Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully e...Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.展开更多
In this study, the effect of cyclosporin A （CsA） eye drop on keratoconjunctivitis Sicca （KCS） and its mechanism were studied. The KCS models were established by injecting Pertussis vaccine, complete freund＇s adju...In this study, the effect of cyclosporin A （CsA） eye drop on keratoconjunctivitis Sicca （KCS） and its mechanism were studied. The KCS models were established by injecting Pertussis vaccine, complete freund＇s adjuvant （CFA） and antigen of conjunctiva from isotype mice. Then the KCS models were treated with cyclosporin A eye drop. Changes in breaking-up time （BUT）, lacrimal secretion in 30 min and diversion in 24 h were measured. The percentage of beaker cells, the lymphocytic infiltration in conjunctiva were observed. The expression levels of Aquaporin-3 （AQP3） in conjunctiva epithelial cells, beaker cells and accessory lacrimal gland were immunohistochemically detected. The results showed that there were significant differences in BUT, the percentage of beaker cells, lacrimal secretion in 30 min, the lymphocytic infiltration and the expression of AQP3 between the experimental group and an control group. It was concluded.that CsA eye drop exerts marked therapeutic effect on KCS by inhibiting T lymph cells, increasing the goblet cells and AQP3 expression in conjunctiva.展开更多
Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are prese...Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography,coupled with linear ion-trap quadrupole Orbitrap highresolution mass spectrometry.The targets with a potential laxative effect were identified from databases and the literature,then used with rhubarb-derived substances in molecular docking modeling.The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting.Finally,potentially bioactive compounds were traced back to their prototype components.Results:We identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats.G-scoring identified three potential mediators of the laxative effect:c-kit,5-hydroxytryptamine receptor 4(5-HT4),and aquaporin-3(AQP3).In addition,10 rhubarb-derived components(aloeemodin,emodin,rhein,chrysophanol,physcion,sennoside A,sennoside C,physcionanthrone,aloeemodinanthrone,and rheinanthrone),which have strong binding affinities for more than one of the three potential targets,were selected as likely active compounds.Rhubarb extract increased the expression of c-kit and 5-HT4,and reduced the expression of AQP3 in the colon of constipated rats,which might mediate its laxative effect.We also found that a single prototype component may be metabolized into several active metabolites,and a single active ingredient can also be generated from various prototype compounds.Conclusion:The present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit,5-HT4 and/or AQP3.展开更多
Objective To investigate the changes of aquaporin （AQP-1） expressions on peritonea in liver cirrhotic rats with ascites,and to study the correlation between AQP-1 expressions and ascites form.Methods32 healthy Sprag...Objective To investigate the changes of aquaporin （AQP-1） expressions on peritonea in liver cirrhotic rats with ascites,and to study the correlation between AQP-1 expressions and ascites form.Methods32 healthy Sprague-Dawley（SD） rats were divided into two groups randomly, 20 rats were used to produce liver cirrhotic models induced with phenobarbitol sodium and CCl4. The distribution and protein expressions of AQP-1 on the rats′ peritonea were measured with immunohistochemistry assay, and the expressions of APQ-1 mRNA were tested with relative GAPDH quantitative RT-PCR. Results （1）The expressions of AQP-1 were mainly on the endothelial cells of capillary vessels and venules on the rats′ peritonea, and also on mesothelial cells. （2）There was no statistically significant difference between the expressions of AQP-1 protein and mRNA in the two groups on the early stage of liver cirrhosis. （3） Downregulations of the expressions of AQP-1 protein and mRNA were observed in B group on the advanced cirrhotic stage.Conclusion Expressions of AQP-1 were downregulated on the peritonea of rats with decompensated liver cirrhosis, which may play a role in the formation of ascites. The changes of AQP-1 Expressions on peritoneal mesothelial cells which were fewer than those on the endothelial cells may be few relations to ascites form.展开更多
Violence against the neck can result in a range of macromorphological and micromorphological findings.However,the forensic relevance of the carotid sinus in cases of violence against the neck remains controversial.In ...Violence against the neck can result in a range of macromorphological and micromorphological findings.However,the forensic relevance of the carotid sinus in cases of violence against the neck remains controversial.In this follow-up study of 22 cases of suicidal and accidental strangulations,carotid bifurcations were examined histologically for morphological changes implying direct trauma,including haemorrhage and immunohistochemical expression of heat-shock proteins 27,60,and 70 and aquaporin-3.These cases were compared with a control group(82 cases)without neck compression or head trauma and with variable causes of death.No relevant histopathological findings implying direct trauma of the carotid bifurcation were found.No cases showed positive aquaporin-3 staining and only five cases showed positive heat-shock protein-27 staining,all of which were hangings.Without massive trauma of the carotid bifurcation,histological alterations cannot be expected.Without signs of rapid death,findings of acute circulatory failure,macromorphological and micromorphological findings of neck compression,and reliable markers indicating relevant impact on the carotid bifurcation the diagnosis of a lethal reflex cannot be verified.展开更多
基金grants from the National Natural Science Foundation of China （Nos. 30973336 and 81100762）.
文摘Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.
文摘In this study, the effect of cyclosporin A （CsA） eye drop on keratoconjunctivitis Sicca （KCS） and its mechanism were studied. The KCS models were established by injecting Pertussis vaccine, complete freund＇s adjuvant （CFA） and antigen of conjunctiva from isotype mice. Then the KCS models were treated with cyclosporin A eye drop. Changes in breaking-up time （BUT）, lacrimal secretion in 30 min and diversion in 24 h were measured. The percentage of beaker cells, the lymphocytic infiltration in conjunctiva were observed. The expression levels of Aquaporin-3 （AQP3） in conjunctiva epithelial cells, beaker cells and accessory lacrimal gland were immunohistochemically detected. The results showed that there were significant differences in BUT, the percentage of beaker cells, lacrimal secretion in 30 min, the lymphocytic infiltration and the expression of AQP3 between the experimental group and an control group. It was concluded.that CsA eye drop exerts marked therapeutic effect on KCS by inhibiting T lymph cells, increasing the goblet cells and AQP3 expression in conjunctiva.
基金the National Natural Science Foundation of China(81673562 and 81973467)the Fundamental Research Funds for the Central Universities of China(2020-JYB-ZDGG-033).
文摘Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography,coupled with linear ion-trap quadrupole Orbitrap highresolution mass spectrometry.The targets with a potential laxative effect were identified from databases and the literature,then used with rhubarb-derived substances in molecular docking modeling.The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting.Finally,potentially bioactive compounds were traced back to their prototype components.Results:We identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats.G-scoring identified three potential mediators of the laxative effect:c-kit,5-hydroxytryptamine receptor 4(5-HT4),and aquaporin-3(AQP3).In addition,10 rhubarb-derived components(aloeemodin,emodin,rhein,chrysophanol,physcion,sennoside A,sennoside C,physcionanthrone,aloeemodinanthrone,and rheinanthrone),which have strong binding affinities for more than one of the three potential targets,were selected as likely active compounds.Rhubarb extract increased the expression of c-kit and 5-HT4,and reduced the expression of AQP3 in the colon of constipated rats,which might mediate its laxative effect.We also found that a single prototype component may be metabolized into several active metabolites,and a single active ingredient can also be generated from various prototype compounds.Conclusion:The present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit,5-HT4 and/or AQP3.
文摘Objective To investigate the changes of aquaporin （AQP-1） expressions on peritonea in liver cirrhotic rats with ascites,and to study the correlation between AQP-1 expressions and ascites form.Methods32 healthy Sprague-Dawley（SD） rats were divided into two groups randomly, 20 rats were used to produce liver cirrhotic models induced with phenobarbitol sodium and CCl4. The distribution and protein expressions of AQP-1 on the rats′ peritonea were measured with immunohistochemistry assay, and the expressions of APQ-1 mRNA were tested with relative GAPDH quantitative RT-PCR. Results （1）The expressions of AQP-1 were mainly on the endothelial cells of capillary vessels and venules on the rats′ peritonea, and also on mesothelial cells. （2）There was no statistically significant difference between the expressions of AQP-1 protein and mRNA in the two groups on the early stage of liver cirrhosis. （3） Downregulations of the expressions of AQP-1 protein and mRNA were observed in B group on the advanced cirrhotic stage.Conclusion Expressions of AQP-1 were downregulated on the peritonea of rats with decompensated liver cirrhosis, which may play a role in the formation of ascites. The changes of AQP-1 Expressions on peritoneal mesothelial cells which were fewer than those on the endothelial cells may be few relations to ascites form.
文摘Violence against the neck can result in a range of macromorphological and micromorphological findings.However,the forensic relevance of the carotid sinus in cases of violence against the neck remains controversial.In this follow-up study of 22 cases of suicidal and accidental strangulations,carotid bifurcations were examined histologically for morphological changes implying direct trauma,including haemorrhage and immunohistochemical expression of heat-shock proteins 27,60,and 70 and aquaporin-3.These cases were compared with a control group(82 cases)without neck compression or head trauma and with variable causes of death.No relevant histopathological findings implying direct trauma of the carotid bifurcation were found.No cases showed positive aquaporin-3 staining and only five cases showed positive heat-shock protein-27 staining,all of which were hangings.Without massive trauma of the carotid bifurcation,histological alterations cannot be expected.Without signs of rapid death,findings of acute circulatory failure,macromorphological and micromorphological findings of neck compression,and reliable markers indicating relevant impact on the carotid bifurcation the diagnosis of a lethal reflex cannot be verified.
