Publications by authors named "Xinzhou Zhang"

34 Publications

Label-free quantitative proteomic and phosphoproteomic analyses of renal biopsy tissues in membranous nephropathy.

Proteomics Clin Appl 2021 Sep 20:e2000069. Epub 2021 Sep 20.

Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.

Purpose: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. However, the underlying mechanisms of its occurrence and development are not completely clear. Thus, it is essential to explore the mechanisms.

Experimental Design: Here, we employed label-free quantification and liquid chromatography-tandem mass spectrometry analysis techniques to investigate the proteomic and phosphoproteomic alterations in renal biopsy tissues of MN patients. Samples were collected from 16 MN patients and 10 controls. Immunohistochemistry (IHC) was performed to validate the hub phosphoprotein.

Results: We focused on the changes in the phosphoproteome in MN group versus control group (CG). Totally, 1704 phosphoproteins containing 3241 phosphosites were identified and quantified. The phosphorylation levels of 216 phosphoproteins containing 297 phosphosites were differentially regulated in stage II MN group versus CG, and 333 phosphoproteins containing 461 phosphosites were differentially phosphorylated in stage III MN group versus CG. In each comparison, several differential phosphoproteins were factors, kinases and receptors involved in cellular processes, biological regulation and other biological processes. The subcellular location of most of the differential phosphoproteins was the nucleus. Protein-protein interaction analysis showed that the connections among the differential phosphoproteins were extremely complex, and several signalling pathways probably associated with MN were identified. The hub phosphoprotein was validated by IHC.

Conclusions And Clinical Relevance: This investigation can provide direct insight into the global phosphorylation events in MN group versus CG and may help to shed light on the potential pathogenic mechanisms of MN.
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http://dx.doi.org/10.1002/prca.202000069DOI Listing
September 2021

The Landscape and Potential Regulatory Mechanism of Lysine 2-Hydroxyisobutyrylation of Protein in End-Stage Renal Disease.

Nephron 2021 Sep 3:1-10. Epub 2021 Sep 3.

Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen, China.

Background: Acetylation has a vital role in the pathogenesis of end-stage renal disease (ESRD). Lysine 2-hydroxyisobutyrylation (Khib) is a novel type of acetylation. In this study, we aimed to reveal the key features of Khib in peripheral blood monocytes (PBMCs) of patients with ESRD.

Method: We combined TMT labeling with LC-MS/MS analysis to compare Khib modification of PBMCs between 20 ESRD patients and 20 healthy controls. The pan 2-hydroxyisobutyrylation antibody-based affinity enrichment method was used to reveal the features of Khib, and the bioinformatics analysis was conducted to analyze the pathology of these Khib-modified proteins.

Result: Compared to healthy controls, we identified 440 upregulated proteins and 552 downregulated proteins in PBMCs of ESRD, among which 579 Khib sites on 324 upregulated proteins and 287 Khib sites on 188 downregulated proteins were identified. The site abundance, distribution, and function of the Khib protein were further analyzed. The bioinformatics analysis revealed that the Rho/ROCK signaling pathway was highly enriched in ESRD, suggesting that it might contribute to renal fibrosis in ESRD patients.

Conclusion: In this study, we found that Khib-modified proteins correlated with the occurrence and progression of ESRD.
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http://dx.doi.org/10.1159/000518424DOI Listing
September 2021

Evaluation of the combination of rapid diagnostic tests and microscopy for imported malaria surveillance in Anhui Province, China.

Acta Trop 2021 Oct 10;222:106042. Epub 2021 Jul 10.

School Health Service Management, Anhui Medical University, Hefei 230032, China. Electronic address:

Background: In the Anhui Province, China, efforts to interrupt the local malaria transmission were successful, with no endemic cases reported since 2014. Contrastingly, imported malaria cases are still being reported, indicating a disease reintroduction risk after years of elimination. A good surveillance system is key for avoiding the risk, detecting imported cases and possible cases associated with local transmission early. Therefore, rapid diagnostic tests (RDTs) were combined with microscopy to strengthen malaria surveillance in the province. Herein, we aimed to evaluate the efficacy of this surveillance strategy.

Methods: We conducted a retrospective study using malaria surveillance data from January 2016 to June 2020. Epidemiological characteristics and diagnostic information were analysed using descriptive and comparative statistics. The diagnostic performance of the combined toolbox (Wondfo RDTs plus microscopy) was evaluated based on its sensitivity, specificity, positive and negative predictive values, and Cohen's kappa coefficient, using real-time polymerase chain reaction as the gold standard.

Results: The combined toolbox displayed a higher overall sensitivity for malaria cases than that of microscopy alone (93.74% vs 89.37%; p <0.05), which could detect 94.65%, 88.16%, 95.00%, and 100.00% of Plasmodium falciparum, P. ovale, P. vivax, and P. malariae infections, respectively. In clinical practice, Wondfo RDTs ability to detect P. falciparum infections was better than that of microscopy (97.55% vs 89.67%, p < 0.05). In contrast, microscopy displayed a higher specificity than that of Wondfo RDTs (81.82% vs 63.28%, p <0.05). Moreover, the consistency between microscopy and the gold standard results was also better than that of RDTs (Kappa value:0.669 vs 0.596).

Conclusions: The combination of microscopy and RDTs is an effective strategy for malaria surveillance because it possibly detected more P. falciparum infections due to the introduction of RDTs. In contrast, microscopy is complementary to some limitations related to the use of RDTs in field practice. Thus, monitoring malaria cases in non-endemic areas may require employing more than one diagnostic tool in surveillance strategies. Moreover, further understanding of the advantages and disadvantages of different detection methods is necessary for applying optimum combinations in field settings.
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http://dx.doi.org/10.1016/j.actatropica.2021.106042DOI Listing
October 2021

The identification of circular RNAs from peripheral blood mononuclear cells in systemic lupus erythematosus.

BMC Med Genomics 2021 03 5;14(1):70. Epub 2021 Mar 5.

Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, 518020, People's Republic of China.

Background: The diagnosis of systemic lupus erythematosus (SLE) is complicated. This study explores the expression of circular RNAs (circRNAs), which are closed non-coding RNAs in which the 5' and 3' ends are covalently linked and which work by sponging microRNAs. CircRNAs were extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients to identify novel circRNA species that might be used for SLE diagnosis.

Methods: Microarray was applied to screening circRNAs changes in PBMCs obtained from SLE patients (n = 10) and healthy participants (n = 10), paired for age and sex. We then verified the selected circRNAs in PBMCs using quantitative reverse transcription-polymerase chain reaction amplification (qRT-PCR) in another cohort, including ten paired SLE patients and healthy participants. The correlation between the differential circRNAs and clinical pathology of SLE were analyzed.

Results: 182 up-regulated and 563 significantly down-regulated circRNAs in PBMCs of patients with SLE were identified. Besides, the qRT-PCR results were consistent with the microarray results. The correlation analysis revealed that has_circRNA_100236, has_circRNA_102489, and has_circRNA_101413 were correlated with positive anti-dsDNA, thrombocytopenia, and positive IgG, respectively. Lastly, their miRNAs targets and the binding sites were predicted.

Conclusion: We identified some dysregulated circRNAs in PBMCs from SLE patients, and these circRNAs may be developed as the novel biomarkers for the diagnosis of SLE.
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http://dx.doi.org/10.1186/s12920-021-00919-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941743PMC
March 2021

Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy.

Clin Proteomics 2021 Feb 8;18(1). Epub 2021 Feb 8.

Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, People's Republic of China.

Background: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions.

Methods: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry.

Results: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins.

Conclusions: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.
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http://dx.doi.org/10.1186/s12014-021-09314-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869230PMC
February 2021

Identification of a novel interplay between intestinal bacteria and metabolites in Chinese patients with IgA nephropathy via integrated microbiome and metabolome approaches.

Ann Transl Med 2021 Jan;9(1):32

The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.

Background: Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. The intestinal microbial ecosystem and metabolic network of IgAN have not been systematically analyzed. The present study aims to improve understanding of the gut microbiota and its metabolic capabilities to facilitate the development of diagnostic, therapeutic, and prognostic methods for IgAN.

Methods: We characterized the gut microbiota and metabolic patterns of fecal and serum samples of IgAN patients and healthy controls from the south of China using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches.

Results: We found that the relative abundances of and were higher in IgAN patients, whereas and were lower. Changes in the gut microbiota of IgAN affected the metabolism and absorbance of microbiota-associated metabolites, in particular polyunsaturated fatty acids, free amino acid, and oligopeptides, and activated the phenylalanine metabolism pathway, thereby constructing a unique metabolic system of IgAN. We identified six pivotal metabolites, including bilirubin, trimethoprim, stearamide, phenylalanine, cis-9,10-epoxystearic acid, and phosphatidylethanolamine 17:0, that connected the metabolic networks of the gut and blood. Additionally, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were shown to be associated with the classification of glomerular sclerosis.

Conclusions: We establish a relational network between microbiota, fecal metabolites, and serum metabolites in IgAN. The core microbiota and metabolites identified have promising value in therapeutic applications.
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http://dx.doi.org/10.21037/atm-20-2506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859797PMC
January 2021

Establishment of an induced pluripotent stem cell line SPHi001-A from a systemic lupus erythematosus patient combined with preeclampsia and psoriasis.

Stem Cell Res 2021 03 22;51:102192. Epub 2021 Jan 22.

Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China. Electronic address:

Systemic lupus erythematosus (SLE) is a heterogeneous, autoimmune disease that can affect multiple organs and systems such as skin, joints, kidneys, hematologic system or central nervous system. Women of childbearing age are the predominate population affected by SLE. In this study, we generated an iPS cell line from a 30-year-old female who was pregnant with a gestational age of 27 weeks and diagnosed with severe preeclampsia, SLE and psoriasis. This patient-specific iPSC line will be useful to create the specific disease model of systemic lupus erythematosus to elucidate the pathological mechanisms and develop drug screening.
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http://dx.doi.org/10.1016/j.scr.2021.102192DOI Listing
March 2021

NPHS2 gene polymorphism aggravates renal damage caused by focal segmental glomerulosclerosis with COL4A3 mutation.

Biosci Rep 2021 01;41(1)

Shenzhen Key Laboratory of Renal, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Guangdong, China.

Focal segmental glomerulosclerosis (FSGS), a type of primary glomerular disease, is the leading cause of end-stage renal disease (ESRD). Several studies have revealed that certain single-gene mutations are involved in the pathogenesis of FSGS; however, the main cause of FSGS has not been fully elucidated. Homozygous mutations in the glomerular basement membrane gene can lead to early renal failure, while heterozygous carriers develop renal failure symptoms late. Here, molecular genetic analysis of clinical information collected from clinical reports and medical records was performed. Results revealed that nephrosis 2 (NPHS2) gene polymorphism aggravated renal damage in three FSGS families with heterozygous COL4A3 mutation, leading to early renal failure in index patients. Our findings suggest that COL4A3 and NPHS2 may have a synergistic effect on renal injury caused by FSGS. Further analysis of the glomerular filtration barrier could help assess the cause of kidney damage. Moreover, a detailed analysis of the glomerular basement membrane-related genes and podocyte structural proteins may help us better understand FSGS pathogenesis and provide insights into the prognosis and treatment of hereditary glomerulonephropathy.
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http://dx.doi.org/10.1042/BSR20203248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786326PMC
January 2021

Report of a rare case of congenital mitral valve prolapse with chronic kidney disease--reconsidered genotype-phenotypic correlations.

Mol Genet Genomic Med 2021 01 22;9(1):e1558. Epub 2020 Nov 22.

Shenzhen Key Laboratory of Renal, Department of Nephrology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

Background: Mitral valve prolapse (MVP) is a common cardiovascular disease defined as a late systolic click or mitral valve lobes that move up into the left atrium during ventricular systole, with or without mitral insufficiency. Dachsous catherin-related 1 (DCHS1) is one of the two known pathogenic genes associated with MVP. However, there is little information about the renal dysfunction caused by MVP and DCHS1 mutations.

Methods: We analyzed the genetic etiology in a rare case of 9-year-old boy affected by chronic renal failure with MVP. Subsequently, we constructed stable cell lines overexpressing wild-type DCHS1 or mutant DCHS1 (c.8309G>A, p.R2770Q) to evaluate the influence of the DCHS1 mutation on the proliferation, apoptosis, and autophagy.

Results: Complete exome sequencing and pedigree verification revealed a mutation p.R2770Q (c.8309G>A) in exon 21 of the DCHS1 gene carried by the patient, which may affect the DNA binding. No such mutation was detected in his parents, indicating that this was a new mutation. Potential functional impact of sequence variants was predicted using in silico prediction programs including SIFT, Polyphen2, and Condel. This variant was determined to be a pathogenic mutation that has not been reported elsewhere. Subsequently, we used a stable DCHS1 gene-mutated HK-2 cell line to analyse proliferation, apoptosis, and autophagy, showed that kidney volume decreased with increasing cell death associated with a reduced proliferation.

Conclusions: Our analysis revealed a heterozygous variation of DCHS1 in a child with MVP. Our observations highlight previously unrecognized phenotypes of the currently recognized MVP genotype, including distinct chronic renal failure.
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http://dx.doi.org/10.1002/mgg3.1558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963429PMC
January 2021

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors in Patients with Renal Anemia: A Meta-Analysis of Randomized Trials.

Nephron 2020 31;144(11):572-582. Epub 2020 Aug 31.

Department of Nephrology, Shenzhen People's Hospital, The Second Affiliated Hospital, Jinan University, Shenzhen, China.

Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of treatment for renal anemia in patients with chronic kidney disease (CKD). This meta-analysis was designed to evaluate their efficacy and safety.

Method: Eight databases were searched for randomized controlled trials (RCTs). Information about efficacy and safety was extracted and combined using random-effects or fixed-effects models, depending on heterogeneity. Risk of bias was assessed using the method recommended by the Cochrane Centre.

Results: Nineteen articles on RCTs were selected, involving 3,289 participants. We found that HIF-PHIs improved the level of hemoglobin (Hb) (weighted mean difference [WMD] 1.40; 95% CI: 0.96-1.84; p < 0.001), response rate of Hb (risk ratio [RR] 5.95; 95% CI: 3.95-8.96; p < 0.001), and total iron-binding capacity (WMD 42.94; 95% CI: 31.39-54.49; p < 0.001), while reducing the level of hepcidin (WMD -40.42; 95% CI: -50.44 to -30.39; p < 0.001), ferritin (WMD -64.60; 95% CI: -78.56 to -50.64; p < 0.001), and transferrin saturation (WMD -5.57; 95% CI: -8.53 to -2.61; p < 0.001). Meanwhile, there was no evidence of effect on serum iron (WMD 1.60; 95% CI: -3.72 to 6.93; p = 0.55), nor on the incidence of adverse events (AEs) (RR 1.06; 95% CI: 0.99-1.15; p = 0.51) or of serious adverse events (SAEs) (RR 1.14; 95% CI: 0.88-1.46; p = 0.32).

Conclusion: HIF-PHIs ameliorate renal anemia and rectify iron metabolism in the short term without increasing the incidence of AEs and SAEs.
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http://dx.doi.org/10.1159/000508812DOI Listing
October 2021

Tissue-engineered parathyroid gland and its regulatory secretion of parathyroid hormone.

J Tissue Eng Regen Med 2020 10 13;14(10):1363-1377. Epub 2020 Aug 13.

Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.

Parathyroid glands (PTGs) are important endocrine organs being mainly responsible for the secretion of parathyroid hormone (PTH) to regulate the balance of calcium (Ca) /phosphorus (P) ions in the body. Once PTGs get injured or removed, their resulting defect or loss of PTH secretion should disturb the level of Ca/P in blood, thus damaging other related organs (bone, kidney, etc.) and even causing death. Recently, tissue-engineered PTGs (TE-PTGs) have attracted lots of attention as a potential treatment for the related diseases of PTGs caused by hypoparathyroidism and hyperparathyroidism, including tetany, muscle cramp, nephrolithiasis, nephrocalcinosis, and osteoporosis. Although great progress has been made in the establishment of TE-PTGs with an effective strategy to integrate the key factors of cells and biomaterials, its regulatory secretion of PTH to mimic its natural rhythms in the body remains a huge challenge. This review comprehensively describes an overview of PTGs from physiology and pathology to cytobiology and tissue engineering. The state of the arts in TE-PTGs and the feasible strategies to regulate PTH secretion behaviors are highlighted to provide an important foundation for further investigation.
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http://dx.doi.org/10.1002/term.3080DOI Listing
October 2020

MiR-182 inhibits kidney fibrosis by regulating transforming growth factor β1/Smad3 pathway in autosomal dominant polycystic kidney disease.

IUBMB Life 2020 07 17;72(7):1340-1348. Epub 2020 Feb 17.

Key Renal Laboratory of Shenzhen, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, China.

The aim of the present study was to investigate the molecular mechanism of miR-182 in kidney fibrosis in polycystic kidney disease (PKD). We measured the expression of miR-182 in kidney tissue of autosomal dominant PKD. Additionally, we investigated the relationship between miR-182 and fibrotic protein by transfecting miR-182 mimics and miR-182 inhibitor into polycystic kidney cyst-lined epithelial cells, respectively. Furthermore, we observed the interaction between transforming growth factor β1 (TGF-β1) and miR-182 and fibrinogen factors of cyst-lined epithelial cells after TGF-β1 intervention, and measured the expression of Smad2 and Smad3 protein. Results are presented as follows: (a) MiR-182 was positively correlated with fibrosis of cyst-lined epithelial cells; (b) TGF-β1 could induce fibrosis of cyst-lined epithelial cells; (c) the expression of miR-182 had a remarkably impact on the fibrosis induced by TGF-β1, but had little effect on the expression of TGF-β1; (d) the expression of Smad3 protein in TGF-β1 induce-cyst-lined epithelial cells was increased. TGF-β1 and miR-182 promoting the fibrosis of polycystic kidney cyst-lined epithelial cells may be mediated by the TGF-β1/Smad3 signaling pathway, of which Smad3 was an important regulator.
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http://dx.doi.org/10.1002/iub.2255DOI Listing
July 2020

Central arterial and peripheral arterial blood pressure in patients with chronic kidney disease undergoing versus not undergoing hemodialysis.

J Int Med Res 2020 Apr 31;48(4):300060519895848. Epub 2019 Dec 31.

Key Renal Laboratory of Shenzhen, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.

Objective: We assessed the consistency of noninvasive and invasive measurements of central arterial pressure (CAP) and the difference between peripheral brachial artery pressure and CAP in patients with chronic kidney disease (CKD) undergoing versus not undergoing hemodialysis.

Methods: This single-center cross-sectional study was performed from May to December 2018. The patients were divided into a control group (n = 50), CKD group (stages 3-5, n = 50), and dialysis group (n = 20), and all underwent measurement of peripheral humeral arterial pressure and noninvasive and invasive measurement of CAP. Group differences and correlations between CAP and peripheral arterial pressure were assessed.

Results: The consistency between noninvasive and invasive CAP was better in the control and CKD groups than in the dialysis group. In the dialysis group, the noninvasive equipment underestimated the actual CAP. The CAP was close to the peripheral brachial artery pressure in the dialysis group, while the CAP was significantly lower than the peripheral brachial artery pressure in the control and CKD groups.

Conclusion: Noninvasive equipment underestimates the actual CAP in patients undergoing dialysis and should be used with caution. The difference between the peripheral arterial pressure and CAP was smaller in patients undergoing dialysis than in patients with CKD and controls.
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http://dx.doi.org/10.1177/0300060519895848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783254PMC
April 2020

A single-cell map for the transcriptomic signatures of peripheral blood mononuclear cells in end-stage renal disease.

Nephrol Dial Transplant 2021 03;36(4):599-608

Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China.

Background: Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited.

Methods: We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types.

Results: We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified.

Conclusions: We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD.
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http://dx.doi.org/10.1093/ndt/gfz227DOI Listing
March 2021

Histone Deacetylase Inhibitors Reduce Cysts by Activating Autophagy in Polycystic Kidney Disease.

Kidney Dis (Basel) 2019 Jun 10;5(3):163-172. Epub 2019 May 10.

Key Renal Laboratory of Shenzhen, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, China.

Background: Histone deacetylase inhibitors (HDACi) have therapeutic effects on various models of renal diseases including autosomal dominant polycystic kidney disease (ADPKD), but the molecular mechanism is unclear.

Objectives: Here, we studied the role of trichostatin A (TSA), a specific HDACi, in regulating cyst growth to test the possibility that HDACi might help manage ADPKD by enhancing autophagy.

Results: Autophagy protein expression was higher in cultured knockout (Pkd1-/-) cells, an in vitro model of cystogenesis, compared with control cells. TSA prevented cyst formation in Pkd1-/- cells. We further tested whether TSA could not reduce the size of an already established cyst after inhibition of autophagy by chloroquine in Pkd1-/- cells. In vivo, treatment with TSA significantly slowed cyst growth in Pkd1-/- mice. Moreover, TSA treatment stimulated AMPK and inactivated mTOR during cyst growth in Pkd1-/- cells and kidneys in mice.

Conclusions: Our results suggest that HDACi may prevent cyst formation by activation of the AMPK pathway and autophagy. They also imply that HDACi could have therapeutic potential for ADPKD treatment.
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http://dx.doi.org/10.1159/000499368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587212PMC
June 2019

Differential expression study of circular RNAs in exosomes from serum and urine in patients with idiopathic membranous nephropathy.

Arch Med Sci 2019 May 30;15(3):738-753. Epub 2019 Apr 30.

Department of Nephrology, Shenzhen People's Hospital, Shenzhen Key Laboratory of Kidney Disease, Second Clinical Medical College, Jinan University, Guangzhou city, Guangdong province, China.

Introduction: The aim of the study was to further explore the pathogenesis of idiopathic membranous nephropathy (IMN), gene-sequencing was used to analyze the differentially expressed circRNAs in exosomes of patients with IMN, which may lay the foundation for the research of circRNAs as a new class of exosome-based IMN diagnosis biomarkers.

Material And Methods: Ten patients with IMN and ten normal controls were recruited as experimental subjects in our study. The exosomes were extracted from the collected serum and urine. Then, pure circRNAs were extracted from the exosomes with a series of enzymatic reactions. Afterwards, the significantly differentially expressed circRNAs were chosen by the method of gene-sequencing.

Results: Compared with normal controls, the circRNAs were reduced in the exosomes from serum of patients with IMN, which mostly originated from intron gene regions. Meanwhile, a total of 89 circRNAs were significantly differentially expressed, which were also mostly derived from intron gene regions, including 49 up-regulated and 40 down-regulated genes. However, the species were increased in the exosomes from the urine of patients with IMN compared to normal controls, and they mainly originated from exon gene regions. Simultaneously, 60 circRNAs were significantly differentially expressed, which primarily belonged to intron gene regions, including 54 up-regulated and 6 down-regulated regions.

Conclusions: The significant differential and specific expression of circRNAs in the exosomes from patients with IMN were observed. For example, MUC3A, which originated from chr7:100550808|100551062, could be considered a potential diagnostic biomarker of IMN. Furthermore, these figures may be used as a reference or supplement in the research of the pathogenesis of IMN.
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http://dx.doi.org/10.5114/aoms.2019.84690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524185PMC
May 2019

Three-Dimensional Printing of Biodegradable Piperazine-Based Polyurethane-Urea Scaffolds with Enhanced Osteogenesis for Bone Regeneration.

ACS Appl Mater Interfaces 2019 Mar 13;11(9):9415-9424. Epub 2019 Feb 13.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering , Chongqing University , Chongqing 400030 , China.

Synthetic biodegradable polymeric scaffolds with uniformly interconnected pore structure, appropriate mechanical properties, excellent biocompatibility, and even enhanced osteogenesis ability are urgently required for in situ bone regeneration. In this study, for the first time, a series of biodegradable piperazine (PP)-based polyurethane-urea (P-PUU) scaffolds with a gradient of PP contents were developed by air-driven extrusion 3D printing technology. The P-PUU ink of 60 wt % concentration was demonstrated to have appropriate viscosity for scaffold fabrication. The 3D-printed P-PUU scaffolds exhibited an interconnected porous structure of about 450 μm in macropore size and about 75% in porosity. By regulating the contents of PP in P-PUU scaffolds, their mechanical properties could be moderated, and P-PUU1.4 scaffolds with the highest PP contents exhibited the highest compressive modulus (155.9 ± 5.7 MPa) and strength (14.8 ± 1.1 MPa). Moreover, both in vitro and in vivo biological results suggested that the 3D-printed P-PUU scaffolds possessed excellent biocompatibility and osteoconductivity to facilitate new bone formation. The small molecular PP itself was confirmed for the first time to regulate osteogenesis of osteoblasts in a dose-dependent manner and the optimum concentration for osteoconductivity was about ∼0.5 mM, which suggests that PP molecules, together with the mechanical behavior, nitrogen-contents, and hydrophilicity of P-PUUs, play an important role in enhancing the osteoconductive ability of P-PUU scaffolds. Therefore, the 3D-printed P-PUU scaffolds, with suitable interconnected pore structure, appropriate mechanical properties, and intrinsically osteoconductive ability, should provide a promising alternative for bone regeneration.
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http://dx.doi.org/10.1021/acsami.8b20323DOI Listing
March 2019

Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant.

Arch Med Sci 2018 Aug 20;14(5):1102-1111. Epub 2017 Oct 20.

Department of Nephrology, Shenzhen People's Hospital, Shenzhen Key Laboratory of Kidney Disease, Second Clinical Medical College, Jinan University, Shenzhen, China.

Introduction: To analyze the microRNA expression of tumor necrosi factor α (TNF-α) stimulated mesenchymal stem cells (MSCs) and exosomes from their culture supernatant.

Material And Methods: TNF-α (20 ng/ml) was used to stimulate MSCs, which were then regarded as TNF-α cells (TC), while unstimulated cells were the normal control cells (NCC). MSCs and their culture supernatant were harvested after 48 h. Subsequently, exosomes were isolated from culture supernatants with ExoQuick-TC and were divided into two groups, TNF-α exosomes (TE) and normal control exosomes (NCE). Then, the microRNAs were measured by high-throughput sequencing and the results were differentially analyzed. Finally, the correlation of the target genes corresponding to differently expressed microRNAs was analyzed by gene ontology (GO) and KEGG pathway analysis.

Results: High-throughput sequencing showed that the cellular compartment (TC vs. NCC) had 280 microRNAs. miR-146a-5p was a uniquely up-regulated microRNA ( < 0.001) and the most significantly down-regulated microRNA among the 279 microRNAs included was miR-150-5p ( < 0.001). There were 180 differentially expressed microRNAs in the exosome compartment (TE vs. NCE), where miR-146-5p ( < 0.001) was one of 176 upregulated microRNAs and miR-203b-5p ( < 0.001) was one of 4 downregulated microRNAs. Coincidentally, bioinformatics analysis showed that IRAK1 was a critical target gene of miR-146-5p related to the Toll-like receptor (TLR) signaling pathway.

Conclusions: In contrast with the control group, there were significantly differentially expressed microRNAs in both MSCs and exosomes. Interestingly, miR-146a-5p was up-regulated in both comparative groups, and its target gene IRAK1 plays a crucial part in the TLR signaling pathway. These investigations demonstrate a new direction for subsequent inflammation mechanistic studies.
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http://dx.doi.org/10.5114/aoms.2017.70878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6111343PMC
August 2018

Protective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.

Am J Physiol Renal Physiol 2018 09 16;315(3):F469-F478. Epub 2018 May 16.

Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center , Augusta, Georgia.

As a potent chemotherapy drug, cisplatin is also notorious for its side-effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extraterminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the measurements of kidney function, histopathology, and renal tubular apoptosis. JQ1 also partially prevented the body weight loss during cisplatin treatment in mice. Consistently, JQ1 inhibited cisplatin-induced apoptosis in renal proximal tubular cells. Mechanistically, JQ1 suppressed cisplatin-induced phosphorylation or activation of p53 and Chk2, key events in DNA damage response. JQ1 also attenuated cisplatin-induced MAP kinase (p38, ERK1/2, and JNK) activation. In addition, JQ1 enhanced the expression of antioxidant genes including nuclear factor erythroid 2-related factor 2 and heme oxygenase-1, while diminishing the expression of the nitrosative protein inducible nitric oxide synthase. JQ1 did not suppress cisplatin-induced apoptosis in A549 nonsmall cell lung cancer cells and AGS gastric cancer cells. These results suggest that JQ1 may protect against cisplatin nephrotoxicity by suppressing DNA damage response, p53, MAP kinases, and oxidative/nitrosative stress pathways.
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http://dx.doi.org/10.1152/ajprenal.00527.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172575PMC
September 2018

Integrated analysis of B‑cell and T‑cell receptors by high‑throughput sequencing reveals conserved repertoires in IgA nephropathy.

Mol Med Rep 2018 May 20;17(5):7027-7036. Epub 2018 Mar 20.

Clinical Medical Research Center of Second Clinical Medical College, Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.

Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.001). There were also certain conserved amino acid residues between unique clones or groups, and the residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition, some VDJ gene recombinations indicated great variation between groups, including 4 high‑frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ gene recombinations with great variation may be potential therapeutic targets for IgAN patients.
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http://dx.doi.org/10.3892/mmr.2018.8793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5928659PMC
May 2018

Characterization of the T-cell receptor repertoire by deep T cell receptor sequencing in tissues from patients with prostate cancer.

Oncol Lett 2018 Feb 23;15(2):1744-1752. Epub 2017 Nov 23.

Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong 518020, P.R. China.

Prostate cancer (PC) is the most prevalent urological cancer in men. T cells serve a central role in the cancer's immunological microenvironment. In the present study, we applied multiplex PCR and Illumina next-generation sequencing to study the clonal diversity of the T-cell receptor (TCR) repertoire in cancer tissues and paracancer tissues from patients with PC. It was found that the TCR repertoire in the PC samples had a notably more skewed clonotype composition, with a greater number of highly expanded clones (HECs) compared with the prostate paracancer samples. The amino acid sequences ATSRVAGETQY (1.008 vs. 0.002%), ATSRTGRWETQY (3.985 vs. 0.007%), ATSDSSDYEQY (12.464 vs. 0.027%), ATSDFRGQPQETQY (2.205 vs. 0.06%), ASSQQDEAF (1.109 vs. 0.002%) and ARPTRTEETQY (1.263 vs. 0.002%) were found to vary markedly between cancer and paracancer tissues, respectively. In conclusion, the present study identified PC-specific HECs, which are critical to improving understanding of the TCR repertoire in PC. This may accelerate the screening process for potential new autoantigens and provide information for generating more effective T cell-targeted diagnostic and therapeutic strategies.
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http://dx.doi.org/10.3892/ol.2017.7479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774533PMC
February 2018

Neural regulation of bone remodeling: Identifying novel neural molecules and pathways between brain and bone.

J Cell Physiol 2019 05 7;234(5):5466-5477. Epub 2018 Dec 7.

The Brain Cognition & Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

The metabolism and homeostasis of the skeletal system have historically been considered to be associated with the endocrine system. However, this view has been expanded with the recognition of several neural pathways playing important roles in the regulation of bone metabolism via central relays. In particular, bone metabolism and homeostasis have been reported to be precisely modulated by the central neural signaling. Initiated by the finding of leptin, the axis of neural regulation on bone expands rapidly. The semaphorin-plexin system plays an important role in the cross-talk between osteoclasts and osteoblasts; a complex system has also been identified and includes neuropeptide Y and cannabinoids. These findings facilitate our understanding of the central neuropeptides and neural factors in the modulation of bone metabolism and homeostasis, and these neuronal pathways also represent an area of research scenario that identifies the novel regulation between brain and bone. These regulatory mechanisms correlate with other homeostatic networks and demonstrate a more intricate and synergetic bone biology than previously envisioned. As such, this review summarizes the current knowledge of the neural regulation of bone metabolism and homeostasis, as well as its role in skeletal diseases and discusses the emerging challenges presented in this field.
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http://dx.doi.org/10.1002/jcp.26502DOI Listing
May 2019

Frequency of virulence factors in high biofilm formation bla producing Klebsiella pneumoniae strains from hospitals.

Microb Pathog 2018 Mar 20;116:168-172. Epub 2018 Feb 20.

Department of Pathogenic Biology, School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

The aim of this study is to determine the frequency of virulence genes in high biofilm formation bla producing Klebsiella pneumoniae strains collected over a period of two years. A total of 43 non-repetitive high biofilm bla producing isolates were screened from 429 strains. The MIC of carbapenems (imipenem and meropenem) ranged from 4 to 32 μg/ml. The OD595 value of the biofilm ranged from 0.56 to 2.56. The K1, K2, K5, K20, K54, K57 genotypes, MLST and virulence factors, including entB, ybtS, mrkD, fimH, rmpA, allS, iutA, kfu, wcaG, aerobaction, fecIRA, shiF, magA and pagO gene, were determined by PCR. The results showed that, among the 43 isolates, 5 of 43 were K1 type, 25 of 43 were K2 type, 4 strains and 2 strains were K5 and K57 respectively. The MLST results showed that 23/43 strains were ST11, followed by ST433(4/43), ST107(4/43), ST690(4/43), ST304(2/43), ST2058(1/43), ST1(1/43), ST146(1/43), ST914(1/43), ST2636(1/43), ST2637(1/43). As to the virulence factors, all 43 strains carried entB, ybtS and mrkD gene, followed by fimH(38/43), rmpA(14/43), allS(34/43), iutA(27/43), kfu(25/43), wcaG(21/43), aerobaction(16/43), fecIRA(15/43), shiF(10/43), magA(5/43) and pagO(5/43). This study demonstrated that high frequency of virulence factors emerging in high biofim bla producing strains. It also suggested that we should continue to focus on the toxicity variation and it's high time to enhance clinical awareness to the infections causing by Klebsiella pneumoniae.
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http://dx.doi.org/10.1016/j.micpath.2018.01.030DOI Listing
March 2018

Risk Factor Analysis for AKI Including Laboratory Indicators: a Nationwide Multicenter Study of Hospitalized Patients.

Kidney Blood Press Res 2017 24;42(5):761-773. Epub 2017 Oct 24.

Department of Nephrology, the 306th Hospital of PLA, Beijing, China.

Background/aims: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators.

Methods: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes' definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality.

Results: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set.

Conclusion: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.
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http://dx.doi.org/10.1159/000484234DOI Listing
August 2018

The interfacial pH of acidic degradable polymeric biomaterials and its effects on osteoblast behavior.

Sci Rep 2017 07 28;7(1):6794. Epub 2017 Jul 28.

Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.

A weak alkaline environment is established to facilitate the growth of osteoblasts. Unfortunately, this is inconsistent with the application of biodegradable polymer in bone regeneration, as the degradation products are usually acidic. In this study, the variation of the interfacial pH of poly (D, L-lactide) and piperazine-based polyurethane ureas (P-PUUs), as the representations of acidic degradable materials, and the behavior of osteoblasts on these substrates with tunable interfacial pH were investigated in vitro. These results revealed that the release of degraded products caused a rapid decrease in the interfacial pH, and this could be relieved by the introduction of alkaline segments. On the contrary, when culturing with osteoblasts, the variation of the interfacial pH revealed an upward tendency, indicating that cell could construct the microenvironment by secreting cellular metabolites to satisfy its own survival. In addition, the behavior of osteoblasts on substrates exhibited that P-PUUs with the most PP units were better for cell growth and osteogenic differentiation of cells. This is due to the hydrophilic surface and the moderate N% in P-PUUs, key factors in the promotion of the early stages of cellular responses, and the interfacial pH contributing to the enhanced effect on osteogenic differentiation.
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http://dx.doi.org/10.1038/s41598-017-06354-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533751PMC
July 2017

Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China.

Nephrol Dial Transplant 2017 Aug;32(8):1373-1386

FibroGen, Inc., San Francisco, CA, USA.

Background: FG-4592 (roxadustat) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor (HIF-PHI) promoting coordinated erythropoiesis through the transcription factor HIF. Two Phase 2 studies were conducted in China to explore the safety and efficacy of FG-4592 (USAN name: roxadustat, CDAN name: ), a HIF-PHI, in patients with anemia of chronic kidney disease (CKD), both patients who were dialysis-dependent (DD) and patients who were not dialysis-dependent (NDD).

Methods: In the NDD study, 91 participants were randomized to low (1.1-1.75 mg/kg) or high (1.50-2.25 mg/kg) FG-4592 starting doses or to placebo. In the DD study, 87 were enrolled to low (1.1-1.8 mg/kg), medium (1.5-2.3 mg/kg) and high (1.7-2.3 mg/kg) starting FG-4592 doses or to continuation of epoetin alfa. In both studies, only oral iron supplementation was allowed.

Results: In the NDD study, hemoglobin (Hb) increase ≥1 g/dL from baseline was achieved in 80.0% of subjects in the low-dose cohort and 87.1% in the high-dose cohort, versus 23.3% in the placebo arm (P < 0.0001, both). In the DD study, 59.1%, 88.9% (P = 0.008) and 100% (P = 0.0003) of the low-, medium- and high-dose subjects maintained their Hb levels after 5- and 6-weeks versus 50% of the epoetin alfa-treated subjects. In both studies, significant reductions in cholesterol were noted in FG-4592-treated subjects, with stability or increases in serum iron, total iron-binding capacity (TIBC) and transferrin (without intravenous iron administration). In the NDD study, hepcidin levels were significantly reduced across all FG-4592-treated arms as compared with no change in the placebo arm. In the DD study, hepcidin levels were also reduced in a statistically significant dose-dependent manner in the highest dose group as compared with the epoetin alfa-treated group. Adverse events were similar for FG-4592-treated and control subjects.

Conclusions: FG-4592 may prove an effective alternative for managing anemia of CKD. It is currently being investigated in a pivotal global Phase 3 program.
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http://dx.doi.org/10.1093/ndt/gfx011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837707PMC
August 2017

TRAF3 delays cyst formation induced by NF-κB signaling.

IUBMB Life 2017 03 10;69(3):170-178. Epub 2017 Feb 10.

Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.

This study aims to investigate the effects of TNF receptors associated factor 3 (TRAF3) on the signaling pathway and expression of downstream products of nuclear factor kappa B (NF-κB) in the epithelial cells of renal ducts in individuals with polycystic kidney disease (PKD). We observe the TRAF3 genic overexpression of the epithelial cells, which form a tubular branch structure, in polycystic kidneys and to explore the protective effect of TRAF3 on the cystogenesis and progression of PKD. Western blotting analysis was conducted to examine the signaling changes of NF-κB in PKD the epithelial cells and TRAF3 transgenic PKD epithelial cells. Changes in the downstream apoptosis factor and cell proliferation in PKD epithelial cells and TRAF3 transgenic PKD epithelial cells were detected. A three-dimensional matrigel culture experiment was performed to examine abnormal tubulomorphogenesis in vitro. The overexpression of TRAF3 significantly inhibited the signaling pathway of NF-κB in the PKD epithelial cells, downregulated the expression of downstream factors Bcl-2 and Bcl-xl, and significantly decreased cystic epithelial cell proliferation. Additional branch structures were observed in the PKD epithelial cells with a three-dimensional culture compared to wildtype cells. TRAF3 may likely induce apoptosis and resistance to proliferation and may be a new target to inhibit the cyst formation in PKD by regulating the NF-κB signaling pathway Bcl-2 and Bcl-xl activity. © 2017 IUBMB Life, 69(3):170-178, 2017.
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http://dx.doi.org/10.1002/iub.1601DOI Listing
March 2017

The effect of esculentoside A on lupus nephritis-prone BXSB mice.

Arch Med Sci 2013 Apr 30;9(2):354-60. Epub 2012 Oct 30.

Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.

Introduction: EsA was reported to have the effect of modulating immune response, cell proliferation and apoptosis as well as anti-inflammatory effects in acute and chronic experimental models. However, the effects of EsA on LN remain poorly understood. To investigate the roles of EsA in LN, the effects of EsA were tested on BXSB mice, a SLE model, in which male SB/Le mice and female C57BL/6 mice were hybridized through recombinant inbred species.

Material And Methods: Twenty four BXSB mice were divided into three groups. After 4 weeks, blood samples, urine samples and kidney tissues were collected. Measurement of cytokine levels was carried out using sandwich ELISA reagent kits. Apoptotic scores were obtained with a TUNEL assay. PCNA and Caspase-3 mRNA was detected using the In Situ Hybridization Detection Kit.

Results: The results demonstrated that compared with the control group, EsA administration markedly controlled urine protein excretion, improved renal function, alleviated kidney damage and promoted the apoptosis of glomerular intrinsic cells and renal tubular epithelial cells in animals of the treated group (p < 0.05). Meanwhile, EsA reduced the serum IL-6 and TNF-α levels (p < 0.05), inhibited the expression of PCNA and promoted the expression of caspase-3, Fas and FasL in animals of the treated group (p < 0.05). The effects of EsA on BXSB mice were similar to dexamethasone.

Conclusions: All these findings indicated that EsA might play significant roles in the treatment of BXSB mice through modulation of inflammatory cytokines, inhibition of renal cell proliferation and induction of apoptosis. The special targets of EsA in lupus nephritis are worth further exploration.
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http://dx.doi.org/10.5114/aoms.2012.31439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648817PMC
April 2013

Human umbilical mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis.

Am J Med Sci 2013 Dec;346(6):486-93

Department of Nephrology (HM, LS, XZ), Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China; Life Science Division (YW), Graduate School at Shenzhen, Tsinghua University, Shenzhen, China; and Department of Rehabilitation, Chancheng District Central Hospital of Foshan City, Foshan, China.

Previous studies have suggested the potential of mesenchymal stem cells (MSCs) to repair damaged kidney diseases. However, the effect of human umbilical cord MSCs (HuMSCs) on the progression of focal segmental glomerulosclerosis (FSGS) remains poorly understood. Adriamycin-induced nephropathy is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of FSGS. This study aimed to investigate the role of HuMSCs on the progression of kidney disease using a model of adriamycin-induced nephropathy. Human MSCs were labeled with 5-bromo-2'-deoxyuridine to track their localization to the kidneys after infusion. Clinical parameters and histology suggested amelioration of FSGS in MSC-treated animals at 12 weeks, especially in those that received repeated doses. These results were associated with reduced serum interleukin (IL)-6 and tumor necrosis factor-α, transforming growth factor-β levels, connective tissue growth factor messenger RNA expression and upregulated serum IL-10 levels. In short, this experiment found that HuMSCs improved kidney fibrosis and modulated the inflammatory response, suggesting that xenogenic transplantation of HuMSCs is a novel approach for improving the progression of FSGS and may be a promising therapeutic intervention in the future.
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http://dx.doi.org/10.1097/MAJ.0b013e3182831777DOI Listing
December 2013

The effect of mesenchymal stromal cells on doxorubicin-induced nephropathy in rats.

Cytotherapy 2013 Jun 14;15(6):703-11. Epub 2013 Mar 14.

Department of Nephrology, Shenzhen People's Hospital, Second Clinical Medical College, Jinan University, Shenzhen, China.

Background Aims: The potential protective effects of mesenchymal stromal cells (MSCs) on some kidney diseases has been reported. However, the effect of MSCs on doxorubicin-induced nephropathy is still poorly understood.

Methods: Rats with doxorubicin-induced kidney injuries were treated with human cord-derived MSCs. Human MSCs were first labeled with 5-bromo-2'-deoxyuridine to track their homing in kidneys after infusion.

Results: Alleviation of proteinuria, decreased serum albumin, alleviation of lipid disorders and histologic alterations were found in rats 4 weeks after treatment with MSCs, particularly in rats that were given repeat doses. Decreases in serum levels of interleukin-6, tumor necrosis factor-α and prostaglandin E2 and decreases in messenger RNA levels of kidney tissue cylooxygenase-2 and EP4 were found in MSC-treated rats. MSC-treated rats also displayed an increase in serum interleukin-10 levels.

Conclusions: These results indicate that MSCs ameliorate doxorubicin-induced kidney injuries and inflammation, suggesting a potential clinical treatment for inflammatory kidney diseases.
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http://dx.doi.org/10.1016/j.jcyt.2013.02.002DOI Listing
June 2013
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