Search

Stress triggers a set of adaptative reactions that can compromise the homeostasis of the organism, such as transport from one environment to another. The aim of the present study was to determine whether there is a periodic variation in serotonin levels following transport stress. We used a databank to obtain data on plasma serotonin levels of healthy adult horses collected at regular eight-hour intervals for three consecutive days on two different occasions: before and after transport. The results were tabulated and submitted to Hurst statistical analysis procedures. Curves were created of the variation in serotonin levels as a function of time using the cosinor method. Plasma serotonin levels exhibited circadian variations independently of sex and age. The circadian variation pattern was significantly affected when the animals experienced transport stress (p < 0.05). Thus, plasma serotonin levels can be used as an indicator of physiological disorders and the promotion of animal wellbeing. [ABSTRACT FROM AUTHOR]

Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood–brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors. [ABSTRACT FROM AUTHOR]

Background: Social behaviour is the expression of one of the most generally accepted independent dimensions of personality. Serotonergic neurotransmission has been implicated in typical social response and drugs that promote serotonin (5-hydroxytryptamine (5-HT)) release have prosocial effects. By using the social interaction test, we have previously demonstrated sociability as a temperamental trait in male Wistar rats. Aims: To assess sociability in male rats of the Sprague–Dawley strain and in female rats of both Wistar and Sprague–Dawley strain, and extracellular levels of 5-HT in rats with high and low sociability (high sociability (HS)- and low sociability (LS)-rats). Methods: Social interaction test conducted with different weight-matched partners was used to assess sociability, and in vivo, microdialysis was performed before and after administration of a low dose (2 mg/kg) of parachloroamphetamine (PCA) in the prefrontal cortex, dorsamedial striatum and ventral tegmental area. Results: Similarly to male Wistar rats, female Wistars and Sprague–Dawley rats of both sexes displayed trait-wise sociability. Male Wistar HS-rats had lower extracellular levels of 5-HT in prefrontal cortex at baseline and after administration of PCA, and higher PCA-induced increase of extracellular 5-HT in ventral tegmental area. In dorsomedial striatum, PCA elicited a comparable increase in extracellular dopamine in HS- and LS-rats, but higher release of 5-HT in HS-rats. Comparison of PCA-induced 5-HT release in prefrontal cortex of male and female Sprague–Dawley rats revealed a larger 5-HT response in female HS-rats. Conclusions: 5-HT release potential is higher in rats with high expression of sociability trait, whereas some regionally variable differences may be related to relative contributions of social motivation and anxiety in shaping social behaviour. [ABSTRACT FROM AUTHOR]

Background: Current evidence underlines the active role of neural infiltration and axonogenesis within the tumor microenvironment (TME), with implications for tumor progression. Infiltrating nerves stimulate tumor growth and dissemination by secreting neurotransmitters, whereas tumor cells influence nerve growth and differentiation through complex interactions, promoting tumor progression. However, the role of neural infiltration in the progression of non-small cell lung cancer (NSCLC) remains unclear. Methods: This study employs the techniques of immunohistochemistry, immunofluorescence, RNA sequencing, molecular biology experiments, and a murine orthotopic lung cancer model to deeply analyze the specific mechanisms behind the differential efficacy of NSCLC immunotherapy from the perspectives of neuro-tumor signal transduction, tumor metabolism, and tumor immunity. Results: This study demonstrates that nerve growth factor (NGF) drives neural infiltration in NSCLC, and 5-hydroxytryptamine (5-HT), which is secreted by nerves, is significantly elevated in tumors with extensive neural infiltration. Transcriptome sequencing revealed that 5-HT enhanced glycolysis in NSCLC cells. Pathway analysis indicated that 5-HT activated the PI3K/Akt/mTOR pathway, promoting tumor metabolic reprogramming. This reprogramming exacerbated immunosuppression in the TME. Neutralizing 5-HT-mediated metabolic reprogramming in tumor immunity enhanced the efficacy of PD-1 monoclonal antibody treatment in mice. Conclusions: The findings of this study provide a novel perspective on the crosstalk between nerves and lung cancer cells and provide insights into further investigations into the role of nerve infiltration in NSCLC progression. [ABSTRACT FROM AUTHOR]

Spiders are an abundant group of natural enemies preying on insect pests in agroecosystem. But their potential in biological control has not been fully realized due to difficult mass production. One hindrance is the intense intraspecific aggression in spiders. Neurotransmitters such as serotonin play important roles in modulating aggression. Here, we investigated the regulatory function of serotonin (5‐hydroxytryptamine [5‐HT]) signaling in the intraspecific aggression in a wandering spider Pardosa pseudoannulata (Araneae, Lycosidae). The aggression was quantified with 5 escalated aggression behaviors as approach, chasing, lunging, boxing, and biting. Virgin (VG) females exhibited higher aggression levels but less 5‐HT content than post‐reproductive (PR) females. Systemic increase of 5‐HT via 5‐HT injection decreased aggression, while decrease of 5‐HT via RNA interference (RNAi) of the tryptophan hydroxylase gene, increased aggression. The involvement of the four 5‐HT receptors were determined via individual or combined RNAi. Co‐RNAi of the three 5‐HT1 genes increased overall aggression with decreased incidents of approach, chasing, lunging, and increased biting. RNAi of 5‐HT1B decreased approach and increased biting, whereas RNAi of 5‐HT1A or 5‐HT1C did not affect aggression. RNAi of 5‐HT7 decreased approach only. Therefore, different 5‐HT receptor types contribute to different aspects of the inhibitory effects of 5‐HT on aggression and provide several pharmacological targets for manipulating spider aggression. 5‐HT injection did not affect spiders’ predation on their insect prey, the brown planthopper Nilaparvata lugens. The findings reveal 1 neuronal mechanism regulating intraspecific aggression in spiders and provide an insight in developing aggression suppression strategies for spider mass rearing. [ABSTRACT FROM AUTHOR]

Background: Chewing Khat (Catha edulis) releases cathine and cathinone, which may reduce appetite via an unknown mechanism. This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract (CEWE) on appetite biomarkers, gene expression, and body weight, using in vivo, ex vivo, and in silico models. Methods: Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments. Liquid chromatography-mass spectroscopy (LC-MS)-MS was used to detect cathinone and cathine in the murine blood. The effect of Khat on serotonin receptors was studied in isolated rat fundus samples. Docking of the two Khat ligands was performed on G (The 5-hydroxytryptamine-type 2C receptor (5-HT2C) in an agonist-bound active conformation) and H (5-HT2C in an antagonist-bound inactive conformation) proteins to determine which ligands are most likely to act as agonists or antagonists. Results: Significant differences (P < 0.05) in body weight were observed between the CEWE-treated groups and the controls over eight weeks. However, the plasma leptin and ghrelin levels did not change significantly (P > 0.05). The expression of the ghrelin and leptin genes was also unaffected, but the expression of the 5-hydroxytryptamine (5-HT) gene decreased (P < 0.05) with CEWE treatment. CEWE antagonizes 5-HT receptors in isolated rat fundus samples. Docking findings indicated that the khat ligands bound to 5-HT2C receptors. Cathine and cathinone levels in rat plasma were measured. Conclusion: Khat extract may suppress appetite by antagonizing the 5-HT receptors. Further research is required to understand its mechanism and potential applications. [ABSTRACT FROM AUTHOR]

Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a -knockout (Htr1a –/–) rats and vascular smooth muscle cell (VSMC)–specific Htr1a -knockout (Htr1a ΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3′,5′-cyclic monophosphate pathway–mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation–, and partial PV ligation–induced PH. Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment. HTR1A antagonist, such as alverine, decreases portal hypertension in preclinical animals by targeting the portal vein and is expected to become a candidate for the clinical treatment of portal hypertension. [ABSTRACT FROM AUTHOR]

Depression is a prevalent mental disorder, but the side effects of antidepressants also make depressed patients resistant. Effective and safe antidepressants should be developed from traditional herbs, with the aim of reducing the side effects of antidepressants and improving the efficacy of drugs. In this study, the new macamide compound‐4 (NMC‐4) was synthesized for the first time, addressing the problem of difficult extraction, isolation, and low content of natural macamide. NMC‐4 was characterized using mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy. The protective effect of NMC‐4 against cell injury was demonstrated to be stronger than that of natural macamide (N‐benzylhexadecanamide, XA) using a PC12 cell injury model. The study explored the effects of NMC‐4 on chronic unpredictable mild stress (CUMS)‐induced depressive symptoms. NMC‐4 significantly improved depressive‐like behaviors. NMC‐4 ameliorated CUMS‐induced depressive‐like behaviors by mitigating neuroinflammation and modulating the NF‐κB/Nrf2 and BDNF/PI3K/Akt pathways. [ABSTRACT FROM AUTHOR]

5-Hydroxytryptamine (5-HT) is an inhibitory neurotransmitter widely distributed in mammalian tissues, exerting its effects through binding to various receptors. It plays a crucial role in the proliferation of granulosa cells (GCs) and the development of follicles in female animals, however, its effect on porcine follicle development is not clear. The aim of this study is to investigate the expression of 5-HT and its receptors in various parts of the pig ovary, as well as the effect of 5-HT on porcine follicular development by using ELISA, quantitative real-time PCR (qPCR) and EdU assays. Firstly, we examined the levels of 5-HT and its receptors in porcine ovaries, follicles, and GCs. The findings revealed that the expression of different 5-HT receptors varied among follicles of different sizes. To investigate the relationship between 5-HT and its receptors, we exposed the GCs to 5-HT and found a decrease in 5-HT receptor expression compared to the control group. Subsequently, the treatment of GCs with 0.5 μM, 5 μM, and 50 μM 5-HT showed an increase in the expression of cell cycle-related genes, and EdU results indicated cell proliferation after the 0.5 μM 5-HT treatment. Additionally, the expression of genes involved in E2 synthesis was examined after the treatment of granulosa cells with 0.5 μM 5-HT. The results showed that CYP19A1 and HSP17β1 expression was decreased. These results suggest that 5-HT might affect the development of porcine follicle by promoting the proliferation of GCs and inhibiting the synthesis of estrogen. This provides a new finding for exploring the effect of 5-HT on follicular development, and lays a foundation for further research on the mechanism of 5-HT in follicles. [ABSTRACT FROM AUTHOR]

Background: Premature ejaculation (PE) is the most prevalent sexual dysfunction among men. Eejaculation involves a complex nervous mechanism in which the ejaculatory centers play a key role in modulating sperm emission. Although treatment possibilities span from psychotherapy to pharmacological approaches, results show inconsistent efficacy. In this context, the emergence of repetitive transcranial magnetic stimulation (rTMS) as a non‐invasive neuromodulatory approach represents a compelling avenue for potential therapeutic exploration. Objective: To investigate whether high‐frequency transcranial magnetic stimulation can modulate the ejaculatory behavior of rats with rapid ejaculation by altering neurotransmitter levels and neuroplasticity in the hippocampus. Methods: Rats have been screened for rapid ejaculation by observing behavioral indices of mating, and subsequently divided into two groups. The intervention group was administered with a 10 Hz rTMS stimulation, whereas the control group received a sham procedure. Upon the delivery of rTMS, we investigated ejaculation latency (EL), the hippocampal 5‐hydroxytryptamine (5‐HT) concentration, brain‐derived neurotrophic factor (BDNF), synaptophysin (SYN), and postsynaptic density protein 95 (PSD95) expressions, as well as BDNF‐receptor tyrosine kinase receptor B (TrkB) pathway upregulation. Results: After 14 days, EL was increased in the intervention group compared with the control group. 5‐HT concentration in the hippocampal region was increased, and high‐frequency rTMS activated the BDNF and TrkB pathways, including phosphorylation of cAMP response element‐binding protein (CREB), and upregulated the transcription and protein expression of SYN, and PSD95. Conclusion: RTMS upregulates BDNF, SYN, and PSD95 expression through activation of the BDNF–TrkB pathway and increases brain 5‐hydroxytryptamine thereby regulating neuroplasticity and improving ejaculation. [ABSTRACT FROM AUTHOR]

Abstract Background Current evidence underlines the active role of neural infiltration and axonogenesis within the tumor microenvironment (TME), with implications for tumor progression. Infiltrating nerves stimulate tumor growth and dissemination by secreting neurotransmitters, whereas tumor cells influence nerve growth and differentiation through complex interactions, promoting tumor progression. However, the role of neural infiltration in the progression of non-small cell lung cancer (NSCLC) remains unclear. Methods This study employs the techniques of immunohistochemistry, immunofluorescence, RNA sequencing, molecular biology experiments, and a murine orthotopic lung cancer model to deeply analyze the specific mechanisms behind the differential efficacy of NSCLC immunotherapy from the perspectives of neuro-tumor signal transduction, tumor metabolism, and tumor immunity. Results This study demonstrates that nerve growth factor (NGF) drives neural infiltration in NSCLC, and 5-hydroxytryptamine (5-HT), which is secreted by nerves, is significantly elevated in tumors with extensive neural infiltration. Transcriptome sequencing revealed that 5-HT enhanced glycolysis in NSCLC cells. Pathway analysis indicated that 5-HT activated the PI3K/Akt/mTOR pathway, promoting tumor metabolic reprogramming. This reprogramming exacerbated immunosuppression in the TME. Neutralizing 5-HT-mediated metabolic reprogramming in tumor immunity enhanced the efficacy of PD-1 monoclonal antibody treatment in mice. Conclusions The findings of this study provide a novel perspective on the crosstalk between nerves and lung cancer cells and provide insights into further investigations into the role of nerve infiltration in NSCLC progression.

Objective(s): Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease with high mortality. Isorhamnetin (ISO), one of the main natural flavonoids extracted from sea buckthorn, has pharmacological effects such as anti-inflammatory, anti-proliferative and antioxidant. This study aimed to investigate the protective effect of ISO on PAH and its relationship with the phosphorylation of the c-Src tyrosine kinase (p-c-src)/NOX1 signaling pathway. Materials and Methods: Ninety-five rats were randomly divided into five groups. The normal group received only a subcutaneous injection of saline, while the other groups received a subcutaneous injection of monocrotaline(MCT) (60 mg/kg) to establish a PAH model. The treatment group received ISO (50, 100, 150 mg/kg/d) treatment for 21 days, and after 21 days, all rat lung tissues were separated. Results: The results showed that ISO could significantly improve the hemodynamics of MCT-induced PAH rats, such as mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), and had inhibitory effects on right ventricular hypertrophy in PAH rats, and on pulmonary vascular remodeling in PAH rats. In addition, ISO can reduce the content of 5-hydroxytryptamine (5-HT) in PAH rats, increase the expression of Nrf2 protein in the lung tissue of PAH rats, activate the antioxidant system, enhance the activity of SOD in lung tissue of PAH rats, and inhibit NOX1, 5-HTT, p-c-src and Proliferating Cell Nuclear Antigen(PCNA) protein expression, and decrease MDA content. Conclusion: Our research confirmed the therapeutic effect of ISO on MCT-induced PAH rats, which may be related to regulating the p-c-src/NOX1 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate the hemostatic effect of modified Sijunzi Granules (MSG) in primary immune thrombocytopenia (ITP) zebrafish model and explore the potential mechanism. Methods: AB strain wild type zebrafish were treated with simvastatin (6 µmol/L) for 24 h to establish the hemorrhage model (model control group). The zebrafish were treated with MSG at different doses (55.6, 167, and 500 µg/mL), respectively. The hemostatic effect was assessed by examining the intestinal bleeding and hemostatic rate. 5-Hydroxytryptamine (5-HT) content was determined using enzyme-linked immunosorbent assay (ELISA) assay. The expressions of 5-HT2aR, 5-HT2bR, and SERT genes were detected by quantitative real-time polymerase chain reaction(PCR). The protein expressions of protein kinase B (Akt), p-Akt, extracellular regulated protein kinases (Erk), and p-Erk were examined using Western blot analysis. Results: The intestinal bleeding rate was 37%, 40%, and 80% in the 55.6, 167, and 500 µg/mL dose of MSG, respectively, in which 55.6 and 167 µg/mL MSG dose groups were associated with significantly decreased intestinal bleeding rate when compared with the model control group (70%, P<0.05). Significantly higher hemostatic rates were also observed in the 55.6 (54%) and 167 (52%) µg/mL MSG dose groups (P<0.05). MSG increased the 5-HT content and mRNA expression levels of 5-HT2aR, 5-HT2bR, and SERT (P<0.05). In addition, caspase3/7 activity was inhibited (P<0.05). Significant increase in p-Akt and p-Erk was also detected after treatment with MSG (P<0.05). Conclusions: MSG could reduce the incidence and severity of intestinal bleeding in zebrafish by activating MAPK/Erk and PI3K/Akt signal pathways through regulating the levels of 5-HT and its receptors, which may provide evidence for the treatment of ITP. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of baicalein on T helper cells (Th) 1/2, obestatin and 5-hydroxytryptamine (5-HT) in rats with ulcerative colitis. Methods Forty SPF grade male SD rats were randomly divided into normal group (group N), model group (group M), sulfasalazine group (group S), and baicalein group (group B), with 10 rats in each group. The ulcerative colitis models were established in group M, S and B by trinitrobenzenesulfonic acid. After successful modeling, 0.3 g/kg sulfasalazine was given to group S by gavage, and 50 mg/kg baicalein was given to group B by gavage. Group N and group M were given the same volume of normal saline by gavage at the same time. The disease activity index (DAI) score and colon mucosa damage index (CMDI) score of rats were evaluated, and the pathological morphology of colon tissue was detected by hematoxylin and eosin staining. The protein expression of Th1 cytokine interferon-γ (IFN-γ) and Th2 cytokine interleukin-4 (IL-4) in colon tissues was detected by western blot, and the levels of obestatin and 5-HT in rat serum were detected by ELISA. Results All rats were successfully modeled. The DAI score and CMDI score were significantly increased in group M compared to those in group N (P

Abstract Background Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.

ABSTRACT: High Fischer ratio oligopeptides (HFROs) are a group of oligopeptides containing high levels of branched-chain amino acids (BCAA) and low levels of aromatic amino acids (AAA). HFROs have received a lot of attention as they are believed to have significant physiological activities, including antioxidant, liver damage repair, anti-fatigue, anti-tumor and energy supply to the body. HFROs are available from a wide range of sources and both plant and animal proteins can be used to prepare HFROs but the physiological tolerability and rejection of special populations needs to be considered. Enzymatic hydrolysis is the most common method for the preparation of HFROs, but optimization of the separation and purification process is still needed in the future. Diseases caused by disruptions in the balance of BCAA and AAA in the blood, such as hepatic encephalopathy, can be treated by supplementing HFROs with drugs or food. In addition, HFROs are able to reduce fatigue feedback and assist in the treatment of phenylketonuria at the molecular nutrient level. The aim of this review is to review recent research on HFROs and provide new perspectives on the high value use of crops and the development of novel functional and special medical purpose foods.

To better understand mechanisms of serotonin‐ (5‐HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5‐HT or selective 5‐HT receptor agonists. Vessels were pre‐contracted with 1 × 10−4 M phenylephrine and exposed to increasing concentrations of 5‐HT or 5‐HT receptor agonists that were selective for 5‐HT1B, 5‐HT2B, 5‐HT4, and 5‐HT7. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre‐contraction. At 1 × 10−7 M 5‐HT, a relaxation was observed with an 88.7% decrease (p < 0.01) from the phenylephrine maximum. At 1 × 10−4 M 5‐HT, a contraction was observed with a 165% increase (p < 0.01) from the phenylephrine maximum. Increasing concentrations of agonists selective for 5‐HT2B, 5‐HT4, or 5‐HT7 resulted in a 27%, 92%, or 44% (p < 0.01) decrease from the phenylephrine maximum, respectively. Of these 5‐HT receptor agonists, the selective 5‐HT4 receptor agonist resulted in the greatest potency (−log EC50) value (6.30) compared with 5‐HT2B and 5‐HT7 receptor agonists (4.21 and 4.66, respectively). To confirm the involvement of 5‐HT4 in 5‐HT‐mediated vasorelaxation, blood vessels were exposed to either DMSO (solvent control) or a selective 5‐HT4 antagonist (1 × 10−5 M) for 5‐min prior to the phenylephrine pre‐contraction and 5‐HT additions. Antagonism of the 5‐HT4 receptor attenuated the vasorelaxation caused by 5‐HT. Approximately 94% of the vasorelaxation occurring in response to 5‐HT could be accounted for through 5‐HT4, providing strong evidence that 5‐HT‐mediated vasorelaxation occurs through 5‐HT4 activation in bovine peripheral vasculature. [ABSTRACT FROM AUTHOR]

Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. Methods: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. Results: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. Conclusion: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects. [ABSTRACT FROM AUTHOR]

Background: Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods: The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results: In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion: Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice. [ABSTRACT FROM AUTHOR]

BACKGROUND: The treatment of post-stroke dysphagia with Lipopharyngeal Qibi Formula has achieved good efficacy, and 5-hydroxytryptamine in peripheral serum and neurotransmitters in the nucleus tractus solitarius are closely related to swallowing. Therefore, this study was conducted to explore the modulatory effects of peripheral serum and nucleus tractus solitarius neurotransmitters in swallowing by using modern medical experimental methods such as molecular biology, thereby developing new ideas for the exploration of their mechanisms. OBJECTIVE: To verify the therapeutic effect of Lipopharyngeal Qibi Formula on post-stroke dysphagia and to investigate its mechanism of action. METHODS: Thirty-eight Sprague-Dawley rats were randomly divided into model group (n=14), treatment group (n=14) and sham-operated group (n=10). Animals in the model and treatment groups were modeled by reperfusion after 90 minutes of transient cerebral ischemia by wire bolus method. At 6 hours after modeling, neurological function was scored, and rats with a score of 2 were selected for subsequent experiments. The treatment group was given compound Lipopharyngeal Qibi Formula by gavage starting from the 2nd day after modeling and the remaining two groups were given normal saline by gavage. Changes in body mass, 24-hour food and water intake were recorded on days 2, 7, 14 and 30. The swallowing initiation response time and the number of swallows were detected using a biosignal collector and a tonic transducer on days 14 and 30. After the swallowing test, the ischemic area of the brain in each group was measured by TTC staining. The expression of 5-hydroxytryptamine in the nucleus tractus solitarius of the medulla oblongata was measured by immunohistochemistry. The mRNA and protein expression levels of BCL-2 and BAX in the insula, premotor cortex, cingulate cortex and thalamus of rats in each group were measured by RT-PCR and Western blot, respectively. RESULTS AND CONCLUSION: Compared with the sham-operated group, the body mass, 24-hour food intake and water intake were reduced, the swallow initiation response time was prolonged, and the number of swallows was reduced in the treatment and model groups at day 14 of gavage (P < 0.05). Compared with the model group, the body mass, 24-hour food intake and water intake of rats were increased in the treatment group at day 30 of gavage (P < 0.05), but were still lower than those in the sham-operated group. Compared with the model group, the swallow initiation reaction time was shortened and the number of swallows increased in the treatment group, but the number of swallows was still significantly lower than that in the sham-operated group (P < 0.05). Cerebral ischemia area was reduced in the treatment group compared with the model group, and the number of 5-hydroxytryptamine-positive cells in the nucleus tractus solitarius of the medulla oblongata was increased in the treatment group compared with the model group, but it was still significantly lower than that in the sham-operated group (P < 0.05). Compared with the model group, the expression of BCL-2 mRNA and protein in the insula, cingulate cortex and thalamus of rats in the treatment group were significantly increased, the expression of BAX mRNA and protein were significantly decreased, and the BCL-2/BAX ratio was significantly increased (P < 0.05). To conclude, the Chinese herbal compound Lipopharyngeal Qibi Formula could improve the number of swallows and swallowing initiation response time, as well as 24-hour food intake, body mass and other swallowing-related indexes in rats with post-stroke dysphagia. The mechanism of action may be achieved by improving the area of cerebral ischemia, inhibiting the apoptosis of neuronal cells in the insula, cingulate cortex and thalamus of rats, thus improving the regulation of the higher centers on the medulla oblongata swallowing center, and regulating the level of 5-hydroxytryptamine in the nucleus tractus solitarius. [ABSTRACT FROM AUTHOR]

Background and Purpose: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N‐dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA‐treated rats. Experimental Approach: We focused on the 5‐HT1A and 5‐HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. Key Results: A single oral treatment with AYA containing 0.3 mg·kg−1 of DMT increased the within‐session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1‐ and 21‐day‐old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA‐ and vehicle‐treated animals showed no differences when tested in the elevated plus‐maze. The 5‐HT2A receptor antagonist MDL‐11,939 and the 5‐HT1A receptor antagonist WAY‐100635 infused into the infralimbic cortex respectively blocked within‐ and between‐session fear extinction effects resulting from repeated oral administration of AYA. Conclusion and Implications: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress‐related disorders. [ABSTRACT FROM AUTHOR]

Essential hypertension is a psychosomatic disease associated with emotions and behaviors. Although Mongolian mind–body interactive therapy can help patients with essential hypertension reduce their systolic blood pressure (SBP), the mechanism is unclear. We assigned patients who underwent Mongolian mind–body interactive therapy to groups that were treated with (DT) or without (NDT) antihypertensive drugs (Clinical registration no: ChiCTR2000034918). We screened differentially expressed genes (DEGs) using targeted metabolic and transcriptomic analyses of blood samples before and after intervention. Sequenced data were analyzed using quantitative polymerase chain reaction (qPCR) and validated using enzyme-linked immunosorbent assays (ELISAs). Small interfering (Si)-RNA interference on key DEGs in human umbilical vein endothelial cells (HUVECs) was experimentally verified. Omics analysis identified 187 DEGS, including human 5-hydroxytryptamine (5-HT) receptor 2B (5-HTR2B), human endothelin receptor type B (EDNRB), and the metabolite N-acetylserotonin. The qPCR and transcriptome sequencing results were consistent. Post-intervention ELISA assays revealed significantly elevated 5-HT in the NDT group after intervention (P

Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic. [ABSTRACT FROM AUTHOR]

Stress is a common risk factor for emotional and cognitive dysfunction during mammalian growth and development. The hippocampal neurogenesis, which regulates the stress response, is highly susceptible to stress stimuli. This review focuses on the pathomechanism underlying how stress stimuli affect hippocampal neurogenesis and explores the impact of aberrant 5-hydroxytryptamine (5-HT) system, including 5-HT, 5-HT receptors and 5-HT neurons, on stressinduced impairment of hippocampal neurogenesis. By summarizing existing research, we aim to provide new ideas for the treatment of post-traumatic stress disorder and depression. [ABSTRACT FROM AUTHOR]

Objective To investigate the changes in levels of serum monocyte chemotactic protein-1 (MCP-1) and 5-hydroxytryptamine (5-HT) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and their clinical significance. Methods Totally 107 OSAHS patients (OSAHS group) were selected and divided into the MCI group (43 cases) and NMCI group (64 cases) according to whether mild cognitive impairment (MCI) occurred or not, and 48 healthy volunteers with medical checkups in the same period (control group) were selected. Serum MCP-1 and 5-HT levels were measured by ELISA. Factors affecting the occurrence of MCI in OSAHS patients were analyzed by multifactorial Logistic regression, and the predictive value of serum MCP-1 and 5-HT levels for MCI in OSAHS patients was analyzed by receiver operating characteristic (ROC) curve. Results Compared with the control group, the serum MCP-1 level increased and 5-HT level decreased in the OSAHS group (both P<0. 05). The incidence of MCI in 107 OSAHS patients was 40. 19% (43/107). Compared with the NMCI group, the serum MCP-1 level increased and 5-HT level decreased in the MCI group (both P<0. 05). Increasing age, severity of disease and elevated MCP-1 were independent risk factors for the development of MCI in patients with OSAHS, and elevated 5-HT was an independent protective factor (all P<0. 05). The area under the curve of serum MCP-1 and 5-HT in predicting MCI in patients with OSAHS was 0. 906, which was greater than that (0. 805, 0. 828) of serum MCP-1 and 5-HT alone (both P<0. 05). Conclusion The elevated serum MCP-1 level and reduced 5-HT level in OSAHS patients are closely associated with MCI, and the combination detection of serum MCP-1 and 5-HT has a high predictive value for the occurrence of MCI in OSAHS patients. [ABSTRACT FROM AUTHOR]

Objective We aimed to investigate the hemostatic effect and mechanism of modified Sijunzi Decoction (MSJZT), consisting of tangshen, India bread, largehead atractylodes rhizome, liquorice root, milkvetch root, ass hide glue, and India madder root, on the zebrafish intestinal bleeding model through 5-hydroxytryptamine (5-HT) and its receptors (5-HT2aR, 5-HT2bR). Methods Zebrafish at 4 days post fertilization were used as the research object. An intestinal bleeding model was established by induction with 6 µmol/L simvastatin for 24 hours. The zebrafish were divided into normal group, model group, MSJZT low-, mid- and high-concentration groups (55.6, 167, 500 mg/L), and after modeling, the corresponding concentration of MSJZT was administered. The samples were collected after 24 hours. Platelet count (PLT) and bleeding status were observed. The content of 5-HT and Caspase 3/7 activity were detected by colorimetry. The gene expressions of 5-HT2aR, 5-HT2bR and serotonin transporter (SERT) were detected by real-time PCR. The protein expressions of protein kinase B (AKT), phosphorylated AKT (p-AKT), extracellular signal-regulated protein kinase (ERK), and phosphorylated ERK (p-ERK) were detected by Western blotting. Results The intestinal bleeding rate in the model group was 70.0%, and that in the MSJZT low-, mid- and high-concentration groups was 36.7%, 40.0%, and 80.0%, respectively; the intestinal hemostatic effect was 54%, 52%, and 7%, respectively. Compared with the model group, the PLT in the MSJZT low- and mid-concentration groups decreased; the content of 5-HT in all MSJZT groups increased, and the gene expressions of 5-HT2aR and 5-HT2bR were up-regulated. The gene expression of SERT was up-regulated in the low- and mid-concentration groups; the Caspase 3/7 activity in the mid- and high-concentration groups was reduced; the expressions of p-AKT and p-ERK proteins were up-regulated in the low- and mid-concentration groups (all P<0.05). Conclusion MSJZT can reduce the incidence and severity of intestinal bleeding in zebrafish intestinal bleeding models. The mechanism may be achieved by activating AKT and ERK signaling pathways through 5-HT and its receptors. [ABSTRACT FROM AUTHOR]

5-hydroxytryptamine (5-HT) is an important neurotransmitter in brain-gut axis pathway, and its secretion is closely related to intestinal flora, intestinal immunity and intestinal motility. Abnormal metabolic pathway of 5-HT is involved in the occurrence and development of gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, chronic constipation and functional dyspepsia. This article reviews the mechanism of 5-HT in different gastrointestinal diseases in order to explore new ideas for clinical treatment. [ABSTRACT FROM AUTHOR]

The ratiometric electrochemical sensors have been highly explored to minimize system errors and environmental interference. However, it is extremely desirable on the development of an effective ratiometric electrochemical sensor in a facile approach without the complicated assembly process. In this work, an effective internal reference probe was coupled based on the polymerized thionine (pTh) via a one‐step electrodeposition method. The ratiometric electrochemical sensing platform was applied for 5‐hydroxytryptamine (5‐HT) detection, where the internal reference probe, Th, presented the robust redox signal and can be clearly distinguished from the oxidation signal of 5‐HT. The proposed pTh modified GCE presented the outstanding electrochemical performance on sensing 5‐HT in a wide concentration range with a detection limit of 8.4 nΜ. Further, the fabricated sensor was efficiently employed for the detection of 5‐HT in various human serum samples and the obtained results were consistent with the reported range in serum samples. This work offers the great possibility on the fabrication of efficient ratiometric sensors in a facile approach and presents great application prospects in clinical diagnosis. [ABSTRACT FROM AUTHOR]

The risk of acquiring new intramammary infections is high at the end of lactation, especially for the high milk-producing dairy animals. Resistance to bacterial infection increases following the completion of mammary gland involution after milking cessation. The serotonin precursor 5-hydroxytryptophan (5-HTP) could accelerate involution by increasing circulating serotonin levels, but ruminal microbes may degrade 5-HTP if orally administered to adult ruminants. It is unclear whether rumen-protected 5-HTP could effectively mediate circulating serotonin (5-hydroxytryptamine, 5-HT) and therefore accelerate mammary gland involution in ruminants. Goats were used as a model in the current study to investigate the effects of rumen-protected 5-HTP on behaviour, 5-HT metabolism, and mammary involution in ruminants. In the first experiment, 16 female Dazu black goats were assigned to one of four groups in a randomised block design. The treatments included a basal diet plus 0, 4, 20, or 100 mg/kg BW of rumen-protected 5-HTP. Serum was collected at 0, 3, 6, 12, and 24 h after offering the rumen-protected 5-HTP in the morning feed, and the behaviours were monitored. In the second experiment, 12 female Dazu black goats (Somatic cell count

Abstract To better understand mechanisms of serotonin‐ (5‐HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5‐HT or selective 5‐HT receptor agonists. Vessels were pre‐contracted with 1 × 10−4 M phenylephrine and exposed to increasing concentrations of 5‐HT or 5‐HT receptor agonists that were selective for 5‐HT1B, 5‐HT2B, 5‐HT4, and 5‐HT7. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre‐contraction. At 1 × 10−7 M 5‐HT, a relaxation was observed with an 88.7% decrease (p

Research has shown that a significant portion of cancer patients experience depressive symptoms, often accompanied by neuroendocrine hormone imbalances. Depression is frequently associated with decreased levels of serotonin with the alternate name 5-hydroxytryptamine (5-HT), leading to the common use of selective serotonin reuptake inhibitors (SSRIs) as antidepressants. However, the role of serotonin in tumor regulation remains unclear, with its expression levels displaying varied effects across different types of tumors. Tumor initiation and progression are closely intertwined with the immune function of the human body. Neuroimmunity, as an interdisciplinary subject, has played a unique role in the study of the relationship between psychosocial factors and tumors and their mechanisms in recent years. This article offers a comprehensive review of serotonin's regulatory roles in tumor onset and progression, as well as its impacts on immune cells in the tumor microenvironment. The aim is to stimulate further interdisciplinary research and discover novel targets for tumor treatment.

Objective To investigate the relationship between Helicobacter pylori （Hp） infection and serum gastrointestinal hormones and monoamine neurotransmitter levels in patients with ulcerative colitis. Methods 145 patients newly diagnosed with ulcerative colitis were selected into the study group，and 140 patients without abnormal results by gastrointestinal endoscopy were assigned into the control group. In two groups，Hp infection was diagnosed by using 13C urea breath test （13C-UBT）. The levels of gastrointestinal hormones（substance P （SP），endothelin （ET），vasoactive intestinal peptide （VIP））and monoamine neurotransmitters（norepinephrine （NE），5-hydroxytryptamine （5-HT）） were detected. Serum levels of gastrointestinal hormones and monoamine neurotransmitters were compared between active and remission phase patients in the study group. Serum levels of gastrointestinal hormones and monoamine neurotransmitters were compared between Hp-positive and -negative patients. The relationship between Hp infection and gastrointestinal hormone- and monoamine neurotransmitter-related indexes in patients with ulcerative colitis was assessed by Logistic regression analysis. Results Hp infection rate and VIP level in the study group were lower，whereas the levels of SP，ET，NE，and 5-HT were higher than those in the control group （all P<0.05）. Hp infection rate and VIP level in the active phase group were lower，while the levels of SP，ET，NE，and 5-HT were higher than those in the remission phase group （all P<0.05）. In the study group，the levels of SP，ET，NE and 5-HT in Hp-positive patients were lower，whereas the level of VIP was higher compared with those in Hp-negative counterparts （all P<0.05）. Logistic regression analysis showed that SP，ET，NE and 5-HT were the protective factors for Hp infection in patients with ulcerative colitis （all P<0.05），while elevated level of VIP was the risk factor （P<0.05）. Conclusions In ulcerative colitis patients，there are differences in the levels of gastrointestinal hormones and monoamine neurotransmitters between patients with and without Hp infection. Hp infection may be correlated with the changes in the levels of gastrointestinal hormones and monoamine neurotransmitters.

Sepsis can impair gastrointestinal (GI) barrier integrity. Oral probiotics (PT) can maintain the balance of GI microflora and improve GI function. 5-Hydroxytryptamine (5-HT) is a key promoter of GI injury caused by sepsis. However, the mechanism by which PT attenuates sepsis by regulating 5-HT is not fully understood. In this study, C57BL6 mice were intragastric administrated with normal saline (NC) or PT once a day for 4 weeks before cecal ligation and puncture (CLP). Compared with NC-CLP mice, PT-CLP mice had lower clinical score, higher body temperature. The survival rate of PT-CLP mice was significantly improved. The levels of inflammatory cytokines and 5-HT were obviously decreased in PT-CLP mice, and GI peristalsis and barrier function were enhanced. Moreover, sepsis downregulated the expression of tight junction proteins, while PT pretreatment could maintain them at the level of sham operation group. Furthermore, PT pretreatment increased the expression of serotonin transporter and monoamine oxidase A. PT administration could inhibit NF-κB activity, and activate ERK activity. In conclusion, long-term supplementation of PT before CLP can prevent sepsis-induced GI mucosal barrier dysfunction in mice, which may be partially mediated by upregulating the 5-HT degradation pathway via activating ERK signaling.

Lin Sheng,1– 4,&ast; Yumeng Wei,1,3,&ast; Chao Pi,1,3,&ast; Ju Cheng,3,4 Zhilian Su,1– 4 Yuanyuan Wang,1,5 Tao Chen,1– 4 Jie Wen,1– 4 Yuxun Wei,1– 4 Jingwen Ma,1– 4 Jia Tang,1– 4 Huiyang Liu,1– 4 Zerong Liu,6,7 Hongping Shen,8 Ying Zuo,9 Wenwu Zheng,10 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Clinical Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Central Nervous System Drug Key Laboratory of Sichuan Province, Sichuan Credit Pharmaceutical CO., Ltd. Luxian County, Luzhou City, People’s Republic of China; 7Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People’s Republic of China; 8Clinical Trial Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 9Department of Comprehensive Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 10Department of cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenwu Zheng, Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3165311, Email zhengwenwu888@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling@swmu.edu.cnPurpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.Keywords: turmeric extract, curcuminoids, nanoemulsion, stability, antidepressant effect, 5-hydroxytryptamine

Abstract Background Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. Methods We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients’ fecal supernatants exposed to the QGP-1 cell model in vitro. Results Our study demonstrated that patient’s constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients’ fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. Conclusion FMT can relieve patients’ constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood–brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HT2ARs) on neurons. Since microglia express all three 5-HT2R isoforms, we hypothesized that, by interacting with these receptors, psilocin beneficially modulates select neuroimmune functions of microglia. We used microglia-like cell lines to demonstrate that psilocin, at non-toxic concentrations, did not affect the secretion of tumor necrosis factor (TNF) by immune-stimulated microglial cells, but significantly inhibited their phagocytic activity, the release of reactive oxygen species (ROS), and nitric oxide (NO) production. The inhibitory activity of psilocin on the latter two functions was similar to that of two selective 5-HT2R agonists, namely, 25I-NBOH and Ro60-0175. The role of this subfamily of receptors was further demonstrated by the application of 5-HT2R antagonists cyproheptadine and risperidone. Psilocin should be considered a novel drug candidate that might be effective in treating neuroimmune disorders, such as neurodegenerative diseases, where reactive microglia are significant contributors.

Objective To investigate the relationship between Helicobacter pylori (Hp） infection and serum gastrointestinal hormones and monoamine neurotransmitter levels in patients with ulcerative colitis. Methods 145 patients newly diagnosed with ulcerative colitis were selected into the study group, and 140 patients without abnormal results by gastrointestinal endoscopy were assigned into the control group. In two groups, Hp infection was diagnosed by using 13C urea breath test (13C-UBT). The levels of gastrointestinal hormones(substance P (SP), endothelin (ET), vasoactive intestinal peptide (VIP) and monoamine neurotransmitters(norepinephrine (NE), 5-hydroxytryptamine (5-HT) were detected. Serum levels of gastrointestinal hormones and monoamine neurotransmitters were compared between active and remission phase patients in the study group. Serum levels of gastrointestinal hormones and monoamine neurotransmitters were compared between Hp-positive and -negative patients. The relationship between Hp infection and gastrointestinal hormone- and monoamine neurotransmitter-related indexes in patients with ulcerative colitis was assessed by Logistic regression analysis. Results Hp infection rate and VIP level in the study group were lower, whereas the levels of SP, ET, NE, and 5-HT were higher than those in the control group (all P < 0.05). Hp infection rate and VIP level in the active phase group were lower, while the levels of SP, ET, NE, and 5-HT were higher than those in the remission phase group (all P < 0.05). In the study group, the levels of SP, ET,NE and 5-HT in Hp-positive patients were lower, whereas the level of VIP was higher compared with those in Hp-negative counterparts (all P < 0.05). Logistic regression analysis showed that SP, ET, NE and 5-HT were the protective factors for Hp infection in patients with ulcerative colitis (all P < 0.05), while elevated level of VIP was the risk factor (P < 0.05). Conclusions In ulcerative colitis patients, there are differences in the levels of gastrointestinal hormones and monoamine neurotransmitters between patients with and without Hp infection. Hp infection may be correlated with the changes in the levels of gastrointestinal hormones and monoamine neurotransmitters. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. Methods: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). Results: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). Conclusion: EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response. [ABSTRACT FROM AUTHOR]

Introduction: Slow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear. Methods: Pseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis. Results: After treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria. Conclusion: Our study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Objective To explore the intervention effect of lychee seed aromatherapy on hippocampus and serum 5-hydroxytryptamine(5-HT) and dopamine(DA) in chronic unpredictable mild stress(CUMS) depression model rats. Methods The isolatedfeed model rats withchronic unpredictable mild stress were used as the research object, the body weight gain and sugar and water consumption of rats in each group were recorded and calculated on the 7th, 14th, 21st and 28th days of the experiment. The contents of excitatory neurotransmitters 5-HT and DA in hippocampus and serum of rats in each group were detected after treatment on the 35th day of the experiment. Results (1) Weight gain:From 14th to 21st day, compared with the blank group, the weight gain of rats in the model group, the prozac group and the prozac supplemented aromatherapy group was decreased(P <0. 01) at the 14th to 21st day;From the 28th to the 35th day, compared with the blank group, the weight gain of rats in the model group decreased(P >0. 05), compared with the model group, the weight gain of rats in the prozac group and the prozac supplemented aromatherapy group increased(P > 0. 05), compared with the prozac supplemented aromatherapy group, the weight gain of rats in the prozac group increased(P >0. 05). The number of body weight gain of rats in the prozac supplemented aromatherapy group was increased(P <0. 01). (2) Changes in sugar water consumption:on the 14th and 21st day, compared with the blank group, rats in the model group, the prozac group and the prozac supplemented aromatherapy group all decreased(P <0. 01);On the 35th day, compared with the blank group, the number of rats in the model group decreased(P <0. 01), the number of rats in the prozac group decreased(P <0. 05), the number of rats in the prozac group supplemented with aromatherapy decreased(P >0. 05), and the number of rats in the prozac group increased(P <0. 05), while the number of rats in the model group increased(P <0. 05). The number of rats in the prozacsupplemented aromatherapy group increased(P <0. 01);Compared with the prozac group, the number of rats in the prozac supplemented aromatherapy group was increased(P <0. 05). (3) Compared with the blank group, 5-HT and DA concentrations in the model group and the prozac group were significantly decreased(P <0. 01), and 5-HT and DA concentrations in the prozac supplemented aromatherapy group were significantly decreased(P >0. 05). Compared with the model group, the concentrations of 5-HT and DA in the blank group, the prozac group and the prozac supplemented aromatherapy group were significantly increased(P <0. 01). Compared with the prozac group, the concentrations of 5-HT and DA in the prozac supplemented aromatherapy group were significantly increased(P <0. 05). Conclusion Lychee seed aromatherapy can increase the content of monoamine neurotransmitters in the depressed model rats. The anti-depression mechanism of lychee seed aromatherapy may be related to the increase of monoamine neurotransmitters in the brain. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted. Methods: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro. Results: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells. Conclusion: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms. [ABSTRACT FROM AUTHOR]

All resolved high-resolution structures of the transporters in the neurotransmitter sodium symporter (NSS) family revealed that the NSS members share common structural and mechanistic features for substrate and ion binding and transport. However, a recently reported bacterial orthologue of the human serotonin transporter (hSERT), TuriSERT, possesses a structural characteristic specific for amino acid substrate binding but does transport a biogenic amine. The unique structural feature of TuriSERT requires a novel configuration for coordinating its substrate and ions. In the present study, we characterized TuriSERT expressed in Escherichia coli cells with a fluorescent substrate by biochemical, structural, and pharmacological approaches. Substrate transport by TuriSERT requires Na+ but not Cl−. Replacement of Asp262 by asparagine renders TuriSERT Cl−-dependent. Substitutions of the corresponding Na1 residues did not alter Na+ dependence on substrate transport, whereas the mutation of a Na2 site residue led to a loss of transport activity, suggesting that Na+ binds only to the Na2 site in TuriSERT. In addition, substitutions of several residues essential for recognizing 5-hydroxytryptamine (5-HT) in hSERT had little effect on 5-HT displacement potency in transport assay for TuriSERT. In contrast, mutations of the residues that are proposed to coordinate with 5-HT in our docking model dramatically reduced 5-HT displacement. Furthermore, our results indicated that all tested antidepressants showed a weak inhibitory effect on TuriSERT. The present study demonstrated the existence of a unique substrate binding site and 1:1 stoichiometry of sodium–substrate binding in TuriSERT, a novel structural finding for the NSS transporters. [ABSTRACT FROM AUTHOR]

General anesthesia is widely used in various clinical practices due to its ability to cause loss of consciousness. However, the exact mechanism of anesthesia-induced unconsciousness remains unclear. It is generally thought that arousal-related brain nuclei are involved. 5-Hydroxytryptamine (5-HT) is closely associated with sleep arousal. Here, we explore the role of the 5-HT system in anesthetic awakening through pharmacological interventions and optogenetic techniques. Our data showed that exogenous administration of 5-hydroxytryptophan (5-HTP) and optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DR) could significantly shorten the emergence time of sevoflurane anesthesia in mice, suggesting that regulation of the 5-HT system using both endogenous and exogenous approaches could mediate delayed emergence. In addition, we first discovered that the different 5-HT receptors located in the DR, known as 5-HT autoreceptors, are essential for the regulation of general anesthetic awakening, with 5-HT1A and 5-HT2A/C receptors playing a regulatory role. These results can provide a reliable theoretical basis as well as potential targets for clinical intervention to prevent delayed emergence and some postoperative risks. [ABSTRACT FROM AUTHOR]

With complex pathogenesis, myopia is a common ophthalmology disease and a major causation for visual impairment in children. For years, studies found that neurotransmitters, such as dopamine, nitric oxide, acetylcholine, γ-aminobutyric acid, 5-hydroxytryptamine, insulin and prostaglandins, are associated with children's refractive development and axial length growth. However, there are still many disagreements in their mechanisms of action. This article makes a systematic review on the roles of neurotransmitters in the pathogenesis of myopia including neurotransmitter receptors and antagonists to clarify the influence of different neurotransmitters on the occurrence and development of myopia, thus giving a comprehensive insight into its pathogenesis, building a basis for further research on the changes of neurotransmitters and providing new ideas and directions for the prevention and treatment of myopia.

Abstract Background Female mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets 5-HTR1 (encoding secreted 5-hydroxytryptamine receptor1), is essential for mosquito reproduction. Methods The spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays. Results miR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production. 5-HTR1 was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of 5-HTR1 expression. Knockdown of 5-HTR1 rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting 5-HTR1. Conclusions We found that miR-989 targets 5-HTR1 and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes. Graphical Abstract

5-hydroxytryptamine (5-HT) is an important brain intestinal peptide that affects gastrointestinal function in patients with diarrhea-type irritable bowel syndrome. In recent years, it has been found that any abnormality in any of the signal transduction processes such as synthesis, release, binding to receptors and reuptake of 5-HT may lead to the development of diarrhoeal irritable bowel syndrome. In order to explore the potential therapeutic value of serotonin in diarrhea type irritable bowel syndrome, but also to provide a theoretical reference and basis for Chinese medicine for the prevention and treatment of diarrhea type irritable bowel syndrome. Through reviewing a large number of domestic and foreign literatures, the author found that traditional Chinese medicine (TCM) had a significant effect in the treatment of diarrhea type irritable bowel syndrome by regulating 5-HT. Therefore, the author reviewed the modern medical understanding of 5-HT, the correlation between 5-HT and diarrhea-type irritable bowel syndrome, and the research progress of TCM intervention with 5-HT in the treatment of diarrhea-type irritable bowel syndrome, in order to explore the potential therapeutic value of 5-HT in diarrhea-type irritable bowel syndrome. Meanwhile, it also provides a theoretical reference and basis for TCM in the prevention and treatment of diarrhea-type irritable bowel syndrome.

We aimed to clarify the effect of nafamostat mesilate (nafamostat) on intestinal mucositis as well as the potentiation of intestinal 5-hydroxytryptamine (5-HT) dynamics induced by methotrexate, an anti-cancer drug, in rats. Rats received intraperitoneal methotrexate at 12.5 mg/kg/day for 4 days. In addition, 1, 3, or 10 mg/kg/day of nafamostat was given subcutaneously for 4 days. Ninety-six hours after the first administration of methotrexate, jejunal tissues were collected for analysis. The results showed that 1 mg/kg, but not 3 or 10 mg/kg, of nafamostat significantly ameliorated the methotrexate-induced body weight loss. Moreover, 1 mg/kg of nafamostat significantly improved methotrexate-induced mucositis, including villus atrophy. Nafamostat (1 mg/kg) significantly inhibited the methotrexate-induced mRNA expression of pro-inflammatory cytokines and cyclooxygenase-2, as well as methotrexate-induced 5-HT content and tryptophan hydroxylase (TPH) activity. In addition, it tended to inhibit the number of anti-TPH antibody-positive cells and significantly inhibited the number of anti-substance P antibody-positive cells. These findings suggest that low-dose nafamostat ameliorates tissue injury and 5-HT and substance P synthesis in methotrexate-induced mucositis. Nafamostat may be a novel therapeutic strategy for the prevention and treatment of mucositis as well as 5-HT- and/or substance P-related adverse effects in cancer chemotherapy.

Background: The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs). Methods: Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis. Results: After controlling relevant covariates, our results found the higher the abundance of Candidatus_Soleaferrea, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to unclassified_c_Clostridia and NK4A214_group. However, results of this study did not support the moderating effect of plasma 5-HT on the association of Candidatus_Soleaferrea or propionic acid with prenatal depression. Conclusions: Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy.

Background: Female mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets 5-HTR1 (encoding secreted 5-hydroxytryptamine receptor1), is essential for mosquito reproduction. Methods: The spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays. Results: miR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production. 5-HTR1 was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of 5-HTR1 expression. Knockdown of 5-HTR1 rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting 5-HTR1. Conclusions: We found that miR-989 targets 5-HTR1 and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes. [ABSTRACT FROM AUTHOR]