BACKGROUND The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease(CAD),especially in women.Therefore,there is a growing need for the assessment of novel biomarkers to id...BACKGROUND The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease(CAD),especially in women.Therefore,there is a growing need for the assessment of novel biomarkers to identify women at risk.The receptor for advanced glycation end products(RAGE)and its interaction with the advanced glycation end product(AGE)ligand have been associated with atherogenesis.The soluble fraction of RAGE(sRAGE)antagonizes RAGE signaling and exerts an antiatherogenic effect.AIM The study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women.METHODS This case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups.Group I included 55 angiographically proven CAD subjects with>50%stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had<50%stenosis of the coronary arteries.Stenosis was confirmed by invasive angiography.Plasma sRAGE was determined by an enzyme-linked immunosorbent assay.RESULTS We observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls(P<0.05).Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD(P=0.01).Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL(lowest quartile)had a 6-fold increase in CAD prevalence independent of other risk factors.CONCLUSION Our findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women.Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.展开更多
Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aim...Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion （I/R） injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE （sRAGE group, n=5） or saline （control group, n=5）. Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor （TGF）-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume （from （19.5±5.1） to （32.3±5.6） ml, P 〈0.05） and end-systolic volume （from （8.3±3.2） to （15.2±4.1） ml, P 〈0.05） were significantly increased, whereas ejection fraction was decreased （from （61.6±13.3）% to （50.2±11.9）%, P 〈0.05）. No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group （both P 〈0.01）. Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals （P〈0.05）. Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.展开更多
Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to heal...Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.展开更多
AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples...AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radio- immunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the con- trols (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). The- re was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multiva- riate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently rela- ted to serum leptin levels. CONCLUSION: Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R con- centration, which suggests higher resistance of periphe- ral tissues towards the action of leptin.展开更多
AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chro...AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.展开更多
Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPas...Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.展开更多
Objective To establish and evaluate a protein serum ferritin （SF） and soluble transferrin receptor microarray method for combined measurement of （sTfR）. Methods Microarrayer was used to print both anti-SF antibodi...Objective To establish and evaluate a protein serum ferritin （SF） and soluble transferrin receptor microarray method for combined measurement of （sTfR）. Methods Microarrayer was used to print both anti-SF antibodies I and anti-sTfR antibodies I on each protein microarray. Anti-SF antibodies II and anti-sTfR antibodies II were used as detection antibodies and goat antibodies coupled to Cy3 were used as antibodies Ill. The detection conditions of the quantitative analysis method for simultaneous measurement of SF and sTfR with protein microarray were optimized and evaluated. The protein microarray was compared with commercially available traditional tests with 26 serum samples. Results By comparison experiment, mouse monoclonal antibodies were chosen as the probes and contact printing was chosen as the printing method. The concentrations of SF and sTfR probes were 0.5 mg/mL and 0.5 mg/mL respectively, while those of SF and sTfR detection antibodies were 5 μg/mL and 0.36 μg/mL respectively. Intra- and inter-assay variability was between 3.26% and 18.38% for all tests. The regression coefficients comparing protein microarray with traditional test assays were better than 0.81 for SF and sTfR. Conclusion The present study has established a protein microarray method for combined measurement of SF and sTfR.展开更多
To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was d...To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.展开更多
Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group...Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.展开更多
Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effec...Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.展开更多
Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications...Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.展开更多
Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The differ...Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.展开更多
Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF R, permitting the recruitment of gp130 and L...Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF R, permitting the recruitment of gp130 and LIF R, forming a tripartite receptor complex. Cells that only express gp130 and LIF R, but not CNTF R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH terminus of sCNTF R to the NH 2 terminus of CNTF. Recombinant CNTF/sCNTF R fusion protein (Hyper CNTF) was successfully expressed in COS 7 cells. The apparent molecular mass of the Hyper CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF R and LIF R receptor subunit whereas Hyper CNTF required heterodimerization of the gp130 and LIF R receptor subunit. We concluded that the fusion protein Hyper CNTF had superagonistic activity on target cells expressing gp130 and LIF R, but lacking membrane bound CNTF R.展开更多
Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle ce...Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.展开更多
Objective: To investigate the effect of high throughput hemodialysis on soluble transferrin receptor in hemodialysis patients and the improvement of renal anemia. Methods: 132 patients receiving maintenance hemodialys...Objective: To investigate the effect of high throughput hemodialysis on soluble transferrin receptor in hemodialysis patients and the improvement of renal anemia. Methods: 132 patients receiving maintenance hemodialysis in our hospital from July 2017 to July 2019 were selected and divided into control group and observation group according to the random number table method, with 66 cases each. The observation group was treated with high-flux hemodialysis, while the control group was treated with low-flux hemodialysis for 6 months. Compare two groups before and after treatment serum beta 2 microglobulin (beta 2 - MG), serum creatinine (Scr), blood urea nitrogen (BUN) level, anemia related index [red blood cells deposited (HCT), hemoglobin (Hb), reticulocyte percentage (Ret%)], iron metabolism index [serum ferritin (SF), transferrin saturation (TSAT)、Hepcidin(Hepc)], soluble transferrin receptor (sTfR) levels and adverse reactions. Results: the levels of 2-MG, Scr and BUN in the two groups before treatment were compared (P>0.05). After treatment, Scr and BUN levels in the two groups were significantly decreased (P<0.05), but were compared between the two groups (P>0.05). The level of 2-MG in the observation group was lower than that in the control group (P<0.05). Before treatment, sTfR, Hb, HCT level and Ret% of the two groups were compared(P>0.05). After treatment, Hb and HCT levels in the observation group were higher than those in the control group, while Ret% were lower than those in the control group, (P<0.05). Before treatment, the levels of ST、TAST、sTfR and Hepc in the two groups were compared (P>0.05). After treatment, the level of ST and TAST in the observation group was higher than that in the control group, The levels of sTfR and Hepc were lower than the control group (P<0.05). The overall incidence of adverse reactions in the observation group (8.93%) was lower than that in the control group (10.14%), with no significant difference (P>0.05). Conclusion: The high-throughput hemodialysis department significantly improved renal anemia in hemodialysis patients, reduced serum sTfR level, and had fewer adverse reactions and higher safety.展开更多
Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodi...Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.展开更多
Objectives To investi gate the association of soluble Fas ligand( sFasL) and soluble Fas receptor( sFas) with human chronic con gestive heart failure( CHF) . Methods The serum level of sFasL and sFas in 33 patients wi...Objectives To investi gate the association of soluble Fas ligand( sFasL) and soluble Fas receptor( sFas) with human chronic con gestive heart failure( CHF) . Methods The serum level of sFasL and sFas in 33 patients with CHF (13 in cardiac function class Ⅱ, 17 in class Ⅲ, 3 in class Ⅳ, NYHA) was assessed with enzyme - linked immunosorbent assay, and was compared with that of 18 age - , blood pressure - matched patients with car diac function class Ⅰ (NYHA). Results There was no difference in the level of sFasL between the two groups [CHF group: 231. 50 + / - 84. 50 (cardiac function class Ⅱ216. 50 + / - 96. 00 , class Ⅲ 226. 80 + / - 85. 70, class Ⅳ 244. 00 + / - 73. 00) vs. cardiac function class I group: 217. 50 + /-89. 00 pg/mL, P>0. 05]. However, the level of sFas was significantly higher in the patients with CHF than those of cardiac function class I group [CHF group: 1353. 30 +/-507. 71 (cardiac function class Ⅱ 1154. 85 + /-371. 20 , class Ⅲ1412.88 + /-493. 62, classⅣ1875. 67 + / - 806. 10) vs. cardiac function class I group: 983. 11+/ -461. 26 pg/mL, P<0. 05 ] . Conclusions sFasL was not associated with human CHF. However, the elevation of serum level of sFas was proportion to the severity of human CHF. sFas may play an important role in the patho- genesis of human CHF.展开更多
Summary: By using semi-quantitative RT-PCR method, it was found that PD-L1 mRNA but not PD-L2 mRNA was expressed in H22 hepatoma cells and both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mi...Summary: By using semi-quantitative RT-PCR method, it was found that PD-L1 mRNA but not PD-L2 mRNA was expressed in H22 hepatoma cells and both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mice and upregulated as compared with muscle tissues in normal mice and H22 hepatoma cells. PD-L1 and PD-L2 were also expressed on the surface of the activated T cells. The soluble recombinant sPD-1 expressed from the constructed eukaryotic expression vector could enhance the lysis of tumor cells by lymphocytes stimulated specifically with antigen. The expresssion of sPD-1 by local gene therapy on the inoculation site of H22 hepatoma cells could inhibit the growth of tumor. The results of this study indicate that expression of soluble receptor of negative costimulatory molecules could reduce the inhibitory effect on T cells in tumor microenvironment and enhance the cytotoxicity of T cells on tumor cells. This possibly provides a new method of improving efficacy of tumor gene therapy.展开更多
Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels an...Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.展开更多
BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accu...BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.展开更多
文摘BACKGROUND The established cardiovascular risk factors cannot explain the overall risk of coronary artery disease(CAD),especially in women.Therefore,there is a growing need for the assessment of novel biomarkers to identify women at risk.The receptor for advanced glycation end products(RAGE)and its interaction with the advanced glycation end product(AGE)ligand have been associated with atherogenesis.The soluble fraction of RAGE(sRAGE)antagonizes RAGE signaling and exerts an antiatherogenic effect.AIM The study aim was to explore the association between plasma levels of sRAGE and CAD in nondiabetic postmenopausal women.METHODS This case-control study included 110 nondiabetic postmenopausal women who were enrolled in two groups.Group I included 55 angiographically proven CAD subjects with>50%stenosis in at least one of the major coronary arteries and Group II included 55 healthy control women who did not have CAD or had<50%stenosis of the coronary arteries.Stenosis was confirmed by invasive angiography.Plasma sRAGE was determined by an enzyme-linked immunosorbent assay.RESULTS We observed significantly lower plasma sRAGE concentrations in subjects with CAD vs healthy controls(P<0.05).Univariate and multivariate logistic regression analysis also revealed a significant correlation between plasma sRAGE levels and CAD(P=0.01).Multivariate odds ratios for CAD revealed that subjects with sRAGE concentrations below 225 pg/mL(lowest quartile)had a 6-fold increase in CAD prevalence independent of other risk factors.CONCLUSION Our findings indicated that low sRAGE levels were independently associated with CAD in nondiabetic postmenopausal women.Risk assessment of CAD in postmenopausal women can be improved by including sRAGE along with other risk factors.
文摘Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion （I/R） injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE （sRAGE group, n=5） or saline （control group, n=5）. Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor （TGF）-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume （from （19.5±5.1） to （32.3±5.6） ml, P 〈0.05） and end-systolic volume （from （8.3±3.2） to （15.2±4.1） ml, P 〈0.05） were significantly increased, whereas ejection fraction was decreased （from （61.6±13.3）% to （50.2±11.9）%, P 〈0.05）. No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group （both P 〈0.01）. Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals （P〈0.05）. Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.
基金supported by the Nicolaus Copernicus University in Toruń,Ludwik Rydygier Collegium Medicum in Bydgoszcz,Poland(Grant No.2/WF-SD)
文摘Objective： Type 2 diabetes coexistent with lower extremity artery disease （peripheral arterial disease （PAD）） can be observed in numerous patients. The mechanism compensating for ischemia and contributing to healing is angiogenesis-the process of forming new blood vessels. The purpose of this study was to assess the likely impact of type 2 diabetes on the plasma levels of proangiogenic factor （vascular endothelial growth factor A （VEGF-A）） and angiogenesis inhibitors （soluble VEGF receptors type 1 and type 2 （sVEGFR-1 and sVEGFR-2）） in patients with PAD. Methods： Among 46 patients with PAD under pharmacological therapy （non-invasive）, we identified, based on medical history, a subgroup with coexistent type 2 diabetes （PAD-DM2＋, n=15） and without diabetes （PAD-DM2-, n=31）. The control group consisted of 30 healthy subjects. Plasma levels of VEGF-A, sVEGFR-1, and sVEGFR-2 were measured using the enzyme-linked immunosorbent assay （ELISA） method. Results： The subgroups of PAD-DM2＋ and PAD-DM2- revealed significantly higher concentrations of VEGF-A （P=-0.000007 and P=0.0000001, respectively） and significantly lower sVEGFR-2 levels （P=-0.02 and P=-0.00001, respectively）, when compared with the control group. Patients with PAD and coexistent diabetes tended to have a lower level of VEGF-A and higher levels of sVEGFR-1 and sVEGFR-2 comparable with non-diabetic patients. Conclusions： The coexistence of type 2 diabetes and PAD is demonstrated by a tendency to a lower plasma level of proangiogenic factor （VEGF-A） and higher levels of anglogenesis inhibitors （sVEGFR-1 and sVEGFR-2） at the same time. Regardless of the coexistence of type 2 diabetes, hypoxia appears to be a crucial factor stimulating the processes of angiogenesis in PAD patients comparable with healthy individuals, whereas hyperglycemia may have a negative impact on angiogenesis in lower limbs.
文摘AIM: To determine the role of leptin system in non-al- coholic fatty liver disease (NAFLD) development by deli- neating the changes in serum levels of leptin and soluble leptin receptor (sOB-R). METHODS: Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis (stationary phase) as controls. Serum leptin levels were determined by radio- immunoassay and concentration of sOB-R was measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the con- trols (both P < 0.001), but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group (all P < 0.001). The- re was a significant negative correlation between serum leptin and sOB-R levels (r = -0.725, P < 0.001). Multiva- riate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance (HOMA IR) were independently rela- ted to serum leptin levels. CONCLUSION: Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R con- centration, which suggests higher resistance of periphe- ral tissues towards the action of leptin.
基金Supported by the Namral Science Foundation of Gansu Province,No.ZR-96-078
文摘AIM： To investigate the relationship between serum soluble interleukin-2 receptor （sIL-2R） level and anti-HBc in patients with chronic hepatitis B virus （HBV） infection. METHODS： Sera from 100 patients with chronic HBV infection and 30 healthy controls were included in this study. The patients were divided into group A [HBsAg （＋）, HBeAg （＋） and anti-HBc （＋）, n = 50] and group B [HBsAg （＋）, HBeAg （＋） and anti-HBc （-）, n = 50]. sIL-2R levels were determined using ELISA. HBV DNA and alanine aminotransferase （ALT） were also detected. RESULTS： Serum sIL-2R levels were significantly higher in patients with chronic HBV infection than in healthy controls. Moreover, serum sIL-2R levels were significantly higher in patients with HBsAg （＋）, HBeAg （＋） and antiHBc （＋） （976.56±213.51×10^3 U/L） than in patients with HBsAg （＋）, HBeAg （＋） and anti-HBc （-） （393.41±189.54 ×10^3 U/L, P〈 0.01）. A significant relationship was found between serum sIL-2R and ALT levels （P〈 0.01） in patients with chronic HBV infection, but there was no correlation between sIL-2R and HBV DNA levels. The anti-HBc status was significantly related to the age of patients （P〈 0.01）. CONCLUSION： The high sIL-2R level is related to positive anti-HBc in chronic hepatitis B patients. Positive anti-HBc may be related to T-lymphocyte activation and negative anti-HBc may imply immune tolerance in these patients.
文摘Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.
基金funded by the 863 Program entitled as"The research and exploration of nutrition fortified food for improving growth and development(2010AA023004)"performed by the Trace Elements Nutrition Key Laboratory of the Ministry of Health
文摘Objective To establish and evaluate a protein serum ferritin （SF） and soluble transferrin receptor microarray method for combined measurement of （sTfR）. Methods Microarrayer was used to print both anti-SF antibodies I and anti-sTfR antibodies I on each protein microarray. Anti-SF antibodies II and anti-sTfR antibodies II were used as detection antibodies and goat antibodies coupled to Cy3 were used as antibodies Ill. The detection conditions of the quantitative analysis method for simultaneous measurement of SF and sTfR with protein microarray were optimized and evaluated. The protein microarray was compared with commercially available traditional tests with 26 serum samples. Results By comparison experiment, mouse monoclonal antibodies were chosen as the probes and contact printing was chosen as the printing method. The concentrations of SF and sTfR probes were 0.5 mg/mL and 0.5 mg/mL respectively, while those of SF and sTfR detection antibodies were 5 μg/mL and 0.36 μg/mL respectively. Intra- and inter-assay variability was between 3.26% and 18.38% for all tests. The regression coefficients comparing protein microarray with traditional test assays were better than 0.81 for SF and sTfR. Conclusion The present study has established a protein microarray method for combined measurement of SF and sTfR.
文摘To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.
文摘Objective: to explore the mechanism of leeching in treating systemic lupus erythematosus (SLE). Methods: Forty-four patients with SLE were randomly divided into conventional corticosteroid treated group (control group, n =20) and conventional treatment group with leeching intervention added (leeching group, n =24). Before and after treatment the concentration of plasma endothelin (ET) and soluble interleukin-2 receptor (sIL-2R) were determined. Results: Before treatment the level of plasma ET and sIL-2R in the SLE patients were all higher than those in the normal healthy group, ( P <0.01). But after treatment the level of these in both groups were significantly improved than those of before treatment ( P <0.05), and comparison between these two treated groups showed that the difference between them was significant ( P <0.05). Conclusion: Leeching added to conventional treatment of SLE could be more effective in improving the level of plasma ET and sIL-2R, and ameliorating the impairment of renal tissues.
基金a grant from the NationalNatural Science Foundation of China (No. 39270658).
文摘Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve (s) replacement were randomly divided into two groups: control group (n=10) and apro- tinin group (n=10). In aprotinin group, 1 000 000 KIU aprotinin was given by vein injection and then 2 000 000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and slL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.
基金supported by NIAMS,of the National Institutes of Health,under award numbers R01AR062074 (to DJD) and R01AR060636 (to S-JL)the Harry Headley Charitable and Research Foundation,Punta Gorda,FL(to ELG-L)
文摘Osteogenesis imperfecta（OI） comprises a group of heritable connective tissue disorders generally defined by recurrent fractures, low bone mass, short stature and skeletal fragility. Beyond the skeletal complications of OI,many patients also report intolerance to physical activity, fatigue and muscle weakness. Indeed, recent studies have demonstrated that skeletal muscle is also negatively affected by OI, both directly and indirectly. Given the well-established interdependence of bone and skeletal muscle in both physiology and pathophysiology and the observations of skeletal muscle pathology in patients with OI, we investigated the therapeutic potential of simultaneous anabolic targeting of both bone and skeletal muscle using a soluble activin receptor 2B（ACVR2B） in a mouse model of type Ⅲ OI（oim）. Treatment of 12-week-old oim mice with ACVR2 B for 4 weeks resulted in significant increases in both bone and muscle that were similar to those observed in healthy,wild-type littermates. This proof of concept study provides encouraging evidence for a holistic approach to treating the deleterious consequences of OI in the musculoskeletal system.
文摘Primary focal and segmental glomerulosclerosis(FSGS) may be due to genetic or acquired etiologies and is a common cause of nephrotic syndrome with high morbidity that often leads to end-stage renal failure. The different available therapeutic approaches are unsuccessful, in part due to partially deciphered heterogeneous and complex pathophysiological mechanisms. Moreover, the term FSGS, even in its primary form, comprises a histological description shared by a number of different causes with completely different molecular pathways of disease. This review focuses on the latest developments regarding the pathophysiology of primary acquired FSGS caused by soluble factor urokinase type plasminogen activator receptor, a circulating permeability factor involved in proteinuria and edema formation, and describes recent advances with potential success in therapy.
文摘Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF R, permitting the recruitment of gp130 and LIF R, forming a tripartite receptor complex. Cells that only express gp130 and LIF R, but not CNTF R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH terminus of sCNTF R to the NH 2 terminus of CNTF. Recombinant CNTF/sCNTF R fusion protein (Hyper CNTF) was successfully expressed in COS 7 cells. The apparent molecular mass of the Hyper CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF R and LIF R receptor subunit whereas Hyper CNTF required heterodimerization of the gp130 and LIF R receptor subunit. We concluded that the fusion protein Hyper CNTF had superagonistic activity on target cells expressing gp130 and LIF R, but lacking membrane bound CNTF R.
文摘Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.
基金Zhongshan Municipal Science and Technology Plan Project(No.2017B1061)
文摘Objective: To investigate the effect of high throughput hemodialysis on soluble transferrin receptor in hemodialysis patients and the improvement of renal anemia. Methods: 132 patients receiving maintenance hemodialysis in our hospital from July 2017 to July 2019 were selected and divided into control group and observation group according to the random number table method, with 66 cases each. The observation group was treated with high-flux hemodialysis, while the control group was treated with low-flux hemodialysis for 6 months. Compare two groups before and after treatment serum beta 2 microglobulin (beta 2 - MG), serum creatinine (Scr), blood urea nitrogen (BUN) level, anemia related index [red blood cells deposited (HCT), hemoglobin (Hb), reticulocyte percentage (Ret%)], iron metabolism index [serum ferritin (SF), transferrin saturation (TSAT)、Hepcidin(Hepc)], soluble transferrin receptor (sTfR) levels and adverse reactions. Results: the levels of 2-MG, Scr and BUN in the two groups before treatment were compared (P>0.05). After treatment, Scr and BUN levels in the two groups were significantly decreased (P<0.05), but were compared between the two groups (P>0.05). The level of 2-MG in the observation group was lower than that in the control group (P<0.05). Before treatment, sTfR, Hb, HCT level and Ret% of the two groups were compared(P>0.05). After treatment, Hb and HCT levels in the observation group were higher than those in the control group, while Ret% were lower than those in the control group, (P<0.05). Before treatment, the levels of ST、TAST、sTfR and Hepc in the two groups were compared (P>0.05). After treatment, the level of ST and TAST in the observation group was higher than that in the control group, The levels of sTfR and Hepc were lower than the control group (P<0.05). The overall incidence of adverse reactions in the observation group (8.93%) was lower than that in the control group (10.14%), with no significant difference (P>0.05). Conclusion: The high-throughput hemodialysis department significantly improved renal anemia in hemodialysis patients, reduced serum sTfR level, and had fewer adverse reactions and higher safety.
文摘Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.
文摘Objectives To investi gate the association of soluble Fas ligand( sFasL) and soluble Fas receptor( sFas) with human chronic con gestive heart failure( CHF) . Methods The serum level of sFasL and sFas in 33 patients with CHF (13 in cardiac function class Ⅱ, 17 in class Ⅲ, 3 in class Ⅳ, NYHA) was assessed with enzyme - linked immunosorbent assay, and was compared with that of 18 age - , blood pressure - matched patients with car diac function class Ⅰ (NYHA). Results There was no difference in the level of sFasL between the two groups [CHF group: 231. 50 + / - 84. 50 (cardiac function class Ⅱ216. 50 + / - 96. 00 , class Ⅲ 226. 80 + / - 85. 70, class Ⅳ 244. 00 + / - 73. 00) vs. cardiac function class I group: 217. 50 + /-89. 00 pg/mL, P>0. 05]. However, the level of sFas was significantly higher in the patients with CHF than those of cardiac function class I group [CHF group: 1353. 30 +/-507. 71 (cardiac function class Ⅱ 1154. 85 + /-371. 20 , class Ⅲ1412.88 + /-493. 62, classⅣ1875. 67 + / - 806. 10) vs. cardiac function class I group: 983. 11+/ -461. 26 pg/mL, P<0. 05 ] . Conclusions sFasL was not associated with human CHF. However, the elevation of serum level of sFas was proportion to the severity of human CHF. sFas may play an important role in the patho- genesis of human CHF.
文摘Summary: By using semi-quantitative RT-PCR method, it was found that PD-L1 mRNA but not PD-L2 mRNA was expressed in H22 hepatoma cells and both PD-L1 and PD-L2 mRNAs were expressed in tumor tissues of tumor-bearing mice and upregulated as compared with muscle tissues in normal mice and H22 hepatoma cells. PD-L1 and PD-L2 were also expressed on the surface of the activated T cells. The soluble recombinant sPD-1 expressed from the constructed eukaryotic expression vector could enhance the lysis of tumor cells by lymphocytes stimulated specifically with antigen. The expresssion of sPD-1 by local gene therapy on the inoculation site of H22 hepatoma cells could inhibit the growth of tumor. The results of this study indicate that expression of soluble receptor of negative costimulatory molecules could reduce the inhibitory effect on T cells in tumor microenvironment and enhance the cytotoxicity of T cells on tumor cells. This possibly provides a new method of improving efficacy of tumor gene therapy.
基金supported by the National Natural Science Foundation of China(No.81471507)
文摘Soluble receptor for advanced glycation end products（s RAGE） can decoy the toxic AGEs and is considered to be a protective factor.This study aimed to evaluate the correlation between intrafollicular s RAGE levels and clinical outcomes in infertile women of young or advanced maternal age（AMA） undergoing in vitro fertilization（IVF）.A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study.The intrafollicular s RAGE concentration was measured to determine its association with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy in young and AMA women,respectively.Besides,correlations between sR AGE and age or follicle-stimulating hormone（FSH） were examined.We found that the intrafollicular s RAGE levels were higher in young patients than those in AMA patients,suggesting that the s RAGE levels were inversely correlated with age.In young patients,sR AGE showed no correlation with the number of retrieved oocytes,fertilized oocytes,high-quality embryos or achievement of clinical pregnancy.But it was found that AMA patients with more retrieved oocytes,fertilized oocytes and high-quality embryos demonstrated higher sR AGE levels,which were a prognostic factor for getting clinical pregnancy independent of age or FSH level.In conclusion,the s RAGE levels decrease with age.Elevated intrafollicular s RAGE levels indicate good follicular growth,fertilization and embryonic development,and successful clinical pregnancy in AMA women,while in young women,the role of s RAGE may not be so predominant.
基金National Natural Science Foundation of China,No.81970550,No.82070613 and No.82370638Natural Science Foundation of Hunan Province,China,No.2021JJ31067 and No.2021JJ41048+1 种基金Hunan innovative province construction project,No.2023JJ10095Innovative Talented Project of Hunan province,China,No.2022RC1212.
文摘BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.
