BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotoni...BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.展开更多
Background Compelling evidence has established a strong link between the gut microbiota and host reproductive health.However,the specific regulatory roles of individual bacterial species on reproductive performance ar...Background Compelling evidence has established a strong link between the gut microbiota and host reproductive health.However,the specific regulatory roles of individual bacterial species on reproductive performance are not well-understood.In the present study,Jinhua sows with varying reproductive performances under the same diet and management conditions were selected to explore potential mechanisms on the intricate relationship between the gut microbiome and host reproductive performance using 16S rRNA sequencing,metagenomics and serum metabolomics.Results Our findings revealed that the KEGG pathways for base excision repair and DNA replication were enriched,along with gene-level enhancements in spore formation,in sows with higher reproductive performance,indicating that the gut microbiome experiences stress.Further analysis showed a positive correlation between these changes and litter size,indicating that the host acts as a stressor,reshaping the microbiome.This adaptation allows the intestinal microbes in sows with high reproductive performance to enrich specific serotonin-related bacteria,such as Oxalobacter formigenes,Ruminococcus sp.CAG 382,Clostridium leptum,and Clostridium botulinum.Subsequently,the enriched microbiota may promote host serotonin production,which is positively correlated with reproductive performance in our study,known to regulate follicle survival and oocyte maturation.Conclusion Our study provides a theoretical basis for understanding the interactions between gut microbes and the host.It highlights new insights into reassembling gut microbiota in sows with higher litter sizes and the role of serotonin-related microbiota and serotonin in fertility.展开更多
Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it ...Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.展开更多
Broody behavior is regulated by hypothalamic prolactin secretion,which seriously affects egg production in poulty production.Numerous studies have provided evidence that animal behavior is governed by dynamic bidirect...Broody behavior is regulated by hypothalamic prolactin secretion,which seriously affects egg production in poulty production.Numerous studies have provided evidence that animal behavior is governed by dynamic bidirectional communication between specific gut bacteria and their host via the brain-gut-microbiome axis.However,little research focused on how the gut microbiota influence broody behavior in poultry.In this study,Zhedong white geese in laying and brooding phases were selected.Ten differentially abundant bacteria in cecum were detected between brooding and laying geese through metagenomic analyses and 16S rRNA sequencing(P<0.05),and Bacteroides fragilis was specifically identified as a key driver species in the brooding geese.Moverover,the serum metabolites were quantified,and the 313 differentially abundant metabolites were found between the two groups of different physiological geese.They were primarily enriched in the tryptophan metabolism pathways.Pearson correlation analyses revealed there was a significant positive correlation between B.fragilis abundance and the context of 11 tryptophan metabolism-related metabolites(such as serotonin,etc.)in broody geese,which hinted that those tryptophan metabolites might be produced or driven by B.fragilis.Finally,the serum hormone levels were also measured.We found there was a positive correlation between B.fragilis abundance and content of serotonin.Besides,prolactin secreted by the pituitary gland was greater in brooding geese than that in laying geese,which was also highly correlated with B.fragilis abundance.This result implied that B.fragilis could promote the secretion of prolactin by the pituitary gland.Together,the current study findings provided the information on gut microbiota influencing broody behavior,B.fragilis produced or driven more serum serotonin,and stimulated the pituitary gland to secret more prolactin,which potentially offered a new enlightenment for the intervention of broody behavior in poultry.展开更多
This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It c...This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It compared this innovative medium(5-HT/L-C/CoQ10 SWM)with two widely used commercial media(SWM 1 and SWM 2).Ninety-eight volunteers from an infertility clinic provided semen samples,which were divided into three aliquots for analysis in different SWMs:group 1,SWM was composed of hydroxyethyl piperazineethanesulfonic acid(HEPES),sodium bicarbonate,human serum albumin(HSA),taurine,and gentamicin sulfate(SWM 1);group 2,SWM was composed of HEPES,sodium bicarbonate,and HSA(SWM 2);and group 3,SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT,L-C,and CoQ10(5-HT/L-C/CoQ10 SWM).Sperm motility was categorized as progressive,nonprogressive,or immotile.Apoptosis,reactive oxygen species(ROS)production,and DNA fragmentation were also assessed.There were no significant differences in total or progressive sperm motility among the groups.Spermatozoa in group 3 exhibited reduced apoptosis,necrosis,and ROS levels and increased viability.No significant differences were observed in the DNA fragmentation index among groups.The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs,suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.展开更多
Cold stress severely limits the distribution of mangrove species worldwide and it remains unclear how mangroves respond and adapt to cold temperatures.In this study,we investigated the effects of cold acclimation and/...Cold stress severely limits the distribution of mangrove species worldwide and it remains unclear how mangroves respond and adapt to cold temperatures.In this study,we investigated the effects of cold acclimation and/or inhibition of serotonin levels on reactive oxygen species(ROS),reactive nitrogen species(RNS),melatonin(MEL)and serotonin(SER)accumulation during cold stress in Kandelia obovata.Morphologic observation and param-eter analysis revealed that cold acclimation mitigated the photoinhibition of photosystem I(PSI)and photosystem II(PSII),maintained optimal ROS and RNS redox homeosta-sis,and increased the contents of SER and MEL in leaves.This suggests that cold acclimation reshapes the MEL/ROS/RNS redox network.In particular,the tryptophan/tryptamine/Ser/N-acetylserotonin/MER pathway was identi-fied as a branch of the MEL synthesis pathway.Inhibition of endogenous SER exacerbated damage caused by cold stress,indicating the crosstalk of SER synthesis and cold acclima-tion.In this study,we report a coordinated regulation of cold stress by a complex defense network in K.obovata.展开更多
Objective:To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis(K...Objective:To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis(KOA).Methods:Forty SpragueeDawley rats were equally divided into control,model(1 mg of mono-iodoacetate into the right knee joint cavity),sham operation,manual acupuncture at right Tianjing acupoint(MAR-SJ 10),and left SJ 10 groups.Safranine-O and fast green staining were used to assess the modeling.The morphological and functional changes in mast cells(MCs)were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining.The levels of serotonin,histamine,substance P(SP),and tryptase at skin acupoints and serum levels of IL-β,IL-6,and TNF-αwere detected using ELISA.Results:After 14 days of treatment,the number of MCs and their degranulation rates were statistically higher in the model group than in the control group(both P<0.001).After applying acupuncture,the levels of 5-HT,HA,and SP at skin acupoints were lower than those in the model group(all P<0.05),and tryptase level was higher(both P<0.05).Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint(P=0.004).Compared with the model group,the serum levels of IL-1β,IL-6,and TNF-αin the MAR-SJ 10 and MAL-SJ 10 groups were lower(all P<0.05).Conclusion:Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidi-rectionally regulate local MCs of these acupoints.This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment,but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.展开更多
BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To eva...BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To evaluate the epidemiological,clinical,and other aspects of the insidious onset SS.METHODS We retrospectively evaluated 14 consecutive adult patients(>18 years)who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.RESULTS The mean age was 41.1 years(range:21-61 years),with a male preponderance(64%).Although tremors were observed in all patients,this was a presenting complaint in only 43%of patients.Generalized body pain,insomnia,and restlessness were common presenting features(50%each).Other common clinical features were stiffness of the limbs(43%),diaphoresis(43%),gait disturbances(36%),bowel disturbances(36%),dizziness(29%),sexual dysfunctions(21%),incoordination(14%),and fatigue(14%)The mean duration of symptoms before the diagnosis of SS was 13.5±5.8 wk(range:6-24 wk).Amitriptyline was the most common drug(n=6,43%),followed by tramadol(n=5,36%)and sodium valproate(n=5,36%).All patients received cyproheptadine,a 5-hydroxytryptamine2A antagonist,as treatment and noted an excellent response CONCLUSION This study represents the largest study on chronic SS.We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.展开更多
<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyze...<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Ultra high-speed </span></span><span style="font-family:""><span style="font-family:Verdana;">liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive </span><span><span style="font-family:Verdana;">patients. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.展开更多
BACKGROUND: Serotonin transporter (5-HTT) polymorphisms comprise 5-HTT gene-linked polymorphism region (5-HTTLPR) and variable number of tandem repeats (VNTR). Studies have revealed an association between 5-HTT...BACKGROUND: Serotonin transporter (5-HTT) polymorphisms comprise 5-HTT gene-linked polymorphism region (5-HTTLPR) and variable number of tandem repeats (VNTR). Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the "S" allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE: To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING: Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS: A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale (24 items) ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS: Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES: 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS: No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls (P 〉 0.05). However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected (P 〈 0.01 ). The Stin2.10 allele and 10/10 genotype associated with major depressive disorder (OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01). CONCLUSION: Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.展开更多
We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the ...We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P 〈 0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.展开更多
Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is th...Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.展开更多
Serotonin(5-HT) and the serotonin transporter(SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome(IBS). Considering that enteric 5-HT is responsible for the secret...Serotonin(5-HT) and the serotonin transporter(SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome(IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mR NA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microR NAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.展开更多
AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD ...AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD were measured by high-performance liquid chromatography.A rat model of IBS was induced by chronic water avoidance stress(WAS).The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension.Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-αin colonic tissue and calcitonin-gene-related peptide(CGRP)in serum were measured by ELISA.The protein expression of serotonin[5-hydroxytryptamide(5-HT)],serotonin transporter(SERT),chromogranin A(Cg A)and CGRP incolon tissue was measured by immunohistochemistry.RESULTS:SGD inhibited colonic motility dysfunction and VHL in rats with IBS.Blockers of transient receptor potential(TRP)vanilloid 1(TRPV1)(Ruthenium Red)and TRP ankyrin-1(TRPA1)(HC-030031)and activator of protease-activated receptor(PAR)4 increased the pain pressure threshold,whereas activators of PAR2and TRPV4 decreased the pain pressure threshold in rats with IBS.The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1(capsaicin),TRPV4(RN1747),TRPA1(Polygodial)and PAR2(AC55541).In addition,CGRP levels in serum and colonic tissue were both increased in these rats.TNF-αlevel in colonic tissue was also significantly upregulated.However,the levels of 5-HT,SERT and Cg A in colonic tissue were decreased.All these pathological changes in rats with IBS were attenuated by SGD.CONCLUSION:SGD alleviated VHL and attenuated colon motility in IBS,partly by regulating TRPV1,TRPV4,TRPA1,PAR2,5-HT,Cg A and SERT,and reducing CGRP and TNF-αlevel.展开更多
AIM To evaluate the effect of Lactobacillus rhamnosus GG supernatant(LGG-s) on the expression of serotonin transporter(SERT) in rats with post-infectious irritable bowel syndrome(PI-IBS).METHODS Campylobacter jejuni 8...AIM To evaluate the effect of Lactobacillus rhamnosus GG supernatant(LGG-s) on the expression of serotonin transporter(SERT) in rats with post-infectious irritable bowel syndrome(PI-IBS).METHODS Campylobacter jejuni 81-176(1010 CFU/m L) was used to induce intestinal infection to develop a PI-IBS model. After evaluation of the post-infectious phase by biochemical tests, Dn A agarose gel electrophoresis, abdominal withdrawal reflex(AWR) test, and the intestinal motility test, four PI-IBS groups received different concentrations of LGG-s for 4 wk. The treatments were maintained for 1.0, 2.0, 3.0 or 4.0 wk during the experiment, and the colons and brains were removed for later use each week. SERT m Rn A and protein levels were detected by real-time PCR and Western blot, respectively.RESULTS The levels of SERT m Rn A and protein in intestinal tissue were higher in rats treated with LGG-s than in control rats and PI-IBS rats gavaged with PBS during the whole study. Undiluted LGG-s up-regulated SERT m Rn A level by 2.67 times compared with the control group by week 2, and SERT m Rn A expression kept increasing later. Double-diluted LGG-s was similar to undiluted-LGG-s, resulting in high levels of SERT m Rn A. Triple-diluted LGG-s up-regulated SERT m Rn A expression level by 6.9-times compared with the control group, but SERT m Rn A expression decreased rapidly at the end of the second week. At the first week, SERT protein levels were basically comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triplediluted LGG-s, which were higher than those in the control group and PBS-treated PI-IBS group. SERT protein levels in the intestine were also comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triple-diluted LGG-s by the second and third weeks. SERT m Rn A and protein levels in the brain had no statistical difference in the groups during the experiment.CONCLUSION LGG-s can up-regulate SERT m Rn A and protein levels in intestinal tissue but has no influence in brain tissue in rats with PI-IBS.展开更多
Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE), Our objective in this study was to characterize the efficac...Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE), Our objective in this study was to characterize the efficacy of on-demand dapoxetine (30 and 60 mg) and daily paroxetine (20 mg) usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine (30 mg), Group 2 with on-demand dapoxetine (60 mg) and Group 3 with daily paroxetine (20 rag), Our outcome measurement was increased from baseline intravaginal ejaculatory latency time (IELT) after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group (P 〈 0,01), 30 mg dapoxetine group (P 〈 0,01) and 60 mg dapoxetine group (P 〈 0.01), respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups (P 〉 0,05), while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine (P〈 0.05) and paroxetine (P〈 0.01) groups, Dapoxetine (60 mg) 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.展开更多
文摘BACKGROUND Traumatic brain injury(TBI)poses a considerable risk to human health.After TBI,individuals are susceptible to a range of psychiatric disorders,with depression being a primary complication.Selective serotonin reuptake inhibitors(SSRIs)are frequently used in the treatment of depression;however,their efficacy in addressing major depressive disorder(MDD)in adults following TBI remains uncertain.AIM To investigate the efficacy of SSRIs in the treatment of MDD after TBI.METHODS A comprehensive search across multiple databases was conducted following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement,encompassing studies published until May 2024.This review focused on studies that examined the efficacy of SSRIs in the treatment of MDD following TBI.Studies were assessed based sample size,treatment duration,treatment methodologies,severity of brain injury,assessment techniques,and drug response.A random-effects model was used to derive the summary effect size.RESULTS Eight studies compared the reduction in depression scores in patients with MDD after TBI and SSRI treatment.The eight studies did not exhibit heterogeneity(I^(2)=38%).The depression score for MDD after TBI in the SSRI group decreased more than that in the control group[odds ratio(OR)1.68,95%CI:1.09-2.58,P=0.02].The adverse reactions after treatment included diarrhea,dizziness,dry mouth,nausea,or vomiting.There was no difference in the incidence of adverse reactions after treatment between the two groups(OR 1.16,95%CI:0.78-1.73,P=0.46).These studies did not show significant heterogeneity(I^(2)=44%).CONCLUSION SSRIs may be effective in treating patients with MDD after TBI.Adequately powered,randomized,controlled trials are required to confirm these findings.
基金supported by Fundamental Research Funds for the Central Universities(226-2024-00080)Zhejiang Provincial Natural Science Foundation Program of China(LZ25C170001)+2 种基金National Natural Science Foundation of China(32372889,U21A20249)China Agriculture Research System(CARS-35)National Center of Technology Innovation for Pigs。
文摘Background Compelling evidence has established a strong link between the gut microbiota and host reproductive health.However,the specific regulatory roles of individual bacterial species on reproductive performance are not well-understood.In the present study,Jinhua sows with varying reproductive performances under the same diet and management conditions were selected to explore potential mechanisms on the intricate relationship between the gut microbiome and host reproductive performance using 16S rRNA sequencing,metagenomics and serum metabolomics.Results Our findings revealed that the KEGG pathways for base excision repair and DNA replication were enriched,along with gene-level enhancements in spore formation,in sows with higher reproductive performance,indicating that the gut microbiome experiences stress.Further analysis showed a positive correlation between these changes and litter size,indicating that the host acts as a stressor,reshaping the microbiome.This adaptation allows the intestinal microbes in sows with high reproductive performance to enrich specific serotonin-related bacteria,such as Oxalobacter formigenes,Ruminococcus sp.CAG 382,Clostridium leptum,and Clostridium botulinum.Subsequently,the enriched microbiota may promote host serotonin production,which is positively correlated with reproductive performance in our study,known to regulate follicle survival and oocyte maturation.Conclusion Our study provides a theoretical basis for understanding the interactions between gut microbes and the host.It highlights new insights into reassembling gut microbiota in sows with higher litter sizes and the role of serotonin-related microbiota and serotonin in fertility.
文摘Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.
基金supported by the Modern Agro-industry Technology Research System,China(CARS-42-3)the“JBGS”Project of Seed Industry Revitalization in Jiangsu Province,China(JBGS(2021)023)the Project in Ministry of Agriculture and Rural Affairs of China(19211168).
文摘Broody behavior is regulated by hypothalamic prolactin secretion,which seriously affects egg production in poulty production.Numerous studies have provided evidence that animal behavior is governed by dynamic bidirectional communication between specific gut bacteria and their host via the brain-gut-microbiome axis.However,little research focused on how the gut microbiota influence broody behavior in poultry.In this study,Zhedong white geese in laying and brooding phases were selected.Ten differentially abundant bacteria in cecum were detected between brooding and laying geese through metagenomic analyses and 16S rRNA sequencing(P<0.05),and Bacteroides fragilis was specifically identified as a key driver species in the brooding geese.Moverover,the serum metabolites were quantified,and the 313 differentially abundant metabolites were found between the two groups of different physiological geese.They were primarily enriched in the tryptophan metabolism pathways.Pearson correlation analyses revealed there was a significant positive correlation between B.fragilis abundance and the context of 11 tryptophan metabolism-related metabolites(such as serotonin,etc.)in broody geese,which hinted that those tryptophan metabolites might be produced or driven by B.fragilis.Finally,the serum hormone levels were also measured.We found there was a positive correlation between B.fragilis abundance and content of serotonin.Besides,prolactin secreted by the pituitary gland was greater in brooding geese than that in laying geese,which was also highly correlated with B.fragilis abundance.This result implied that B.fragilis could promote the secretion of prolactin by the pituitary gland.Together,the current study findings provided the information on gut microbiota influencing broody behavior,B.fragilis produced or driven more serum serotonin,and stimulated the pituitary gland to secret more prolactin,which potentially offered a new enlightenment for the intervention of broody behavior in poultry.
基金financially supported by the Turkish Scientific and Technological Research Council(TUBITAK,No.TUBITAK-7218008)the Scientific Research Projects Unit of Istanbul Kultur University(No.IKU-BAP2212).
文摘This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It compared this innovative medium(5-HT/L-C/CoQ10 SWM)with two widely used commercial media(SWM 1 and SWM 2).Ninety-eight volunteers from an infertility clinic provided semen samples,which were divided into three aliquots for analysis in different SWMs:group 1,SWM was composed of hydroxyethyl piperazineethanesulfonic acid(HEPES),sodium bicarbonate,human serum albumin(HSA),taurine,and gentamicin sulfate(SWM 1);group 2,SWM was composed of HEPES,sodium bicarbonate,and HSA(SWM 2);and group 3,SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT,L-C,and CoQ10(5-HT/L-C/CoQ10 SWM).Sperm motility was categorized as progressive,nonprogressive,or immotile.Apoptosis,reactive oxygen species(ROS)production,and DNA fragmentation were also assessed.There were no significant differences in total or progressive sperm motility among the groups.Spermatozoa in group 3 exhibited reduced apoptosis,necrosis,and ROS levels and increased viability.No significant differences were observed in the DNA fragmentation index among groups.The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs,suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracellular calcium mobilization[5].5-HT2B receptors are widely expressed throughout the gut,and experimental evidence suggests that the primary function of 5-HT2B receptors is to mediate contractile responses to 5-HT through its action on smooth muscle[6].The 5-HT2B receptor is localized to both neurons of the myenteric nerve plexus and smooth muscle in the human colon.The 5-HT2B receptor mediates 5-HT-evoked contraction of longitudinal smooth muscle[6].These findings suggest that the 5-HT2B receptor could play an important role in modulating colonic motility,which could affect sensory signaling in the gut.Other laboratories have shown that the 5-HT2B receptor participates in the development of mechanical and formalin-induced hyperalgesia[7,8].A 5-HT2B receptor antagonist reduced 2,4,6-trinitrobenzene sulfonic acid(TNBS)and stress-induced visceral hyperalgesia in rats[9,10].However,the role of the 5-HT2B receptor in IBS-D patients and in acetic acid-and wrap restraint-induced IBS-D rat models was not investigated.
基金supported by the National Science Foundation of China (32071503)the project of Wenzhou Science and Technology Plan (S20220011)
文摘Cold stress severely limits the distribution of mangrove species worldwide and it remains unclear how mangroves respond and adapt to cold temperatures.In this study,we investigated the effects of cold acclimation and/or inhibition of serotonin levels on reactive oxygen species(ROS),reactive nitrogen species(RNS),melatonin(MEL)and serotonin(SER)accumulation during cold stress in Kandelia obovata.Morphologic observation and param-eter analysis revealed that cold acclimation mitigated the photoinhibition of photosystem I(PSI)and photosystem II(PSII),maintained optimal ROS and RNS redox homeosta-sis,and increased the contents of SER and MEL in leaves.This suggests that cold acclimation reshapes the MEL/ROS/RNS redox network.In particular,the tryptophan/tryptamine/Ser/N-acetylserotonin/MER pathway was identi-fied as a branch of the MEL synthesis pathway.Inhibition of endogenous SER exacerbated damage caused by cold stress,indicating the crosstalk of SER synthesis and cold acclima-tion.In this study,we report a coordinated regulation of cold stress by a complex defense network in K.obovata.
基金supported by the National Natural Science Foundation of China(81590952)the“Jiebang Guashuai”Project of the Beijing University of Chinese Medicine(2022-JYB-JBZR-024).
文摘Objective:To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis(KOA).Methods:Forty SpragueeDawley rats were equally divided into control,model(1 mg of mono-iodoacetate into the right knee joint cavity),sham operation,manual acupuncture at right Tianjing acupoint(MAR-SJ 10),and left SJ 10 groups.Safranine-O and fast green staining were used to assess the modeling.The morphological and functional changes in mast cells(MCs)were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining.The levels of serotonin,histamine,substance P(SP),and tryptase at skin acupoints and serum levels of IL-β,IL-6,and TNF-αwere detected using ELISA.Results:After 14 days of treatment,the number of MCs and their degranulation rates were statistically higher in the model group than in the control group(both P<0.001).After applying acupuncture,the levels of 5-HT,HA,and SP at skin acupoints were lower than those in the model group(all P<0.05),and tryptase level was higher(both P<0.05).Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint(P=0.004).Compared with the model group,the serum levels of IL-1β,IL-6,and TNF-αin the MAR-SJ 10 and MAL-SJ 10 groups were lower(all P<0.05).Conclusion:Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidi-rectionally regulate local MCs of these acupoints.This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment,but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.
文摘BACKGROUND Serotonin syndrome(SS)is an underdiagnosed drug-induced clinical syndrome resulting from the excess intrasynaptic concentration of serotonin.Very limited information is available about chronic SS.AIM To evaluate the epidemiological,clinical,and other aspects of the insidious onset SS.METHODS We retrospectively evaluated 14 consecutive adult patients(>18 years)who had complaints for more than 6 wk at the time of consultation and met the Hunter criteria for SS.RESULTS The mean age was 41.1 years(range:21-61 years),with a male preponderance(64%).Although tremors were observed in all patients,this was a presenting complaint in only 43%of patients.Generalized body pain,insomnia,and restlessness were common presenting features(50%each).Other common clinical features were stiffness of the limbs(43%),diaphoresis(43%),gait disturbances(36%),bowel disturbances(36%),dizziness(29%),sexual dysfunctions(21%),incoordination(14%),and fatigue(14%)The mean duration of symptoms before the diagnosis of SS was 13.5±5.8 wk(range:6-24 wk).Amitriptyline was the most common drug(n=6,43%),followed by tramadol(n=5,36%)and sodium valproate(n=5,36%).All patients received cyproheptadine,a 5-hydroxytryptamine2A antagonist,as treatment and noted an excellent response CONCLUSION This study represents the largest study on chronic SS.We suggest that patients receiving serotonergic drugs should be physically examined for the presence of SS upon the development of new symptoms.
文摘<b><span style="font-family:Verdana;">Background:</span></b><span style="font-family:""><span style="font-family:Verdana;"> It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Ultra high-speed </span></span><span style="font-family:""><span style="font-family:Verdana;">liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive </span><span><span style="font-family:Verdana;">patients. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.
基金a grant from the Foundation of Guangdong Province of Science and Technology,No. 2003C3380
文摘BACKGROUND: Serotonin transporter (5-HTT) polymorphisms comprise 5-HTT gene-linked polymorphism region (5-HTTLPR) and variable number of tandem repeats (VNTR). Studies have revealed an association between 5-HTT polymorphism and major depressive disorder, which suggests that the "S" allele of 5-HTTLPR and Stin2.9 of 5-HTTVNTR are associated with major depressive disorder. However, there are a number of studies that do not support the 5-HTT polymorphism effect in major depressive disorder. OBJECTIVE: To study the relationship between 5-HTT gene polymorphism and major depressive disorder in Chinese Han population. DESIGN, TIME AND SETTING: Case-controlled study of 5-HTT gene polymorphism. The experiment was performed at the Central Laboratory, Third Affiliated Hospital of Sun Yat-sen University, China from March 2005 to January 2006. PARTICIPANTS: A total of 99 depressive patients of Chinese Han nationality were recruited for this study. All patients met DSM-IV diagnostic criteria for major depressive disorder and had a total score of Hamilton Depression Scale (24 items) ≥21 points. In addition, 101 healthy subjects, matched for age and gender, served as the control group. METHODS: Venous blood was collected from all subjects. 5-HTT genotypes and alleles were determined by polymerase chain reaction. Consistent with the Hardy-Weinberg equilibrium, the association between 5-HTT gene polymorphism and major depressive disorder were analyzed by Chi-square test. MAIN OUTCOME MEASURES: 5-HTTLPR and 5-HTTVNTR genotypes and allele frequencies were measured. RESULTS: No significant differences in 5-HTTLPR genotypes and allele frequencies were determined between patients and controls (P 〉 0.05). However, significant differences in 5-HTTVNTR genotypes and allele frequencies were detected (P 〈 0.01 ). The Stin2.10 allele and 10/10 genotype associated with major depressive disorder (OR = 2.61,7.7, P 〈 0.05; analysis of dose-response relationships Х^2 = 12.35, P 〈 0.01). CONCLUSION: Results from the present study revealed no association between 5-HTTLPR and major depressive disorder. However, a significant association between 5-HTTVNTR and major depressive disorder existed in a population of Chinese Han. The presence of Stin2.10 and 10/10 genotypes increased the risk for major depressive disorder in a dose-dependent manner.
文摘We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P 〈 0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.
文摘Serotonin (5-hydroxytryptamine, 5-HT) influences the cortical and subcortical excitatory/inhibitory balance and participates in the pathophysiological processes of epilepsy. The serotonin transporter (5-HTT) is the most important factor in serotonin inactivation. We tested whether 5-HTT polymorphisms are involved in the pathogenesis of epilepsy in Chinese Han population. We did not find a significant difference in the frequencies of genotypes and alleles in the 5-HTT gene-linked poLymorphic region (5-H-I-FLPR) in patients with non-lesional temporal lobe epilepsy and normal controls (P〉 0.05). Frequencies of the 5-H1-1- intron 2 variable number tandem repeat (5-HTTVNTR) 12/12 genotype and allele 12 were higher in the patients with non-lesional temporal lobe epilepsy than normal controls (P 〈 0.01). The odds ratio of affecting non-lesional temporal lobe epilepsy was 1.435 (95% Cl, 1.096 1.880) in patients carrying allele 12 (P 〈 0.05). Although the 5-HTTLPR may not be a genetic locus of non-lesional temporal lobe epilepsy in Chinese Hart population, allele 12 in the 5-HTTVNTR may correlate with non-lesional temporal lobe epilepsy. The Stin2.12 allele and 12/12 genotype could be predisposing to non-lesional temporal lobe epilepsy.
基金Supported by the National Natural Science Foundation of China,No.81300272,No.81470796,No.81570489 and No.81570478the Tianjin Research Program of Application Foundation and Advanced Technology of China,No.15JCZDJC36600
文摘Serotonin(5-HT) and the serotonin transporter(SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome(IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mR NA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microR NAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.
基金Supported by Innovation Program of the Shanghai Municipal Education Commission,No.12YZ065National Natural Science Foundation of China,No.81072786,No.81473630 and No.81202665+2 种基金Longhua Medical Project,No.D-09High level Project of the University of Educational Commission of Shanghai,China,No.2008GSP19Shanghai Leading Academic Discipline Project,No.J50305
文摘AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD were measured by high-performance liquid chromatography.A rat model of IBS was induced by chronic water avoidance stress(WAS).The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension.Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-αin colonic tissue and calcitonin-gene-related peptide(CGRP)in serum were measured by ELISA.The protein expression of serotonin[5-hydroxytryptamide(5-HT)],serotonin transporter(SERT),chromogranin A(Cg A)and CGRP incolon tissue was measured by immunohistochemistry.RESULTS:SGD inhibited colonic motility dysfunction and VHL in rats with IBS.Blockers of transient receptor potential(TRP)vanilloid 1(TRPV1)(Ruthenium Red)and TRP ankyrin-1(TRPA1)(HC-030031)and activator of protease-activated receptor(PAR)4 increased the pain pressure threshold,whereas activators of PAR2and TRPV4 decreased the pain pressure threshold in rats with IBS.The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1(capsaicin),TRPV4(RN1747),TRPA1(Polygodial)and PAR2(AC55541).In addition,CGRP levels in serum and colonic tissue were both increased in these rats.TNF-αlevel in colonic tissue was also significantly upregulated.However,the levels of 5-HT,SERT and Cg A in colonic tissue were decreased.All these pathological changes in rats with IBS were attenuated by SGD.CONCLUSION:SGD alleviated VHL and attenuated colon motility in IBS,partly by regulating TRPV1,TRPV4,TRPA1,PAR2,5-HT,Cg A and SERT,and reducing CGRP and TNF-αlevel.
基金the National Natural Science Foundation of China,No.81570489
文摘AIM To evaluate the effect of Lactobacillus rhamnosus GG supernatant(LGG-s) on the expression of serotonin transporter(SERT) in rats with post-infectious irritable bowel syndrome(PI-IBS).METHODS Campylobacter jejuni 81-176(1010 CFU/m L) was used to induce intestinal infection to develop a PI-IBS model. After evaluation of the post-infectious phase by biochemical tests, Dn A agarose gel electrophoresis, abdominal withdrawal reflex(AWR) test, and the intestinal motility test, four PI-IBS groups received different concentrations of LGG-s for 4 wk. The treatments were maintained for 1.0, 2.0, 3.0 or 4.0 wk during the experiment, and the colons and brains were removed for later use each week. SERT m Rn A and protein levels were detected by real-time PCR and Western blot, respectively.RESULTS The levels of SERT m Rn A and protein in intestinal tissue were higher in rats treated with LGG-s than in control rats and PI-IBS rats gavaged with PBS during the whole study. Undiluted LGG-s up-regulated SERT m Rn A level by 2.67 times compared with the control group by week 2, and SERT m Rn A expression kept increasing later. Double-diluted LGG-s was similar to undiluted-LGG-s, resulting in high levels of SERT m Rn A. Triple-diluted LGG-s up-regulated SERT m Rn A expression level by 6.9-times compared with the control group, but SERT m Rn A expression decreased rapidly at the end of the second week. At the first week, SERT protein levels were basically comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triplediluted LGG-s, which were higher than those in the control group and PBS-treated PI-IBS group. SERT protein levels in the intestine were also comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triple-diluted LGG-s by the second and third weeks. SERT m Rn A and protein levels in the brain had no statistical difference in the groups during the experiment.CONCLUSION LGG-s can up-regulate SERT m Rn A and protein levels in intestinal tissue but has no influence in brain tissue in rats with PI-IBS.
文摘Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE), Our objective in this study was to characterize the efficacy of on-demand dapoxetine (30 and 60 mg) and daily paroxetine (20 mg) usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine (30 mg), Group 2 with on-demand dapoxetine (60 mg) and Group 3 with daily paroxetine (20 rag), Our outcome measurement was increased from baseline intravaginal ejaculatory latency time (IELT) after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group (P 〈 0,01), 30 mg dapoxetine group (P 〈 0,01) and 60 mg dapoxetine group (P 〈 0.01), respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups (P 〉 0,05), while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine (P〈 0.05) and paroxetine (P〈 0.01) groups, Dapoxetine (60 mg) 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.