2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group ...2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group in 1 binding to CPA,2-benzyl-5- benzyloxy-4-oxopentanoic acid 2 was also synthesized and evaluated.The inhibition constants show that both L-1 and D-1 were shown to have strong binding affinity with L-1 being more potent than its enantiomer by 165-fold.On the other hand,the inhibition constant ...展开更多
AIM: To develop novel biomarkers of rectal radiotherapy, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. METHODS: Six patients presenting with a locally advanced rec...AIM: To develop novel biomarkers of rectal radiotherapy, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. METHODS: Six patients presenting with a locally advanced rectal cancer (T>T2, N0/Nx, M0) eligible for preoperative radiotherapy (45 Gy in 25 fractions) were selected in a pilot study. Six tumor and 3 normal tissues biopsies were taken before and during radiotherapy,after a dose of 7.2 Gy at a median time of 1 h following irradiation (0:27-2:12). Tumor or normal tissue purity was assessed by a pathologist prior to RNA extraction. Mean RNA content was 23 μg/biopsy (14-37) before radiotherapy and 22.7 μg/biopsy (12-35) during radiotherapy. After RNA amplification, biopsies were analysed with 54K HG-U133A Plus 2.0 Affymetrix expression micro-arrays. Data were normalized according to MAS5 algorithm. A gene expression ratio was calculated as: (gene expression during radiotherapy-gene expression before radiotherapy)/gene expression before radiotherapy. Were selected genes that showed a ratio higher than ± 0.5 in all 6 patients. RESULTS: Microarray analysis showed that preoperative radiotherapy significantly up-regulated 31 genes and down-regulated 6 genes. According to the Gene Ontology project classification, these genes are involved in protein metabolism (ADAMDEC1 ; AKAP7 ; CAPN5 ; CLIC5 ; CPE ; CREB3L1 ; NEDD4L ; RAB27A), ion transport (AKAP7 ; ATP2A3 ; CCL28 ; CLIC5 ; F2RL2 ; NEDD4L ; SLC6A8), transcription (AKAP7 ; CREB3L1 ; ISX ; PAB-PC1L ; TXNIP), signal transduction (CAPN5 ; F2RL2 ; RA- B27A ; TNFRSF11A), cell adhesion (ADAMDEC1 ; PXDN ; SPON1 ; S100A2), immune response (CCL28 ; PXDN ; TNFRSF11A) and apoptosis (ITM2C ; PDCD4 ; PVT1). Up-regulation of 3 genes (CCL28 ; CLIC5 ; PDCD4) was detected by 2 different probes and up-regulation of 2 genes (RAB27A ; TXNIP) by 3 probes. CONCLUSION: Micro-arrays can efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer, and may help better understand tumor radioresistance.展开更多
Diabetes mellitus refers to a group of diseases that cause high blood sugar levels.The most common type is type 2 diabetes,which is caused by insulin resistance and inadequate insulin production.However,diabetes can a...Diabetes mellitus refers to a group of diseases that cause high blood sugar levels.The most common type is type 2 diabetes,which is caused by insulin resistance and inadequate insulin production.However,diabetes can also result from conditions affecting the exocrine pancreas.Both type 1 and type 2 diabetes patients may experience changes in their pancreatic exocrine function,leading to reduced levels of fecal elastase-1 in many cases.This review article focuses on the role of specific pancreatic biomarkers in diabetes mellitus,including cholecystokinin,trypsin,chymotrypsin,carboxypeptidase,amylase,lipase,secretin,elastase-1,and retinol-binding protein 4 about recent advances and discoveries,significant gaps in the literature,current debates,and potential directions for future research related to these biomarkers about diabetes mellitus.This review article discusses various biomarkers related to pancreatic exocrine and endocrine function and their implications in diabetes.It suggests that gut cholecystokinin may play a role in lowering glucose synthesis through a neural network and resistance to it could contribute to hyperglycemia in diabetic patients.It also discusses the use of various markers such as serum trypsin concentration,amylase and lipase levels,pancreatic elastase levels,and fasting secretin levels to assess pancreatic exocrine function.Additionally,the article explores the role of carboxypeptidase E in the endocrine and neurological systems and its association with disorders.Moreover,it also highlights the involvement of retinol-binding protein 4 in the development of type 2 diabetes and insulin resistance.展开更多
文摘2-Benzyl-5-hydroxy-4-oxopentanoic acid 1 and its enantiomers were designed,synthesized and assayed for inhibitory activity against carboxypeptidase A(CPA,EC 3.4.17.1).To verify the role of the terminal hydroxyl group in 1 binding to CPA,2-benzyl-5- benzyloxy-4-oxopentanoic acid 2 was also synthesized and evaluated.The inhibition constants show that both L-1 and D-1 were shown to have strong binding affinity with L-1 being more potent than its enantiomer by 165-fold.On the other hand,the inhibition constant ...
基金Supported by Ligue Contre le Cancer, Programme Hospitalier de Recherche Clinique (20-R6)
文摘AIM: To develop novel biomarkers of rectal radiotherapy, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. METHODS: Six patients presenting with a locally advanced rectal cancer (T>T2, N0/Nx, M0) eligible for preoperative radiotherapy (45 Gy in 25 fractions) were selected in a pilot study. Six tumor and 3 normal tissues biopsies were taken before and during radiotherapy,after a dose of 7.2 Gy at a median time of 1 h following irradiation (0:27-2:12). Tumor or normal tissue purity was assessed by a pathologist prior to RNA extraction. Mean RNA content was 23 μg/biopsy (14-37) before radiotherapy and 22.7 μg/biopsy (12-35) during radiotherapy. After RNA amplification, biopsies were analysed with 54K HG-U133A Plus 2.0 Affymetrix expression micro-arrays. Data were normalized according to MAS5 algorithm. A gene expression ratio was calculated as: (gene expression during radiotherapy-gene expression before radiotherapy)/gene expression before radiotherapy. Were selected genes that showed a ratio higher than ± 0.5 in all 6 patients. RESULTS: Microarray analysis showed that preoperative radiotherapy significantly up-regulated 31 genes and down-regulated 6 genes. According to the Gene Ontology project classification, these genes are involved in protein metabolism (ADAMDEC1 ; AKAP7 ; CAPN5 ; CLIC5 ; CPE ; CREB3L1 ; NEDD4L ; RAB27A), ion transport (AKAP7 ; ATP2A3 ; CCL28 ; CLIC5 ; F2RL2 ; NEDD4L ; SLC6A8), transcription (AKAP7 ; CREB3L1 ; ISX ; PAB-PC1L ; TXNIP), signal transduction (CAPN5 ; F2RL2 ; RA- B27A ; TNFRSF11A), cell adhesion (ADAMDEC1 ; PXDN ; SPON1 ; S100A2), immune response (CCL28 ; PXDN ; TNFRSF11A) and apoptosis (ITM2C ; PDCD4 ; PVT1). Up-regulation of 3 genes (CCL28 ; CLIC5 ; PDCD4) was detected by 2 different probes and up-regulation of 2 genes (RAB27A ; TXNIP) by 3 probes. CONCLUSION: Micro-arrays can efficiently assess early transcriptomic changes during preoperative radiotherapy for rectal cancer, and may help better understand tumor radioresistance.
文摘Diabetes mellitus refers to a group of diseases that cause high blood sugar levels.The most common type is type 2 diabetes,which is caused by insulin resistance and inadequate insulin production.However,diabetes can also result from conditions affecting the exocrine pancreas.Both type 1 and type 2 diabetes patients may experience changes in their pancreatic exocrine function,leading to reduced levels of fecal elastase-1 in many cases.This review article focuses on the role of specific pancreatic biomarkers in diabetes mellitus,including cholecystokinin,trypsin,chymotrypsin,carboxypeptidase,amylase,lipase,secretin,elastase-1,and retinol-binding protein 4 about recent advances and discoveries,significant gaps in the literature,current debates,and potential directions for future research related to these biomarkers about diabetes mellitus.This review article discusses various biomarkers related to pancreatic exocrine and endocrine function and their implications in diabetes.It suggests that gut cholecystokinin may play a role in lowering glucose synthesis through a neural network and resistance to it could contribute to hyperglycemia in diabetic patients.It also discusses the use of various markers such as serum trypsin concentration,amylase and lipase levels,pancreatic elastase levels,and fasting secretin levels to assess pancreatic exocrine function.Additionally,the article explores the role of carboxypeptidase E in the endocrine and neurological systems and its association with disorders.Moreover,it also highlights the involvement of retinol-binding protein 4 in the development of type 2 diabetes and insulin resistance.
