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
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
Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present stud...Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.展开更多
BACKGROUND Diabetic cardiomyopathy(DCM) is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6(TRPC6) protein i...BACKGROUND Diabetic cardiomyopathy(DCM) is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6(TRPC6) protein is a very important selective calcium channel that is closely related to the development of various cardiomyopathies.AIM To explore whether TRPC6 affects cardiomyocyte apoptosis and proliferation inhibition in DCM.METHODS We compared cardiac function and myocardial pathological changes in wild-type mice and mice injected with streptozotocin(STZ), in addition to comparing the expression of TRPC6 and P-calmodulin-dependent protein kinase Ⅱ(P-CaMKⅡ) in them. At the same time, we treated H9C2 cardiomyocytes with high glucose and then evaluated the effects of addition of SAR, a TRPC6 inhibitor, and KN-93, a CaMKⅡ inhibitor, to such H9C2 cells in a high-glucose environment.RESULTS We found that STZ-treated mice had DCM, decreased cardiac function, necrotic cardiomyocytes, and limited proliferation. Western blot and immunofluorescence were used to detect the expression levels of various appropriate proteins in the myocardial tissue of mice and H9C2 cells. Compared to those in the control group, the expression levels of the apoptosis-related proteins cleaved caspase 3 and Bax were significantly higher in the experimental group, while the expression of the proliferation-related proteins proliferating cell nuclear antigen(PCNA) and CyclinD1 was significantly lower. In vivo and in vitro, the expression of TRPC6 and P-CaMKⅡ increased in a high-glucose environment. However, addition of inhibitors to H9C2 cells in a high-glucose environment resulted in alleviation of both apoptosis and proliferation inhibition.CONCLUSION The inhibition of apoptosis and proliferation of cardiomyocytes in a high-glucose environment may be closely related to activation of the TRPC6/P-CaMKⅡ pathway.展开更多
The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whe...The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.展开更多
BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaici...BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.展开更多
Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. S...Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.展开更多
目的探究N-乙酰半胱氨酸对支气管哮喘大鼠CXC趋化因子配体(CXCL)8-CXC趋化因子受体(CXCR)1/2及瞬时受体电位通道蛋白(TRP)V1神经元敏感性的影响。方法选取80只SPF级SD雄性大鼠,随机分为正常(NO)组、模型(MO)组、N-乙酰半胱氨酸(NAC)组...目的探究N-乙酰半胱氨酸对支气管哮喘大鼠CXC趋化因子配体(CXCL)8-CXC趋化因子受体(CXCR)1/2及瞬时受体电位通道蛋白(TRP)V1神经元敏感性的影响。方法选取80只SPF级SD雄性大鼠,随机分为正常(NO)组、模型(MO)组、N-乙酰半胱氨酸(NAC)组、急支糖浆(ES)组,每组20只,对MO组、NAC组、ES组进行支气管哮喘建模,建模成功后,NAC组、ES组每天分别于腹腔内注射2 ml N-乙酰半胱氨酸注射液、急支糖浆灌胃10 g/kg剂量,NO组、MO组同期灌胃同体积生理盐水,通过苏木素-伊红(HE)染色法检测肺组织病理形态、酶联免疫吸附试验(ELISA)、实时荧光定量聚合酶链反应(RT-PCR)、Western印迹检测血清及肺组织中CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达,并分析N-乙酰半胱氨酸对支气管哮喘大鼠CXCL8-CXCR1/2及TRPV1神经元敏感性。结果与NO组相比,MO组咳嗽次数明显增加(P<0.05),而NAC组、ES组与MO组相比,其咳嗽次数明显降低(P<0.05),且NAC组比ES组降低明显(P<0.05);与NO组相比,MO组细支气管管腔、肺泡腔内可见渗出液、脱落的上皮细胞等,远端肺泡可见局部肺不张及周围肺大泡,且肺间质明显增厚,炎性细胞浸润明显,而与MO组比较,ES组、NAC组症状明显减少,部分肺间质的组织结构趋向正常,部分肺泡轻度扩张,且NAC组比ES组明显降低(P<0.05);与NO组对比,MO组CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达均明显升高(P<0.05),NAC组、ES组与MO组相比均显著降低(P<0.05),且NAC组比ES组明显降低(P<0.05)。结论N-乙酰半胱氨酸可以显著降低咳嗽次数,减少支气管哮喘症状,可使CXCL8-CXCR1/2及TRPV1神经元敏感性显著降低。展开更多
目的观察疏肝和胃方对胃食管反流大鼠模型背根神经节中内脏敏感因子瞬时受体电位香草酸亚型1(TRPV1)表达的影响,探讨其治疗胃食管反流病的机理。方法将40只SD大鼠按随机数字表法分为正常组、模型组、中药组及西药组,每组10只,除正常组...目的观察疏肝和胃方对胃食管反流大鼠模型背根神经节中内脏敏感因子瞬时受体电位香草酸亚型1(TRPV1)表达的影响,探讨其治疗胃食管反流病的机理。方法将40只SD大鼠按随机数字表法分为正常组、模型组、中药组及西药组,每组10只,除正常组外均行贲门肌切开术加幽门半结扎术制备反流性食管炎模型,并分别给予相应干预措施。免疫组化法及实时荧光定量核酸扩增检测(QPCR)方法观察各组大鼠背根神经节TRPV1受体及TRPV1 m RNA的表达。结果与正常组相比,模型组、西药组大鼠背根神经节中TRPV1阳性表达明显增高(P<0.05);中药组与正常组比较无统计学差异(P>0.05);与西药组比较,中药组TRPV1阳性表达明显降低(P<0.05)。模型组背根神经节组织中TRPV1 m RNA表达水平明显高于正常组、中药组及西药组(P<0.05);中药组、西药组与正常组比较差异无统计学意义(P>0.05);中药组与西药组比较,两组背根神经节组织中TRPV1 m RNA表达差异无统计学意义(P>0.05)。结论疏肝和胃方可能通过抑制TRPV1过度表达来发挥其治疗胃食管反流病的作用。展开更多
Objective::This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1(TRPV1)and the secretion of thymic stromal lymphopoietin(TSLP)in a human benign ep...Objective::This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1(TRPV1)and the secretion of thymic stromal lymphopoietin(TSLP)in a human benign epidermal keratinocyte line(HaCaT).Methods::HaCaT keratinocytes were cultivated and divided into six groups:capsaicin-induced model control group,capsazepine control group,solvent control group,and three honokiol treatment groups(7.81,15.63,and 31.25 mg/L of honokiol).The effect of honokiol on calcium(Ca^(2+))influx was measured by a Ca^(2+)fluorescence imaging system.The fluorescence intensity(F)of cells was measured.The rate of change in F(ΔF/F0)was calculated,and theΔF/F0-time curve was constructed.HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid,recombinant human tumor necrosis factorα,and recombinant human interleukin 4.Different concentrations of honokiol(15.63,7.81,and 3.91 mg/L)were added to the cells in the respective honokiol groups;20 mg/L of dexamethasone or 0.5%dimethyl sulfoxide was added to the cells in the positive control group or solvent control group.The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay.Statistical analysis was performed by one-way analysis of variance and Dunnett t test.Results::The capsaicin-induced Ca^(2+)fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group;ΔF/F0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group.The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group(t=7.382,P=0.003,and t=2.766,P=0.023,respectively),while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group(t=1.872,P=0.124).Conclusions::Honokiol inhibited the Ca^(2+)influx induced by capsaicin(TRPV1 agonist)in HaCaT keratinocytes.Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.展开更多
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.
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supported by the Research Basis Formation Supporting Project for Private University
文摘Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.
文摘BACKGROUND Diabetic cardiomyopathy(DCM) is a serious complication of end-stage diabetes that presents symptoms such as cardiac hypertrophy and heart failure. The transient receptor potential channel 6(TRPC6) protein is a very important selective calcium channel that is closely related to the development of various cardiomyopathies.AIM To explore whether TRPC6 affects cardiomyocyte apoptosis and proliferation inhibition in DCM.METHODS We compared cardiac function and myocardial pathological changes in wild-type mice and mice injected with streptozotocin(STZ), in addition to comparing the expression of TRPC6 and P-calmodulin-dependent protein kinase Ⅱ(P-CaMKⅡ) in them. At the same time, we treated H9C2 cardiomyocytes with high glucose and then evaluated the effects of addition of SAR, a TRPC6 inhibitor, and KN-93, a CaMKⅡ inhibitor, to such H9C2 cells in a high-glucose environment.RESULTS We found that STZ-treated mice had DCM, decreased cardiac function, necrotic cardiomyocytes, and limited proliferation. Western blot and immunofluorescence were used to detect the expression levels of various appropriate proteins in the myocardial tissue of mice and H9C2 cells. Compared to those in the control group, the expression levels of the apoptosis-related proteins cleaved caspase 3 and Bax were significantly higher in the experimental group, while the expression of the proliferation-related proteins proliferating cell nuclear antigen(PCNA) and CyclinD1 was significantly lower. In vivo and in vitro, the expression of TRPC6 and P-CaMKⅡ increased in a high-glucose environment. However, addition of inhibitors to H9C2 cells in a high-glucose environment resulted in alleviation of both apoptosis and proliferation inhibition.CONCLUSION The inhibition of apoptosis and proliferation of cardiomyocytes in a high-glucose environment may be closely related to activation of the TRPC6/P-CaMKⅡ pathway.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3Scientific Research Foundation of Shanxi Province of China for the Returned Overseas Chinese Scholars,No.2013011054-2
文摘The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.
文摘BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.
文摘Background: It is important to maintain skin homeostasis for cosmetic and medical reasons. Many ceramide-related ingredients and cosmetics have been developed to improve the skin barrier function and skin hydration. Similar to extracellular lipids, the cornified envelope, which is a structure formed beneath the plasma membrane, contributes to the skin barrier function as a scaffold for extracellular lipids. Therefore, in this study, we focused on transglutaminase 1 (TGM1) which is the key enzyme for formation of the cornified envelope Objective: The objectives of this study were to identify compounds that could upregulate the expression of TGM1 and evaluate their underlying action mechanisms. Methods: Expression of the transient receptor potential channel vanilloid subfamily member 4 (TRPV4) at the mRNA and protein levels was estimated by PCR and western blotting. Effects of baicalein and Salvia officinalis (SO) extract on TGM1 mRNA expression were measured by PCR. The involvement of TRPV4 in TGM1 mRNA expression was evaluated by the inhibition and silencing of TRPV4. Results: TRPV4 was expressed in both basal cell-like HaCaT cells and suprabasal cell-like HaCaT cells. Baicalein and SO extract upregulated TGM1 mRNA expression in basal cell-like HaCaT cells. However, inhibition and silencing of TRPV4 abrogated the effects of baicalein and SO extract. Conclusion: Baicalein and SO extract upregulated the expression of TGM1 mRNA via the activation of TRPV4, suggesting that it may improve the skin barrier function by enhancing cornified envelope formation.
文摘目的探究N-乙酰半胱氨酸对支气管哮喘大鼠CXC趋化因子配体(CXCL)8-CXC趋化因子受体(CXCR)1/2及瞬时受体电位通道蛋白(TRP)V1神经元敏感性的影响。方法选取80只SPF级SD雄性大鼠,随机分为正常(NO)组、模型(MO)组、N-乙酰半胱氨酸(NAC)组、急支糖浆(ES)组,每组20只,对MO组、NAC组、ES组进行支气管哮喘建模,建模成功后,NAC组、ES组每天分别于腹腔内注射2 ml N-乙酰半胱氨酸注射液、急支糖浆灌胃10 g/kg剂量,NO组、MO组同期灌胃同体积生理盐水,通过苏木素-伊红(HE)染色法检测肺组织病理形态、酶联免疫吸附试验(ELISA)、实时荧光定量聚合酶链反应(RT-PCR)、Western印迹检测血清及肺组织中CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达,并分析N-乙酰半胱氨酸对支气管哮喘大鼠CXCL8-CXCR1/2及TRPV1神经元敏感性。结果与NO组相比,MO组咳嗽次数明显增加(P<0.05),而NAC组、ES组与MO组相比,其咳嗽次数明显降低(P<0.05),且NAC组比ES组降低明显(P<0.05);与NO组相比,MO组细支气管管腔、肺泡腔内可见渗出液、脱落的上皮细胞等,远端肺泡可见局部肺不张及周围肺大泡,且肺间质明显增厚,炎性细胞浸润明显,而与MO组比较,ES组、NAC组症状明显减少,部分肺间质的组织结构趋向正常,部分肺泡轻度扩张,且NAC组比ES组明显降低(P<0.05);与NO组对比,MO组CXCL8、CXCR1、CXCR2、TRPV1含量、mRNA及蛋白表达均明显升高(P<0.05),NAC组、ES组与MO组相比均显著降低(P<0.05),且NAC组比ES组明显降低(P<0.05)。结论N-乙酰半胱氨酸可以显著降低咳嗽次数,减少支气管哮喘症状,可使CXCL8-CXCR1/2及TRPV1神经元敏感性显著降低。
文摘目的观察疏肝和胃方对胃食管反流大鼠模型背根神经节中内脏敏感因子瞬时受体电位香草酸亚型1(TRPV1)表达的影响,探讨其治疗胃食管反流病的机理。方法将40只SD大鼠按随机数字表法分为正常组、模型组、中药组及西药组,每组10只,除正常组外均行贲门肌切开术加幽门半结扎术制备反流性食管炎模型,并分别给予相应干预措施。免疫组化法及实时荧光定量核酸扩增检测(QPCR)方法观察各组大鼠背根神经节TRPV1受体及TRPV1 m RNA的表达。结果与正常组相比,模型组、西药组大鼠背根神经节中TRPV1阳性表达明显增高(P<0.05);中药组与正常组比较无统计学差异(P>0.05);与西药组比较,中药组TRPV1阳性表达明显降低(P<0.05)。模型组背根神经节组织中TRPV1 m RNA表达水平明显高于正常组、中药组及西药组(P<0.05);中药组、西药组与正常组比较差异无统计学意义(P>0.05);中药组与西药组比较,两组背根神经节组织中TRPV1 m RNA表达差异无统计学意义(P>0.05)。结论疏肝和胃方可能通过抑制TRPV1过度表达来发挥其治疗胃食管反流病的作用。
基金This work was supported by Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.CAMS-2017-I2M-1-011).
文摘Objective::This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1(TRPV1)and the secretion of thymic stromal lymphopoietin(TSLP)in a human benign epidermal keratinocyte line(HaCaT).Methods::HaCaT keratinocytes were cultivated and divided into six groups:capsaicin-induced model control group,capsazepine control group,solvent control group,and three honokiol treatment groups(7.81,15.63,and 31.25 mg/L of honokiol).The effect of honokiol on calcium(Ca^(2+))influx was measured by a Ca^(2+)fluorescence imaging system.The fluorescence intensity(F)of cells was measured.The rate of change in F(ΔF/F0)was calculated,and theΔF/F0-time curve was constructed.HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid,recombinant human tumor necrosis factorα,and recombinant human interleukin 4.Different concentrations of honokiol(15.63,7.81,and 3.91 mg/L)were added to the cells in the respective honokiol groups;20 mg/L of dexamethasone or 0.5%dimethyl sulfoxide was added to the cells in the positive control group or solvent control group.The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay.Statistical analysis was performed by one-way analysis of variance and Dunnett t test.Results::The capsaicin-induced Ca^(2+)fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group;ΔF/F0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group.The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group(t=7.382,P=0.003,and t=2.766,P=0.023,respectively),while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group(t=1.872,P=0.124).Conclusions::Honokiol inhibited the Ca^(2+)influx induced by capsaicin(TRPV1 agonist)in HaCaT keratinocytes.Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.
