D-alanine （D-Ala） is an essential amino acid that has a key role in bacterial unique enzyme that interconverts L-alanine and D-alanine in most bacteria, antimicrobial drug development. Streptococcus mutans is a majo...D-alanine （D-Ala） is an essential amino acid that has a key role in bacterial unique enzyme that interconverts L-alanine and D-alanine in most bacteria, antimicrobial drug development. Streptococcus mutans is a major causative cell wall synthesis. Alanine racemase （Air） is a making this enzyme a potential target for factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Air in S. mutans. We constructed air mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that air deletion was lethal to S. mutans. A minimal supplement of D-Ala （150 pg.mL- 1） was required for the optimal growth of the air mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the air mutant strain. We also determined the compromised competitiveness of the air mutant strain relative to the wild-type S. mutans against other oral streptococci （S. sanguinis or S. gordonil~, demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of air to the growth and competitiveness of S. mutans, Air may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.展开更多
Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiol...Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiological conditions. Methods Biotin-switch assay, electrophysiological recording, RNA interference, full ESI-MS scan et al. Results Herein, we found that the protein sulfhydration was dynamically regulated by neuro- nal activity. H2S sulfhydrated and activated serine racemase （SR） in the hippocampus, resuhantly increased D- serine level. Notably, sulfhydration of SR was markedly promoted by neuronal stimulation and underlay activity-de- pendent changes of D-serine availability. Both genetic knockdown and pharmacological inhibition of cystathionine β-synthase （CBS）, the key H2S-producing enzyme in brain, attenuated hippoeampal long-term potentiation （LTP） , which can be reversed by exogenous supplement of H2S or D-serine. We also observed that the increase in LTP induced by H2S is dependent on D-serine and polysulfides. In aged rats, sulfhydration of SR was significantly decreased. Furthermore, exogenous supplement of H2S restored the level of sulfhydration and reversed the age-re- lated deficits in hippocampal LTP. Conclusion Our data provide direct evidence for the biological significance of endogenous sulfhydration in physiological conditions and demonstrate a pivotal role of activity-dependent sulfhydra- tion in synaptic plasticity.展开更多
AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic color...AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe dyplasia and carcinoma in situ).AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e.gender,age,localization,grade of dysplasia,size and conf iguration.RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years);37 patients were males and 18 were females.Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm),including 18 tubular,16 villous,20 mixed or tubulovillous,and 1 giant sessile villous adenoma.AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P = 0.002).Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%),(P = 0.005).In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas,AMACR staining was not necessarily observed in the in situ component.Positivity in intra-lesion of mild,moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ,intramucosal or inf iltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%),P < 0.001].Strong AMACR expression was found in 11 out of 17 villous adenomas,but in only 1 out of 18 tubular lesions (P = 0.005).Larger lesions,i.e.> 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%),P = 0.02].Overall,AMACR expression was associated with the grade of dysplasia,as well as with the size and conf iguration of adenomas,i.e.the consensus risk factors applied to colorectal adenoma patient surveillance.CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.展开更多
BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mi...BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.展开更多
Objective:To explore the combined application of multiple markers for diagnosis of prostate cancer.Methods:To choose the hospital in September, 2015 to September 2012, initially determined both by serum PSA test for p...Objective:To explore the combined application of multiple markers for diagnosis of prostate cancer.Methods:To choose the hospital in September, 2015 to September 2012, initially determined both by serum PSA test for prostate cancer patients 117 cases, for patients with confirmed will be divided into three groups (39 cases further examination, compared with the pathological diagnosis of three groups of patients with prostate cancer diagnosis accuracy. Results: The detection rate in group A patients compared with the pathological diagnosis coincidence rate was 77.2%, B group was 90.3%, and 98.2% of group C, A, B two groups were lower in group C, group A and group B was higher than that that P504s inspection diagnosis rate is higher than about, CK34 beta E12 at 11:45, joint detection and diagnosis rate is highest. Three groups of patients were compared with difference had statistical significance . A group of 13 cases of benign specimen, 10 cases were negative, false positive in 3, coincidence rate was 76.9%, B group of 12 cases of benign specimens, the negative in 11 cases, false positives in 1 case, the coincidence rate is 91.7%, group C of 11 cases of benign specimens, negative in 11 cases, false positive 0 cases, coincidence rate was 100%. Combined detection of false positive diagnosis rate was lower than that in group A, B two patients, three groups of patients were compared with difference had statistical significance. Group A in 26 cases of prostate cancer, positive 22 cases, 4 cases were missed diagnosis coincidence rate was 84.6%. Group B in 27 cases of prostate cancer, positive 25 cases, 2 cases of misdiagnosis, the coincidence rate is 92.6%, group C in 27 cases of prostate cancer, 26 patients, positive, 1 case of misdiagnosis, the coincidence rate was 96.3%. Three groups of patients were compared with difference had statistical significance.Conclusion: Combination of P504s (AMACR), basal cell specific markers (about and CK34 beta E12 at 11:45) detection diagnosis can improve the early diagnostic rate of prostate cancer, have important significance on clinical.展开更多
基金financially supported through grants from the National Natural Science Foundation of China (81400501 to Ming-Yun Li, 81371135 to Ji-Yao Li and 81430011 to Xue-Dong Zhou)the International Science and Technology Cooperation Programme of China (2014DFE30180 to Xue-Dong Zhou)+1 种基金the Talented Young Investigator Award of Sichuan University (2082604184224 to Xin Xu)the Special Fund of State Key Laboratory of Oral Diseases, Sichuan University (SKLOD201525 to Ming-Yun Li)
文摘D-alanine （D-Ala） is an essential amino acid that has a key role in bacterial unique enzyme that interconverts L-alanine and D-alanine in most bacteria, antimicrobial drug development. Streptococcus mutans is a major causative cell wall synthesis. Alanine racemase （Air） is a making this enzyme a potential target for factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Air in S. mutans. We constructed air mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that air deletion was lethal to S. mutans. A minimal supplement of D-Ala （150 pg.mL- 1） was required for the optimal growth of the air mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the air mutant strain. We also determined the compromised competitiveness of the air mutant strain relative to the wild-type S. mutans against other oral streptococci （S. sanguinis or S. gordonil~, demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of air to the growth and competitiveness of S. mutans, Air may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.
文摘Aims More and more advances show that hydrogen sulfide （H2S） sulfhydrates functional proteins and regulates their actions. However, much less is known about the endogenous sulfhydration of key proteins under physiological conditions. Methods Biotin-switch assay, electrophysiological recording, RNA interference, full ESI-MS scan et al. Results Herein, we found that the protein sulfhydration was dynamically regulated by neuro- nal activity. H2S sulfhydrated and activated serine racemase （SR） in the hippocampus, resuhantly increased D- serine level. Notably, sulfhydration of SR was markedly promoted by neuronal stimulation and underlay activity-de- pendent changes of D-serine availability. Both genetic knockdown and pharmacological inhibition of cystathionine β-synthase （CBS）, the key H2S-producing enzyme in brain, attenuated hippoeampal long-term potentiation （LTP） , which can be reversed by exogenous supplement of H2S or D-serine. We also observed that the increase in LTP induced by H2S is dependent on D-serine and polysulfides. In aged rats, sulfhydration of SR was significantly decreased. Furthermore, exogenous supplement of H2S restored the level of sulfhydration and reversed the age-re- lated deficits in hippocampal LTP. Conclusion Our data provide direct evidence for the biological significance of endogenous sulfhydration in physiological conditions and demonstrate a pivotal role of activity-dependent sulfhydra- tion in synaptic plasticity.
文摘AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe dyplasia and carcinoma in situ).AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e.gender,age,localization,grade of dysplasia,size and conf iguration.RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years);37 patients were males and 18 were females.Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm),including 18 tubular,16 villous,20 mixed or tubulovillous,and 1 giant sessile villous adenoma.AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P = 0.002).Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%),(P = 0.005).In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas,AMACR staining was not necessarily observed in the in situ component.Positivity in intra-lesion of mild,moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ,intramucosal or inf iltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%),P < 0.001].Strong AMACR expression was found in 11 out of 17 villous adenomas,but in only 1 out of 18 tubular lesions (P = 0.005).Larger lesions,i.e.> 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%),P = 0.02].Overall,AMACR expression was associated with the grade of dysplasia,as well as with the size and conf iguration of adenomas,i.e.the consensus risk factors applied to colorectal adenoma patient surveillance.CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.
文摘BACKGROUND Inborn error of bile acid synthesis type 4 is a peroxisomal disease with impaired bile acid synthesis caused by a-methylacyl-CoA racemase(AMACR)gene mutation.The disease is usually found in children with mild to severe liver disease,cholestasis and poor fat-soluble vitamin absorption.At present,there is no report of inborn errors of bile acid synthesis type 4 in adults with liver disease and poor fat-soluble vitamin absorption.CASE SUMMARY A 71-year-old man was hospitalized in our department for recurrent liver dysfunction.The clinical manifestations were chronic liver disease and yellow skin and sclera.Serum transaminase,bilirubin and bile acid were abnormally increased;and fat-soluble vitamins decreased.Liver cirrhosis and ascites were diagnosed by computed tomography.The patient had poor coagulation function and ascites and did not undergo liver puncture.Genetic testing showed AMACR gene missense mutation.The patient was diagnosed with inborn error of bile acid synthesis type 4.He was treated with ursodeoxycholic acid,liver protection and vitamin supplementation,and jaundice of the skin and sclera was reduced.The indicators of liver function and the quality of life were significantly improved.CONCLUSION When adults have recurrent liver function abnormalities,physicians should be alert to genetic diseases and provide timely treatment.
文摘Objective:To explore the combined application of multiple markers for diagnosis of prostate cancer.Methods:To choose the hospital in September, 2015 to September 2012, initially determined both by serum PSA test for prostate cancer patients 117 cases, for patients with confirmed will be divided into three groups (39 cases further examination, compared with the pathological diagnosis of three groups of patients with prostate cancer diagnosis accuracy. Results: The detection rate in group A patients compared with the pathological diagnosis coincidence rate was 77.2%, B group was 90.3%, and 98.2% of group C, A, B two groups were lower in group C, group A and group B was higher than that that P504s inspection diagnosis rate is higher than about, CK34 beta E12 at 11:45, joint detection and diagnosis rate is highest. Three groups of patients were compared with difference had statistical significance . A group of 13 cases of benign specimen, 10 cases were negative, false positive in 3, coincidence rate was 76.9%, B group of 12 cases of benign specimens, the negative in 11 cases, false positives in 1 case, the coincidence rate is 91.7%, group C of 11 cases of benign specimens, negative in 11 cases, false positive 0 cases, coincidence rate was 100%. Combined detection of false positive diagnosis rate was lower than that in group A, B two patients, three groups of patients were compared with difference had statistical significance. Group A in 26 cases of prostate cancer, positive 22 cases, 4 cases were missed diagnosis coincidence rate was 84.6%. Group B in 27 cases of prostate cancer, positive 25 cases, 2 cases of misdiagnosis, the coincidence rate is 92.6%, group C in 27 cases of prostate cancer, 26 patients, positive, 1 case of misdiagnosis, the coincidence rate was 96.3%. Three groups of patients were compared with difference had statistical significance.Conclusion: Combination of P504s (AMACR), basal cell specific markers (about and CK34 beta E12 at 11:45) detection diagnosis can improve the early diagnostic rate of prostate cancer, have important significance on clinical.
