Publications by authors named "Junxia Wu"

11 Publications

  • Page 1 of 1

Retinoic Acid Alleviates Cisplatin-Induced Acute Kidney Injury Through Activation of Autophagy.

Front Pharmacol 2020 3;11:987. Epub 2020 Jul 3.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.

Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA's effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA's effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice. , RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis. , RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI and .Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.
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http://dx.doi.org/10.3389/fphar.2020.00987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348052PMC
July 2020

Trib1 Contributes to Recovery From Ischemia/Reperfusion-Induced Acute Kidney Injury by Regulating the Polarization of Renal Macrophages.

Front Immunol 2020 20;11:473. Epub 2020 Mar 20.

Department of Nephrology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Increasing evidence suggests that macrophage polarization is involved in the recovery from ischemia-reperfusion (I/R)-induced acute kidney injury (AKI), implying that the regulation of macrophage polarization homeostasis might mediate AKI recovery. Trib1 is a key regulator of macrophage differentiation, but its role in AKI remains unclear. Here, we aimed to investigate the role of Trib1 and its link with the macrophage phenotype in the process of adaptive recovery from I/R-induced renal injury. Lentiviral vector-mediated RNA interference (RNAi) was used to knock down Trib1 expression and , and a mouse model of moderate AKI was established by the induction of I/R injury. Renal function measurements and inflammatory factors were determined by the corresponding kits. Histomorphology was assessed by hematoxylin-eosin, Masson and PAS staining. Western blot and flow cytometry were employed for the analysis of signal transduction, cell apoptosis and macrophage phenotypes. Trib1 knockdown inhibited cell viability of tubular epithelial cells (TECs) by inhibiting proliferation and enhancing apoptosis . I/R-induced AKI significantly impaired renal function in mice via increasing the levels of BUN, Scr, NGAL and renal tubular damage, leading to renal fibrosis from days 1 to 3. Through the adaptive self-repair mechanism, renal dysfunction recovered over time and returned to almost normal levels on day 28 after I/R intervention. However, Trib1 depletion worsened renal damage on day 3 and blunted the adaptive repair process of the renal tissue. Mechanistically, Trib1 inhibition suppressed renal tubular cell proliferation under adaptive self-repair conditions by affecting the expression of the proliferation-related proteins cyclin D1, cyclin B, p21, and p27, the apoptosis-related proteins Bcl-2 and Bax, and the fibrosis-related proteins collagen I and III. Furthermore, the M1/M2 macrophage ratio increased in the first 3 days and decreased from day 7 to day 28, consistent with changes in the expression of inflammatory factors, including TNFα, IL-6, IL-12, IL-10, and IL-13. Trib1 inhibition blocked macrophage polarization during adaptive recovery from I/R-induced moderate AKI. Our results show that Trib1 plays a role in kidney recovery and regeneration via the regulation of renal tubular cell proliferation by affecting macrophage polarization. Thus, Trib1 might be a viable therapeutic target to improve renal adaptive repair following I/R injury.
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http://dx.doi.org/10.3389/fimmu.2020.00473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098949PMC
March 2021

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.

Biochem Biophys Res Commun 2019 04 13;512(2):163-169. Epub 2019 Mar 13.

Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Background: Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms.

Methods: We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed.

Results: The levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro.

Conclusions: RA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.
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http://dx.doi.org/10.1016/j.bbrc.2019.03.013DOI Listing
April 2019

Organic charge transfer complexes on graphene with ultrahigh near infrared photogain.

Nanotechnology 2019 Jun 11;30(25):254003. Epub 2019 Feb 11.

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People's Republic of China. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

Photodetectors have widespread applications in fields including telecommunications, thermal imaging and bio-medical imaging. The photogating effect, arising from charge trapping at defects and/or interfaces, can have extremely high photoelectric gain which can be a benefit to high-sensitivity room temperature photodetection. Here, we introduce thin layered organic charge transfer complexes (CPXs) integrated on graphene transistors for the development of hybrid phototransistors with ultra-high photoresponsivity of ∼10 A W in the near infrared (NIR) region at room temperature. Our study has demonstrated a graphene-organic CPX with a broadband photoresponse ranging from the visible to the NIR region. The high photoelectric gain was from the photogating effect at the graphene/CPX interface. In addition, the photoresponse properties of the graphene-organic CPX can be regulated by electrical gating of graphene.
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http://dx.doi.org/10.1088/1361-6528/ab0608DOI Listing
June 2019

Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus.

Biomed Res Int 2018 27;2018:8167538. Epub 2018 Nov 27.

Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226000, China.

Objectives: AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in and genes and the risk of type 2 diabetes (T2DM) in Chinese population.

Methods: Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol-chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes.

Results: The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between SNPs and T2DM risk.

Conclusions: SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.
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http://dx.doi.org/10.1155/2018/8167538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288565PMC
April 2019

Molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with type 1 diabetes mellitus.

Biochem Biophys Res Commun 2018 10 19;504(2):393-399. Epub 2018 Jun 19.

Department of Environmental Health, School of Public Health, Nantong University, Nantong, 226001, China. Electronic address:

Arsenic is associated with several adverse health outcomes, and people with diabetes may be more susceptible to arsenic. In this study, we found that arsenic levels in some tissues such as liver, kidney, and heart but not lung of type 1 diabetes mellitus (T1DM) mice were higher than in those of normal mice after a single oral dose of arsenic trioxide for 2 h. However, little is known about the molecular mechanism of the increased tissue uptake of trivalent inorganic arsenic in mice with T1DM. This study aimed to investigate the expression of the mammalian arsenic transporters aquaglyceroporins (AQPs) and glucose transporter 1 (GLUT1) in T1DM mice and compare them with those in normal mice. Results showed that the levels of AQP9 and GLUT1 mRNA and protein were higher in T1DM mouse liver than in the normal one. The levels of AQP7 mRNA and protein were higher in T1DM mouse kidney. In the heart, we observed that the levels of AQP7 and GLUT1 mRNA and protein were higher in T1DM mice, but the levels of AQP9 mRNA and protein in the lung had no significant difference between both mice. These results suggested that T1DM may increase the expression of transporters of trivalent inorganic arsenic and thus increase the arsenic uptake in specific tissues.
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http://dx.doi.org/10.1016/j.bbrc.2018.06.029DOI Listing
October 2018

Development of bunch shape monitor for high-intensity beam on the China ADS proton LINAC Injector II.

Rev Sci Instrum 2018 May;89(5):053303

Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

The development, performance, and testing of the longitudinal bunch shape monitor, namely, the Fast Faraday Cup (FFC), are presented in this paper. The FFC is an invasive instrument controlled by a stepper motor, and its principle of operation is based on a strip line structure. The longitudinal bunch shape was determined by sampling a small part of the beam hitting the strip line through a 1-mm hole. The rise time of the detector reached 24 ps. To accommodate experiments that utilize high-intensity beams, the materials of the bunch shape monitor were chosen to sustain high temperatures. Water cooling was also integrated in the detector system to enhance heat transfer and prevent thermal damage. We also present an analysis of the heating caused by the beam. The bunch shape monitor has been installed and commissioned at the China ADS proton LINAC Injector II.
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http://dx.doi.org/10.1063/1.5027608DOI Listing
May 2018

Cisplatin nephrotoxicity as a model of chronic kidney disease.

Lab Invest 2018 08 1;98(8):1105-1121. Epub 2018 Jun 1.

Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Cisplatin (CP)-induced nephrotoxicity is widely accepted as a model for acute kidney injury (AKI). Although cisplatin-induced chronic kidney disease (CKD) in rodent has been reported, the role of phosphate in the cisplatin-induced CKD progression is not described. In this study, we gave a single peritoneal injection of CP followed by high (2%) phosphate diet for 20 weeks. High dose CP (20 mg/Kg) led to high mortality; whereas a lower dose (10 mg/Kg) resulted in a full spectrum of AKI with tubular necrosis, azotemia, and 0% mortality 7 days after CP injection. After consuming a high phosphate diet, mice developed CKD characterized by low creatinine clearance, interstitial fibrosis, hyperphosphatemia, high plasma PTH and FGF23, low plasma 1,25(OH) Vitamin D and αKlotho, and classic uremic cardiovasculopathy. The CP model was robust in demonstrating the effect of aging, sexual dimorphism, and dietary phosphate on AKI and also AKI-to-CKD progression. Finally, we used the CP-high phosphate model to examine previously validated methods of genetically manipulated high αKlotho and therapy using exogenous soluble αKlotho protein supplementation. In this CP CKD model, αKlotho mitigated CKD progression, improved mineral homeostasis, and ameliorated cardiovascular disease. Taken together, CP and high phosphate nephrotoxicity is a reproducible and technically very simple model for the study of AKI, AKI-to-CKD progression, extrarenal complications of CKD, and for evaluation of therapeutic efficacy.
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http://dx.doi.org/10.1038/s41374-018-0063-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528473PMC
August 2018

Expression patterns and role of PTEN in rat peripheral nerve development and injury.

Neurosci Lett 2018 05 9;676:78-84. Epub 2018 Apr 9.

Department of Orthopedic and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China. Electronic address:

Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury.
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http://dx.doi.org/10.1016/j.neulet.2018.04.016DOI Listing
May 2018

Current Smoking Dose-Dependently Associated with Decreased β-Cell Function in Chinese Men without Diabetes.

J Diabetes Res 2015 5;2015:841768. Epub 2015 Jul 5.

Department of Chronic Non-Communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China.

The aim of this study was to evaluate the associations between chronic smoking and insulin resistance and β-cell function in Chinese men without diabetes. A total of 1,568 participants were recruited by multistage sampling. Using homeostatic model assessment (HOMA), geometric means of insulin resistance (HOMA-IR) and β-cell function (HOMA-β) with 95% confidence interval (CI) were calculated by general linear model. Odds ratios (ORs) with 95% CI were estimated to evaluate the associations between smoking status and insulin resistance and β-cell deficiency under a logistic regression model. Current smokers had higher levels of 2 h glucose (6.66 versus 6.48 mmol/L) for oral glucose tolerance test and lower levels of fasting insulin (5.68 versus 6.03 mU/L) than never smokers. The adjusted means for HOMA-β (%) were 54.86 in current smokers and 58.81 in never smokers (P = 0.0257). Current smoking was associated with β-cell deficiency (OR 1.29, 95% CI 1.01-1.64) compared to never smoking. The β-cell function gradually decreased with increasing smoking intensity (P trend = 0.0026), and the differences were statistically significant when the pack-year of smoking was 20 or above. No association was observed between smoking status and HOMA-IR. Our study suggested that chronic smoking may dose-dependently suppress insulin secretion in Chinese men.
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http://dx.doi.org/10.1155/2015/841768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506814PMC
March 2016
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