Summary:In various autoimmune diseases,Galecin-9(Gal-9)has been shown to regulate the T-cell balance by decreasing Th1 and Th17,while increasing the number of regulatory T cells(Tregs).However,the role of Gal-9 in the...Summary:In various autoimmune diseases,Galecin-9(Gal-9)has been shown to regulate the T-cell balance by decreasing Th1 and Th17,while increasing the number of regulatory T cells(Tregs).However,the role of Gal-9 in the patients with acute coronary syndrome(ACS)and chronic kidney disease(CKD)remains unclear.This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells(PBMCs)in patients with ACS plus CKD and examine their clinical implication.The serum levels of Gal-9 were determined by enzyme linked immunosorbent assay(ELISA),the expression levels of Gal-9,Tim-3,and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR),and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry.Furthermore,the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed.The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group,followed by the ACS+CKD group,and the normal coronary artery(NCA)group,.respectively.Serum Gal-9 levels were increased along with the progression of glomerular filtration rate(GFR)categories of G1 to G4.Additionally,serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein(hs-CRP),estimated GFR(eGFR),and lipoprotein(a),but positively with creatinine,age,osmotic pressure,and blood urea nitrogen(BUN).Notably,serum Gal-9 was independently associated with hs-CRP,osmotic pressure,and lipoprotein(a).Furthermore,serum Gal-9 levels were elevated in patients with type 2 diabetes(T2DM)and impaired glucose tolerance(IGT)in ACS group.It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD,and hs-CRP,eGFR,osmotic pressure and T2DM may have an influence on serum Gal-9 levels.展开更多
The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or c...The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.展开更多
Acute kidney injury(AKI),characterized by acute renal dysfunction,is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease(CKD).Regardless of the ...Acute kidney injury(AKI),characterized by acute renal dysfunction,is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease(CKD).Regardless of the initial insults,the progression of CKD after AKI involves multiple types of cells,including renal resident cells and immune cells such as macrophages.Recently,the involvements of macrophages in AKI-to-CKD transition have garnered significant attention.Furthermore,substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis.In this review,we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization,and transdifferentiation in the development of AKI-to-CKD transition.In addition,the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.展开更多
High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-...High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
基金This project was supported by grants from National Natural Science Foundation of China(No.81270354)Natural Science for Youth Foundation(No.81300213).
文摘Summary:In various autoimmune diseases,Galecin-9(Gal-9)has been shown to regulate the T-cell balance by decreasing Th1 and Th17,while increasing the number of regulatory T cells(Tregs).However,the role of Gal-9 in the patients with acute coronary syndrome(ACS)and chronic kidney disease(CKD)remains unclear.This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells(PBMCs)in patients with ACS plus CKD and examine their clinical implication.The serum levels of Gal-9 were determined by enzyme linked immunosorbent assay(ELISA),the expression levels of Gal-9,Tim-3,and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction(RT-PCR),and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry.Furthermore,the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed.The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group,followed by the ACS+CKD group,and the normal coronary artery(NCA)group,.respectively.Serum Gal-9 levels were increased along with the progression of glomerular filtration rate(GFR)categories of G1 to G4.Additionally,serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein(hs-CRP),estimated GFR(eGFR),and lipoprotein(a),but positively with creatinine,age,osmotic pressure,and blood urea nitrogen(BUN).Notably,serum Gal-9 was independently associated with hs-CRP,osmotic pressure,and lipoprotein(a).Furthermore,serum Gal-9 levels were elevated in patients with type 2 diabetes(T2DM)and impaired glucose tolerance(IGT)in ACS group.It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD,and hs-CRP,eGFR,osmotic pressure and T2DM may have an influence on serum Gal-9 levels.
文摘The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.
基金Research Grants Council of Hong Kong(Nos.14117418,14104019,14101121,C7018-16G)the Lui Che Woo Institute of Innovative Medicine(CARE program)+1 种基金the Guangdong-Hong Kong-Macao-Joint Labs Program from Guangdong Science and Technology(No.2019B121205005)National Natural Science Foundation of China(Nos.81970584,82100727)。
文摘Acute kidney injury(AKI),characterized by acute renal dysfunction,is an increasingly common clinical problem and an important risk factor in the subsequent development of chronic kidney disease(CKD).Regardless of the initial insults,the progression of CKD after AKI involves multiple types of cells,including renal resident cells and immune cells such as macrophages.Recently,the involvements of macrophages in AKI-to-CKD transition have garnered significant attention.Furthermore,substantial progress has also been made in elucidating the pathophysiological functions of macrophages from the acute kidney to repair or fibrosis.In this review,we highlight current knowledge regarding the roles and mechanisms of macrophage activation and phenotypic polarization,and transdifferentiation in the development of AKI-to-CKD transition.In addition,the potential of macrophage-based therapy for preventing AKI-to-CKD transition is also discussed.
基金funded by the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University(No.20150218)Program for New Century Excellent Talents in University(NCET-13-0605)+1 种基金the National Natural Science Foundation of China(No.81102512)Hunan Provincial Natural Science Foundation of China(No.14JJ7001)
文摘High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
