Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniati...Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.展开更多
Microbiome is an endocrine organ that refers to both the complicated biological system of microbial species that colonize our bodies and their genomes and surroundings.Recent studies confirm the connection between the...Microbiome is an endocrine organ that refers to both the complicated biological system of microbial species that colonize our bodies and their genomes and surroundings.Recent studies confirm the connection between the microbiome and eye diseases,which are involved in the pathogenesis of eye diseases,including age-related macular disorders,diabetic retinopathy,glaucoma,retinitis pigmentosa,dry eye,and uveitis.The aim of this review is to investigate the microbiome in relation to eye health.First,a brief introduction of the characteristics of the gut microorganisms terms of composition and work,the role of dysbiosis,the gut microbiome and the eye microbiome in the progression of eye illnesses are highlighted,then the relationship among the microbiome and the function of the immune system and eye diseases,the role of inflammation and aging and the immune system,It has been reviewed and finally,the control and treatment goals of microbiome and eye diseases,the role of food factors and supplements,biotherapy and antibiotics in relation to microbiome and eye health have been reviewed.展开更多
Diagnoses Background: Delirium is a common finding in elderly patients with sepsis. Early identification of the cause of delirium and treatment is important to avoid any worsening of mental or physical status. Sepsis ...Diagnoses Background: Delirium is a common finding in elderly patients with sepsis. Early identification of the cause of delirium and treatment is important to avoid any worsening of mental or physical status. Sepsis secondary to colonic micro-perforation (CMP) in a patient with a history of diverticulosis should be high on the list of differential diagnosis. Case Report: We present a case of a patient who presented with hyperactive sepsis-associated delirium (SAD). Six days after the presentation, the patient started complaining of abdominal pain. An abdominal and pelvic computed tomography (CT) scan showed free air in the abdomen. The patient underwent surgical intervention and treatment with intravenous antibiotics. Pathological examination showed CMP connected to the patient’s history of diverticulosis. Delirium superimposed on dementia (DSD) resulted in the worsening of both the mental and physical status of our patient with the need for placement in a nursing home.展开更多
Since its emergence in 2019,it has become apparent that coronavirus 2019(COVID-19)infection can result in multi systemic involvement.In addition to pulmonary symptoms,hepatobiliary involvement has been widely reported...Since its emergence in 2019,it has become apparent that coronavirus 2019(COVID-19)infection can result in multi systemic involvement.In addition to pulmonary symptoms,hepatobiliary involvement has been widely reported.Extent of hepatic involvement ranges from minor elevation in liver function tests(LFTs)to significant hepatocellular or cholestatic injury.In majority of cases,resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection.However,severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation.Due to the timing of its presentation,this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy,and can result in devastating consequences for patients.COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury.Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase.Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis.Etiology of COVID-19 cholangiopathy is unclear.Several mechanisms have been proposed,including direct cholangiocyte injury,vascular compromise,and cytokine release syndromes.This review summarizes existing data on COVID-19 cholangiopathy,including reported cases in the literature,proposed pathophysiology,diagnostic testing,and long-term implications.展开更多
目的:研究丙型肝炎病毒(hepatitis C virus,HCV)基因组转染的肝癌细胞中精氨酸酶Ⅰ的表达及其意义,探究其在HCV-肝细胞肝癌(HCC)发病中的作用。方法:以转染HCV基因组的人肝癌细胞系(Huh7)为研究对象,采用蛋白印迹技术研究HCV基因组转染...目的:研究丙型肝炎病毒(hepatitis C virus,HCV)基因组转染的肝癌细胞中精氨酸酶Ⅰ的表达及其意义,探究其在HCV-肝细胞肝癌(HCC)发病中的作用。方法:以转染HCV基因组的人肝癌细胞系(Huh7)为研究对象,采用蛋白印迹技术研究HCV基因组转染对细胞内精氨酸酶Ⅰ表达的影响;运用小干扰RNA(siRNA)技术抑制细胞精氨酸酶Ⅰ表达,并探讨其对细胞生长的影响及作用机制。结果:精氨酸酶Ⅰ在HCV阳性肝癌细胞系(Huh7-HCV)中的表达上调,且与对照细胞相比,Huh7-HCV细胞的精氨酸酶Ⅰ含量升高4.3倍。运用siRNA抑制细胞精氨酸酶Ⅰ表达,可明显抑制细胞生长并导致其死亡,且可使细胞周期发生明显改变。结论:精氨酸酶Ⅰ在HCV阳性肝细胞Huh7中表达上调,可能对促进Huh7-HCV细胞生长具重要意义。展开更多
AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was gi...AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia.展开更多
There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as...There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.展开更多
基金support by R01AR055655, R01AR074813, and R01AG073349 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute on Aging (NIA)supported by PXE International.
文摘Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.
文摘Microbiome is an endocrine organ that refers to both the complicated biological system of microbial species that colonize our bodies and their genomes and surroundings.Recent studies confirm the connection between the microbiome and eye diseases,which are involved in the pathogenesis of eye diseases,including age-related macular disorders,diabetic retinopathy,glaucoma,retinitis pigmentosa,dry eye,and uveitis.The aim of this review is to investigate the microbiome in relation to eye health.First,a brief introduction of the characteristics of the gut microorganisms terms of composition and work,the role of dysbiosis,the gut microbiome and the eye microbiome in the progression of eye illnesses are highlighted,then the relationship among the microbiome and the function of the immune system and eye diseases,the role of inflammation and aging and the immune system,It has been reviewed and finally,the control and treatment goals of microbiome and eye diseases,the role of food factors and supplements,biotherapy and antibiotics in relation to microbiome and eye health have been reviewed.
文摘Diagnoses Background: Delirium is a common finding in elderly patients with sepsis. Early identification of the cause of delirium and treatment is important to avoid any worsening of mental or physical status. Sepsis secondary to colonic micro-perforation (CMP) in a patient with a history of diverticulosis should be high on the list of differential diagnosis. Case Report: We present a case of a patient who presented with hyperactive sepsis-associated delirium (SAD). Six days after the presentation, the patient started complaining of abdominal pain. An abdominal and pelvic computed tomography (CT) scan showed free air in the abdomen. The patient underwent surgical intervention and treatment with intravenous antibiotics. Pathological examination showed CMP connected to the patient’s history of diverticulosis. Delirium superimposed on dementia (DSD) resulted in the worsening of both the mental and physical status of our patient with the need for placement in a nursing home.
文摘Since its emergence in 2019,it has become apparent that coronavirus 2019(COVID-19)infection can result in multi systemic involvement.In addition to pulmonary symptoms,hepatobiliary involvement has been widely reported.Extent of hepatic involvement ranges from minor elevation in liver function tests(LFTs)to significant hepatocellular or cholestatic injury.In majority of cases,resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection.However,severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation.Due to the timing of its presentation,this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy,and can result in devastating consequences for patients.COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury.Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase.Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis.Etiology of COVID-19 cholangiopathy is unclear.Several mechanisms have been proposed,including direct cholangiocyte injury,vascular compromise,and cytokine release syndromes.This review summarizes existing data on COVID-19 cholangiopathy,including reported cases in the literature,proposed pathophysiology,diagnostic testing,and long-term implications.
文摘目的:研究丙型肝炎病毒(hepatitis C virus,HCV)基因组转染的肝癌细胞中精氨酸酶Ⅰ的表达及其意义,探究其在HCV-肝细胞肝癌(HCC)发病中的作用。方法:以转染HCV基因组的人肝癌细胞系(Huh7)为研究对象,采用蛋白印迹技术研究HCV基因组转染对细胞内精氨酸酶Ⅰ表达的影响;运用小干扰RNA(siRNA)技术抑制细胞精氨酸酶Ⅰ表达,并探讨其对细胞生长的影响及作用机制。结果:精氨酸酶Ⅰ在HCV阳性肝癌细胞系(Huh7-HCV)中的表达上调,且与对照细胞相比,Huh7-HCV细胞的精氨酸酶Ⅰ含量升高4.3倍。运用siRNA抑制细胞精氨酸酶Ⅰ表达,可明显抑制细胞生长并导致其死亡,且可使细胞周期发生明显改变。结论:精氨酸酶Ⅰ在HCV阳性肝细胞Huh7中表达上调,可能对促进Huh7-HCV细胞生长具重要意义。
文摘AIM: To investigate the role of DNA-PKcs subunits inradiosensitization by hyperthermia on hepatocellularcarcinoma HepG2 cell lines.METHODS: Hep G2 cells were exposed to hyperthermiaand irradiation. Hyperthermia was given at 45.5 ℃Cellsurvival was determined by an in vitro clonogenic assay forthe cells treated with or without hyperthermia at varioustime points. DNA DSB rejoining was measured usingasymmetric field inversion gel electrophoresis (AFIGE). TheDNA-PKcs activities were measured using DNA-PKcs enzymeassay system.RESULTS: Hyperthermia can significantly enhanceirradiation-killing cells. Thermal enhancement ratio ascalculated at 10 % survival was 2.02. The difference inradiosensitivity between two treatment modes manifestedas a difference in the α components and the almost sameβ components, which α value was considerably higher inthe cells of combined radiation and hyperthermia ascompared with irradiating cells (1.07 Gy-1 versus 0.44 Gy1). Survival fraction showed 1 logarithm increase after an8-hour interval between heat and irradiation, whereas DNA-PKcs activity did not show any recovery. The cells wereexposed to heat 5 minutes only, DNA-PKcs activity wasinhibited at the nadir, even though the exposure time waslengthened. Whereas the ability of DNA DSB rejoining wasinhibited with the increase of the length of hyperthermictime. The repair kinetics of DNA DSB rejoining aftertreatment with Wortmannin is different from thehyperthermic group due to the striking high slow rejoiningcomponent.CONCLUSION: Determination with the cell extracts andthe peptide phosphorylation assay, DNA-PKcs activity wasinactivated by heat treatment at 45.5 C, and could notrestore. Cell survival is not associated with the DNA-PKcsinactivity after heat. DNA-PKcs is not a unique factor affectingthe DNA DSB repair. This suggests that DNA-PKcs do notplay a crucial role in the enhancement of cellularradiosensitivity by hyperthermia.
文摘There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.
