m2 (-1.41 to - 0.25, P = 0.005); proteinuria: 0.18 g/24 h (0.11-0.25) P < 0.001 and 0.07 g/24 h (0.005-0.14) P = 0.033} analyses by the mixed linear model. Accordingly, in a combined analysis of the two cohorts accounting for the competitive risk of death (Fine and Gray model), NPY predicted (P = 0.005) the renal endpoint [sub-distribution hazard ratio (SHR): 1.09; 95% CI: 1.03-1.16; P = 0.005] and the SHR in the first cohort (1.14, 95% CI: 1.04-1.25) did not differ (P = 0.25) from that in the second cohort (1.06, 95% CI: 0.98-1.15)., Conclusions: NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPY molecule may play a role in CKD progression.

Aim: To analyze inducible nitric oxide synthase (iNOS) and neuropeptide Y (NPY) expression in maternal plasma and placentas of human with intrahepatic cholestasis of pregnancy (ICP)., Methods: The plasma and placentas were collected from 35 women with normal pregnancies and 33 women with ICP. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS and NPY levels. The mRNA levels and cell-specific localization of iNOS and NPY were determined by quantitative PCR, Western Blotting and immunohistochemical analysis in placentas., Results: In human placentas, it revealed iNOS and NPY were mainly localized in syncytiotrophoblast, cytotrophoblastin and vascular endothelium cells using immunohistochemistry analysis. iNOS protein and mRNA expression in ICP maternal plasma and placental tissue were significantly lower than in control groups (P <0.01). In maternal plasma and placentas tissue from ICP patients, a marked up-regulation of NPY protein and mRNA expression were observed (P <0.01)., Conclusion: iNOS and NPY may play a role in the effect of maternal cholestasis on the placenta. The down-regulation of iNOS and up-regulation of NPY in ICP may influence the blood flow of the utero-placental-fetal unit, which may play a significant role in poor fetoplacental vascular perfusion, acute hypoxia and adverse pregnancy outcomes., (© 2018 Japan Society of Obstetrics and Gynecology.)

Objective: ADHD is one of the most common childhood psychiatric disorders. Research indicates that there is some link between obesity/overweight and ADHD, though the mechanism of this association remains uncertain. It is the aim of the present study to explore the association between ADHD, obesity, and plasma leptin, neuropeptide Y (NPY), and adiponectin levels., Method: Thirty-six patients diagnosed with ADHD were included in the study. The control group consisted of 40 healthy children and adolescents who had similar age and gender features with the patient group. Plasma leptin, adiponectin, NPY levels were measured, and body mass index (BMI), weight for height, and standard deviation scores (SDS) of height, weight, and BMI were calculated., Results: No significant difference was found between patients and healthy children in terms of BMI and BMI percentile. Participants were classified into three groups according to their weight to height values. There was no significant difference between the two groups, but 10% of the control group and 30.6% of the ADHD group were classified as overweight, which was 3 times higher than the control group. The adiponectin plasma level was significantly lower and leptin/adiponectin (L/A) ratio was significantly higher in the ADHD group. There was no significant difference between serum NPY levels. In the ADHD group, the mean leptin plasma level was high, but was not statistically significant., Conclusion: We think that a low adiponectin level and high L/A ratio may be the underlying mechanism of the obesity in ADHD patients.

Objective: To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients., Methods: A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups., Results: After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all P <0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all P <0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all P <0.01). After treatment, ESCV scores were all increased remarkably in every group (all P <0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups ( P <0.05, P <0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all P <0.01) and the differences were significant among the groups (all P <0.01)., Conclusion: The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).

Central nervous serotonin (5-HT) can influence behaviour and neuropsychiatric disorders. Evidence from animal models suggest that lowered levels of neuropeptide Y (NPY) may have similar effects, although it is currently unknown whether decreased central nervous 5-HT impact NPY concentrations. Given that the production of NPY is dependent on the essential amino acid methionine (MET), it is imperative to account for the presence of MET in such investigations. Hence, this study sought to examine the effects of acute tryptophan depletion (ATD; a dietary procedure that temporarily lowers central nervous 5-HT synthesis) on serum concentrations of NPY, whilst using the potential renal acid load indicator (PRAL) to control for levels of MET. In a double-blind repeated measures design, 24 adult humans randomly received an AA-load lacking in TRP (ATD) on one occasion, and a balanced control mixture with TRP (BAL) on a second occasion, both with a PRAL of nearly 47.3 mEq of MET. Blood samples were obtained at 90, 180, and 240 min after each of the AA challenges. ATD, and therefore, diminished substrate availability for brain 5-HT synthesis did not lead to significant changes in serum NPY concentrations over time, compared to BAL, under an acute acidotic stimulus.

Purpose: Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group., Method: 48 patients (25 VPA, 23 TPM) aged between 6 and 15.5 years, presenting to the Karadeniz Technical University Medical Faculty Pediatric Neurology Clinic, diagnosed with idiopathic epilepsy or location-related idiopathic epilepsy, and receiving VPA or TPM monotherapy for at least 6 months were included in the study. Twenty-five healthy subjects with similar demographic characteristics were enrolled as the control group. Blood samples were collected from the patient and control groups after fasting for at least 10-12 h and again 1 and 2 h postprandially. Body mass index (BMI) values were calculated for all cases. VPA levels, glucose, insulin, leptin, neuropeptide Y and ghrelin were investigated in all three separate blood samples., Results: Age, height, weight and BMI were similar between the patient and control groups. Significant weight gain was observed throughout treatment in the VPA group compared to the TPM group. High fasting and postprandial insulin levels were observed in the VPA group. VPA group leptin and neuropeptide Y (NPY) levels were also higher than in the TPM and control groups. No significant difference was determined in ghrelin levels in the patient groups compared to the controls., Conclusion: Low blood sugar not being observed, even though insulin levels are high, after fasting and in the postprandial period in epileptic children receiving VPA is indicative of insulin resistance. The elevation in leptin and neuropeptide Y levels observed in the VPA group also suggest this., (Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

In order to decrease the risk of developing stress-related disorders after military deployment, biological vulnerability factors should be identified. Neuropeptide Y (NPY) is a peptide neurotransmitter that is associated with modulation of the stress response. Using the data of two longitudinal prospective cohort studies (N = 892 and N = 2427), plasma NPY (pNPY) was assessed as a possible susceptibility biomarker for the development of PTSD symptoms over time. Data collection started prior to deployment and follow-up assessments were completed up to two years after deployment. In pNPY levels, measured before and shortly after deployment, three distinct trajectories were identified. In both cohorts, these trajectories were not related to the level of reported PTSD symptoms over time and neither were pre-deployment pNPY levels. Whereas previous research suggested that high NPY levels might be a marker for resilience, the current findings suggest limited usefulness of peripherally measured NPY in the development of PTSD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine associations between postpartum depression (PPD) and plasma neurotransmitters.
 Methods: We conducted a case-control study nested to a prospective cohort established in 3 comprehensive tertiary hospitals in Changsha, Hunan, China from February to September 2007. The Chinese version of the Edinburgh Postnatal Depression Scale (EPDS) was used at 2 weeks postpartum to screen PPD, with a score of 13 or higher as the cut-off for PPD. The women with matched age but without PPD and delivery within 5 years were selected as controls. The levels of plasma monoamine neurotransmitters including serotonin (5-hydroxytryptamine, 5-HT), dopamine (DA), and norepinephrine (NE), and peptide neurotransmitters including neuropeptide Y (NPY) and substance P (SP) in maternal blood samples taken at 2 weeks postpartum were measured and compared between PPD women (n=42) and controls (n=42).
 Results: Plasma levels of 5-HT and NPY were significantly lower while plasma levels of NE and SP were significantly higher in PPD women than those in the controls. For women with PPD, a negative correlation between NPY and NE (r=-0.36, P﹤0.05) was observed.
 Conclusion: There are changes in plasma levels of neurotransmitters in women with PPD, and there are potential interactions between different neurotransmitters.

Background Melatonin, an important neurohormone released from the pineal gland, is generally accepted to exercise an inhibitor effect on the thyroid gland. Zinc mediates the effects of many hormones and is found in the structure of numerous hormone receptors. Aim The present study aims to examine the effect of melatonin supplementation and pinealectomy on leptin, neuropeptide Y (NPY), melatonin and zinc levels in rats with hypothyroidism and hyperthyroidism. Methods This study was performed on the 70 male rats. Experimental animals in the study were grouped as follows: control (C); hypothyroidism (PTU); hypothyroidism + melatonin (PTU + M); hypothyroidism + pinealectomy (PTU + Pnx); hyperthyroidism (H); hyperthyroidism + melatonin (H + M) and hyperthyroidism + pinealectomy (H + Pnx). Blood samples collected at the end of 4-week procedures were analyzed to determine melatonin, leptin, NPY and zinc levels. Results It was found that thyroid parameters thyroid stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), total T3 (TT3) and total T4 (TT4) decreased in hypothyroidism groups and increased in the groups with hyperthyroidism. The changes in these hormones remained unaffected by melatonin supplementation and pinealectomy. Melatonin levels rose in hyperthyroidism and fell in hypothyroidism. Leptin and NPY levels increased in both hypothyroidism and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and pinealectomy, but increased in hyperthyroidism. Conclusion The results of the study demonstrate that hypothyroidism and hyperthyroidism affect leptin, NPY, melatonin and zinc values in different ways in rats. However, melatonin supplementation and pinealectomy do not have any significant influence on the changes occurring in leptin, NPY and zinc levels in thyroid dysfunction.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in adolescence, however, the etiology has not been described. Neuropeptide Y (NPY) is one potential factor that may be involved in the etiology of ADHD. The goal of this study was to evaluate NPY levels in children with ADHD and compare the findings to healthy controls., Methods: Forty-eight ADHD patients and 40 healthy controls were included in this study. The age range of ADHD patients was 6 to 16 years. All patients were diagnosed according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V)., Results: The NPY levels of children with ADHD were compared to healthy controls but were not significantly different (t (86)= -0.887,  p= 0.378). NPY levels were similar (F= 0.191, p= 0.826) between ADHD presentations, and included 8 children with predominantly hyperactive-impulsive type (14.3%), 14 children with predominantly inattentive type (30.4%), and 26 children with a combined type (55.4%). There was also no difference between ADHD patients using medical treatment, ADHD patients not using medical treatment, and control subjects in terms of NPY levels (F= 0.572, p= 0.566). There was a significant positive correlation between age and NPY levels in the ADHD group (r= 0.349, p= 0.015)., Conclusion: This study demonstrated that the NPY levels of ADHD subjects were not different than those of controls. Future studies with homogeneous phenotypes and a larger sample population are needed.