OBJECTIVE: To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI). METHODS: First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro. RESULTS: MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model. CONCLUSIONS THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.
Humans ; Matrix Metalloproteinase 9 ; Network Pharmacology ; Cyclooxygenase 2 ; Molecular Docking Simulation ; PPAR gamma ; Myocardial Ischemia/genetics* ; Glucose ; RNA ; Drugs, Chinese Herbal/therapeutic use* ; Serotonin Plasma Membrane Transport Proteins

OBJECTIVE: To assess the association of SLC6A4 gene c.*670T>G polymorphism with the risk for asthma and peripheral blood cytological characteristics among ethnic Zhuang Chinese from Guangxi, China. METHODS: From May 2017 to March 2020, 258 patients diagnosed with asthma and 244 healthy controls were recruited from the Affiliated Hospital of Youjiang Minzhu Medical College and the People's Hospital of Hechi. Genotypes of the c.*670T>G polymorphism were determined by Sanger sequencing. Flow cytometry was used in combination with an electrical impedance method for the counting and classification of peripheral blood cells. RESULTS: Compared with the T allele, the G allele of the c.*670T>G polymorphism was associated with the risk for asthma in the population (OR = 1.54, 95%CI = 1.15-2.06; P = 0.004). Compared with the GT and TT genotypes, homozygous GG genotype also comprised a risk factor (OR = 1.66, 95%CI = 1.16-2.38; P = 0.005). Stratification of the risk factors showed that the homozygous GG genotype has increased the risk of asthma in males and urban residents (P < 0.01). The erythrocyte, hemoglobin and platelet counts of the asthma group were significantly higher than the control group (P < 0.001). The GG, GT and TT genotypes have respectively accounted for 82.35%, 17.65% and 0% of the samples with platelets exceeding the normal value. The overall platelet level of GG genotype was higher than GT+TT genotype (P < 0.05). The significant association was verified by the false positive report probability, and at a prior probability level of 0.1, G vs. T false positive probability was 0.071, and GG vs. GT+TT false positive probability was 0.153. CONCLUSION The GG genotype of the c.*670T>G polymorphism is associated with the risk for asthma among ethnic Zhuang Chinese from northwest Guangxi. Above finding has also enriched the genotypic data and peripheral blood phenotype for this polymorphism.
Male ; Humans ; East Asian People ; China ; Genotype ; Alleles ; Asthma/genetics* ; Serotonin Plasma Membrane Transport Proteins

OBJECTIVE: To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating METHODS: A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating RESULTS: After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment ( CONCLUSION Acupuncture for regulating
Acupuncture Therapy ; Diarrhea/therapy* ; Humans ; Irritable Bowel Syndrome/therapy* ; Quality of Life ; Serotonin Plasma Membrane Transport Proteins/genetics* ; Spleen ; Treatment Outcome

Premature ejaculation (PE), as one of the most common male sexual dysfunctions, has a serious negative impact on the sexual satisfaction of the patients and their sexual partners. Lifelong PE is a most common type and a current focus of research as well. The etiology and pathogenesis of this disease are not yet clear and genetic factors are considered to be closely related to lifelong PE. Studies show that the 5-hydroxytryptamine transporter (5-HTT) gene plays an important role in the development and progression of lifelong premature ejaculation and the 5-HTT-linked polymorphic region (5-HTTLPR) has attracted much attention in recent years. This article presents an overview on the correlation between 5-HTTLPR and lifelong PE.
Adult ; Ejaculation ; Humans ; Male ; Polymorphism, Genetic ; Premature Ejaculation ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

OBJECTIVETo examine the association between the genotype (LL, LS and SS) of serotonin transporter promoter gene polymorphism(5-HTTLPR) and clinicopathological factors, and to investigate the effect of 5-HTTLPR on the prognosis of colorectal cancer patients.

METHODSData of peripheral blood samples of 161 colorectal cancer patients at the Second Affiliated Hospital of Guangzhou Medical University from October 2009 to January 2014 were collected retrospectively. The genotyping of 5-HTTLPR was determined by PCR and agarose gel electrophoresis. Coincidence Chi-square test was used to examine the 5-HTTLPR genotype with Hardy-Weinberg law. Chi-square test and Cox multifactor model were used to analyze the association of 5-HTTLPR genotype with clinicopathology and prognosis. All the patients were informed and agreed to participate in the study. This study was approved by the Hospital Ethics Committee (2015056).

RESULTSOf 161 colorectal cancer patients, 89 were male and 72 were female; the median age was 64 (25-85) years; 86 (53.5%) cases were colon cancer and 75 (46.5%) were rectal cancer. Genotype was LL in 12 cases, LS in 59 cases and SS in 90 cases, which complied with the law of Hardy-Weinberg genetic balance (χ²=0.288, P=0.592). Univariate analysis showed that 5-HTTLPR gene polymorphism was only associated with lymph node metastasis [lymph node metastasis rate: LL and LS genotype 21.1% (15/71);SS genotype 40.0% (36/90), χ²= 6.532, P=0.011]. The 3-year and 5-year overall survival rates of whole patients were 71% and 63% respectively. Multivariate analysis revealed that the SS genotype was an independent risk factor affecting the overall survival of colorectal cancer patients(HR=1.933, 95%CI:1.090-3.428, P=0.024).

CONCLUSIONAmong genotypes of 5-HTTLPR gene, colorectal cancer patients with SS genotype have higher risk of lymph node metastasis and poorer prognosis.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; genetics ; pathology ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Prognosis ; Retrospective Studies ; Serotonin Plasma Membrane Transport Proteins ; genetics

Adult ; Asian People ; China/epidemiology* ; Exons ; Humans ; Male ; Negative Results ; Polymorphism, Genetic/genetics* ; Polymorphism, Single Nucleotide ; Premature Ejaculation/genetics* ; Serotonin Plasma Membrane Transport Proteins/genetics*

OBJECTIVETo investigate the association between anxiety-depression and 5-HTTLPR gene polymorphism in school-aged twins.

METHODSA total of 147 pairs of twins (47 pairs of monozygotic twins, 100 pairs of dizygotic twins) aged 8-12 years from Baotou and Hohhot were selected as respondents. The Achenbach Child Behavior Checklist (CBCL) was used to calculate the scores of anxiety-depression factors in school-aged twins. The DNA was extracted from oral epithelial cells, and polymerase chain reaction was applied for 5-HTTLPR genotyping. The generalized estimating equation (GEE) was used to analyze the effect of 5-HTTLPR polymorphism and family environment on anxiety-depression in school-aged twins.

RESULTSThe children with LS and SS genotypes had significantly higher scores of anxiety-depression factors than those with LL genotype (χ2=3.938, P<0.05). The interaction of 5-HTTLPR genotype with family cohesion and family rearing patterns had a significant impact on the scores of anxiety-depression factors in twins (χ2=6.129 and 7.665, both P<0.05).

CONCLUSIONS5-HTTLPR genotype is significantly correlated with the scores of anxiety-depression factors in school-aged twins. In the family with high cohesion and an autocratic family rearing pattern, S allele may increase the possibility of anxiety-depression in twin children.

Anxiety ; genetics ; Child ; Depression ; genetics ; Female ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Twins ; genetics

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.
Adult ; Age Factors ; Alleles ; Case-Control Studies ; Catechol O-Methyltransferase/*genetics ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Panic Disorder/genetics/*pathology ; Polymorphism, Single Nucleotide ; *Quality of Life ; Regression Analysis ; Serotonin Plasma Membrane Transport Proteins/*genetics ; Sex Factors

OBJECTIVETo assess the association between the serotonin transporter linked polymorphic region (5-HTTLPR) 44 bp variable number of tandem repeat (VNTR) polymorphism and Tourette syndrome (TS) in ethnic Han Chinese trios.

METHODSA total of 252 TS trios (patients and their parents) were recruited. Genetic contribution of the 5-HTTLPR 44 bp VNTR polymorphism was evaluated by genotyping, haplotype relative risk (HRR) analysis and transmission disequilibrium test (TDT) statistics. To enhance the efficiency of the test, haplotype-based HRR (HHRR) was also performed.

RESULTSThe TDT, HRR and HHRR analyses have revealed a significant association of the 5-HTTLPR 44 bp VNTR polymorphism with TS, and provided a strong evidence for an over-transmission of L allele from parents to the affected children (TDT: χ² = 6.680, df= 1, P= 0.012; HRR: χ² = 9.345, P= 0.002, OR= 1.739, 95% CI for 1.218-2.483). For 204 male and 48 female TS trios, TDT and HRR were analyzed separately. The results showed a significant association between 5-HTTLPR and male TS (for males. TDT: χ² = 4.643, df= 1, P= 0.038; for females, TDT: χ² = 2.189, df= 1, P= 0.188).

CONCLUSION5-HTTLPR may be the susceptibility gene for male TS patients among the Chinese Han population. However, the results need to be replicated in datasets collected from different populations.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; Male ; Minisatellite Repeats ; genetics ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Sex Factors ; Tourette Syndrome ; genetics ; Young Adult

Compounds with serotonin reuptake inhibition/5-HT(1A) dual activity were used to build 3D pharmacophore model as a training molecules by Discover Studio. Based on the model, 8 novel aryl piperazine benzo[b][1,4] oxazine derivatives were designed and synthesized, and their structures were confirmed by 1H NMR and HR-MS. Biological evaluation illustrated that compounds VI(1) and VI(7) showed potent functional activities at both 5-HT transporter and 5-HT(1A) receptor, which can be used as lead compounds to guide future research of design and synthesis of potent novel compounds.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Drug Design ; Genetic Vectors ; Molecular Structure ; Oxazines ; chemical synthesis ; chemistry ; pharmacology ; Piperazines ; chemical synthesis ; chemistry ; pharmacology ; Plasmids ; Protein Binding ; Receptor, Serotonin, 5-HT1A ; genetics ; metabolism ; Serotonin Plasma Membrane Transport Proteins ; genetics ; metabolism ; Serotonin Uptake Inhibitors ; metabolism ; Structure-Activity Relationship ; Transfection