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Huang M.,East China University of Science and Technology | Huang M.,Tsinghua University | Zhu C.,East China University of Science and Technology | Zhu C.,Tsinghua University | And 6 more authors.
Yaoxue Xuebao | Year: 2011

This study was to report the effect of Tangshen Formula on phospholipids metabolism in diabetic nephropathy patients. A normal phase-HPLC-TOF/MS method was used in this study for the determination of seven species of phospholipids in human plasma. Then, the concentration changes of potential phospholipids biomarkers were discussed in diabetic nephropathy phase III and phase IV patients among different groups, including before and 3, 6 months after administration of Tangshen Formula. Significant increases of PE750, PI885, PC792, PC826, PC830, PC854 and PC802 levels were observed 6 months after administration of Tangshen Formula and conventional western medicine, as well as a decrease of LPC540 level, when compared with those before medication. Concentrations of all the potential phospholipids biomarkers showed a tendency towards normal levels; however, both the improvement degree and onset time of these compounds were not same. Additionally, Tangshen Formula treatment based on conventional western medicine treatment was more efficient in adjusting the levels of these compounds when compared with western medicine treatment alone, especially for the phase IV patients. These results indicated that Tangshen Formula was capable in regulating and improving phospholipids metabolism in diabetic nephropathy patients, which may be related with the direct or indirect inhibition of protein kinase C pathway and the corresponding reduction of phospholipase A2 activity. Therefore, Tangshen Formula may be used as an effective drug for diabetic nephropathy therapy, at least as an adjunctive therapeutic drug. Source

Huang M.,Tsinghua University | Huang M.,East China University of Science and Technology | Huang M.,CAS Shanghai Institutes for Biological Sciences | Liang Q.,Tsinghua University | And 14 more authors.
Molecular BioSystems | Year: 2013

Diabetic nephropathy is a devastating disease that affects a growing number of diabetic patients. A complete cure is very hard to achieve once the disease has been diagnosed, therefore the diagnosis of early stages in diabetic nephropathy has become a hot area. Numbers of molecules have been proposed to be potential biomarkers for this purpose. However, some problems still remain, such as discovering effective biomarkers to diagnose the disease before obvious clinical evidence appears. Thus, the main purpose of this study was to find plasma biomarkers for early diagnosis of type 2 diabetic nephropathy stage 1 and stage 2, as well as separating them from diabetes. 182 subjects (Chinese) were recruited for this study, including 50 healthy controls, 33 type 2 diabetic patients and 99 type 2 diabetic nephropathy patients (33 of these were stage 3). Important clinical indicators including proteinuria, serum creatinine, and urea nitrogen were measured and the glomerular filtration rate was estimated to assess kidney function; fasting blood glucose, postprandial blood glucose and glycated hemoglobin were measured to assess the blood glucose control. Key metabolites and genes in plasma samples were identified and determined using -omic and quantitative techniques. The potential biomarkers were then combined and carefully screened to determine the most informative ones for early diagnosis of type 2 diabetic nephropathy. An integrated biomarker system (IBS) incorporating 6 clinical indicators, 40 metabolites and 5 genes was established. Correlation analysis results revealed that most of the potential biomarkers significantly correlated with the 6 clinical indicators. Discriminant analysis results showed that the developed IBS gave the highest total predictive accuracy (98.9%). Significant test and receiver operating characteristic analysis results indicated that inosine had the highest sensitivity (0.889), specificity (1.000), positive predictive rate (1.000) and negative predictive rate (0.900) amongst the 48 potential biomarkers when separating patients with diabetes from patients with diabetic nephropathy stage 3. Finally, inosine with a cutoff of 0.086 mg L-1 was combined with estimated GFR to differentiate between diabetic nephropathy stages 1 and 2 from diabetes. The results demonstrate that IBS combined with a proper statistical analysis technique is a powerful tool for biomarker screening. © 2013 The Royal Society of Chemistry. Source

Wei L.,Hunan Provincial Peoples Hospital | Chen W.,Hunan Provincial Peoples Hospital | Zou Y.,Hunan Provincial Peoples Hospital | Huang H.,Hunan Provincial Peoples Hospital | And 5 more authors.
Genetics and Molecular Research | Year: 2015

Although the nephrotoxicity of cisplatin has been well documented as a major side effect of chemotherapy, the exact mechanism by which prosurvival and apoptotic pathways interplay to determine renal pathology remains elusive. Recent studies suggested that autophagy might serve as an adaptive mechanism to promote cell survival during acute kidney injury (AKI). We have used AKI as a disease model to investigate the mechanism regulating the cytoprotective role of autophagy in cisplatin-induced tissue damage. Pharmacological inhibitors such as chloroquine were used to manipulate autophagy during AKI, and DNA damage was evaluated by using the cellular marker gH2AX. Cisplatin induced extensive DNA damage during AKI. Autophagy activation served as a survival strategy to suppress cisplatin-induced DNA damage in the pathology of AKI both in vitro and in vivo. Interestingly, in the kidney, cisplatin treatment can activate AMP-activated protein kinase (AMPK), a signaling molecule that is also critical for p53-mediated inactivation of mammalian target of rapamycin (mTOR) pathways. As a result, inhibition or knockdown of AMPK can lead to repressed autophagy in cisplatin-induced AKI, resulting in more DNA damage. Activation of AMPK regulates autophagy during cisplatin-induced AKI. Given the fact that p53 can regulate autophagy by inactivating mTOR via AMPK, our results suggest that the p53 pathway may also play a critical role in the pathogenesis of cisplatin-induced renal damage. This study may further our understanding of the physiological roles of autophagy in the pathogenesis of renal injuries, and thus may have pathological implications in the clinical setting. © FUNPEC-RP. Source

Zhu C.,East China University of Science and Technology | Zhu C.,Tsinghua University | Huang M.,East China University of Science and Technology | Huang M.,Tsinghua University | And 8 more authors.
Gaodeng Xuexiao Huaxue Xuebao/Chemical Journal of Chinese Universities | Year: 2011

As one of the most common endocrine diseases, diabetic mellitus (DM) has a very close relationship with phospholipids metabolism. Tangshen Formula (TSF) is an often-used prescription with good efficacy for treating DM and diabetic nephropathy (DN). The aim of this study is to understand the effect of TSF on phospholipids metabolism of DM. In this paper, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of slowly progressive obese type II diabetes, were employed. Phospholipids profiling of rat plasma was established using normal phase liquid chromatography-time of flight mass spectrometry (NPLC-TOF/MS). Partial least-squares discriminant analysis (PLS-DA) and quantification of 14 compounds were applied to evaluate the effect of TSF on phospholipids metabolism of OLETF rats and to discover potential biomarkers. The results showed that plasma phospholipids metabolic disorders occurred in OLETF rats. The good effect of TSF on phospholipids metabolism was compared with the adverse impact of Monopril. TSF could significantly improve phospholipids metabolism of OLETF rats, whereas Monopril exacerbated disturbance of phospholipids metabolism. According to the quantitative results, a total of 8 phospholipids compounds which have significant concentration variation between control group and model group were considered as potential biomarkers of type II diabetes. Source

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