Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)mode...Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.展开更多
Flexible piezoresistive pressure sensors have attracted much attention for applications in health monitoring and human-machine interfaces due to their simple device structures and easy-to-read signals.For practical ap...Flexible piezoresistive pressure sensors have attracted much attention for applications in health monitoring and human-machine interfaces due to their simple device structures and easy-to-read signals.For practical applications,the deployment of flexible pressure sensors characterized by high sensitivity and fast response time is imperative for the rapid and accurate detection and monitoring of tiny signals.Such capabilities are essential for facilitating immediate feedback and informed decision-making across a spectrum of contexts.Drawing lessons from the hypersensitive and fast-responding pressure sensing structures in the dragonfly’s neck(for stable imaging during its highly maneuverable flight),a Biomimetic Piezoresistive Pressure Sensor(BPPS)with exquisite mechanically interlocking sensing microstructures is developed.Each interlocking perceptual structure pair consists of an ox-horn-shaped and a mushroom-shaped structural unit.Through the characteristic configuration of the perceptual structure pair,the BPPS realizes a fast gradient accumulation of the contact area,thus synergistically enhancing the sensitivity and fast response capability.Remarkably,the sensitivity of the BPPS reaches 0.35 kPa^(−1),which increased by 75%compared to the 0.2 kPa^(−1) of the pressure sensors without biomimetic structures.Moreover,the BPPS also achieves rapid response/recovery times(<90/15 ms).Our BPPS finds utility in tasks such as identifying objects of different weights,monitoring human respiratory status,and tracking motion,demonstrating its potential in wearable healthcare devices,assistive technology,and intelligent soft robotics.Moreover,it possesses the advantages of high sensitivity and fast response time in practical applications.展开更多
BACKGROUND Prompt and effective cardiopulmonary resuscitation(CPR)can promote the recovery of spontaneous circulation to some extent and can save patients’lives.The minimum target of cardiac resuscitation is the rest...BACKGROUND Prompt and effective cardiopulmonary resuscitation(CPR)can promote the recovery of spontaneous circulation to some extent and can save patients’lives.The minimum target of cardiac resuscitation is the restoration of spontaneous circulation(ROSC).However,owing to prolonged sudden cardiac arrest,there is relatively high mortality within 24 h after cardiac resuscitation.Moreover,severe cerebral anoxia can deteriorate the prognosis of patients.Therefore,it is important to adopt an effective clinical evaluation of acute myocardial infarct(AMI)patients’prognosis after cardiac resuscitation for the purpose of prevention and management.AIM To investigate early CPR effects on human myeloperoxidase(MPO),soluble ST2(sST2),and hypersensitive C-reactive protein(hs-CRP)levels in AMI patients.METHODS In total,54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group,and 50 other patients with AMI were selected as the control group.The differences in serum levels of MPO,sST2,and hs-CRP between the observation group and the control group were tested,and the differences in the serum levels of MPO,sST2,and hs-CRP in ROSC and non-ROSC patients,and in patients who died and in those who survived,were analyzed.RESULTS Serum levels of MPO,sST2,hs-CRP,lactic acid,creatine kinase isoenzyme(CKMB),and cardiac troponin I(cTnI)were significantly higher in the observation group than in the control group(P<0.05).Serum levels of MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI in the observation group were lower after CPR than before CPR(P<0.05).In the observation group,MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI serum levels were lower in ROSC patients than in non-ROSC patients(P<0.05).MPO,sST2,hs-CRP,and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived(P<0.05).The areas under receiver operating characteristic curve predicted by MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI were 0.616,0.681,0.705,0.704,0.702,and 0.656,respectively(P<0.05).The areas under receiver operating characteristic curve for MPO,SST2,hs-CRP,and lactic acid to predict death were 0.724,0.800,0.689,and 0.691,respectively(P<0.05).Logistic regression analysis showed that MPO,sST2,and hs-CRP were the influencing factors of ROSC[odds ratios=1.667,1.589,and 1.409,P<0.05],while MPO,sST2,hs-CRP,and lactic acid were the influencing factors of death(odds ratios=1.624,1.525,1.451,and 1.365,P<0.05).CONCLUSION Serum levels of MPO,sST2,hs-CRP,and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.展开更多
hrp mutants were produced from strain JXOIII of Xanthomonas oryzae pv. oryzae (Xoo) and strain RS105 of X.o. pv. oryzicola (Xooc), respectively, by using diethyl sulfate (DES) as a mutagenic che ...hrp mutants were produced from strain JXOIII of Xanthomonas oryzae pv. oryzae (Xoo) and strain RS105 of X.o. pv. oryzicola (Xooc), respectively, by using diethyl sulfate (DES) as a mutagenic che mical. All the hrp mutants lost their pathogenicity on a susceptible host plant, rice (Shanyou63), and elicitation of the hypersensitive response (HR) on a nonhost plant, tobacco (NC89). Extracellular enzyme (amy lase, pectate lyase, proteinase, cellulase and lipase) activities of all the hrp mutants were similar to those of the corresponding wild type strains. The response of tobacco to cell sonicated integrations of the wild type strains and the hrp mutants demonstrated that there existed an HR eliciting substance which was heat stable and sensitive to protease. No HR appeared on tobacco after infiltration of the lipopolysaccharide (LPS) of both the wild strains and hrp mutants into tobacco leaves. The ability of the Xooc hrp mutants to induce HR on tobacco and cause streak disease on rice was restored by complementation with pUHRX245 from JXOIII genomic DNA library and by pUHRS138 from RS105 genomic DNA library, respectively. Subcloning of a 38.6 kb hrp fragment insert in pUHRX245 and a 39.3 kb insert in pUHRS138 revealed that a 3.3 kb Sac Ⅰ fragment from pUHRX245 and a 4.5 kb Bam HⅠ Kpn Ⅰ fragment from pUHRS138 were the minimal functional portions required for restoration of the ability of Xooc hrp mutants to induce HR on tobacco and cause disease on rice. The disease symptom caused by the conjugant (M1005 plus 3.3 kb) on rice was similar to that caused by the wild type of Xooc. It suggests that the two fragments contain the same hrp gene(s) and are responsible reciprocally for HR induction on tobacco and pathogenicity on rice.展开更多
Alpha-picolinic acid (PA),a metabolite of tryptophan and an inducer of apoptosis in the animal cell,has been reported to be a toxin produced by some of plant fungal pathogens and used in screening for disease resistan...Alpha-picolinic acid (PA),a metabolite of tryptophan and an inducer of apoptosis in the animal cell,has been reported to be a toxin produced by some of plant fungal pathogens and used in screening for disease resistant mutants. Here,we report that PA is an efficient apoptosis agent triggering cell death of hypersensitive-like response in planta. Confirmed by Fluorescence Activated Cell Sorter (FACS),rice suspension cells and leaves exhibited programmed cell death induced by PA. The PA-induced cell death was associated with the accumulation of reactive oxygen species that could be blocked by diphenylene iodonium chloride,indicating that the generation of reactive oxygen species was NADPHoxidase dependent. We also demonstrated the induction of rice defense-related genes and subsequent resistant enhancement by PA against the rice blast fungus Magnaporthe grisea. Hence,it was concluded that the PA-stimulated defense response likely involves the onset of the hypersensitive response in rice,which also provides a simple eliciting tool for studying apoptosis in the plant cell.展开更多
The plant cytoskeleton is a highly dynamic and versatile intracellular scaffold composed of microtubules and microfilaments,serving a multiplicity of functions in plant cells.To reveal the relationship between the cyt...The plant cytoskeleton is a highly dynamic and versatile intracellular scaffold composed of microtubules and microfilaments,serving a multiplicity of functions in plant cells.To reveal the relationship between the cytoskeleton in wheat(Triticum aestivum L.)cv.Suwon 11 attacked by the non-host pathogen Sphaerotheca fuliginea and the initiation of the hypersensitive response,the microtubule inhibitor oryzalin was injected into the wheat leaves immediately prior to inoculation.The incidence of hypersensitive cell death was significantly lower than that in water-treated control.In addition,the occurrence of hypersensitive cell death was also delayed and S.fuliginea was able to penetrate and form haustoria in epidermal tissues of wheat.All the results above indicated that hypersensitive cell death was associated with depolymerisation of microtubules,suggesting that microtubules might play an important role in the expression of non-host resistance of wheat.展开更多
Harpins play a key role in inducing disease resistance in crops,and identifying their core functional regions and establishing a system for their efficient expression would be very valuable.In this study,large amounts...Harpins play a key role in inducing disease resistance in crops,and identifying their core functional regions and establishing a system for their efficient expression would be very valuable.In this study,large amounts of soluble fusion proteins of harpin HrpZ and its subpeptides were obtained via the optimized induction conditions(28℃ with 0.5 mmol·L^(-1) IPTG for 6 h)in Escherichia coli BL21(DE3).Hypersensitive response(HR)assays demonstrated that the C-terminal 66 aa of HrpZ(HrpZ_C_2_2)elicited a strong HR in tobacco(Nicotiana benthamiana)and grape(Flame Seedless)leaves.Additionally,treatment with HrpZ,and particularly HrpZ_C_2_2,significantly reduced the disease incidence and severity index of field vine leaves and those inoculated with downy mildew.The determination of the physiological parameters indicated that HrpZ,and especially HrpZ_C_2_2,improved the photosynthesis-and chlorophyll fluorescence-related parameters,enhanced the activity of defense-related enzymes,including SOD,POD,CAT and PAL,and increased the H_(2)O_(2) level.Collectively,we efficiently expressed a core peptide of HrpZ and elucidated its strong ability to elicit a HR and resistance to downy mildew.This research provides insight into understanding the structure and function of HrpZ and will advance the application of HrpZ_C_2_2 to increase the resistance of grapevine to downy mildew.展开更多
Nonhost resistance is a phenomenon that enables plants to protect themselves against the majority of potential pathogens, and thus has a great potential for application in plant protection. We recently found that CfHN...Nonhost resistance is a phenomenon that enables plants to protect themselves against the majority of potential pathogens, and thus has a great potential for application in plant protection. We recently found that CfHNNI1 （for Cladosporium fulvum host and nonhost plant necrosis inducer 1） is an inducer of plant hypersensitive response （HR） and nonhost resistance. In this study, its functional mechanism was analyzed. CfHNN11 was a single copy gene in C. fulvum genome. The functional ORF of the CfHNN11 cDNA was ATG3-TAG780, which showed homology with genes encoding bZIP transcription factors. The functional ORF included in frame an inner one ATG273-TAG780, which was sufficient to induce HR in plants. CfIINN11 induced plant HR in a dose-dependent manner. CfHNNIl-induced necrosis in NahG transgenic tomato plants was significantly stronger than that in their wild type controls. However, the necrosis in Nr and defl tomato mutants was similar to that in their corresponding wild type plants. These data demonstrate that induction of HR and nonhost resistance by CfHNNI1 is negatively regulated by salicylic acid signalling pathway but independent of ethylene and jasmonic acid signalling pathways.展开更多
Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into...Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into one flexible strain sensor remains a huge challenge.Herein,inspired by the hysteresis strategy of the scorpion slit receptor,a bio-inspired flexible strain sensor(BFSS)with parallel through-slit arrays is designed and fabricated.Specifically,BFSS consists of conductive monolayer graphene and viscoelastic styrene–isoprene–styrene block copolymer.Under the synergistic effect of the bio-inspired slit structures and flexible viscoelastic materials,BFSS can achieve both hypersensitivity and highly selective frequency response.Remarkably,the BFSS exhibits a high gage factor of 657.36,and a precise identification of vibration frequencies at a resolution of 0.2 Hz through undergoing different morphological changes to high-frequency vibration and low-frequency vibration.Moreover,the BFSS possesses a wide frequency detection range(103 Hz)and stable durability(1000 cycles).It can sense and recognize vibration signals with different characteristics,including the frequency,amplitude,and waveform.This work,which turns the hysteresis effect into a"treasure,"can provide new design ideas for sensors for potential applications including human–computer interaction and health monitoring of mechanical equipment.展开更多
OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pat...OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.展开更多
Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of stan...Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.展开更多
BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and...BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.展开更多
OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model wa...OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.展开更多
Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to ...Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.展开更多
[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial ...[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
基金supported by the National Natural Science Foundation of China(No.82471229)Science and Technology Collaborative Innovation Fund of Fujian Province(No.2021Y9172)the Natural Science Foundation of Fujian Province,China(No.2023J01169)。
文摘Oxytocin has been found to modulate and improve pain in humans,but the mechanisms underlying these antinociceptive properties,especially in visceral hypersensitivity,are still unclear.Irritable bowel syndrome(IBS)models were established by colorectal distention in newborn rats aged 8 to 14 days,and visceral hypersensitivity was assessed using electromyogram(EMG).Oxytocin or saclofen was administered intrathecally to evaluate visceral hypersensitivity in the rats.The protein expressions of oxytocin receptor(OTR),γ-aminobutyric acid type B1 receptor(GABAB1),and transient receptor potential vanilloid 1(TRPV1)in the lumbosacral spinal cord regions were measured.IBS rats exhibited a unique spinal cord molecular signature comprising decreased OTR/GABAB1 and increased TRPV1 expression.Intrathecal oxytocin treatment not only normalized these molecular alterations(increasing GABAB1 while decreasing TRPV1)but also ameliorated visceral pain behaviors.Crucially,this therapeutic effect was fully reversed by GABAB1 inhibition,establishing the necessity of intact GABAergic signaling for oxytocin-mediated analgesia.Collectively,these findings indicate that oxytocin relieves visceral hypersensitivity through the regulation of GABAB1 and TRPV1 in the spinal cord of IBS rats.
基金supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(No.52021003)National Natural Science Foundation of China(Nos.52222509,52105301)+1 种基金the Natural Science Foundation of Jilin Province(Grant No.20220101220JC)supported by“Fundamental Research Funds for the Central Universities”.
文摘Flexible piezoresistive pressure sensors have attracted much attention for applications in health monitoring and human-machine interfaces due to their simple device structures and easy-to-read signals.For practical applications,the deployment of flexible pressure sensors characterized by high sensitivity and fast response time is imperative for the rapid and accurate detection and monitoring of tiny signals.Such capabilities are essential for facilitating immediate feedback and informed decision-making across a spectrum of contexts.Drawing lessons from the hypersensitive and fast-responding pressure sensing structures in the dragonfly’s neck(for stable imaging during its highly maneuverable flight),a Biomimetic Piezoresistive Pressure Sensor(BPPS)with exquisite mechanically interlocking sensing microstructures is developed.Each interlocking perceptual structure pair consists of an ox-horn-shaped and a mushroom-shaped structural unit.Through the characteristic configuration of the perceptual structure pair,the BPPS realizes a fast gradient accumulation of the contact area,thus synergistically enhancing the sensitivity and fast response capability.Remarkably,the sensitivity of the BPPS reaches 0.35 kPa^(−1),which increased by 75%compared to the 0.2 kPa^(−1) of the pressure sensors without biomimetic structures.Moreover,the BPPS also achieves rapid response/recovery times(<90/15 ms).Our BPPS finds utility in tasks such as identifying objects of different weights,monitoring human respiratory status,and tracking motion,demonstrating its potential in wearable healthcare devices,assistive technology,and intelligent soft robotics.Moreover,it possesses the advantages of high sensitivity and fast response time in practical applications.
基金Key R&D Projects in Shanxi Province,China,No.201903D321184.
文摘BACKGROUND Prompt and effective cardiopulmonary resuscitation(CPR)can promote the recovery of spontaneous circulation to some extent and can save patients’lives.The minimum target of cardiac resuscitation is the restoration of spontaneous circulation(ROSC).However,owing to prolonged sudden cardiac arrest,there is relatively high mortality within 24 h after cardiac resuscitation.Moreover,severe cerebral anoxia can deteriorate the prognosis of patients.Therefore,it is important to adopt an effective clinical evaluation of acute myocardial infarct(AMI)patients’prognosis after cardiac resuscitation for the purpose of prevention and management.AIM To investigate early CPR effects on human myeloperoxidase(MPO),soluble ST2(sST2),and hypersensitive C-reactive protein(hs-CRP)levels in AMI patients.METHODS In total,54 patients with cardiac arrest caused by AMI in our hospital were selected as the observation group,and 50 other patients with AMI were selected as the control group.The differences in serum levels of MPO,sST2,and hs-CRP between the observation group and the control group were tested,and the differences in the serum levels of MPO,sST2,and hs-CRP in ROSC and non-ROSC patients,and in patients who died and in those who survived,were analyzed.RESULTS Serum levels of MPO,sST2,hs-CRP,lactic acid,creatine kinase isoenzyme(CKMB),and cardiac troponin I(cTnI)were significantly higher in the observation group than in the control group(P<0.05).Serum levels of MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI in the observation group were lower after CPR than before CPR(P<0.05).In the observation group,MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI serum levels were lower in ROSC patients than in non-ROSC patients(P<0.05).MPO,sST2,hs-CRP,and lactic acid serum levels of patients who died in the observation group were higher than those of patients who survived(P<0.05).The areas under receiver operating characteristic curve predicted by MPO,sST2,hs-CRP,lactic acid,CK-MB,and cTnI were 0.616,0.681,0.705,0.704,0.702,and 0.656,respectively(P<0.05).The areas under receiver operating characteristic curve for MPO,SST2,hs-CRP,and lactic acid to predict death were 0.724,0.800,0.689,and 0.691,respectively(P<0.05).Logistic regression analysis showed that MPO,sST2,and hs-CRP were the influencing factors of ROSC[odds ratios=1.667,1.589,and 1.409,P<0.05],while MPO,sST2,hs-CRP,and lactic acid were the influencing factors of death(odds ratios=1.624,1.525,1.451,and 1.365,P<0.05).CONCLUSION Serum levels of MPO,sST2,hs-CRP,and lactic acid have a certain value in predicting recovery and prognosis of patients with ROSC.
文摘hrp mutants were produced from strain JXOIII of Xanthomonas oryzae pv. oryzae (Xoo) and strain RS105 of X.o. pv. oryzicola (Xooc), respectively, by using diethyl sulfate (DES) as a mutagenic che mical. All the hrp mutants lost their pathogenicity on a susceptible host plant, rice (Shanyou63), and elicitation of the hypersensitive response (HR) on a nonhost plant, tobacco (NC89). Extracellular enzyme (amy lase, pectate lyase, proteinase, cellulase and lipase) activities of all the hrp mutants were similar to those of the corresponding wild type strains. The response of tobacco to cell sonicated integrations of the wild type strains and the hrp mutants demonstrated that there existed an HR eliciting substance which was heat stable and sensitive to protease. No HR appeared on tobacco after infiltration of the lipopolysaccharide (LPS) of both the wild strains and hrp mutants into tobacco leaves. The ability of the Xooc hrp mutants to induce HR on tobacco and cause streak disease on rice was restored by complementation with pUHRX245 from JXOIII genomic DNA library and by pUHRS138 from RS105 genomic DNA library, respectively. Subcloning of a 38.6 kb hrp fragment insert in pUHRX245 and a 39.3 kb insert in pUHRS138 revealed that a 3.3 kb Sac Ⅰ fragment from pUHRX245 and a 4.5 kb Bam HⅠ Kpn Ⅰ fragment from pUHRS138 were the minimal functional portions required for restoration of the ability of Xooc hrp mutants to induce HR on tobacco and cause disease on rice. The disease symptom caused by the conjugant (M1005 plus 3.3 kb) on rice was similar to that caused by the wild type of Xooc. It suggests that the two fragments contain the same hrp gene(s) and are responsible reciprocally for HR induction on tobacco and pathogenicity on rice.
基金supported by the National Natural Science Foudation of China(30125030)the Chinese Academy of Sciences project(KSCX2-SW-301-02)Z.He is a fellow of the CAS“One-Hundred Talent”program.
文摘Alpha-picolinic acid (PA),a metabolite of tryptophan and an inducer of apoptosis in the animal cell,has been reported to be a toxin produced by some of plant fungal pathogens and used in screening for disease resistant mutants. Here,we report that PA is an efficient apoptosis agent triggering cell death of hypersensitive-like response in planta. Confirmed by Fluorescence Activated Cell Sorter (FACS),rice suspension cells and leaves exhibited programmed cell death induced by PA. The PA-induced cell death was associated with the accumulation of reactive oxygen species that could be blocked by diphenylene iodonium chloride,indicating that the generation of reactive oxygen species was NADPHoxidase dependent. We also demonstrated the induction of rice defense-related genes and subsequent resistant enhancement by PA against the rice blast fungus Magnaporthe grisea. Hence,it was concluded that the PA-stimulated defense response likely involves the onset of the hypersensitive response in rice,which also provides a simple eliciting tool for studying apoptosis in the plant cell.
基金financially supported by the National Natural Science Foundation of China(30771398)the 111 Project from Ministry of Education of China(B07049)
文摘The plant cytoskeleton is a highly dynamic and versatile intracellular scaffold composed of microtubules and microfilaments,serving a multiplicity of functions in plant cells.To reveal the relationship between the cytoskeleton in wheat(Triticum aestivum L.)cv.Suwon 11 attacked by the non-host pathogen Sphaerotheca fuliginea and the initiation of the hypersensitive response,the microtubule inhibitor oryzalin was injected into the wheat leaves immediately prior to inoculation.The incidence of hypersensitive cell death was significantly lower than that in water-treated control.In addition,the occurrence of hypersensitive cell death was also delayed and S.fuliginea was able to penetrate and form haustoria in epidermal tissues of wheat.All the results above indicated that hypersensitive cell death was associated with depolymerisation of microtubules,suggesting that microtubules might play an important role in the expression of non-host resistance of wheat.
基金Major Project of Science and Technology of Shandong Province(Grant No.2022CXGC010605)Fruit Industrial Technology System of Shandong Province(Grant No.SDAIT-06-03)+1 种基金Key Research and Development Program of Shandong Province(Grant No.2022LZGCQY019)Agriculture Improved Variety Project of Shandong Province(Grant No.2020 LZGC008).
文摘Harpins play a key role in inducing disease resistance in crops,and identifying their core functional regions and establishing a system for their efficient expression would be very valuable.In this study,large amounts of soluble fusion proteins of harpin HrpZ and its subpeptides were obtained via the optimized induction conditions(28℃ with 0.5 mmol·L^(-1) IPTG for 6 h)in Escherichia coli BL21(DE3).Hypersensitive response(HR)assays demonstrated that the C-terminal 66 aa of HrpZ(HrpZ_C_2_2)elicited a strong HR in tobacco(Nicotiana benthamiana)and grape(Flame Seedless)leaves.Additionally,treatment with HrpZ,and particularly HrpZ_C_2_2,significantly reduced the disease incidence and severity index of field vine leaves and those inoculated with downy mildew.The determination of the physiological parameters indicated that HrpZ,and especially HrpZ_C_2_2,improved the photosynthesis-and chlorophyll fluorescence-related parameters,enhanced the activity of defense-related enzymes,including SOD,POD,CAT and PAL,and increased the H_(2)O_(2) level.Collectively,we efficiently expressed a core peptide of HrpZ and elucidated its strong ability to elicit a HR and resistance to downy mildew.This research provides insight into understanding the structure and function of HrpZ and will advance the application of HrpZ_C_2_2 to increase the resistance of grapevine to downy mildew.
基金financially supported by grants from the National Basic Research Program of China (2009CB119000)the Genetically Modified Organisms Breeding Major Projects (2009ZX08009-044B)+2 种基金the PCSIRT Project (IRT0943)the Fundamental Research Funds for the Central Universities (2011XZZX006)the Program for New Century 151 Talents of Zhejiang Province, China
文摘Nonhost resistance is a phenomenon that enables plants to protect themselves against the majority of potential pathogens, and thus has a great potential for application in plant protection. We recently found that CfHNNI1 （for Cladosporium fulvum host and nonhost plant necrosis inducer 1） is an inducer of plant hypersensitive response （HR） and nonhost resistance. In this study, its functional mechanism was analyzed. CfHNN11 was a single copy gene in C. fulvum genome. The functional ORF of the CfHNN11 cDNA was ATG3-TAG780, which showed homology with genes encoding bZIP transcription factors. The functional ORF included in frame an inner one ATG273-TAG780, which was sufficient to induce HR in plants. CfIINN11 induced plant HR in a dose-dependent manner. CfHNNIl-induced necrosis in NahG transgenic tomato plants was significantly stronger than that in their wild type controls. However, the necrosis in Nr and defl tomato mutants was similar to that in their corresponding wild type plants. These data demonstrate that induction of HR and nonhost resistance by CfHNNI1 is negatively regulated by salicylic acid signalling pathway but independent of ethylene and jasmonic acid signalling pathways.
基金This work was supported by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(Grant No.52021003)National Natural Science Foundation of China(Grant No.51835006)+6 种基金the National Natural Science Foundation of China(Grant Nos.52222509,52105301,U19A20103)Jilin University Science and Technology Innovative Research Team(Grant No.2020TD-03)Interdisciplinary Integration and Innovation Project of JLU(Grant No.JLUXKJC2021ZZ03)the Natural Science Foundation of Jilin Province(Grant No.20220101220JC)Education Department of Jilin Province(Grant No.JJKH20220979KJ)Graduate Innovation Fund of Jilin University(2023CX077)supported by“Fundamental Research Funds for the Central Universities.”。
文摘Flexible strain sensors are promising in sensing minuscule mechanical signals,and thereby widely used in various advanced fields.However,the effective integration of hypersensitivity and highly selective response into one flexible strain sensor remains a huge challenge.Herein,inspired by the hysteresis strategy of the scorpion slit receptor,a bio-inspired flexible strain sensor(BFSS)with parallel through-slit arrays is designed and fabricated.Specifically,BFSS consists of conductive monolayer graphene and viscoelastic styrene–isoprene–styrene block copolymer.Under the synergistic effect of the bio-inspired slit structures and flexible viscoelastic materials,BFSS can achieve both hypersensitivity and highly selective frequency response.Remarkably,the BFSS exhibits a high gage factor of 657.36,and a precise identification of vibration frequencies at a resolution of 0.2 Hz through undergoing different morphological changes to high-frequency vibration and low-frequency vibration.Moreover,the BFSS possesses a wide frequency detection range(103 Hz)and stable durability(1000 cycles).It can sense and recognize vibration signals with different characteristics,including the frequency,amplitude,and waveform.This work,which turns the hysteresis effect into a"treasure,"can provide new design ideas for sensors for potential applications including human–computer interaction and health monitoring of mechanical equipment.
基金National Natural Science Foundation of China:Study on the Molecular Mechanism of the Regulation of Crypt Goblet Cell Pyroptosis and Exocytosis to Repair Ulcerative Colitis Mucus Barrier by the Method of Clearing and Opening the Xuanfu from the Perspective of"Xuanfu-Crypt"(No.82305143),and National Natural Science Foundation of China:Exploring the Molecular Mechanism of"Hewei Jiangni Fang"Intervention in Non-erosive Reflux Disease Esophageal Hypersensitivity from the Perspective of Mas-related Gene X2/Stromal Interaction Molecule 1/Cell Adhesion Molecule 1 Pathway Regulation of Mast Cell/Dorsal Root Ganglion Communication based on the"Xinkai-Kujiang"Method(No.82374401)。
文摘OBJECTIVE:To explore if Hewei Jiangni granule(和胃降逆颗粒,HWJNG)could regulate esophageal hypersensitivity via stromal interaction molecule 1(STIM1)/transient receptor potential vanilloid subfamily member 1(TRPV1)pathway.METHODS:Qualitative analysis of HWJNG was analysis by high performance of liquid and gas chromatography.In vivo,animal model of non-erosive reflux disease(NERD)was established by fructose intake and restraint stress.HWJNG and Omeprazole were administered by gavage to the drug intervention group.Reflux and visceral hypersensitivity were analyzed by pathological changes,PH value test,mechanical paw withdrawal threshold,thermal withdrawal latency and mast cells(MCs)degranulation.In vitro,substance P(SP)-induced P815 cells and dorsal root ganglion(DRG)cells were cocultured.Expression in both mice and cells of STIM1,TRPV1,and esophageal visceral hypersensitivity-related gastrointestinal neurochemicals were validated by enzyme linked immunosorbent assays,quantitative realtime polymerase chain reaction(qRT-PCR)and Western blot.Moreover,overexpression and small interfering RNA against STIM1 were utilized to verify of the role of HWJNG in DRG cells.RESULTS:HWJNG significantly suppressed intercellular space widening,injury of mitochondrial,MCs degranulation,mechanical allodynia and heat neuropathic sensory and increased pH value of esophageal mucosa in NERD mice.HWJNG inhibited expression of visceral hypersensitivityrelated gastrointestinal neurochemicals in esophageal mucosa and activated P815 cells,and expression of the STIM1,TRPV1 and related neurotransmitters in DRG and DRG cells.STIM1 siRNA and HWJNG both reduced P815 cells adhesion to DRGs cells and Ca2+flow into the cytoplasmic space of DRG cells.Furthermore,HWJNG could reversed STIM1 overexpression induced upregulation of TRPV1.CONCLUSION:HWJNG suppressed intercellular space widening in NERD mice,stabilized MCs and restored neuronal hyperexcitability by regulating visceral hypersensitivity via STIM1/TRPV1 pathway.
基金supported in part by grants from the Tianshan Innovation Team Fund Project of Xinjiang Uygur Autonomous Region(2023D14005)the General Project of the Natural Science Foundation of the Xinjiang Uygur Autonomous Region(2022D01A109).
文摘Drug hypersensitivity reactions(DHRs),which produce symptoms from skin rash to anaphylaxis,are immune-mediated adverse reactions caused by drug formulations.The diagnosis of DHRs is challenging due to the lack of standardization for many drugs,and both underdiagnosis and overdiagnosis hamper the follow-up treatment of patients.Therefore,improved methods for diagnosing patients with suspected DHRs are needed.In this review,we analyzed traditional methods used to diagnose DHRs as well as new diagnostic advances made during the last 2 years.None of the diagnostic methods is perfect,as each exhibits varying sensitivities to different types of DHRs.Overall,our analysis indicates that the accuracy of DHR diagnosis can be improved by obtaining a detailed clinical history,physical examination,in vivo and in vitro testing.
基金Supported by the Foundation of the Second Affiliated Hospital of Xi’an Jiaotong University,No.YJ(ZD)202301.
文摘BACKGROUND Reflux hypersensitivity(RH)constitutes roughly 14%of patients with heartburn and 34%of those with refractory heartburn,yet it is inadequately comprehended.AIM To investigate the clinical characteristics and risk factors associated with RH.METHODS We conducted a retrospective analysis of 109 patients with RH and 384 healthy controls from three medical centers between January 2022 and December 2023.Comprehensive data encompassing symptoms,motility,impedance-pH monitoring,and psychological evaluations were collected.RESULTS RH patients encountered a greater frequency of weakly acidic reflux(WAR)events compared to acidic reflux or nonacidic reflux(NAR)events.Upright reflux time(1.22%)exceeds supine reflux time(0.54%)(P<0.05).Extraesophageal symptoms were more prevalent among younger patients and those with elevated NAR(P<0.05).The acidic reflux,WAR,NAR,and peristaltic contraction break length in male patients exceeded those in female patients(P<0.05).Age[odds ratio(OR)=5.633],hiatal hernia(OR=13.103),and anxiety(OR=17.342)constituted independent risk factors for RH.CONCLUSION WAR and NAR are pivotal in RH.Patients with increased NAR are more likely to experience extraesophageal symptoms.Age,hiatal hernia,and anxiety are significant independent risk factors for RH.
基金the National Natural Science Foundation of China(No.81373724,Transient Potential Vanilloid Receptor1 Participates In The Mechanism Of Acupuncture Alleviating Visceral Hypersensitivity)the Joint Innovation Funds of China Academy of Chinese Medical Sciences(No.ZJYB2021-06,Clinical observation of acupuncture in the treatment of chronic urticaria)。
文摘OBJECTIVE:this study to investigate the mechanism underlying the electroacupuncture(EA)alleviates colorectal hypersensitivity,a feature of irritable bowel syndrome(IBS).METHODS:The colorectal hypersensitivity model was established by treating mice with zymosan.Electrophysiological techniques,Western blotting and immunofluorescence staining were used to detect the changes of the sensitive state of the colorectum and the response in spinal ganglion and spinal cord after acupuncture intervention.RESULTS:colorectal distension studies revealed that repetitive applied electroacupuncture treatment on mice could significant alleviates colorectal intensity.Western blotting studies with nerve growth factor(NGF)in the colorectum,substance P(SP)in the spinal ganglion,protein kinase C gamma(PKCγ)in the spinal cord,and transient receptor potential vanilloid 1(TRPV1)showed that electroacupuncture suppressed zymosan-induced expression of TRPV1,NGF and SP in multiple tissues.Immunofluorescence labeling results showed that EA attenuated the expression of NGF in the colorectum,SP in the spinal ganglion,PKCγin the spinal cord,and TRPV1 in all three tissues in zymosan-treated mice.Moreover,the number of neurons double-positive for TRPV1/Isolectin B4(IB4)and TRPV1/Neurofilament(NF)200 was increased in the spinal ganglion.CONCLUSION:these results provide molecular-level evidence that EA alleviates zymosan-induced colorectal hypersensitivity by altering the expression of pain-associated proteins in the colorectum and spinal cord.EA has a potential to be therapeutic intervention option for IBS treatment.
基金supported by the National Key Research and Development Program of China(2021YFD2100700)the National Natural Science Foundation of China(32021005)+1 种基金the 111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘Irritable bowel syndrome-diarrhea(IBS-D)is a prevalent functional bowel disease severely impairs the quality of life of patients.Visceral hypersensitivity(VH)is the main symptom of IBS-D.Probiotics have been found to effectively alleviate VH.In this study,neonatal maternal separation(NMS)was used to induce VH in 72 rats and investigated the effects of daily gavage of 3×10^(9) CFU of Lactobacillus and Bifidobacterium on alleviating the symptoms of IBS-D and behavioral interventions,as well as exploring potential mechanisms.The results demonstrated that L.acidophilus and B.breve could alleviate the symptoms of IBS-D such as VH and increased frequency of bowel movements,as well as improving non-spatial memory in NMS rats.These effects were achieved by modulating the composition of gut microbiota and metabolites(including short-chain fatty acids,deoxycholic acid and adenosine),and by regulating the expression of genes and proteins associated with the NGF/TrkA signaling pathway,tryptophan metabolism,and inflammatory factors in the hippocampus.This finding suggests that L.acidophilus and B.breve have promising potential for the alleviation of IBS.
基金Supported by Science and Technology Plan Project of Zhongshan City(2022B1126).
文摘[Objectives]To explore the mechanism of action of Tongxieyaofang ultrafine granular powder in treating visceral hypersensitivity in rats with diarrhea-predominant irritable bowel syndrome(IBS-D)based on enteric glial cells(EGCs).[Methods]Eighty-four healthy male Wistar rats of SPF grade were selected and randomly assigned to seven groups,each comprising 12 rats:a normal control group,a model control group,a traditional Tongxieyaofang granular powder group(4.060 g/kg),three Tongxieyaofang ultrafine granular powder groups at low,medium,and high doses(1.015,2.030,and 4.060 g/kg of raw drug,respectively),and a pinaverium bromide group(0.018 g/kg).With the exception of the normal control group,all other groups were subjected to an IBS-D visceral hypersensitivity sensitivity model in rats developed by the chronic water avoidance stress method.Three days post modeling,the rats received continuous oral gavage administration for 8 d.Following the treatment period,serum and colon tissue samples were collected from each group.The BDNF level in the serum was quantified using ELISA.Additionally,the protein expression levels of GFAP,BDNF,and TrkB in colon tissues were assessed via Western blot assay.[Results]Compared to the normal control group,the serum BDNF levels in the model control group were significantly elevated(P<0.01).In contrast,each treatment group exhibited a significant reduction in serum BDNF levels relative to the model control group(P<0.01).Furthermore,the protein expression levels of GFAP,BDNF,and TrkB in colon tissue were significantly higher in the model control group compared to the normal control group(P<0.05,P<0.01).Conversely,these protein expressions were significantly decreased in each treatment group compared to the model control group(P<0.05,P<0.01).[Conclusions]Tongxieyaofang ultrafine granular powder effectively alleviates visceral sensitivity in IBS-D rats and inhibits the activation of EGCs,speculating that its mechanism of action involves the suppression of abnormal EGC activation.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
