OBJECTIVE: To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes in patients with multiple myeloma (MM). METHODS: Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RT-qPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve. RESULTS: The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group (P<0.001), while the expression level of miR-146a between the two groups was not significantly different (P>0.05). The expression level of miR-21 was strongly negatively correlated with serum β₂-microglobulin concentration (r=-0.830), and weakly negatively correlated with serum creatinine, corrected serum calcium, and cystatin C (r=-0.488, -0.282, -0.627). The expression levels of Let-7b and miR-18a were also weakly negatively correlated with the corrected serum calcium, β₂-microglobulin, and cystatin C concentration (r=-0.305, -0.362, -0.461; -0.317, -0.542, -0.434). However, there was no significant correlation between the expression level of miR-146a and routine laboratory parameters in MM patients. The overall survival rate of MM patients with low expression level of miR-21, miR-18a, and Let-7b significantly decreased compared with high expression level group (P<0.05), however, the expression level of miR-146a was not related to the overall survival rate. CONCLUSION Aberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM, which are associated with a worse overall survival rate.
Calcium/metabolism* ; Creatinine/metabolism* ; Cystatin C/metabolism* ; Exosomes/metabolism* ; Humans ; MicroRNAs/metabolism* ; Multiple Myeloma/metabolism*

OBJECTIVE: To explore the predicting performance of renal resistive index (RRI), semi quantitative power Doppler ultrasound (PDU) score and serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with cardiac failure or sepsis. METHODS: A prospective, observational study was conducted. Critically ill patients with acute cardiac failure or sepsis admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 1st to December 31st in 2018 were enrolled. In addition to the demographic data, serum Cys C, RRI, and PDU score were measured within 6 hours after admission to ICU. Renal function was assessed on day 5 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients who proceeded to AKI stage 2 or 3 within 5 days from admission were defined as the AKI 2-3 group; other patients were classified into the AKI 0-1 group. The differences of each index were compared in all patients, cardiac failure patients and sepsis patients between the two groups. Multivariate binary Logistic regression was carried out to identify the independent risk predictors of AKI 2-3. Receiver operator characteristic (ROC) curves were plotted to examine the values of Cys C, RRI, PDU score, and RRI+PDU in predicting AKI 2-3. RESULTS: Thirty-seven patients with cardiac failure (11 with no AKI, 10 with AKI stage 1, 3 with AKI stage 2, and 13 with AKI stage 3) and 26 patients with sepsis (8 with no AKI, 2 with AKI stage 1, 7 with AKI stage 2, and 9 with AKI stage 3) were recruited. In all patients as well as the subgroup of cardiac failure, compared with the AKI 0-1 group, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, rate of continuous renal replacement therapy (CRRT), 28-day mortality, serum creatinine (SCr), Cys C and RRI were higher in AKI 2-3 group, and urine output, PDU score were lower; in the subgroup of sepsis, rate of CRRT, SCr, and Cys C were higher in AKI 2-3 group, and urine output was lower. Multivariate Logistic regression analysis found that Cys C and PDU score were independent risk factors for AKI 2-3 in all patients [Cys C: odds ratio (OR) = 11.294, 95% confidence interval (95%CI) was 2.801-45.541, P = 0.001; PDU score: OR = 0.187, 95%CI was 0.056-0.627, P = 0.007]; RRI and PDU score were independent risk factors for AKI 2-3 in patients with cardiac failure [RRI (×10): OR = 6.172, 95%CI was 0.883-43.153, P = 0.067; PDU score: OR = 0.063, 95%CI was 0.007-0.584, P = 0.015]; Cys C was the independent risk factor for AKI 2-3 in patients with sepsis (OR = 22.830, 95%CI was 1.345-387.623, P = 0.030). It was shown by ROC curve analysis that: in the subgroup of cardiac failure, the predictive values of RRI, PDU score and Cys C were well [area under the curve (AUC) and 95%CI was 0.839 (0.673-0.942), 0.894 (0.749-0.971), 0.777 (0.610-0.897), all P < 0.01]. RRI+PDU performed best in predicting AKI (AUC = 0.956, 95%CI was 0.825-0.997, P < 0.01), and the predictive value was higher than Cys C [AUC (95%CI): 0.956 (0.825-0.997) vs. 0.777 (0.610-0.897), P = 0.034]. In the subgroup of sepsis, the predictive value of Cys C was well (AUC = 0.913, 95%CI was 0.735-0.987, P < 0.01), however, the predictive value of RRI, PDU, RRI+PDU were poor. CONCLUSIONS RRI and PDU score effectively predict AKI stage 2 or 3 in cardiac failure patients, but not in patients with sepsis. The predictive values of Cys C for AKI are similar in patients with cardiac failure or sepsis.
Acute Kidney Injury/diagnosis* ; Cystatin C/metabolism* ; Heart Failure ; Humans ; Intensive Care Units ; Prognosis ; Prospective Studies ; ROC Curve ; Sepsis ; Ultrasonography

Animals ; Cognitive Dysfunction ; metabolism ; Cystatin C ; pharmacology ; Hippocampus ; drug effects ; Insulin Resistance ; physiology ; Neurons ; drug effects ; Rats ; Rodentia

OBJECTIVETo study the relationship between cystatin C and cerebral infarction and explore the role of cystatin C in the protection against cerebral infarction.

METHODEighty-three patients with cerebral infarction and 71 randomly selected age- and gender-matched patients in the Department of Neurology (control group) were enrolled in this study. Fasting whole blood (3 ml) was obtained from the patients in both groups and the sera were separated to determine the levels of cystatin C using particle reinforced immunoturbidimetric assay.

RESULTSThe serum cystatin C level was significantly lower in the cerebral infarction group than in the control group (1.62-/+0.31 vs 2.23-/+0.22 mg/L, P<0.01).

CONCLUSIONSCystatin C is closely related to cerebral infarction probably as a protective factor against cerebral infarction.

Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Cerebral Infarction ; blood ; metabolism ; Cystatin C ; blood ; metabolism ; Female ; Humans ; Male ; Middle Aged

We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.
Animals ; Autophagy ; physiology ; Beclin-1 ; metabolism ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; therapy ; Cystatin C ; genetics ; metabolism ; Disease Models, Animal ; Gene Expression ; Gene Knockdown Techniques ; Hyperbaric Oxygenation ; Lysosomes ; metabolism ; pathology ; Male ; Microtubule-Associated Proteins ; metabolism ; Neurons ; metabolism ; pathology ; Neuroprotection ; physiology ; Oxygen ; therapeutic use ; Random Allocation ; Rats, Sprague-Dawley ; Rats, Transgenic ; Reperfusion Injury ; metabolism ; pathology ; therapy

OBJECTIVETo investigate the in vivo inhibition of extract of Fructus lycii (FL) on the expressions of cathepsin B (Cat B) and cystatin C (Cys C) in high-fat diet and hydroquinone (HQ) induced model mice with age-related macular degeneration (AMD), and to explore the in vitro effects of lutein and zeaxanthin on hydrogen peroxide (H2O2,) induced expressions of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) on ARPE-19 cells.

METHODSFifty female 8-month-old C57BL/6 mice were recruited in this research. Ten mice fed with regular diet was taken as the age control group. The rest 40 mice were fed with high fat diet for 6 months, followed by adding HQ (0. 8%) in the drinking water for 3 consecutive months. Then the modeled mice were randomly divided into the model control group (n =10), the high (at the daily dose of 3.75 g/kg), middle (at the daily dose of 2.50 g/kg), and low dose (at the daily dose of 1.25 g/kg) FL groups, 10 in each group. The extract of FL at each dose was respectively administered to mice by gastrogavage for 3 successive months. By the end of the experiment, the mice were killed and their eyeballs were removed. The protein expressions of Cat B and Cys C were observed by immunohistochemical assay. The mRNA and protein expressions of Cat B and Cys C were detected by real-time PCR and Western blot respectively. The drug concentrations of H2O2, lutein, and zeaxanthin were screened and detected using the activity of cell proliferation. The protein expressions of MMP-2 and TIMP-2 were detected using Western blot.

RESULTSCompared with the age control group, the mRNA and protein expressions of Cat B and Cys C were significantly higher in the in vivo model control group (P <0.05, P <0.01). The mRNA expressions of Cat B and Cys C were weaker in the middle and high dose FL groups than in the model control group (P <0. 05, P <0. 01). In in vitro cells, lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells (P <0. 05, P <0. 01).

CONCLUSIONSExtract of FL could down-regulate the high protein expressions of Cat B and Cys C in high-fat diet and HQ induced model mice. Lutein and zeaxanthin could down-regulate the protein expressions of MMP-2 and TIMP-2 in H202 induced ARPE-19 cells.

Animals ; Cathepsin B ; metabolism ; Cystatin C ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hydrogen Peroxide ; Lutein ; pharmacology ; Macular Degeneration ; prevention & control ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Inbred C57BL ; Pigment Epithelium of Eye ; drug effects ; metabolism ; Tissue Inhibitor of Metalloproteinase-2 ; metabolism ; Xanthophylls ; pharmacology ; Zeaxanthins

OBJECTIVETo observe the effects of Jinshuibao Capsule (JC) combined losartan potassium on some indices of early renal damage of hypertension patients of yin and yang deficiency syndrome (YYDS), such as levels of serum cystatin C (Cys C), beta2-microglobulin (beta2-MG), hypersensitive C-reactive protein (hs-CRP), uric acid (UA), blood pressure, blood lipids, and fasting blood glucose (FBG), and to explore their protective effects on early renal damage of hypertension patients and on the metabolisms of blood lipids and blood glucose.

METHODSTotally 106 hypertension patients of YYDS were randomly assigned to two groups, 53 patients in the control group (treated by losartan potassium) and 53 patients in the treatment group (treated by JC + losartan potassium). The treatment lasted for 16 weeks. The serum changes of UA, Cys C, beta2-MG, hs-CRP, blood lipids [including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C)], and FBG levels were measured to evaluate the renal protective effects and to assess their effect on the metabolisms of blood lipids and blood glucose.

RESULTSCompared with before treatment in the same group, the systolic blood pressure (SBP) decreased in the two groups after treatment, showing statistical difference (P < 0.05, P < 0.01), but there was no statistical difference between the two groups (P > 0.05). The diastolic blood pressure (DBP) was not obviously declined in the two groups after treatment, showing no statistical difference. Compared with before treatment in the same group, the LDL-C level decreased obviously after treatment in the control group. But there was no obvious change in FBG, TC, HDL-C, and TG in the control group, showing no statistical difference when compared with before treatment (P < 0.05). The FBG, TC, and LDL-C obviously decreased in the treatment group more obviously after treatment than before treatment, showing statistical difference (P < 0.05, P < 0.01). There was no statistical difference when compared with the control group after treatment (P > 0.05). Compared with before treatment in the same group, the levels of UA, Cys C, beta2-MG, and hs-CRP all decreased in the two groups, showing statistical difference (P < 0.05, P < 0.01). The SCr level decreased in the treatment group more obviously after treatment than before treatment, showing statistical difference (P < 0.05). Compared with the control group after treatment, the levels of Cys C, beta2-MG, and hs-CRP decreased more obviously after treatment in the treatment group, showing statistical difference (P < 0.05).

CONCLUSIONSJC combined losartan potassium showed better effects in treating early renal damage of hypertension patients of YYDS. They could protect and stabilize the renal functions more effectively. JC could regulate blood lipids and blood glucose.

Aged ; Aged, 80 and over ; C-Reactive Protein ; metabolism ; Cystatin C ; blood ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypertension ; diagnosis ; drug therapy ; pathology ; Kidney ; pathology ; Losartan ; therapeutic use ; Male ; Middle Aged ; Phytotherapy ; Yang Deficiency ; drug therapy ; Yin Deficiency ; drug therapy ; beta 2-Microglobulin ; blood

BACKGROUND/AIMS: Several studies suggested that serum cystatin C (CysC) is more useful than serum creatinine (Cr) for the assessment of renal function in patients with liver cirrhosis. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and normal Cr level. METHODS: We enrolled patients with cirrhotic ascites and a normal serum Cr level (<1.2 mg/dL). GFR was measured by 99mTc-DTPA renal scan. Serum Cr, CysC, and Cr clearance (CCr) were measured on the same day. Significant renal impairment and severe renal impairment were defined as GFR <60 mL/min and GFR <30 mL/min, respectively. RESULTS: Eighty-nine patients with cirrhotic ascites were enrolled in the study (63 men and 26 women; age, 55+/-11 years). Forty-seven (52.8%) and 42 (47.2%) patients were in Child-Pugh grade B and C, respectively. Serum Cr and CysC levels and GFR were 0.8+/-0.2 mg/dL, 1.1+/-0.3 mg/L, and 73.4+/-25.5 mL/min, respectively. Significant and severe renal impairment were noted in 28 (31.5%) and 2 (2.2%) patients, respectively. GFR was well correlated with serum Cr, CysC, and e-GFRMDRD, while it was not correlated with e-GFRC&G. In multivariate analysis, only CysC was significantly correlated with GFR (beta, 45.620; 95% CI, 23.042-68.198; P<0.001). Serum CysC level was the only independent predictor for significant renal impairment. CONCLUSIONS: Significant renal dysfunction was not rare in patients with cirrhotic ascites, even their serum Cr level is normal. Serum CysC is a useful marker for detecting significant renal dysfunction in these patients.
Adult ; Aged ; Area Under Curve ; Biological Markers/blood ; Creatinine/blood ; Cystatin C/*blood ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Diseases/complications/*diagnosis/metabolism ; Kidney Function Tests ; Liver Cirrhosis/*complications/metabolism ; Male ; Middle Aged ; Multivariate Analysis ; ROC Curve ; Severity of Illness Index ; Technetium Tc 99m Pentetate/diagnostic use

Serum creatinine level is the most commonly used indices for assessment of glomerular filtration rate (GFR), even though these indices have been shown to have some limitations in clinical practice. We investigated the diagnostic efficacy of serum cystatin C compared to that of serum creatinine levels and identified the relating factors associated with changes in serum cystatin C levels in gout patients with renal impairment. A total of 68 gouty patients with renal impairment were enrolled in this study. Diagnostic efficacy of serum cystatin C levels was evaluated through non-parametric receiver operating characteristic (ROC) analysis. The risk factors for changes in serum cystatin C levels were confirmed using multivariate regression analysis. With 24-hr urine creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702, P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the clinical parameters for increased serum cystatin C are a higher stage of chronic kidney disease, older age, use of allopurinol, and lower high density lipoprotein-cholesterol. The area under the curve (AUC) at ROC plots identified that of serum cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C is a reliable endogenous marker for the assessment of renal function or GFR in gout patients with renal impairment.
Age Factors ; Aged ; Allopurinol/therapeutic use ; Area Under Curve ; Biological Markers/metabolism ; Cholesterol, HDL/blood ; Creatinine/blood/urine ; Cystatin C/*blood ; Glomerular Filtration Rate ; Gout/complications/*diagnosis ; Gout Suppressants/therapeutic use ; Humans ; Male ; Middle Aged ; ROC Curve ; Renal Insufficiency/complications/*diagnosis ; Risk Factors