OBJECTIVE: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. METHODS: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. RESULTS: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). CONCLUSIONS MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP.
Animals ; Zebrafish ; Serotonin/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Hemostatics/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Receptors, Serotonin/genetics* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Signal Transduction/drug effects* ; Hemostasis/drug effects*

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals ; Interneurons/metabolism* ; Mice ; Neurons/metabolism* ; Parvalbumins/metabolism* ; Receptors, Serotonin, 5-HT3/genetics* ; Serotonin ; Somatostatin/metabolism*

Adult ; China ; Cognitive Dysfunction ; genetics ; Electric Power Supplies ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Power Plants ; Receptors, N-Methyl-D-Aspartate ; genetics ; metabolism ; Receptors, Serotonin ; genetics ; metabolism ; Young Adult

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.
Antipsychotic Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; China ; Genome-Wide Association Study ; Genotype ; Humans ; Lipid Metabolism ; genetics ; Neurosecretory Systems ; drug effects ; Pharmacogenomic Testing ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; genetics ; Receptors, Dopamine ; genetics ; Receptors, Histamine ; genetics ; Receptors, Serotonin ; genetics ; Weight Gain ; drug effects ; genetics

PURPOSE: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV. MATERIALS AND METHODS: Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated. RESULTS: Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery. CONCLUSION: The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV.
Adult ; Aged ; Anesthesia, General ; Antiemetics/administration & dosage/*pharmacology ; Cholecystectomy, Laparoscopic ; Female ; Genome, Human ; Genotype ; Humans ; Incidence ; Injections, Intravenous ; Male ; Middle Aged ; Ondansetron/administration & dosage/*pharmacology ; Polymorphism, Genetic ; Postoperative Nausea and Vomiting/chemically induced/*drug therapy/epidemiology ; Receptors, Serotonin, 5-HT3/*drug effects/*genetics ; Time Factors

OBJECTIVETo investigate the relationship between 5-HTTLPR and/or DRD4 gene polymorphisms and the accident tendentiousness of drivers.

METHODSA case-control study, including 42 patients and 46 controls, were performed using type-A behavior questionnaire and EPQ scale. 5-HTTLPR and DRD4 gene -521 C/T were detected by the PCR-RFLP technique.

RESULTSThe scores of type-A behavior questionnaires, such as TH and TH + CH in exposure group were significantly higher than those in control group (P < 0.05). P and N scores of EPQ questionnaires in exposure group were significantly higher than those in control group, and L score in exposure group was significantly lower than that in control group (P < 0.05 or P < 0.01). There were significant differences in the frequencies of the genotypes and alleles of 5-HTTLPR gene between the cases and the controls (P < 0.05), but there were no significant differences in the frequencies of the genotypes and alleles of DRD4 gene between the two groups (P > 0.05). In the drivers with the accident tendentiousness, P scores in the cases with homozygous genotypes of the S/S in 5-HTTLPR gene were significantly higher than those in the cases with the genotypes of S/L and L/L in 5-HTTLPR gene (P > 0.05). E scores in subjects with homozygous genotypes of the T/T in DRD4 gene were significantly higher than those in subjects with genotypes of the T/C+C/C in DRD4 gene (P > 0.05).

CONCLUSIONThe driver accident tendentiousness may be associated with 5-HTTLPR gene, but not associated with DRD4 gene. The two genes are associated with the type-A behavior and personality characteristics of drivers with accident tendentiousness. However, 5-HTTLPR and DRD4 gene may not have synergism in these behaviors and personality.

Accidents, Traffic ; statistics & numerical data ; Adult ; Automobile Driving ; Case-Control Studies ; Genotype ; Humans ; Male ; Personality ; genetics ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
Animals ; Antidepressive Agents ; pharmacology ; Depressive Disorder, Major ; genetics ; metabolism ; physiopathology ; Drug Delivery Systems ; Gene Knockout Techniques ; Humans ; Neuronal Plasticity ; Polymorphism, Genetic ; Potassium Channels, Tandem Pore Domain ; genetics ; metabolism ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT4 ; Serotonin ; pharmacology

OBJECTIVEDisruptive behavior disorder (DBD) is one of the main comorbidity of attention deficit hyperactivity disorder (ADHD). Previous studies showed significantly different serotonin function between ADHD children with and without the comorbidity of DBD. Therefore, it is needed to compare these two groups in terms of serotonin receptor gene polymorphisms, which may provide further evidence for the previous studies. The current study aimed to investigate the relationship between two serotonin receptor 2C (HTR2C) gene polymorphisms, that are C-759T and G-697C polymorphisms, and ADHD with or without concomitant DBD.

METHODBlood samples were taken from 237 trios with probands of ADHD with DBD comorbidity and 251 trios with probands of ADHD without comorbidity of DBD. All the subjects were from the ADHD clinic of Peking University Sixth Hospital. DNA was extracted and PCR was performed to amplify the fragments containing both C-759T and G-697C polymorphisms. AciI was used to detect different alleles of the two polymorphisms. Both allele-based and haplotype-based TDT analyses were used to test the association of the two polymorphisms of HTR2C gene and ADHD with or without comorbidity of DBD.

RESULTSThe haplotypes -759C (chi(2) = 4.25, P = 0.04), -697G(chi(2) = 3.21, P = 0.07), as well as -759C/-697G were over-transmitted (chi(2) = 4.31, P = 0.04) to the probands of ADHD without DBD. No biased transmission of any allele and haplotype were found in families with probands of ADHD with DBD.

CONCLUSIONADHD with or without the comorbidity DBD was different at the level of HTR2C gene polymorphisms of C-759T and G-697C. HTR2C is related to ADHD without DBD, while not related to ADHD with DBD. The results suggested that the two groups may have different genetic background, at least in HTR2C.

Alleles ; Attention Deficit Disorder with Hyperactivity ; complications ; genetics ; Attention Deficit and Disruptive Behavior Disorders ; complications ; genetics ; Child ; Comorbidity ; Gene Frequency ; Genetic Predisposition to Disease ; Genetic Testing ; Genotype ; Haplotypes ; Humans ; Linkage Disequilibrium ; Polymorphism, Genetic ; Receptor, Serotonin, 5-HT2C ; genetics ; Receptors, Serotonin ; Serotonin ; genetics

BACKGROUNDThe 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS.

METHODSA rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity.

RESULTSThe models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P < 0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P < 0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P < 0.05). Real time-PCR results showed that the expression level of the 5-HT(7) receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P < 0.05). The expression level of 5-HT(7) receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P < 0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P < 0.01 and P < 0.05). The cAMP accumulation in the IBS-C group was higher than that in the control group in the proximal and distal colon (P < 0.05).

CONCLUSIONSThe increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

Animals ; Brain ; metabolism ; Cyclic AMP ; metabolism ; Disease Models, Animal ; Immunohistochemistry ; Intestines ; metabolism ; Irritable Bowel Syndrome ; etiology ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin ; analysis ; genetics ; physiology ; Serotonin ; analysis

OBJECTIVEThis study is purposed to explore the relationship between aggressively driving behavior and functional polymorphism in the promoter region of the monoamine oxidase-A (MAOA) gene.

METHODSA total of 348 automobile drivers were investigated with Deffenbacher's driver anger scale, driving vengeance questionnaire (DVQ) and driver aggression behavior questionnaire. Eighty-eight drivers were selected as more, medium and less aggressive group, each. Polymerase chain reaction (PCR) and 2.5% agarose gel electrophoresisi were adopted to detect the polymorphism of functional 30 bp-uVNTR in the promoter region of the X-chromosomal MAOA gene and their frequencies of varied genotypes were estimated.

RESULTSTwo alleles with 3 and 4 repeats of 30 bp-uVNTR were detected in the drivers. Among the more aggressive group, number of the allele with 3 repeats of 30 bp-uVNTR (63/88) was significantly more than that with 4 repeats (25/88) (chi(2) = 10.21, P < 0.01), and number of the allele with 4 repeats of 30 bp-uVNTR was more in the less aggressive group, indicating that persons with allele of 3 repeats of 30 bp VNTR were more aggressive in their driving than those with 4 repeats.

CONCLUSIONSAggressively driving behavior in drivers possibly related to their functional MAOA-uVNTR polymorphism. Effect of the gene on aggressively driving behavior should be further studied.

Adult ; Aggression ; physiology ; Automobile Driving ; psychology ; Brain ; physiopathology ; Humans ; Impulsive Behavior ; genetics ; physiopathology ; Male ; Monoamine Oxidase ; genetics ; Polymorphism, Genetic ; genetics ; Promoter Regions, Genetic ; Receptors, Serotonin ; genetics ; Serotonin ; physiology ; Surveys and Questionnaires