Chronic Kidney Disease Induces Cognitive Impairment in the Early Stage.

OBJECTIVE: Previous research indicates a link between cognitive impairment and chronic kidney disease (CKD), but the underlying factors are not fully understood. This study aimed to investigate the progression of CKD-induced cognitive impairment and the involvement of cognition-related proteins by developing early- and late-stage CKD models in Sprague-Dawley rats. METHODS: The Morris water maze test and the step-down passive avoidance task were performed to evaluate the cognitive abilities of the rats at 24 weeks after surgery. Histopathologic examinations were conducted to examine renal and hippocampal damage. Real-time PCR, Western blotting analysis, and immunohistochemical staining were carried out to determine the hippocampal expression of brain-derived neurotrophic factor (BDNF), choline acetyltransferase (ChAT), and synaptophysin (SYP). RESULTS: Compared with the control rats, the rats with early-stage CKD exhibited mild renal damage, while those with late-stage CKD showed significantly increased serum creatinine levels as well as apparent renal and brain damage. The rats with early-stage CKD also demonstrated significantly impaired learning abilities and memory compared with the control rats, with further deterioration observed in the rats with late-stage CKD. Additionally, we observed a significant downregulation of cognition-related proteins in the hippocampus of rats with early-stage CKD, which was further exacerbated with declining renal function as well as worsening brain and renal damage in rats with late-stage CKD. CONCLUSION: These results suggest the importance of early screening to identify CKD-induced cognitive dysfunction promptly. In addition, the downregulation of cognition-related proteins may play a role in the progression of cognitive dysfunction.

Tanshinone IIA attenuates high glucose-induced epithelial-to-mesenchymal transition in HK-2 cells through VDR/Wnt/ß-catenin signaling pathway.

INTRODUCTION: The progression of diabetic kidney disease (DKD) is closely related to renal tubular epithelial- to-mesenchymal transition (EMT) and tubulointerstitial fibrosis. Tanshinone IIA (TSIIA), extracted from a traditional Chinese medicine named Salvia miltiorrhiza, has been proved to have anti-fibrosis effects. The aim of this study was to investigate the effect of TSIIA on high glucose-induced EMT in human proximal tubular cells (HK-2 cells) and its possible mechanism. MATERIAL AND METHODS: The proliferation of cells exposed to different concentrations of glucose was measured by light microscopy and CCK-8 test. The cells were stimulated with 30 mM glucose and different concentrations of TSIIA (5 µM or 10 µM) for 48 h. Vitamin D receptor (VDR)-siRNA was used to transfect cells, and high glucose and TSIIA treatment were further used to treat cells. The expression of alpha smooth muscle actin (a-SMA) mRNA was detected by qPCR to ensure successful induction of EMT, and the expression of VDR mRNA was detected by qPCR to ensure successful transfection of VDR-siRNA. Protein expression of a-SMA, E-cadherin, VDR, b-catenin and glycogen synthase kinase 3b (GSK-3b) was detected by Western blot analysis. RESULTS: The results showed that high glucose concentration inhibited cell proliferation and promoted EMT in HK-2 cells. TSIIA could reverse high glucose-induced EMT by increasing the level of VDR protein and inhibiting the levels of b-catenin and GSK-3b proteins suggestive of a negative correlation between VDR and the Wnt/b-catenin pathway. After VDR-siRNA transfection and incubation of cells at high glucose concentration, the inhibitory effect of VDR on the expression of b-catenin and GSK-3b of Wnt pathway was suppressed and the b-catenin pathway was activated. When VDR level was restored by TSIIA, the inhibitory effect of VDR on the pathway was also restored and the activation of the pathway was suppressed. CONCLUSIONS: TSIIA was able to attenuate high glucose-induced EMT in HK-2 cells by up-regulating VDR levels, which might be related to the inhibitory effect of VDR on the Wnt pathway.

Expression pattern of aquaporins in patients with primary nephrotic syndrome with edema.

The association between the expression of aquaporins (AQPs) in kidney tissues and the occurrence of edema in nephrotic syndrome (NS) remains unclear. The current study aimed to investigate this association. A total of 54 patients with primary glomerular disease, diagnosed by renal biopsy, were divided into three groups: Control, NS without edema and NS with edema. The expression of AQP1, AQP2, AQP3 and AQP4 in kidney tissues from these patients was assessed using immunohistochemistry, and urinary AQP concentrations were quantified by ELISA. Comparison of the three groups was conducted using one way analysis of variance, independent samples t­test or the Chi­square test. AQP1 was strongly expressed in the proximal tubules. The proportion of the AQP1­positive area in kidney tissues from patients with NS with edema was significantly reduced, in comparison with the other two groups. By contrast, the proportion of the AQP2­positive area in the NS with edema group was significantly higher than that of the other two groups; significant differences were also observed between the control and NS without edema groups for this parameter. Urinary AQP2 concentrations in patients with NS (with and without edema) were significantly higher than that of the control group, and exhibited a significant positive correlation with kidney tissue AQP2 concentrations. The present study demonstrated the abnormal expression pattern of AQP1­AQP4 in the kidney tissues of patients with NS, providing a basis for an improved understanding of the role of AQP in the pathogenesis of NS.

[Pyrolysates of novel latent fragrant compound 3,6-dimethyl-2,5-pyrazinedicarboxylic acid menthol ester].

In order to develop a new tobacco flavor released at high-temperature, the novel latent fragrant compound 3,6-dimethyl-2,5-pyrazinedicarboxylic acid menthol ester (DPAME) was synthesized by esterification using 2,3,5,6-tetramethylpyrazine and menthol as raw materials. In air atmosphere, the pyrolysis behavior of DPAME was investigated using an on-line pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) method at three temperature levels of 300, 600 and 900 degrees C, separately. The pyrolysis products were directly introduced into GC-MS and were qualitatively and semi-quantitatively analyzed. The results showed that a variety of aroma compounds of aldehydes, 3-p-menthene and menthol were released and identified at 300 degrees C. While at 600 degrees C and 900 degrees C, flavor alkene class, the alkyl pyrazines, menthol and 3-p-menthene were generated. And the types and relative amounts of pyrazines were significantly increased, at these two temperatures. Combined the analytical results of DPAME pyrolysates and the results of sensory evaluation of the cigarette, the possible pyrolysis mechanism was preliminarily speculated. The Py-GC-MS technique for the study of the pyrolysis products of DPAME was convenient and rapid. The investigation provided a reliable theoretical foundation for the perfume reinforcement technology in tobacco products, contributing to the development of cigarette products with better aroma and taste. This method is an accurate and quick way to study the pyrolysis products of latent fragrant substance.

Effects of uric acid on hearts of rats with chronic kidney disease.

AIMS: To study the effects of uric acid on cardiac lesions and its possible mechanism by establishing an early-stage CKD animal model with hyperuricemia. Allopurinol was used to see whether it could reduce cardiac lesions. METHODS: The experimental rats were randomly divided into 4 groups (n = 15): Group A (sham-operative group), Group B (CKD group), Group C (CKD with hyperuricemia group), Group D (CKD with hyperuricemia + allopurinol group). After 16 weeks, the rats were sacrificed and blood samples were collected for detection of Scr, SUA, hs-CRP and IL-6. Kidney and heart tissues were pathologically examined. The collagen I of heart tissues was examined by immunohistochemistrical methods. RESULTS: Obvious pathological changes could be observed in Group C. However, compared to Group C, the pathological changes in Group D were lighter. The proportion of collagen I positive area (PCIPA) in Group C was significantly higher than that in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with PCIPA in myocardium. IL-6 and hs-CRP levels in Group C were significantly higher than in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with IL-6 and hs-CRP, and PCIPA in myocardium had a significant positive correlation with hs-CRP and IL-6 levels. CONCLUSIONS: There were obvious cardiac lesions in early-stage CKD rats with hyperuricemia, and the severity of cardiac lesions was positively related to the level of SUA. Micro-inflammation might be one mechanism causing cardiac lesions. Allopurinol could alleviate cardiac lesions in early-stage CKD rats by lowering the SUA level, which, in turn, could reduce the severity of micro-inflammation.