HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory event...HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and could be further elevated by opiates.This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat,including the mediating role of mu opioid receptor(MOR)and CCR2 as well as the possible signal transduction pathways within the cells.Finally,it will make some future perspectives on the exact pathways,new receptors and target cells,and the vulnerability to neurodegeneration with HIV and opiates.展开更多
Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the...Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.展开更多
AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 1...AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.展开更多
Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriog...Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriogenesis in AMI.Male Sprague-Dawley rats were randomly assigned into the sham-operation group(SO),myocardial infarction(MI)group,and 13 IE subgroups treated according to training intensity,frequency,duration,or monocyte chemoattractant protein-1(MCP-1),or/and fibroblast growth factor-2(FGF-2)inhibitors for eight weeks.Our results demonstrated that the IE group achieved superior improvement compared with the MI group in terms of left ventricular ejection fraction(LVEF),myocardial infarction size(MIS),arterial density(AD),monocytes(MNCs),smooth muscle cells(SMCs),endothelial cells(ECs),relative collateral blood flow(RCBF),MCP-1,and FGF-2 at the endpoint.Positive correlations between MCP-1 and MNCs,MNCs and FGF-2,FGF-2 and SMCs,SMCs and AD,as well as AD and RCBF were observed.This study demonstrated that with MI of 100%load 20 times daily for eight weeks,the arteriogenesis was improved,which may be attributed to the recruitment of MNCs and SMCs in remote ischemic myocardium caused by increases in MCP-1 and FGF-2 expression.展开更多
Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephrop...Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephropathy(SCN).Although common,SCN remains diagnostically elusive.Conventional studies performed in the context of renal disorders often fail to detect early stage SCN.This makes the quest for early diagnosis and treatment more challenging,and it increases the burden of chronic kidney disease-related morbidity among patients.Novel diagnostic tools have been employed to overcome this limitation.In this study,we discuss various biomarkers of SCN,including those employed in clinical practice and others recently identified in experimental settings,such as markers of vascular injury,endothelial dysfunction,tubulo-glomerular damage,and oxidative stress.These include kidney injury molecule-1,monocyte chemoattractant protein-1,N-acetyl-B-D-glucosaminidase,ceruloplasmin,orosomucoid,nephrin,and cation channels,among others.Furthermore,we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome.We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers.Finally,we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits,with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.展开更多
Background:Mizoribine(MZR)is a selective inhibitor of inosine monophosphate dehydrogenase,a key enzyme in the pathway responsible for de novo synthesis of guanine nucleotides.As an immunosuppressant,MZR has been used ...Background:Mizoribine(MZR)is a selective inhibitor of inosine monophosphate dehydrogenase,a key enzyme in the pathway responsible for de novo synthesis of guanine nucleotides.As an immunosuppressant,MZR has been used successfully without any serious adverse effects in the treatment of renal diseases in children as well as adults.Besides its immunosuppressive effect,MZR has been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration.Data Sources:In this review,we summarize reported possible benefits of MZR in the treatment of pediatric-onset glomerular disease.Results:We recently observed that MZR itself selectively attenuates the expression of monocyte chemoattractant protein-1 at both the mRNA and protein levels in human mesangial cells.Since MZR binds specifically to 14-3-3 proteins and heat shock protein 60,both of which are reportedly expressed in inflamed glomeruli,MZR may bind directly to inflamed glomerular cells,thereby possibly preventing progressive damage from glomerulonephritis through a suppressive effect on activated macrophages and intrinsic renal cells.Moreover,it has recently been reported that MZR directly prevents podocyte injury through correction of the intracellular energy balance and nephrin biogenesis in cultured podocyte and rat models,suggesting a direct anti-proteinuric effect of MZR.Conclusions:These beneficial mechanisms of action of MZR as well as its immunosuppressive effect would warrant its use in the treatment of pediatric-onset glomerular disease.Although further studies remain to be done,we believe that MZR may be an attractive treatment of choice for children with glomerular diseases from a histologic as well as clinical standpoint.展开更多
基金supported by the National Natural Science Foundation of China(No.30671856 and No.30772536)
文摘HIV-associated dementia(HAD)is a public health problem and is particularly prevalent in drug abusers.The neuropathogenesis of human immunodeficiency virus(HIV)infection involves a complex cascade of inflammatory events,including monocyte/macrophage infiltration in the brain,glial immune activation and release of neurotoxic substances.In these events,astrocytic-derived monocyte chemoattractant protein-1(MCP-1)plays an important role,whose release is elevated by HIV transactivator of transcription(HIV tat)and could be further elevated by opiates.This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat,including the mediating role of mu opioid receptor(MOR)and CCR2 as well as the possible signal transduction pathways within the cells.Finally,it will make some future perspectives on the exact pathways,new receptors and target cells,and the vulnerability to neurodegeneration with HIV and opiates.
文摘Acute liver failure (ALF) is a devastating clinical syndrome characterised by progressive encephalopathy, coagulopathy, and circulatory dysfunction, which commonly leads to multiorgan failure and death. Central to the pathogenesis of ALF is activation of the immune system with mobilisation of cellular effectors and massive production of cytokines. As key components of the innate immune system, monocytes and macrophages are postulated to play a central role in the initiation, progression and resolution of ALF. ALF in humans follows a rapidly progressive clinical course that poses inherent difficulties in delineating the role of these pivotal immune cells. Therefore, a number of experimental models have been used to study the pathogenesis of ALF. Here we consider the evidence from experimental and human studies of ALF on the role of monocytes and macrophages in acute hepatic injury and the ensuing extrahepatic manifestations, including functional monocyte deactivation and multiple organ failure.
文摘AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.
基金supported by the research grants from the National Natural Science Foundation of China(Grant No.8177244,No.81902288,and No.82072546)Nanjing Municipal Science and Technology Bureau(Grant No.2019060002).
文摘Isometric exercise(IE)is a promising intervention of noninvasive revascularization in patients with acute myocardial infarction(AMI).This study aimed to investigate the impact and mechanisms of IE training on arteriogenesis in AMI.Male Sprague-Dawley rats were randomly assigned into the sham-operation group(SO),myocardial infarction(MI)group,and 13 IE subgroups treated according to training intensity,frequency,duration,or monocyte chemoattractant protein-1(MCP-1),or/and fibroblast growth factor-2(FGF-2)inhibitors for eight weeks.Our results demonstrated that the IE group achieved superior improvement compared with the MI group in terms of left ventricular ejection fraction(LVEF),myocardial infarction size(MIS),arterial density(AD),monocytes(MNCs),smooth muscle cells(SMCs),endothelial cells(ECs),relative collateral blood flow(RCBF),MCP-1,and FGF-2 at the endpoint.Positive correlations between MCP-1 and MNCs,MNCs and FGF-2,FGF-2 and SMCs,SMCs and AD,as well as AD and RCBF were observed.This study demonstrated that with MI of 100%load 20 times daily for eight weeks,the arteriogenesis was improved,which may be attributed to the recruitment of MNCs and SMCs in remote ischemic myocardium caused by increases in MCP-1 and FGF-2 expression.
文摘Whether the underlying mutations are homozygous,heterozygous,or coinherited with other hemoglobinopathies,sickle cell disease is known to afflict the kidneys,leading to the clinical entity known as sickle cell nephropathy(SCN).Although common,SCN remains diagnostically elusive.Conventional studies performed in the context of renal disorders often fail to detect early stage SCN.This makes the quest for early diagnosis and treatment more challenging,and it increases the burden of chronic kidney disease-related morbidity among patients.Novel diagnostic tools have been employed to overcome this limitation.In this study,we discuss various biomarkers of SCN,including those employed in clinical practice and others recently identified in experimental settings,such as markers of vascular injury,endothelial dysfunction,tubulo-glomerular damage,and oxidative stress.These include kidney injury molecule-1,monocyte chemoattractant protein-1,N-acetyl-B-D-glucosaminidase,ceruloplasmin,orosomucoid,nephrin,and cation channels,among others.Furthermore,we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome.We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers.Finally,we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits,with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.
基金supported by grants-in-aid for Science from the Ministry of Education,Culture,Sports,Science and Technology of Japan(TH and IT).
文摘Background:Mizoribine(MZR)is a selective inhibitor of inosine monophosphate dehydrogenase,a key enzyme in the pathway responsible for de novo synthesis of guanine nucleotides.As an immunosuppressant,MZR has been used successfully without any serious adverse effects in the treatment of renal diseases in children as well as adults.Besides its immunosuppressive effect,MZR has been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration.Data Sources:In this review,we summarize reported possible benefits of MZR in the treatment of pediatric-onset glomerular disease.Results:We recently observed that MZR itself selectively attenuates the expression of monocyte chemoattractant protein-1 at both the mRNA and protein levels in human mesangial cells.Since MZR binds specifically to 14-3-3 proteins and heat shock protein 60,both of which are reportedly expressed in inflamed glomeruli,MZR may bind directly to inflamed glomerular cells,thereby possibly preventing progressive damage from glomerulonephritis through a suppressive effect on activated macrophages and intrinsic renal cells.Moreover,it has recently been reported that MZR directly prevents podocyte injury through correction of the intracellular energy balance and nephrin biogenesis in cultured podocyte and rat models,suggesting a direct anti-proteinuric effect of MZR.Conclusions:These beneficial mechanisms of action of MZR as well as its immunosuppressive effect would warrant its use in the treatment of pediatric-onset glomerular disease.Although further studies remain to be done,we believe that MZR may be an attractive treatment of choice for children with glomerular diseases from a histologic as well as clinical standpoint.
