Ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 for the treatment of primary retinitis pigmentosa / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of ginsenoside Rg1 injection combined with inosine tablets and vitamin B1 on serum brain-derived neurotrophic factor(BDNF), pituitary adenylate cyclase activating polypeptide(PACAP)and clinical efficacy in primary retinitis pigmentosa.METHODS: A total of 50 patients(100 eyes)with primary retinitis pigmentosa who admitted to the Department of Ophthalmology, the Second Affiliated Hospital of Hebei North University from August 2019 to March 2022 were selected as the research object. They were divided into the study group and the control group according to random number table, with 50 eyes in each group. Patients in the control group were treated with inosine tablets and vitamin B1, while patients in the study group were treated with ginsenoside Rg1 injection on the basis of the control group. The expression of BDNF and PACAP in serum, electroretinogram and spectral-domain optical coherence tomography(SD-OCT)were compared before and after treatment, and the retinal thickness(RT), mean deviation(MD), clinical efficacy and safety indexes were compared between the two groups.RESULTS: There were no differences in the MD of the two groups before treatment(t=1.670, P=0.098), while the MD of the study group was significantly lower than that of the control group after treatment(t=3.628, P<0.01). Before treatment, RT with a diameter of 1mm at the circle of macular fovea was compared between the two groups(t=0.108, P=0.914), it was significantly higher than that in the control group after treatment(t=6.125, P<0.01). Before treatment, there was no significant difference in the results of dark adaptation of electroretinogram between the two groups(all P>0.05). After treatment, the results of dark adaptation in the study group were significantly better than those in the control group(all P<0.01). Before treatment, there was no significant difference in the results of electroretinogram adaptation between the two groups(all P>0.05). After treatment, the results of electroretinogram adaptation in the study group were significantly better than those in the control group(all P<0.01). There was no significant difference in BDNF and PACAP between the two groups before treatment(all P>0.05). BDNF and PACAP in the study group were higher than those of the control group after treatment(all P<0.01). After treatment, no adverse reactions were observed in both groups.CONCLUSION: The treatment of patients with primary retinitis pigmentosa with ginsenoside will improve the retinal function and promote the prognosis of the disease by regulating the expression of BDNF and PACAP, and it is highly safe.

Clinical Observation of Modified Buzhong Yiqitang Combined with Erxian Decoction in Treatment of Stress Urinary Incontinence in Perimenopausal Women / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of the modified Buzhong Yiqitang combined with Erxian decoction in treating stress urinary incontinence （SUI） of perimenopausal women due to spleen and kidney Qi deficiency. Method:One hundred and six patients were randomly divided into a control group （52 cases） and an observation group（54 cases）. Patients in both groups received lifestyle intervention and pelvic floor muscle training （PFMT）. On this basis， patients in the observation group were further treated with the modified Buzhong Yiqitang combined with Erxian decoction， 1 bag/day， while those in the control group were provided with Suoquan pills， 6 g/time， 2 times/day， for eight weeks. Following the international consultation on incontinence questionnaire-short form （ICIQ-SF） scoring before and after treatment， the urodynamic parameters such as maximum urinary flow rate （Q_max）， maximum urethral closure pressure （MUCP）， residual urine volume （RUV）， abdominal pressure leakage point pressure （ALPP）， and bladder capacity （BC） were measured. The number of incontinence episodes per 24 h， the degree of urinary incontinence， the amount of 1 h urine leakage， and the spleen and kidney Qi deficiency syndrome score were recorded before and after treatment. The levels of estradiol （E₂）， follicle stimulating hormone （FSH）， pituitary adenylate cyclase activating peptide （PACAP）， and vasoactive intestinal peptide （VIP） were measured before and after treatment. Result:The ICIQ-SF sub-scores of the urinary incontinence frequency， severity， and impact on quality of life as well as the total score in the observation group were all lower than those in the control group （<italic>P</italic><0.01）. Q_max， MUCP， ALPP and BC in the observation group were elevated in contrast to those in control group （<italic>P</italic><0.01）， while the RUV declined （<italic>P</italic><0.01）. Compared with the control group， the observation group exhibited a decreased number of incontinence episodes per 24 h， milder degree of urinary incontinence， reduced amount of 1 h urine leakage， and lower spleen and kidney Qi deficiency syndrome score （<italic>P</italic><0.01）. The E₂， PACAP， and VIP in the observation group were up-regulated as compared with those in the control group （<italic>P</italic><0.01）， whereas the FSH was down-regulated （<italic>P</italic><0.01）. The cure and effective rates of the observation group were （29/50） 58.00% and （47/50）94.00%， respectively， significantly better than （18/48）37.50% and （38/48）79.17% of the control group （<italic>χ</italic>²=4.124， <italic>χ</italic>²=4.683， <italic>P</italic><0.05）. Conclusion:On the basis of the lifestyle intervention and PFMT， the modified Buzhong Yiqitang combined with Erxian decoction obviously alleviates urinary incontinence， adjusts sex hormones， PACAP and VIP， ameliorates urodynamic parameters， and enhances the quality of life of patients with SUI due to spleen and kidney Qi deficiency. The resulting cure and effective rates are superior to those of the positive control.

Association of adenylate cyclase-associated protein 2 expression with histopathology and long-term prognosis of gastric cancer / 南方医科大学学报

OBJECTIVE@#To explore association of the expression levels of adenylate cyclase-associated protein 2 (CAP2) in gastric cancer tissues with the histopathology and long-term prognosis of the malignancy.@*METHODS@#This study was conducted among a total of 105 patients with gastric cancer undergoing radical gastrectomy in our hospital between January, 2010 and October, 2013. Immunohistochemistry was used to quantitatively assess the expression of CAP2 in gastric cancer tissues and the adjacent tissues. Based on the median relative expression level of CAP2 of 3.5, the patients were divided into low CAP2 expression group (=52) and high CAP2 expression group (=53). The Cox regression model was used to analyze the effect of CAP2 expression on the 5-year survival rate of the patients, and ROC curve analysis was used to assess the predictive value of CAP2 expression for the patients' long-term survival.@*RESULTS@#Immunohistochemical analysis showed that the expression levels of CAP2 ( < 0.01) and Ki67 ( < 0.01) were significantly higher in gastric cancer tissues than in the adjacent tissues, and the expression level of CAP2 was positively correlated with Ki67 ( < 0.01), peripheral blood CEA ( < 0.01) and CA19-9 ( < 0.01). The percentages of patients with CEA≥5 μg/L, CA19-9≥37 kU/L, pathological grade of G3-G4, T stage of 3-4, and N stage of 2-3 were significantly higher in patients with high CAP2 expression than in those with low CAP2 expression ( < 0.05). Kaplan- Meier survival analysis showed that the 5-year survival rate was significantly lower in patients with a high CAP2 expression ( < 0.01). A high expression level of CAP2, CEA≥5μg/L, CA19-9≥37 and pathological grades G3-G4 were all independent risk factors for shortened 5-year survival after radical gastrectomy ( < 0.01). With the relative expression level of 3.45 as the cut-off value, the sensitivity of CAP2 was 70.15% for predicting death 5 years after the surgery, with a specificity of 71.05% and an area under the curve of 0.779 ( < 0.01).@*CONCLUSIONS@#CAP2 is highly expressed in gastric cancer tissues in close relation with the tumor progression. CAP2 is an independent risk factor for 5-year survival rate after radical gastrectomy for gastric cancer and can be of clinical value in prognostic evaluation of the patients.

Neuroprotective Effects of Brain-Gut Peptides: A Potential Therapy for Parkinson's Disease / 神经科学通报·英文版

Parkinson's disease (PD) is the second most common neurodegenerative disease and is typically associated with progressive motor and non-motor dysfunctions. Currently, dopamine replacement therapy is mainly used to relieve the motor symptoms, while its long-term application can lead to various complications and does not cure the disease. Numerous studies have demonstrated that many brain-gut peptides have neuroprotective effects in vivo and in vitro, and may be a promising treatment for PD. In recent years, some progress has been made in studies on the neuroprotective effects of some newly-discovered brain-gut peptides, such as glucagon-like peptide 1, pituitary adenylate cyclase activating polypeptide, nesfatin-1, and ghrelin. However, there is still no systematic review on the neuroprotective effects common to these peptides. Thus, here we review the neuroprotective effects and the associated mechanisms of these four peptides, as well as other brain-gut peptides related to PD, in the hope of providing new ideas for the treatment of PD and related clinical research.

Pertussis: enfermedad reemergente / Pertussis: reemerging disease / Pertussis: doença reemergente

RESUMEN Introducción: Actualmente a pesar de las estrategias de vacunación a nivel mundial, B. pertussis se ha convertido en un problema de salud pública, sigue siendo una de las enfermedades menos prevenibles por vacunación en todo el mundo, aún en países desarrollados con amplia cobertura de vacunación. Objetivo: Describir los principales mecanismos de virulencia asociados a la infección mediante los cuales la bacteria logra evadir la respuesta inmune, además de dar a conocer un panorama actual del estado de inmunización contra la tos ferina y la problemática de su reemergencia a nivel mundial. Métodos: Se realizó una revisión mediante búsqueda electrónica de literatura; entre las estrategias de búsqueda se destaca el empleo de las bases de datos como PubMed, ScienceDirect, SciELO, Redalyc; y búsqueda en portales de salud; sobre aspectos generales de la enfermedad y su agente causal, además de últimas actualizaciones sobre el tema. Resultados: Como lo confirman recientes estudios, el incremento del riesgo de infección por B. pertussis sigue presentándose en adolescentes y adultos debido a la disminución en la respuesta inmune inducida por la vacunación y la infección natural, por ende, la información actual indica que está reemergiendo la tos ferina en todo el mundo, situación que es necesario conocer para un oportuno diagnóstico y tratamiento. Conclusiones: Análisis de la literatura demuestra la necesidad de ampliar el uso de técnicas moleculares; llevar a cabo la modificación de los programas de vacunación, con la administración de dosis de refuerzo entre adolescentes y adultos; además programas de monitoreo epidemiológico eficaces de recolección de casos con tos ferina y sistemas adecuados de notificación para lograr la reducción equitativa y sustentable de la morbilidad y mortalidad de ésta enfermedad.

ABSTRACT Introduction: Currently despite vaccination strategies worldwide, B. pertussis has become a public health problem, it remains one of the least vaccine preventable diseases in the world, even in developed countries with extensive coverage of vaccination. Objective: To describe the main mechanisms of virulence associated with the infection through which the bacterium manages to evade the immune response, as well as to present a current picture of the state of immunization against pertussis and the problem of its reemergence worldwide. Methods: Electronic literature search was performed; among the search strategies we highlight the use of databases such as PubMed, ScienceDirect, SciELO, Redalyc; and search in health portals; on general aspects of the disease and its causal agent, in addition to the latest updates on the subject. Results: As confirmed by recent studies, the increased risk of B. pertussis infection continues to occur in adolescents and adult's due to the decrease in the immune response induced by vaccination and natural infection, therefore, current information indicates that reemerging whooping cough around the world, a situation that is necessary to know for a timely diagnosis and treatment. Conclusions: Analysis of the literature demonstrates the need to expand the use of molecular techniques; to carry out the modification of the vaccination programs, with the administration of doses of reinforcement between adolescents and adults; In addition to effective epidemiological monitoring programs for the collection of pertussis cases and adequate notification systems to achieve an equitable and sustainable reduction in the morbidity and mortality of this disease.

RESUMO Introdução: Atualmente, apesar das estratégias de vacinação em todo o mundo, B. pertussis tornou-se um problema de saúde pública, continua a ser uma das doenças menos evitáveis pela vacina no mundo, mesmo em países desenvolvidos com ampla cobertura de vacinação. Objetivo: Descrever os principais mecanismos de virulência associados à infecção através dos quais a bactéria consegue evadir a resposta imune, bem como apresentar uma imagem atual do estado da imunização contra a tosse convulsa e o problema da ressurgência em todo o mundo. Métodos: Pesquisa eletrônica de literatura foi realizadantre as estratégias de Investigação, destacamos o uso de bancos de dados como PubMed, ScienceDirect, SciELO, Redalyc; e investigação em portais de saúde; sobre aspectos gerais da doença e seu agente causal, além das atualizações mais recentes sobre o assunto. Resultados: Conforme confirmado por estudos recentes, o aumento do risco de infecção por B. pertussis continua a ocorrer em adolescentes e adultos devido à diminuição da resposta imune induzida por vacinação e infecção natural, portanto, informações atuais indicam que a ressurreição de tosse convulsa ao redor do mundo, uma situação que é necessário conhecer para um diagnóstico e tratamento oportunos. Conclusões: A análise da literatura demonstra a necessidade de ampliar o uso de técnicas moleculares; para realizar a modificação dos programas de vacinação, com a administração de doses de reforço entre adolescentes e adultos; além de programas efetivos de monitoramento epidemiológico para a coleta de casos de tosse convulsa e sistemas de notificação adequados para alcançar uma redução sustentável e equitativa na morbidade e mortalidade desta doença.

Effect of adenylate cyclase antagonists andagonist in acute lung injury induced by lipopolysaccharide / 中国药理学通报

Aim To explore the effect of adenylate cyclase(AC) antagonists SQ22536 and agonist forskolin on acute lung injury induced by lipopolysaccharide.Methods ICR mice were randomly divided into normal saline control group(N group), model group(group L), dexamethasone group(group D),AC antagonists s(group SQ) and AC agonist group(group F).The ALI mouse model was induced by instilling intratracheally with LPS(2 mg·kg-1), and 6 h later, the lung tissue and alveolar lavage fluid(BALF) were harvested, pathological changes in lung were observed, white blood cell and neutrophil, albumin content in BALF and myeloperoxidase(MPO) activity of lung tissue homogenate were determined, and tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β), interleukin 6(IL-6) and cAMP content in lung homogenates were detected by ELISA.Results Compared with normal saline group, a large number of neutrophils infiltrated around the pulmonary vessel and airway 6 h after LPS intratracheal instillation in model group.White blood cells and neutrophils and protein content increased in BALF;MPO activity and cAMP levels increased in lung tissues.In the lung tissue TNF-α and IL-6, IL-1β content increased, compared with model group.Forskolin could improve the pathological changes of lung tissue, reduce the total number of leukocytes, number of neutrophils and protein content in BALF, and reduce MPO activity and TNF-α content in lung tissue, at the same time it increased the cAMP content;SQ22536 had no significant effect when compared with model group.Conclusion AC agonists have protective effects on LPS-induced acute lung injury in mice, and the mechanism may be related to elevating cAMP levels, inhibiting neutrophil adhesion and chemotaxis and reducing inflammatory factor levels.

Genetic analysis and cAMP measurement: comparison between lean and obese anovulating mice / Análise genética e dosagem de AMP cíclico: comparação entre camundongos fêmeas anovuladoras magras e obesas

PURPOSE: To evaluate genes differentially expressed in ovaries from lean (wild type) and obese (ob/ob) female mice and cyclic AMP production in both groups. METHODS: The expression on messenger RNA levels of 84 genes concerning obesity was analyzed through the PCR array, and cyclic AMP was quantified by the enzyme immunoassay method. RESULTS: The most downregulated genes in the Obesity Group included adenylate cyclase-activating polypeptide type 1, somatostatin, apolipoprotein A4, pancreatic colipase, and interleukin-1 beta. The mean decrease in expression levels of these genes was around 96, 40, 9, 4.2 and 3.6-fold, respectively. On the other hand, the most upregulated genes in the Obesity Group were receptor (calcitonin) activity-modifying protein 3, peroxisome proliferator activated receptor alpha, calcitonin receptor, and corticotropin-releasing hormone receptor 1. The increase means in the expression levels of such genes were 2.3, 2.7, 4.8 and 6.3-fold, respectively. The ovarian cyclic AMP production was significantly higher in ob/ob female mice (2,229±52 fMol) compared to the Control Group (1,814±45 fMol). CONCLUSIONS: Obese and anovulatory female mice have reduced reproductive hormone levels and altered ovogenesis. Several genes have their expression levels altered when leptin is absent, especially adenylate cyclase-activating polypeptide type 1. .

OBJETIVO: Avaliar os genes diferencialmente expressos em ovários de camundongos fêmeas magras (tipo selvagem) e obesas (ob/ob) e a produção de AMP cíclico em ambos os grupos. MÉTODOS: A expressão nos níveis de RNA mensageiro de 84 genes relacionados à obesidade foi analisada por PCR Array, e o AMP cíclico foi quantificado por método imunoenzimático. RESULTADOS: Os genes que mais sofreram diminuição da expressão no Grupo Obesidade incluíram o tipo 1 de polipeptídeo ativador da adenilato ciclase, o da somatostatina, da apolipoproteína A4, da colipase pancreática e da beta interleucina 1. A média de redução na expressão desses genes foi de aproximadamente 96, 40, 9, 4,2 e 3,6 vezes, respectivamente. Por outro lado, os genes que mais tiveram aumento na expressão no Grupo Obesidade foram o gene da proteína modificadora da atividade do receptor de calcitonina 3, do proliferador de peroxissomos ativados por proteína alfa, do receptor de calcitonina e do receptor para hormônio liberador de corticotropinas 1. As médias de acréscimo nos níveis de expressão de tais genes foram de 2,3, 2,7, 4,8 e 6,3 vezes, respectivamente. A produção de AMP cíclico ovariana foi significantemente aumentada em camundongos fêmeas ob/ob (2.229±52 fMol) quando comparada ao Grupo Controle (1.814±45 fMol). CONCLUSÕES: Camundongos fêmeas obesas e anovuladoras possuem níveis de hormônio reprodutivo reduzidos e ovulogênese alterada. Vários genes mostram níveis de expressão alterados quando a leptina está ausente, principalmente o tipo 1 de polipeptídeo ativador da adenilato ciclase. .

Pituitary Adenylate Cyclase-activating Polypeptide Inhibits Pacemaker Activity of Colonic Interstitial Cells of Cajal

This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K+ channel blocker). However, neither N(G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K+ channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.

Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

The aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (p<0.05) of RL compared to control rats. Terb, PACAP38 and PACAP38 analog reversed significantly the MeCh-induced bronchial constriction, smooth muscle (SM) layer thickness and bronchial lumen mucus abundance. PACAP38 analog prevents effectively bronchial smooth muscle layer thickness, mucus hypersecretion and lumen decrease. Therefore, it may constitute a potent therapeutic bronchodilator.

O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (p<0,05) de RL em comparação com ratos do grupo controle. Terb e PACAP1-38 e análogo do PACAP-38 reverteram, significativamente, a constrição brônquica induzida por Mech, a espessura do músculo liso (SM) e abundância de muco do lume brônquico. O análogo PACAP-38 do mesmo modo que a Terb impediu a responsividade brônquica a MeCh e pode se constituir em um importante regulador no desenvolvimento da doença inflamatório pulmonar. Contudo, o uso do peptídeo nativo para aplicações terapêuticas é limitado por sua baixa estabilidade metabólica. Consequentemente, o análogo metabolicamente estável representa ferramenta promissora no tratamento de doenças pulmonares inflamatórias.

Cyclic AMP and Cyclic AMP-Receptor Protein are Required for Optimal Capsular Polysaccharide Expression

Vibrio vulnificus causes fatal infections in susceptible individuals. Group 1 capsular polysaccharide (CPS) operon is responsible for CPS expression, which plays an essential role in the pathogenesis of this pathogen. Cyclic AMP (cAMP) and cAMP receptor protein (crp) complex, which responds to glucose availability and functions as a global regulator, has been known to affect CPS production in this pathogen. This study was undertaken to experimentally verify whether cAMP-Crp directly or indirectly affects CPS production. A mutation in cyaA encoding adenylate cyclase, which is required for cAMP biosynthesis, inhibited V. vulnificus growth and changed opaque colonies to translucent colonies, and these changes were recovered by complementing cyaA or by adding exogenous cAMP. A mutation in crp encoding Crp also inhibited V. vulnificus growth and changed opaque colonies to translucent colonies, and these changes were recovered by complementing crp. Moreover, the crp or cyaA mutation decreased the susceptibility of V. vulnificus against NaOCl. The crp mutation reduced the transcription levels of group 1 CPS operon on a per cell basis. Glucose addition in the absence of Crp stimulated V. vulnificus growth, changed translucent colonies to opaque colonies, and increased the transcription levels of group 1 CPS operon. These results indicate that cAMP or Crp is indirectly involved in optimal CPS production by positively affecting metabolism or V. vulnificus growth rather than by directly controlling the expression of group 1 CPS operon.

Correlation of serotonin 2A receptor and adenylate cyclase single gene polymorphisms and bipolar disorder / 中华行为医学与脑科学杂志

Objective To explore whether there is association between the polymorphisms of serotonin 2A receptor(5-HT2A) rs6311,rs6305 and adenylate cyclase rs2230739 with episode of bipolar disorder.Methods A case-control association study was done in this study,152 bipolar disorder patients (patients group),and 187 ageand gender-matched controls (control group) were recruited.Ligase detection reaction(LDR) was used to detect the distributive frequency of rs6311,rs6305 and rs2230739 of 152 bipolar disorder patients and 187 normal people.Results The 5-HT2A receptor rs6311 genotypes and alleles frequency distribution between patients group(11,12,22 genotypes:21％,61％,18％ ; 1,2 alleles:51％,49％) and control group(11,12,22 genotypes:44％,45％,11％ ; 1,2 alleles:66％,34％) showed statistically significance (P＜0.01).There were no differences of 5-HT2A receptor rs6305 genotypes and alleles between patients group and control group.The frequency of rs2230739 genotypes and alleles distribution between patients group (11,12,22 genotypes: 20％,43％,37％ ; 1,2 alleles: 42％,58％) and control group(11,12,22 genotypes: 17％,48％,35％ ; 1,2 alleles: 41％,59％) showed no significant difference(P=0.661,P=0.846).Conclusion The 5-HT2A receptor rs6311 polymorphism may be responsible for an increase in susceptibility to bipolar disorder,indicating that it maybe an marker to bipolar disorder.

Effects of pituitary adenylate cyclase activating polypeptide on CD4+/CD8+ T cell levels after traumatic brain injury in a rat model / 世界急诊医学杂志（英文）

BACKGROUND: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI. METHODS: Male Sprague Dawley rats were randomly divided into 3 treatment groups (n=6, each): sham-operated, vehicle (normal saline)+TBI, and PACAP+TBI. Normal saline or PACAP (1g/5L) was administered intracerebroventricularly 20 minutes before TBI. Right parietal cortical contusion was produced via a weight-dropping method. Brains were extracted 24 hours after trauma. Histological changes in brains were examined by HE staining. The numbers of CD4+ and CD8+ T cells in blood and the spleen were detected via flow cytometry. RESULTS: In injured brain regions, edema, hemorrhage, inflammatory cell infiltration, and swollen and degenerated neurons were observed under a light microscope, and the neurons were disorderly arrayed in the hippocampi. Compared to the sham group, average CD4+ CD8– lymphocyte counts in blood and the spleen were significantly decreased in rats that received TBI+vehicle, and CD4– CD8+ were increased. In rats administered PACAP prior to TBI, damage was attenuated as evidenced by significantly increased CD4+, and decreased CD8+, T lymphocytes in blood and the spleen. CONCLUSION: Pretreatment with PACAP may protect against TBI by influencing periphery T cellular immune function.

Pituitary adenylate cyclase-activating polypeptide modulates immune function of LPS-stimulatd dendritic cells / 第二军医大学学报

Objective: To investigate whether pituitary adenylate cyclase-activating polypeptide (PACAP) can modulate the immune function of mouse LPS-stimulated dendritic cells. Methods: DCs were derived from bone marrow of C57BL/6 using rmGM-CSF and rmIL-4, then the DCs were exposed to different stimuli for indicated time periods. The stimulated DCs and their culture supernatant were subjected to ELISA and FACS analysis. The total RNA was extracted from the stimulated DC for RT-PCR and RNase Protection Assay. Results: PACAP significantly inhibited the production of IL-2, IL-12,TNF-α and MIP-2 in LPS-stimulated DCs (P<0. 05,P<0. 01,P<0. 01 ,P<0. 01.respectirely), but the inhibition of LPS-induced IL-6, MIP-1α and MIP-1β production was not apparent. Conclusion: PACAP can negatively modulate the immunity of LPS-stimulated DCs.

Mechanism of angiotensin Ⅱ in regulation of renin synthesis in juxtaglomerular granular cells / 中华肾脏病杂志

Objective To elucidate the mechanism of angiotensin (Ang) Ⅱ in regulation of renin synthesis and secretion in primary cultured juxtaglomerular granular cells (JGCs). Methods Mice JGCs were isolated and cultured as described before. Real-time PCR was used to demonstrate the expression of angiotensin converting enzyme (CE) and angiotencin receptor (AT1, AT2) in JGCs. Ang Ⅱ was co-cultured with JGCs stimulated by PGE2 and isoproternol or not. Renin activity in supernatant was detected by radioimmunoassay and renin mRNA expression was examined by real-time PCR. Different concentrations of Ang Ⅱ were co-cultured with JGCs with different time (1 h, 4 h and 24 h), cAMP in cell lysate and supernatant was measured by Cayman Cyclic AMP EIA Kit. The cytoplasmic calcium was decreased by BAPTA-AM, and increased by thapsigargin and cyclopiazonic acid, which could be used to observe the cAMP concentration affected by calcium. Adenylyl cyclase type 5, 6 (AC5, AC6) mRNA expression of JGCs co-cultured with Ang Ⅱ was measured by real-time PCR. Results Real-time PCR confirmed the expression of ACE and AT mRNA in JGCs of WT mice. Angiotensin Ⅱ reduced renin secretion in primary cultures of JGCs [(370.6±36.9) vs (299.6±25.7) ng AngI'ml~(-1)·h~(-1), P=0.014]. Angiotensin Ⅱ dose-dependently down-regulated forskolin-stimulated cAMP production in JGCs. Thapsigargin and cyclopiazonic acid decreased cAMP level. BAPTA-AM increased cAMP production obviously [(11.09±0.48) vs (3.55±0.47) nmol/L, P<0.01]. Ang Ⅱ inhibited AC5 mRNA expression by 42.12%, but did not inhibit AC6 mRNA expression. Conclusions Angiotensin Ⅱ can directly inhibit renin synthesis and secrestion maybe through reducing AC-stimulated cAMP levels. Crosstalk between calcium and cAMP system may exist in precise regulation of renin in JGCs.

Effects of pituitary adenylate cyclase-activating polypeptide on the expressions of caspase-3 and X-linked inhibitor of apoptosis protein after cerebral hy0oxia-ischemia in neonatal rats / 国际脑血管病杂志

Objective To observe the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the expressions of caspase-3 and X-linked inhibitor of apoptosis protein (XIAP) after hypoxic-ischemic brain damage (HIBD) in neonatal rats and to investigate its neuroprotection and effective dose. Methods Sixty neonatal rats were randomly allocated to one of three groups: sham operation, saline control and PACAP groups. The PACAP group was redivided into high (10-8 mol), medium (10-9 mol) and low (10-12 mol) dose groups. An animal model of HIBD was established. Real-time fluorescent quantitative polymerase chain re-action method was used to detect the expressions of caspase-3 mRNA and XIAP mRNA on af-fected side of brain 24 hours after HIBD in neonatal rats, and spectrophotometry was used to detect the activities of caspase-3. Results Twenty-four hours after HIBD, caspase-3 mRNA expression and enzyme activity, as well as XIAP mRNA expression in the saline control group were increased significantly compared to the sham operation group (all P <0.01). Caspase-3 mRNA expression and enzyme activity in all the PACAP groups were significantly lower than those in the saline control group (all P <0.01), while XIAP mRNA expression was significantly higher than that in the saline control group (all P < 0.01 ). Conclusions PACAP may upregu-late XIAP mRNA expression, inhibit caspase-3 mRNA expression and enzyme activity. It has neuroprotective effect on HIBD in neonatal rats, and it is effective with high, medium and low doses.

Effects of Activated ACM on Expression of Signal Transducers in Cerebral Cortical Neurons of Rats / 华中科技大学学报（医学）（英德文版）

To explore the roles of astrocytes in the epileptogenesis, astrocytes and neurons were isolated, purified and cultured in vitro from cerebral cortex of rats. The astrocytes were activated by ciliary neurotrophic factor (CNTF) and astrocytic conditioned medium (ACM) was collected to treat neurons for 4, 8 and 12 h. By using Western blot, the expression of calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ), inducible nitric oxide synthase (iNOS) and adenylate cyclase (AC) was detected in neurons. The results showed that the expression of CaMK Ⅱ, iNOS and AC was increased significantly in the neurons treated with ACM from 4 h to 12 h (P＜0.05), and that of iNOS and AC peaked at 8 h and 12 h respectively. It was suggested that there might be some epileptogenic factors in the ACM and such signal pathways as NOS-NO-cGMP, Ca2+/CaM-CaMK Ⅱ and AC-cAMP-PKA might take part in the signal transduction of epileptogenesis.

Control Mechanisms of Ovarian Follicle Development by Follicle Stimulating Hormone and Pituitary Adenylate Cyclase-activating Polypeptide / 대한불임학회지

OBJECTIVE: Pituitary adenylate cyclase-activating polypeptide (PACAP), a novel hypothalamic neuropeptide, has been suggested to play a role in ovarian folliculogenesis. The present study evaluated the effect of PACAP on the growth of preantral follicles. METHODS: Preantral follicles were mechanically isolated from ovaries of 21-day-old rats and cultured in groups for 3 days in serum-free medium in the absence or presence of PACAP-38 (10-6 M). RESULTS: Treatment with PACAP-38 resulted in an increase in follicle diameter by 75% whereas treatment with follicle stimulating hormone (FSH) increased follicle diameter by 65%. PACAP-38 treatment enhanced the granulosa cell proliferation as measured by thymidine incorporation analysis. Furthermore, the production of progesterone by cultured granulosa cells and GFSHR-17 cell line was stimulated by PACAP-38. Interestingly, PACAP enhanced FSH action on stimulation of SF-1 and aromatase gene expression. CONCLUSION: The present results demonstrate that PACAP stimulated preantral follicle growth by potentiating proliferation and by stimulating steroidogenesis.

Therapeutic effect of neuropeptide PACAP27 on Parkinson's disease in mice / 中华神经科杂志

Objective To investigate the effects of different doses of pituitary adenylate cyclase- activating polypeptide(PACAP)on the functional and morphological outcome in a mice model of Parkinson' s disease(PD)rendered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods Male mice were treated with PACAP 0.02, 0.20 or 2.00 ?g by iv bolus for 7 days after MPTP was administered, and were compared with the saline-treated mice.The immunohistochemistry and Western blot were used to detect the alterations of PD biomarker including tyrosine hydroxylase(TH), dopamine transporter(DAT)and vesicular monoamine transporter2(VAMT2).In addition, monoamine neurotransmitters in the striatum of mice were measured by the high performance liquid chromatography (HPLC).Results TH immunohistochemistry indicated that the number of TH-positive neurons in the substantia nigra was increased in all PACAP-treated mice(PACAP(0.02 ?g/d)group was 93.33?4.87, F=85.85,P

Control Mechanisms of Ovulation by Pituitary Adenylate Cyclase-Activating Polypeptide / 대한불임학회지

No abstract available.

Effect of P2 Nucleotide Receptor Activation on Phosphate Transport in Rabbit Proximal Tubular Cells / 대한신장학회잡지

BACKGROUND: Extracellular nucleotides act as agonists to regulate a broad range of physiological processes by interacting with P2 receptors in various tissues including the kidney tubules. This study was undertaken to evaluate the effect of P2 receptor activation on PTH-dependent regulation of phosphate transport in the renal proximal tubular cells. METHODS: Proximal tubular cells were isolated from the rabbit kidney and grown as monolayers on 24 well culture plates. Phosphate uptake was determined by measuring the uptake of radiolabeled phosphate into cell monolayers. Cyclic AMP content was determined by radioimmunoassay using [3H]cAMP assay kit. RESULTS: Activation of P2 receptors with ATP exerted differential effects on phosphate uptake and cAMP generation. In the absence of PTH, it inhibited phosphate uptake and stimulated cAMP generation. In contrast, in the presence of PTH, it attenuated PTH-induced stimulation of cAMP generation and inhibition of phosphate uptake. The profile of the effects of different P2 agonists suggested that P2Y1- and P2Y2-like receptors are involved in the effects of ATP. The effect of ATP to interfere with the PTH-induced regulation was significantly blocked by calphostin C, pertussis toxin or PKC-depletion, whereas, the effects of ATP in the absence of PTH were abolished by indomethacin. CONCLUSION: Our results suggest that PKC-dependent modification of Gi proteins and, subsequently, reduced responsiveness of adenylate cyclases is responsible for the attenuating effect of ATP on the PTH-dependent regulation of phosphate transport in rabbit proximal tubule cells.