In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Intere...In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells.Major differences have been found between differentiated cells and stem cells.Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases,such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions.Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition,recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting,the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.展开更多
Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into ...Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.展开更多
Background This study was conducted to investigate retrospectively the indications for renal biopsy(RB)in native kidneys and to analyze pathological findings in a single tertiary pediatric hospital in Southern Italy f...Background This study was conducted to investigate retrospectively the indications for renal biopsy(RB)in native kidneys and to analyze pathological findings in a single tertiary pediatric hospital in Southern Italy for the last 36 years.Methods All patients who underwent RB at our hospital from 1979 to 2014 were included.All renal tissue specimens were studied under light and immunofluorescent microscopy,while electron microscopy was performed only for specific clinical indications.Results The study group included 213 patients(female 43.2%)who underwent 225 percutaneous native kidney biopsies.Median age was 10.4 years(range 0.6-24 years).The most frequent indication for RB was nephrotic syndrome(44.4%),fol-lowed by proteinuria(27.6%),asymptomatic hematuria(17.3%)and acute kidney injury(9.8%).Gross hematuria appeared after biopsy in less than 5%of the patients,but none of them needed blood transfusion.Adequate renal tissue sample was obtained in 95.5%of the renal biopsies.Primary glomerulonephritis(GN)was the most common finding(61.4%),followed by secondary GN(21.4%),tubulointerstitial diseases(3.7%)and hereditary nephropathy(2.8%),while in 10.7%of the cases,normal renal tissues were found.According to histopathological diagnosis,the most common causes of primary GN were IgA nephropathy(20.9%),followed by minimal change disease(18.1%)and focal segmental glomerulosclerosis(11.6%).Conclusions The epidemiology of glomerular disease in our single-center cohort is similar to that shown in other national and international reports.Moreover,our study shows that percutaneous ultrasound-guided RB is a safe,reliable and effec-tive technique in children.展开更多
文摘In 1975, Holliday and Pugh as well as Riggs independently hypothesized that DNA methylation in eukaryotes could act as a hereditary regulation mechanism that influences gene expression and cell differentiation. Interest in the study of epigenetic processes has been inspired by their reversibility as well as their potentially preventable or treatable consequences. Recently, we have begun to understand that the features of DNA methylation are not the same for all cells.Major differences have been found between differentiated cells and stem cells.Methylation influences various pathologies, and it is very important to improve the understanding of the pathogenic mechanisms. Epigenetic modifications may take place throughout life and have been related to cancer, brain aging, memory disturbances, changes in synaptic plasticity, and neurodegenerative diseases,such as Parkinson's disease and Huntington's disease. DNA methylation also has a very important role in tumor biology. Many oncogenes are activated by mutations in carcinogenesis. However, many genes with tumor-suppressor functions are "silenced" by the methylation of CpG sites in some of their regions.Moreover, the role of epigenetic alterations has been demonstrated in neurological diseases. In neuronal precursors, many genes associated with development and differentiation are silenced by CpG methylation. In addition,recent studies show that DNA methylation can also influence diseases that do not appear to be related to the environment, such as IgA nephropathy, thus affecting,the expression of some genes involved in the T-cell receptor signaling. In conclusion, DNA methylation provides a whole series of fundamental information for the cell to regulate gene expression, including how and when the genes are read, and it does not depend on the DNA sequence.
文摘Nowadays,it is clear that adult stem cells,also called as tissue stem cells,play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells.As stem cells age,their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired.From a molecular perspective,these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration(i.e epigenomic profile)as well as changes in the tissue microenviroment,both into the niche and by systemic circulating factors.Strikingly,it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders.Therefore,understanding how resident stem cell age and affects near and distant tissues is fundamental.Here,we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number,function and phenotype that determine the loss of tissue renewal properties.Furthermore,we examine the possible cell rejuvenation strategies.Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases.
文摘Background This study was conducted to investigate retrospectively the indications for renal biopsy(RB)in native kidneys and to analyze pathological findings in a single tertiary pediatric hospital in Southern Italy for the last 36 years.Methods All patients who underwent RB at our hospital from 1979 to 2014 were included.All renal tissue specimens were studied under light and immunofluorescent microscopy,while electron microscopy was performed only for specific clinical indications.Results The study group included 213 patients(female 43.2%)who underwent 225 percutaneous native kidney biopsies.Median age was 10.4 years(range 0.6-24 years).The most frequent indication for RB was nephrotic syndrome(44.4%),fol-lowed by proteinuria(27.6%),asymptomatic hematuria(17.3%)and acute kidney injury(9.8%).Gross hematuria appeared after biopsy in less than 5%of the patients,but none of them needed blood transfusion.Adequate renal tissue sample was obtained in 95.5%of the renal biopsies.Primary glomerulonephritis(GN)was the most common finding(61.4%),followed by secondary GN(21.4%),tubulointerstitial diseases(3.7%)and hereditary nephropathy(2.8%),while in 10.7%of the cases,normal renal tissues were found.According to histopathological diagnosis,the most common causes of primary GN were IgA nephropathy(20.9%),followed by minimal change disease(18.1%)and focal segmental glomerulosclerosis(11.6%).Conclusions The epidemiology of glomerular disease in our single-center cohort is similar to that shown in other national and international reports.Moreover,our study shows that percutaneous ultrasound-guided RB is a safe,reliable and effec-tive technique in children.
