Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encod...Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the promoter of the DNMT1 gene through a potential OCT1 site and the binding is required for maintaining a transcriptional active configuration of the promoter in both mouse and human cells. We further demonstrated that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration in several types of tissues examined in a BRCA1 mutant mouse model at premaligant stages. BRCA1 deficiency is also associated with significantly increased expression levels of several protooncogenes, including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while premalignant mammary epithelial cells displayed an intermediate state between tumors and controls. In human clinical samples, reduced expression of BRCA1 correlates with decreased levels of DNMT1, and reduced methylation of CpG islands. Thus, BRCA1 prevents global DNA hypomethylation through positively regulating DNMT1 expression, and this provides one of mechanisms for BRCAl-associated breast cancer formation.展开更多
This case report describes the unusual presentation of a patient who had findings which were initially suggestive of a type Ⅳ choledochal cyst. Her liver biopsy demonstrated biliary cirrhosis. She was treated with en...This case report describes the unusual presentation of a patient who had findings which were initially suggestive of a type Ⅳ choledochal cyst. Her liver biopsy demonstrated biliary cirrhosis. She was treated with endoscopic retrograde cholangiopancreatography and biliary stent exchanges over one year. Her cholangiogram one year later demonstrated resolution of the biliary cystic dilation which led to her initial diagnosis, with beading and stricturing of the hepatic ducts consistent with primary sclerosing cholangitis. Liver-associated enzymes and physical findings also improved. A liver biopsy one year later demonstrated a marked improvement in hepatic fibrosis with no evidence of cirrhosis.展开更多
Infectious diseases caused by arboviruses are a public health concern in Pakistan.However,studies on data prevalence and threats posed by arboviruses are limited.This study investigated the seroprevalence of arbovirus...Infectious diseases caused by arboviruses are a public health concern in Pakistan.However,studies on data prevalence and threats posed by arboviruses are limited.This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan,including severe fever with thrombocytopenia syndrome virus(SFTSV),Crimean-Congo hemorrhagic fever virus(CCHFV),Tamdy virus(TAMV),and Karshi virus(KSIV)based on a newly established luciferase immunoprecipitation system(LIPS)assays,and Zika virus(ZIKV)by enzyme-linked immunosorbent assays(ELISA).Neutralizing activities against these arboviruses were further examined from the antibody positive samples.The results showed that the seroprevalence of SFTSV,CCHFV,TAMV,KSIV,and ZIKV was 17.37%,7.58%,4.41%,1.10%,and 6.48%,respectively,and neutralizing to SFTSV(1.79%),CCHFV(2.62%),and ZIKV(0.69%)were identified,as well as to the SFTSV-related Guertu virus(GTV,0.83%).Risk factors associated with the incidence of exposure and levels of antibody response were analyzed.Moreover,co-exposure to different arboviruses was demonstrated,as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing activity.Males,individuals aged40 years,and outdoor workers had a high risk of exposure to arboviruses.All these results reveal the substantial risks of infection with arboviruses in Pakistan,and indicate the threat from co-exposure to multiple arboviruses.The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.展开更多
Primary cutaneous marginal zone B-cell lymphoma (MZL) is considered a cutaneous counterpart of extranodal MZL of mucosa-associated lymphoid tissue and an indolent lymphoma. Amyloid deposition in this tumor is very rar...Primary cutaneous marginal zone B-cell lymphoma (MZL) is considered a cutaneous counterpart of extranodal MZL of mucosa-associated lymphoid tissue and an indolent lymphoma. Amyloid deposition in this tumor is very rare. We report here a case of primary cutaneous MZL with massive amyloid deposition. The tumor disseminated to the dura and mimicked primary dural MZL. The patient had a four year history of the recurrence cutaneous lesions with a misdiagnosis of amyloidosis. The correct diagnosis was made after the metastatic dural lesion was confirmed by radiology, pathology and molecular biology approaches. It is of crucial importance for differential diagnosis to avoid misdiagnosis and the patients are indeed required long-term regular examinations and treatment because of the possibility of recurrence or dissemination.展开更多
Erdheim-Chester disease (ECD) is a rare systemic histiocytic disease. The authors present a case report detailing the presentation and treatment of a 26-year-old man diagnosed with seizures and a well - circumscribed ...Erdheim-Chester disease (ECD) is a rare systemic histiocytic disease. The authors present a case report detailing the presentation and treatment of a 26-year-old man diagnosed with seizures and a well - circumscribed temporoparietal mass that had been demonstrated on imaging studies. Both preoperative and intraoperative diagnoses were consistent with a low - grade astrocytic neoplasm. Subsequent pathological examination indicated a histiocytic proliferation positive for CD68 and factor Ⅷ, and negative for CDla and S100, with Touton giant cells characteristic of ECD. This case represents the first isolated occurrence of intracranial ECD and its potential to mimic glial neoplasms.展开更多
Liver fibrosis is a wound-healing response of liver cells to chronic injuries caused by viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), toxins, and alcohol abuse. The ability to stage dis...Liver fibrosis is a wound-healing response of liver cells to chronic injuries caused by viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), toxins, and alcohol abuse. The ability to stage diseases for treatment na?ve patients to initiate proper medical procedures and predict the clinical causes of the disease or the treatment response is important given the increased prevalence of liver fibrosis caused by HBV, HCV and fatty liver diseases. CHI3L1 (chitinase-3-like protein 1, also known as YKL-40), which belongs to the chitinase family but lacks chitinolytic activity and is highly expressed in the liver, seems to fulfill this role. CHI3L1 is a non-invasive staging marker for liver fibrosis caused by HBV, HCV and non-alcoholic fatty liver disease as well as a predictor of the clinical causes and fibrotic changes after treatments. CHI3L1 predicts histological progression of liver fibrosis and fibrosis progression rate (fibrosis unit/year), rapid fibrosis progression after liver transplantation and response to interferon and recent direct acting antiviral therapy in chronic HCV patients. CHI3L1 also predicts response to antiviral therapy in chronic HBV patients.展开更多
文摘Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1. BRCA1 binds to the promoter of the DNMT1 gene through a potential OCT1 site and the binding is required for maintaining a transcriptional active configuration of the promoter in both mouse and human cells. We further demonstrated that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration in several types of tissues examined in a BRCA1 mutant mouse model at premaligant stages. BRCA1 deficiency is also associated with significantly increased expression levels of several protooncogenes, including c-Fos, Ha-Ras, and c-Myc, with a higher expression in tumors, while premalignant mammary epithelial cells displayed an intermediate state between tumors and controls. In human clinical samples, reduced expression of BRCA1 correlates with decreased levels of DNMT1, and reduced methylation of CpG islands. Thus, BRCA1 prevents global DNA hypomethylation through positively regulating DNMT1 expression, and this provides one of mechanisms for BRCAl-associated breast cancer formation.
文摘This case report describes the unusual presentation of a patient who had findings which were initially suggestive of a type Ⅳ choledochal cyst. Her liver biopsy demonstrated biliary cirrhosis. She was treated with endoscopic retrograde cholangiopancreatography and biliary stent exchanges over one year. Her cholangiogram one year later demonstrated resolution of the biliary cystic dilation which led to her initial diagnosis, with beading and stricturing of the hepatic ducts consistent with primary sclerosing cholangitis. Liver-associated enzymes and physical findings also improved. A liver biopsy one year later demonstrated a marked improvement in hepatic fibrosis with no evidence of cirrhosis.
基金supported by the National Key Research and Development Programme of China[Grant Number 2021YFC2300900,2022YFC2302700]International Partnership Programme of the Bureau of International Cooperation,Chinese Academy of Sciences[Grant Number 153B42KYSB20200013]+1 种基金National Natural Science Foundation of China[Grant Number U22A20363]Biological Resources Programme,Chinese Academy of Sciences[Grant Number KFJ-BRP-017-74].
文摘Infectious diseases caused by arboviruses are a public health concern in Pakistan.However,studies on data prevalence and threats posed by arboviruses are limited.This study investigated the seroprevalence of arboviruses in a healthy population in Pakistan,including severe fever with thrombocytopenia syndrome virus(SFTSV),Crimean-Congo hemorrhagic fever virus(CCHFV),Tamdy virus(TAMV),and Karshi virus(KSIV)based on a newly established luciferase immunoprecipitation system(LIPS)assays,and Zika virus(ZIKV)by enzyme-linked immunosorbent assays(ELISA).Neutralizing activities against these arboviruses were further examined from the antibody positive samples.The results showed that the seroprevalence of SFTSV,CCHFV,TAMV,KSIV,and ZIKV was 17.37%,7.58%,4.41%,1.10%,and 6.48%,respectively,and neutralizing to SFTSV(1.79%),CCHFV(2.62%),and ZIKV(0.69%)were identified,as well as to the SFTSV-related Guertu virus(GTV,0.83%).Risk factors associated with the incidence of exposure and levels of antibody response were analyzed.Moreover,co-exposure to different arboviruses was demonstrated,as thirty-seven individuals were having antibodies against multiple viruses and thirteen showed neutralizing activity.Males,individuals aged40 years,and outdoor workers had a high risk of exposure to arboviruses.All these results reveal the substantial risks of infection with arboviruses in Pakistan,and indicate the threat from co-exposure to multiple arboviruses.The findings raise the need for further epidemiologic investigation in expanded regions and populations and the necessity to improve health surveillance in Pakistan.
文摘Primary cutaneous marginal zone B-cell lymphoma (MZL) is considered a cutaneous counterpart of extranodal MZL of mucosa-associated lymphoid tissue and an indolent lymphoma. Amyloid deposition in this tumor is very rare. We report here a case of primary cutaneous MZL with massive amyloid deposition. The tumor disseminated to the dura and mimicked primary dural MZL. The patient had a four year history of the recurrence cutaneous lesions with a misdiagnosis of amyloidosis. The correct diagnosis was made after the metastatic dural lesion was confirmed by radiology, pathology and molecular biology approaches. It is of crucial importance for differential diagnosis to avoid misdiagnosis and the patients are indeed required long-term regular examinations and treatment because of the possibility of recurrence or dissemination.
文摘Erdheim-Chester disease (ECD) is a rare systemic histiocytic disease. The authors present a case report detailing the presentation and treatment of a 26-year-old man diagnosed with seizures and a well - circumscribed temporoparietal mass that had been demonstrated on imaging studies. Both preoperative and intraoperative diagnoses were consistent with a low - grade astrocytic neoplasm. Subsequent pathological examination indicated a histiocytic proliferation positive for CD68 and factor Ⅷ, and negative for CDla and S100, with Touton giant cells characteristic of ECD. This case represents the first isolated occurrence of intracranial ECD and its potential to mimic glial neoplasms.
文摘Liver fibrosis is a wound-healing response of liver cells to chronic injuries caused by viral infections, including hepatitis B virus (HBV), hepatitis C virus (HCV), toxins, and alcohol abuse. The ability to stage diseases for treatment na?ve patients to initiate proper medical procedures and predict the clinical causes of the disease or the treatment response is important given the increased prevalence of liver fibrosis caused by HBV, HCV and fatty liver diseases. CHI3L1 (chitinase-3-like protein 1, also known as YKL-40), which belongs to the chitinase family but lacks chitinolytic activity and is highly expressed in the liver, seems to fulfill this role. CHI3L1 is a non-invasive staging marker for liver fibrosis caused by HBV, HCV and non-alcoholic fatty liver disease as well as a predictor of the clinical causes and fibrotic changes after treatments. CHI3L1 predicts histological progression of liver fibrosis and fibrosis progression rate (fibrosis unit/year), rapid fibrosis progression after liver transplantation and response to interferon and recent direct acting antiviral therapy in chronic HCV patients. CHI3L1 also predicts response to antiviral therapy in chronic HBV patients.
