Yongcheng He

Sarcosine is an important marker for the diagnosis of prostate cancer in urine. A chemiluminescence (CL) sensor based upon silver doped iron-based metal-organic gels (Ag/Fe-MOGs) was constructed for sarcosine determination. The Ag/Fe-MOGs with peroxidase-like activities were synthesized by a simple room temperature method to catalyze hydrogen peroxide to generate reactive oxygen species. During detection, sarcosine was oxidized by sarcosine oxidase (SOx) to produce H₂O₂ which was catalyzed by Ag/Fe-MOGs and accompanied by luminol chemiluminescence. Due to the peroxidase-like activity and high stability of Ag/Fe-MOGs, the luminol chemiluminescence was applied to measure sarcosine from 1 to 50 mM with a detection limit of 0.23 mM. Practical applicability was validated by determining sarcosine in human urine. This work not only offers a simple approach to a prepare catalyst with enzyme-like activity, but also provides an efficient and sensitive strategy for other substances in a rapid and cost-effective approach by replacing enzymes.

Significance Statement: Several microRNAs have been shown to play significant roles in the development of renal injury. The microRNA miR-204-5p is highly enriched in the kidney but its involvement in chronic renal injury is unknown. In this study, the authors report that miR-204-5p abundance is significantly decreased in kidney biopsy samples from patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy. They also found, in a rat model of salt-sensitive hypertension, a mouse model of hypertension, and a mouse model of type 2 diabetes, inhibition of miR-204-5p, or deletion of the Mir204 gene results in upregulation of an injurious molecular pathway and substantial exacerbation of renal injury. These findings provide evidence of a prominent role for miR-204-5p in safeguarding the kidneys against common causes of chronic renal injury. Background: Aberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown. Methods: We used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid–modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury. Results: Kidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13^BN26 rats. Administering anti–miR-204-5p to SS.13^BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti–miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2. Conclusions: These findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDL receptor (LDLR) regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we have identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silico analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of the (P)RR mRNA. Mutating the binding sites for miR-148a in the 3’-UTR of (P)RR mRNA completely abolished the inhibitory effects of miR-148a on (P)RR expression. In line with our recent findings, reduced (P)RR expression resulted in decreased cellular LDL uptake, likely as a consequence of decreased LDLR protein abundance. Overexpressing the (P)RR prevented miR-148a-induced reduction in LDLR abundance and cellular LDL uptake. Our study supports a new concept that miR-148a is a regulator of (P)RR expression. By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.

Indicators for predicting the efficacy of mycophenolate mofetil (MMF) have so far remained elusive. The present study aimed to identify predictive indicators of the efficacy of MMF combined with low-dose prednisone in patients with IgA nephropathy. A total of 598 patients presenting with primary IgA nephropathy at our center were screened. Patients were followed up for 18 months, where the end-point was defined as complete clinical remission. Cox proportional hazards models were performed for analyzing the initial serum creatinine (SCr) concentration to predict incomplete clinical remission. In total, 7 of 71 patients (9.86%) were in complete clinical remission at the final visit. Logistic regression indicated that the hazard ratio (HR) for quartile 4 was significantly higher than the HR for quartile 1 (quartile 4 vs. quartile 1: HR, 2.51; 95% CI, 1.20-5.21; P=0.01). Additional adjustment for the confounding variables, including age, sex, systolic BP, diastolic BP, proteinuria, uric acid, serum triglyceride, hemoglobin, serum albumin, serum total cholesterol and The Oxford classification of the models, did not reduce the HRs for the association between the initial SCr concentration and risk of incomplete clinical remission (quartile 4 vs. quartile 1: HR, 7.27; 95% CI, 1.21-43.63; P=0.03). Each unit increase in the initial SCr concentration was associated with a 67 and 194% increase in the risk of incomplete clinical remission based on model 1 (95% CI, 1.02-2.73; P=0.04) and model 2 (95% CI, 1.01-8.60; P=0.048), respectively. In conclusion, in the present cohort of patients with IgA nephropathy treated with MMF plus low-dose prednisone, the initial SCr concentration was an independent risk factor for incomplete clinical remission.

High plasma LDL cholesterol (LDL-c) concentration is a major risk factor for atherosclerosis. Hepatic LDLR regulates LDL metabolism, and thereby plasma LDL-c concentration. Recently, we identified the (pro)renin receptor [(P)RR] as a novel regulator of LDL metabolism, which regulates LDLR degradation and hence its protein abundance and activity. In silicon analysis suggests that the (P)RR is a target of miR-148a. In this study we determined whether miR-148a could regulate LDL metabolism by regulating (P)RR expression in HepG2 and Huh7 cells. We found that miR-148a suppressed (P)RR expression by binding to the 3’-untranslated regions (3’-UTR) of (P)RR mRNA. Mutating the binding sites for miR-148a in the 3’-UTR of (P)RR mRNA abolished the inhibitory effects of miR-148a on (P)RR expression. In line with our recent findings, reduced (P)RR expression resulted in decreased cellular LDL uptake, likely as a consequence of decreased LDLR protein abundance. Overexpressing the (P)RR prevented miR-148a-induced reduction in LDLR abundance and cellular LDL uptake. Our study supports a new concept that miR-148a is a regulator of (P)RR expression. By reducing (P)RR abundance, miR-148a decreases LDLR protein abundance and consequently cellular LDL uptake.

The heart and kidney are of utmost importance for the maintenance of cardiovascular (CV) homeostasis. The relationship between cardiac remodeling, especially the left ventricular hypertrophy (LVH) and renal damage reflected by the estimated glomerular filtration rate (eGFR), decline in type 2 diabetes mellitus (T2DM) patients is unclear. And it is also unknown whether cardiac remodeling can be used to assess the eGFR decline in T2DM patients.

Dietary salt intake has significant effects on arterial blood pressure and the development of hypertension. Mechanisms underlying salt-dependent changes in blood pressure remain poorly understood, and it is difficult to assess blood pressure salt-sensitivity clinically.