Serum Soluble Receptor Research Articles

Association between serum soluble (pro)renin receptor level and worsening of cardiac function in hemodialysis patients: A prospective observational study.

The (pro)renin receptor ((P)RR) is cleaved to generate soluble (P)RR (s(P)RR), which reflects the status of the tissue renin-angiotensin system. Hemodialysis (HD) patients have a poor prognosis due to the increased prevalence of cardiovascular diseases. The present study aimed to investigate whether serum s(P)RR level is associated with the worsening of cardiac function in HD patients. A total of 258 maintenance HD patients were recruited and serum s(P)RR concentration was measured. Background factors in patients who survived (S group) and patients who died (D group) during the 12-month follow-up period and relationships between serum s(P)RR level and changes in cardiac function during the follow-up period in the S group were investigated. The median serum s(P)RR value at baseline was 29.8 ng/ml. Twenty-four patients died during the follow-up period. Cardiothoracic ratio, human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), and E over e-prime were significantly higher in the D group. In the S group, changes in hANP or BNP were significantly greater in the higher serum s(P)RR group than in the lower serum s(P)RR group. High serum s(P)RR level was significantly correlated with changes in BNP, independent of other factors. High serum s(P)RR level was associated with increases in BNP, independent of other risk factors, suggesting that an increased expression of (P)RR may be associated with a progression of heart failure in HD patients and that serum s(P)RR concentration could be used as a biomarker for selecting patients requiring intensive care.

Utility of reticulocyte hemoglobin in diagnosing latent iron deficiency and iron deficiency anemia

Background: Iron deficiency is the most common cause of anemia and studies have shown poor cognition, psychomotor and social/emotional development in children who are deficient in iron, even with normal hemoglobin levels, the so-called Latent phase of Iron deficiency. It is therefore crucial to identify LID, as well as IDA at the earliest stage, in order to initiate treatment. Many tests like serum ferritin and soluble transferring receptor(sTfR) have been described collectively as a panel to detect iron deficiency; however no single test is specific enough to be used independently. Also during treatment it takes weeks to observe changes in Hb, hematocrit or RBC indices, hence the need for a more sensitive and reliable test. Objective was to evaluate effectiveness of CHr in diagnosing LID and IDA.Methods: Samples were collected from 180 children, clinically suspected to be anemic. Complete hemogram and Iron profile were measured. Three groups were defined, LID (Tfsat <20%, Hb >11g/dL; n=52), IDA (Tfsat <20%, Hb <11g/dL; (n=84) and controls (Tfsat >20%, Hb >11g/dL; n=44). The mean values of RBC indices, Iron profile and CHr was compared across the groups. A cut off value of <26 pg CHr was taken to represent Iron deficiency state.Results: Comparison between anemic group and control found that all RBC indices were found to be significantly lower including Reticulocyte hemoglobin. All of the variables in anemic group were lower compared to latent iron deficient group except MCHC and reticulocyte count. CHr was found to be statistically lower in LID and IDA group in comparison to control group.Conclusions: CHr can be used as a valuable indicator in diagnosis as well as follow-up of LID and IDA, which is easily available and inexpensive.

Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients.

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.

Serum level of soluble interleukin 6 receptor is a useful biomarker for identification of treatment-resistant major depressive disorder.

AimA substantial proportion of major depressive disorder patients are treatment‐resistant to antidepressant therapy, who require augmentation drugs, or other treatments including electroconvulsive therapy or transcranial magnetic stimulation. Identifying treatment‐resistant major depressive disorder patients before the actual administration of antidepressant is, however, often difficult. Accordingly, the serum biomarker to identify treatment‐resistant patients will be helpful in clinical settings. This study aims to clarify the appropriate biomarkers for identification of treatment‐resistant major depressive disorder.MethodGiven that immune‐inflammatory processes are involved in the pathogenesis of major depressive disorder, it is possible that certain cytokine‐related molecules could serve as clinically useful biomarkers of treatment‐resistant major depressive disorder patients. In this study, we measured serum levels of tumor necrosis factor‐α, interleukin 6, and soluble interleukin 6 receptor after major depressive disorder patients underwent antidepressant therapy.ResultsThe serum level of soluble interleukin 6 receptor, but not interleukin 6 or tumor necrosis factor‐α, was significantly higher in treatment‐resistant major depressive disorder patients than in remitted patients, suggesting that serum soluble interleukin 6 receptor could be a good biomarker of treatment‐resistant major depressive disorder. Receiver operating characteristic analysis confirmed that serum soluble interleukin‐6 receptor level measurement was useful for identification of treatment‐resistant major depressive disorder patients. Multiple regression analysis using the serum levels of the aforementioned cytokines as explanatory variables and the Quick Inventory of Depressive Symptomatology‐Self Report score (QIDS‐SR16) as a target variable showed that only serum soluble interleukin‐6 receptor level could explain the severity of major depressive disorder.ConclusionBased on these results, we recommend measurement of serum soluble interleukin‐6 receptor level to discriminate treatment‐resistant major depressive disorder patients. High serum soluble interleukin‐6 receptor level is associated with the pathogenesis of treatment‐resistant major depressive disorder, suggesting the involvement of the interleukin 6 trans‐signaling system in onset of treatment‐resistant major depressive disorder.

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study

ObjectiveAlcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically. MethodWe measured and compared (median) serum lipids (triglycerides and total, HDL, and LDL cholesterol) and leptin activities (leptin, soluble leptin receptor [ObRe], and free leptin index) in 200 (males 56.5 %) early-abstinent alcohol-dependent in-patients and 240 (males 55.4 %) healthy controls and assessed alcohol-related readmissions during a 24 -month post-inclusion period. ResultsMale patients showed higher HDL cholesterol (61 versus 48 mg/dl), lower LDL/HDL ratios (2.06 versus 3.04), and lower free leptin index (0.30 versus 0.59) at study inclusion compared to healthy controls. In patients, ObRe levels were higher than in controls and decreased from inclusion to the second study-visit (at median 5 days later; males: 16.7–13.8 versus 11.0 ng/ml; females: 17.0–13.4 versus 12.1 ng/ml). The free leptin index increased between the two time points in females (0.80 versus 1.20). Lipids and leptin activities correlated with carbohydrate-deficient transferrin levels and liver enzyme activities. None of the serum parameters were significantly associated with alcohol-related readmissions. ConclusionOur data support that serum lipid levels and leptin activities are involved in alcohol dependence. The parameters appear as possible indirect biomarkers for alcohol dependence.

Serum soluble toll-like receptor 2 and 4 as diagnostic and prognostic biomarkers for non-Hodgkin lymphoma.

Aim of the studyTo assess the serum levels of soluble toll-like receptor 2 (sTLR2) and soluble toll-like receptor 4 (sTLR4) in a group of patients with non-Hodgkin lymphoma (NHL) and to investigate their correlations with the clinicopathological parameters of NHL.Material and methodsFifty patients with early-stage NHL and 50 patients with advanced-stage NHL along with 50 age- and sex-matched healthy volunteers were enrolled in the study. Serum levels of sTLR2 and sTLR4 were measured using enzyme-linked immunosorbent assay (ELISA).ResultsA significant increase in the serum levels of sTLR2 (pg/ml) was detected in early stage NHL (group I) (2381.1 ±1822.0) and advanced stage NHL (group II) (2864.9 ±2599.9) when compared to levels in the control group (1229.2 ±70.55) (p < 0.001). A significant increase in the serum levels of sTLR4 (pg/ml) was detected in early stage NHL (2465.4 ±3501.8) and advanced stage NHL (4759.7 ±5176.2) when compared to levels in the control group (1242.3 ±53) (p < 0.001). A significant positive correlation was detected between the serum levels of both sTLR2 and sSTLR4 and the Ann Arbor staging of NHL.ConclusionssTLR2 and sTLR4 might be diagnostic and prognostic biomarkers for NHL.

The clinical value of the combined detection of sEGFR, CA125 and HE4 for epithelial ovarian cancer diagnosis.

This study aims to investigate the clinical value of combined detection of serum soluble epidermal growth factor receptor (sEGFR), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in the diagnosis of epithelial ovarian cancer (EOC). From December 2017 to October 2018, the serum samples were obtained from the Affiliated Hospital of Xuzhou Medical University, with 30 patients as EOC group, 30 patients with benign ovarian neoplasms as benign group, and 17 healthy subjects as healthy group. Besides, among 30 EOC patients, 9 serum samples were obtained from pre-operative and post-operative EOC patients. The levels of serum sEGFR were detected by enzyme-linked immunosorbent assay (ELISA), while CA125 and HE4 were detected by enhanced chemiluminescence immunoassay (ECLIA). The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. The levels of serum sEGFR, CA125, and HE4 in EOC group were significantly higher than those in benign group (p<0.05) and healthy group (p<0.05). When using a single tumor marker, the CA125 shows the highest sensitivity (93.30%) and HE4 shows the highest specificity (97.87%). The specificity of combined detection of serum sEGFR, CA125, and HE4 was 100%, which was significantly higher than that using a single tumor marker. The area under the ROC curve (AUC) of combined detection of serum sEGFR, CA125, and HE4 (0.965) was much higher than that of the single detection and higher than that of combined detection of CA125 and HE4 (0.940). Moreover, the level of serum sEGFR in post-operative EOC group was significantly lower than that in the corresponding pre-operative EOC group (p<0.05). Our study shows that combined detection of serum sEGFR, CA125, and HE4 increases the specificity and efficiency in EOC diagnosis, indicating that sEGFR could be a potential biomarker for the diagnosis and prognosis of EOC.

Serum soluble Toll-like receptor 4 and the risk of hepatocellular carcinoma in hepatitis C virus patients.

IntroductionSoluble Toll-like receptor 4 (sTLR4) is a negative regulator of TLR4 signalling that has been reported in different diseases. In this study, we aimed to assess the serum levels of sTLR4 in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the correlation of sTLR4 with clinicopathological and biochemical parameters among HCV-related HCC patients and hepatitis C without HCC patients.Material and methodsFifty patients with HCV-related HCC, 50 patients with hepatitis C without HCC and 50 healthy control volunteers were enrolled. Clinicopathological and biochemical parameters were examined in all patients. Serum levels of sTLR4 were measured using enzyme-linked immunosorbent assay.ResultsA significant increase in serum sTLR4 was detected in patients with HCV-related HCC (4436.1 ±7089.8) (pg/ml) ± compared to the level in patients with hepatitis C without HCC (1561.4 ±532.0) (pg/ml) (p = 0.002) and the level in the control group (1170.38 ±159.42) (pg/ml) (p < 0.001). Serum sTLR4 was positively correlated with serum AST activity, serum direct bilirubin levels, serum alpha fetoprotein levels, tumour stages of HCC according to the Barcelona Clinic Liver Cancer staging system (BCLC), and the severity of liver cirrhosis according to the Child-Pugh classification among the patients with HCV-related HCC. The combination of serum alpha fetoprotein and serum sTLR4 increased the sensitivity of HCC detection to 76% and the specificity to 94%.ConclusionsSerum sTLR4 may be a marker for HCC susceptibility among HCV-infected patients.

Cell Cycle Biomarkers and Soluble Urokinase-Type Plasminogen Activator Receptor for the Prediction of Sepsis-Induced Acute Kidney Injury Requiring Renal Replacement Therapy: A Prospective, Exploratory Study

Sepsis-induced acute kidney injury is the dominant acute kidney injury etiology in critically ill patients and is often associated with a need for renal replacement therapy. The indication and timing of renal replacement therapy are controversially discussed. We hypothesized that the product of the G1-cell cycle arrest biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), and the soluble urokinase-type plasminogen activator receptor are of diagnostic value for the prediction of septic acute kidney injury courses requiring renal replacement therapy. In this prospective study, critically ill patients were enrolled immediately after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2] × [IGFBP7] levels over time and serum soluble urokinase-type plasminogen activator receptor levels once at inclusion were measured. The primary endpoint was the development of septic acute kidney injury with the need for renal replacement therapy. Area under the receiver operating characteristic curves, de Long's tests, and logistic regression models were calculated. Two ICUs at Heidelberg University Hospital between May 2017 and July 2018. One-hundred critically ill patients with positive Sepsis-3 criteria. None. Nineteen patients required renal replacement therapy. Diagnostic performance of urinary [TIMP-2] × [IGFBP7] improved over time with the highest area under the receiver operating characteristic curve of 0.89 (95% CI, 0.80-0.98) 24 hours after study inclusion. Soluble urokinase-type plasminogen activator receptor levels at inclusion showed an area under the receiver operating characteristic curve of 0.83 (0.75-0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2] × [IGFBP7] at 24 hours after inclusion by applying a cutoff value of greater than or equal to 0.6 (ng/mL)/1,000 (sensitivity 90.9, specificity 67.1). Soluble urokinase-type plasminogen activator receptor performed best by using a cutoff value of greater than or equal to 8.53 ng/mL (sensitivity 84.2, specificity 82.7). A combination of newly tested biomarkers with cystatin C resulted in a significantly improved diagnostic accuracy. Cystatin C in combination with [TIMP-2] × [IGFBP7] 24 hours outperformed all standard renal parameters (area under the receiver operating characteristic curve 0.93 [0.86-1.00]). [TIMP-2] × [IGFBP7] and soluble urokinase-type plasminogen activator receptor are promising biomarker candidates for the risk stratification of septic acute kidney injury patients with the need for renal replacement therapy.

The N125S polymorphism in the cathepsin G gene (rs45567233) is associated with susceptibility to osteomyelitis in a Spanish population.

Osteomyelitis is a bone infection, most often caused by Staphylococcus aureus, in which neutrophils play a key role. Cathepsin G (CTSG) is a bactericidal serine protease stored in the neutrophil azurophilic granules. CTSG regulates inflammation, activating matrix metalloproteinases (MMPs), and coagulation. Lactoferrin (LF), a neutrophil glycoprotein, increases CTSG catalytic activity and induces inflammation. The aim of this study was to analyze a potential association between a CTSG gene polymorphism (Asn125Ser or N125S, rs45567233), that modifies CTSG activity, and could affect susceptibility to, or outcome of, bacterial osteomyelitis. CTSG N125S polymorphism was genotyped in 329 osteomyelitis patients and 415 controls), Blood coagulation parameters, serum CTSG activity, LF, MMP-1, MMP-13, and soluble receptor activator for nuclear factor κ B ligand (sRANKL) levels were assessed in carriers of the different CTSG genotypes. CTSG N125S (AG) genotype was significantly more frequent among osteomyelitis patients than controls (15.5% vs. 9.4%, p = 0.014). CTSG N125S variant G allele (AG +GG) was also more frequent among osteomyelitis patients (8.1% vs. 4.7%, p = 0.01). Serum CTSG activity and LF levels were significantly higher in osteomyelitis patients carrying the G allele compared to those with the AA genotype, (p<0.04). Serum MMP-1 was lower in the G allele carriers (p = 0.01). There was no association between these genotypes and clinical characteristics of osteomyelitis, or coagulation parameters, MMP-13, and sRANKL serum levels. Differences in the CTSG gene might enhance osteomyelitis susceptibility by increasing CTSG activity and LF levels.

Unique Sjögren's syndrome patient subsets defined by molecular features.

To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes. pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200. Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell-attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1α, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters. Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.

Serum plasminogen activator urokinase receptor predicts elevated risk of acute respiratory distress syndrome in patients with sepsis and is positively associated with disease severity, inflammation and mortality.

The present study aimed to evaluate the predictive value of serum soluble urokinase plasminogen activator receptor (suPAR) regarding the risk of acute respiratory distress syndrome (ARDS) in sepsis patients, and investigate its correlation/association with disease severity, inflammation and mortality in sepsis patients with ARDS. A total of 57 sepsis patients with ARDS and 58 sepsis patients without ARDS were recruited for the present case-control study. Laboratory tests, acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score were evaluated, and mortality during hospitalization was recorded. Blood samples were collected and serum suPAR was detected by ELISA. Furthermore, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-10 and IL-17, as well as C-reactive protein (CRP) were detected. The results indicated that the serum levels of suPAR in sepsis patients with ARDS were higher than those in sepsis patients without ARDS. Receiver operating characteristics (ROC) curve analysis indicated that it was possible to distinguish sepsis patients with ARDS from sepsis patients without ARDS based on their serum suPAR levels, and multivariate logistic regression analysis suggested that serum suPAR levels were an independent predictor of the risk of ARDS in sepsis patients. In sepsis patients with ARDS, serum suPAR levels were positively correlated with the APACHE II score, SOFA score and the levels of CRP, TNF-α, IL-1β and IL-8. In addition, serum suPAR levels were lower in survivors compared with those in non-survivors, and ROC curve analysis suggested that serum suPAR was able to predict the probability of mortality. In conclusion, serum suPAR independently predicted an elevated risk of ARDS in patients with sepsis, and was correlated/associated with greater disease severity, higher inflammation and increased mortality in patients with sepsis and ARDS.

Serum-soluble (pro)renin receptor concentration as a biomarker for organ damage in primary aldosteronism.

Primary aldosteronism is characterized by inappropriate overproduction of aldosterone by adrenal lesions and leads to hypertension. Excess aldosterone causes organ damage; therefore, finding a biomarker for organ damage risk is vital. The (pro)renin receptor regulates the tissue renin-angiotensin-aldosterone system. The blood soluble (pro)renin receptor concentration is a candidate biomarker that reflects the activity of the tissue renin-angiotensin-aldosterone system. This study investigated the relationships between serum soluble (pro)renin receptor concentrations and indices of organ damage in patients with primary aldosteronism. We examined plasma aldosterone and serum soluble (pro)renin receptor concentrations in patients with primary aldosteronism and evaluated the relationships between these values and organ damage indices, such as the cardio-ankle vascular index, urinary albumin excretion, estimated glomerular filtration rate, and high-sensitivity C-reactive protein levels. We enrolled 121 patients with primary aldosteronism (46 males, 54.9 ± 12.2 years of age). Serum soluble (pro)renin receptor concentrations were significantly positively correlated with the cardio-ankle vascular index, urinary albumin excretion, and high-sensitivity C-reactive protein levels and negatively associated with estimated glomerular filtration rates, independent of other factors. Plasma aldosterone concentrations showed no significant relationships with these indices. In patients with primary aldosteronism, serum soluble (pro)renin receptor concentrations, but not plasma aldosterone concentrations, showed significant associations with organ damage, suggesting that the serum soluble (pro)renin receptor level could be a high-risk biomarker of organ damage.

Serum Soluble Receptor for AGE (sRAGE) Levels Are Associated With Unhealthy Lifestyle and Nonalcoholic Fatty Liver Disease.

OBJECTIVES:Nonalcoholic fatty liver disease (NAFLD) has been demonstrated to be positively associated with serum advanced glycation end products (AGEs) and negatively with soluble receptor for AGE (sRAGE) in a few small studies. We aimed to test the association between lifestyle and sRAGE levels and the association between sRAGE levels or AGEs intake and NAFLD, insulin resistance (IR), and elevated alanine aminotransferase (ALT).METHODS:Cross-sectional analysis among participants of a screening study. Fasting blood tests and serum sRAGE levels were obtained. NAFLD and insulin resistance were evaluated by ultrasonography and homeostasis model assessment, respectively. Nutritional intake was measured by food frequency questionnaire, and the intake of dietary AGEs was calculated.RESULTS:A total of 743 subjects were included (52.6% men, mean age 58.83 ± 6.58 years, 38.7% NAFLD). Exercise was independently protective from low sRAGE levels (odds ratio [OR] = 0.71, 95% confidence interval 0.52–0.97, P = 0.031). Pack-years, working time, and sedentary time (OR = 1.51, 1.03–2.22, P = 0.036; OR = 1.66, 1.18–2.35, P = 0.004; OR = 1.64, 1.18–2.29, P = 0.004, respectively), and intake of red and/or processed meat or processed meat alone (OR = 1.01, 1.04–2.21, P = 0.045; OR = 1.49, 1.00–2.21, P = 0.048, respectively) were associated with increased odds for low sRAGE levels. Low sRAGE levels were independently associated with elevated ALT (OR = 1.69, 1.11–2.57, P = 0.014) and NAFLD with elevated ALT (OR = 2.17, 1.23–3.83, P = 0.007). High intake of dietary AGEs was associated with IR (OR = 2.04, 1.25–3.34 P = 0.004).DISCUSSION:Lifestyle is associated with sRAGE levels and, in turn, low levels of sRAGE are associated with NAFLD and elevated ALT.

Increased Serum Soluble Urokinase Plasminogen Activator Receptor Predicts Short-Term Outcome in Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure.

Aims Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR > 16.26 ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients.

Methotrexate use, not interleukin 33, is associated with lower carotid intima-media thickness in patients with rheumatoid arthritis

BackgroundRheumatoid arthritis is a risk factor for early mortality due to cardiovascular disease. Interleukin-33 appears to protect against the development of atherosclerosis. The purpose of this study was to investigate the relationship between serum levels of interleukin-33 and its soluble receptor with the presence of subclinical carotid atherosclerosis in rheumatoid arthritis patients.MethodsRheumatoid arthritis patients without atherosclerotic disease were subjected to clinical and laboratory assessments, including carotid ultrasound. Interleukin-33 and its soluble receptor serum levels were measured by ELISA.Results102 patients were included. The prevalence of carotid plaques was 23.5% and the median intima-media thickness was 0.7 mm. The median interleukin-33 and its soluble receptor concentration was 69.1 and 469.8 pg/ml. No association was found between serum interleukin-33 or its soluble receptor and intima-media thickness or plaque occurrence. Each 0.1 mm increase of intima-media thickness raised the odds of plaque occurrence by 5.3-fold, and each additional year of rheumatoid arthritis duration increased the odds of plaque occurrence by 6%. Each additional year in patients age and each one-point increase in the Framingham Risk Score were associated with a 0.004 mm and 0.012 mm increase in intima-media thickness. Methotrexate use was associated with a 0.07 mm reduction in intima-media thickness.ConclusionsInterleukin-33 and its soluble receptor were not associated with subclinical atherosclerosis. Traditional risk factors for atherosclerosis and rheumatoid arthritis duration were associated with intima-media thickness and plaque occurrence; methotrexate use was associated with a lower intima-media thickness.

Cytokine profile of macrophage activation syndrome associated with Kawasaki disease

The present study aimed to assess the kinetics of cytokine release and compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) associated with Kawasaki disease (KD). Serum neopterin, interleukin (IL)-18, IL-6 and soluble tumour necrosis factor receptor type I (sTNFR-I) and sTNFR-II levels were determined using enzyme-linked immunosorbent assay in 78 patients with KD, including five with MAS. Results were compared to the clinical features of MAS. Serum neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were significantly elevated in KD patients with MAS compared to those in the acute phase. Receiver operating characteristic curve analysis revealed areas under the curve and cutoff values of neopterin, IL-18, sTNFR-II levels and sTNFR-II/I ratio were 0.9750/30.0 nmol/L, 0.9813/1165 ng/mL, 0.9969/16,600 pg/mL and 0.9875/4.475, respectively. Serum sTNFR-II levels correlated positively with disease activity. These findings indicate that overproduction of interferon (IFN)–γ and TNF-α reflected by increased serum levels of neopterin and sTNFR-II are closely associated with the pathogenesis of MAS associated with KD. Serum sTNFR-II levels might be a useful marker to diagnose the transition to MAS.

Vitamin D3 supplementation ameliorates ovariectomy-induced cardiac apoptotic and structural changes in adult albino rats.

The effect of vitamin D on cardiac dysfunction after menopause is still under investigation. Therefore, we investigated the effect of vitamin D3 on cardiac apoptotic and structural changes in ovariectomized rats. Forty adult female albino rats were divided into 4 equal groups: sham rats, sham rats treated with vitamin D3, ovariectomized rats, and ovariectomized rats treated with vitamin D3 (500 IU/kg per day for 6 weeks, orally). Body mass, blood pressure, heart rate, and whole heart mass (WHM) were measured. Serum soluble receptors of advanced glycation end products (sRAGE), C-reactive protein, malondialdehyde, and total antioxidant capacity were estimated. Cardiac sections were stained with haematoxylin-eosin and Masson's trichrome stain. Fas and FasL apoptosis-related proteins were detected by immunohistochemistry. Vitamin D3 treatment significantly decreased ovariectomy-induced cardiac Fas and FasL apoptosis-related proteins, whole heart mass, body mass, C-reactive protein, and malondialdehyde accompanied by decreased inflammation and reduced collagen deposition between cardiac muscle fibres. However, vitamin D3 significantly increased total antioxidant capacity and sRAGE in ovariectomized and sham treated groups. Our findings suggest that vitamin D3 treatment can prevent ovariectomy-induced cardiac structural and apoptotic changes in rats via increasing sRAGE and antioxidant activity. Our results suggest that vitamin D3 has therapeutic effect against postmenopausal cardiovascular disease.

Correlation of Serum and Ascitic Fluid Soluble Form Urokinase Plasminogen Activator Receptor Levels With Patient Complications, Disease Severity, Inflammatory Markers, and Prognosis in Patients With Severe Acute Pancreatitis.

Objectives The aim of the study was to investigate the correlation of serum and ascitic fluid soluble form urokinase plasminogen activator receptor (suPAR) levels with patients' complications, disease severity, inflammatory markers, and prognosis in patients with severe acute pancreatitis (SAP). Methods Fifty patients with SAP, 47 patients with mild acute pancreatitis, and 50 healthy controls were enrolled. Serum samples were obtained from all participants after enrollment; meanwhile, ascitic fluid samples were collected from 20 patients with SAP who developed ascites. Serum and ascitic fluid suPAR levels were determined by enzyme-linked immunosorbent assay. Results Serum suPAR level was greatly elevated in patients with SAP than patients with mild acute pancreatitis and healthy controls. Receiver operating characteristic curve showed that serum suPAR presented with good value in predicting risk of pancreatic necrosis, pancreatic infection, and multiple organ dysfunction syndrome, whereas serum suPAR did not predict mortality. Serum suPAR level was also positively correlated with Acute Physiology and Chronic Health Evaluation II score, Balthazar index, and Sequential Organ Failure Assessment score. As to ascitic fluid suPAR, it was positively correlated with serum suPAR level, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, risk of pancreatic infection, and multiple organ dysfunction syndrome. Conclusions Serum and ascetic fluid suPAR levels could be served as markers for disease severity and risk of severe complications in patients with SAP.

Polymorphisms of T149C and T950C genes in osteoprotegerin promoter sites and the relationship between serum osteoprotegerin levels and coronary heart disease

To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD). 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD. All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD. The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.