• Title/Summary/Keyword: cystatin

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Inhibitory Effects of a Recombinant Viral Cystatin Protein on Insect Immune and Development (바이러스 유래 시스타틴 재조합 단백질의 곤충 면역 및 발육 억제효과)

  • Kim, Yeongtae;Eom, Seonghyun;Park, Jiyeong;Kim, Yonggyun
    • Korean journal of applied entomology
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    • v.53 no.4
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    • pp.331-338
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    • 2014
  • Cystatins (CSTs) are reversible and competitive inhibitors of C1A cysteine proteases, corresponding to papain-like cathepsins in plants and animals. A viral CST (CpBV-CST1) was identified from a polydnavirus, Cotesia plutellae bracovirus (CpBV). Our previous study indicated that a transient expression of CpBV-CST1 interfered with immune response and development of Plutella xylostella larvae. To directly demonstrate the protein function, this study produced a recombinant CpBV-CST1 protein (rCpBV-CST1) using bacterial expression system to determine its inhibitory activity against cysteine protease and to assess its physiological alteration in insect immune and development. The open reading frame of CpBV-CST1 encodes a polypeptide of 138 amino acids (${\approx}15kDa$). rCpBV-cystatin protein in BL21 STAR (DE3) competent cells containing a recombinant pGEX4T-3:CpBV-CST1 was over-expressed by 0.5 mM IPTG for 4 h. In biological activity assay, the purified rCpBV-CST1 showed a significant inhibition against papain activity. It inhibited a cellular immune response of hemocyte nodule formation in the beet armyworm, Spodoptera exigua. Moreover, its oral administration retarded larval development of the diamondback moth, Plutella xylostella in a dose-dependent manner. These results suggest that CpBV-CST1 may be applied to control insect pest populations.

Nanotechnology-enabled diagnostics for the correlation between serum APN, Cystatin C and MMP-9 levels in patients with hypertension during pregnancy

  • Hui Deng;Yu-Lan Fan;Yu-Qi Wang;Yin Yang;Da-Yong Jiang
    • Advances in nano research
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    • v.17 no.3
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    • pp.213-219
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    • 2024
  • Nanotechnology is one of the critical factors involved in enhancing the sensitivity of serum biomarker detection. To explore the relationship between serum APN, Cystatin C and MMP-9 levels in patients with hypertension during pregnancy and the severity and prognosis of the disease. A total of 75 cases of hypertensive disorder complicating pregnancy (HDCP) patients who were admitted to the hospital from February 5, 2023 to May 9, 2024, were selected as the study group, and 70 healthy pregnant women who were in the same gestational week were selected as the control group. The serum APN, MMP-9 and Cys C levels of pregnant women and HDCP patients with different disease severity were compared between the two groups, and the receiver characteristic curve (ROC) was used to analyze its diagnostic value. The serum APN, MMP-9 and Cys C levels of HDCP patients with different prognosis were compared, and the factors affecting the prognosis of patients were analyzed by Logistic regression. Nanoparticles could aslo enable the sensitive detection and quantification of APN, Cystatin C, and MMP-9 in serum samples, thus increasing the accuracy of the study. The serum MMP-9 and Cys C levels of pregnant women in the study group were significantly increased, and the APN level was significantly decreased (P<0.05). Serum MMP-9 and Cys C levels in patients with pregnancy-induced hypertension, mild preeclampsia, and severe preeclampsia gradually increased (r=0.768, 0.766; P<0.001), and APN levels gradually decreased (r=-0.748, P< 0.001). In the diagnosis of patients with HDCP, the sensitivity, specificity and AUC of APN single diagnosis were 70.00%, 82.67% and 9.848 respectively. The sensitivity, specificity and AUC of MMP-9 single diagnosis were 82.86%, 74.67% and 298.300 respectively. The sensitivity, specificity and AUC of Cys C single diagnosis were 80.00%, 74.67% and 1.301 respectively. There were significant differences in age, BMI, parity, dysthymia, disease severity, APN, MMP-9 and Cys between patients with poor prognosis of HDCP and patients with good prognosis of HDCP (P<0.001). The patient's age, BMI, disease severity, APN, MMP-9 and Cys Cwere all related to HDCP. They were related risk factors of HDCP (P<0.05).

Usefulness of serum cystatin C to determine the dose of vancomycin in neonate

  • Shin, Jeong Eun;Lee, Soon Min;Eun, Ho Seon;Park, Min Soo;Park, Kook In;Namgung, Ran
    • Clinical and Experimental Pediatrics
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    • v.58 no.11
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    • pp.421-426
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    • 2015
  • Purpose: The vancomycin dosage regimen is regularly modified according to the patient's glomerular filtration rate (GFR). In the present study, we aimed to assess the usefulness of serum cystatin C (Cys-C) concentration, compared with serum creatinine (SCr) concentration, for predicting vancomycin clearance (CLvcm) in neonates. Methods: We retrospectively analyzed the laboratory data of 50 term neonates who were admitted to the neonatal intensive care unit and received intravenous vancomycin, and assessed the pharmacokinetic profiles. Creatinine clearance (CLcr) and GFR based on Cys-C (GFRcys-c) were estimated using the Schwartz and Larsson formulas, respectively. Results: The mean CLvcm (${\pm}$standard deviation) was $74.52{\pm}31.17L/hr$, the volume of distribution of vancomycin was $0.67{\pm}0.14L$, and vancomycin half-life was $9.16{\pm}17.42hours$. The SCr was $0.46{\pm}0.25mg/dL$ and serum Cys-C was $1.43{\pm}0.34mg/L$. The peak and trough concentrations of vancomycin were $24.65{\pm}14.84$ and $8.10{\pm}5.35mcg/mL$, respectively. The calculated GFR based on serum creatinine concentration (GFR-Cr) and GFRcys-c were $70.2{\pm}9.45$ and $63.6{\pm}30.18mL/min$, respectively. The correlation constant for CLvcm and the reciprocal of Cys-C (0.479, P=0.001) was significantly higher than that for CLvcm and the reciprocal of SCr (0.286, P=0.044). GFRcys-c was strongly correlated with CLvcm (P=0.001), and the correlation constant was significantly higher than that for CLvcm and CLcr (0.496, P=0.001). Linear regression analysis showed that only GFRcys-c was independently and positively correlated with CLvcm (F=41.9, P<0.001). Conclusion: The use of serum Cys-C as a marker of CLvcm could be beneficial for more reliable predictions of serum vancomycin concentrations, particularly in neonates.

Association between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus without Nephropathy

  • Kim, Hye Jeong;Byun, Dong Won;Suh, Kyoil;Yoo, Myung Hi;Park, Hyeong Kyu
    • Diabetes and Metabolism Journal
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    • v.42 no.6
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    • pp.513-518
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    • 2018
  • Background: Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment. Methods: A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ${\leq}0.65mg/L$; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ${\geq}0.95mg/L$). Results: The proportion of patients with diabetic retinopathy (DR) (P for trend <0.001), coronary heart disease (CHD) (P for trend <0.001), and stroke (P for trend <0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables. Conclusion: Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.

Influence of Postconceptional Age on the Renal Biomarkers in Very-Low-Birth-Weight Infants

  • Lee, Ro Sie;Shin, So Young;Jung, Won Ho;Park, Jae Hyun
    • Neonatal Medicine
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    • v.28 no.2
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    • pp.65-71
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    • 2021
  • Purpose: We investigated whether consecutive levels of new emerging renal biomarkers, including serum cystatin C (CysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL)/creatinine (Cr) ratio, were affected by postconceptional age in very-low-birth-weight (VLBW) infants. Methods: Repeatedly measured samples for each infant were divided into four groups according to postnatal age: at birth (stage I), 3 to 7 days postnatally (stage II), 8 to 28 days postnatally (stage III), and >28 days postnatally (stage IV). The association between renal biomarkers and postconceptional age was assessed using Pearson's correlation coefficient, and the mean values of renal biomarkers in the four stages were compared using repeated-measures analysis of variance. Results: For samples measured at birth, serum CysC (r=-0.358, P=0.032) and urinary NGAL/Cr ratio (r=-0.522, P=0.001) were negatively correlated with gestational age, whereas serum Cr (r=0.148, P=0.390) was not. In addition, for all samples measured, serum CysC (r=-0.209, P=0.012), urinary NGAL/Cr ratio (r=-0.536, P<0.001), and serum Cr (r=-0.311, P<0.001) were negatively correlated with postconceptional age. Compared with the mean values of the postnatal age-specific stages, serum CysC showed no significant differences in any of the four stages. However, the urinary NGAL/Cr ratio in stage IV was significantly different from those in stages I to III. Conclusion: Although urinary NGAL/Cr ratio and serum CysC were negatively correlated with postconceptional age considering renal development, serum CysC showed no significant differences in any of the four postnatal age-specific stages. Urinary NGAL/Cr ratio at >28 days postnatally seems to be more affected by postconceptional age than serum CysC in VLBW infants.

Low Skeletal Muscle Mass and Clinical Outcomes in Chronic Obstructive Pulmonary Disease

  • Yong Jun Choi;Hye Jung Park;Jae Hwa Cho;Min Kwang Byun
    • Tuberculosis and Respiratory Diseases
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    • v.86 no.4
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    • pp.272-283
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    • 2023
  • Background: In patients with chronic obstructive pulmonary disease (COPD), decreased muscle mass is a frequently encountered comorbidity in clinical practice. However, the evaluation of muscle mass in patients with COPD in real-world practice is rare. Methods: We retrospectively reviewed the electronic medical records of all patients with COPD who underwent bioelectrical impedance analysis at least once between January 2011 and December 2021 in three hospitals. Then, we analyzed the performance rate of muscle mass measurement in the patients and the correlation between muscle mass, clinical parameters, and COPD prognosis. Results: Among the 24,502 patients with COPD, only 270 (1.1%) underwent muscle mass measurements. The total skeletal muscle mass index was significantly correlated with albumin, alanine transaminase, and creatinine to cystatin C ratio in patients with COPD (r=0.1614, p=0.011; r=0.2112, p=0.001; and r=0.3671, p=0.001, respectively). Acute exacerbation of COPD (AE COPD) was significantly correlated with muscle mass, especially the truncal skeletal muscle mass index (TSMI) in males (r=-0.196, p=0.007). In the multivariate analysis, TSMI and cystatin C were significant risk factors for AE COPD (hazard ratio, 0.200 [95% confidence interval, CI, 0.048 to 0.838] and 4.990 [95% CI, 1.070 to 23.278], respectively). Conclusion: Low muscle mass negatively affects the clinical outcomes in patients with COPD. Despite its clinical significance, muscle mass measurement is performed in a small proportion of patients with COPD. Therefore, protocols and guidelines for the screening of sarcopenia in patients with COPD should be established.

Construction of a Transgenic Tobacco Expressing a Polydnaviral Cystatin (폴리드나바이러스 유래 시스타틴 유전자 발현 형질전환 담배 제작)

  • Kim, Yeongtae;Kim, Eunsung;Park, Youngjin;Kim, Yonggyun
    • Korean journal of applied entomology
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    • v.54 no.1
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    • pp.7-15
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    • 2015
  • CpBV (Cotesia plutellae bracovirus) is a polydnavirus and encodes a cystatin (CpBV-CST1) gene. Its overexpression suppresses insect immunity and alters insect developmental processes. This study aimed to construct a genetically modified (GM) tobacco to further explore the physiological function of the viral cystatin and to apply to control insect pests. To this end, the transgenic tobacco lines were screened in expression of the target gene and assessed in insecticidal activity. A recombinant vector (pBI121-CST) was prepared and used to transform a bacterium, Agrobacterium tumefasciens. The transformed bacteria were used to generate transgenic tobacco lines, which were induced to grow callus and resulted in about 92% of shoot regeneration. The regenerated plants were screened by PCR analysis to confirm the insertion of the target gene in the plant genome. In addition, the expression of the target gene was assessed in the regenerated plants by quantitative real-time PCR (qRT-PCR). The qRT-PCR analysis showed that the transgenic line plant expressed the target gene about 17 times more than the control tobacco, indicating a stable insertion and expression of the target gene in the transgenic tobacco line. The insecticidal activity was then analyzed using the screened transgenic tobacco lines against the teneral 1st instar larvae of the oriental tobacco budworm, Helicoverpa assulta. Though there was a variation in the insecticidal efficacy among transgenic lines, T9 and T12 lines exhibited more than 95% mortality at 7 days after feeding treatment. These results suggest that CpBV-CST1 is a useful genetic resource to be used to generate GM crop against insect pests.

Glomerular Filtration Rate Measurements Using $^{99m}$Technetium-mercaptoacetyltriglycine Dynamic Renal Scintigraphy in Children with Renal Disease (신장 질환이 있는 소아에서 $^{99m}$Technetium-mercaptoacetyltriglycine ($^{99m}Tc$-MAG3) 신장 스캔에 의한 사구체 여과율 측정)

  • Yoon, In Ae;Yun, Ki Wook;Lim, In Seok;Choi, Eung Sang;Yoo, Byung Hun
    • Childhood Kidney Diseases
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    • v.17 no.2
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    • pp.57-64
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    • 2013
  • Purpose: In children, 24-hour urine collections are unreliable for evaluating glomerular filtration rate (GFR) because of the difficulty of regulating voiding and the daily variation of urinary creatinine up to 25%. Additionally, creatinine clearance (Ccr) based on urinary creatinine is considered inaccurate. The purpose of this study was to compare estimated GFR determined using Ccr, formulas with serum cystatin C and creatinine, and $^{99m}Tc$-mercaptoacetyltriglycine (MAG3) dynamic renal scintigraphy. Methods: This retrospective study included 101 patients (age, <18 years) who visited Chung-Ang University Hospital between July 2011 and August 2012. GFR was estimated using 24-hour urinary creatinine, five formulas with serum creatinine and cystatin C, and $^{99m}Tc$-MAG3 renal scan. Results: Of the 101 patients, glomerular renal diseases were present in 60 patients (59.4%) and non-glomerular diseases were present in 41 patients (40.6%). There was a significant correlation between estimated GFR determined using $^{99m}Tc$-MAG3 renal scan and Ccr (r=0.389, P <0.001). The correlation values between estimated GFR determined using $^{99m}Tc$-MAG3 renal scan and each formula of Schwartz, Counahan-Barratt, Cockcroft-Gault, Filler and Lepage, and Bokencamp were 0.265 (P=0.007), 0.128 (P=0.044), 0.230 (P=0.021), 0.356 (P<0.001), and 0.355 (P <0.001), respectively. $^{99m}Tc$-MAG3 renal scan was correlated with estimated-GFR by all formulas in decreased renal function. Conclusion: Estimated GFRs determined using serum creatinine and cystatin C, and $^{99m}Tc$-MAG3 renal scan correlated well with estimated GFR determined using Ccr. $^{99m}Tc$-MAG3 renal scan may be replaced for evaluation of renal function with convenience in patients with renal disease and decreased renal function in childhood.