DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical...DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical step followed by annealing with various staple strands to make stiff DNAtriangles. Atomic force microcopy(AFM), native polyacrylamide gel electrophoresis(PAGE), UVanalysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 mm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane(500 bp level) with the loss of electrophoretic mobility during the PAGE(native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNANWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%) compared to the apoptosis(7%)induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC_(50) of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC_(50) of 51.2 n M.Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2) compared with the control cell line.展开更多
Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of S...Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.展开更多
The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in macrophages. It has been reported that genetic polymorphis...The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians. However, whether it links genetically to coronary artery disease (CAD) in Chinese is not defined. Here, we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms (SNPs) of MSR1. We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio (OR) of 1.56 [95% confidence interval (CI) = 1.28-1.90; P 〈 0.001] and 1.70 (95% CI = 1.27-2.27; P 〈 0.001), re- spectively. Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD / in combination with traditional risk factors of CAD in Chinese population.展开更多
Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol...Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.展开更多
Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno patholo...Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno pathological lesion in the local blood vessel. Methods With the Digoxenin labeled Oligonucleotide probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP 1, bFGF, PDGF and IL 10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP 1, bFGF, PDGF and IL 10 in a dose dependent manner after incubating with OxLDL (10,15,20,25,30?mg·L -1 , respectively)for 24 hours( P < 0.001 ). Fucoidin(50,100,150,200,250?mg·mL -1 , respectively)completely inhibited OxLDL(20?mg·L -1 )from inducing monocyte the mRNA expression of above proinflammatory cytokines( P < 0.001 ). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose dependent manner, while a peculiarly inhibitory ligand for SR A fucoidin has an obviously opposed role.展开更多
BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)is one of the most frequent causes of liver diseases,with markedly increased prevalence.However,its mechanisms are not clear.The present study was undertaken to illus...BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)is one of the most frequent causes of liver diseases,with markedly increased prevalence.However,its mechanisms are not clear.The present study was undertaken to illustrate the role of caveolin-1(cav1)and the scavenger receptor class B type 1(SR-B1)in NAFLD.METHODS:Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol(HFC)diet for 14 weeks.The mice were sacrificed to collect plasma and harvest the liver;their plasma lipid concentration was measured.Hepatic cav1and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.In order to study cav1 and SR-B1distribution and change in hepatocytes,immunohistochemical analysis was performed.RESULTS:HFC diet increased plasma lipids,induced NAFLD and increased the liver/body weight ratio.Compared to the control mice(n=6),the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice(n=12)increased significantly(cav1 mRNA:1.536±0.226 vs 0.980±0.272,P【0.05;protein:0.643±0.240 vs 0.100±0.130,P【0.01;SR-B1 mRNA:1.377±0.125 vs 0.956±0.151,P【0.01;protein:2.156±0.507vs 0.211±0.211,P【0.01).Furthermore,both cav1 and SR-B1immunoreactivity increased and their distribution was also changed,mainly in the plasma membrane of hepatocytes,cytoplasm and membrane of lipid droplets and around.CONCLUSION:NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions,which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.展开更多
Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion. However, the underlying mechanism remains unclear. We previously found that 78 kDa glucose-regulated protein (GRP78) inhibited SR- ...Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion. However, the underlying mechanism remains unclear. We previously found that 78 kDa glucose-regulated protein (GRP78) inhibited SR- A-mediated ligand internalization into macrophage by binding to SR-A. The aim of the study was to investigate whether GRP78 could regulate SR-A-mediated cell adhesion. We demonstrated that GRP78 bound directly to SR-A by fluorescence resonance energy transfer (FRET) assay. Overexpression of GRP78 inhibited macrophage adhesion via SR-A. These results suggest that GRP78 may act as an inhibitor of macrophage adhesion via SR-A.展开更多
Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high de...Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein(HDL) are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1(SR-B1),an adaptor protein(PDZK1) that binds to the cytosolic C terminus of SR-B1,Akt1 activation and(at least in endothelial cells) activation of endothelial NO synthase(eNOS).Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice(apoE or LDLR KO) develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling(above)in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.展开更多
The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistan...The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA + AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.展开更多
Lutein,a type of carotenoids,is found to delay the onset and progression of age-related macular degeneration(AMD).Several lutein supplementation studies showed that after an initial increase,lutein serum levels demons...Lutein,a type of carotenoids,is found to delay the onset and progression of age-related macular degeneration(AMD).Several lutein supplementation studies showed that after an initial increase,lutein serum levels demonstrated a subsequent decrease despite continuous supplementation.In this systematic literature review,this obscure phenomenon was tried to be explained.The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B typeⅠ(SR-BI)in the gastrointestinal tract,upregulation of lutein degrading enzymeβ-carotene dioxygenase(BCDO2),or perhaps a combination of both.Some single nucleotides polymorphisms(SNPs)that could have influence on the occurrence of this phenomenon.To date,an exact scientific explanation for this phenomenon has not been established.Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation,giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.展开更多
AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 ta...AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects.RESULTS: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group.CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.展开更多
The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread(CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed ...The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread(CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT.Atomic force microscopy(AFM)characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm.The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis,as large the molecular-weight(polymeric)DNA-NT did not split into constituting strands under applied current and voltage.The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration(512 nM)with a viability of 92%as evidence of its biocompatibility for drug delivery.MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization.The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT(from DNA-NT),as illustrated in confocal images.Therefore,in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis(72.7%)with CPT-DNA-NT(compared to free CPT;64.4%).CPT-DNA-NT,being poly-anionic,showed enhanced endocytosis via scavenger receptors.展开更多
AIM To investigate the effect of a single amino acid mutation in human class B scavenger receptor I(SR-BI) on the infectivity of cell culture-derived hepatitis C virus(HCVcc) in SR-BI knock-down Huh7-si SR-BI cells.ME...AIM To investigate the effect of a single amino acid mutation in human class B scavenger receptor I(SR-BI) on the infectivity of cell culture-derived hepatitis C virus(HCVcc) in SR-BI knock-down Huh7-si SR-BI cells.METHODS Site-directed mutagenesis was used to construct the SR-BI S112 F mutation,and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-si SR-BI cells were transfected with SR-BI S112 F,SR-BI wild type(WT) and control plasmids,and then infected with HCVpp(HCV pseudoparticles) and hepatitis C virus derived from cell culture(HCVcc). A fluorescence assay was performed to analyze the effect of the S112 F mutation on HCV entry; quantitative real-time PCR,immunofluorescence,and Western blot assays were used to analyze the effect of the S112 F mutation on HCV infectivity. CHO cells expressing WT and SRBI S112 F were incubated with the HCV E2 protein expressed in HEK 293 T cells,and flow cytometry was performed to examine the ability of SR-BI S112 F to bind to the HCV E2 protein. Huh7-si SR-BI cells were transfected with SR-BI WT and the S112 F mutant,andthen Di I-HDL was added and images captured under the microscope to assess the ability of SR-BI S112 F to take up HDL.RESULTS The SR-BI S112 F mutation was successfully constructed. The S112 F mutation decreased the expression of the SR-BI m RNA and protein. SR-BI S112 F decreased HCV entry and HCVcc infectivity in Huh7-si SR-BI cells. The S112 F mutation impaired the binding of SR-BI to HCV E2 protein and decreased the HDL uptake of SR-BI.CONCLUSION The S112 F single amino acid mutation in SR-BI decreased the levels of the SR-BI m RNA and protein,as well as the ability of SR-BI to bind to the HCV E2 protein. Amino acid 112 in SR-BI plays important roles in HCV entry and the infectivity of HCVcc in vitro.展开更多
The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells c...The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.展开更多
Class B scavenger receptors (SR-Bs) are cell surface glycoproteins involved in various physiological processes in vivo, including the transport and metabolism of lipids, binding and phagoeytosis of xenobiotics, and ...Class B scavenger receptors (SR-Bs) are cell surface glycoproteins involved in various physiological processes in vivo, including the transport and metabolism of lipids, binding and phagoeytosis of xenobiotics, and signaling. But little information is available about silkworm SR-Bs; it is necessary to study these SR-Bs for revealing their function. In this study, we cloned the full-length coding sequence of BrnSCRBQ4, a SR-B gene from the silkworm Bombyx mori L. We found that the BmSCRBQ4 gene consists of nine exons and eight introns, with an open reading frame of 1371 bp encoding 456 amino acids. Gene expression studies determined that BmSCRBQ4 messenger RNA (mRNA) was expressed in unfertilized eggs, during embryonic development and throughout the majority of the larval period. Expression of mRNA was detected in the mid gut, middle silk gland, posterior silk gland, head, integumentum, fat body, testes and the ovaries of the larval B. mori Dazao strain, as well as in the silkworm cell lines BmN and BmE. Protein expression studies found BmSCRBQ4 protein was expressed only in the testes, fat body and middle silk gland of larvae, as well as in the silkworm cell lines BmN and BmE. The BmSCRBQ4 protein showed variability in banding patterns in different tissues and cells when analyzed by Western blotting. Immunohistochemical staining showed that the BmSCRBQ4 protein localizes to the constitutive membranes or cellular membranes of these tissues. These results indicated that BmSCRBQ4 gene may play some physiologically relevant roles at the cell surface in each tissue.展开更多
Background We investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.Methods According to the criteria by WHO...Background We investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.Methods According to the criteria by WHO, diabetic patients were classified into two groups: well controlled diabetic patients (WCP) and poorly controlled diabetic patients (PCP). The expression of CD36 protein and mRNA were evaluated by flow cytometry and reversal transcription polymerase chain reaction (RT-PCR). Plasma levels of accumulution of oxidized LDL (oxLDL) were immunosorbent assay (ELISA) method. directly measured by sandwich enzyme-linkedResults Flow cytometry and RT-PCR showed that the mean fluorescence intensity (MFI) of CD36 in monocyte and CD36 mRNA were significantly higher in the PCP and WCP in comparison with healthy controls (P 〈 O. O1 ). CD36 MFI and mRNA in the PCP were increased by 78% and 36% compared to the WCP. In both groups, CD36 MFI and mRNA were significantly higher in patients with diabetic atherosclerosis in comoparison with those without diabetic atherosclerosis (P 〈0. 05). No significant difference was found in CDt4 expression between the groups (P〉0. 05 ). The concentrations of plasma oxLDL were higher in the PCP group compared to WCP and control group (P 〈0. 05 ), whereas oxLDL average values did not differ significantly between WCP and control groups (P〉0.05 ) . In the WCP and PCP groups, oxLDL levels were higher in patients with diabetic atherosclerosis than those without diabetic atherosclerosis ( P 〈0.05 ).Conclusions The increased expression of scavenger receptor CD36 may be one of the mechanism of accelerated atherosclerosis in diabetic. The poorly controlled diabetes patients are at higher risk for the vascular complications than the well controlled diabetic patients.展开更多
Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes ...Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.展开更多
Objective To observe the effect of Shengqing Capsule(SC)on serum contents of TC,LDL-C,and HDLC,hepatic scavenger receptor BⅠ(SRBⅠ),and CD36 in rats with cholesterol calculus.Methods
Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Inform...Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED (1997-2006) online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.展开更多
Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-α mediated mechan...Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-α mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell (SMC) proliferation, we'presume that the monocyte SR-PSOX/CXCL16 detection in the patients' peripheral blood will be important for early diagnosis and prognosis of atherosclerosis (AS). Methods Enrolled in this study were 40 patients with acute coronary syndrome (ACS), including 20 patients with acute myocardial infarction (AMI) and 20 patients with unstable angina pectoris (UAP), and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR), with β-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR- PSOX was analyzed with a confocal microscope. Results The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls (P〈0.05); however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group (P〉0.05). Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was proportionate to the degree of inflammation in the portal hepatis and folia. Conclusions The expression of CXCL16/SR-PSOX in the monocytes of peripheral blood was significantly higher in ACS patients than in the controls. CXCL16/SR-PSOX-mediated inflammation may contribute to the pathogenesis of ACS, and CXCL16 may play an important role in the pathogenesis and development of AS in humans.展开更多
基金the State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University, Chinathe State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China, for support。
文摘DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand(84-NT) was the critical step followed by annealing with various staple strands to make stiff DNAtriangles. Atomic force microcopy(AFM), native polyacrylamide gel electrophoresis(PAGE), UVanalysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 mm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane(500 bp level) with the loss of electrophoretic mobility during the PAGE(native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNANWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%) compared to the apoptosis(7%)induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC_(50) of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC_(50) of 51.2 n M.Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2) compared with the control cell line.
基金Supported by Top Institute Pharma (TIPharma Project T2-110 Hoekstra M and Van Berkel TJC)+2 种基金Grant 2008T070 from the Netherlands Heart Foundation (Hoekstra M)VIDI Grant 917.66.301 from the Netherlands Organization for Scientific Research (Van Eck M)Van Eck Mis an Established Investigator of the Netherlands Heart Foundation (Grant 2007T056)
文摘Scavenger receptor class B type Ⅰ (SR-BI) is an important member of the scavenger receptor family of integral membrane glycoproteins. This review highlights studies in SR-BI knockout mice, which concern the role of SR-BI in cholesterol and steroid metabolism. SR-BI in hepatocytes is the sole molecule involved in selective uptake of cholesteryl esters from high-density lipoprotein (HDL). SR-BI plays a physiological role in binding and uptake of native apolipoprotein B (apoB)-containing lipoproteins by hepatocytes, which identif ies SR-BI as a multipurpose player in lipid uptake from the blood circulation into hepatocytes in mice. In adrenocortical cells, SR-BI mediates the selective uptake of HDL-cholesteryl esters, which is eff iciently coupled to the synthesis of glucocorticoids (i.e. corticosterone). SR-BI knockout mice suffer from adrenal glucocorticoid insuff iciency, which suggests that functional SR-BI protein is necessary for optimal adrenal steroidogenesis in mice. SR-BI in macrophages plays a dual role in cholesterol metabolism as it is able to take up cholesterol associated with HDL and apoBcontaining lipoproteins and can possibly facilitate cholesterol efflux to HDL. Absence of SR-BI is associated with thrombocytopenia and altered thrombosis susceptibility, which suggests a novel role for SR-BI in regulating platelet number and function in mice. Transgenic expression of cholesteryl ester transfer protein in humanized SR-BI knockout mice normalizes hepatic delivery of HDL-cholesteryl esters. However, other pathologies associated with SR-BI def iciency, i.e. increased atherosclerosis susceptibility, adrenal glucocorticoid insuffi ciency, and impaired platelet function are not normalized, which suggests an important role for SR-BI in cholesterol and steroid metabolism in man. In conclusion, generation of SR-BI knockout mice has signif icantly contributed to our knowledge of the physiological role of SR-BI. Studies using these mice have identif ied SR-BI as a multi-purpose player in cholesterol and steroid metabolism because it has distinct roles in reverse cholesterol transport, adrenal steroidogenesis, and platelet function.
基金supported by the 973 Project of National Basic Research Program (No. 2012CB517503 and 2011CB503903)National Natural Science Foundation of China (No. 81070120)
文摘The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 (MSR1) gene, is a pattern recognition receptor (PPR) primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians. However, whether it links genetically to coronary artery disease (CAD) in Chinese is not defined. Here, we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms (SNPs) of MSR1. We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio (OR) of 1.56 [95% confidence interval (CI) = 1.28-1.90; P 〈 0.001] and 1.70 (95% CI = 1.27-2.27; P 〈 0.001), re- spectively. Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD / in combination with traditional risk factors of CAD in Chinese population.
基金Supported by A grant from the Netherlands Organization for Scientif ic Research (NWO, VIDI Grant 917-56-358)
文摘Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease. With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophysiological determinant of cholesterol gallstone formation. This review summarizes current knowledge on the origins of cholesterol secreted into the bile as well as the relevant processes and transporters involved. Next to the established ATP-binding cassette (ABC) transporters mediating the biliary secretion of bile acids (ABCB11), phospholipids (ABCB4) and cholesterol (ABCG5/G8), special attention is given to emerging proteins that modulate or mediate biliary cholesterol secretion. In this regard, the potential impact of the phosphatidylserine flippase ATPase class Ⅰ type 8B member 1, the Niemann Pick C1-like protein 1 that mediatescholesterol absorption and the high density lipoprotein cholesterol uptake receptor, scavenger receptor class B type Ⅰ, is discussed.
文摘Objective To study the significance of scavenger receptor class A(SR A)in mediating human peripheral blood monocyte to uptake oxidized low density lipoprotein(OxLDL) and promoting the atherosclerotic immuno pathological lesion in the local blood vessel. Methods With the Digoxenin labeled Oligonucleotide probes In situ Hybridization, this research investigated the effects of OxLDL on the mRNA expression of proinflammatory cytokines including MCP 1, bFGF, PDGF and IL 10 in the human peripheral blood monocyte and whether fucoidin, a peculiarly inhibitory ligand for SR A, would influence this process. Results Monocyte was significantly increased the mRNA expression of MCP 1, bFGF, PDGF and IL 10 in a dose dependent manner after incubating with OxLDL (10,15,20,25,30?mg·L -1 , respectively)for 24 hours( P < 0.001 ). Fucoidin(50,100,150,200,250?mg·mL -1 , respectively)completely inhibited OxLDL(20?mg·L -1 )from inducing monocyte the mRNA expression of above proinflammatory cytokines( P < 0.001 ). Conclusion OxLDL can stimulate human peripheral blood monocyte to give expression to proinflammatory cytokines mRNA in a dose dependent manner, while a peculiarly inhibitory ligand for SR A fucoidin has an obviously opposed role.
基金supported by a grant from the National Natural Science Foundation of China(491010-N11026)
文摘BACKGROUND:Non-alcoholic fatty liver disease(NAFLD)is one of the most frequent causes of liver diseases,with markedly increased prevalence.However,its mechanisms are not clear.The present study was undertaken to illustrate the role of caveolin-1(cav1)and the scavenger receptor class B type 1(SR-B1)in NAFLD.METHODS:Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol(HFC)diet for 14 weeks.The mice were sacrificed to collect plasma and harvest the liver;their plasma lipid concentration was measured.Hepatic cav1and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction(qPCR)and Western blotting,respectively.In order to study cav1 and SR-B1distribution and change in hepatocytes,immunohistochemical analysis was performed.RESULTS:HFC diet increased plasma lipids,induced NAFLD and increased the liver/body weight ratio.Compared to the control mice(n=6),the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice(n=12)increased significantly(cav1 mRNA:1.536±0.226 vs 0.980±0.272,P【0.05;protein:0.643±0.240 vs 0.100±0.130,P【0.01;SR-B1 mRNA:1.377±0.125 vs 0.956±0.151,P【0.01;protein:2.156±0.507vs 0.211±0.211,P【0.01).Furthermore,both cav1 and SR-B1immunoreactivity increased and their distribution was also changed,mainly in the plasma membrane of hepatocytes,cytoplasm and membrane of lipid droplets and around.CONCLUSION:NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions,which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.
基金supported by grants from the National Basic ResearchProgram(973)(No.2012CB517503,No.2011CB503903,and No.2012CB945003)National Natural Science Foundation of China(No.81070120)to Qi Chen+1 种基金National Natural Science Foundation ofChina(No.81000118)University Natural Science Foundation ofJiangsu(No.10KJB310005)to Jingjing Ben
文摘Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion. However, the underlying mechanism remains unclear. We previously found that 78 kDa glucose-regulated protein (GRP78) inhibited SR- A-mediated ligand internalization into macrophage by binding to SR-A. The aim of the study was to investigate whether GRP78 could regulate SR-A-mediated cell adhesion. We demonstrated that GRP78 bound directly to SR-A by fluorescence resonance energy transfer (FRET) assay. Overexpression of GRP78 inhibited macrophage adhesion via SR-A. These results suggest that GRP78 may act as an inhibitor of macrophage adhesion via SR-A.
基金supported by funds from the Canadian Institutes of Health Research (MOP74765)the Heart and Stroke Foundation of Canada(G-13-0002833 and G-15-0009016)
文摘Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein(HDL) are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1(SR-B1),an adaptor protein(PDZK1) that binds to the cytosolic C terminus of SR-B1,Akt1 activation and(at least in endothelial cells) activation of endothelial NO synthase(eNOS).Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice(apoE or LDLR KO) develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling(above)in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.
文摘The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA + AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Hart population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.
基金Supported by DSR Scholarship Support,King Saud University。
文摘Lutein,a type of carotenoids,is found to delay the onset and progression of age-related macular degeneration(AMD).Several lutein supplementation studies showed that after an initial increase,lutein serum levels demonstrated a subsequent decrease despite continuous supplementation.In this systematic literature review,this obscure phenomenon was tried to be explained.The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B typeⅠ(SR-BI)in the gastrointestinal tract,upregulation of lutein degrading enzymeβ-carotene dioxygenase(BCDO2),or perhaps a combination of both.Some single nucleotides polymorphisms(SNPs)that could have influence on the occurrence of this phenomenon.To date,an exact scientific explanation for this phenomenon has not been established.Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation,giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.
基金Supported by The NOVO Nordisk foundationthe Aarhus University Research FoundationClinical Institute,Aarhus University,Denmark
文摘AIM: To study the effect of a new anti-CD163-dexamethasone conjugate targeting activated macrophages on the hepatic acute phase response in rats. METHODS: Wistar rats were injected intravenous with either the CD163 targeted dexamethasone-conjugate(0.02 mg/kg) or free dexamethasone(0.02 or 1 mg/kg) 24 h prior to lipopolysaccharide(LPS)(2.5 mg/kg intraperitoneal). We measured plasma concentrations of tumour necrosis factor-a(TNF-a) and interleukin 6(IL-6) 2 h post-LPS and liver m RNAs and serum concentrations of the rat acute phase protein a-2-macroglobulin(a-2-M) 24 h after LPS. Also, plasma concentrations of alanine aminotransferase and bilirubin were measured at termination of the study. Spleen weight served as an indicator of systemic steroid effects.RESULTS: The conjugate halved the a-2-M liver m RNA(3.3 ± 0.6 vs 6.8 ± 1.1, P < 0.01) and serum protein(201 ± 48 μg/mL vs 389 ± 67 μg/mL, P = 0.04) after LPS compared to low dose dexamethasone treated animals, while none of the free dexamethasone doses had an effect on liver m RNA or serum levels of a-2-M. Also, the conjugate reduced TNF-a(7208 ± 1977 pg/mL vs 21583 ± 7117 pg/mL, P = 0.03) and IL-6(15685 ± 3779 pg/mL vs 25715 ± 4036 pg/mL, P = 0.03) compared to the low dose dexamethasone. The high dose dexamethasone dose decreased the spleen weight(421 ± 11 mg vs 465 ± 12 mg, P < 0.05) compared to controls, an effect not seen in any other group.CONCLUSION: Low-dose anti-CD163-dexamethasone conjugate effectively decreased the hepatic acute phase response to LPS. This indicates an anti-inflammatory potential of the conjugate in vivo.
基金supported by the China Scholarship Council(CSC)grant(Grant No.20180500458)。
文摘The study aimed to achieve enhanced targeted cytotoxicity and cell-internalization of cisplatin-loaded deoxyribonucleic acid-nanothread(CPT-DNA-NT),mediated by scavenger receptors into HeLa cells.DNA-NT was developed with stiff-topology utilizing circular-scaffold to encapsulate CPT.Atomic force microscopy(AFM)characterization of the DNA-NT showed uniformity in the structure with a diameter of 50-150 nm and length of 300-600 nm.The successful fabrication of the DNA-NT was confirmed through native-polyacrylamide gel electrophoresis analysis,as large the molecular-weight(polymeric)DNA-NT did not split into constituting strands under applied current and voltage.The results of cell viability confirmed that blank DNA-NT had the least cytotoxicity at the highest concentration(512 nM)with a viability of 92%as evidence of its biocompatibility for drug delivery.MTT assay showed superior cytotoxicity of CPT-DNA-NT than that of the free CPT due to the depot release of CPT after DNA-NT internalization.The DNA-NT exhibited targeted cell internalizations with the controlled intracellular release of CPT(from DNA-NT),as illustrated in confocal images.Therefore,in vitro cytotoxicity assessment through flow cytometry showed enhanced apoptosis(72.7%)with CPT-DNA-NT(compared to free CPT;64.4%).CPT-DNA-NT,being poly-anionic,showed enhanced endocytosis via scavenger receptors.
基金Supported by National Natural Science Foundation of China,No.31370196the National 973 Program,No.2013CB531601
文摘AIM To investigate the effect of a single amino acid mutation in human class B scavenger receptor I(SR-BI) on the infectivity of cell culture-derived hepatitis C virus(HCVcc) in SR-BI knock-down Huh7-si SR-BI cells.METHODS Site-directed mutagenesis was used to construct the SR-BI S112 F mutation,and the mutation was confirmed by nucleotide sequencing. SR-BI knock-down Huh7-si SR-BI cells were transfected with SR-BI S112 F,SR-BI wild type(WT) and control plasmids,and then infected with HCVpp(HCV pseudoparticles) and hepatitis C virus derived from cell culture(HCVcc). A fluorescence assay was performed to analyze the effect of the S112 F mutation on HCV entry; quantitative real-time PCR,immunofluorescence,and Western blot assays were used to analyze the effect of the S112 F mutation on HCV infectivity. CHO cells expressing WT and SRBI S112 F were incubated with the HCV E2 protein expressed in HEK 293 T cells,and flow cytometry was performed to examine the ability of SR-BI S112 F to bind to the HCV E2 protein. Huh7-si SR-BI cells were transfected with SR-BI WT and the S112 F mutant,andthen Di I-HDL was added and images captured under the microscope to assess the ability of SR-BI S112 F to take up HDL.RESULTS The SR-BI S112 F mutation was successfully constructed. The S112 F mutation decreased the expression of the SR-BI m RNA and protein. SR-BI S112 F decreased HCV entry and HCVcc infectivity in Huh7-si SR-BI cells. The S112 F mutation impaired the binding of SR-BI to HCV E2 protein and decreased the HDL uptake of SR-BI.CONCLUSION The S112 F single amino acid mutation in SR-BI decreased the levels of the SR-BI m RNA and protein,as well as the ability of SR-BI to bind to the HCV E2 protein. Amino acid 112 in SR-BI plays important roles in HCV entry and the infectivity of HCVcc in vitro.
基金the National Natural Science Foundation of China(No.12032007,31971242 to G.Wang)the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(No.jfkyjf202203001 to G.Wang).
文摘The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.
基金This research was supported by grants from the Na- tional Natural Science Foundation of China (Grant Nos. 31272505, 31172269 and 31360586).
文摘Class B scavenger receptors (SR-Bs) are cell surface glycoproteins involved in various physiological processes in vivo, including the transport and metabolism of lipids, binding and phagoeytosis of xenobiotics, and signaling. But little information is available about silkworm SR-Bs; it is necessary to study these SR-Bs for revealing their function. In this study, we cloned the full-length coding sequence of BrnSCRBQ4, a SR-B gene from the silkworm Bombyx mori L. We found that the BmSCRBQ4 gene consists of nine exons and eight introns, with an open reading frame of 1371 bp encoding 456 amino acids. Gene expression studies determined that BmSCRBQ4 messenger RNA (mRNA) was expressed in unfertilized eggs, during embryonic development and throughout the majority of the larval period. Expression of mRNA was detected in the mid gut, middle silk gland, posterior silk gland, head, integumentum, fat body, testes and the ovaries of the larval B. mori Dazao strain, as well as in the silkworm cell lines BmN and BmE. Protein expression studies found BmSCRBQ4 protein was expressed only in the testes, fat body and middle silk gland of larvae, as well as in the silkworm cell lines BmN and BmE. The BmSCRBQ4 protein showed variability in banding patterns in different tissues and cells when analyzed by Western blotting. Immunohistochemical staining showed that the BmSCRBQ4 protein localizes to the constitutive membranes or cellular membranes of these tissues. These results indicated that BmSCRBQ4 gene may play some physiologically relevant roles at the cell surface in each tissue.
基金This study was supported by a grant from the Natioal Natural ScienceFoundation of China (No.30370310) and Foundation for ReturneesStudying Abroad from Personnel Department of Hubei Province(No.301140200).
文摘Background We investigated the pathogenesis of atherosclerosis in diabetes, and detected the expression of scavenger receptor CD36 in monocytes in patients with type 2 diabetes.Methods According to the criteria by WHO, diabetic patients were classified into two groups: well controlled diabetic patients (WCP) and poorly controlled diabetic patients (PCP). The expression of CD36 protein and mRNA were evaluated by flow cytometry and reversal transcription polymerase chain reaction (RT-PCR). Plasma levels of accumulution of oxidized LDL (oxLDL) were immunosorbent assay (ELISA) method. directly measured by sandwich enzyme-linkedResults Flow cytometry and RT-PCR showed that the mean fluorescence intensity (MFI) of CD36 in monocyte and CD36 mRNA were significantly higher in the PCP and WCP in comparison with healthy controls (P 〈 O. O1 ). CD36 MFI and mRNA in the PCP were increased by 78% and 36% compared to the WCP. In both groups, CD36 MFI and mRNA were significantly higher in patients with diabetic atherosclerosis in comoparison with those without diabetic atherosclerosis (P 〈0. 05). No significant difference was found in CDt4 expression between the groups (P〉0. 05 ). The concentrations of plasma oxLDL were higher in the PCP group compared to WCP and control group (P 〈0. 05 ), whereas oxLDL average values did not differ significantly between WCP and control groups (P〉0.05 ) . In the WCP and PCP groups, oxLDL levels were higher in patients with diabetic atherosclerosis than those without diabetic atherosclerosis ( P 〈0.05 ).Conclusions The increased expression of scavenger receptor CD36 may be one of the mechanism of accelerated atherosclerosis in diabetic. The poorly controlled diabetes patients are at higher risk for the vascular complications than the well controlled diabetic patients.
文摘Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.
文摘Objective To observe the effect of Shengqing Capsule(SC)on serum contents of TC,LDL-C,and HDLC,hepatic scavenger receptor BⅠ(SRBⅠ),and CD36 in rats with cholesterol calculus.Methods
文摘Objective To review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED (1997-2006) online resources using the key term LOX-1. Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed. Conclusions Identification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.
基金This work was supported by grants from the National Natural Science Foundation of China (No. 30400265 and 30671047), Ministry of Education Science and Technology Key Project (No. 207078) and the Youth Foundation of Hunan Province Education Department (No. 06B079).
文摘Background Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-α mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell (SMC) proliferation, we'presume that the monocyte SR-PSOX/CXCL16 detection in the patients' peripheral blood will be important for early diagnosis and prognosis of atherosclerosis (AS). Methods Enrolled in this study were 40 patients with acute coronary syndrome (ACS), including 20 patients with acute myocardial infarction (AMI) and 20 patients with unstable angina pectoris (UAP), and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR), with β-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR- PSOX was analyzed with a confocal microscope. Results The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls (P〈0.05); however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group (P〉0.05). Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was proportionate to the degree of inflammation in the portal hepatis and folia. Conclusions The expression of CXCL16/SR-PSOX in the monocytes of peripheral blood was significantly higher in ACS patients than in the controls. CXCL16/SR-PSOX-mediated inflammation may contribute to the pathogenesis of ACS, and CXCL16 may play an important role in the pathogenesis and development of AS in humans.