Publications by authors named "Xiaodong Geng"

24 Publications

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LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricaemia.

J Cell Mol Med 2021 Jul 22. Epub 2021 Jul 22.

Department of Nephrology, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Long non-coding RNA (lncRNA) plays an important role in the renal inflammatory response caused by hyperuricaemia. However, the underlying molecular mechanisms through which lncRNA is involved in endothelial injury induced by hyperuricaemia remain unclear. In this study, we investigated the regulatory role of lncRNA-HOTAIR in high concentration of uric acid (HUA)-induced renal injury. We established hyperuricaemia mouse model and an in vitro uric acid (UA)-induced human umbilical vein endothelial cell (HUVEC) injury model. In HUA-treated HUVECs and hyperuricaemia mice, we observed increased HOTAIR and decreased miR-22 expression. The expression of pyroptosis-associated protein (NLRP3, Caspase-1, GSDMD-N, GSDMD-FL) was increased. The release of LDH, IL-1β and IL-18 in cell supernatants and the sera of model mice was also increased. The proliferation of HUVECs stimulated by HUA was significantly inhibited, and the number of TUNEL-positive cells in hyperuricaemia mouse kidney was increased. Bioinformatics analysis and luciferase reporter and RIP assays confirmed that HOTAIR promoted NLRP3 inflammasome activation by competitively binding miR-22. In gain- or loss-of-function experiments, we found that HOTAIR and NLRP3 overexpression or miR-22 knock down activated the NLRP3 inflammasome and promoted pyroptosis in HUA-treated HUVECs, while NLRP3 and HOTAIR knockdown or a miR-22 mimic exerted the opposite effects. Furthermore, in vivo experiments validated that HOTAIR knockdown alleviated renal inflammation in hyperuricaemia mice. In conclusion, we demonstrated that in hyperuricaemia, lncRNA-HOTAIR promotes endothelial cell pyroptosis by competitively binding miR-22 to regulate NLRP3 expression.
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http://dx.doi.org/10.1111/jcmm.16812DOI Listing
July 2021

Wearable Helical Molybdenum Nitride Supercapacitors for Self-Powered Healthcare Smartsensors.

ACS Appl Mater Interfaces 2021 Jun 15;13(25):29780-29787. Epub 2021 Jun 15.

Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China.

To meet the increasing demand for wearable sensing devices, flexible supercapacitors (SCs) as energy storage devices play significant roles in powering sensors/biosensors for healthcare monitoring. Because of its high conductivity and remarkable specific capacitance in SCs, molybdenum nitride (MoN) has been widely used. Herein, a flexible helical structure of MoN modified on nitrogen-doped carbon cloth ([email protected]@MoN) has been prepared by a simple nitride process, delivering an ultralong cycle life of 10,000 cycles and high areal capacitance of 467.6 mF cm as SCs. Moreover, the as-fabricated flexible all-solid-state asymmetrical SCs (ASCs) of [email protected]@MoN//[email protected] demonstrated outstanding electrochemical behavior after 10,000 cycles and over 90% retention, and the value of areal capacitance could reach 90.8 mF cm at 10 mA cm. Integrated with solar energy, ASCs could be used as a self-powered energy system for strain sensors in detecting human movement, and finger movements could be further real-time monitored remotely via a smartphone. Prospectively, wearable helical MoN solid-state SCs for self-powered strain smartsensors would inspire the development of structured materials in the application of energy storage, portable self-powering, and strain or chemical/biochemical smartsensors.
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http://dx.doi.org/10.1021/acsami.1c05247DOI Listing
June 2021

Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury.

Front Med (Lausanne) 2021 28;8:655787. Epub 2021 May 28.

State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese People's Liberation Army (PLA) Institute of Nephrology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia-reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.
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http://dx.doi.org/10.3389/fmed.2021.655787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193099PMC
May 2021

Ultrasound enhances the therapeutic potential of mesenchymal stem cells wrapped in greater omentum for aristolochic acid nephropathy.

Stem Cell Res Ther 2021 05 3;12(1):261. Epub 2021 May 3.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China.

Background: Mesenchymal stem cells (MSCs) have been reported to promote regeneration in both subjects with acute kidney injury (AKI) and chronic kidney disease (CKD), but their efficacy remains limited, probably because most of the cells accumulate in the lungs, liver, and spleen after an intravenous infusion. Therefore, ultrasound-guided administration of MSCs represents a possible approach to solve this problem. The greater omentum is used to promote cell survival due to its rich vasculature. We hypothesized that ultrasound-guided administration of MSCs combined with greater omentum might be more curative than currently available approaches.

Methods: In this study, we established an aristolochic acid nephropathy (AAN) model by intraperitoneally administering aristolochic acid I sodium salt (AA-I) at a dose of 5 mg/kg body weight on alternate days for 4 weeks. Subsequently, a laparotomy was performed, and the left kidney from which the capsule had been removed was wrapped with the greater omentum. A dose of 2 × 10 MSCs was injected into the space between the greater omentum and the left kidney. Equal amounts of MSCs were administered under ultrasound guidance every second week for a total of 4 treatments. Mice were sacrificed 4 weeks after surgery. Serum creatinine and blood urea levels were measured to assess renal function. qPCR, Western blot, and histological analyses were conducted to further investigate the therapeutic mechanism of MSCs.

Results: Ultrasound-guided injection of MSCs into the greater omentum that surrounds the kidney enriched cells in the kidney region for up to 5 days. Renal function tests indicated that MSCs improved renal function to a great extent, as reflected by decreased blood urea nitrogen and serum creatinine levels. In addition, histological analyses showed that MSCs noticeably attenuated kidney injury, as evidenced by the amelioration of tubular necrosis and peritubular interstitial fibrosis. Mitigation of renal interstitial fibrosis was further confirmed by immunohistochemistry, qPCR, and western blotting after MSC treatment. Moreover, immunofluorescence staining revealed that MSCs alleviated inflammatory responses by increasing the counts of CD206+ cells and decreasing the counts of CD68+ cells. MSC migration was initiated in response to AA-I-treated renal epithelial cells in an in vitro migration assay.

Conclusions: These findings suggested that administration of MSCs into the cavity formed by the injured kidney and the greater omentum under ultrasound guidance improved renal function, attenuated kidney injury, and mitigated renal interstitial fibrosis and inflammatory responses. Thus, this approach might be a safe and effective therapy for CKD.
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http://dx.doi.org/10.1186/s13287-021-02243-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091698PMC
May 2021

Interpretable Machine Learning Model for Early Prediction of Mortality in ICU Patients with Rhabdomyolysis.

Med Sci Sports Exerc 2021 Mar 31. Epub 2021 Mar 31.

Medical School of Chinese PLA, Beijing, China Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China School of Biological Science and Medical Engineering, Beihang University, Beijing, China Department of Critical Care Medicine, Chinese PLA General Hospital, Beijing, China Department of Anesthesiology, The 920 Hospital of Joint Logistic Support Force of Chinese PLA, Kunming Yunnan, China.

Purpose: Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from rhabdomyolysis is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients.

Method: Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care III (MIMIC- III) database. We extracted data from the first 24h after patient ICU admission. Data from the two datasets were merged for further analysis. The merged datasets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model XGBoost (extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model.

Results: In total, 938 patients with RM were eligible for this analysis. The AUC of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915 and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression (AUC = 0.862), support vector machine (AUC = 0.843), random forest (AUC = 0.825) and naive Bayesian (AUC = 0.805) and clinical scores (SOFA (AUC = 0.747) and APS III (AUC = 0.721)).

Conclusions: Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24h of admission to the ICU.
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http://dx.doi.org/10.1249/MSS.0000000000002674DOI Listing
March 2021

Development and validation of a model for the early prediction of the RRT requirement in patients with rhabdomyolysis.

Am J Emerg Med 2021 Mar 8;46:38-44. Epub 2021 Mar 8.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China. Electronic address:

Introduction: Rhabdomyolysis (RM) is a complex set of clinical syndromes involving the rapid dissolution of skeletal muscles. The early detection of patients who need renal replacement therapy (RRT) is very important and may aid in delivering proper care and optimizing the use of limited resources.

Methods: Retrospective analyses of the following three databases were performed: the eICU Collaborative Research Database (eICU-CRD), the Medical Information Mart for Intensive Care III (MIMIC-III) database and electronic medical records from the First Medical Centre of the Chinese People's Liberation Army General Hospital (PLAGH). The data from the eICU-CRD and MIMIC-III datasets were merged to form the derivation cohort. The data collected from the Chinese PLAGH were used for external validation. The factors predictive of the need for RRT were selected using a LASSO regression analysis. A logistic regression was selected as the algorithm. The model was built in Python using the ML library scikit-learn. The accuracy of the model was measured by the area under the receiver operating characteristic curve (AUC). R software was used for the LASSO regression analysis, nomogram, concordance index, calibration, and decision and clinical impact curves.

Results: In total, 1259 patients with RM (614 patients from eICU-CRD, 324 patients from the MIMIC-III database and 321 patients from the Chinese PLAGH) were eligible for this analysis. The rate of RRT was 15.0% (92/614) in the eICU-CRD database, 17.6% (57/324) in the MIMIC-III database and 5.6% in the Chinese PLAGH (18/321). After the LASSO regression selection, eight variables were included in the RRT prediction model. The AUC of the model in the training dataset was 0.818 (95% CI 0.78-0.87), the AUC in the test dataset was 0.794 (95% CI 0.72-0.86), and the AUC in the Chinese PLAGH dataset (external validation dataset) was 0.820 (95% CI 0.70-0.86).

Conclusions: We developed and validated a model for the early prediction of the RRT requirement among patients with RM based on 8 variables commonly measured during the first 24 h after admission. Predicting the need for RRT could help ensure appropriate treatment and facilitate the optimization of the use of medical resources.
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http://dx.doi.org/10.1016/j.ajem.2021.03.006DOI Listing
March 2021

Investigation of hub genes involved in diabetic nephropathy using biological informatics methods.

Ann Transl Med 2020 Sep;8(17):1087

Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China.

Background: The aim of this study was to find genes with significantly aberrant expression in diabetic nephropathy (DN) and determine their underlying mechanisms.

Methods: GSE30528 and GSE1009 were obtained by querying the Gene Expression Omnibus (GEO) database. The difference in target gene expression between normal renal tissues and kidney tissues in patients with DN was screened by using the GEO2R tool. Using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, differentially expressed genes (DEGs) were analysed by Gene Ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Then, the protein-protein interactions (PPIs) of DEGs were analyzed by Cytoscape with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the hub genes in this PPI network were recognized by centrality analysis.

Results: There were 110 genes with significant expression differences between normal and DN tissues. The differences in gene expression involved many functions and expression pathways, such as the formation of the extracellular matrix and the construction of the extracellular domain. The correlation analysis and subgroup analysis of 14 hub genes and the clinical characteristics of DN showed that CTGF, ALB, PDPN, FLT1, IGF1, WT1, GJA1, IGFBP2, FGF9, BMP2, FGF1, BMP7, VEGFA, and TGFBR3 may be involved in the progression of DN.

Conclusions: We confirmed the differentially expressed hub genes and other genes which may be the novel biomarker and target candidates in DN.
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http://dx.doi.org/10.21037/atm-20-5647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575993PMC
September 2020

Divergence in ecosystem carbon fluxes and soil nitrogen characteristics across alpine steppe, alpine meadow and alpine swamp ecosystems in a biome transition zone.

Sci Total Environ 2020 Dec 22;748:142453. Epub 2020 Sep 22.

Key Laboratory of Alpine Ecology, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing 100101, China; CAS Center for Excellence in Tibetan Plateau Earth Sciences, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Alpine ecosystem carbon cycling is sensitive to climate change, particularly in the transition zones between biomes. Soil nitrogen conditions, including the ammonium to nitrate (NH/NO) ratio, regulate ecosystem carbon uptake by coupling carbon‑nitrogen cycle. The largest alpine pasture on Earth is distributed on the Tibetan Plateau, where alpine biome transition zones are also widely distributed. However, it is largely unknown how the soil NH/NO ratio and net ecosystem CO exchange vary among vegetation types in the alpine biome transition zones due to a lack of in situ field observations. Here, we investigated soil NH/NO ratio and ecosystem carbon fluxes across alpine steppe, alpine meadow and alpine swamp ecosystems in a biome transition zone on the central Tibetan Plateau. The results showed that soil NH/NO ratio was lowest in the alpine steppe (driest environment), which had the highest soil pH, and highest in the alpine swamp (wettest environment), which had the lowest soil pH. We proposed a theoretical framework describing how soil moisture regulates soil NH/NO ratio by altering both the denitrification process and soil pH. We further found that the growing season average net ecosystem CO exchange for the alpine steppe, alpine meadow and alpine swamp was -1.46, -1.90 and -5.43 μmol m s, respectively. This divergence in net ecosystem CO exchange across the three grasslands is primarily explained by divergence in gross ecosystem photosynthesis, rather than ecosystem respiration. The air temperature sensitivity of ecosystem respiration (Q) for the alpine steppe, alpine meadow and alpine swamp was 1.73 ± 0.05, 1.44 ± 0.03 and 2.43 ± 0.45, respectively. Our study highlights large differences in both soil nutrient and ecosystem carbon uptake across different vegetation types in an alpine biome transition zone. More in situ investigations in various biome transition zones are urgently needed to quantitatively understand the spatial pattern of alpine ecosystem carbon‑nitrogen cycling processes.
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http://dx.doi.org/10.1016/j.scitotenv.2020.142453DOI Listing
December 2020

The top 100 most cited articles on rhabdomyolysis: A bibliometric analysis.

Am J Emerg Med 2020 09 17;38(9):1754-1759. Epub 2020 May 17.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China. Electronic address:

Introduction: Over the past few decades, the incidence of Rhabdomyolysis (RM) has significantly increased. The prognosis is substantially worse if renal failure develops. Many problems remain to be addressed regarding the pathogenesis, prevention, and treatment of RM. The purpose of this study was to identify and characterize the top 100 most cited publications regarding rhabdomyolysis (RM) by performing a bibliometric analysis.

Methods: Publications focusing on RM were identified from the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC). Bibliographic information was collected, including year of publication, authorship, publishing journals, institution, country of origin and keywords. CiteSpace V5.6.R2 and the Online Analysis Platform of Literature Metrology were used for descriptive analysis.

Results: The 100 most cited articles were published between 1995 and 2016, with citation numbers ranging from 116 to 904. The United States (60) has been the largest contributor to RM research. Hartford Hospital and University of Texas were found to be the most productive institutions, with five articles each. Thompson, PD, who authored six articles, was the most productive author. The American Journal of Cardiology published the most articles (5), followed by the New England Journal of Medicine (4). The top three co-cited journals were the New England Journal of Medicine (74), Lancet (59) and JAMA (54).

Conclusions: This study provides valuable information on the study of RM. These findings may be used to guide clinical decision-making and identify new research fields.
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http://dx.doi.org/10.1016/j.ajem.2020.05.031DOI Listing
September 2020

Research Progress on the Role of Inflammasomes in Kidney Disease.

Mediators Inflamm 2020 29;2020:8032797. Epub 2020 Jan 29.

Department of Nephrology, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, 28 Fuxing Road, Beijing 100853, China.

Inflammasomes are multimeric complexes composed of cytoplasmic sensors, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC or PYCARD), and procaspase-1 and play roles in regulating caspase-dependent inflammation and cell death. Inflammasomes are assembled by sensing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and initiate inflammatory responses by activating caspase-1. Activated caspase-1 promotes the release of the inflammatory cytokines interleukin-1 (IL-1) and IL-18 and eventually induces pyroptosis. Inflammasomes are closely related to kidney diseases. In particular, the NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome has been shown to cause acute and chronic kidney diseases by regulating canonical and noncanonical mechanisms of inflammation. Small-molecule inhibitors that target NLRP3 and other components of the inflammasome are potential options for the treatment of kidney-related diseases such as diabetic nephropathy. This article will focus on the research progress on inflammasomes and the key pathogenic roles of inflammasomes in the development and progression of kidney diseases and explore the potential of this intracellular inflammation to further prevent or block the development of the kidney disease.
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http://dx.doi.org/10.1155/2020/8032797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204206PMC
July 2021

Insulin-Like Growth Factor Binding Protein 5-A Probable Target of Kidney Renal Papillary Renal Cell Carcinoma.

Biomed Res Int 2019 11;2019:3210324. Epub 2019 Nov 11.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, China.

Kidney renal papillary renal cell carcinoma (KIRP) accounts for 10-15% of renal cell carcinoma (RCC). The need to find more therapeutic targets for KIRP is urgent because most targeted drugs have limited effects on advanced KIRP. Insulin-like growth factor (IGF) binding protein 5 (IGFBP5) is a secreted protein related to cell proliferation, cell adhesion, cell migration, the inflammatory response and fibrosis; these functions are independent of IGF. In our study, we determined the expression and functions of IGFBP5 with data from the database of The Cancer Genome Atlas (TCGA). We found that IGFBP5 is down regulated in KIRP kidney tissues compared to its expression in control tissues and that the expression of IGFBP5 is negatively related to patient survival. Bioinformatic analysis showed the probable processes and pathways involved in altered IGFBP5 expression, including blood vessel development, the cellular response to growth factor stimulus, the response to transforming growth factor (TGF-), and extracellular matrix organization. We proposed that VEGFA and TGF- act as upstream regulatory factors of IGFBP5 and verified this in the Caki-2 cell line. Based on our results, we suggest that IGFBP5 might be a therapeutic target of KIRP.
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http://dx.doi.org/10.1155/2019/3210324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925670PMC
May 2020

Mesenchymal Stem Cells Loaded with Gelatin Microcryogels Attenuate Renal Fibrosis.

Biomed Res Int 2019 31;2019:6749326. Epub 2019 Oct 31.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, 28 Fuxing Road, Beijing 100853, China.

Background: The treatment of chronic kidney diseases (CKDs) by different approaches using mesenchymal stem cells (MSCs) has made great strides. In this study, we aimed to explore the potential mechanism of gelatin microcryogels (GMs) as a cell therapeutic vector to block the progression of CKD.

Methods: In vivo, the pedicled omentum valve with MSC-loaded GMs was packed onto 5/6 nephrectomized kidneys derived from rats. The therapeutic effects were evaluated. In vitro, TNF-, TGF-, and MSCs were added to the medium of the HK-2 cell culture system, and key genes involved in anti-inflammatory and antifibrosis effects were evaluated by qPCR.

Results: After 12 weeks of MSC transplantation, kidney functions, such as serum creatinine, urea nitrogen, and 24-hour urine protein, were significantly improved. The pedicled omentum valve was packed with MSC-loaded GMs onto the 5/6 nephrectomized kidney, and the expressions of collagen IV, -SMA, and TGF- were all evaluated by immunohistochemical staining and western blot analysis. MSC-loaded-GMs also showed antifibrotic effects by inducing the upregulation of HO-1, BMP-7, and HGF and the downregulation of MCP-1 at the mRNA level. Four weeks after MSC-loaded GM treatment, we found that the mRNA levels of TNF- and IL-6 were clearly reduced. MSC-conditional medium (MSC-CM) showed that the TNF--induced expression of IL-8 and IL-6 mRNA was reversed; E-cadherin mRNA was upregulated; and the TGF--induced expression of collagen IV, -SMA, and fibronectin (FN) mRNA in HK-2 cells was reduced.

Conclusions: We demonstrated that the pedicled omentum valve packed with MSC-loaded GMs had a renal protective effect on the 5/6 nephrectomized kidney by observing the anti-inflammatory and antifibrosis effects.
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http://dx.doi.org/10.1155/2019/6749326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6875199PMC
April 2020

Functional nano-catalyzed pyrolyzates from branch of .

Saudi J Biol Sci 2019 Sep 4;26(6):1227-1246. Epub 2019 Jun 4.

College of Forestry/Henan Province Engineering Research Center for Forest Biomass Value-added Products, Henan Agricultural University, Zhengzhou 450002, China.

is an excellent tree species for construction of forest construction of Henan Province, China. The diverse bioactive components of nano-catalyzed pyrolyzates form cold-acclimated branch (CCB) in North China were explored. The raw powder of CCB treated with nano-catalyst (Ag, NiO, /Ag + /NiO) were pyrolyzed at two temperatures (550 °C and 700 °C), respectively. The main pyrolyzates are bioactive components of bioenergy, biomedicines, food additive, spices, cosmetics and chemical, whose total relative contents at 550 °C pyrolyzates are higher than those at 700 °C pyrolyzates. There are abundant components of spices and biomedicine at 550 °C pyrolyzates, while more spices and food additive at 700 °C pyrolyzates. At 550 °C, the content of biomedicine components reaches the highest by /Ag + /NiO nanocatalysis, while the contents of spices and food additive components reach the highest by NiO nanocatalysis. At 700 °C, the content of bioenergy components reaches the highest by /Ag + /NiO nanocatalysis, and the content of cosmetics components reaches the highest by Ag nanocatalysis. The findings suggested that the branch of the cold-acclimated have the potential to develop into valued-added products of bioenergy, biomedicine, cosmetics, spices and food additive by nanocatalysis.
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http://dx.doi.org/10.1016/j.sjbs.2019.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733784PMC
September 2019

From tricritical ferromagnetism to metamagnetism in quasi-two dimensional Tl(Co Ni )S (x = 0, 0.05).

J Phys Condens Matter 2018 Jul 11;30(29):295801. Epub 2018 Jun 11.

College of Science, Henan Institute of Engineering, Xinzheng 451191, People's Republic of China. Department of Physics, Zhejiang University, Hangzhou 310027, People's Republic of China.

We have investigated the critical behavior near the ferromagnetic transition of TlCoS single crystals and the magnetic properties of Tl(CoNi)S by means of magnetization measurements. The obtained critical exponents β, γ and δ of TlCoS could basically satisfy the scaling equations and are found very close to the prediction of the tricritical mean-field theory. 5[Formula: see text] Ni doping drives the system to an antiferromagnetic ground state which is unstable to magnetic field, yielding metamagnetic transition. The possible existence of a tricritical point (TCP) in Tl(CoNi)S is also discussed.
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http://dx.doi.org/10.1088/1361-648X/aacbb4DOI Listing
July 2018

Gene Microarray Integrated with High-Throughput Proteomics for the Discovery of Transthyretin in Rhabdomyolysis-Induced Acute Kidney Injury.

Cell Physiol Biochem 2017 18;43(4):1673-1688. Epub 2017 Oct 18.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Background/aims: Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI.

Methods: In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis. Isobaric tagging with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between RM-induced AKI and normal murine renal tissue. Verification experiments included immunohistochemistry (IHC), real-time PCR, Western blotting, and the measurement of ATP and ROS production. HK-2 cells were incubated in vitro with ferrous myoglobin and pcDNA-TTR, followed by assays to detect cell proliferation, ROS and apoptosis.

Results: According to gene microarray and iTRAQ-MS analysis, we screened 17 common elements. After multiple analyses, we selected transthyretin (TTR) as our focus and investigated TTR in the kidney. Verification experiments with IHC confirmed differential expression levels of TTR proteins. Furthermore, Western blotting showed a stepwise decrease in TTR in AKI renal tissues. Cell-based experiments showed that overexpression of TTR could improve HK-2 cell viability and inhibit apoptosis. TTR reduced apoptosis by decreasing the accumulation of reactive oxygen species (ROS).

Conclusion: This study reports a possible mechanism for RM-induced AKI and suggests that reductions in TTR could increase the generation of ROS and induce apoptosis. TTR may be a potentially valuable target for RM-induced AKI.
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http://dx.doi.org/10.1159/000484028DOI Listing
December 2017

Protein Array-Based Detection of Proteins in Kidney Tissues from Patients with Membranous Nephropathy.

Biomed Res Int 2017 27;2017:7843584. Epub 2017 Feb 27.

Department of Nephrology, PLA General Hospital, Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China.

Membranous nephropathy (MN) is an autoimmune inflammatory disease in which proteins related with plenty of biological processes play an important role. However, the role of these proteins in the pathogenesis of MN is still unclear. This study aimed to screen differential proteins in kidney tissue samples from MN patients by using protein arrays and determine the pathways involved in the pathogenesis of MN. This study first tested a quantitative protein array (QAH-INF-3) and two semiquantitative protein arrays (L-493 and L-507) with normal renal tissue and identified L-493 as the most appropriate assay to compare protein levels between MN tissues and normal control tissues. The L-493 array identified 66 differentially expressed proteins (DEPs) that may be associated with MN. The gene oncology (GO) and protein-protein interaction (PPI) analyses revealed several processes potentially involved in MN, including extracellular matrix disassembly and organization, cell adhesion, cell-cell signaling, cellular protein metabolic process, and immune response ( < 0.05). We suggest that these different pathways work together via protein signaling and result in the pathogenesis and progression of MN.
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http://dx.doi.org/10.1155/2017/7843584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350302PMC
April 2017

Biological Membrane-Packed Mesenchymal Stem Cells Treat Acute Kidney Disease by Ameliorating Mitochondrial-Related Apoptosis.

Sci Rep 2017 01 24;7:41136. Epub 2017 Jan 24.

Department of Nephrology, PLA General Hospital, Institute of Nephrology, Beijing Key Laboratory of Kidney Disease, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing 100853, China.

The mortality of rhabdomyolysis-induced AKI remains high because no effective therapy exists. We investigated a new therapeutic method using MSCs. The aim of this study was to investigate the therapeutic potential and anti-apoptotic mechanisms of action of MSCs in the treatment of AKI induced by glycerol in vivo and in vitro. We used Duragen as a biological membrane to pack MSCs on the glycerol-injured renal tissue in vivo. The anti-apoptotic mechanism was investigated. In vitro, HK-2 cells were incubated with ferrous myoglobin and MSCs-conditioned medium, followed by cell proliferation and apoptosis assays. We founded that packing MSCs on the injured renal tissue preserved renal function, ameliorated renal tubular lesions, and reduced apoptosis in the mice with glycerol-induced AKI. The MSC-conditioned medium improved HK-2 cell viability and inhibited apoptosis. These effects were reversed by the PI3K inhibitor LY294002. Biological membrane packing of MSCs on the renal tissue has a therapeutic rescue function by inhibiting cell apoptosis in vivo. MSCs protect renal cells from apoptosis induced by myoglobin in vitro. We have thus demonstrated MSCs reduced rhabdomyolysis-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway and inhibiting apoptosis.
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http://dx.doi.org/10.1038/srep41136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259718PMC
January 2017

Cardiovascular metabolic risk factors and glomerular filtration rate: a rural Chinese population study.

Lipids Health Dis 2016 Oct 12;15(1):180. Epub 2016 Oct 12.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Methods: A total of 2426 study subjects from rural China aged 35 years and above (934 men and 1492 women) were enrolled in a cross-sectional survey. The eGFR calculation was based on the Modification of Diet in Renal Disease (MDRD) equation. The strength of the association between cardiovascular metabolic risk factors and eGFR was analyzed using a linear regression model.

Results: Cardiovascular metabolic risk factors, including age, body weight, waist circumference, fasting plasma glucose (FPG), creatinine (Cr), high-density lipoprotein-cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), systolic pressure, and diastolic pressure, were associated with eGFR. Additionally, the eGFR level gradually decreased and showed a linear trend with the increase in metabolic syndrome risk factors.

Conclusion: Metabolic risk factors are correlated with a reduction in renal function and CKD.
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http://dx.doi.org/10.1186/s12944-016-0346-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062868PMC
October 2016

Differences in gene expression profiles and signaling pathways in rhabdomyolysis-induced acute kidney injury.

Int J Clin Exp Pathol 2015 1;8(11):14087-98. Epub 2015 Nov 1.

Department of Nephrology, PLA General Hospital, Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases Beijing, P. R. China.

Purpose: Rhabdomyolysis is a threatening syndrome because it causes the breakdown of skeletal muscle. Muscle destruction leads to the release of myoglobin, intracellular proteins, and electrolytes into the circulation. The aim of this study was to investigate the differences in gene expression profiles and signaling pathways upon rhabdomyolysis-induced acute kidney injury (AKI).

Methods: In this study, we used glycerol-induced renal injury as a model of rhabdomyolysis-induced AKI. We analyzed data and relevant information from the Gene Expression Omnibus database (No: GSE44925). The gene expression data for three untreated mice were compared to data for five mice with rhabdomyolysis-induced AKI. The expression profiling of the three untreated mice and the five rhabdomyolysis-induced AKI mice was performed using microarray analysis. We examined the levels of Cyp3a13, Rela, Aldh7a1, Jun, CD14. And Cdkn1a using RT-PCR to determine the accuracy of the microarray results.

Results: The microarray analysis showed that there were 1050 downregulated and 659 upregulated genes in the rhabdomyolysis-induced AKI mice compared to the control group. The interactions of all differentially expressed genes in the Signal-Net were analyzed. Cyp3a13 and Rela had the most interactions with other genes. The data showed that Rela and Aldh7a1 were the key nodes and had important positions in the Signal-Net. The genes Jun, CD14, and Cdkn1a were also significantly upregulated. The pathway analysis classified the differentially expressed genes into 71 downregulated and 48 upregulated pathways including the PI3K/Akt, MAPK, and NF-κB signaling pathways.

Conclusion: The results of this study indicate that the NF-κB, MAPK, PI3K/Akt, and apoptotic pathways are regulated in rhabdomyolysis-induced AKI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713508PMC
October 2016

Using Next-Generation Sequencing to Identify a Mutation in Human MCSU that is Responsible for Type II Xanthinuria.

Cell Physiol Biochem 2015 24;35(6):2412-21. Epub 2015 Apr 24.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Hypouricemia is caused by various diseases and disorders, such as hepatic failure, Fanconi renotubular syndrome, nutritional deficiencies and genetic defects. Genetic defects of the molybdoflavoprotein enzymes induce hypouricemia and xanthinuria. Here, we identified a patient whose plasma and urine uric acid levels were both extremely low and aimed to identify the pathogenic gene and verify its mechanism.

Methods: Using next-generation sequencing (NGS), we detected a mutation in the human molybdenum cofactor sulfurase (MCSU) gene that may cause hypouricemia. We cultured L02 cells, knocked down MCSU with RNAi, and then detected the uric acid and MCSU concentrations, xanthine oxidase (XOD) and xanthine dehydrogenase (XDH) activity levels, and xanthine/hypoxanthine concentrations in cell lysates and culture supernatants.

Results: The NGS results showed that the patient had a mutation in the human MCSU gene. The in vitro study showed that RNAi of MCSU caused the uric acid, human MCSU concentrations, the XOD and XDH activity levels among cellular proteins and culture supernatants to be extremely low relative to those of the control. However, the xanthine/hypoxanthine concentrations were much higher than those of the control.

Conclusions: We strongly confirmed the pathogenicity of the human MCSU gene.
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http://dx.doi.org/10.1159/000374042DOI Listing
February 2016

High Concentrations of Uric Acid Inhibit Endothelial Cell Migration via miR-663 Which Regulates Phosphatase and Tensin Homolog by Targeting Transforming Growth Factor-β1.

Microcirculation 2015 May;22(4):306-14

State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center of Kidney Diseases, Chinese PLA Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.

Background: Whether microRNAs participate in endothelial dysfunction HUA remains unknown. A previous study indicated that miR-663 was the most significantly differentially expressed endothelial microRNA under HUA conditions. Some studies have demonstrated that the miR-663 target gene and TGF-β1, promoted endothelial cell migration by inhibiting PTEN deleted on chromosome 10. Therefore, we hypothesized that HUA inhibits endothelial migration via miR-663, which regulates PTEN by targeting TGF-β1.

Methods: PCR analysis was performed to determine miR-663 expression levels. A luciferase assay was performed to validate whether miR-663 targets TGF-β1 directly. Western blot analysis was performed to determine TGF-β1 and PTEN expression levels. An miR-663 inhibitor and TGF-β1- and PTEN-specific siRNAs were transfected into EA.hy926 cells to inhibit miR-663, TGF-β1, and PTEN expression, respectively. A wound healing assay was performed to determine the migratory ability of EA.hy926 cells.

Results: miR-663 had higher expression levels in HUA-stimulated endothelial cells and in the sera of hyperuricemic patients and animals. TGF-β1 was targeted directly by miR-663. Endothelial miR-663 was up-regulated under HUA conditions, and HUA inhibited endothelial cell migration via miR-663, which targeted TGF-β1. Thus, TGF-β1 regulated cell migration in a PTEN-dependent manner.

Conclusion: HUA inhibits endothelial cell migration via miR-663, which regulates PTEN by targeting TGF-β1.
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http://dx.doi.org/10.1111/micc.12200DOI Listing
May 2015

Evaluation antibacterial activity of quaternary-based chitin/chitosan derivatives in vitro.

J Food Sci 2013 Jan;78(1):M90-7

College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, PR China.

Unlabelled: Total of 3 water-soluble quaternary-based chitin/chitosan derivatives, which have an identical molecular weight and anion, were synthesized and characterized. Their antibacterial activities against Salmonella cholerae-suis and Bacillus subtilis were evaluated in vitro. The polysaccharides exhibited the antibacterial efficiency. Their minimum inhibitory concentration (MIC) values vary from 0.02 to 20.48 mg/mL, and their minimum bactericidal concentration (MBC) values vary from 0.08 to 40.96 mg/mL against S. cholerae-suis and B. subtilis, respectively. Futhermore, the extent of Bacillus subtilis cells damage was examined via transmission electron microscopy (TEM) to show how N,N,N-trimethylchitosan (TMC) gradually destroyed and killed B. subtilis cells when they were treated with TMC. One of those quaternary polymers, O-([2-hydroxy-3-trimethylammonium])propyl chitin (OHT-chitin), which can be directly and easily synthesized from chitin in bulk quantities, also was demonstrated its antibacterial activity. These water soluble quaternary-based chitin/chitosan derivatives that have antibacterial effect should be potentially used as antimicrobial agents in many fields.

Practical Application: The main practical application behind the investigation and evaluation antibacterial activity of 3 water-soluble quaternary-based chitin/chitosan derivatives could be potentially used as antimicrobial agents in many fields. These polysaccharides represent a renewable source of natural biodegradable polymers and meet with the emergence of more and more food safe problems.
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http://dx.doi.org/10.1111/j.1750-3841.2012.02999.xDOI Listing
January 2013

Antibacterial activity evaluation of quaternary chitin against Escherichia coli and Staphylococcus aureus.

Int J Biol Macromol 2013 Jan 27;52:85-91. Epub 2012 Oct 27.

College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, 310035, PR China.

Water-soluble quaternary chitin/chitosan derivatives, O-[(2-hydroxy-3-trimethylammonium)propyl chitin (OHT-chitin), N-[(2-hydroxy-3-trimethylammonium)propyl chitosan (NHT-chitosan), and N,N,N-trimethylchitosan (TMC), having identical molecular weight and same anion, were prepared, and their antibacterial activities against Escherichia coli and Staphylococcus aureus were evaluated. Their minimum inhibitory concentration (MIC) values varied from 0.04 mg/mL to 20.48 mg/mL, and the minimum bactericidal concentration (MBC) values varied from 0.16 mg/mL to 40.96 mg/mL against E. coli and S. aureus, respectively. Transmission electron microscopy (TEM) clearly showed that there was serious damage on the bacterial walls, whereas there was some dissimilarity between TMC-treated E. coli and S. aureus.
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http://dx.doi.org/10.1016/j.ijbiomac.2012.10.017DOI Listing
January 2013

Synthesis and characteristics of chitin and chitosan with the (2-hydroxy-3-trimethylammonium)propyl functionality, and evaluation of their antioxidant activity in vitro.

Carbohydr Polym 2012 Jun 20;89(2):486-91. Epub 2012 Mar 20.

College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310035, PR China.

Quaternary amino groups were introduced into chitin and chitosan to obtain O-(2-hydroxy-3-trimethylammonium)propyl chitin (OHT-chitin) and N-(2-hydroxy-3-trimethylammonium)propyl chitosan (NHT-chitosan). They were characterized by FTIR spectra, and GPC. The molecular weight Mw of OHT-chitin and NHT-chitosan were 8986 and 9723 with polydispersity of 1.01 and 1.0 2, respectively. Their antioxidant activities in vitro were further studied. It was found that β-carotene-linoleic acid values of OHT-chitin and NHT-chitosan at 0.8 mg/mL were up to 91% and 96%, while that of chitosan was 40%. Based on photobleaching of α,α-diphenyl-β-picrylhydrazyl (DPPH) at 326 nm, the DPPH inhibitory activity of OHT-chitin and NHT-chitosan was 30.9% and 31.9% at 5 mg/mL, whereas chitosan only gave 4.8%. It was also exhibited that OHT-chitin and NHT-chitosan had better antioxidant activity than chitosan according to the reducing power as well as H2O2 scavenging activity.
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http://dx.doi.org/10.1016/j.carbpol.2012.03.032DOI Listing
June 2012
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