Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation

SUMMARY OBJECTIVE: Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. METHODS: Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. RESULTS: There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. CONCLUSION: Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Ghrelin and appetite regulation: Mechanism and clinical application / 中华内分泌代谢杂志

The development of obesity is closely related to the disruption of central appetite regulation. Gastric growth hormone-releasing peptide is the only appetite-promoting peptide known to be present in the circulatory system. Ghrelin may act on the central homeostatic and hedonic feeding neural pathways to promote appetite and feeding behavior, and may be a new target for appetite regulation. In addition, Ghrelin is also involved in the regulation of energy homeostasis via promoting growth, regulating gastrointestinal function, and suppressing inflammatory response. Therefore, the research on the mechanism of ghrelin and its receptors will help understand the pathophysiological changes in the central appetite regulation process of obese patients, and to find potential targets for the treatment of obesity. In this paper, we focus on the molecular mechanism of appetite regulation by Ghrelin and its clinical application.

Histopathological and immunohistochemical changes of gastric fundus and duodenum after bariatric embolization in the New Zealand rabbits / 中华放射学杂志

Objective:To investigate the histopathological and immunohistochemical changes of gastric fundus and duodenum after bariatric embolization of left gastric artery and gastroduodenal artery in obesity New Zealand rabbit models.Methods:Twenty obesity New Zealand rabbit models were successfully established and divided into two groups using stratified randomization. Left gastric artery and gastroduodenal artery were embolized with gelatin sponge (350-560 μm) in experimental group, left gastric artery and gastroduodenal artery were perfused with normal saline in control group. All animals were sacrificed for pathological, immunohistochemical examination and Western Blot analysis 4 weeks post embolization, the density of ghrelin producing cells and the gray ratio of ghrelin protein band were measured and compared by the independent sample t test. Results:Macropathological examination showed ulceration in the anterior wall of the gastric body in one rabbit, histopathological examination showed mucosa ulceration in the gastric body in 3 rabbits in experimental group. Immunohistochemical examination showed that the ghrelin producing cells of gastric fundus and duodenum in the experimental group were significantly less than those in the control group (10.0±5.1 vs.27.7±3.4, t=12.35, P<0.05;5.6±2.6 vs. 12.3±2.1, t=4.73, P<0.05). Western Blot analysis showed that the gray ratio of ghrelin bands of gastric fundus and duodenum in the experimental group were significantly lower than that in the control group (0.65±0.05 vs.1.12±0.09, t=9.62, P<0.05;0.55±0.03 vs. 0.94±0.08, t=7.98, P<0.05). Conclusions:Immunohistochemical and Western Blot analysis showed that the ghrelin-producing cells of gastric fundus and duodenum in the experimental group were significantly less than those in the control group after bariatric embolization, histopathologic analysis indicated that bariatric embolization was a safe technique.

Short sleep duration is associated with high energy and total lipid intake in obese women: a pilot study / A curta duração do sono está associada ao elevado consumo energético e de lipídios totais em mulheres com obesidade: um estudo piloto

ABSTRACT Objective To evaluate the influence of self-reported sleep duration on ghrelin secretion and nutritional indicators in obese women. Methods This is an observational study, including 36 adult women with obesity. Sleep duration was reported while completing the general questionnaire. Dietary, laboratory, anthropometric, and body composition indicators, and resting metabolic rate, were evaluated. For statistical analysis, sleep duration data were grouped into tertiles: less than six (first tertile); equal to or above six; and less than eight (second tertile); equal to or greater than eight hours of sleep per day (third tertile). The indicators were compared for the different ranges of the sleep duration. Results There was no significant difference when comparing anthropometric, laboratory, and energy expenditure indicators between sleep tertiles. However, women with shorter sleep duration (less than 6 hours per day) had a higher mean caloric intake, compared with the tertile of eight hours or more of sleep per day. For total lipid intake, the mean consumption was higher in the first tertile (up to six hours a day). Conclusion Sleeping less than six hours a day led to an increase in energy and lipid intake in obese women. However, it did not change the plasma ghrelin concentration.

RESUMO Objetivo Avaliar a influência da duração de sono autorrelatada na secreção de grelina e indicadores nutricionais na obesidade. Métodos Trata-se de um estudo observacional, incluindo 36 mulheres adultas com obesidade. A duração do sono foi relatada durante o preenchimento do questionário de dados gerais. Foram avaliados indicadores dietéticos, laboratoriais, antropométricos e de composição corporal, além da taxa metabólica de repouso. Para análise estatística, os dados de duração de sono foram agrupados em tercis, sendo menor do que seis (primeiro tercil), igual ou acima seis e menor do que oito (segundo tercil), igual ou maior do que oito horas de sono por dia (terceiro tercil). Os indicadores supracitados foram comparados entre as diferentes faixas dos tercis de duração de sono. Resultados Não houve diferença significativa ao comparar os indicadores antropométricos, laboratoriais e do gasto de energia, entre os tercis de sono. Porém, mulheres com menor tempo de duração do sono (menos de 6 horas por dia) apresentaram maior média da ingestão calórica, comparado com o tercil de oito horas ou mais de sono por dia. Para a ingestão de lipídios totais, a média de consumo foi maior no primeiro tercil (até seis horas por dia). Conclusão Dormir menos do que seis horas por dia levou ao aumento na ingestão energética e de lipídios em mulheres com obesidade, porém, não alterou a concentração de grelina plasmática.

Mediators of energy homeostasis in hyperthyroidism

ABSTRACT Objective: The aim of this study was to assess the effect of hyperthyroidism and its treatment on body weight and composition, insulin resistance, and mediators of appetite and energy homeostasis, namely ghrelin, leptin, adiponectin, and fibroblast growth factor 21 (FGF21). Subjects and methods: Thirty-five adult patients (27 female and 8 male, aged 39.63 ± 9.70 years) with overt hyperthyroidism were evaluated for leptin, ghrelin, adiponectin, and FGF21 levels; insulin resistance; and body composition using DEXA both at baseline and a minimum of two months following normalization of serum thyroxin on carbimazole treatment. Comparison of means between the baseline and post treatment values was performed by the paired t test for normally distributed parameters and by the Wilcoxon signed-rank test for non-normally distributed data. Results: Hyperthyroidism correction resulted in an increase in weight from 51.15 ± 8.50 kg to 55.74 ± 8.74 kg (P < 0.001), paradoxically accompanied by a decrease in insulin resistance as measured by HOMA-IR from 1.35 (1.02-1.72) to 0.73 (0.52-0.93) ( P < 0.001). Correction of hyperthyroidism was also associated with a decrease in FGF21 from 58 (55-64) to 52 (47-58) pg/mL ( P < 0.001) and in leptin levels from 17 (7-36) to 11 (4.6-28) ng/mL ( P = 0.03). Conclusion: Despite lower body weight, thyrotoxicosis is associated with insulin resistance. High levels of thermogenic hormones, leptin, and FGF21 were observed in thyrotoxicosis and may be partly responsible for the excessive heat production typical of this condition.

Correlation of body mass index to Ghrelin and IGF-1 among children with short stature

Abstract Objective: To assess the BMI among children with Growth Hormone Deficiency (GHD) and Idiopathic Short Stature (ISS) and its correlation to ghrelin, Growth Hormone (GH), and Insulin-like Growth Factor-1 (IGF-1) levels. Methods: A cross-sectional descriptive study in which 42 patients attending the Pediatric endocrine clinic were enrolled, allocated into two groups: group I: GHD children; group II: ISS children. Ghrelin, IGF-1 and GH in both groups were measured. Results: Ghrelin was significantly higher among GHD group (p < 0.001). Overall, there was a strong negative correlation between IGF-1 and ghrelin (r = -0.977, p-value = < 0.001) while a moderate positive correlation between ghrelin and BMI (r = 0.419, p-value = 0.006). There was a weak positive non-significant correlation between IGF-1 and BMI (r = 0.276, p-value = 0.077). In GHD group, there was a weak positive non-significant correlation between ghrelin and GHmax measurement (r = 0.052, p-value = 0.824), while a weak negative non-significant correlation between both variables in ISS group (r = -0.243, p-value = 0.288). In GHD group, there was a moderate positive correlation between ghrelin and BMI (r = 0.500, p-value = 0.021), but weak negative non-significant correlation between both variables in ISS group (r = -0.255, p-value = 0.265). Conclusion: There was a negative feedback loop between ghrelin and IGF-1, whereas a positive feedback between ghrelin and BMI. BMI was more affected in the ISS group but was non-signifi-cantly correlated with ghrelin. There was no significant compensatory response of ghrelin suggesting its contribution to the pathogenesis of ISS.

Fasting levels of appetite regulating hormones predict caloric intake at breakfast in a group of Chilean adolescents / Los niveles en ayunas de hormonas reguladoras del apetito predicen la ingesta energética en el desayuno en adolescentes

BACKGROUND: Appetite regulation is integral to food intake and is modulated by complex interactions between internal and external stimuli. Hormonal mechanisms which stimulate or inhibit intake have been characterized, but the physiologic effects of serum levels of such hormones in short-term appetite regulation have received little attention. AIM: To evaluate whether fasting levels of orexigenic/anorexigenic hormones were associated with energy intake at breakfast, served soon after drawing a fasting blood sample, in a group of adolescents. MATERIAL AND METHODS: Anthropometry, body composition and fasting blood levels of leptin, insulin, ghrelin, and orexin-A were measured in 655 Chilean adolescents aged 16.8 ± 0.3 years (52% males). Energy intake was measured at a semi-standardized breakfast. Associations between hormone levels and energy intake were studied using multivariate linear models. RESULTS: Thirty nine percent of participants were overweight/ obese. After an overnight fast, median values for leptin, insulin, ghrelin and orexin-A were 7.3 ng/mL, 6.7 IU/dL, 200.8 pg/mL, and 16.1 pg/mL, respectively. Participants ate on average 637 ± 239 calories at breakfast. In multivariable models, insulin levels were inversely and independently associated with caloric intake at breakfast (β = −18.65; p < 0.05), whereas leptin, ghrelin and orexin-A levels were positively and independently associated with intake: β= 5.56, β = 0.34 and β = 8.40, respectively, p < 0.05. CONCLUSIONS: Fasting leptin, ghrelin and orexin-A were positively associated with energy intake during breakfast provided soon after the blood draw. Insulin was negatively associated with energy intake. Modifiable factors influencing levels of appetite regulating hormones could be a potential target for influencing food intake.

ANTECEDENTES: La regulación del apetito es parte integral de la ingesta alimentaria y es modulada por complejas interacciones entre estímulos internos y externos. Se han caracterizado los mecanismos hormonales que estimulan o inhiben la ingesta, pero los efectos fisiológicos de los niveles séricos de tales hormonas en la regulación del apetito a corto plazo han recibido poca atención. OBJETIVO: Evaluar si los niveles en ayunas de hormonas orexigénicas/ anorexigénicas se asocian con la ingesta energética en el desayuno, entregado inmediatamente después de una muestra de sangre en ayunas, en un grupo de adolescentes. MATERIAL Y MÉTODO: Se efectuaron mediciones antropométricas, composición corporal y medición de niveles en ayunas de leptina, insulina, grelina y orexina-A en 655 adolescentes de 16,8 ± 0,26 años. La ingesta energética se midió en un desayuno semiestandarizado. Se estudiaron las asociaciones entre los niveles hormonales y la ingesta energética mediante modelos lineales multivariados. RESULTADOS: Los valores de leptina, insulina, grelina y orexina-A fueron 7,3 ng/mL, 6,7 UI/dL, 200,8 pg/mL y 16,1 pg/mL respectivamente. Los participantes comieron un promedio de 637 ± 239 calorías en el desayuno. Los niveles de insulina se asociaron inversa e independientemente con la ingesta del desayuno (β = −18,65; p < 0,05), mientras que los niveles de leptina, grelina y orexina-A se asociaron positiva e independientemente con la ingesta: β = 5,65; β = 0,34; β = 8,40, (p < 0,05). CONCLUSIONES: La leptina, grelina y orexina-A en ayunas se asociaron positivamente con la ingesta de energía durante el desayuno proporcionado poco después de la muestra de sangre. La insulina se asoció negativamente con la ingesta de energía. Los factores modificables que influyen en las hormonas reguladoras del apetito podrían ser un objetivo potencial para influir en la ingesta de alimentos.

Effect and mechanism of transcutaneous electrical acustimulation on the improving gastrointestinal motility and inflammation in patients with acute pancreatitis / 中华消化杂志

Objective:To explore the regulation effect and possible mechanism of transcutaneous electrical acustimulation (TEA) on the improvement of gastrointestinal motility and inflammation in patients with acute pancreatitis (AP).Methods:A randomized, single-blinded, sham-controlled study was performed. A total of 62 AP patients were randomly divided into the TEA group ( n=31) and sham-TEA group ( n=31), on the basis of regular treatment, who received TEA treatment at Neiguan (PC6) and Zusanli (ST36) or sham-TEA treatment at corresponding pseudo stimulation acupoints for 2 days. Abdominal distension score, time to first defecation, gastric slow wave, heart rate variability (low frequency and high frequency, reflecting sympathetic and vagal activity, respectively), serum level of tumor tecrosis factor (TNF)-α, plasma levels of motilin, ghrelin and vasoactive intestinal peptide(VIP) tested by enzyme linked immunosorbent assay were compared before and after the treatment. Wilcoxon rank test, Mann-Whitney U test, t-test and two factor repeated measurement analysis of variance were used for statistical analysis. Results:After the treatment, abdominal distension score of TEA group was lower than that of sham-TEA group(1 (0 to 2) vs.5(3 to 6)) and time to first defecation was earlier than that of sham-TEA group((55.00±24.27) h vs.(67.95±23.84) h), the percentage of normal gastric slow wave was higher than that of sham-TEA group((57.42±11.16)% vs. (40.92±8.52)%), and the differences were statistically significant ( Z=-4.95、 t=-2.12、 F=61.53, all P<0.05). After the treatment, the serum level of TNF-α of TEA group was significantly lower than that of sham-TEA group((4.27±1.28) ng/L vs.(6.19±2.03) ng/L), and the difference was statistically significant ( F=28.65, P<0.05). The ratio of post/pre-treatment of low frequency heart rate variability of the TEA group was significantly lower than that of sham-TEA group, however, the result of high frequency was opposite (0.87±0.18 vs.1.14±0.16, 1.19±0.18 vs.0.96±0.13), and the differences were statistically significant ( t=-6.22 and 5.74, both P<0.05). After the treatment, the plasma level of ghrelin of TEA group was higher than that of sham-TEA group ((2.02±0.62) μg/L vs. (0.93±0.49) μg/L), the VIP level was lower than of sham-TEA group ((30.58±12.20) μg/L vs.(44.35±29.52) μg/L), and the differences were statistically significant ( F=59.22 and 5.50, both P<0.05). However, there was no significant difference in motilin levels between two groups ((24.57±9.58) ng/L vs. (22.75±9.58) ng/L, P>0.05). Conclusion:TEA treatment can improve gastrointestinal motility and inhibit the inflammation in early AP, which may be related with the regulation of autonomic function, gastrointestinal hormone ghrelin and VIP.

Impact of Yuyetang on Cognitive Impairment of Rats with Type 2 Diabetes Mellitus Based on Regulation of Ghrelin Level / 中国实验方剂学杂志

ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus （T2DM）-induced cognitive impairment （DCI） and explore the pathway in the prevention and treatment of DCI. MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin （STZ） combined with the high-fat and high-sugar diet （STZ）. The model rats were divided into model group， metformin group （200 mg·kg-1）， and low-，medium-， and high-dose Yuyetang groups（4.575，9.15， 18.3 g·kg-1）according to the blood glucose， with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days， and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention， the learning and memory abilities of rats were tested by the Morris water maze. After the test， the whole brains of rats were sampled for hematoxylin-eosin （HE） staining to observe the pathological changes in the hippocampal CA1 region， and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry. ResultCompared with the normal group ， the model group showed increased blood glucose（P<0.01），reduced body weight（P<0.01），prolonged escape latency（P<0.05，P<0.01）， shortened retention time and movement distance in the target area，decreased number of platform crossings（P<0.01）， abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region， and decreased expression of Ghrelin in the serum，hippocampal CA1 region， and gastric tissues（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Yuyetang groups showed increased body weight， while all Yuyetang groups showed reduced blood glucose（P<0.01）， shortened escape latency （P<0.05）， prolonged retention time and movement distance in the target area，increased platform crossings （P<0.05， P<0.01）， improved morphology and structure of cells， increased number of normal cell in the hippocampal CA1 region， and elevated Ghrelin levels in the serum， gastric tissues， and hippocampal CA1 region（P<0.05， P<0.01）. ConclusionYuyetang can effectively improve the cognitive ability of DCI rats， and its mechanism may be related to the regulation of Ghrelin levels in the serum， hippocampal CA1 region， and gastric tissues.

Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Protective effects and mechanism of ghrelin on human retinal vascular endothelial cells under high glucose / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the protective effect and mechanism of ghrelin on human retinal vascular endothelial cells under high glucose.<p>METHODS: A hyperglycemic injury model as a research object was established on human retinal vascular endothelial cells. CCK-8 kit was used to detect the effects of ghrelin with different concentrations on cell proliferation under high glucose, so as to screen the optimal concentration of ghrelin. The cells were then divided into normal control group(NC), ghrelin group(ghrelin), high glucose group(HG)and ghrelin+ high glucose group(ghrelin+HG). Cell proliferation was detected by CCK-8 kit, apoptosis was detected by Annexin-APC/7-AAD kit, and the expressions of NLRP3, Caspase-1, IL-1β and IL-18 proteins were detected by western blotting.<p>RESULTS: Compared with NC group(100.00%±0.00%), the cell proliferation rate of HG group(69.87%±0.68%, <i>P</i><0.05)was significantly decreased. Compared with HG group, the cell proliferation rate of ghrelin + HG group was significantly increased(92.31%±3.62%, <i>P</i><0.05). Compared with NC group(4.94%±0.15%), the cellular apoptosis rate of HG group(28.33%±1.37%, <i>P</i><0.05)was significantly increased. Compared with HG group, the cellular apoptosis rate of ghrelin+HG group(14.24%±0.32%, <i>P</i><0.05)was significantly decreased. Compared with NC group, the expressions of NLRP3, Caspase-1, IL-1β and IL-18 proteins were all significantly increased(all <i>P</i><0.05). Compared with HG group, the expressions of NLRP3, Caspase-1, IL-1β and IL-18 proteins in ghrelin + HG group were all significantly decreased(all <i>P</i><0.05).<p>CONCLUSION: Ghrelin can protect retinal vascular endothelial cells damaged by high glucose, it may function by inhibiting NLRP3 inflammasome signaling pathway.

Association between functional dyspepsia and serum levels of brain-gut peptides in children / 中国当代儿科杂志

OBJECTIVES@#To study the association between functional dyspepsia (FD) and serum levels of brain-gut peptides including calcitonin gene-related peptide (CGRP), nesfatin-1, and ghrelin in children.@*METHODS@#A total of 38 children with FD who attended Shengjing Hospital of China Medical University from November 2019 to December 2020 were enrolled as the FD group. Thirty-four healthy children were enrolled as the control group. Serum samples were collected from all of the children. Enzyme-linked immunosorbent assay was used to measure serum levels of CGRP, ghrelin, and nesfatin-1 for comparison between the two groups. The scores of clinical symptoms were determined for the children with FD. Spearman rank correlation analysis was used to investigate the correlation of symptom scores with the serum levels of brain-gut peptides.@*RESULTS@#The FD group had significantly higher serum levels of nesfatin-1 and CGRP than the control group (P<0.05), while there was no significant difference in the serum level of ghrelin between the two groups (P>0.05). The serum level of nesfatin-1 was positively correlated with the symptom score of early satiety (rs=0.553, P<0.001), but was not significantly correlated with the total score of FD (rs=0.191, P=0.250). The serum level of CGRP was positively correlated with the scores of abdominal pain (rs=0.479, P=0.002) and belching (rs=0.619, P<0.001) and the total score of FD (rs=0.541, P<0.001).@*CONCLUSIONS@#CGRP and nesfatin-1 may play an important role in the pathophysiological process of FD.

Role of cholinergic anti-inflammatory pathway in Ghrelin regulation of peptide transporter 1 expression in small intestinal epithelium of septic rats / 中华危重病急救医学

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.

Effects of exogenous ghrelin on the tissue structure and somato-statin secretion in the pancreas of African ostrich chicks / Efectos de la grelina exógena en la estructura del tejido y la secreción de somato-estatinas en el páncreas de los polluelos de avestruz africanos

SUMMARY: This study aimed to investigate the effect of exogenous ghrelin on pancreatic growth and development in African ostrich chicks. Sixteen 40-day-old African ostrich chicks (male or female) were randomly divided into four groups and injected intravenously metatarsal vein with saline (control) or ghrelin (10, 50, and 100 μg/kg) for 6 days. Body and pancreas weight were determined, structural characteristics were observed using HE staining, somatostatin-immunopositive cells were detected using immunohistochemistry. The results were as follows: 1. The 50 and 100 μg/kg groups showed lower relative pancreas weight than the control group (P 0.05. Moreover, compared with the control, the islet cells in treatment groups were loosely arranged and showed reduced cytoplasm. In the exocrine pancreas, the volume of acinar cells in the 10, 50, and 100 μg/kg groups all decreased to varying degrees. 3. Somatostatin immunopositive cells were mainly located around the periphery of the islets and sporadically distributed in the center. The density of the somatostatin immunopositive cells in the 10, 50, and 100 μg/kg groups was higher than that in the control (P < 0.05). These findings suggest that exogenous ghrelin increases the area and number of islets and number of somatostatin immunopositive cells but reduces relative pancreas weight and effects the morphological and structural development of the pancreas, which may inhibit the pancreatic growth and development in African ostrich chicks.

RESUMEN: Este estudio tuvo como objetivo investigar el efecto de la grelina exógena sobre el crecimiento y desarrollo del páncreas en polluelos de avestruz africana. Dieciséis pollos de avestruz africana de 40 días (machos o hembras) se dividieron al azar en cuatro grupos y se inyectaron por vía intravenosa con solución salina (control) o grelina (10, 50 y 100 μg / kg) durante 6 días. determinadas, se observaron las características estructurales mediante tinción Hematoxilina-Eosina, se detectaron células inmunopositivas a somatostatina mediante inmunohistoquímica. Los resultados fueron los siguientes: ¨Los grupos de 50 y 100 μg / kg mostraron un menor peso relativo del páncreas que el grupo de control (P <0,05). El área de islotes por unidad de área del páncreas fue mayor en los grupos de 10, 50 y 100 μg / kg grupos que en el grupo de control (P <0,05). El número de islotes por unidad de área del páncreas fue menor en el grupo de 10 μg / kg que en el control (P <0,05). Además, en comparación con el control, las células de los islotes en los grupos de tratamiento estaban dispuestas de forma holgada y mostraban un citoplasma reducido. En el páncreas exocrino, el volumen de células acinares en los grupos de 10, 50 y 100 μg / kg disminuyó en diversos grados. Las células inmunopositivas de somatostatina se ubicaron principalmente alrededor de la periferia de los islotes y se distribuyeron esporádicamente en el centro. La densidad de las células inmunopositivas a la somatostatina en los grupos de 10, 50 y 100 μg / kg fue mayor que la del control (P <0,05). Estos hallazgos sugieren que la grelina exógena aumenta el área y el número de islotes y el número de células inmunopositivas a la somatostatina, pero reduce el peso relativo del páncreas, lo que puede inhibir el crecimiento y desarrollo pancreático en los polluelos de avestruz africana.

Níveis de grelina circulante e a suscetibilidade ao câncer colorretal / Circulating ghrelin levels and susceptibility to colorectal câncer

ABSTRACT BACKGROUND AND OBJECTIVE: Considering the association between colorectal cancer (CRC) and both insulin resistance and obesity, and the prominent role of ghrelin in these metabolic disorders, we explored whether plasma levels of ghrelin were associated with CRC. Moreover, in the patients with CRC the possible correlations between ghrelin and insulin, insulin resistance, and body mass index (BMI) as an indicator of obesity were examined. METHODS: A total of 170 subjects, including 82 cases with CRC and 88 controls were enrolled in this study. Plasma levels of ghrelin, insulin, and glucose were measured in all the subjects using ELISA and glucose oxidase methods. Furthermore, insulin resistance was assessed by calculating HOMA-IR index. RESULTS: The cases with CRC had decreased ghrelin levels (P<0.001) and a higher HOMA-IR index (P<0.001) than controls. Interestingly, when CRC patients were stratified based on tumor site, lower ghrelin levels and a higher HOMA-IR index were observed in the patients with either colon or rectal cancer vs. controls too. Additionally, there were an age and BMI-independent negative correlation between ghrelin levels and HOMA-IR (r=-0.365, P<0.05), and an age-independent negative correlation between ghrelin levels and BMI (r=-0.335, P<0.05) in the rectal subgroup. CONCLUSION: Our findings support a role for ghrelin in connection with insulin resistance and obesity in CRC susceptibility; however, it needs to be corroborated by further studies.

RESUMO CONTEXTO E OBJETIVO: Considerando a associação entre câncer colorretal (CCR), a resistência à insulina, à obesidade e o papel proeminente da grelina nessas doenças metabólicas, foi explorado se os níveis plasmáticos de grelina estavam associados ao CCR. Além disso, nos pacientes com CCR foram pesquisadas as possíveis correlações entre a grelina, insulina, resistência insulínica e índice de massa corporal (IMC) como indicadores de obesidade. MÉTODOS: Foram incluídos neste estudo 170 indivíduos, sendo 82 com CRC e 88 controles. Os níveis plasmáticos de grelina, insulina e glicose foram medidos em todos os sujeitos utilizando métodos ELISA e glicose oxidase. Além disso, a resistência à insulina foi avaliada pelo cálculo do índice HOMA-IR. RESULTADOS: Os pacientes com CRC apresentaram redução dos níveis de grelina (P<0,001) e maior índice HOMA-IR (P<0.001) do que os controles. Curiosamente, quando os pacientes com CRC foram estratificados com base no local do tumor, níveis mais baixos de grelina e maior índice de HOMA-IR foram observados nos indivíduos com câncer de cólon ou retal versus controles também. Além disso, houve uma correlação negativa entre idade e IMC independente entre os níveis de grelina e HOMA-IR (r=-0,365, P<0,05) e uma correlação negativa independente da idade entre os níveis de grelina e IMC (r=-0,335, P<0,05) no subgrupo retal. CONCLUSÃO: Nossos achados apoiam o papel da grelina em relação à resistência à insulina e à obesidade na suscetibilidade do CRC; no entanto, ela precisa ser corroborada por estudos posteriores.

Comparación del tipo de cirugía bariátrica sobre la reducción de peso corporal y su relación con la ghrelina / Comparison between type of bariatric surgery on reduction of body weight and its ghrelin relationship

Resumen Objetivo: La cirugía bariátrica es un procedimiento para disminuir de peso a largo plazo en pacientes con obesidad. El objetivo de este estudio fue evaluar los niveles de ghrelina y la reducción del peso de acuerdo al tipo de cirugía bariátrica, comparando el bypass de una sola anastomosis y la gastrectomía formadora de manga. Materiales y Métodos: Estudio de cohorte que incluyó a 50 pacientes con obesidad, 22 mini-bypass y 28 mangas gástricas. Se evaluó el peso corporal y las concentraciones de ghrelina en la etapa prequirúrgica, en el día 7 y en los meses 1, 3 y 6 después de la cirugía. Resultados: Del total de pacientes, el 86% presentaron > 50% pérdida del exceso de peso (PEPP) a los 6 meses. La concentración de ghrelina disminuyó desde la primera semana en el grupo total de participantes. A los 6 meses, se observó mayor reducción de ghrelina en los pacientes con la manga gástrica (4.636 ± 2.535 vs 1.340 ± 1.001 pg/mL, p < 0,0001). El PEPP en pacientes con mini-bypass fue superior, en comparación con manga gástrica. Conclusiones: La comparación entre las técnicas indicó que, a los 6 meses de evolución posquirúrgica, los pacientes con mini-bypass presentaron mayor reducción de peso corporal y del nivel de ghrelina, en comparación con el grupo de manga gástrica. La concentración de ghrelina es una variable que participa en el control de peso; sin embargo, el tipo de abordaje quirúrgico probablemente tiene mayor relación con la pérdida de peso en estos pacientes.

Introduction: Bariatric surgery is a procedure to reduce weight in the long term in patients with obesity. The objective of this study was to evaluate ghrelin levels and weight reduction according to the type of bariatric surgery, comparing the single anastomosis bypass and the sleeve-forming gastrectomy. Materials and Method: Cohort study that included 50 patients with obesity, 22 Mini-Bypass and 28 gastric sleeve. Body weight and ghrelin concentrations were evaluated in the presurgical stage, on day 7 and in months 1, 3 and 6 after surgery. Results: Of the total of patients, 86% had > 50% excess weight loss (PEPP) at 6 months. The concentration of ghrelin decreased within the first week of the intervention. At 6 months, greater reduction of ghrelin was observed in patients with gastric sleeve (4636 ± 2535 vs 1340 ± 1001 pg/mL, p < 0.0001). The PEPP in patients with Mini-Bypass was superior, compared to gastric sleeve. Conclusion: The comparison between the techniques indicated that, after 6 months of post-surgical evolution, patients with Mini-Bypass had a greater reduction in body weight and ghrelin levels, compared to the gastric sleeve group. Ghrelin concentration is a variable that participates in weight control; however, the type of surgical approach is probably more related to weight loss in these patients.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study

SUMMARY OBJECTIVE: Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. METHODS: This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. RESULTS: The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). CONCLUSIONS: The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Role of ghrelin and obestatin in the progression of nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a disease caused by multiple factors and can progress to liver cirrhosis and hepatocellular carcinoma. At present, the pathogenesis of NAFLD remains unclear and there are still no effective therapeutic drugs in clinical practice; therefore, it is particularly important to search for new therapeutic drugs that have few side effects and can effectively delay or reverse disease progression. Some studies have shown that related hormones produced by gastric tissue have a variety of effects in the regulation of energy homeostasis and obesity, and the expression level of inflammation-related genes in gastric fundus is consistent with the severity of liver disease; thus we have reason to believe that the stomach is one of the important participants in NAFLD. This article summarizes the role of ghrelin and obestatin produced by the stomach in the progression of NAFLD, which provides a new idea for the pathogenesis of NAFLD and a new direction for treatment.

Homeostasis Research Model Based on Yin-Yang Theory: Five Examples / 中国结合医学杂志

In recent years, the ancient Yin-Yang theory has been gradually adopted by modern researchers, especially European and American scholars, and it has also been applied to modern scientific research on sleep, viruses, metabolism, cancer, genes, autoimmune diseases, and so on. It is very promising and fruitful results have been reported. However, the understanding of the connotations of Yin-Yang theory is not sufficient and thorough enough in these studies. If we understand and apply Yin-Yang theory more comprehensively, it may provide us with additional potential mechanisms and research directions worthy of study. On the basis of promoting a comprehensive understanding of all three connotations of Yin-Yang theory, this review attempts to illustrate this theory, summarize its applications in modern scientific research, and reveal the potential research direction of modern medicine.