Publications by authors named "Zhanting Li"

10 Publications

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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

miR-181c protects CsA-induced renal damage and fibrosis through inhibiting EMT.

FEBS Lett 2017 11 19;591(21):3588-3599. Epub 2017 Oct 19.

Nephrology Division, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Cyclosporine A (CsA), a widely used immunosuppressive drug in organ transplantation and autoimmune disorders, frequently induces renal damage and fibrosis. Recent evidence has implicated epithelial-mesenchymal transition (EMT) in CsA-induced nephrotoxicity. Microarray analysis disclosed miR-181c as the microRNA most dramatically repressed by CsA. Downregulation of miR-181c expression at the transcriptional level by CsA is dependent on the transcription factor Nrf2. miR-181c mimics or inhibitors attenuate or aggravate CsA-induced EMT gene changes, respectively. Importantly, in Nrf2-/- mice, CsA-induced renal damage, fibrosis, and EMT gene changes are restored by miR-181c mimics. Mechanistically, we identified Notch2 as a potential target of miR-181c. Collectively, our data support the notion that miR-181c may serve as an important factor for protecting renal tissues from CsA-induced nephrotoxicity.
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http://dx.doi.org/10.1002/1873-3468.12872DOI Listing
November 2017

Proposed Hydrogen-Bonding Index of Donor or Acceptor Reflecting Its Intrinsic Contribution to Hydrogen-Bonding Strength.

J Chem Inf Model 2017 07 16;57(7):1535-1547. Epub 2017 Jun 16.

School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, P. R. China.

In this work, we tentatively propose that the hydrogen-bonding strength E (referring to the minimal hydrogen-bonding energy) and its corresponding hydrogen-bond (HB) distance (referring to the optimal HB distance d) for simple mono-HB systems have an exponential relationship on the basis of MP2 and DFT computational results. We take a step further and propose that the hydrogen-bonding indices of the donor (I) and acceptor (I), reflecting their intrinsic contributions to hydrogen-bonding strength, also have an exponential relation with the hypothetical effective hydrogen-bond radii of the donor (r) and acceptor (r), respectively. On the basis of extensive quantum-mechanical calculations, relevant assumptions about the hydrogen-bonding index are rationalized. Moreover, the hydrogen-bonding index is also suggested as an additional prefiltering criterion for virtual screening besides the widely accepted Lipinski's rule of five. Finally, a "Hydrogen-Bond Index Estimator (HBIE)" module has been implemented in our Visual Force Field Derivation Toolkit (VFFDT) program to approximately and rapidly estimate the hydrogen-bonding indices of any small molecules in batch and screen possible stronger donors or acceptors from the small-molecule database. To the best of our knowledge, the concept of the hydrogen-bonding index and its potential application are proposed here for the first time.
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http://dx.doi.org/10.1021/acs.jcim.7b00022DOI Listing
July 2017

Studies on immunoregulatory and anti-tumor activities of a polysaccharide from Salvia miltiorrhiza Bunge.

Carbohydr Polym 2013 Jan 2;92(1):479-83. Epub 2012 Oct 2.

Department of Digestive Interventional Radiology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China.

In this study, we purified and characterized a polysaccharide (SMP-W1) from Salvia miltiorrhiza and investigated its anticancer and immunoregulatory potential in vitro and in vivo. The monosaccharide composition, protein content, uronic acid content, total carbohydrate content, viscosity and molecular weight of SMP-W1 were analyzed. In vitro, SMP-W1 had an antiproliferative effect on hepatocellular carcinoma H22 cells, especially at the high concentration of 400 μg/ml. Simultaneously the polysaccharide SMP-W1 significantly inhibited tumor growth and increased serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in rats, as well as the secretion of TNF-α. In addition, the body weight, spleen index and thymus index in tumor-bearing mice were significantly improved by SMP-W1 treatment. Taken together, these results indicated that SMP-W1 possessed strong in vivo and in vitro anti-tumor activity and improves the immune response in tumor-bearing mice. Therefore, it could be developed as an anti-tumor agent with immunomodulatory activity.
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http://dx.doi.org/10.1016/j.carbpol.2012.09.061DOI Listing
January 2013

Long-term and stable correction of uremic anemia by intramuscular injection of plasmids containing hypoxia-regulated system of erythropoietin expression.

Exp Mol Med 2012 Nov;44(11):674-83

Department of Nephrology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.

Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate- early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test were used to analyze between- group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats.
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http://dx.doi.org/10.3858/emm.2012.44.11.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509184PMC
November 2012

Protective effect of a polysaccharide from stem of Codonopsis pilosula against renal ischemia/reperfusion injury in rats.

Carbohydr Polym 2012 Nov 31;90(4):1739-43. Epub 2012 Jul 31.

Nephrology Division, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710038, China.

In this study, we purified a homogeneous polysaccharide (S-CPPA1) with a molecular weight (Mw) of 133.2 kDa from the stem of Codonopsis pilosula for the first time. Gas chromatography (GC) analysis identified that S-CPPA1 contained glucose, galactose, and arabinose with a molar ratio of 10.5:3.4:1.7, along with a trace of mannose. Methylation analysis suggested S-CPPA1 was a branched polysaccharide, with five glucosidic linkage forms, namely (1→4)-linked Glcp (residue A), (1→6)-linked Galp (residue B), (1→2,6)-linked Glcp (residue C), (1→5)-linked Araf (residue D), and non-reducing terminal (1→)-linked Glcp (residue E). The protective effect of S-CPPA1 on kidney ischemia/reperfusion (I/R) injury was also evaluated. Blood urea nitrogen (BUN), creatinine and TNF-α levels, as well as lactate dehydrogenase (LDH) and alanine transaminase (AST) activities were elevated in the I/R group as compared to the sham group. On the other hand, S-CPPA1 treatment reversed all these biochemical indices, as well as histopathological alterations, which were induced by I/R. The findings imply that S-CPPA1 plays a causal role in the protection against I/R-induced renal injury and its renoprotective effect is probably mediated by inhibiting the proinflammatory cytokine TNF-α release.
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http://dx.doi.org/10.1016/j.carbpol.2012.07.062DOI Listing
November 2012

Synergetic effect of Andrographis paniculata polysaccharide on diabetic nephropathy with andrographolide.

Int J Biol Macromol 2012 Dec 2;51(5):738-42. Epub 2012 Jul 2.

Department of Periodontology and Oral Medicine, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.

A water-soluble polysaccharide (APP), with a molecular weight of 4.6×10(4) Da, was isolated from Andrographis paniculata and gas chromatography (GC) analysis showed APP was composed of galactose, mannose, fucose, arabinose and rhamnose with molar ratios of 15.4:2.5:4.3:1.5:1.6. The synergetic effect of APP in combination with andrographolide on renal complication in streptozotocin (STZ) induced diabetic mice was investigated. Wistar rats were made diabetic by injection of STZ, and APP and/or andrographolide was administered to diabetic mice for continuous two weeks. APP plus andrographolide not only increased the body weight and creatinine clearance rate (Ccr), but also decreased the levels of serum creatinine, serum urea nitrogen, urinary albumin excretion (UAE), serum urea and blood glucose in diabetic rats, as well as the relative kidney weight. In summary, APP plus andrographolide can improve the metabolic abnormalities of diabetic mice and prevent or delay the progression of diabetic renal complications, which may be useful as a therapeutic agent for inhibiting the progression of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.ijbiomac.2012.06.035DOI Listing
December 2012

Geometrical Preferences of the Hydrogen Bonds on Protein-Ligand Binding Interface Derived from Statistical Surveys and Quantum Mechanics Calculations.

J Chem Theory Comput 2008 Nov;4(11):1959-73

State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. China.

We have conducted potential of mean force (PMF) analyses to derive the geometrical parameters of various types of hydrogen bonds on protein-ligand binding interface. Our PMF analyses are based on a set of 4535 high-quality protein-ligand complex structures, which are compiled through a systematic mining of the entire Protein Data Bank. Hydrogen bond donor and acceptor atoms are classified into several basic types. Both distance- and angle-dependent statistical potentials are derived for each donor-acceptor pair, from which distance and angle cutoffs are obtained in an objective, unambiguous manner. These donor-acceptor pairs are also studied by quantum mechanics (QM) calculations at the MP2/6-311++G** level on model molecules. Comparison of the outcomes of PMF analyses and QM calculations suggests that QM calculation may serve as an alternative approach for characterizing hydrogen bond geometry. Both of our PMF analyses and QM calculations indicate that C-H···O hydrogen bonds are relatively weak as compared to common hydrogen bonds formed between nitrogen and oxygen atoms. A survey on the protein-ligand complex structures in our data set has revealed that Cα-H···O hydrogen bonds observed in protein-ligand binding are frequently accompanied by bifurcate N-H···O hydrogen bonds. Thus, the Cα-H···O hydrogen bonds in such cases would better be interpreted as secondary interactions.
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http://dx.doi.org/10.1021/ct800267xDOI Listing
November 2008

Engineering a polymeric chiral catalyst by using hydrogen bonding and coordination interactions.

Angew Chem Int Ed Engl 2006 Jun;45(25):4108-12

State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P.R. China.

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http://dx.doi.org/10.1002/anie.200600432DOI Listing
June 2006

Discrete and polymeric self-assembled dendrimers: hydrogen bond-mediated assembly with high stability and high fidelity.

Proc Natl Acad Sci U S A 2002 Apr 26;99(8):5099-104. Epub 2002 Mar 26.

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL 61801, USA.

Hydrogen bond-mediated self-assembly is a powerful strategy for creating nanoscale structures. However, little is known about the fidelity of assembly processes that must occur when similar and potentially competing hydrogen-bonding motifs are present. Furthermore, there is a continuing need for new modules and strategies that can amplify the relatively weak strength of a hydrogen bond to give more stable assemblies. Herein we report quantitative complexation studies on a ureidodeazapterin-based module revealing an unprecedented stability for dimers of its self-complementary acceptor-acceptor-donor-donor (AADD) array. Linking two such units together with a semirigid spacer that carries a first-, second-, or third-generation Fréchet-type dendron affords a ditopic structure programmed to self assemble. The specific structure that is formed depends both on the size of the dendron and the solvent, but all of the assemblies have exceptionally high stability. The largest discrete nanoscale assembly is a hexamer with a molecular mass of about 17.8 kDa. It is stabilized by 30 hydrogen bonds, including six AADD x DDAA contacts. The hexamer forms and is indefinitely stable in the presence of a hexamer containing six ADD x DAA hydrogen-bonding arrays.
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http://dx.doi.org/10.1073/pnas.062641199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC122728PMC
April 2002
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