Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progres...Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.展开更多
It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good d...It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.展开更多
AIM： To determine the factors affecting mortality in pa- tients who developed graft-versus-host disease （GvHD） after liver transplantation （LT）. METHODS： We performed a review of studies of GvHD following LT pub...AIM： To determine the factors affecting mortality in pa- tients who developed graft-versus-host disease （GvHD） after liver transplantation （LT）. METHODS： We performed a review of studies of GvHD following LT published in the English literature and ac- cessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phras- es, 88 articles were identified. Of these, 62 articles con- raining most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association （P 〈 0.05） were then sub- jected to multivariate analyses using a Cox proportional- hazards model. RESULTS： The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years （range： 8 mo to 74 years）, who met the inclusion criteria for the present study. Deaths occurred in 59 （67.8%） patients, whereas 28 （32.2%） survived after a mean follow-up period of 280.8 ± 316.2 d （range： 27-2285 d）. Among the most frequent symptoms were rash （94.2%）, fever （66.6%）, diarrhea （54%）, and pancytopenia （54%）. The average time period between LT and first symptom on- set was 60.6 ± 190.1 d （range： 2-1865 d）. The Kaplan- Meier analysis revealed that pancytopenia （42.8% vs 59.3%, P = 0.03）, diarrhea （39.2% vs 61.0%, P = 0.04）, age difference between the recipient and the donor （14.6 ± 3.1 years vs 22.6 ± 2.7 years, P 〈 0.0001）, and time From first symptom occurrence to diagnosis or treatment （13.3 ± 2.6 mo vs 15.0 ± 2.3 mo, P 〈 0.0001） were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, de- termined that an age difference between the recipient and donor was an independent risk Factor （P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7）. CONCLUSION： This study showed that an age differ- ence between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.展开更多
The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypot...The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportinand the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH. More defined studies are required to improve our understanding of these effects.展开更多
In this paper, we review the concept of quality of ulcer healing （QOUH） in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease （PUD） has been a chronic disease with a...In this paper, we review the concept of quality of ulcer healing （QOUH） in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease （PUD） has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori （H. pylorl~, which is also the cause of ulcer recur- rence. However, H. pylori-negative ulcers are pres- ent in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macro- phages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer re- currence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a defi- ciency and/or an imbalance of endogenous growth fac- tors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn＇s disease and ulcer- ative colitis.展开更多
AIM： TO evaluate the prophylaxis of chronic kidney dis- ease （CKD） after liver transplantation （LT） with low-dose calcineurin inhibitor （CNI） and mycophenolate mofetil （MMF）.
The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with lifethreatening liver diseases dying while on the waiting list. The use of cell transplantation for liver disease is a...The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with lifethreatening liver diseases dying while on the waiting list. The use of cell transplantation for liver disease is an attempt to correct metabolic defects, or to support liver function as a bridge to liver transplantation and, as such, has raised a number of expectations. Most of the available studies briefly reported here focus on adult hepatocyte transplantation (HT), and the results are neither reproducible nor comparable, because the means of infusion, amount of injected cells and clinical variability differ among the studies. To better understand the specif ic role of HT in the management of end-stage liver disease, it is important that controlled studies, designed on the principles of evidence-based medicine, be done in order to guarantee the reproducibility of results.展开更多
Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clin...Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains unclear.Although OBI has been well documented in human immunodeficiency virus(HIV) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIV setting.展开更多
Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholi...Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.展开更多
Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of...Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of the enzyme glucocerebrosidase.This leads to he-matologic,visceral and skeletal maifestions.Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly.The normal bone marrow is re-placed by the accumulating substrate leading to many of the hematologic signs including anemia.The visceral and skeletal manifestations can be visualized with vari-ous imaging modalities including radiography,com-puted tomography,magnetic resonance imaging(MRI)and radionuclide scanning.Prior to the development of enzyme replacement therapy,treatment was only sup-portive.However,once intravenous enzyme replace-ment therapy became available in the 1990s it quickly became the standard of care.Enzyme replacement therapy leads to improvement in all manifestations.Thevisceral and hematologic manifestations respond more quickly usually within a few months or years.The skel-etal manifestations take much longer,usually several years,to show improvement.In recent years newer treatment strategies,such as substrate reduction thera-py,have been under investigation.Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.展开更多
To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects,1322 subjects were sub-jected to a questionnaire survey ...To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects,1322 subjects were sub-jected to a questionnaire survey and physical examination.Fasting blood samples were collected to test serum TSH,plasma glucose and lipids.Fatty liver was diagnosed by type B ultrasonography.The rela-tionship between serum TSH level and body mass index (BMI),percentage of body fat and NAFLD was analyzed.The results showed that serum TSH level was significantly higher in females than in males at the same group,and it was significantly higher in overweight group than in control group.Levels of body weight,BMI,waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women.However,plasma lipids showed no significant differences.In males all the parameters showed no significant differences between two groups.Serum TSH was sig-nificantly correlated with body weight,BMI,waist circumference and percentage of body fat after ad-justment for age in females.Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH.Serum TSH level was significantly higher in non-alcoholic fatty liver group than in normal group in females.Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD.Taken together the data suggest that se-rum TSH in normal range is significantly correlated with BMI and percentage of body fat in females.And the change of TSH level would not influence the prevalence of NAFLD.展开更多
The inflammatory bowel diseases(IBD),Crohn's disease(CD) and ulcerative colitis(UC),may be complicated by colorectal cancer(CRC).In a recent populationbased cohort study of 47 347 Danish patients with IBD by Tine ...The inflammatory bowel diseases(IBD),Crohn's disease(CD) and ulcerative colitis(UC),may be complicated by colorectal cancer(CRC).In a recent populationbased cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation.The overall risk of CRC among patients with UC and CD was comparable with that of the general population.However,patients diagnosed with UC during childhood or as adolescents,patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk.In this commentary,we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients.Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC.The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD.The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients.The achieved knowledge may also be relevant for other inflammation-associated cancers.展开更多
Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been ...Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.展开更多
Aim It is well known that menopause could worsen age-related ventricular concentric remodeling and increased incidence of arrhythmias following estrogen （E2） deficiency. However, the underlying mechanisms of such ph...Aim It is well known that menopause could worsen age-related ventricular concentric remodeling and increased incidence of arrhythmias following estrogen （E2） deficiency. However, the underlying mechanisms of such phenomena are not fully understood. Mitochondria, as the ＇cellular power station＇ of hearts, play an impor- tant role in maintaining normal cardiac function and structure. Therefore, the present study aims to investigate whether mitochondrial compromise and gap junction impairment induced by miR-23a is responsible for E2 deficien- cy associated structural and electrical remodeling. Results： We found mitochondrial structural damages and respira- tory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mito- chondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the lar remodeling, which can be regulated via MicroRNAs （miRNAs）-dependent mechanism. We recently identified Asymmetric dimethylarginine （ADMA） positively correlates to vascular remodeling-based diseases. Here, we hy- pothesized that ADMA induces SMC phenotypic change via a miRNA-dependent mechanism. Methods and Results Microarray analysis enabled the identification of 7 deregulated microRNAs in ADMA-treated human aortic artery smooth muscle cells （hASMCs）. miR-182 was validated by real-time-PCR. Isobaric tags for relative and absolute quantitation （iTRAQ） based analysis of the hASMC proteome revealed that transfection of an miR-182 inhibitor sig- nificantly increased myeloid-associated differentiation marker （MYADM）, which was verified using Western blot and reporter activity quantization with the MYADM 3＇-UTR dual-luciferase reporter system, miR-182 knockdown further repressed Sprouty2 and enhanced MYADM, leading to ERIC/MAP kinase-dependent and MYADM-depend- ent hASMC phenotypic change including proliferation, migration and differentiation marker gene expression change. In vivo, adeno-miR-182 markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression. Atherosclerotic lesions from patients with high ADMA plas- ma levels exhibited decreased miR-182 expression levels and elevated MYADM expression levels. In patients with coronary heart disease （n- 164）, the miR-182 expression level in plasma was negatively correlated with the plas- ma ADMA levels. Conclusions miR-182 is a novel SMC phenotypic modulator by targeting MYADM and can be a potential therapeutic target combating vascular remodeling-associated diseases. Reduced plasma miR-182 levels might be a new predictor of high vascular remodeling risk especially in patient with coronary heart disease.展开更多
Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further su...Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.展开更多
Background and Aim Vascular smooth muscle cell （SMC） phenotype change is a hallmark of vascu-lar remodeling, which can be regulated via MicroRNAs （miRNAs）-dependent mechanism. We recently identified Asymmetric dim...Background and Aim Vascular smooth muscle cell （SMC） phenotype change is a hallmark of vascu-lar remodeling, which can be regulated via MicroRNAs （miRNAs）-dependent mechanism. We recently identified Asymmetric dimethylarginine （ADMA） positively correlates to vascular remodeling-based diseases. Here, we hy-pothesized that ADMA induces SMC phenotypic change via a miRNA-dependent mechanism. Methods and Results Microarray analysis enabled the identification of 7 deregulated microRNAs in ADMA-treated human aortic artery smooth muscle cells （hASMCs）. miR-182 was validated by real-time-PCR. Isobaric tags for relative and absolute quantitation （iTRAQ） based analysis of the hASMC proteome revealed that transfection of an miR-182 inhibitor sig- nificantly increased myeloid-associated differentiation marker （MYADM）, which was verified using Western blot and reporter activity quantization with the MYADM 3＇-UTR dual-luciferase reporter system, miR-182 knockdown further repressed Sprouty2 and enhanced MYADM, leading to ERICZMAP kinase-dependent and MYADM-depend- ent hASMC phenotypic change including proliferation, migration and differentiation marker gene expression change. In vivo, adeno-miR-182 markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression. Atherosclerotic lesions from patients with high ADMA plas- ma levels exhibited decreased miR-182 expression levels and elevated MYADM expression levels. In patients with coronary heart disease （n- 164）, the miR-182 expression level in plasma was negatively correlated with the plas- ma ADMA levels. Conclusions miR-182 is a novel SMC phenotypic modulator by targeting MYADM and can be a potential therapeutic target combating vascular remodeling-associated diseases. Reduced plasma miR-182 levels might be a new predictor of high vascular remodeling risk especially in patient with coronary heart disease.展开更多
In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher compared to normal population. The TE is a common extraintesti...In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher compared to normal population. The TE is a common extraintestinal complication of IBD, squarely associated with the IBD activity. The application of antico-agulant and thrombolytic therapy in severe IBD is an unresolved issue. Herein we report the first case in literature of an active IBD patient with an upper limb acute arterial occlusion and successful catheter-directed thrombolysis (CDT). A 46-year-old male patient is reported who had Crohn's disease for 10 years. His right hand suddenly became cold and painful. Angiography proved acute occlusion of the brachial and radial artery. Vascular surgery intervention was not applicable. Endoscopy showed extended, severe inflammation of the colon. Despite the severe endoscopic findings, frequent bloody stools and moderate anaemia, CDT with recombinant tissue plasminogen activator was performed. The control angiography proved improvement, the radial artery pulse appeared. No bleeding complication was observed. This case supports that CDT-after careful estimation of the bleeding risk-can be effective and safe in patients with severe or life-threatening TE and active IBD.展开更多
AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published articles.METHODS:We aimed to evaluate all Pub Med-reg...AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published articles.METHODS:We aimed to evaluate all Pub Med-registered articles related to the field of IBD from January1,1993 and until December 31,2011.We searched for articles using the key words"inflammatory bowel disease"or"Crohn’s disease"or"ulcerative colitis"or"undetermined colitis",using the age filters of"child"or"adult".We repeated the search according to the total number per year of articles per type of article,for each year of the specified period.We studied randomized controlled trials,clinical trials,case reports,meta-analyses,letters to the editor,reviews,systematic reviews,practice guidelines,and editorials.RESULTS:We identified 44645 articles over the 19year-period.There were 8687 pediatric-tagged articles vs 19750 adult-tagged articles.Thus 16208 articles were unaccounted and not assigned a"pediatric"or"adult"tag by Pub Med.There was an approximately3-fold significant increase in all articles recorded both in pediatric and adult articles.This significant increase was true for nearly every category of article but the number of clinical trials,meta-analysis,and randomized controlled trials increased proportionally more than the number of"lower quality"articles such as editorials or letters to the editor.Very few guidelines were published every year.CONCLUSION:There is a yearly linear increase in publications related to IBD.Relatively,there are more and more clinical trials and higher quality articles.展开更多
Objective: To prepare an apoptosis cell model of Alzheimer Disease (AD) by PC-12 cells treated with β-amyloid protein (Aβ). Methods: PC-12 cells were incubated with different concentrations of Aβ25-35 for different...Objective: To prepare an apoptosis cell model of Alzheimer Disease (AD) by PC-12 cells treated with β-amyloid protein (Aβ). Methods: PC-12 cells were incubated with different concentrations of Aβ25-35 for different duration in vitro. The cell viability was detected by MTT assay. Morphological features of apoptosis were analyzed, with Hoechst 33258/ Propidium iodide dual staining, The level of intracellular free calcium ([Ca2+]i) was calculated by Fura-2/AM fluorescence ratio imaging. Results: ① The viability of PC-12 cells was significantly decreased in proportion to concentration of Aβ25-35 and duration of exposure to Aβ25-35. ② The apoptotic cells appeared in a time and concentration-dependent manner, and the maximal apoptosis happened at 48 h after exposure to 20 μmol/L of Aβ25-35 and 36 h to 30 μmol/L, Cell death reached the peak at 12-24 h later than the apoptotic peak. (3) [Ca2+]i of PC-12 cells was increased in proportion to duration of exposure to the same concentration of Aβ25-35. The time of the highest increase rate of [Ca2+]i was about 12 h earlier than that of apoptosis. Conclusion: An AD cell model using the PC-12 cells induced with Aβ25-35 displays a series of changes related to apoptosis, which may be related to elevation of [Ca2+]i.展开更多
文摘Nonalcoholic fatty liver disease(NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse.Nonalcoholic steatohepatitis(NASH),a severe form of NAFLD,can progress to liver cirrhosis and hepatocellular carcinoma.NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity,type 2 diabetes,and hyperlipemia.Animal models of NAFLD/NASH give crucial information,not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents.An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH.Animal models of NAFLD/NASH are divided into genetic,dietary,and combination models.In this paper,we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.
文摘It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.
文摘AIM： To determine the factors affecting mortality in pa- tients who developed graft-versus-host disease （GvHD） after liver transplantation （LT）. METHODS： We performed a review of studies of GvHD following LT published in the English literature and ac- cessed the PubMed, Medline, EBSCO, EMBASE, and Google Scholar databases. Using relevant search phras- es, 88 articles were identified. Of these, 62 articles con- raining most of the study parameters were considered eligible for the study. Risk factors were first examined using a univariate Kaplan-Meier model, and variables with a significant association （P 〈 0.05） were then sub- jected to multivariate analyses using a Cox proportional- hazards model. RESULTS： The 61 articles reported 87 patients, 58 male and 29 female, mean age, 40.4 ± 15.5 years （range： 8 mo to 74 years）, who met the inclusion criteria for the present study. Deaths occurred in 59 （67.8%） patients, whereas 28 （32.2%） survived after a mean follow-up period of 280.8 ± 316.2 d （range： 27-2285 d）. Among the most frequent symptoms were rash （94.2%）, fever （66.6%）, diarrhea （54%）, and pancytopenia （54%）. The average time period between LT and first symptom on- set was 60.6 ± 190.1 d （range： 2-1865 d）. The Kaplan- Meier analysis revealed that pancytopenia （42.8% vs 59.3%, P = 0.03）, diarrhea （39.2% vs 61.0%, P = 0.04）, age difference between the recipient and the donor （14.6 ± 3.1 years vs 22.6 ± 2.7 years, P 〈 0.0001）, and time From first symptom occurrence to diagnosis or treatment （13.3 ± 2.6 mo vs 15.0 ± 2.3 mo, P 〈 0.0001） were significant factors affecting mortality, whereas age, sex, presence of rash and fever, use of immunosuppressive agents, acute rejection before GvHD, etiological causes, time of onset, and donor type were not associated with mortality risk. The Cox proportional-hazards model, de- termined that an age difference between the recipient and donor was an independent risk Factor （P = 0.03; hazard ratio, 7.395, 95% confidence interval, 1.2-46.7）. CONCLUSION： This study showed that an age differ- ence between the recipient and donor is an independent risk factor for mortality in patients who develop GvHD after LT.
文摘The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportinand the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH. More defined studies are required to improve our understanding of these effects.
文摘In this paper, we review the concept of quality of ulcer healing （QOUH） in the gastrointestinal tract and its role in the ulcer recurrence. In the past, peptic ulcer disease （PUD） has been a chronic disease with a cycle of repeated healing/remission and recurrence. The main etiological factor of PUD is Helicobacter pylori （H. pylorl~, which is also the cause of ulcer recur- rence. However, H. pylori-negative ulcers are pres- ent in 12%-20% of patients; they also recur and are on occasion intractable. QOUH focuses on the fact that mucosal and submucosal structures within ulcer scars are incompletely regenerated. Within the scars of healed ulcers, regenerated tissue is immature and with distorted architecture, suggesting poor QOUH. The abnormalities in mucosal regeneration can be the basis for ulcer recurrence. Our studies have shown that persistence of macrophages in the regenerated area plays a key role in ulcer recurrence. Our studies in a rat model of ulcer recurrence have indicated that proinflammatory cytokines trigger activation of macro- phages, which in turn produce increased amounts of cytokines and chemokines, which attract neutrophils to the regenerated area. Neutrophils release proteolytic enzymes that destroy the tissue, resulting in ulcer re- currence. Another important factor in poor QOUH can be deficiency of endogenous prostaglandins and a defi- ciency and/or an imbalance of endogenous growth fac- tors. Topically active mucosal protective and antiulcer drugs promote high QOUH and reduce inflammatory cell infiltration in the ulcer scar. In addition to PUD, the concept of QOUH is likely applicable to inflammatory bowel diseases including Crohn＇s disease and ulcer- ative colitis.
基金Supported by Chinese Key Project for Prophylaxis and Treatment of Infection Diseases,No.2008ZX10002-025 and No.2008 ZX10002-026
文摘AIM： TO evaluate the prophylaxis of chronic kidney dis- ease （CKD） after liver transplantation （LT） with low-dose calcineurin inhibitor （CNI） and mycophenolate mofetil （MMF）.
文摘The shortage of organ donors is a problem worldwide, with approximately 15% of adult patients with lifethreatening liver diseases dying while on the waiting list. The use of cell transplantation for liver disease is an attempt to correct metabolic defects, or to support liver function as a bridge to liver transplantation and, as such, has raised a number of expectations. Most of the available studies briefly reported here focus on adult hepatocyte transplantation (HT), and the results are neither reproducible nor comparable, because the means of infusion, amount of injected cells and clinical variability differ among the studies. To better understand the specif ic role of HT in the management of end-stage liver disease, it is important that controlled studies, designed on the principles of evidence-based medicine, be done in order to guarantee the reproducibility of results.
基金Supported by CIBERehd is funded by the Instituto de Salud Carlos Ⅲ
文摘Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains unclear.Although OBI has been well documented in human immunodeficiency virus(HIV) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIV setting.
基金Supported by An NHMRC Practitioner Fellowship to Lewin SRan am FAR Mathilde Krim Fellowship in Basic Biomedical Science to Crane Man NHMRC postgraduate scholarship to Iser D
文摘Liver disease in human immunodeficiency virus(HIV)-infected individuals encompasses the spectrum from abnormal liver function tests,liver decompensation,with and without evidence of cirrhosis on biopsy,to non-alcoholic liver disease and its more severe form,non-alcoholic steatohepatitis and hepatocellular cancer.HIV can infect multiple cells in the liver,leading to enhanced intrahepatic apoptosis,activation and fibrosis.HIV can also alter gastro-intestinal tract permeability,leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function.This review focuses on recent changes in the epidemiology,pathogenesis and clinical presentation of liver disease in HIV-infected patients,in the absence of co-infection with hepatitis B virus or hepatitis C virus,with a specific focus on issues relevant to low and middle income countries.
文摘Gaucher disease is the prototypical lysosomal storage disease.It results from the accumulation of undegrad-ed glucosylceramide in the reticuloendothelial system of the bone marrow,spleen and liver due to deficiency of the enzyme glucocerebrosidase.This leads to he-matologic,visceral and skeletal maifestions.Build up of glucosylceramide in the liver and spleen results in hepatosplenomegaly.The normal bone marrow is re-placed by the accumulating substrate leading to many of the hematologic signs including anemia.The visceral and skeletal manifestations can be visualized with vari-ous imaging modalities including radiography,com-puted tomography,magnetic resonance imaging(MRI)and radionuclide scanning.Prior to the development of enzyme replacement therapy,treatment was only sup-portive.However,once intravenous enzyme replace-ment therapy became available in the 1990s it quickly became the standard of care.Enzyme replacement therapy leads to improvement in all manifestations.Thevisceral and hematologic manifestations respond more quickly usually within a few months or years.The skel-etal manifestations take much longer,usually several years,to show improvement.In recent years newer treatment strategies,such as substrate reduction thera-py,have been under investigation.Imaging plays a key role in both initial diagnosis and routine monitoring of patient on treatment particularly volumetric MRI of the liver and spleen and MRI of the femora for evaluating bone marrow disease burden.
基金supported by grants from the epidemiological study on the thyroid disease in tencity communities in ChinaWuhan Science and Technology Research Program of China (No. 201161038340-02)
文摘To explore the relationship between serum thyroid stimulating hormone (TSH) level and obesity and nonalcoholic fatty liver disease (NAFLD) in euthyroid subjects,1322 subjects were sub-jected to a questionnaire survey and physical examination.Fasting blood samples were collected to test serum TSH,plasma glucose and lipids.Fatty liver was diagnosed by type B ultrasonography.The rela-tionship between serum TSH level and body mass index (BMI),percentage of body fat and NAFLD was analyzed.The results showed that serum TSH level was significantly higher in females than in males at the same group,and it was significantly higher in overweight group than in control group.Levels of body weight,BMI,waist circumference and percentage of body fat were increased in TSH >2.5 group compared to TSH ≤2.5 group in women.However,plasma lipids showed no significant differences.In males all the parameters showed no significant differences between two groups.Serum TSH was sig-nificantly correlated with body weight,BMI,waist circumference and percentage of body fat after ad-justment for age in females.Multiple linear regression analysis revealed that percentage of body fat and BMI contributed significantly to the variance of TSH.Serum TSH level was significantly higher in non-alcoholic fatty liver group than in normal group in females.Multiple logistic regression analysis showed that TSH level was not the independent risk factor of NAFLD.Taken together the data suggest that se-rum TSH in normal range is significantly correlated with BMI and percentage of body fat in females.And the change of TSH level would not influence the prevalence of NAFLD.
文摘The inflammatory bowel diseases(IBD),Crohn's disease(CD) and ulcerative colitis(UC),may be complicated by colorectal cancer(CRC).In a recent populationbased cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation.The overall risk of CRC among patients with UC and CD was comparable with that of the general population.However,patients diagnosed with UC during childhood or as adolescents,patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk.In this commentary,we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients.Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC.The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD.The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients.The achieved knowledge may also be relevant for other inflammation-associated cancers.
文摘Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.
文摘Aim It is well known that menopause could worsen age-related ventricular concentric remodeling and increased incidence of arrhythmias following estrogen （E2） deficiency. However, the underlying mechanisms of such phenomena are not fully understood. Mitochondria, as the ＇cellular power station＇ of hearts, play an impor- tant role in maintaining normal cardiac function and structure. Therefore, the present study aims to investigate whether mitochondrial compromise and gap junction impairment induced by miR-23a is responsible for E2 deficien- cy associated structural and electrical remodeling. Results： We found mitochondrial structural damages and respira- tory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mito- chondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the lar remodeling, which can be regulated via MicroRNAs （miRNAs）-dependent mechanism. We recently identified Asymmetric dimethylarginine （ADMA） positively correlates to vascular remodeling-based diseases. Here, we hy- pothesized that ADMA induces SMC phenotypic change via a miRNA-dependent mechanism. Methods and Results Microarray analysis enabled the identification of 7 deregulated microRNAs in ADMA-treated human aortic artery smooth muscle cells （hASMCs）. miR-182 was validated by real-time-PCR. Isobaric tags for relative and absolute quantitation （iTRAQ） based analysis of the hASMC proteome revealed that transfection of an miR-182 inhibitor sig- nificantly increased myeloid-associated differentiation marker （MYADM）, which was verified using Western blot and reporter activity quantization with the MYADM 3＇-UTR dual-luciferase reporter system, miR-182 knockdown further repressed Sprouty2 and enhanced MYADM, leading to ERIC/MAP kinase-dependent and MYADM-depend- ent hASMC phenotypic change including proliferation, migration and differentiation marker gene expression change. In vivo, adeno-miR-182 markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression. Atherosclerotic lesions from patients with high ADMA plas- ma levels exhibited decreased miR-182 expression levels and elevated MYADM expression levels. In patients with coronary heart disease （n- 164）, the miR-182 expression level in plasma was negatively correlated with the plas- ma ADMA levels. Conclusions miR-182 is a novel SMC phenotypic modulator by targeting MYADM and can be a potential therapeutic target combating vascular remodeling-associated diseases. Reduced plasma miR-182 levels might be a new predictor of high vascular remodeling risk especially in patient with coronary heart disease.
文摘Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.
文摘Background and Aim Vascular smooth muscle cell （SMC） phenotype change is a hallmark of vascu-lar remodeling, which can be regulated via MicroRNAs （miRNAs）-dependent mechanism. We recently identified Asymmetric dimethylarginine （ADMA） positively correlates to vascular remodeling-based diseases. Here, we hy-pothesized that ADMA induces SMC phenotypic change via a miRNA-dependent mechanism. Methods and Results Microarray analysis enabled the identification of 7 deregulated microRNAs in ADMA-treated human aortic artery smooth muscle cells （hASMCs）. miR-182 was validated by real-time-PCR. Isobaric tags for relative and absolute quantitation （iTRAQ） based analysis of the hASMC proteome revealed that transfection of an miR-182 inhibitor sig- nificantly increased myeloid-associated differentiation marker （MYADM）, which was verified using Western blot and reporter activity quantization with the MYADM 3＇-UTR dual-luciferase reporter system, miR-182 knockdown further repressed Sprouty2 and enhanced MYADM, leading to ERICZMAP kinase-dependent and MYADM-depend- ent hASMC phenotypic change including proliferation, migration and differentiation marker gene expression change. In vivo, adeno-miR-182 markedly suppressed carotid neointimal formation by using balloon-injured rat carotid artery model, specifically via decreased MYADM expression. Atherosclerotic lesions from patients with high ADMA plas- ma levels exhibited decreased miR-182 expression levels and elevated MYADM expression levels. In patients with coronary heart disease （n- 164）, the miR-182 expression level in plasma was negatively correlated with the plas- ma ADMA levels. Conclusions miR-182 is a novel SMC phenotypic modulator by targeting MYADM and can be a potential therapeutic target combating vascular remodeling-associated diseases. Reduced plasma miR-182 levels might be a new predictor of high vascular remodeling risk especially in patient with coronary heart disease.
文摘In patients with inflammatory bowel diseases (IBD) the prevalence of thrombosis is 6.2%, the average incidence of thromboembolism (TE) is 3.6 times higher compared to normal population. The TE is a common extraintestinal complication of IBD, squarely associated with the IBD activity. The application of antico-agulant and thrombolytic therapy in severe IBD is an unresolved issue. Herein we report the first case in literature of an active IBD patient with an upper limb acute arterial occlusion and successful catheter-directed thrombolysis (CDT). A 46-year-old male patient is reported who had Crohn's disease for 10 years. His right hand suddenly became cold and painful. Angiography proved acute occlusion of the brachial and radial artery. Vascular surgery intervention was not applicable. Endoscopy showed extended, severe inflammation of the colon. Despite the severe endoscopic findings, frequent bloody stools and moderate anaemia, CDT with recombinant tissue plasminogen activator was performed. The control angiography proved improvement, the radial artery pulse appeared. No bleeding complication was observed. This case supports that CDT-after careful estimation of the bleeding risk-can be effective and safe in patients with severe or life-threatening TE and active IBD.
文摘AIM: To determine whether temporal changes occurred in the pediatric vs adult inflammatory bowel disease(IBD), both in terms of number and type of yearly published articles.METHODS:We aimed to evaluate all Pub Med-registered articles related to the field of IBD from January1,1993 and until December 31,2011.We searched for articles using the key words"inflammatory bowel disease"or"Crohn’s disease"or"ulcerative colitis"or"undetermined colitis",using the age filters of"child"or"adult".We repeated the search according to the total number per year of articles per type of article,for each year of the specified period.We studied randomized controlled trials,clinical trials,case reports,meta-analyses,letters to the editor,reviews,systematic reviews,practice guidelines,and editorials.RESULTS:We identified 44645 articles over the 19year-period.There were 8687 pediatric-tagged articles vs 19750 adult-tagged articles.Thus 16208 articles were unaccounted and not assigned a"pediatric"or"adult"tag by Pub Med.There was an approximately3-fold significant increase in all articles recorded both in pediatric and adult articles.This significant increase was true for nearly every category of article but the number of clinical trials,meta-analysis,and randomized controlled trials increased proportionally more than the number of"lower quality"articles such as editorials or letters to the editor.Very few guidelines were published every year.CONCLUSION:There is a yearly linear increase in publications related to IBD.Relatively,there are more and more clinical trials and higher quality articles.
基金Supported by Grant from the National Natural Science Foundation of China(39880008)the Natural Science Foundation of Shaanxi Province(98sm61)
文摘Objective: To prepare an apoptosis cell model of Alzheimer Disease (AD) by PC-12 cells treated with β-amyloid protein (Aβ). Methods: PC-12 cells were incubated with different concentrations of Aβ25-35 for different duration in vitro. The cell viability was detected by MTT assay. Morphological features of apoptosis were analyzed, with Hoechst 33258/ Propidium iodide dual staining, The level of intracellular free calcium ([Ca2+]i) was calculated by Fura-2/AM fluorescence ratio imaging. Results: ① The viability of PC-12 cells was significantly decreased in proportion to concentration of Aβ25-35 and duration of exposure to Aβ25-35. ② The apoptotic cells appeared in a time and concentration-dependent manner, and the maximal apoptosis happened at 48 h after exposure to 20 μmol/L of Aβ25-35 and 36 h to 30 μmol/L, Cell death reached the peak at 12-24 h later than the apoptotic peak. (3) [Ca2+]i of PC-12 cells was increased in proportion to duration of exposure to the same concentration of Aβ25-35. The time of the highest increase rate of [Ca2+]i was about 12 h earlier than that of apoptosis. Conclusion: An AD cell model using the PC-12 cells induced with Aβ25-35 displays a series of changes related to apoptosis, which may be related to elevation of [Ca2+]i.
