Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeol...Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the“masking”effect caused by high-abundance proteins.The relative abundance of middleand low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 highabundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins identified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.展开更多
Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor progn...Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor prognosis and a growing worldwide prevalence.The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging,especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA,or distal CCA and pancreatic head adenocarcinoma.Most patients present with an advanced disease,unresectable disease,and there is a lack in non-surgical therapeutic modalities.Not least,there is an acute lack of prognostic biomarkers which further complicates disease management.Therefore,there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result,either singlehandedly or combined with other methods.In the"-omics"era,this goal can be attained by various means,as it has been successfully demonstrated in other primary tumors.Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins,metabolites,extracellular vesicles,and ultimately circulating tumor cells.However,given the relatively heterogeneous data,extracting clinical meaning from the inconsequential noise might become a tall task.The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.展开更多
The influence of chitosaccharides on the symbiotic interaction between Bradyrhizobium and soybean was examined. The results show that chitosaccharides either positively or negatively affect soybean nodulation or plant...The influence of chitosaccharides on the symbiotic interaction between Bradyrhizobium and soybean was examined. The results show that chitosaccharides either positively or negatively affect soybean nodulation or plant growth depending on their molecular weight, concentration and the application methods. When directly added to the in vitro culture media, chitosan of high molecular weight inhibit Bradyrhizobium viability in a dose dependent manner while chitooligosaccharides reduce slightly the bacteria viability only at concentration equal or higher than 50 mg·L<sup>-1</sup>. Chitooligosaccharides significantly enhance nodule formation and dry mass in soybean roots at doses between 10 and 100 mg·L<sup>-1</sup>. Both types of chitosaccharides, at the highest doses (>500 mg·L<sup>-1</sup>), negatively affect plant height and root size, whereas medium doses (50 to 100 mg·L<sup>-1</sup>) increase slightly leave number. Under field conditions, foliar application of both chitosaccharides enhances growth and nodulation of soybean plants. Nevertheless, using this application method, chitosan remains more effective than chitooligosaccharides.展开更多
C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology chara...C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology characterized by accumulation of C3 with absent or scanty immunoglobulin deposition. The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. Specifically, in C3 glomerulopathy patients, there exists a prolongation of C3 cleavage which causes the uncontrolled alternative pathway activation. Many treatments have been investigated for treating C3 glomerulopathy to little or no avail, including calcineurin inhibitors, plasmapharesis, and anti-CD20 monoclonal antibodies. The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. Here in this paper we discuss and present various case studies and clinical trials available that experiment with Eculizumab in patients with either dense deposit disease or C3 glomerulonephritis. In most of these patients, treatment with Eculizumab has demonstrated clinical and biochemical improvements in kidney function. These results provide encouraging evidence that suggest Eculizumab as a promising therapy for patients with C3 glomerulopathy and warrant that more extensive clinical trials can be designed as a next step.展开更多
Background and Aims:Nonalcoholic fatty liver disease(NAFLD)includes a range of progressive disorders generated by excess lipid accumulation in the liver leading to hepatic steatosis and eventually fibrosis.We aimed to...Background and Aims:Nonalcoholic fatty liver disease(NAFLD)includes a range of progressive disorders generated by excess lipid accumulation in the liver leading to hepatic steatosis and eventually fibrosis.We aimed to identify by high performance mass spectrometry-based proteomics the main signaling pathways and liver proteome changes induced by hypercholesterolemia in a rabbit atherosclerotic model that induced high accumulation of lipids in the liver.Methods:The effect of combined lipid-lowering drugs(statins and anti-PCSK9 monoclonal antibody)were used after the interruption of the hypercholesterolemic diet to identify also the potential mediators,such as alarmins,responsible for the irreversible NAFLD build up under the hyperlipidemic sustained stress.Results:Proteomic analysis revealed a number of proteins whose abundance was altered.They were components of metabolic pathways including fatty-acid degradation,glycolysis/gluconeogenesis,and nonalcoholic fatty liver disease.Mitochondrial dysfunction indicated alteration at the mitochondrial respiratory chain level and down-regulation of NADH:ubiquinone oxidoreductase.The expression of a majority of cytochromes(P4502E1,b5,and c)were up-regulated by lipid-lowering treatment.Long-term hyperlipidemic stress,even with a low-fat diet and lipid-lowering treatment,was accompanied by alarmin release(annexins,galectins,HSPs,HMGB1,S100 proteins,calreticulin,and fibronectin)that generated local inflammation and induced liver steatosis and aggressive fibrosis(by high abundance of galectin 3,fibronectin,and calreticulin).Conclusions:The novel findings of this study were related to the residual effects of hyperlipidemic stress with consistent,combined lipid-lowering treatment with statin and inhibitor of PCSK9.展开更多
基金supported by the National Natural Science Foundation of China(Grant No:51773151)。
文摘Proteomic characterization of plasma is critical for the development of novel pharmacodynamic biomarkers.However,the vast dynamic range renders the profiling of proteomes extremely challenging.Here,we synthesized zeolite NaY and developed a simple and rapid method to achieve comprehensive and deep profiling of the plasma proteome using the plasma protein corona formed on zeolite NaY.Specifically,zeolite NaY and plasma were co-incubated to form plasma protein corona on zeolite NaY(NaY-PPC),followed by conventional protein identification using liquid chromatography-tandem mass spectrometry.NaY was able to significantly enhance the detection of low-abundance plasma proteins,minimizing the“masking”effect caused by high-abundance proteins.The relative abundance of middleand low-abundance proteins increased substantially from 2.54%to 54.41%,and the top 20 highabundance proteins decreased from 83.63%to 25.77%.Notably,our method can quantify approximately 4000 plasma proteins with sensitivity up to pg/mL,compared to only about 600 proteins identified from untreated plasma samples.A pilot study based on plasma samples from 30 lung adenocarcinoma patients and 15 healthy subjects demonstrated that our method could successfully distinguish between healthy and disease states.In summary,this work provides an advantageous tool for the exploration of plasma proteomics and its translational applications.
基金Supported by The Romanian National Ministry of Research,Innovation and Digitalization,CNCS-UEFISCDI:Postdoctoral Research Project PN-Ⅲ-P1-1.1-PD-2019-0852/PD113 within PNCDIⅢ,awarded to Maria Ilie?。
文摘Cholangiocarcinoma(CCA)arises from the ductular epithelium of the biliary tree,either within the liver(intrahepatic CCA)or more commonly from the extrahepatic bile ducts(extrahepatic CCA).This disease has a poor prognosis and a growing worldwide prevalence.The poor outcomes of CCA are partially explained by the fact that a final diagnosis is challenging,especially the differential diagnosis between hepatocellular carcinoma and intrahepatic CCA,or distal CCA and pancreatic head adenocarcinoma.Most patients present with an advanced disease,unresectable disease,and there is a lack in non-surgical therapeutic modalities.Not least,there is an acute lack of prognostic biomarkers which further complicates disease management.Therefore,there is a dire need to find alternative diagnostic and follow-up pathways that can lead to an accurate result,either singlehandedly or combined with other methods.In the"-omics"era,this goal can be attained by various means,as it has been successfully demonstrated in other primary tumors.Numerous variants can reach a biomarker status ranging from circulating nucleic acids to proteins,metabolites,extracellular vesicles,and ultimately circulating tumor cells.However,given the relatively heterogeneous data,extracting clinical meaning from the inconsequential noise might become a tall task.The current review aims to navigate the nascent waters of the non-invasive approach to CCA and provide an evidence-based input to aid clinical decisions and provide grounds for future research.
文摘The influence of chitosaccharides on the symbiotic interaction between Bradyrhizobium and soybean was examined. The results show that chitosaccharides either positively or negatively affect soybean nodulation or plant growth depending on their molecular weight, concentration and the application methods. When directly added to the in vitro culture media, chitosan of high molecular weight inhibit Bradyrhizobium viability in a dose dependent manner while chitooligosaccharides reduce slightly the bacteria viability only at concentration equal or higher than 50 mg·L<sup>-1</sup>. Chitooligosaccharides significantly enhance nodule formation and dry mass in soybean roots at doses between 10 and 100 mg·L<sup>-1</sup>. Both types of chitosaccharides, at the highest doses (>500 mg·L<sup>-1</sup>), negatively affect plant height and root size, whereas medium doses (50 to 100 mg·L<sup>-1</sup>) increase slightly leave number. Under field conditions, foliar application of both chitosaccharides enhances growth and nodulation of soybean plants. Nevertheless, using this application method, chitosan remains more effective than chitooligosaccharides.
文摘C3 glomerulopathy is a disease including both dense deposit disease and C3 glomerulonephritis has an estimated prevalence of 2 to 3 per million. Originally, these pathologies were defined as glomerular pathology characterized by accumulation of C3 with absent or scanty immunoglobulin deposition. The keystone defect in both of these pathologies is the unregulated hyperactivity of alternative complement pathway. Specifically, in C3 glomerulopathy patients, there exists a prolongation of C3 cleavage which causes the uncontrolled alternative pathway activation. Many treatments have been investigated for treating C3 glomerulopathy to little or no avail, including calcineurin inhibitors, plasmapharesis, and anti-CD20 monoclonal antibodies. The next logical step is exploring the efficacy of anti-C5 monoclonal antibody therapy in C3 glomerulopathies to target the specific pathophysiology of this particular disease. Eculizumab is an anti-C5 monoclonal antibody that blocks the terminal step of complement activation. This drug has proven to be an effective treatment in other nephrologic pathologies that are caused by complement dysregulation. Here in this paper we discuss and present various case studies and clinical trials available that experiment with Eculizumab in patients with either dense deposit disease or C3 glomerulonephritis. In most of these patients, treatment with Eculizumab has demonstrated clinical and biochemical improvements in kidney function. These results provide encouraging evidence that suggest Eculizumab as a promising therapy for patients with C3 glomerulopathy and warrant that more extensive clinical trials can be designed as a next step.
基金supported by the Romanian Academy and in part by a grant from the Romanian National Authority for Scientific Research and Innovation,CCCDI-UEFISCDI project COFUND-ERA-CVD-XploreCAD,No.41/2018 within PNCDI III.
文摘Background and Aims:Nonalcoholic fatty liver disease(NAFLD)includes a range of progressive disorders generated by excess lipid accumulation in the liver leading to hepatic steatosis and eventually fibrosis.We aimed to identify by high performance mass spectrometry-based proteomics the main signaling pathways and liver proteome changes induced by hypercholesterolemia in a rabbit atherosclerotic model that induced high accumulation of lipids in the liver.Methods:The effect of combined lipid-lowering drugs(statins and anti-PCSK9 monoclonal antibody)were used after the interruption of the hypercholesterolemic diet to identify also the potential mediators,such as alarmins,responsible for the irreversible NAFLD build up under the hyperlipidemic sustained stress.Results:Proteomic analysis revealed a number of proteins whose abundance was altered.They were components of metabolic pathways including fatty-acid degradation,glycolysis/gluconeogenesis,and nonalcoholic fatty liver disease.Mitochondrial dysfunction indicated alteration at the mitochondrial respiratory chain level and down-regulation of NADH:ubiquinone oxidoreductase.The expression of a majority of cytochromes(P4502E1,b5,and c)were up-regulated by lipid-lowering treatment.Long-term hyperlipidemic stress,even with a low-fat diet and lipid-lowering treatment,was accompanied by alarmin release(annexins,galectins,HSPs,HMGB1,S100 proteins,calreticulin,and fibronectin)that generated local inflammation and induced liver steatosis and aggressive fibrosis(by high abundance of galectin 3,fibronectin,and calreticulin).Conclusions:The novel findings of this study were related to the residual effects of hyperlipidemic stress with consistent,combined lipid-lowering treatment with statin and inhibitor of PCSK9.
