There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous sys...There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.展开更多
Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of dep...Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.展开更多
BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CR...BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;however,at high concentrations(≥25μmol/L),it can also promote epithelial-mesenchymal transition and invasion in CRC cells.IAAD activates AhR and directly binds MMP9,ACE,PARP1,MMP2,and MPO,which partly reveals why it has a bidirectional effect.展开更多
Background Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator,promoting intestinal development and regulating intestinal flora in the gut.However,the relevant mechanisms remain obscure.In this...Background Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator,promoting intestinal development and regulating intestinal flora in the gut.However,the relevant mechanisms remain obscure.In this study,pigs were fed a corn-soybean meal-based diet supplemented with either 5%microcrystalline cellulose(MCC)or 5%pectin for 3 weeks,to investigate the metabolites and anti-inflammatory properties of the jejunum.Result The results showed that dietary pectin supplementation improved intestinal integrity(Claudin-1,Occludin)and inflammatory response[interleukin(IL)-10],and the expression of proinflammatory cytokines(IL-1β,IL-6,IL-8,TNF-α)was down-regulated in the jejunum.Moreover,pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets.Pectin specifically increased the abundance of Lactococcus,Enterococcus,and the microbiota-derived metabolites(skatole(ST),3-indoleacetic acid(IAA),3-indolepropionic acid(IPA),5-hydroxyindole-3-acetic acid(HIAA),and tryptamine(Tpm)),which activated the aryl hydrocarbon receptor(AhR)pathway.AhR activation modulates IL-22 and its downstream pathways.Correlation analysis revealed the potential relationship between metabolites and intestinal morphology,intestinal gene expression,and cytokine levels.Conclusion In conclusion,these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway,which is activated through tryptophan metabolites.展开更多
Background Ochratoxin A(OTA)is a mycotoxin widely present in raw food and feed materials and is mainly pro-duced by Aspergillus ochraceus and Penicillium verrucosum.Our previous study showed that OTA principally induc...Background Ochratoxin A(OTA)is a mycotoxin widely present in raw food and feed materials and is mainly pro-duced by Aspergillus ochraceus and Penicillium verrucosum.Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder,especially Bacteroides plebeius(B.plebeius)overgrowth.However,whether OTA or B.plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown.This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver.Materials and methods A total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups.The control group was given 0.1 mol/L NaHCO3 solution,and the OTA group was given 235μg/kg body weight OTA for 14 consecutive days.Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics.AMPK-related signaling pathway factors were analyzed by Western blot-ting and mRNA expression.Results Metabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intesti-nal nicotinuric acid levels,the downstream product of tryptophan metabolism,which were significantly negatively correlated with B.plebeius abundance.In contrast,OTA induced a significant increase in indole-3-acetamide levels,which were positively correlated with B.plebeius abundance.Simultaneously,OTA decreased the levels of ATP,NAD+and dipeptidase in the liver.Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine,anthranilic acid and nicotinic acid.Moreover,OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein.Conclusion OTA decreased the level of nicotinuric acid in the intestinal tract,which was negatively correlated with B.plebeius abundance.The abnormal metabolism of tryptophan led to a deficiency of NAD+and ATP in the liver,which in turn activated the AMPK signaling pathway.Our results provide new insights into the toxic mechanism of OTA,and tryptophan metabolism might be a target for prevention and treatment.展开更多
Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that partici...Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.展开更多
Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-diox...Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-dioxygenase(TDO),by cortisol,leading to decreased Trp availability to the brain for serotonin synthesis.Subsequently,the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase(IDO)by proinflammatory cytokines,with inflammation being the underlying cause.Recent evidence,however,challenges this latter concept,as not all MDD patients are immune-activated and,when present,inflammation is mild and/or transient.A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme,but not to IDO.IDO induction is not a major event in MDD,but,when it occurs,its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase(KMO),the gateway to production of modulators of immune and neuronal functions.KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation.We demonstrate the ability of the antidepressant ketamine to dock(bind)to KMO.The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation.Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.展开更多
Background: Tryptophan metabolites such as serotonin, kynurenine, or kynurenic acids are considered to be the most important metabolites of gut microbiota. We wanted to know about changes in tryptophan metabolites in ...Background: Tryptophan metabolites such as serotonin, kynurenine, or kynurenic acids are considered to be the most important metabolites of gut microbiota. We wanted to know about changes in tryptophan metabolites in various diseases in which the etiology gut microbiota are considered to participate. Methods: Ultra-high speed liquid chromatography/mass spectroscopy (LC/MS) has been used to analyze simultaneously all the tryptophan metabolites, which we have explored for the first time in the world. Results: We analyzed plasma levels of tryptophan metabolites in patients with depression, autism, diabetes mellitus ‘DM’), and acute coronary syndrome (ACS). Of all the metabolites serotonin and kynurenine levels of these patients were higher than those of controls. Conclusion: Measurements of tryptophan metabolites in plasma of various diseases are important to know roles of gut microbiota in etiology, further therapeutic measures.展开更多
AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved ...AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups(r s = 0.494, P = 0.0001 and r s= 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls(controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.展开更多
Oxidative stress can induce abnormal tryptophan metabolism. The present study was mainly conducted to determine the effect of dietary tryptophan levels on oxidative stress in the liver of weaned pigs challenged by diq...Oxidative stress can induce abnormal tryptophan metabolism. The present study was mainly conducted to determine the effect of dietary tryptophan levels on oxidative stress in the liver of weaned pigs challenged by diquat. A total of 36 PIC piglets weaned at 21 days of age were randomly allotted to 1 of 3 diets containing dietary tryptophan levels of 0.18, 0.30, and 0A5% for 14 d. On day 8, the piglets were injected intraperitoneally with sterile 0.9% NaCI solution or diquat (10 mg/kg body weight). During the first 7 d of trial, increasing dietary tryptophan levels enhanced average daily gain (P = 0.09) and average daily feed intake (P = 0.08), and decreased the feed efficiency (P 〈 0.05) of piglets. The growth performance was decreased by diquat injection (P 〈 0.05). Diquat injection also decreased the activities of the superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma and liver (P 〈 0.05), increased plasma malondialdehyde (MDA) (P 〈 0.05) and urea nitrogen (P 〈 0.05) concentrations, and enhanced MDA concentration (P = 0.09) and tryptophan 2,3-dioxygenase (TDO) activity (P = 0.07) in liver of piglets. Increasing dietary tryptophan levels could attenuate the effects of diquat injection on the MDA (P = 0.06) concentration and the activities of SOD (P = 0.09) and GPx (P = 0.05) of the liver, and plasma urea nitrogen (P = 0.06) concentration in the piglet. There was a synergistic role for increasing TDO activity in the liver between dietary tryptophan levels and diquat injection (P 〈 0.05). These results suggest that increasing dietary tryptophan levels could attenuate the oxidative stress of the liver in weaned piglets intraperitoneally injected with diquat via enhancing the antioxidant capacity.展开更多
Background: Highly automated cage-rearing systems are becoming increasingly popular in China. However, a high stocking density can cause oxidative stress and decrease broiler performance. The tryptophan (TRP) deriv...Background: Highly automated cage-rearing systems are becoming increasingly popular in China. However, a high stocking density can cause oxidative stress and decrease broiler performance. The tryptophan (TRP) derivative 5-hydroxytryptophan (5-HT) has been shown to preserve membrane fluidity in birds suffering from oxidative stress Therefore, this experiment was conducted to determine the effects of dietan/TRP supplementation on performance, breast meat quality and oxidative stress in broilers reared in cages with a high or low stocking density. Methods: Female Arbor Acres broilers (25-d-old, n = 144) were randomly allocated to 1 of 4 treatments. The birds were fed a diet based on corn, soybean meal, cottonseed meal and corn gluten meal containing either 0.18 or 0.27% TRP and were housed with stocking densities of 11 or 15.4 birds/m2 in a 2 x 2 factorial experiment. Broiler performance was evaluated from d 25 to 42. Eight birds from each treatment were slaughtered on d 42 and plasma and breast muscle samples were collected to measure biochemical indices. Results: A higher stocking density tended to be associated with reduced weight gain (P 〈 0.10), and significantly increased plasma glutamic-pyruvic transaminase (GPT) activity (P 〈 0.001). Increased dietary TRP significantly reduced the activities of lactic dehydrogenase and GPT while increasing total cholesterol in the plasma (P 〈 0.01), reducing drip loss of breast muscle (P 〈 0.10) and improving feed efficiency (P 〈 0.10). Conclusions: An increase in dietary TRP, ].S-fold higher than the standard supplementation level, can alleviate oxidative stress as well as improve welfare and feed efficiency in broilers reared in cages with a high stocking density.展开更多
Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further...Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mecha- nism of exercise-induced central fatigue at spinal level. Methods Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analysized quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. Results Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P 〈 0.05). Conclusion 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue.展开更多
Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydr...Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2(TPH2). In the present study, the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer(SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth.However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality.展开更多
A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine (Lys) (0.95, 1.10, 1.25%), methionine (Met) (0.26, 0.46, 0.66%) and tryptophan (Trp) (0.20, 0....A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine (Lys) (0.95, 1.10, 1.25%), methionine (Met) (0.26, 0.46, 0.66%) and tryptophan (Trp) (0.20, 0.30, 0.40%) for those ducklings during a phase of 0-2 weeks. Ducklings were randomly allotted to 27 groups according to a 3 × 3× 3 factorial arrangement and fed a basal corn-soybean-peanut meal diet containing 20.26% CP, 12.45 MJ kg^-1 ME. The results from this study indicate that Lys affected body weight (P〈0.01), feed intake (0-14 d) (P〈0.01), but had no effect on feed/gain (0-14 d) (P〉0.05), uric acid concentration (P 〉 0.05). Methionine influenced body weight (P 〈 0.01), feed/gain (P 〈 0.05), and feed intake (P 〈 0.01). Tryphtophan had no effect on indices measured. The requirement of the Lys and Met for Beijing ducklings of 0-2 weeks of age were 1.10 and 0.46%. The requirement of Trp for Beijing ducklings of 0-2 weeks of age was not more than 0.20%.展开更多
Tamarindus[Tamarindus indica L.(T.Indira)],belongs to the family Leguminosae(Fabaceae),commonly known as Tamarind tree,is one of the fruit tree species that is used as traditional medicine.The aim of this article is t...Tamarindus[Tamarindus indica L.(T.Indira)],belongs to the family Leguminosae(Fabaceae),commonly known as Tamarind tree,is one of the fruit tree species that is used as traditional medicine.The aim of this article is to review the current literatue on health related effect of T.indir.a.Literature review about this plant was conducted between 2003 and 2014 through Pubmed and Google.The keywords Tamarind,T.indica were used for search.Only the health related articles selected.Tamarind tree is found especially in the Indian subcontinent,Africa,Pakistan,Bangladesh,Nigeria and most of the tropical countries.It is preferred to be used for abdominal pain,diarrhea and dysentery,some bacterial infections and parasitic infestations,wound healing,constipation and inflammation.It is a rich source of most of the essential amino acids and phytochemicals,and hence the plant is reported to possess antidiabetic,antimicrobial,antivenomic,antioxidant,antimalarial,cardioprotective,hepatoprotective,antiasthmatic,laxative and anti-hyperlipidemir activity.T.indica has ameliorative effects on many diseases.It can also be preferred as a nutritious support for malnourished patients as it is cheap and easy to access.Those effects should be clarified with further research.展开更多
Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers p...Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.展开更多
A modified chitosan adsorbent was synthesized through a simple preparation procedure, and it demonstrated good adsorption performance for selective removal of low density lipoprotein in human plasma. Phase inversion ...A modified chitosan adsorbent was synthesized through a simple preparation procedure, and it demonstrated good adsorption performance for selective removal of low density lipoprotein in human plasma. Phase inversion technique was employed to form chitosan beads, to which epoxy groups were then introduced by reacting with ethyleneglycol diglycidylether, and tryptophan was subsequently coupled to the epoxy-activated beads.展开更多
Tryptophan(Trp) residues in a pullulanase were modified by N-bromosuccinimide(NBS). The results of the Spande method indicate that there are 18 Trp residues in the pullulanase and nine of them are located on the s...Tryptophan(Trp) residues in a pullulanase were modified by N-bromosuccinimide(NBS). The results of the Spande method indicate that there are 18 Trp residues in the pullulanase and nine of them are located on the surface af the enzyme. Three of these Trp residues are nonessential residues which show the fastest reaction rate according to the Zou's plot. Two of the seven relative faster reacting residues are essential for the activity of the enzyme. The other eight are the slowest in the reaction rate or non-reactive residues for the reaction. The fluorescence and circular dichroism(CD) spectra of the pullulanase have been changed after the reaction with NBS. Potassium iodide(KI) and acrylamide also have remarkable influences on the fluorescence spectra of the pullulanase.展开更多
A high sensitive flow-injection chemiluminescence (FI-CL) method for the determination of tryptophan has been developed. The method is based on the chemiluminescence reaction of galangin-potassium permanganate-trypt...A high sensitive flow-injection chemiluminescence (FI-CL) method for the determination of tryptophan has been developed. The method is based on the chemiluminescence reaction of galangin-potassium permanganate-tryptophan in polyphosphoric acid (PPA) media. Under the optimized conditions, tryptophan was determined in the range 0.05-10 μg/mL with the detection limit (3tr) of 5.0 × 10^-3 μg/mL. The relative standard deviation (RSD) was 1.0% for 11 replicate determinations of 1.0 μg/mL tryptophan. Three synthetic samples were determined selectively with recoveries in the range from 99.6% to 102.0% in the presence of other amino acids.展开更多
Over the past two decades,it is improved gut microbiota plays an important role in the health and disease pathogenesis.Metabolites,small molecules produced as intermediate or end products of microbial metabolism,is co...Over the past two decades,it is improved gut microbiota plays an important role in the health and disease pathogenesis.Metabolites,small molecules produced as intermediate or end products of microbial metabolism,is considered as one of the major interaction way for gut microbiota with the host.Bacterial metabolisms of dietary substrates,modification of host molecules or bacteria are the major source of metabolites.Signals from microbial metabolites affect immune maturation and homeostasis,host energy metabolism as well as mucosal integrity maintenance.Based on many researches,the composition and function of the microbiota can be changed,which is also seen in the metabolite profiles of patients with inflammatory bowel disease(IBD).Additionally,some specific classes of metabolites also can trigger IBD.In this paper,definition of the key classes of microbialderived metabolites which are changed in IBD,description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82105019(to YC),82271218(to CZ)Natural Science Foundation of Tianjin Municipality Foundation,No.20JCZDJC00540(to CZ).
文摘There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.
基金supported by the National Natural Science Foundation of China(81373584)。
文摘Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGD23C040008,No.LBY23H200006,and No.LQ22H030004.
文摘BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;however,at high concentrations(≥25μmol/L),it can also promote epithelial-mesenchymal transition and invasion in CRC cells.IAAD activates AhR and directly binds MMP9,ACE,PARP1,MMP2,and MPO,which partly reveals why it has a bidirectional effect.
基金supported by National Natural Science Foundation of China(NSFC)(31802072)China Scholarship Council(CSC NO.202103250006)+1 种基金the Central Public-interest Scientific Institution Basal Research Fund(No.Y2022GH02&PJ01618301)State Key Laboratory of Animal Nutrition(2004DA125184G2102)。
文摘Background Pectin is a heteropolysaccharide that acts as an intestinal immunomodulator,promoting intestinal development and regulating intestinal flora in the gut.However,the relevant mechanisms remain obscure.In this study,pigs were fed a corn-soybean meal-based diet supplemented with either 5%microcrystalline cellulose(MCC)or 5%pectin for 3 weeks,to investigate the metabolites and anti-inflammatory properties of the jejunum.Result The results showed that dietary pectin supplementation improved intestinal integrity(Claudin-1,Occludin)and inflammatory response[interleukin(IL)-10],and the expression of proinflammatory cytokines(IL-1β,IL-6,IL-8,TNF-α)was down-regulated in the jejunum.Moreover,pectin supplementation altered the jejunal microbiome and tryptophan-related metabolites in piglets.Pectin specifically increased the abundance of Lactococcus,Enterococcus,and the microbiota-derived metabolites(skatole(ST),3-indoleacetic acid(IAA),3-indolepropionic acid(IPA),5-hydroxyindole-3-acetic acid(HIAA),and tryptamine(Tpm)),which activated the aryl hydrocarbon receptor(AhR)pathway.AhR activation modulates IL-22 and its downstream pathways.Correlation analysis revealed the potential relationship between metabolites and intestinal morphology,intestinal gene expression,and cytokine levels.Conclusion In conclusion,these results indicated that pectin inhibits the inflammatory response by enhancing the AhR-IL22-signal transducer and activator of transcription 3 signaling pathway,which is activated through tryptophan metabolites.
基金Guangdong Province Natural Science Funds for Distinguished Young Scholar(2022B1515020016)the National Science Fund for Outstanding Young Scholars(32222080)+5 种基金National Key Research Program(2021YFD1300404)National Science Fund Project of China(32072751)Guangdong Basic and Applied Basic Research Foundation(2022B1515130003)China Agriculture Research System(CARS-42-15)Modern Agricultural Industrial Technology System Innovation Team of Guangdong Province(2022KJ137)Natural Science Foundation of Guangdong Province(2019B1515210012).
文摘Background Ochratoxin A(OTA)is a mycotoxin widely present in raw food and feed materials and is mainly pro-duced by Aspergillus ochraceus and Penicillium verrucosum.Our previous study showed that OTA principally induces liver inflammation by causing intestinal flora disorder,especially Bacteroides plebeius(B.plebeius)overgrowth.However,whether OTA or B.plebeius alteration leads to abnormal tryptophan-related metabolism in the intestine and liver is largely unknown.This study aimed to elucidate the metabolic changes in the intestine and liver induced by OTA and the tryptophan-related metabolic pathway in the liver.Materials and methods A total of 30 healthy 1-day-old male Cherry Valley ducks were randomly divided into 2 groups.The control group was given 0.1 mol/L NaHCO3 solution,and the OTA group was given 235μg/kg body weight OTA for 14 consecutive days.Tryptophan metabolites were determined by intestinal chyme metabolomics and liver tryptophan-targeted metabolomics.AMPK-related signaling pathway factors were analyzed by Western blot-ting and mRNA expression.Results Metabolomic analysis of the intestinal chyme showed that OTA treatment resulted in a decrease in intesti-nal nicotinuric acid levels,the downstream product of tryptophan metabolism,which were significantly negatively correlated with B.plebeius abundance.In contrast,OTA induced a significant increase in indole-3-acetamide levels,which were positively correlated with B.plebeius abundance.Simultaneously,OTA decreased the levels of ATP,NAD+and dipeptidase in the liver.Liver tryptophan metabolomics analysis showed that OTA inhibited the kynurenine metabolic pathway and reduced the levels of kynurenine,anthranilic acid and nicotinic acid.Moreover,OTA increased the phosphorylation of AMPK protein and decreased the phosphorylation of mTOR protein.Conclusion OTA decreased the level of nicotinuric acid in the intestinal tract,which was negatively correlated with B.plebeius abundance.The abnormal metabolism of tryptophan led to a deficiency of NAD+and ATP in the liver,which in turn activated the AMPK signaling pathway.Our results provide new insights into the toxic mechanism of OTA,and tryptophan metabolism might be a target for prevention and treatment.
基金National Natural Science Foundation of China,No.82200695。
文摘Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.
文摘Serotonin deficiency in major depressive disorder(MDD)has formed the basis of antidepressant drug development and was originally attributed to induction of the major tryptophan(Trp)-degrading enzyme,liver Trp 2,3-dioxygenase(TDO),by cortisol,leading to decreased Trp availability to the brain for serotonin synthesis.Subsequently,the serotonin deficiency was proposed to involve induction of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase(IDO)by proinflammatory cytokines,with inflammation being the underlying cause.Recent evidence,however,challenges this latter concept,as not all MDD patients are immune-activated and,when present,inflammation is mild and/or transient.A wide range of antidepressant drugs inhibit the activity of liver TDO and bind specifically to the enzyme,but not to IDO.IDO induction is not a major event in MDD,but,when it occurs,its metabolic consequences may be masked and overridden by upregulation of kynurenine monooxygenase(KMO),the gateway to production of modulators of immune and neuronal functions.KMO appears to be activated in MDD by certain proinflammatory cytokines and antidepressants with anti-inflammatory properties may block this activation.We demonstrate the ability of the antidepressant ketamine to dock(bind)to KMO.The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation.Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.
文摘Background: Tryptophan metabolites such as serotonin, kynurenine, or kynurenic acids are considered to be the most important metabolites of gut microbiota. We wanted to know about changes in tryptophan metabolites in various diseases in which the etiology gut microbiota are considered to participate. Methods: Ultra-high speed liquid chromatography/mass spectroscopy (LC/MS) has been used to analyze simultaneously all the tryptophan metabolites, which we have explored for the first time in the world. Results: We analyzed plasma levels of tryptophan metabolites in patients with depression, autism, diabetes mellitus ‘DM’), and acute coronary syndrome (ACS). Of all the metabolites serotonin and kynurenine levels of these patients were higher than those of controls. Conclusion: Measurements of tryptophan metabolites in plasma of various diseases are important to know roles of gut microbiota in etiology, further therapeutic measures.
文摘AIM: To evaluate how Helicobacter pylori(H. pylori) is able to evade the immune response and whether it enhances systemic immune tolerance against colorectal cancer.METHODS: This prospective randomized study involved 97 consecutive colorectal cancer patients and 108 cancer-free patients with extra-digestive diseases. Colorectal cancer and cancer-free patients were assigned into subgroups according to H. pylori Ig G seropositivity. Exposure to H. pylori was determined by Ig G seropositivity which was detected by enzyme linked immunoassay(ELISA). Serum neopterin levels were measured by ELISA. Serum tryptophan, kynurenine, and urinary biopterin concentrations were measured by high performance liquid chromatography. Serum nitrite levels were detected spectrophotometrically. Serum indoleamine 2,3-dioxygenase activity was estimated by the kynurenine to tryptophan ratio and by assessing the correlation between serum neopterin concentrations and the kynurenine to tryptophan ratio. The frequencies of increased serum kynurenine to tryptophan ratio of H. pylori seronegative and seropositive colorectal cancer subgroups were estimated by comparing them with the average kynurenine to tryptophan ratio of H. pylori seronegative tumor-free patients.RESULTS: Compared with respective controls, in both H. pylori seronegative and seropositive colorectal cancer patients, while serum tryptophan levels were decreased(controls vs patients; seronegative: 20.37 ± 0.89 μmol/L vs 15.71 ± 1.16 μmol/L, P < 0.05; seropositive: 20.71 ± 0.81 μmol/L vs 14.97 ± 0.79 μmol/L, P < 0.01) the kynurenine to tryptophan ratio was significantly increased(controls vs patients; seronegative: 52.85± 11.85 μmol/mmol vs 78.91 ± 8.68 μmol/mmol, P < 0.01, seropositive: 47.31 ± 5.93 μmol/mmol vs 109.65 ± 11.50 μmol/mmol, P < 0.01). Neopterin concentrations in cancer patients were significantly elevated compared with controls(P < 0.05). There was a significant correlation between serum neopterin levels and kynurenine/tryptophan in control and colorectal cancer patients groups(r s = 0.494, P = 0.0001 and r s= 0.293, P = 0.004, respectively). Serum nitrite levels of H. pylori seropositive cancer cases were significantly decreased compared with seropositive controls(controls vs patients; 26.04 ± 2.39 μmol/L vs 20.41 ± 1.48 μmol/L, P < 0.05) The decrease in the nitrite levels of H. pylori seropositive cancer patients may be attributed to excessive formation of peroxynitrite and other reactive nitrogen species.CONCLUSION: A significantly high kynurenine/tryptophan suggested that H. pylori may support the immune tolerance leading to cancer development, even without an apparent upper gastrointestinal tract disease.
基金financially supported by the earmarked fund for the China Agriculture Research System(CARS-36)the grant from the Science and Technology Support Program of Sichuan Province(13ZC2237)
文摘Oxidative stress can induce abnormal tryptophan metabolism. The present study was mainly conducted to determine the effect of dietary tryptophan levels on oxidative stress in the liver of weaned pigs challenged by diquat. A total of 36 PIC piglets weaned at 21 days of age were randomly allotted to 1 of 3 diets containing dietary tryptophan levels of 0.18, 0.30, and 0A5% for 14 d. On day 8, the piglets were injected intraperitoneally with sterile 0.9% NaCI solution or diquat (10 mg/kg body weight). During the first 7 d of trial, increasing dietary tryptophan levels enhanced average daily gain (P = 0.09) and average daily feed intake (P = 0.08), and decreased the feed efficiency (P 〈 0.05) of piglets. The growth performance was decreased by diquat injection (P 〈 0.05). Diquat injection also decreased the activities of the superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the plasma and liver (P 〈 0.05), increased plasma malondialdehyde (MDA) (P 〈 0.05) and urea nitrogen (P 〈 0.05) concentrations, and enhanced MDA concentration (P = 0.09) and tryptophan 2,3-dioxygenase (TDO) activity (P = 0.07) in liver of piglets. Increasing dietary tryptophan levels could attenuate the effects of diquat injection on the MDA (P = 0.06) concentration and the activities of SOD (P = 0.09) and GPx (P = 0.05) of the liver, and plasma urea nitrogen (P = 0.06) concentration in the piglet. There was a synergistic role for increasing TDO activity in the liver between dietary tryptophan levels and diquat injection (P 〈 0.05). These results suggest that increasing dietary tryptophan levels could attenuate the oxidative stress of the liver in weaned piglets intraperitoneally injected with diquat via enhancing the antioxidant capacity.
基金supported by the System for Poultry Production Technology,Beijing Innovation Research Team of Modern Agriculture(CARSPSTP)the National Key Technology R&D Program of China during the 12~(th) five-year plan(2012BAD39B04)
文摘Background: Highly automated cage-rearing systems are becoming increasingly popular in China. However, a high stocking density can cause oxidative stress and decrease broiler performance. The tryptophan (TRP) derivative 5-hydroxytryptophan (5-HT) has been shown to preserve membrane fluidity in birds suffering from oxidative stress Therefore, this experiment was conducted to determine the effects of dietan/TRP supplementation on performance, breast meat quality and oxidative stress in broilers reared in cages with a high or low stocking density. Methods: Female Arbor Acres broilers (25-d-old, n = 144) were randomly allocated to 1 of 4 treatments. The birds were fed a diet based on corn, soybean meal, cottonseed meal and corn gluten meal containing either 0.18 or 0.27% TRP and were housed with stocking densities of 11 or 15.4 birds/m2 in a 2 x 2 factorial experiment. Broiler performance was evaluated from d 25 to 42. Eight birds from each treatment were slaughtered on d 42 and plasma and breast muscle samples were collected to measure biochemical indices. Results: A higher stocking density tended to be associated with reduced weight gain (P 〈 0.10), and significantly increased plasma glutamic-pyruvic transaminase (GPT) activity (P 〈 0.001). Increased dietary TRP significantly reduced the activities of lactic dehydrogenase and GPT while increasing total cholesterol in the plasma (P 〈 0.01), reducing drip loss of breast muscle (P 〈 0.10) and improving feed efficiency (P 〈 0.10). Conclusions: An increase in dietary TRP, ].S-fold higher than the standard supplementation level, can alleviate oxidative stress as well as improve welfare and feed efficiency in broilers reared in cages with a high stocking density.
文摘Objective To investigate changes of 5-hydroxytryptamine (5-HT) and its synthesis rate-limiting enzyme tryp-tophan hydroxylase (TPH) in the ventral horn of spinal cord after exercise-induced fatigue, and to further discuss the mecha- nism of exercise-induced central fatigue at spinal level. Methods Sixteen healthy adult Wistar rats were randomly divided into 2 groups: exercise-induced fatigue group and control group. Immunohistochemical staining for 5-HT and TPH in the ventral horn were performed and analysized quantitatively. The mean optic densities of 5-HT and TPH positive fibers or terminals were measured by computerized image analyzer. Results Both 5-HT and TPH positive fibers/terminals decreased in the exercise-induced fatigue group. The immunohistochemical staining was weaker and the mean optic densities decreased obviously in the fatigue group compared with those in the control group (P 〈 0.05). Conclusion 5-HT and TPH in the ventral horn of spinal cord might be involved in exercise-induced fatigue.
基金supported by a grant from the National Natural Science Foundation of China (No.81570402)a grant from the Jiangsu Key Laboratory of Xenotransplantation (BM2012116)+3 种基金grants from the Sanming Project of Medicine in Shenzhenthe Fund for High Level Medical Discipline Construction of Shenzhen (No.2016031638)the Shenzhen Foundation of Science and Technology (No.JCYJ20160229204849975 and GCZX2015043017281705)grant from the National Basic Research Program of China (2015CB559200)
文摘Unbalanced brain serotonin(5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2(TPH2). In the present study, the clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated(Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer(SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth.However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality.
文摘A feed trial was conducted with a total of 1 134 Beijing ducklings to study the optimum level of dietary lysine (Lys) (0.95, 1.10, 1.25%), methionine (Met) (0.26, 0.46, 0.66%) and tryptophan (Trp) (0.20, 0.30, 0.40%) for those ducklings during a phase of 0-2 weeks. Ducklings were randomly allotted to 27 groups according to a 3 × 3× 3 factorial arrangement and fed a basal corn-soybean-peanut meal diet containing 20.26% CP, 12.45 MJ kg^-1 ME. The results from this study indicate that Lys affected body weight (P〈0.01), feed intake (0-14 d) (P〈0.01), but had no effect on feed/gain (0-14 d) (P〉0.05), uric acid concentration (P 〉 0.05). Methionine influenced body weight (P 〈 0.01), feed/gain (P 〈 0.05), and feed intake (P 〈 0.01). Tryphtophan had no effect on indices measured. The requirement of the Lys and Met for Beijing ducklings of 0-2 weeks of age were 1.10 and 0.46%. The requirement of Trp for Beijing ducklings of 0-2 weeks of age was not more than 0.20%.
文摘Tamarindus[Tamarindus indica L.(T.Indira)],belongs to the family Leguminosae(Fabaceae),commonly known as Tamarind tree,is one of the fruit tree species that is used as traditional medicine.The aim of this article is to review the current literatue on health related effect of T.indir.a.Literature review about this plant was conducted between 2003 and 2014 through Pubmed and Google.The keywords Tamarind,T.indica were used for search.Only the health related articles selected.Tamarind tree is found especially in the Indian subcontinent,Africa,Pakistan,Bangladesh,Nigeria and most of the tropical countries.It is preferred to be used for abdominal pain,diarrhea and dysentery,some bacterial infections and parasitic infestations,wound healing,constipation and inflammation.It is a rich source of most of the essential amino acids and phytochemicals,and hence the plant is reported to possess antidiabetic,antimicrobial,antivenomic,antioxidant,antimalarial,cardioprotective,hepatoprotective,antiasthmatic,laxative and anti-hyperlipidemir activity.T.indica has ameliorative effects on many diseases.It can also be preferred as a nutritious support for malnourished patients as it is cheap and easy to access.Those effects should be clarified with further research.
基金supported by grants from National Natural Science Foundation of China(No.81071307,No.30872440,No.81171259)
文摘Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.
文摘A modified chitosan adsorbent was synthesized through a simple preparation procedure, and it demonstrated good adsorption performance for selective removal of low density lipoprotein in human plasma. Phase inversion technique was employed to form chitosan beads, to which epoxy groups were then introduced by reacting with ethyleneglycol diglycidylether, and tryptophan was subsequently coupled to the epoxy-activated beads.
文摘Tryptophan(Trp) residues in a pullulanase were modified by N-bromosuccinimide(NBS). The results of the Spande method indicate that there are 18 Trp residues in the pullulanase and nine of them are located on the surface af the enzyme. Three of these Trp residues are nonessential residues which show the fastest reaction rate according to the Zou's plot. Two of the seven relative faster reacting residues are essential for the activity of the enzyme. The other eight are the slowest in the reaction rate or non-reactive residues for the reaction. The fluorescence and circular dichroism(CD) spectra of the pullulanase have been changed after the reaction with NBS. Potassium iodide(KI) and acrylamide also have remarkable influences on the fluorescence spectra of the pullulanase.
文摘A high sensitive flow-injection chemiluminescence (FI-CL) method for the determination of tryptophan has been developed. The method is based on the chemiluminescence reaction of galangin-potassium permanganate-tryptophan in polyphosphoric acid (PPA) media. Under the optimized conditions, tryptophan was determined in the range 0.05-10 μg/mL with the detection limit (3tr) of 5.0 × 10^-3 μg/mL. The relative standard deviation (RSD) was 1.0% for 11 replicate determinations of 1.0 μg/mL tryptophan. Three synthetic samples were determined selectively with recoveries in the range from 99.6% to 102.0% in the presence of other amino acids.
基金Supported by Shaanxi Province Natural Science Basic Research Program-General Project,No:2019JM-580 and 2021SF-314Project of Shaanxi Administration of Traditional Chinese Medicine,No. 2019-ZZ-JC010Shaanxi Provincial Hospital of Traditional Chinese Medicine,No. 2018-04
文摘Over the past two decades,it is improved gut microbiota plays an important role in the health and disease pathogenesis.Metabolites,small molecules produced as intermediate or end products of microbial metabolism,is considered as one of the major interaction way for gut microbiota with the host.Bacterial metabolisms of dietary substrates,modification of host molecules or bacteria are the major source of metabolites.Signals from microbial metabolites affect immune maturation and homeostasis,host energy metabolism as well as mucosal integrity maintenance.Based on many researches,the composition and function of the microbiota can be changed,which is also seen in the metabolite profiles of patients with inflammatory bowel disease(IBD).Additionally,some specific classes of metabolites also can trigger IBD.In this paper,definition of the key classes of microbialderived metabolites which are changed in IBD,description of the pathophysiological basis of association and identification of the precision therapeutic modulation in the future are the major contents.