OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Hegu" (LI4) and "Taichong" (LR3) on DNA methylation of the solute carrier family 6 member 4 (SLC6A4) gene promoter region in the hippocampus of depressed rats, and to explore the potential antidepressant mechanism of EA. METHODS: Thirty male Sprague-Dawley rats were randomly divided into a blank group, a model group, a medication group, a 5-Azacytidine (5-AZA) group, and an EA group, 6 rats in each group. Depression models were established in the model group, the medication group, the 5-AZA group, and the EA group using chronic unpredictable mild stress (CUMS) combined with solitary housing. The medication group was treated with intragastric administration of fluoxetine hydrochloride capsules; the 5-AZA group was treated with intraperitoneal injection of 5-AZA; the EA group was treated with EA at bilateral "Hegu" (LI4) and "Taichong" (LR3), with disperse-dense wave, frequency of 2 Hz/100 Hz, and intensity of 1-1.2 mA, 20 min each session. All the treatment was given in three groups once daily for 21 consecutive days. Behavioral changes were evaluated by sucrose preference test, open field test, and novelty-suppressed feeding test. Serum levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured by ELISA. The expression of SLC6A4 and 5-HT1AR protein and mRNA in hippocampus was detected by Western blot and real-time quantitative PCR, respectively. DNA methylation status of the SLC6A4 promoter region in hippocampal tissue was analyzed by bisulfite sequencing PCR (BSP). RESULTS: Compared with the blank group, the model group showed decreased sucrose preference, reduced total locomotor distance, and prolonged latency to feeding (P<0.05), decreased serum 5-HT, DA, and NE levels (P<0.05), downregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and increased CpG site methylation rate of the SLC6A4 promoter region (P<0.05). Compared with the model group, the medication group, the 5-AZA group, and the EA group exhibited increased sucrose preference, increased total locomotor distance, shortened latency to feeding (P<0.05), elevated serum 5-HT, DA, and NE levels (P<0.05), upregulated hippocampal SLC6A4 and 5-HT1AR protein and mRNA expression (P<0.05), and reduced CpG site methylation rate of the SLC6A4 promoter (P<0.05). Compared with the medication group and the 5-AZA group, the EA group showed higher sucrose preference, greater total locomotor distance, shorter latency to feeding (P<0.05), and increased serum DA and NE levels (P<0.05). CONCLUSION EA could improve depressive behaviors in depressed rat models. The underlying mechanism may involve inhibition of SLC6A4 hypermethylation in the hippocampus on the serotonergic system, upregulation of SLC6A4 and 5-HT1AR protein and mRNA expression, and elevation of monoamine neurotransmitters such as 5-HT.
Animals ; Electroacupuncture ; Male ; Hippocampus/metabolism* ; Rats, Sprague-Dawley ; Rats ; Acupuncture Points ; DNA Methylation ; Depression/metabolism* ; Promoter Regions, Genetic ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Humans

OBJECTIVE: To elucidate the mechanism of Banxia Houpo Decoction (BHD) in treating gastroesophageal reflux disease (GERD) by integrating and utilizing the compound analysis, network pharmacology, and empirical verification. METHODS: Ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) was utilized to identify the primary compounds in BHD. Network pharmacology was employed to retrieve target genes. A GERD rat model was developed and 32 SD rats were randomly divided into model, BHD-L (3 g/kg), BHD-H (6 g/kg), and mosapride (0.75 mg/kg) groups using a random number table, 8 rats in each group. Eight rats without the construction of a GERD model were selected as the blank group. Esophageal damage was evaluated through visualization and histopathology evaluation. 5-hydroxytryptamine (5-HT) levels in serum and lower esophageal sphincter (LES) were determined by ELISA. LES contractility was measured with a force transducer, and serotonin transporter (SERT) and 5-HT4R expressions in LES were assessed by RT-PCR, Western blot, and immunofluorescence staining, respectively. RESULTS: UPLC-HRMS analysis identified 37 absorption peaks and 157 compounds in BHD. Functional enrichment identified SERT as a significant target for LES contractility. Histopathological findings indicated less severe esophageal mucosal damage in the BHD-H group compared with the model group. Although serum 5-HT levels showed no significant difference, 5-HT concentration in LES tissue was notably higher in the BHD-H group (P<0.05). Within the range from 10^-10 to 10^-7 mmol/L, LES contractility in the BHD-H and mosapride groups was significantly increased (P<0.05). Within the range from 3 × 10^-7 to 3 × 10^-6 mmol/L 5-HT, LES contractility in the BHD-H group was increased (P<0.05). No significant difference was detected within the range from 10^-5 to 10^-4 mmol/L 5-HT. Notably, SERT expression in the BHD-H group assessed by RT-PCR, Western blot, and immunofluorescence staining were significantly lower than that in the model group (all P<0.01); while 5-HT4R expression remained unchanged. CONCLUSION BHD may increase LES contractility by inhibiting SERT expression in LES tissue.
Animals ; Gastroesophageal Reflux/physiopathology* ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Network Pharmacology ; Male ; Serotonin/metabolism* ; Rats ; Disease Models, Animal ; Serotonin Plasma Membrane Transport Proteins/metabolism* ; Esophagus/drug effects*

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

Antidepressive Agents/therapeutic use* ; Serotonin ; 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

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
3,4-Dihydroxyphenylacetic Acid/pharmacology* ; Animals ; Antidepressive Agents/therapeutic use* ; Chromatography, Liquid ; Depression/drug therapy* ; Disease Models, Animal ; Dopamine ; Eosine Yellowish-(YS)/pharmacology* ; Hematoxylin/pharmacology* ; Hippocampus/metabolism* ; Homovanillic Acid/pharmacology* ; Hydroxyindoleacetic Acid/metabolism* ; Methoxyhydroxyphenylglycol/pharmacology* ; Monoamine Oxidase/metabolism* ; Neurotransmitter Agents/metabolism* ; Norepinephrine/pharmacology* ; Plant Extracts ; Rats ; Rehmannia/chemistry* ; Serotonin/metabolism* ; Serotonin Plasma Membrane Transport Proteins/pharmacology* ; Stress, Psychological/metabolism* ; Tandem Mass Spectrometry ; Tryptophan Hydroxylase/metabolism*

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

OBJECTIVE: This study aimed to investigate whether maternal negative affectivity (MNA) moderates the effect of genetic polymorphism of SLC6A4 on behavior problems in children. METHODS: Study participants comprised 143 preschoolers and their mothers from South Korea. The Childhood Behavior Checklist and Emotionality, Activity, and Sociability adult scale were used to measure child behavior and maternal affectivity. DNA from saliva was genotyped to determine serotonin transporter polymorphism. RESULTS: MNA appeared to exert effects in externalizing (b=5.78, p<0.001) and internalizing problems (b=6.09, p< 0.001). Interaction between SLCA4 polymorphism and MNA showed effects on externalizing (b=−7.62, p<0.01) and internalizing problems (b=−9.77, p<0.01). Children with two short alleles showed considerable differences in both externalizing and internalizing problems according to MNA; however, children with one short allele or none showed relatively few differences in behavior problems due to maternal affectivity. CONCLUSION: The effect of SLC6A4 polymorphism on child behavior seemed to be moderated by MNA. In addition, the impact of MNA was found to vary based on a child’s genetic risk. High MNA may trigger the risk allele while low MNA causes the risk allele to illicit less behavior problems. Children with two short variants of the SLC6A4 gene may benefit from intervention that modulates MNA.
Adult ; Alleles ; Checklist ; Child ; Child Behavior ; DNA ; Gene-Environment Interaction ; Humans ; Korea ; Maternal Behavior ; Mothers ; Polymorphism, Genetic ; Saliva ; Serotonin Plasma Membrane Transport Proteins

Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.
Aggression ; Antipsychotic Agents ; Catechol O-Methyltransferase ; Clozapine ; Comorbidity ; Crime ; Humans ; Neuroimaging ; Promoter Regions, Genetic ; Risk Factors ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins ; Substance-Related Disorders ; Violence

OBJECTIVES: Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. METHODS: A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene (SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene (DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. RESULTS: No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. CONCLUSIONS: Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.
Adult ; Dopamine Plasma Membrane Transport Proteins ; Dopamine* ; Genetic Background ; Genotype ; Humans ; Psychology ; Resilience, Psychological* ; Serotonin Plasma Membrane Transport Proteins ; Serotonin* ; Tandem Repeat Sequences