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
BACKGROUND Food protein-induced enterocolitis syndrome(FPIES)is the most serious type of non-immunoglobulin E(IgE)-mediated food allergic reaction manifesting as sepsis-like symptom,which can lead to shock.Saccharomyc...BACKGROUND Food protein-induced enterocolitis syndrome(FPIES)is the most serious type of non-immunoglobulin E(IgE)-mediated food allergic reaction manifesting as sepsis-like symptom,which can lead to shock.Saccharomyces boulardii(S.boulardii),a probiotic prescribed frequently in clinical settings,has been reported to trigger FPIES in an infant with soy-triggered FPIES.In this report,we describe a new clinical FPIES in which S.boulardii was the sole triggering factor of acute FPIES adverse reaction in seven healthy infants.CASE SUMMARY Seven FPIES cases triggered by only S.boulardii were gathered from 2011 to the present.None of the patients had previously experienced any allergic reaction to cow’s milk,soy,or complementary food.The age of the patients was 4-10-months old,and the symptoms of FPIES developed after ingestion of S.boulardii,which is mostly prescribed for the treatment of gastroenteritis or antibiotic-associated diarrhea.All patients experienced severe repetitive vomiting 1-3 hours after S.boulardii ingestion.Extreme lethargy,marked pallor,and cyanosis were also observed.No IgE-mediated hypersensitivity developed in any patient.Diarrhea was followed by initial intense vomiting in approximately 5-10 hours after S.boulardii ingestion,and only one case showed bloody,purulent,and foul-smelling diarrhea.The patients stabilized quickly,mostly within 6 hours.Symptoms got all improved within 24 hours after discontinuation of S.boulardii.CONCLUSION S.boulardii can be the sole trigger of acute FPIES and be prescribed cautiously even in healthy children without FPIES.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
Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationsh...Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationship between DI,measured as forearm asymmetry,and survivalin the bat Carollia perspicillata.This study aims to test the hypothesis that individuals with higher DI exhibit a lower immune response.We measured a delayed-type hypersensitivity to the antigen phytohemagglutinin(PHA)on 74 males and 65 females of C.perspicillata before and after thebreeding season(BS).Linear models were used to predict the immunological response based on body mass(BM),forearm asymmetry,sex,BS,and testicle length.The best-ftting model accounted for 29% of the variation in immune response and included asymmetry,BM,sex,and BS aspredictors.The immune response was negatively associated with asymmetry and testicle length in males but positively related to asymmetryin females.Both sexes showed a reduced immune response in the late BS.Additionally,the association between immune response and BMchanged direction seasonally,with heavier individuals showing weaker responses early in the BS and stronger responses later.Individual variation in male immunity was predicted by individual attributes,whereas variation in immune response in females was mostly seasonal.Our resultssupport the link between DI,survival,and immune response in short-tailed bats,and suggest that the immunological component measured bythe PHA response may be under fner selection in males due to its stronger correlation with individual traits.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 Esophageal hypersensitivity is an important cause of refractory gastroesophageal reflux disease,in which patients do not respond to standard acid-suppressive therapy and suffer from continuous noncardiac ch...BACKGROUND Esophageal hypersensitivity is an important cause of refractory gastroesophageal reflux disease,in which patients do not respond to standard acid-suppressive therapy and suffer from continuous noncardiac chest pain and regurgitation.The N-methyl-D-aspartate receptor(NMDAR)may play a crucial role in the deve-lopment of visceral hypersensitivity in functional gastrointestinal disorders.However,the specific mechanisms of visceral hypersensitivity in upper digestive tract diseases remain poorly understood.AIM To investigate the role of the NMDAR2B/protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway in the development of esophageal neuropathic pain associated with gastroesophageal reflux disease(GERD).METHODS Thirty-six 6-week-old specific pathogen free rats were randomly assigned to six groups:the control,model,model+NMDAR agonist,model+NMDAR anta-gonist,model+PKA antagonist,and model+NMDAR antagonist+PKA agonist groups,with six rats in each group.The model was induced via an intraperitoneal injection of ovalbumin for sensitization along with local esophageal stimulation.Immunohistochemistry and Western blotting were utilized to assess the expression levels of NMDAR2B signaling pathway-related proteins in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and peripheral esophageal tissues.RT-PCR was used to measure the corresponding mRNA expression,and ELISA was used to determine the serum brain-derived neurotrophic factor(BDNF)concentration.Behavioral scoring was performed during balloon distention and acid perfusion of the lower esophagus.RESULTS Compared with the control group,the model group presented significantly increased expression levels of the NMDAR2B,PKA,CREB,BDNF,substance P,and calcitonin gene-related peptide proteins and mRNAs in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and lower esophagus(P<0.05).Compared with the model group,the model+NMDAR agonist group exhibited even higher expression levels of these proteins and mRNAs(P<0.05),whereas the model+NMDAR antagonist and model+PKA antagonist groups presented lower expression levels(P<0.05).The model+NMDAR antagonist+PKA agonist group presented higher expression levels than did the model+NMDAR antagonist group(P<0.05).The changes in the serum BDNF concentration and behavioral score during balloon distention and acid perfusion were consistent with these changes in expression.CONCLUSION The NMDAR2B signaling pathway plays a critical role in the development of neuropathic pain in GERD through the PKA/CREB/BDNF pathway.展开更多
The parasitic dodder(Cuscuta,Convolvulaceae)species have wide ranges of hosts.However,some plants,including the cultivated tomato(Solanum lycopersicum),have different degrees of resistance to Cuscuta.The cultivated to...The parasitic dodder(Cuscuta,Convolvulaceae)species have wide ranges of hosts.However,some plants,including the cultivated tomato(Solanum lycopersicum),have different degrees of resistance to Cuscuta.The cultivated tomato plants activate a strong hypersensitive response(HR)where Cuscuta haustoria penetrate stems of cultivated tomato,but the underlying mechanisms by which the cultivated tomato perceives Cuscuta and activates resistance remain unclear.In this study,we show that the phytohormones jasmonic acid(JA)and salicylic acid(SA)in cultivated tomato stems were highly induced by Cuscuta australis parasitization.Genetic analyses and experiments of supplementation of JA or SA indicated that the JA and SA pathway not only are both required for activation of HR against Cuscuta parasitization but also function in non-HR-based resistance.The Cuscuta Receptor 1(CuRe1),which is a leucine-rich repeat receptor-like protein,and suppressor of BAK1-interacting receptor kinase(SOBIR1)and SOBIR1-like,two adaptor kinases,are also important for HR-based and non-HR-based resistance.Importantly,we found that the JA and SA pathway both transcriptionally regulate CuRe1.However,in the cure1 mutants,JA and SA levels were still normally induced by C.australis parasitization.We propose a linear model that an unknown receptor perceives Cuscuta parasitization and thus triggers accumulation of JA and SA,which in turn induce the transcription of CuRe1,and CuRe1 and SOBIR1/SOBIR1-like thereby activate HR-based and non-HR-based resistance to Cuscuta.This study underscores the important roles of hormone signaling and resistance(R)genes in host plant-parasitic plant interactions.展开更多
Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory dr...Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory drugs because of their crucial function in triggering immunity.This study set out to examine,for the first time,how hibifolin affected mouse bone-marrow derived(BMDCs)dendritic cells,triggered by lipopolysaccharide(LPS)in vitro.Additionally,a mouse model of contact hypersensitivity(CHS)was used to assess its possible therapeutic effects in vivo.Methods:LPS was administered to BMDCs with or without hibifolin.Major Histocompatibility Complex(MHC)class II,cytokine production,and co-stimulatory molecule(CD80,CD86)expression levels were assessed.To evaluate the functional effects on T-cell activation,mixed lymphocyte responses using OVA specific T-cells were conducted.In vivo,immunoregulatory potential of hibifolin was examined using a CHS mouse model sensitized with 2,4-dinitrofluorobenzene(DNFB).Results:Hibifolin significantly reduced the expression of the proinflammatory cytokines TNF-αand IL-6,as well as the costimulatory molecules CD80,CD86,and MHC II induced by LPS,by about 40-50%.These effects were associated with reduced NF-κB and p38-MAPK pathway activity.JNK and ERK phosphorylation levels did not alter significantly.In vitro,BMDCs treated with hibifolin showed a 40%-45%down-regulated capacity to stimulate T-cell propagation and IFN-γrelease.Oral hibifolin treatment in vivo modestly decreased DNFB-induced CHS responses by 30%-40%.Conclusion:Overall,our results offer new insights that by inhibiting NF-κB and p38-MAPK signaling,hibifolin decreases the expression of costimulatory molecules and cytokines,thereby limiting BMDC activation,suppressing T-cell responses,and exerting immunomodulatory effects in the CHS mouse model.展开更多
The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii...The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.展开更多
Laser therapy is a widely accepted method for tattoo removal,fragmenting tattoo pigments for eventual clearance by the immune system.However,tattoos presenting with signs of allergic reactions—such as erythema,swelli...Laser therapy is a widely accepted method for tattoo removal,fragmenting tattoo pigments for eventual clearance by the immune system.However,tattoos presenting with signs of allergic reactions—such as erythema,swelling,pruritus,or localized dermatitis—pose unique challenges that contraindicate the use of laser treatments.This review explores clinical and immunological reasons why laser therapy should be avoided in tattoos manifesting allergic reactions,focusing on the exacerbation of symptoms,potential systemic hypersensitivity,and increased risk of severe adverse effects.Tattoo inks,particularly those containing red pigments,are known to induce delayed hypersensitivity reactions,driven by the body’s immune response to the injected foreign substances.Laser-induced breakdown of tattoo pigments can trigger an amplified allergic response due to the rapid release of pigment particles,which may further stimulate the immune system.Additionally,photomechanical fragmentation of tattoo inks during laser treatment increases the bioavailability of allergenic compounds,heightening the risk of severe inflammatory reactions and systemic dissemination of these allergens.Histological evidence suggests allergic reactions to tattoo inks are often granulomatous in nature,and the inflammatory environment created by laser therapy can exacerbate this granulomatous process,resulting in hypertrophic scarring or keloid formation.Moreover,patients with underlying allergic sensitivities to tattoo pigments are at an elevated risk of systemic complications,including generalized urticaria or angioedema,upon laser treatment.Current evidences suggests tattoos of allergic reactions should be not undergone laser therapy,emphasizing the need for alternative management strategies,such as topical application of corticosteroids or excision in severe cases.Clinicians must conduct a thorough pre-treatment assessment,including the patch testing,to identify potential allergenic inks and avoid laser-based interventions on reactive tattoos to prevent complications and safeguard patient's safety.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
Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion...Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion channel receptor implicated in the perception of visceral injury.Recent studies indicated that TRPV1 mediates visceral hypersensitivity in IBS-D patients by enhancing the excitability of intestinal sensory neurons.Consequently,inhibiting the TRPV1 may be a promising option for the treatment of IBS-D.Current research demonstrates that various traditional Chinese medicine(TCM)methods,such as herbal prescriptions,acupuncture,and moxibustion,can reduce visceral sensitivity by regulating TRPV1 expression and its activation sensitization.This suggests that TCM methods may serve as safe and effective options for alleviating IBS-D.Therefore,this article summarizes potential therapeutic strategies of TCM as a regulator of TRPV1 for managing IBS-D.It also provides insights into potential TCM methods and natural phytochemical molecular nuclei for future drug research targeting TRPV1 in IBS-D.展开更多
Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental pati...Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.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
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
[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
The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzin...The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.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
OBJECTIVE:To investigate the role of satellite glial cells in irritable bowel syndrome(IBS)and the effect of electroacupuncture(EA)at the Tianshu(ST25)and Shangjuxu(ST37)combination.METHODS:A model for visceral hypers...OBJECTIVE:To investigate the role of satellite glial cells in irritable bowel syndrome(IBS)and the effect of electroacupuncture(EA)at the Tianshu(ST25)and Shangjuxu(ST37)combination.METHODS:A model for visceral hypersensitivity in IBS was induced through colorectal distension(CRD)stimulation.Clean-grade male Sprague-Dawley(SD)rats were randomly divided into four groups:a normal group(NG),a model group(MG),an electroacupuncture group(EA),and a glial cell inhibitor group(FCA).Bilateral EA(2/100 Hz,1 mA,30 min)was administered at the Tianshu(ST25)and Shangjuxu(ST37)in week 6.Abdominal withdrawal reflex(AWR)scores were used to assess the behavioral response associated with visceral hyperalgesia,while hematoxylin-eosin staining was employed to evaluate pathological changes in the colon.The protein and mRNA levels of glial fibrillary acidic protein(GFAP)in the colon and colon-related dorsal root ganglion(DRG)were analyzed using immun-ofluorescence,immunohistochemistry,Western blotting,real-time polymerase chain reaction.The impact of EA on electrophysiological properties of colon-related DRG neurons was observed through whole-cell patch clamp analysis.RESULTS:EA significantly reduced the visceral pain behavior scores in rats with IBS in response to graded(20,40,60,80 mm Hg)CRD stimulation.Additionally,EA downregulated the protein and mRNA expression levels of GFAP in the colon and colon-related DRG of rats with IBS.EA also regulated the resting membrane potential,rheobase and action potential of colon-related DRG neurons in rats with IBS.CONCLUSIONS:EA can regulate the excitatory properties of colon-related DRG neurons by downregulating the protein and mRNA expression of GFAP in the colon and colon-related DRG,indicating a potential neurobiological mechanism by which EA relieves visceral hypersensitivity in rats with IBS.展开更多
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 by The Keimyung University Dongsan Medical Center in 2006.
文摘BACKGROUND Food protein-induced enterocolitis syndrome(FPIES)is the most serious type of non-immunoglobulin E(IgE)-mediated food allergic reaction manifesting as sepsis-like symptom,which can lead to shock.Saccharomyces boulardii(S.boulardii),a probiotic prescribed frequently in clinical settings,has been reported to trigger FPIES in an infant with soy-triggered FPIES.In this report,we describe a new clinical FPIES in which S.boulardii was the sole triggering factor of acute FPIES adverse reaction in seven healthy infants.CASE SUMMARY Seven FPIES cases triggered by only S.boulardii were gathered from 2011 to the present.None of the patients had previously experienced any allergic reaction to cow’s milk,soy,or complementary food.The age of the patients was 4-10-months old,and the symptoms of FPIES developed after ingestion of S.boulardii,which is mostly prescribed for the treatment of gastroenteritis or antibiotic-associated diarrhea.All patients experienced severe repetitive vomiting 1-3 hours after S.boulardii ingestion.Extreme lethargy,marked pallor,and cyanosis were also observed.No IgE-mediated hypersensitivity developed in any patient.Diarrhea was followed by initial intense vomiting in approximately 5-10 hours after S.boulardii ingestion,and only one case showed bloody,purulent,and foul-smelling diarrhea.The patients stabilized quickly,mostly within 6 hours.Symptoms got all improved within 24 hours after discontinuation of S.boulardii.CONCLUSION S.boulardii can be the sole trigger of acute FPIES and be prescribed cautiously even in healthy children without FPIES.
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supported by Conselho Nacional de Desenvolvimento Cientifco e Tecnologico(CNPq),Fundacaode Amparoa Pesquisa do Rio de Janeiro(FAPERJ),Fundacaode Amparoa Pesquisa do Estado de Sao Paulo(FAPESPGrant nº2014/16/320-7)Coordenacao de Aperfeicoamentode Pessoal de Nível Superior(CAPES)-Finance Code 001+1 种基金by grants to LGHM and APCN from the Visiting Research Program of the FAPESP(nº2017-17607-6)supported by the PASPA-DGAPA program of the Universidad Nacional Autonoma de Mexico(nº814-2018).
文摘Developmental instability(DI)is a phenomenon whereby organisms are unable to buffer developmental disturbances,resulting in asymmetricvariation of paired traits.Previous research has demonstrated a negative relationship between DI,measured as forearm asymmetry,and survivalin the bat Carollia perspicillata.This study aims to test the hypothesis that individuals with higher DI exhibit a lower immune response.We measured a delayed-type hypersensitivity to the antigen phytohemagglutinin(PHA)on 74 males and 65 females of C.perspicillata before and after thebreeding season(BS).Linear models were used to predict the immunological response based on body mass(BM),forearm asymmetry,sex,BS,and testicle length.The best-ftting model accounted for 29% of the variation in immune response and included asymmetry,BM,sex,and BS aspredictors.The immune response was negatively associated with asymmetry and testicle length in males but positively related to asymmetryin females.Both sexes showed a reduced immune response in the late BS.Additionally,the association between immune response and BMchanged direction seasonally,with heavier individuals showing weaker responses early in the BS and stronger responses later.Individual variation in male immunity was predicted by individual attributes,whereas variation in immune response in females was mostly seasonal.Our resultssupport the link between DI,survival,and immune response in short-tailed bats,and suggest that the immunological component measured bythe PHA response may be under fner selection in males due to its stronger correlation with individual traits.
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 National Major Project of Science and Technology for the Prevention and Control of the"Four Major Chronic Diseases",No.2024ZD0520903National Natural Science Foundation of China,No.82004324+4 种基金the Training Program for High-caliber Talents of Clinical Research at Affiliated Hospitals of SHUTCMthe Training Project for Xinglin Young and Middle-Aged Talents of Shanghai University of Traditional Chinese Medicine,No.SHUTCM HR(2020)23the Project of National Famous Traditional Chinese Medicine Expert(Shengliang Zhu)Inheritance Studio,No.NATCM HR(2022)75the Zhu Shengliang Academic Experience Research Studio Project of Shanghai Famous Traditional Chinese Medicine,No.SHGZS-202203the Shanghai High-Level Talent Leadership Plan for Traditional Chinese Medicine,No.ZY(2021-2023)-0403.
文摘BACKGROUND Esophageal hypersensitivity is an important cause of refractory gastroesophageal reflux disease,in which patients do not respond to standard acid-suppressive therapy and suffer from continuous noncardiac chest pain and regurgitation.The N-methyl-D-aspartate receptor(NMDAR)may play a crucial role in the deve-lopment of visceral hypersensitivity in functional gastrointestinal disorders.However,the specific mechanisms of visceral hypersensitivity in upper digestive tract diseases remain poorly understood.AIM To investigate the role of the NMDAR2B/protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway in the development of esophageal neuropathic pain associated with gastroesophageal reflux disease(GERD).METHODS Thirty-six 6-week-old specific pathogen free rats were randomly assigned to six groups:the control,model,model+NMDAR agonist,model+NMDAR anta-gonist,model+PKA antagonist,and model+NMDAR antagonist+PKA agonist groups,with six rats in each group.The model was induced via an intraperitoneal injection of ovalbumin for sensitization along with local esophageal stimulation.Immunohistochemistry and Western blotting were utilized to assess the expression levels of NMDAR2B signaling pathway-related proteins in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and peripheral esophageal tissues.RT-PCR was used to measure the corresponding mRNA expression,and ELISA was used to determine the serum brain-derived neurotrophic factor(BDNF)concentration.Behavioral scoring was performed during balloon distention and acid perfusion of the lower esophagus.RESULTS Compared with the control group,the model group presented significantly increased expression levels of the NMDAR2B,PKA,CREB,BDNF,substance P,and calcitonin gene-related peptide proteins and mRNAs in the cingulate gyrus,dorsal thalamus,spinal dorsal horn,and lower esophagus(P<0.05).Compared with the model group,the model+NMDAR agonist group exhibited even higher expression levels of these proteins and mRNAs(P<0.05),whereas the model+NMDAR antagonist and model+PKA antagonist groups presented lower expression levels(P<0.05).The model+NMDAR antagonist+PKA agonist group presented higher expression levels than did the model+NMDAR antagonist group(P<0.05).The changes in the serum BDNF concentration and behavioral score during balloon distention and acid perfusion were consistent with these changes in expression.CONCLUSION The NMDAR2B signaling pathway plays a critical role in the development of neuropathic pain in GERD through the PKA/CREB/BDNF pathway.
基金supported by National Natural Science Foundation of China(32270314(GS))the Key Project of Applied Basic Research Program of Yunnan(202201AS070056(JW),202301AS070064(GS))Yunnan Revitalization Talent Support Program“Yunling Scholar”Project(JW),Chinese Academy of Sciences(CAS)Light of West China Program(GS),Yunnan Revitalization Talent Support Program“Young Talents”Project(XDYC-QNRC-2022-0001(GS)).
文摘The parasitic dodder(Cuscuta,Convolvulaceae)species have wide ranges of hosts.However,some plants,including the cultivated tomato(Solanum lycopersicum),have different degrees of resistance to Cuscuta.The cultivated tomato plants activate a strong hypersensitive response(HR)where Cuscuta haustoria penetrate stems of cultivated tomato,but the underlying mechanisms by which the cultivated tomato perceives Cuscuta and activates resistance remain unclear.In this study,we show that the phytohormones jasmonic acid(JA)and salicylic acid(SA)in cultivated tomato stems were highly induced by Cuscuta australis parasitization.Genetic analyses and experiments of supplementation of JA or SA indicated that the JA and SA pathway not only are both required for activation of HR against Cuscuta parasitization but also function in non-HR-based resistance.The Cuscuta Receptor 1(CuRe1),which is a leucine-rich repeat receptor-like protein,and suppressor of BAK1-interacting receptor kinase(SOBIR1)and SOBIR1-like,two adaptor kinases,are also important for HR-based and non-HR-based resistance.Importantly,we found that the JA and SA pathway both transcriptionally regulate CuRe1.However,in the cure1 mutants,JA and SA levels were still normally induced by C.australis parasitization.We propose a linear model that an unknown receptor perceives Cuscuta parasitization and thus triggers accumulation of JA and SA,which in turn induce the transcription of CuRe1,and CuRe1 and SOBIR1/SOBIR1-like thereby activate HR-based and non-HR-based resistance to Cuscuta.This study underscores the important roles of hormone signaling and resistance(R)genes in host plant-parasitic plant interactions.
基金supported by the grant PTVH112-011 from Pingtung Veterans General Hospital.
文摘Objectives:Professional antigen-presenting cells known as dendritic cells(DCs)assist as a connection between the innate and adaptive components of the immune response.DCs are attractive targets for immunomodulatory drugs because of their crucial function in triggering immunity.This study set out to examine,for the first time,how hibifolin affected mouse bone-marrow derived(BMDCs)dendritic cells,triggered by lipopolysaccharide(LPS)in vitro.Additionally,a mouse model of contact hypersensitivity(CHS)was used to assess its possible therapeutic effects in vivo.Methods:LPS was administered to BMDCs with or without hibifolin.Major Histocompatibility Complex(MHC)class II,cytokine production,and co-stimulatory molecule(CD80,CD86)expression levels were assessed.To evaluate the functional effects on T-cell activation,mixed lymphocyte responses using OVA specific T-cells were conducted.In vivo,immunoregulatory potential of hibifolin was examined using a CHS mouse model sensitized with 2,4-dinitrofluorobenzene(DNFB).Results:Hibifolin significantly reduced the expression of the proinflammatory cytokines TNF-αand IL-6,as well as the costimulatory molecules CD80,CD86,and MHC II induced by LPS,by about 40-50%.These effects were associated with reduced NF-κB and p38-MAPK pathway activity.JNK and ERK phosphorylation levels did not alter significantly.In vitro,BMDCs treated with hibifolin showed a 40%-45%down-regulated capacity to stimulate T-cell propagation and IFN-γrelease.Oral hibifolin treatment in vivo modestly decreased DNFB-induced CHS responses by 30%-40%.Conclusion:Overall,our results offer new insights that by inhibiting NF-κB and p38-MAPK signaling,hibifolin decreases the expression of costimulatory molecules and cytokines,thereby limiting BMDC activation,suppressing T-cell responses,and exerting immunomodulatory effects in the CHS mouse model.
基金supported by the Open Fund of the Key Laboratory of Integrated Pest Management on Crop in Northwestern Oasis,Ministry of Agriculture and Rural Affairsof China(KFJJ202101)the National KeyR&D Program of China(2021YFD1400100)+1 种基金the National Natural Science Foundation of China(31972247)the Tianchi Talent Introduction Program in Xinjiang Uygur Autonomous Region,China and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.
文摘The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.
文摘Laser therapy is a widely accepted method for tattoo removal,fragmenting tattoo pigments for eventual clearance by the immune system.However,tattoos presenting with signs of allergic reactions—such as erythema,swelling,pruritus,or localized dermatitis—pose unique challenges that contraindicate the use of laser treatments.This review explores clinical and immunological reasons why laser therapy should be avoided in tattoos manifesting allergic reactions,focusing on the exacerbation of symptoms,potential systemic hypersensitivity,and increased risk of severe adverse effects.Tattoo inks,particularly those containing red pigments,are known to induce delayed hypersensitivity reactions,driven by the body’s immune response to the injected foreign substances.Laser-induced breakdown of tattoo pigments can trigger an amplified allergic response due to the rapid release of pigment particles,which may further stimulate the immune system.Additionally,photomechanical fragmentation of tattoo inks during laser treatment increases the bioavailability of allergenic compounds,heightening the risk of severe inflammatory reactions and systemic dissemination of these allergens.Histological evidence suggests allergic reactions to tattoo inks are often granulomatous in nature,and the inflammatory environment created by laser therapy can exacerbate this granulomatous process,resulting in hypertrophic scarring or keloid formation.Moreover,patients with underlying allergic sensitivities to tattoo pigments are at an elevated risk of systemic complications,including generalized urticaria or angioedema,upon laser treatment.Current evidences suggests tattoos of allergic reactions should be not undergone laser therapy,emphasizing the need for alternative management strategies,such as topical application of corticosteroids or excision in severe cases.Clinicians must conduct a thorough pre-treatment assessment,including the patch testing,to identify potential allergenic inks and avoid laser-based interventions on reactive tattoos to prevent complications and safeguard patient's safety.
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 Science and Technology Department of Sichuan Province(2023NSFSC1757)the"Xinglin Scholar"Talent Research Promotion Plan of Chengdu University of Traditional Chinese Medicine(grant number MPRC2021020).
文摘Diarrhea predominant irritable bowel syndrome(IBS-D)have a serious impact on the patient’s quality life due to the lack of safe and effective drugs.The transient receptor potential vanilloid subtype 1(TRPV1)is an ion channel receptor implicated in the perception of visceral injury.Recent studies indicated that TRPV1 mediates visceral hypersensitivity in IBS-D patients by enhancing the excitability of intestinal sensory neurons.Consequently,inhibiting the TRPV1 may be a promising option for the treatment of IBS-D.Current research demonstrates that various traditional Chinese medicine(TCM)methods,such as herbal prescriptions,acupuncture,and moxibustion,can reduce visceral sensitivity by regulating TRPV1 expression and its activation sensitization.This suggests that TCM methods may serve as safe and effective options for alleviating IBS-D.Therefore,this article summarizes potential therapeutic strategies of TCM as a regulator of TRPV1 for managing IBS-D.It also provides insights into potential TCM methods and natural phytochemical molecular nuclei for future drug research targeting TRPV1 in IBS-D.
基金supported by the National Research Foundation(NRF)of Korea(grant number:RS-2022-NR072217 to P.RL,RS-2021-NR059709,RS-2023-00264409,and RS-2024-00441103)funded by the Korean government(MSIT).
文摘Piezo2,a mechanosensitive ion channel,serves as a crucial mechanotransducer in dental primary afferent(DPA)neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients.Given Piezo2’s widespread expression across diverse subpopulations of DPA neurons,this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels(VGSCs)and neuropeptide profiles.Using whole-cell patch-clamp recordings,we observed mechanically activated action potentials(APs)and classified AP waveforms based on the presence or absence of a hump during the repolarization phase.Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties,including tetrodotoxin-resistant VGSCs(NaV1.8 and NaV1.9)and TRPV1 expression.Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides—including two CGRP isoforms(α-CGRP andβ-CGRP),Substance P,and Galanin—and the expression of NaV1.8 and NaV1.9,which were linked to defined AP subtypes.These molecular associations were further validated in Piezo2+DPA neurons using fluorescence in situ hybridization.Together,these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
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 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.
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the Zhejiang Natural Science Foundation,China(Grant No.LY21C130004)the Key Research and Development Program of Zhejiang Province,China(Grant No.2021C02056-3)+1 种基金the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202202)the Agricultural Science and Technology Innovation Program,China(Grant No.CAASASTIP-2021-CNRRI).
文摘The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.
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National Basic Research Program of China:Research on the Initiation Mechanism of Moxibustion Effect and Its Endogenous Regulation Mechanism(973 program,No.2015CB554501)National Natural Science Foundation of China:Interaction Mechanism of the Information between Electroacupuncture Stimulation to Zusanli and Visceral Pain in Dorsal Root Ganglion of Rats with Irritable Bowel Syndrome(No.81873367)+2 种基金Study on the Mechanism of Periaqueductal gray Purinergic Ion Channel Receptor 3 Mediated in Electroacupuncture Relieving Visceral Hypersensitivity in Mice with Irritable Bowel Syndrome(No.81904301)Natural Science Foundation of Shanghai:based on Transient Receptor Potential Vanilloid 1 Mediated Calcium/Calmodulin-dependent Protein KinaseⅡSignaling Pathway Involved in Electroacupuncture to Relieve Irritable Bowel Syndrome Mice Visceral Pain Mechanism Study(No.22ZR1458600)Science and Technology Commission of Shanghai Municipality:Shanghai Clinical Research Center for Acupuncture and Moxibustion(No.20MC1920500)。
文摘OBJECTIVE:To investigate the role of satellite glial cells in irritable bowel syndrome(IBS)and the effect of electroacupuncture(EA)at the Tianshu(ST25)and Shangjuxu(ST37)combination.METHODS:A model for visceral hypersensitivity in IBS was induced through colorectal distension(CRD)stimulation.Clean-grade male Sprague-Dawley(SD)rats were randomly divided into four groups:a normal group(NG),a model group(MG),an electroacupuncture group(EA),and a glial cell inhibitor group(FCA).Bilateral EA(2/100 Hz,1 mA,30 min)was administered at the Tianshu(ST25)and Shangjuxu(ST37)in week 6.Abdominal withdrawal reflex(AWR)scores were used to assess the behavioral response associated with visceral hyperalgesia,while hematoxylin-eosin staining was employed to evaluate pathological changes in the colon.The protein and mRNA levels of glial fibrillary acidic protein(GFAP)in the colon and colon-related dorsal root ganglion(DRG)were analyzed using immun-ofluorescence,immunohistochemistry,Western blotting,real-time polymerase chain reaction.The impact of EA on electrophysiological properties of colon-related DRG neurons was observed through whole-cell patch clamp analysis.RESULTS:EA significantly reduced the visceral pain behavior scores in rats with IBS in response to graded(20,40,60,80 mm Hg)CRD stimulation.Additionally,EA downregulated the protein and mRNA expression levels of GFAP in the colon and colon-related DRG of rats with IBS.EA also regulated the resting membrane potential,rheobase and action potential of colon-related DRG neurons in rats with IBS.CONCLUSIONS:EA can regulate the excitatory properties of colon-related DRG neurons by downregulating the protein and mRNA expression of GFAP in the colon and colon-related DRG,indicating a potential neurobiological mechanism by which EA relieves visceral hypersensitivity in rats with IBS.
