BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-...BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.展开更多
BACKGROUND Pancreatic acinar cell carcinoma(PACC)is a rare tumor.Up to 45%of PACCs have alterations in the DNA damage repair pathway and 23%harbor rearrangements in the BRAF or RAF1 genes.We present a PACC case with a...BACKGROUND Pancreatic acinar cell carcinoma(PACC)is a rare tumor.Up to 45%of PACCs have alterations in the DNA damage repair pathway and 23%harbor rearrangements in the BRAF or RAF1 genes.We present a PACC case with a germline BRCA2 likely pathogenic variant(LPV)to highlight the impact of genomic testing on treatment decisions and patient outcomes.In our larger case series,we provide clinic-based information on additional 10 PACC patients treated in our center.CASE SUMMARY A 70-year-old male was diagnosed with advanced PACC.At presentation,he was cachectic with severe arthralgia despite prednisolone and a skin rash that was later confirmed to be panniculitis.He was treated with modified FOLFIRINOX(mFFX)with the knowledge of the germline BRCA2 LPV.Following 11 cycles of mFFX,a computed tomography(CT)scan demonstrated significant tumor response in the pancreatic primary and hepatic metastases,totaling 70%from baseline as per Response Evaluation Criteria in Solid Tumors.Resolution of the skin panniculitis was also noted.We identified two additional PACCs with druggable targets in our case series.Our data contribute to practical evidence for the value of germline and somatic profiling in the management of rare diseases like PACC.CONCLUSION This patient and others in our larger case series highlight the importance of genomic testing in PACC with potential utility in personalized treatment.展开更多
基金Supported by Shanxi Provincial Natural Science Foundation,No.201701D121159Shanxi Provincial Health and Family Planning Commission,No.2014016Health Commission of Shanxi Province,No.2019020.
文摘BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.
文摘BACKGROUND Pancreatic acinar cell carcinoma(PACC)is a rare tumor.Up to 45%of PACCs have alterations in the DNA damage repair pathway and 23%harbor rearrangements in the BRAF or RAF1 genes.We present a PACC case with a germline BRCA2 likely pathogenic variant(LPV)to highlight the impact of genomic testing on treatment decisions and patient outcomes.In our larger case series,we provide clinic-based information on additional 10 PACC patients treated in our center.CASE SUMMARY A 70-year-old male was diagnosed with advanced PACC.At presentation,he was cachectic with severe arthralgia despite prednisolone and a skin rash that was later confirmed to be panniculitis.He was treated with modified FOLFIRINOX(mFFX)with the knowledge of the germline BRCA2 LPV.Following 11 cycles of mFFX,a computed tomography(CT)scan demonstrated significant tumor response in the pancreatic primary and hepatic metastases,totaling 70%from baseline as per Response Evaluation Criteria in Solid Tumors.Resolution of the skin panniculitis was also noted.We identified two additional PACCs with druggable targets in our case series.Our data contribute to practical evidence for the value of germline and somatic profiling in the management of rare diseases like PACC.CONCLUSION This patient and others in our larger case series highlight the importance of genomic testing in PACC with potential utility in personalized treatment.
