OBTECTIVE:To explore the role of transient receptor potential vaniiloid subetype 1(TRPV1) in the increase of the thermal pain threshold by moxibustion.METHODS:Forty Kunming mice(20 ± 2) g were randomized into con...OBTECTIVE:To explore the role of transient receptor potential vaniiloid subetype 1(TRPV1) in the increase of the thermal pain threshold by moxibustion.METHODS:Forty Kunming mice(20 ± 2) g were randomized into control group,capsaicin group,capsazepine group,moxibustion group and moxibustion + capsazepine(MC) group with 8 mice in each,and 16 C57BL/6 wild-type mice(18 ± 2) g were randomized into wild-type(WT) control group and WT moxibustion group with 8 mice in each,and 14 TRPV1 knockout mice(18 ± 2) g were randomized into knockout(KO) control group and KO moxibustion group with 7 in each.Each mouse in the capsaicin group was subcutaneously injected with the amount of 0.1 mL/10 g into L5 and L6 spinal cords;each mouse in the capsazepine group was intraperitoneally injected with the amount of0.1 mL/10 g.Similarly,each mouse in the moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.Each mouse in MC group was intraperitoneally injected with the amount of 0.1 mL/10 g first,then after 15 min was given a suspended moxibustion for 20 min on L5 and L6 spinal cords.Each mouse in WT moxibustion group and KO moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.The control group,WT control group and KO control group were of no treatment in any way.After all treatments were completed,the digital-display measurement instrument for thermal pain was used to measure the threshold of thermal pain in each group respectively.RESULTS:Compared with the control group,the thresholds of thermal pain in the moxibustion group and MC group were significantly increased(P <0.01);no significant changes in the thresholds in the capsaicin group and the capsazepine group(P > 0.05);compared with moxibustion group,he threshold of thermal in MC group was obviously decreased(P < 0.01).Compared with WT control group,the threshold of thermal pain in WT moxibustion group was significantly increased(P <0.01);compared wi展开更多
Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act indepen...Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation.To investigate this,we used two-photon in vivo calcium reco rding to observe the effects of acupuncture stimulation at ST36(Zusanli)in mice.Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes.Chemogenetic inhibition of neurons augmented the astrocytic activity.These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory co rtex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.展开更多
Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is ...Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is necessary to improve prognosis.There is increasing evidence that ion channel dysregulation occurs at multiple stages in primary and secondary brain injury following ICH.Ion channels such as TWIK-related K+channel 1,sulfonylurea 1 transient receptor potential melastatin 4 and glutamate-gated channels affect ion homeostasis in ICH.They in turn participate in the formation of brain edema,disruption of the blood-brain barrier,and the generation of neurotoxicity.In this review,we summarize the interaction between ions and ion channels,the effects of ion channel dysregulation,and we discuss some therapeutics based on ion-channel modulation following ICH.展开更多
Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion chann...Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion channel family,play pivotal roles in sensing the external environment and maintaining internal homeostasis in insects.TRP channels have been widely investigated for their critical roles in regulating various insect behaviors in recent years.In this study,we identified 15 TRP gene loci encoding 26 transcripts in the genome of S.frugiperda and analyzed their expression profiles at different developmental stages.The results revealed that S.frugiperda possesses four TRPC genes,six TRPA genes,one TRPM gene,two TRPV genes,one TRPN gene,and one TRPML gene,while a canonical TRPP is absent.Moreover,the SfruTRPA1 was functionally characterized using the Xenopus oocyte expression system.The results showed that SfruTRPA1 is activated by temperature increases from 20 to 45℃,and there is no significant desensitization after repeated stimuli within the same temperature range.Additionally,SfruTRPA1 is activated by certain natural chemicals,including allyl isothiocyanate(AITC)and cinnamaldehyde(CA).These findings provide valuable insights to the TRP genes in S.frugiperda.展开更多
AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a no...AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.展开更多
BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diar...BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracell展开更多
The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloi...OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.展开更多
●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,...●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increase展开更多
OBJECTIVE:To investigate the efficacy of Zhenxin Anshen formula(镇心安神方,ZXAS)on atopic dermatitis(AD)by transient receptor potential vanilloid 1(TRPV1)and transient receptor potential ankyrin 1(TRPA1)signalling pat...OBJECTIVE:To investigate the efficacy of Zhenxin Anshen formula(镇心安神方,ZXAS)on atopic dermatitis(AD)by transient receptor potential vanilloid 1(TRPV1)and transient receptor potential ankyrin 1(TRPA1)signalling pathway in mice and in vitro.METHODS:AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene(DNCB)to the shaved dorsal skin of BALB/c mice.BALB/c mice were divided into five groups:normal control,model control,cetirizine,low-,medium-,and high-dose of ZXAS.After ZXAS in-tervention,the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines.Immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-13,and thymic stromal lymphopoietin(TSLP)were de-tected by Enzyme-linked immunosorbent assay(ELISA).The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor(GRPR),TRPV1,and TRPA1 by using immunohistochemistry,western blotting,and quantitative real-time polymerase chain reaction(qR T-PCR)analyses.In addition,3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT)assay,flow cytometry,ELISA,and Western blotting were conducted for analysis of primary dorsal root ganglia(DRG)neurons in vitro.RESULTS:ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score,number of scratching and epidermal thickness,accompanied by the de-creased IgE and Th2 inflammatory cytokines.ZXAS also supressed the mRNA and protein expression of GRPR,TRPV1,and TRPA1 in the spinal cord.The medicated sera of ZXAS decreased capsaicin-induced Ca^(2+)influx and downregulated the expression of TRPV1,TRPA1,and phospholipase C in DRG neurons.CONCLUSIONS:The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca^(2+)signals in neurons.展开更多
BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To invest...BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.展开更多
基金Supported by National Key Basic Research Program 973(Dual Effects of Acupuncture on Functional Intestinal Disease and Its Relationship with Autonomic Nervous Function,No.2011cb505206)2013 Jiangsu Province Education Department of Natural Science Research of Major Projects(Research on The Role of Trpv1 About Anti-inflammation And Analgesia Effect of Moxibustion Treatment,No.13kja360001)Academic Propagate Project on Scientific And Technical Innovation Team,Nanjing University Of Chinese Medicine 2013 Scientific And Technical Innovation Team Project
文摘OBTECTIVE:To explore the role of transient receptor potential vaniiloid subetype 1(TRPV1) in the increase of the thermal pain threshold by moxibustion.METHODS:Forty Kunming mice(20 ± 2) g were randomized into control group,capsaicin group,capsazepine group,moxibustion group and moxibustion + capsazepine(MC) group with 8 mice in each,and 16 C57BL/6 wild-type mice(18 ± 2) g were randomized into wild-type(WT) control group and WT moxibustion group with 8 mice in each,and 14 TRPV1 knockout mice(18 ± 2) g were randomized into knockout(KO) control group and KO moxibustion group with 7 in each.Each mouse in the capsaicin group was subcutaneously injected with the amount of 0.1 mL/10 g into L5 and L6 spinal cords;each mouse in the capsazepine group was intraperitoneally injected with the amount of0.1 mL/10 g.Similarly,each mouse in the moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.Each mouse in MC group was intraperitoneally injected with the amount of 0.1 mL/10 g first,then after 15 min was given a suspended moxibustion for 20 min on L5 and L6 spinal cords.Each mouse in WT moxibustion group and KO moxibustion group was given a suspended moxibustion with specially-made moxa-stick for 20 min on L5 and L6 spinal cords.The control group,WT control group and KO control group were of no treatment in any way.After all treatments were completed,the digital-display measurement instrument for thermal pain was used to measure the threshold of thermal pain in each group respectively.RESULTS:Compared with the control group,the thresholds of thermal pain in the moxibustion group and MC group were significantly increased(P <0.01);no significant changes in the thresholds in the capsaicin group and the capsazepine group(P > 0.05);compared with moxibustion group,he threshold of thermal in MC group was obviously decreased(P < 0.01).Compared with WT control group,the threshold of thermal pain in WT moxibustion group was significantly increased(P <0.01);compared wi
基金National Key Research and Development Program of China,No.2016YFC1306702(to KFS and LZ)the National Natural Science Foundation of China,No.81771455(to KFS)+1 种基金Science and Technology Program of Guangdong Province of China,No.2018B030334001(to KFS)the Natural Science Foundation of Guangdong of China,No.2019A1515011772(to LZ)。
文摘Acupuncture is a medical treatment that has been widely pra cticed in China for over 3000 years,yet the neural mechanisms of acupuncture are not fully understood.We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation.To investigate this,we used two-photon in vivo calcium reco rding to observe the effects of acupuncture stimulation at ST36(Zusanli)in mice.Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes.Chemogenetic inhibition of neurons augmented the astrocytic activity.These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory co rtex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.
基金supported by the National Natural Science Foundation of China(82071331,81870942,and 81520108011)the National Key Research and Development Program of China(2018YFC1312200)the Canadian Institutes of Health Research(VWY).
文摘Injury to the brain after intracerebral hemorrhage(ICH)results from numerous complex cellular mechanisms.At present,effective therapy for ICH is limited and a better understanding of the mechanisms of brain injury is necessary to improve prognosis.There is increasing evidence that ion channel dysregulation occurs at multiple stages in primary and secondary brain injury following ICH.Ion channels such as TWIK-related K+channel 1,sulfonylurea 1 transient receptor potential melastatin 4 and glutamate-gated channels affect ion homeostasis in ICH.They in turn participate in the formation of brain edema,disruption of the blood-brain barrier,and the generation of neurotoxicity.In this review,we summarize the interaction between ions and ion channels,the effects of ion channel dysregulation,and we discuss some therapeutics based on ion-channel modulation following ICH.
基金funded by the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the Special Funds for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District,China(pt202101-02)the National Key R&D Program of China(2022YFE0116500).
文摘Spodoptera frugiperda is a highly destructive pest that has become a global problem due to its robust reproductive and migratory capabilities.Transient receptor potential(TRP)channels,which constitute a vast ion channel family,play pivotal roles in sensing the external environment and maintaining internal homeostasis in insects.TRP channels have been widely investigated for their critical roles in regulating various insect behaviors in recent years.In this study,we identified 15 TRP gene loci encoding 26 transcripts in the genome of S.frugiperda and analyzed their expression profiles at different developmental stages.The results revealed that S.frugiperda possesses four TRPC genes,six TRPA genes,one TRPM gene,two TRPV genes,one TRPN gene,and one TRPML gene,while a canonical TRPP is absent.Moreover,the SfruTRPA1 was functionally characterized using the Xenopus oocyte expression system.The results showed that SfruTRPA1 is activated by temperature increases from 20 to 45℃,and there is no significant desensitization after repeated stimuli within the same temperature range.Additionally,SfruTRPA1 is activated by certain natural chemicals,including allyl isothiocyanate(AITC)and cinnamaldehyde(CA).These findings provide valuable insights to the TRP genes in S.frugiperda.
基金Supported by The National Natural Science Foundation of China,No.30270532 and No.30670774Tsinghua-Yue-Yuen Medical Science Foundation,No.20240000531 and No.20240000547
文摘AIM： To explore the possibility of using the Noninvasive Micro-test Technique （NMT） to investigate the role of Transient Receptor Potential Canonical 1 （TRPC1） in regulating Ca^2＋ influxes in HL-7702 cells, a normal human liver cell line.METHODS： Net Ca^2＋ fluxes were measured with NMT, a technology that can obtain dynamic information of specific/selective ionic/molecular activities on material surfaces, non-invasively. The expression levels of TRPCl were increased by liposomal transfection, whose effectiveness was evaluated by Western-blotting and single cell reverse transcription-polymerase chain reaction.RESULTS： Ca^2＋ influxes could be elicited by adding 1 mmol/L CaCl2 to the test solution of HL-7702 cells. They were enhanced by addition of 20 μmol/L noradrenalin and inhibited by 100 μmol/L LaCl3 （a non-selective Ca^2＋ channel blocker）; 5 μmol/L nifedipine did not induce any change. Overexpression of TRPCl caused increased Ca^2＋ influx. Five micromoles per liter nifedipine did not inhibit this elevation, whereas 100 μmol/L LaCI3 did.CONCLUSION： In HL-7702 cells, there is a type of TRPCl-dependent Ca^2＋ channel, which could be detected v/a NMT and inhibited by La^3＋.
基金The Health Commission of Jinshan District,Shanghai,China,No.JSKJ-KTMS-2019-01The Youth Research Foundation of Jinshan Hospital of Fudan University,No.JYQN-JC-202101 and No.JYQN-JC-202216The Reserve Discipline Construction of Jinshan Hospital of Fudan University,No.HBXK-2021-2.
文摘BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain conditions.The possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present study.AIM To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with IBS-D.METHODS Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy controls.The expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain scores.The IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap restraint.Alterations in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist adminis-tration.Changes in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of patients.Although the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal tract.Plasma 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of IBS-D.The serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and 5-HT2c.All 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/11 to increase inositol phosphates and intracell
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
基金High Level Talents Project of Affiliated Hospital of Youjiang Medical University for Nationalities:Study of Soft-Du'an Capsule's Mechanism and Efficacy of Regulating TRPV1 Pashways in Relieving Oral and Maxillofacial Trigeminal Neuralgia (No. YYFYR20213002)Innovative Group Project of Natural Science Foundation of Hubei Province:Study on the Mechanisms of Pain Signal Transduction and Drug Analgesia (No. 2020CFA025)。
文摘OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie(Resina Dracaenae Cochinchinensis)(TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1(TRPV1).METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB.RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion(DRG) neurons of rats and the half inhibitory concentration was(16.7 ± 1.6) mg/L.TFDB(2-20 mg/kg) showed analgesic activity in the phase Ⅱ of formalin test and(0.02-2 mg per paw)reduced capsaicin-induced licking times of rats. TFDB(20 mg/kg) was fully efficacious on complete Freund's adjuvant(CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats.CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.
文摘●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increase
基金the National Natural Science Foundation of China:Study on the Mechanism of Zhenxin Anshen Formula Regulating GRPR/MrgprA3/TRPs Signaling Pathway for Atop-ic Dermatitis based on the Theory of All Kinds of Diseases with PainItching+7 种基金and Sores are Exclusively Related to the HeartNo.81704087the Regulation of Zhenxin Anshen Formula on Neuroimmune Function in Atopic Dermatitis from STIM1-ORAI1 Mediated Store Oper-ated Calcium EntryNo.82274537Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences:Based on PAR2/TRPV1 Pathway to Regulate Nerve-Epidermal Pruritus Information Transmission to Explore the Mechanism of Longmu Decoction on“Stress-Type Atopic Dermatitis”MiceNo.CI2021A02315Belt and Road Initiative Cooperation Project of Traditional Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine:Evaluation of the Effect of Chinese Medicine on Allergic Diseases and Material Basis ResearchNo.GH201910。
文摘OBJECTIVE:To investigate the efficacy of Zhenxin Anshen formula(镇心安神方,ZXAS)on atopic dermatitis(AD)by transient receptor potential vanilloid 1(TRPV1)and transient receptor potential ankyrin 1(TRPA1)signalling pathway in mice and in vitro.METHODS:AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene(DNCB)to the shaved dorsal skin of BALB/c mice.BALB/c mice were divided into five groups:normal control,model control,cetirizine,low-,medium-,and high-dose of ZXAS.After ZXAS in-tervention,the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines.Immunoglobulin E(IgE),interleukin(IL)-4,IL-5,IL-13,and thymic stromal lymphopoietin(TSLP)were de-tected by Enzyme-linked immunosorbent assay(ELISA).The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor(GRPR),TRPV1,and TRPA1 by using immunohistochemistry,western blotting,and quantitative real-time polymerase chain reaction(qR T-PCR)analyses.In addition,3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide(MTT)assay,flow cytometry,ELISA,and Western blotting were conducted for analysis of primary dorsal root ganglia(DRG)neurons in vitro.RESULTS:ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score,number of scratching and epidermal thickness,accompanied by the de-creased IgE and Th2 inflammatory cytokines.ZXAS also supressed the mRNA and protein expression of GRPR,TRPV1,and TRPA1 in the spinal cord.The medicated sera of ZXAS decreased capsaicin-induced Ca^(2+)influx and downregulated the expression of TRPV1,TRPA1,and phospholipase C in DRG neurons.CONCLUSIONS:The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca^(2+)signals in neurons.
文摘背景:内脏高敏感被认为是肠易激综合征的主要病理生理机制之一。目的:探讨内脏高敏感大鼠结肠特异背根神经节(DRG)神经元上的TRPV1表达及其电生理特征。方法:20只10 d龄大鼠随机分为模型组和对照组,模型组以结直肠内灌注乙酸诱导内脏高敏感模型,对照组灌注等量0.9%NaC l溶液。以结肠壁注射DiI荧光染料逆行标记DRG神经元(即结肠特异DRG神经元),免疫荧光法检测DRG神经元上的TRPV1表达,膜片钳技术记录神经元电生理特征。结果:模型组结肠特异DRG神经元上的TRPV1表达阳性率明显高于对照组(46.1%对36.6%,P<0.01),平均阈电流值明显低于对照组[(57.80±1.32)pA对(73.45±4.51)pA,P<0.05],2倍阈电流刺激下动作电位频率明显高于对照组[(8.20±1.10)Hz对(4.54±0.66)Hz,P<0.05],差异均有统计学意义。模型组60 mm Hg结直肠扩张压力下的腹壁回撤反射(AWR)评分与TRPV1表达阳性率、2倍阈电流刺激下动作电位频率呈正相关(r=0.87和r=0.73,P<0.01),与阈电流值呈负相关(r=-0.81,P<0.01)。结论:结肠特异DRG神经元TRPV1表达上调、细胞兴奋性增加,可能是内脏高敏感形成的重要环节。
基金Supported by National Natural Science Foundation of China,No.82260535National Natural Science Foundation of Guizhou Medical University Hospital Incubation Program,No.gyfynsfc-2022-07.
文摘BACKGROUND Members of the transient receptor potential(TRP)protein family shape oncogenic development,but the specific relevance of TRP-related genes in hepatocellular carcinoma(HCC)has yet to be defined.AIM To investigate the role of TRP genes in HCC,their association with HCC development and treatment was examined.METHODS HCC patient gene expression and clinical data were downloaded from The Cancer Genome Atlas database,and univariate and least absolute shrinkage and selection operator Cox regression models were employed to explore the TRP-related risk spectrum.Based on these analyses,clinically relevant TRP family genes were selected,and the association between the key TRP canonical type 1(TRPC1)gene and HCC patient prognosis was evaluated.RESULTS In total,28 TRP family genes were screened for clinical relevance,with multivariate analyses ultimately revealing three of these genes(TRPC1,TRP cation channel subfamily M member 2,and TRP cation channel subfamily M member 6)to be significantly associated with HCC patient prognosis(P<0.05).These genes were utilized to establish a TRP-related risk model.Patients were separated into low-and high-risk groups based on the expression of these genes,and high-risk patients exhibited a significantly poorer prognosis(P=0.001).Functional analyses highlighted pronounced differences in the immune status of patients in these two groups and associated enriched immune pathways.TRPC1 was identified as a candidate gene in this family worthy of further study,with HCC patients expressing higher TRPC1 levels exhibiting poorer survival outcomes.Consistently,quantitative,immunohistochemistry,and western blot analyses revealed increased TRPC1 expression in HCC.CONCLUSION These three TRP genes help determine HCC patient prognosis,providing insight into tumor immune status and immunological composition.These findings will help design combination therapies including immunotherapeutic and anti-TRP agents.
