Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction d...Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.展开更多
BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in pati...BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.展开更多
BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs...BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.展开更多
Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic...Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.展开更多
Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.H...Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.展开更多
BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicat...BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.展开更多
The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies h...The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.展开更多
The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secre...The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secretions have been shown to confer important functions in mediating plant–insect interactions at the molecular level.In this review,we examined the biochemical studies of insect oral secretions to summarize the current knowledge of their compositions.We then moved beyond the functional studies of components of oral secretions,and focused on the literature that pinpointed specific molecular targets of these compounds.Finally,we highlighted the investigations of oral secretion components in the context of insect physiology,which shed light on the potential evolutionary trajectory of these multi-functional molecules.展开更多
Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were f...Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were found toxic to mice with the intraperitoneal LD 50 of 11 5?mg/kg,18 8?mg/kg,and 264?mg/kg,respectively.No acute lethal toxicities were observed for the skin secretions of Rana nigromaculata,Rana guentheri and Rana limnocharis in a dose up to 500?mg/kg.The lethal toxicities of the skin secretions of T verrucosus and B maxima to mice are in the same grade as those of Viperidae snake venoms.The toxic components in T verrucosus and B maxima skin secretions are the proteins with molecular weights ranging from 3 to 60?kDa.All the skin secretions had both proteolytic activity and trypsin inhibitory activity.The skin secretions from T verrucosus , B maxima and B andrewsi also displayed wide spectrum antimicrobial activity.On the other hand,the skin secretions from B andrewsi and B maxima showed cytotoxicity on human cancer cells.All the six samples had not significant effects on mammalian blood coagulation system.Phospholipase A 2 activity was only found in the skin secretions of T verrucosus .None of these skin secretions showed acetylcholine esterase activity.展开更多
Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unco...Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.展开更多
Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free...Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.展开更多
Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (E...Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.展开更多
Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to ...Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.展开更多
AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under system...AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen(263% ± 63% vs 309% ± 45%,227% ± 63% vs 309% ± 45%,P = 0.899,0.626 > 0.05 respectively,by ANOVA).Accordingly,Danshen does not bind with M3 or α1 receptors.These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine.Carbamylcholine activates the M3 receptor to release inositol trisphosphate(IP3) and quickly releases Ca2+ from the calcium stores.The elevation of [Ca2+]i induces chloride release and quick osmosis,resulting in an onset of fluid secretion.An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels.The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen(1.8 ± 0.8 μL/g-min vs 101.9 ± 17.2 μL/g-min,P = 0.00023 < 0.01,by t-test),suggesting the involvement of Ca2+ in the activation of these channels.Therefore,IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen,but rather,there may be a distinct signalling process.CONCLUSION:The present findings suggest that Danshen can be used in the treatment of xerostomia,to avoid the systemic side effects associated with muscarinic drugs.展开更多
Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when ad...Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.展开更多
Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several dru...Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.展开更多
AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially wi...AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.展开更多
AIM To study the peripheral mechanism of the inhibitory effect of intra third ventricular administration (icv) of histamine (HA) on gastric acid secretion in rats. METHODS Gastric acid was continuously washed wit...AIM To study the peripheral mechanism of the inhibitory effect of intra third ventricular administration (icv) of histamine (HA) on gastric acid secretion in rats. METHODS Gastric acid was continuously washed with 37℃ saline by a perfusion pump in male adrenalectomized SD rats. Drugs were injected intravenously (iv) by a syringe pump and their effect on pentagastrin induced (10μg·kg·h, iv) gastric acid secretion was observed. RESULTS The inhibitory effect of HA (1μg, icv) on gastric acid secretion was blocked by subdiaphragmatic vagotomy, and pretreatment with atropine (0 005mg·kg·h, iv). Pretreatment with somatostatin antagonist, cyclo [7 aminoheptanoyl Phe D Trp Lys Thr(Bzl)], ( 2μg - 4μg ·kg· 100min , iv) could also block the inhibitory effect of HA on gastric acid secretion in a dose dependent manner. CONCLUSION The inhibitory effect of centrally administrated HA on gastric acid secretion may be mediated by vagi, acetylcholine M receptor and somatostatin.展开更多
基金supported by the National Natural Science Foundation of China(81673680)the Fundamental Research Funds for the Central Public Welfare Research Institutes(YZX-202306).
文摘Objective:To investigate the relationship between Jiaotai pill(JTP),its main component berberine(BBR),and the serotonin(5-HT)system in regulating islet hormone secretion and alleviating pancreatic b-cell dysfunction during type 2 diabetes mellitus(T2DM)progression.Methods:T2DM rat model was established using a high-fat diet and streptozotocin injection.JTP,BBR,and Metformin were intragastrically administered for 35 days.The analyzed indices included blood glucose,blood lipids,islet hormones,and proteins related to 5-HT synthesis,secretion,and transport.Additionally,an in vitro model of glucose injury in islet cells was established to study the effects of JTP and BBR on islet hormone secretion following tryptophan hydroxylase 1(TPH1)inhibition.Results:JTP and BBR significantly improved blood glucose and lipid levels and islet morphology in T2DM rats.Both models exhibited reduced islet 5-HT levels and impaired islet hormone secretion.However,the administration of JTP and BBR reversed these effects.Furthermore,JTP and BBR upregulated the expression of TPH1(P=.0194,P=.0413)transglutaminase 2(TGase2;P=.0492,P=.0349),serotonin transporter(SERT,P=.0090),and 5-hydroxytryptamine 1F receptor(5-HT1FR)in the islet 5-HT pathway(P=.0194).In the cell model,the regulatory effects of JTP and BBR on islet hormone levels were significantly weakened after TPH1 inhibition(P=.001),suggesting that JTP and BBR influence islet hormone secretion through the pancreatic 5-HT system.Conclusion:The islet 5-HT system is correlated with islet hormone secretion dysfunction in T2DM.JTP and BBR can improve islet hormone secretion by activating the TPH1/TGase2/SERT/5-HT1FR pathway in the islet 5-HT system in T2DM rats.
基金Supported by National Natural Science Foundation of China(General Program),No.82073909Four‘Batches’Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province,No.2023XM022The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059 and No.YDZJSX20231A059。
文摘BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.
文摘BACKGROUND Human milk oligosaccharides(HMOs)are bioactive components of breast milk with diverse health benefits,including shaping the gut microbiota,modulating the immune system,and protecting against infections.HMOs exhibit dynamic secretion patterns during lactation,influenced by maternal genetics and environ-mental factors.Their direct and indirect antimicrobial properties have garnered significant research interest.However,a comprehensive understanding of the secretion dynamics of HMOs and their correlation with antimicrobial efficacy remains underexplored.AIM To synthesize current evidence on the secretion dynamics of HMOs during lactation and evaluate their antimicrobial roles against bacterial,viral,and protozoal pathogens.METHODS A systematic search of PubMed,Scopus,Web of Science,and Cochrane Library focused on studies investigating natural and synthetic HMOs,their secretion dynamics,and antimicrobial properties.Studies involving human,animal,and in vitro models were included.Data on HMO composition,temporal secretion patterns,and mechanisms of antimicrobial action were extracted.Quality assess-ment was performed using validated tools appropriate for study design.RESULTS A total of 44 studies were included,encompassing human,animal,and in vitro research.HMOs exhibited dynamic secretion patterns,with 2′-fucosyllactose(2′-FL)and lacto-N-tetraose peaking in early lactation and declining over time,while 3-fucosyllactose(3-FL)increased during later stages.HMOs demonstrated significant antimicrobial properties through pathogen adhesion inhibition,biofilm disruption,and enzymatic activity impairment.Synthetic HMOs,including bioengineered 2′-FL and 3-FL,were structurally and functionally comparable to natural HMOs,effectively inhibiting pathogens such as Pseudomonas aeruginosa,Escherichia coli,and Campylobacter jejuni.Additionally,HMOs exhibited synergistic effects with antibiotics,enhancing their efficacy against resistant pathogens.CONCLUSION HMOs are vital in antimicrobial defense,supporting infant health by targeting various pathogens.Both natural and synthetic HMOs hold significant potential for therapeutic applications,particularly in infant nutrition and as adjuncts to antibiotics.Further research,including clinical trials,is essential to address gaps in knowledge,validate findings,and explore the broader applicability of HMOs in improving maternal and neonatal health.
基金supported by the National Natural Science Foundation of China(32401919)the Department of Science and Technology of Henan Province(242102111126).
文摘Recent studies have shown that mucilage secretion from aerial roots is an essential feature of modern maize inbred lines,with some retaining the nitrogen-fixing capabilities of ancient landraces.To explore the genetic basis of nitrogen fixation in mucilage and its evolution from teosinte(Zea mays ssp.mexicana)to modern maize,we developed a recombinant inbred line(RIL)population from teosinte and cultivated it under low-nitrogen conditions.Large-scale,multi-year,and multi-environment analyses of RIL-Teo,Doubled Haploid-A(DH-A),Doubled Haploid-B(DH-B),and association populations led to the identification of 15 quantitative trait loci(QTL),68 quantitative trait nucleotides(QTN),and 59 candidate genes linked to mucilage secretion from aerial roots.Functional verification of the candidate gene ZmAco3,which is associated with mucilage secretion in aerial roots,demonstrated that deletion of this gene resulted in a reduction in mucilage secretion in aerial roots.In addition,most maize inbred lines exhibited stronger mucilage secretion from aerial roots under low-nitrogen conditions than under normal-nitrogen conditions.We categorized mucilage secretion into constitutive and low-nitrogen-inducible types.Through genotype-by-environment interaction studies,8 QTL,16 QTN,and 19 candidate genes were identified,revealing the genetic mechanisms underlying mucilage secretion under low-nitrogen conditions.These findings provide a comprehensive genetic analysis of the mucilage-secreting ability of maize aerial roots,contributing to our understanding of nitrogen fixation and offering potential avenues for enhancing nitrogen fixation in modern maize lines.This research advances knowledge of plant nutrient acquisition strategies and has implications for sustainable agricultural practices.
基金the financial support from the National Key Research and Development Program of China(No.2023YFD1701100)the National Natural Science Foundation of China(No.32072450)+2 种基金the National Science Fund for Distinguished Young Scholars of Guangdong Province(No.2021B1515020107)the Opening Foundation of Hubei Key Laboratory of Novel Reactor and Green Chemical Technology(No.NRG202306)the Opening Foundation of Guangdong Province Key Laboratory of Microbial Signals and Disease Control(No.MSDC2023-19)。
文摘Plant bacterial diseases have infiicted substantial economic losses in global crop,fruit,and vegetable production.The conventional methods for managing these diseases typically rely on the application of antibiotics.However,these antibiotics often target the growth factors of the pathogenic bacteria,leading to the accumulation and emergence of drug-resistant strains,which exacerbates antibiotic resistance.Innovative methods are urgently needed to treat and prevent the toxicity caused by these pathogenic bacteria.Targeting virulence mechanisms in pathogens is a globally recognized and effective strategy for mitigating bacterial resistance.TypeⅢsecretion system(T3SS)serves as a crucial virulence determinant in Gram-negative pathogens,and its non-essentials for pathogen growth renders it an ideal target.Targeting the T3SS holds significant potential to alleviate selective pressure for resistance mutations in pathogens.Therefore,targeting T3SS in pathogenic bacteria,while preserving their growth,has emerged as a novel avenue for the development of antimicrobial drugs.In recent years,a multitude of small molecular inhibitors targeting T3SS have been identified.This article offers a comprehensive review of T3SS inhibitors in plant pathogens,while also presenting the latest research advancements in this research direction.
文摘BACKGROUND In diabetic patients,persistent hyperglycemia creates an optimal environment for the proliferation of pathogenic bacteria,resulting in severe complications.Con-sequently,chronic rhinosinusitis(CRS)complicated by diabetes is highly pre-valent in clinical settings.AIM To analyze the results of nasal secretion cultures in diabetic patients with CRS and identify the factors influencing postoperative recurrence.METHODS A retrospective analysis was conducted on the clinical data of 203 diabetic pa-tients with CRS with nasal polyps who underwent the Messerklinger technique at Qingdao Hiser Hospital Affiliated of Qingdao University between January 2021 and January 2023.Preoperative nasal secretions were cultured to determine the types and distribution of pathogenic bacteria and assess antimicrobial suscept-ibility.Based on a one-year follow-up,patients were categorized into recurrence and nonrecurrence groups to analyze differences in their clinical data.Univariate and multivariate analyses were used to identify factors influencing postoperative recurrence.RESULTS Pathogens were detected in 153 of the 203 nasal secretion specimens collected from diabetic patients with CRS.A total of 134 pathogenic bacteria strains were isolated and identified,including 81 strains(60.4%)of gram-positive bacteria and 53 strains(39.6%)of gram-negative bacteria.Gram-positive bacteria exhibited relatively high resistance to penicillin G and erythromycin,while remaining highly sensitive to vancomycin,gentamicin,and rifampicin.Gram-negative bacteria demonstrated relatively high resistance to cefazolin and gentamicin,but showed high sensitivity to imipenem,meropenem,cefepime,and ceftazidime.Univariate analysis revealed statistically significant differences between the recurrence and nonrecurrence groups in fasting blood glucose levels,smoking history,Lund-Mackay scores,visual analog scale(VAS)scores,nasal septum deviation,allergic rhinitis,bronchial asthma,postoperative infection,long-term use of nasal decongestants,and adherence to medical prescriptions.Multivariate regression analysis identified fasting blood glucose levels and VAS-measured nasal symptom severity scores as independent factors influencing postoperative recurrence.CONCLUSION In CRS patients with nasal polyps(CRSwNP),the detection rate of nasal pathogens is relatively high,and most of the isolated bacteria exhibit antimicrobial resistance.Additionally,the blood glucose level of patients with CRS combined with CRSwNP is a risk factor for postoperative recurrence.
基金supported by the Youth innovation Program of Chinese Academy of Agricultural Sciences(No.Y2023QC32)the foundation of Tianjin Natural Science Foundation(No.22JCQNJC01460)the Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs)and the Youth Talent Project of Agro-Environmental Protection Institute,Ministry of Agricultural and Rural Affairs(Xu Yan).
文摘The exponential growth of antibiotic-resistant bacteria and antibiotic-resistant genes(ARGs)in soil-crop systems in recent years has posed a great challenge to ecological security and human health.While many studies have documented the residues of ARGs in soils and crops,but little is known about who drives the proliferation of ARGs in farming systems and what their underlying mechanisms are.Herein,we explored the occurrence and proliferating behavior of ARGs in soil-crop environments in terms of root secretions and plant volatiles.This review highlighted that plant root secretions and volatile organic compounds(VOCs)served as key substances mediating the development of antibiotic resistance in the soil-crop system.Still,there is controversy here as to plant root secretions promote the ARGs proliferation or inhibit.Some studies indicated that root secretions can suppress the colonization of ARGs,mainly attributed by the production of bluntedmetabolic enzymes and blocking of cellular exocytosis systems.Whereas the others have evidenced that root secretions can promote ARGs proliferation,primarily by altering the structure of microbial communities to influence species interactions and thus indirectly affect the proliferation of ARGs.Also,VOCs can act as molecular signals to convey antibiotic resistance information to their neighbors,which in turn drive the up-regulation of ARGs expression.Even so,the mechanism by which VOC-driven antibiotic resistance acquisition and proliferation need to be further probed.Overall,this review contributed to the development of products and technologies to impede the ARGs proliferation in agricultural environment.
基金received financial support from the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the special funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District,China(PT202101-02)。
文摘The oral secretions of insect herbivores are complex mixtures of organic and inorganic solutes and enzymes that are deposited onto plant tissues during the feeding process.Some specific components of insect oral secretions have been shown to confer important functions in mediating plant–insect interactions at the molecular level.In this review,we examined the biochemical studies of insect oral secretions to summarize the current knowledge of their compositions.We then moved beyond the functional studies of components of oral secretions,and focused on the literature that pinpointed specific molecular targets of these compounds.Finally,we highlighted the investigations of oral secretion components in the context of insect physiology,which shed light on the potential evolutionary trajectory of these multi-functional molecules.
文摘Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were found toxic to mice with the intraperitoneal LD 50 of 11 5?mg/kg,18 8?mg/kg,and 264?mg/kg,respectively.No acute lethal toxicities were observed for the skin secretions of Rana nigromaculata,Rana guentheri and Rana limnocharis in a dose up to 500?mg/kg.The lethal toxicities of the skin secretions of T verrucosus and B maxima to mice are in the same grade as those of Viperidae snake venoms.The toxic components in T verrucosus and B maxima skin secretions are the proteins with molecular weights ranging from 3 to 60?kDa.All the skin secretions had both proteolytic activity and trypsin inhibitory activity.The skin secretions from T verrucosus , B maxima and B andrewsi also displayed wide spectrum antimicrobial activity.On the other hand,the skin secretions from B andrewsi and B maxima showed cytotoxicity on human cancer cells.All the six samples had not significant effects on mammalian blood coagulation system.Phospholipase A 2 activity was only found in the skin secretions of T verrucosus .None of these skin secretions showed acetylcholine esterase activity.
基金supported by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)grant LU 2347/3-1(to PL).
文摘Autophagy is well-known for delivering cargo materials to lysosomes for proteolytic digestion.Recently,autophagy has emerged as a key mechanism in unconventional protein secretion(UPS).This perspective introduces unconventional secretion pathways,focusing on secretory autophagy and its role in secreting protein aggregates associated with neurodegenerative disorders.We also explore additional neuronal functions of secretory autophagy beyond the release of protein aggregates.We propose autophagosomes as transport organelles that deliver cargo material directly from the endoplasmatic reticulum(ER)to the plasma membrane rather than solely to lysosomes.
基金Supported by the Ministry of Education.Science and Technology (Grant No.2012RTAL2009172)
文摘Objective:To evaluate anti-diabetic effect of Caulrpa kntillifera(C.lentillifera).Methods:The inhibitory effect of C.lentillifera extract on dipeptidyl peptidase-IV and a-glucosidase enzyme was measured in a cell free system.Then,interleukin-1βand interferon-γinduced cell death and insulin secretion were measured in rat insulinoma(RIN)cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ELISA kit,respectively.Glucose uptake and glucose transporter expression were measured by fluorometry and western blotting,using 3T3-Ll adipocytes.Results:C.lentillifera extract significantly decreased dipeptidyl peptidase-IV and a-glucosidase enzyme activities,and effectively inhibited cell death and iNOS expression in interleukin-1βand interfcron-γinduced RIK cells.Furthermore,C.lntillifera extract significantly enhanced insulin secretion in RTN cells and glucose transporter expression and glucose uptake in 3T3-L1adipocytes.Conclusions:Thus,our results suggest that C.lentillifera could be used as a potential antidiabetic agenl.
文摘Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.
基金Supported by The Health and Labor Sciences Research Grants(Comprehensive Research on Disability,Health,and Welfare H21-kokoro-002)(H.K.)the Core Research for Evolutional Science and Technology Program,CREST,Japan Science and Technology Agency(JST)(T.N.,N.A.and H.K.)+3 种基金the Naito Foundation(N.A)the Takeda Science Foundation(T.N.)a grant from Grant-in-Aid for Scientific Research(B),(JSPS KAKENHI)(T.N.),No.24300139Grant-in-Aid for Challenging Exploratory Research(JSPS KAKENHI)(T.N.)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.25640019
文摘Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.
基金Supported by Grants from The National Institute for Physiological Sciences and Graduate University for Advanced Studies
文摘AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen(263% ± 63% vs 309% ± 45%,227% ± 63% vs 309% ± 45%,P = 0.899,0.626 > 0.05 respectively,by ANOVA).Accordingly,Danshen does not bind with M3 or α1 receptors.These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine.Carbamylcholine activates the M3 receptor to release inositol trisphosphate(IP3) and quickly releases Ca2+ from the calcium stores.The elevation of [Ca2+]i induces chloride release and quick osmosis,resulting in an onset of fluid secretion.An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels.The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen(1.8 ± 0.8 μL/g-min vs 101.9 ± 17.2 μL/g-min,P = 0.00023 < 0.01,by t-test),suggesting the involvement of Ca2+ in the activation of these channels.Therefore,IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen,but rather,there may be a distinct signalling process.CONCLUSION:The present findings suggest that Danshen can be used in the treatment of xerostomia,to avoid the systemic side effects associated with muscarinic drugs.
文摘Ghrelin, a novel growth hormone-releasing peptide, was originally isolated from rat and human stomach. Ghrelin has been known to increase the secretion of growth hormone (GH), food intake, and body weight gain when administered peripherally or centrally. Ghrelin is also known to stimulate the gastric motility and the secretion of gastric acid. In the previous studies, the action of ghrelin on acid secretion was shown to be as strong as that of histamine and gastrin in in-vivo experiment. In the studies, the mechanism for the action of ghrelin was also investigated. It was shown that vagotomy completely inhibited the action of ghrelin on the secretion of gastric acid suggesting that vagal nerve is involved in the mechanism for the action of ghrelin on acid secretion. As famotidine did not inhibit ghrelin-in-duced acid secretion in the study by Masuda et al, they concluded that histamine was not involved in the action of ghrelin on acid secretion. However, we have shown that famotidine completely inhibited ghrelin-induced acid secretion and histidine decarboxylase (HDC) mRNA was increased in gastric mucosa by ghrelin injection which is inhibited by vagotomy Our results indicate that histamine is involved in the action of ghrelin on acid secretion. Furthermore synergistic action of gastrin and ghrelin on gastric acid secretion was shown. Although gastrin has important roles in postprandial secretion of gastric acid, ghrelin may be related to acid secretion during fasting period or at night. However, further studies are needed to elucidate the physiological role of ghrelin in acid secretion.
文摘Irritable bowel syndrome(IBS)is a chronic,recurring,and remitting functional disorder of the gastrointestinal tract characterized by abdominal pain,distention,and changes in bowel habits.Although there are several drugs for IBS,effective and approved treatments for one or more of the symptoms for various IBS subtypes are needed.Improved understanding of pathophysiological mechanisms such as the role of impaired bile acid metabolism,neurohormonal regulation,immune dysfunction,the epithelial barrier and the secretory properties of the gut has led to advancements in the treatment of IBS.With regards to therapies for restoring intestinal permeability,multiple studies with prebiotics and probiotics are ongoing,even if to date their efficacy has been limited.In parallel,much progress has been made in targeting low-grade inflammation,especially through the introduction of drugs such as mesalazine and rifaximin,even if a better knowledge of the mechanisms underlying the low-grade inflammation in IBS may allow the design of clinical trials that test the efficacy and safety of such drugs.This literature review aims to summarize the findings related to new and investigational therapeutic agents for IBS,most recently developed in preclinical as well as Phase 1 and Phase 2clinical studies.
基金Supported by Cooperation survey and research project of the Nippon Foundation of the Japan-China Medical Association (2006-12)the International cooperation project (BZ2006058) of Bureau of Science and Technology of Jiangsu Province,China
文摘AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.
文摘AIM To study the peripheral mechanism of the inhibitory effect of intra third ventricular administration (icv) of histamine (HA) on gastric acid secretion in rats. METHODS Gastric acid was continuously washed with 37℃ saline by a perfusion pump in male adrenalectomized SD rats. Drugs were injected intravenously (iv) by a syringe pump and their effect on pentagastrin induced (10μg·kg·h, iv) gastric acid secretion was observed. RESULTS The inhibitory effect of HA (1μg, icv) on gastric acid secretion was blocked by subdiaphragmatic vagotomy, and pretreatment with atropine (0 005mg·kg·h, iv). Pretreatment with somatostatin antagonist, cyclo [7 aminoheptanoyl Phe D Trp Lys Thr(Bzl)], ( 2μg - 4μg ·kg· 100min , iv) could also block the inhibitory effect of HA on gastric acid secretion in a dose dependent manner. CONCLUSION The inhibitory effect of centrally administrated HA on gastric acid secretion may be mediated by vagi, acetylcholine M receptor and somatostatin.
