BACKGROUND

<em>Nesfatin</em>-<em>1</em> is related to inflammation. Its increased circulating concentrations are associated with the severity and prognosis of subarachnoid hemorrhage. In-hospital major adverse events (IMAEs), including acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction, are correlated with mortality after traumatic brain injury (TBI). The present study was designed to investigate the changes of plasma <em>nesfatin</em>-<em>1</em> concentrations and further assess its association with inflammation, trauma severity, in-hospital mortality and IMAEs following TBI.

METHODS

We measured plasma <em>nesfatin</em>-<em>1</em> concentrations of <em>1</em>00 severe TBI patients and <em>1</em>00 controls. Progressive hemorrhagic injury and posttraumatic cerebral infarction were diagnosed based on a follow-up computerized tomography scan. Acute traumatic coagulopathy was identified according to a coagulation test.

RESULTS

Plasma <em>nesfatin</em>-<em>1</em> concentrations were significantly higher in patients than in controls and associated highly with Glasgow coma scale (GCS) scores and plasma C-reactive protein concentrations. <em>Nesfatin</em>-<em>1</em> was indicated as an independent predictor for in-hospital mortality and IMAEs. In accordance with area under receiver operating characteristic curve, its predictive value was similar to GCS scores.

CONCLUSIONS

Increased plasma <em>nesfatin</em>-<em>1</em> concentrations are associated closely with inflammation, trauma severity and clinical outcomes, indicating that <em>nesfatin</em>-<em>1</em> might be involved in inflammation and become a good prognostic biomarker following TBI.

BACKGROUND

Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. <em>Nesfatin</em>-<em>1</em> is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation.

OBJECTIVE

So this study aimed to investigate if nesfatin-<em>1</em> levels in patients with SAH, could be used as a marker for the severity and prognosis.

METHODS

Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 20<em>1</em><em>1</em> and 20<em>1</em>3 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender.

RESULTS

During the 6-month follow-up, 7 of 48 patients died and <em>1</em>6 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-<em>1</em> level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.0<em>1</em>). The mean nesfatin-<em>1</em> level was <em>1</em><em>1</em>.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± <em>1</em>.89 pg/ml in the survival group. Furthermore, it was <em>1</em>0.22 ± <em>1</em>.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± <em>1</em>.46 pg/ml in those with good outcome. The nesfatin-<em>1</em> levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.0<em>1</em> for all).

CONCLUSIONS

The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-<em>1</em> levels. So levels of nesfatin-<em>1</em> might be useful in SAH management.

OBJECTIVE

Gastric electrical stimulation (GES) is an alternative therapy to treat patients with intractable vomiting. A preclinical study has demonstrated the modulation of the gastrointestinal (GI) peptide ghrelin by GES but such mechanism has never been investigated in patients. The aim of this work was to assess the effect of GES on GI peptide levels in patients with intractable vomiting.

METHODS

Twenty-one patients were randomized to receive either ON or OFF GES, <em>1</em>4 completed the study (<em>1</em>0 ON, 4 OFF stimulation). Vomiting episodes, gastric emptying, and gastrointestinal quality of life index (GIQLI) were assessed. Gastric and blood samples were collected before and four months after the ON period of gastric stimulation. mRNA and/or peptide levels were assessed in gastric biopsies for ghrelin, leptin, and NUCB2/<em>nesfatin</em>-<em>1</em> and in duodenal biopsies for glucagon-like peptide <em>1</em> (GLP-<em>1</em>) and peptide YY (PYY) using RT-qPCR and multiplex technology. Ghrelin, leptin, GLP-<em>1</em>, PYY, gastric inhibitory peptide (GIP), and NUCB2/<em>nesfatin</em>-<em>1</em> levels also were quantified in blood samples.

RESULTS

Among clinical parameters, vomiting episodes were slightly reduced by GES (p = 0.09). In tissue, mRNA or protein levels were not modified following chronic GES. In blood, a significant reduction of postprandial PYY levels (p < 0.05) was observed at M4 and a reduction of NUCB2/<em>nesfatin</em>-<em>1</em> levels in fasted patients (p < 0.05). Increased plasma leptin levels after GES were correlated with reduction of vomiting and improvement of GIQLI.

CONCLUSIONS

GES reduces NUCB2/<em>nesfatin</em>-<em>1</em> levels under fasting conditions and postprandial PYY levels in patients suffering from nausea and/or vomiting refractory to pharmacological therapies.

OBJECTIVE

<em>Nesfatin</em>-<em>1</em>, originates from the precursor protein nucleobindin 2 (NUCB2) and plays an important role in the development of metabolic syndrome (MetS), including obesity and hypertension. This study aimed to determine whether the <em>1</em>0<em>1</em>2C>G polymorphism of NUCB2 gene is correlated with the development of MetS in the Chinese Han population.

METHODS

The <em>1</em>0<em>1</em>2C>G polymorphism of NUCB2 gene was detected in a population of 326 patients with MetS and <em>1</em>65 healthy subjects.

RESULTS

MetS patients showed lower CG and GG genotypes, as well as lower G allele frequencies, compared with healthy subjects. Unconditional logistic regression analysis showed that the GG genotype as well as the G allele were both significantly associated with the decreased risk of developing MetS. In addition, the GG genotype of NUCB2 was significantly correlated with lower levels of waist circumference, body mass index, and fasting plasma glucose in patients with MetS.

CONCLUSIONS

<em>1</em>0<em>1</em>2C>G polymorphism of NUCB2 is correlated with a reduced risk of developing MetS in a Chinese Han population.

OBJECTIVE

Introduction: Obesity-associated arterial hypertension (AH) is characterized by common pathogenetic mechanisms. In this data, the following facet of the obesity/hypertension nexus will be discussed: the potential mechanisms by which <em>nesfatin</em>-<em>1</em> can lead to the left ventricle (LV) myocardium remodeling. The aim: - to estimate a <em>nesfatin</em>-<em>1</em> role in the remodeling of the LV myocardium in patients with AH in combination with obesity and to establish existence and a charatker of communications with cardiohaemodynamics indexes.

METHODS

Materials and methods: In 20<em>1</em>6-20<em>1</em>8 a single screening study in representative sample of <em>1</em>05 individuals aged 59,7±3,27 - 66,43±<em>1</em>,26 years was performed. AH was detected with history stratified by ESH<em>1</em>7 criteria. Body mass index (BMI) was calculated for all individuals. Obesity was diagnosed in BMI>30 kg/m2. The level of <em>nesfatin</em>-<em>1</em> has been determined to participants of a research with the use of test system of Human NES ELISA KIT (China). Echocardiography was performed for all patients.

RESULTS

Results: In patients with AH with normal body weight the level of <em>nesfatin</em>-<em>1</em> was 8,07±0,06 ng/ml that is probable higher, than in persons from control group where the value of this indicator was 4,6<em>1</em>±0,07 ng/ml (р<0,00<em>1</em>), but lower, than in patients without obesity. Also we have obtained data about existence of direct correlation connections between the level of the <em>nesfatin</em>-<em>1</em> and end-diastolic volume (r=0,35, р<0,05), end-systolic volume (r=0,46, р<0,05), end-diastolic size (r=0,54, р<0,05), end-systolic size (r=0,35, р<0,05) and feedback with ejection fraction of LV (r=-0,37, р<0,05) in the examined patients.

CONCLUSIONS

Conclusions: The increased content in blood serum of the <em>nesfatin</em>-<em>1</em> leads to remodeling of a myocardium of LV in the form of reduction of ability of a myocardium to reduction and increase of chambers and the LV sizes and can play a role in pathogenesis AH in patients with obesity.

Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. <em>Nesfatin</em>-<em>1</em>/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central <em>nesfatin</em>-<em>1</em>/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (<em>1</em>80-220 g). Cumulative food intake was remarkably suppressed for at least 24 h and body weight was significantly smaller at 24 h after i.p. administration of cisplatin compared to control group. At 90 min after i.p. administration, they were perfused, followed by carrying out double-immunohistochemistry for Fos and <em>nesfatin</em>-<em>1</em>/NucB2. The percentage of <em>nesfatin</em>-<em>1</em>/NucB2 immunoreactive neurons expressing Fos was marked increased in the hypothalamus and brainstem after i.p. administration of cisplatin. Intracerebroventricularlly administered <em>nesfatin</em>-<em>1</em>/NucB2-antisense resulted in a significant attenuation of decreased food intake for 2 h after i.p. administration of cisplatin compared to <em>nesfatin</em>-<em>1</em>/NucB2-missense treated group. These results suggest that i.p. administration of cisplatin activated, at least in part, <em>nesfatin</em>-<em>1</em>/NucB2 neuron in the CNS and may exert anorexigenic effects in rats.

BACKGROUND

Delay in the diagnosis of ovarian torsion leads to serious histopathological changes and many problems, including infertility. Various agents have been investigated to minimize detorsion-associated potential injury. This study was performed to study the effects of carnosine and vitamin E on tissue and serum expression of Nucleobindin 2 (NUCB2)/<em>nesfatin</em>-<em>1</em>, ghrelin, adropin, and irisin to determine whether they have protective effects in cases of ovarian torsion.

METHODS

Seventy-eight rats were allocated evenly into <em>1</em>3 groups. All rats, excluding those in the control and sham groups and Groups (G) III, IV, and V, were subjected to ovarian torsion for <em>1</em>2 hours. The groups were designated as follows: G-I (control), G-II (sham), G-III (vitamin E), G-IV (carnosine), G-V (carnosine + vitamin E), G-VI (torsion), G-VII (torsion + detorsion), G-VIII (torsion + vitamin E), G-IX (torsion + carnosine), G-X (torsion + carnosine + vitamin E), G-XI (torsion + detorsion + vitamin E), G-XII (torsion + detorsion + carnosine), and G-XIII (torsion + detorsion + carnosine + vitamin E). Serum levels of NUCB2/<em>nesfatin</em>-<em>1</em>, ghrelin, adropin, and irisin were measured by ELISA. Immunohistochemical methods were used to measure the expression of these hormones in ovarian tissue.

RESULTS

The levels of NUCB2/<em>nesfatin</em>-<em>1</em> immunoreactivity were increased in G-VII, G-XI, and G-XII (p<0.05). The immunoreactivity of ghrelin was significantly decreased in G-VI, G-IX, G-XI, and G-XII. However, adropin immunoreactivity did not differ significantly between the groups (p>0.05). The level of irisin immunoreactivity was decreased in G-VI, G-VII, and G-VIII (p<0.05). The serum levels of NUCB2/<em>nesfatin</em>-<em>1</em>, ghrelin, adropin, and irisin paralleled the tissue immunohistochemical results.

CONCLUSIONS

Carnosine and vitamin E protected the ovaries from ischemia-reperfusion injury in ovarian torsion. These antioxidants, especially carnosine, may be useful for the treatment of ovarian torsion.

The giant grouper Epinephelus lanceolatus is an ecologically vulnerable species with high market demand. However, efforts to improve larval husbandry are hindered by a lack of knowledge surrounding larval developmental physiology. To address this shortfall, a transcriptomic approach was applied to larvae between <em>1</em> and <em>1</em>4 days post hatch (dph) to characterise the molecular ontogenesis of genes that influence appetite and digestion. Appetite regulating factors were detected from <em>1</em> dph, including neuropeptide Y, <em>nesfatin</em>-<em>1</em>, cocaine and amphetamine regulated transcript, cholecystokinin and pituitary adenylate cyclase activating peptide and the expression level of several genes changed sharply with the onset of exogenous feeding. The level of expression for proteases, chitinases, lipases and amylases typically followed one of two expression patterns, a general increase as development progressed, or an inverted U-shape with maximal expression at c. 6 dph. Similarly, the tendency among both expression patterns was for the level of expression to increase around the time of mouth-opening. There was also evidence to suggest the presence of putative isoforms for several digestion-related genes. We have provided an insight into appetite-regulation and digestive processes in groupers during early larval development and have developed a transcriptomic database that will aid future efforts to rear this species in an aquaculture setting.

OBJECTIVE

<em>Nesfatin</em>-<em>1</em> was recently discovered anorexigenic peptide in the brain which is derived from nucleobindin-2. Central and peripheral administration of <em>nesfatin</em>-<em>1</em>, inhibits food intake, dose-dependently. Hyperthyroid patients have increased appetite and food intake with a craving for carbohydrate-rich food, at the beginning of disease, but the physiological mechanisms underlying this behavior is not known exactly. In this study, we investigated whether <em>nesfatin</em>-<em>1</em> is involved in the regulation of appetite and body weight in hyperthyroidism, or not.

METHODS

A total of 70 patients with subclinical (35) and overt hyperthyroidism (35) compared with 35 control patients. Serum <em>nesfatin</em>-<em>1</em> level was measured from all samples by commercial ELISA kit.

RESULTS

Serum <em>nesfatin</em>-<em>1</em> levels were similar between three groups (P=0.293). After adjusting for age and body mass index, <em>nesfatin</em>-<em>1</em> levels in control group was not different from subclinical and overt hyperthyroid group, respectively (P=0.567 and P=0.5<em>1</em>9).

CONCLUSIONS

These data showed that serum <em>nesfatin</em>-<em>1</em> levels do not significant change in overt and subclinical hyperthyroidism.

<AbstractText>The aim of this study was to explore the anthropometric status of rheumatoid arthritis (RA) patients, as well as two controversial adipokines, namely <em>nesfatin</em>-<em>1</em> and asymmetric dimethylarginine (ADMA), to reveal the possible relationships between them and RA.</AbstractText><AbstractText>This study included RA patients who fulfilled the American college of rheumatology classification criteria. Anthropometric parameters including height, weight, and waist circumference (WC) were measured and body mass index (BMI) was calculated. Disease activity was assessed by 28 joints disease activity score (DAS28). Fasting plasma samples were collected and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), <em>nesfatin</em>-<em>1</em> and asymmetric dimethylarginine (ADMA) were determined using commercial kits. Statistical analyses were done using the BMI SPSS Statistics.</AbstractText><AbstractText>A total of 77 patients including 63 females, with an average age of 48.45±<em>1</em><em>1</em>.26 and disease duration of 9.99±5.80 years participated the study, 62% of whom were overweight or obese. Disease activity was significantly higher in obese patients. In addition, BMI and WC were correlated with CRP and ESR, indicating higher level of inflammation in obese patients. DAS28 was also found to be correlated with CRP, ESR and ADMA (r=0.38, 0.6<em>1</em>, 0.2<em>1</em> respectively). Higher protein intake was accompanied with higher CRP and ESR and higher carbohydrate intake was related to higher CRP and lower <em>nesfatin</em>-<em>1</em>.</AbstractText><AbstractText>Weight, BMI, and WC were correlated with the activity of RA and the concentrations of CRP and ESR went up in tandem with BMI. In addition, ADMA, but not <em>nesfatin</em>-<em>1</em>, was associated with BMI and disease activity in RA patients.</AbstractText>

<strong class="sub-title"> Background: </strong> Fibrinogen and interleukin-<em>1</em><i>β</i> as a proinflammatory cytokine and interleukin-<em>1</em>0 and <em>nesfatin</em>-<em>1</em> as an anti-inflammatory cytokine have an important role in the development and prevention of systemic inflammation and incidence of obesity-induced diseases. Thus, this study is aimed at the interaction effects of aerobic training and oak husk hydroalcoholic extract consumption on plasma levels of fibrinogen, interleukin-<em>1</em><i>β</i>, <em>nesfatin</em>-<em>1</em>, and interleukin-<em>1</em>0 in obese elderly male mice.

<strong class="sub-title"> Materials and methods: </strong> In this experimental study, 40 fat male mice were fed a high-fat diet for 4 weeks to induce obesity, and subsequently, they were divided randomly into four groups: control, supplement, exercise-placebo, and exercise-supplement. The training groups performed aerobic exercise 5 days a week for 6 weeks (approximately 80-75% VO_max ²). The supplement groups received a solution of oak husk hydroalcoholic extract at a dose of 20 milligram per kilogram of body weight for 6 weeks. Blood samples were taken 48 h after the last training session, and the levels of IL-<em>1</em>0, fibrinogen, IL-<em>1</em><i>β</i>, and <em>nesfatin</em>-<em>1</em> were measured. Data were analyzed using one-way ANOVA and LSD post hoc tests.

<strong class="sub-title"> Results: </strong> The results showed that six-week training and oak husk hydroalcoholic extract consumption significantly increased the levels of IL-<em>1</em>0 and <em>nesfatin</em>-<em>1</em> in experimental groups (<i>P</i> < 0.00<em>1</em>). Also, the levels of fibrinogen and IL-<em>1</em><i>β</i> decreased significantly in training groups. Averages between group variations of all indicators were statistically significant, and they were more meaningfully pronounced in the exercise-supplement group than other groups (<i>P</i> ≤ 0.05).

Conclusions: Considering the results of the present study, the use of moderate aerobic exercise and oak husk hydroalcoholic extract is recommended to reduce the risk of obesity; it may also have a positive effect on inflammatory factors.

Research in the field of food intake regulation is gaining importance. This often includes the measurement of peptides regulating food intake. For the correct determination of a peptide's concentration, it should be stable during blood processing. However, this is not the case for several peptides which are quickly degraded by endogenous peptidases. Recently, we developed a blood processing method employing Reduced temperatures, Acidification, Protease inhibition, Isotopic exogenous controls and Dilution (RAPID) for the use in rats. Here, we have established this technique for the use in humans and investigated recovery, molecular form and circulating concentration of food intake regulatory hormones. The RAPID method significantly improved the recovery for (<em>1</em>25)I-labeled somatostatin-28 (+39%), glucagon-like peptide-<em>1</em> (+35%), acyl ghrelin and glucagon (+32%), insulin and kisspeptin (+29%), <em>nesfatin</em>-<em>1</em> (+28%), leptin (+2<em>1</em>%) and peptide YY3-36 (+<em>1</em>9%) compared to standard processing (EDTA blood on ice, p <0.00<em>1</em>). High performance liquid chromatography showed the elution of endogenous acyl ghrelin at the expected position after RAPID processing, while after standard processing 62% of acyl ghrelin were degraded resulting in an earlier peak likely representing desacyl ghrelin. After RAPID processing the acyl/desacyl ghrelin ratio in blood of normal weight subjects was <em>1</em>:3 compared to <em>1</em>:23 following standard processing (p = 0.03). Also endogenous kisspeptin levels were higher after RAPID compared to standard processing (+99%, p = 0.02). The RAPID blood processing method can be used in humans, yields higher peptide levels and allows for assessment of the correct molecular form.

<em>Nesfatin</em>-<em>1</em> is a novel anorectic neuropeptide with potent metabolic regulatory effects.

We aimed to evaluate the relationship between nesfatin-<em>1</em> levels and slow coronary flow (SCF).

A total of 60 consecutive patients with SCF and 60 consecutive patients with normal coronary flow (NCF) were enrolled into the study. <em>Nesfatin</em>-<em>1</em> level was measured from blood serum samples using enzyme-linked immunosorbent assay test.

Serum nesfatin-<em>1</em> levels were significantly lower in the SCF group compared to the NCF group (p < 0.00<em>1</em>). Low levels of nesfatin-<em>1</em> were found to be significantly and independently associated with the SCF (odds ratio 0.982, 95% confidence interval 0.969-0.995, p = 0.005).

The results of this study showed that serum nesfatin-<em>1</em> level was lower in the SCF group than in the NCF group. <em>Nesfatin</em>-<em>1</em> could play a role in the pathogenesis of SCF phenomenon with mechanisms such as inflammation and endothelial dysfunction. Further studies are needed to determine the relation between SCF and nesfatin-<em>1</em>.

Data on the effects of probiotics on adipokines such as omentin-<em>1</em>, <em>nesfatin</em>-<em>1</em>, and adropin are limited. The aim of this study was to evaluate the effects of probiotic yogurt along with a low-calorie diet (LCD) on serum omentin-<em>1</em>, adropin, and <em>nesfatin</em>-<em>1</em> concentrations in obese and overweight individuals. Sixty obese or overweight individuals aged 20-50 years old were involved in this randomized double-blind placebo-controlled clinical trial. Participants were randomly allocated into two groups to consume either probiotic yogurt containing Lactobacillus acidophilus La5, Bifidobacterium BB<em>1</em>2, and Lactobacillus casei DN00<em>1</em> (<em>1</em>08 CFU/g each) (n = 30) or regular yogurt (n = 30) along with a LCD in both groups for 8 weeks. Fasting blood samples were taken at baseline and after the 8-week intervention to determine related variables. A significant decrease in body fat percentage was observed in the probiotic group compared with the regular group after 8 weeks (- <em>1</em>.5<em>1</em> ± 069 vs - 0.88 ± 0.68%, P = 0.002). After the 8-week intervention, a significant difference in serum adropin concentration (6.04 ± 24.46 vs - 8.<em>1</em>6 ± 24.66 pg/ml, P = 0.03 and serum omentin-<em>1</em> concentration (0.09 ± <em>1</em>.5<em>1</em> vs - <em>1</em>.5 ± <em>1</em>.8 ng/ml, P = 0.003) was observed between two groups. We did not observe any significant changes in <em>nesfatin</em>-<em>1</em> and other anthropometric measures. Overall, probiotic yogurt for 8 weeks among overweight or obese individuals along with LCD had beneficial effects on body fat percentage, serum omentin-<em>1</em>, and adropin concentration, but it did not have any effect on <em>nesfatin</em>-<em>1</em> level.

This study aimed to determine oxidative stress in the tissue after testicular torsion biochemically and histopathologically and to examine the effects of <em>Nesfatin</em>-<em>1</em> treatment on this injury. Thirty-two rats were randomly divided into four groups: sham, torsion + detorsion (4 hr torsion followed by <em>1</em> hr detorsion), ischaemia/reperfusion + saline (I/R + S) and I/R + <em>nesfatin</em>-<em>1</em>. I/R + S group a single-dose saline treatment was administered intraperitoneally at the two-hundred-tenth minute of torsion (ischaemia; <em>1</em>0 cc/kg). Similarly, I/R + <em>nesfatin</em>-<em>1</em> group a single dose of <em>nesfatin</em>-<em>1</em> treatment was administered intraperitoneally at the two-hundred-tenth minute of ischaemia (<em>1</em>0 µg/kg). Myeloperoxidase, total oxidant status and oxidative stress index values were significantly increased in the I/R and I/R + S group compared to the sham group. Superoxide dismutase was significantly decreased in the I/R + S group compared to the sham group. No significant difference was found between the I/R + <em>nesfatin</em>-<em>1</em> group and the other I/R groups (I/R and I/R + S) in terms of biochemical parameters. The mean diameter of the seminiferous tubule decreased in the I/R groups. However, the mean diameter of the seminiferous tubules was not significantly different between the I/R + S group and the I/R + <em>nesfatin</em>-<em>1</em> group. Thus, the administration of <em>nesfatin</em>-<em>1</em> after ischaemia did not reduce testicular-oxidative stress.

<strong class="sub-title"> Keywords: </strong> ischaemia; <em>nesfatin</em>-<em>1</em>; oxidative stress; reperfusion; testis torsion.

<AbstractText>Recombinant human relaxin-2, serelaxin, is being proved as a novel drug with therapeutic efficacy in some cardiovascular diseases, especially heart failure, a disease whose physiopathology and course are firmly correlated with important alterations in cardiac metabolism. The aim of our present work was to investigate changes in the cardiac metabolome following relaxin-2 treatment.</AbstractText><AbstractText>Sprague-Dawley rats were treated with human recombinant relaxin-2 using osmotic minipumps at a dose of 0.4 mg/kg/day for 2 weeks. Body composition was measured with a nuclear magnetic resonance imaging system seven days after surgery and on the final day of the experiment. The last two days of treatment, respiratory quotient, locomotor activity and energy expenditure were measured with a calorimetric system. The plasma levels of relaxin-2, total cholesterol, high- and low- density lipoproteins (HDL, LDL), triglycerides and the hepatic enzymes glutamic-pyruvic transaminase (GTP) and gamma-glutamyltransferase (GGT) levels were analyzed. The metabolic profiling of both atria from relaxin-2-treated and control rats was carried out using two separate ultra-high performance liquid chromatography (UHPLC)-Time of Flight-MS based platforms analyzing methanol and chloroform/methanol extracts combined with a UHPLC-single quadrupole-MS based platform used to analyze aminoacids and with a methanol/water extract platform that covered polar metabolites. Identified ion features in the methanol extract platform included fatty acids, acyl carnitines, bile acids, monoacylglycerophospholipids, monoetherglycerophospholipids, free sphingoid bases, and oxidized fatty acids. The chloroform / methanol extract platform provided coverage over glycerolipids, cholesterol esters, sphingolipids, diacylglycerophospholipids, and acyl-ether-glycerophospholipids. Gene expression levels of the adipokines adiponectin, leptin and <em>nesfatin</em>-<em>1</em> in visceral adipose tissue and cardiac gene expression levels of key enzymes of desaturation and elongation of n-6 and n-3 PUFAs were assessed by Real Time-PCR.</AbstractText><AbstractText>Twenty-eight metabolites out of three hundred sixty-two were significantly altered by human relaxin-2. These included fifteen glycerophospholipids: three phosphatidylethanolamines (PE) and twelve phosphatidylcholines (PC); eight sphingolipids: three ceramides (Cer) and five sphingomyelins (SM); and also five aminoacids and one carboxylic acid. Interestingly, the majority of changes correspond to lipid classes, twelve of them polyunsaturated diacylglycerophosphatidylcholines with long acyl chains, containing mainly docosahexaenoic acid (22:6) and arachidonic acid (20:4). Atrial levels of Elovl5 (Elongation of very long chain fatty acids protein 5), Fads<em>1</em> (Δ5-fatty acid desaturase) and Fads2 (Δ6-fatty acid desaturase), key enzymes of elongation and desaturation of n-6 and n-3 PUFAs like arachidonic acid and DHA, respectively, were significantly increased by relaxin-2 treatment. Atrial tissues from rats treated with relaxin-2 showed a significant increase in the mRNA levels of Srebf<em>1</em>, a transcription factor that activates the gene expression of Elovl5, Fads<em>1</em> and Fads2. The treatment with relaxin-2 significantly decreased the visceral fat mRNA expression levels of adiponectin, leptin and <em>nesfatin</em>-<em>1</em>, adipokines known to exert an important influence on the regulation of cardiovascular function.</AbstractText><AbstractText>Serelaxin (human recombinant relaxin-2) treatment induces significant changes in cardiac major components of the membrane lipid bilayer such as glycerophospholipids and sphingolipids, known to have structural roles but also very relevant regulatory effects in cardiac function. Serelaxin induced also modifications in several aminoacids of high influence in cardiac energy metabolism regulation. Our results highlight the need to further understand the role of relaxin-2 in the regulation of cardiac energy metabolism, in the context of the therapeutic strategies for the treatment of cardiometabolic pathologies as heart failure.</AbstractText>

<em>Nesfatin</em>-<em>1</em>, a recently discovered peptide, was shown to have anti-inflammatory effects. Acute pancreatitis (AP) is a life-threatening condition caused by various reasons. Although the etiology of AP is well-known, its pathogenesis is not clear. The aim of this study is to investigate the possible anti-inflammatory role of <em>nesfatin</em>-<em>1</em> and its probable protective underlying mechanisms in an acute pancreatitis model. Caerulein was applied intraperitoneally to induce acute pancreatitis in Sprague-Dawley female rats. <em>Nesfatin</em>-<em>1</em> was administered 5 minutes before the application of caerulein to determine its potential anti-inflammatory role on AP. Five minutes before <em>nesfatin</em>-<em>1</em> injection, in order to investigate the underlying mechanism, oxytocin receptor antagonist (atosiban), melanocortin receptor antagonist (HS024), or ghrelin receptor antagonist (cortistatin) were administered. Five minutes after <em>nesfatin</em>-<em>1</em> administration, two doses of caerulein were applied one hour apart. The rats were sacrified <em>1</em>2 hours after the first caerulein dose for serum and pancreatic tissue sampling. Microscopic damage scoring, malondialdehyde and glutathione levels, myeloperoxidase activity, luminol and lucigenin chemiluminescence levels in pancreatic tissue and amylase, lipase, trypsinogen-2 levels in serum were evaluated. Oxidative damage was decreased with <em>nesfatin</em>-<em>1</em> treatment in the acute pancreatitis model (P < 0.05 - 0.00<em>1</em>). The administration of HS024 reversed the effect of <em>nesfatin</em>-<em>1</em>, via increasing lipase, amylase, trypsinogen-2, malondialdehyde (MDA), myeloperoxidase (MPO) and lucigenin levels (P < 0.05 - 0.0<em>1</em>). Atosiban pre-treatment elevated MPO activity, luminol and lucigenin chemiluminescence levels (P < 0.0<em>1</em> - 0.00<em>1</em>) and cortistatin increased lucigenin and luminol chemiluminescence (P < 0.05 - 0.0<em>1</em>). Although receptor antagonists reversed the effect of <em>nesfatin</em>-<em>1</em> on related biochemical parameters, no significant difference was found in histological scoring. Our results indicated that <em>nesfatin</em>-<em>1</em> had an anti-inflammatory effect on acute pancreatitis via mainly effecting melanocortin receptors.

<em>Nesfatin</em>-<em>1</em> is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic <em>nesfatin</em>-<em>1</em> inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic <em>nesfatin</em>-<em>1</em> levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in <em>nesfatin</em>-<em>1</em> serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic <em>nesfatin</em>-<em>1</em> and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9<em>1</em><em>1</em>9 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic <em>nesfatin</em>-<em>1</em>. The increase in hypothalamic <em>nesfatin</em>-<em>1</em> participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.

<em>Nesfatin</em>-<em>1</em>, an 82-amino acid peptide encoded by the secreted precursor nucleobinin-2 (NUCB2), exerts potent anorexigenic action independently of leptin signaling. This propensity has propelled this peptide and its analogues as potential anti-obesity drug candidates. However, a more extensive comprehension of its biological actions is needed prior to envisaging its potential use in the treatment of metabolic diseases. Swallowing is an essential motor component of ingestive behavior, which induces the propulsion of the alimentary bolus from the mouth to the esophagus. The dorsal swallowing group (DSG) which constitutes a part of the central pattern generator of swallowing (SwCPG) is located within the solitary tract nucleus (STN), a region reported to contain <em>nesfatin</em>-<em>1</em>/NUCB2 expressing neurons. In this context, we investigate here the possible effects of <em>nesfatin</em>-<em>1</em> on swallowing discharge. <em>Nesfatin</em>-<em>1</em> dose-dependently inhibited swallowing reflex and activated neurons located in the DSG region. In addition, we provide evidences that strongly suggest that this <em>nesfatin</em>-<em>1</em> inhibitory effect involved an oxytocinergic relay. Indeed, oxytocin (OT) injection at the brainstem level inhibited swallowing reflex and OT receptor antagonist prevented <em>nesfatin</em>-<em>1</em> inhibitory action. Altogether, these data constitute the first demonstration that <em>nesfatin</em>-<em>1</em> modulates swallowing reflex by acting at the brainstem level via an oxytocinergic relay.

This study aimed to investigate the role of leptin, ghrelin, neuropeptide Y, and <em>nesfatin</em>-<em>1</em> in young children with autism spectrum disorder (ASD). A total of 44 children with ASD and 44 healthy controls aged <em>1</em>8-60 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 <em>nesfatin</em>-<em>1</em> 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.

<strong class="sub-title"> Keywords: </strong> Autism; Early childhood; Ghrelin; Leptin; Nesfatin-<em>1</em>; Neuropeptide Y.

<strong class="sub-title"> Objective: </strong> This study aims to investigate the levels of <em>nesfatin</em>-<em>1</em>-hormone in patients with Antisocial Personality Disorder (ASPD) and their relationship with clinical variables.

<strong class="sub-title"> Methods: </strong> A total of 90 people (45 ASPD, 45 controls) were included in our study. Sociodemographic Data Form, Beck-Depression-Inventory (BDI), Beck-Anxiety-Inventory (BAI), Barratt Impulsivity Scale (BIS-<em>1</em><em>1</em>), Buss-Durkee-Hostility-Inventory (BDHI) were applied to all participants. Venous blood samples were taken from participants at the same time of the day when they were hungry.

<strong class="sub-title"> Results: </strong> It was found that the BDI and BAI scores of the ASPD were higher than those of the controls (p<0.00<em>1</em>, for both scales). The scores in BIS-<em>1</em><em>1</em>; motor and nonplanning-impulsivity subscales were higher than those of the controls (p<0.00<em>1</em>, 0.036, respectively). The scores obtained by the ASPD were higher in all subscales of BDHI (p<0.00<em>1</em>). For the <em>nesfatin</em>-<em>1</em>-hormone, the values of the ASPD were lower than those of the controls (p=0.044). No relationship was found between the <em>nesfatin</em>-<em>1</em>-hormone and any other laboratory parameters and applied scales (p>0.05).

<strong class="sub-title"> Conclusion: </strong> This is the first study to examine the <em>nesfatin</em>-<em>1</em>-hormone levels in patients with any personality disorder. Further studies with more participants are needed in different types of personality disorders to understand the relationship between personality disorder and <em>nesfatin</em>-<em>1</em>-hormone levels.

<strong class="sub-title"> Keywords: </strong> Aggression; Antisocial personality disorder; Impulsivity; Nesfatin-<em>1</em>.

[No Abstract Available].