Publications by authors named "Haifeng Ni"

17 Publications

  • Page 1 of 1

1,25-Dihydroxyvitamin D3 Supplementation during Pregnancy Is Associated with Allergic Rhinitis in the Offspring by Modulating Immunity.

J Immunol Res 2021 14;2021:6638119. Epub 2021 Apr 14.

Department of Otolaryngology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, China.

Background: Maternal supplementation with 1,25-dihydroxyvitamin D3 (VD3) has immunologic effects on the developing fetus through multiple pathways. This study was aimed at investigating the effects of VD3 supplementation on immune dysregulation in the offspring during allergic rhinitis.

Methods: Different doses of VD3 as well as control were given to pregnant female mice. Ovalbumin (OVA) challenge and aluminum hydroxide gel in sterile saline were used to induce allergic rhinitis in offspring mice. Nasal lavage fluids (NLF) were collected, and eosinophils were counted in NLF 24 hours after the OVA challenge. Th1, Th2, Th17, and Treg subtype-relevant cytokines, including IFN-, IL-4, IL-10, IL-17, TGF-, and OVA-IgE levels from the blood and NLF of offspring mice, were detected by the enzyme-linked immunosorbent assay (ELISA) method. The Treg subtype was analyzed by flow cytometry. Treg cells were purified from offspring and were adoptively transferred to OVA-sensitized allogenic offspring mice. The outcomes were assessed in allogenic offspring.

Results: Our data showed that VD3 supplementation significantly decreased the number of eosinophils, basophils, and lymphocytes in the peripheral blood and NLF. The proportion of CD4CD25FoxP3Tregs had a positive correlation with VD3 in a dose-dependent manner. The levels of serum IgE, IL-4, and IL-17 were decreased while the expressions of IFN-, IL-10, and TGF- were significantly enhanced in VD3 supplementation groups. Adoptive transfer CD4CD25FoxP3Tregs of VD3 supplementation groups promoted Th1 and suppressed Th2 responses in the offspring during allergic rhinitis.

Conclusion: Our findings indicated that low dose VD3 supply in pregnant mice's diet suppressed Th2 and Th17 responses in allergic rhinitis by elevating the Th1 subtype and the proportion of CD4CD25FoxP3Tregs in offspring. It suggested that low dose VD3 supply may have the potential to act as a new therapeutic strategy for allergic rhinitis.
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http://dx.doi.org/10.1155/2021/6638119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062205PMC
April 2021

LncRNA XIST promotes inflammation by downregulating GRα expression in the adenoids of children with OSAHS.

Exp Ther Med 2021 May 17;21(5):500. Epub 2021 Mar 17.

Department of Otolaryngology, Head and Neck Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.

Whether glucocorticoid receptor α (GRα) serves a role in obstructive sleep apnea/hypopnea syndrome (OSAHS) remains unclear. However, it has been reported that GRα expression is decreased in the adenoids of patients with OSAHS. The present study aimed to evaluate the role of GRα in OSAHS and the underlying mechanism. Bioinformatics assays revealed that long noncoding RNA (lncRNA) X inactivate-specific transcript (XIST) was closely associated with GRα. Furthermore, reverse transcription-quantitative PCR showed that the expression of lncRNA XIST was significantly increased in the adenoids of patients with OSAHS compared with healthy controls. Further studies by Pearson correlation analysis, RNA pull-down assay, western blot analysis and ELISA demonstrated that XIST significantly decreased the expression of GRα and that significantly increased the production of inflammatory cytokines, including interleukin (IL)-8, tumor necrosis factor α, IL-6 and IL-1β, while the overexpression of GRα significantly decreased the production of these inflammatory cytokines in NP69 cells, a human nasopharyngeal epithelial cell line. Furthermore, XIST significantly increased the protein levels of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) subunits, including Rel-B, c-Rel, P52, P50 and P65, which are associated with the transcription of cytokines. The stimulatory effect of XIST was significantly inhibited by the NF-κB inhibitor EVP4593. These results indicated that the stimulatory effect of XIST was dependent on NF-κB. In summary, the present study demonstrated that the XIST-GRα-NF-κB signaling pathway contributed to inflammation in the adenoids of patients with OSAHS.
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http://dx.doi.org/10.3892/etm.2021.9931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005745PMC
May 2021

High nitrogen concentration alter microbial community in Allium fistulosum rhizosphere.

PLoS One 2020 20;15(11):e0241371. Epub 2020 Nov 20.

Institute of Agricultural Resources and Environment, Shandong Academy of Agricultural Sciences, Jinan, China.

Welsh onion (Allium fistulosum L.) constitutes an important plant species cultivated in China due the benefits and applications in different areas. Moreover, nitrogen is an essential nutrient during the growth and development of plant. Here, we present the effects of nitrogen on soil microbiome in welsh onion plants. We used High-throughput sequencing analysis to determine the diversity and abundances of microbes associated to soil rhizosphere in welsh onion under the influence of nitrogen application. Nitrogen application significantly influenced in the diversity of fungal community. The relative abundance of Orbiliomycetes increased with the nitrogen concentration. Nitrogen application did not affect the diversity of bacterial community, whereas the relative abundance of Acidobacteria_Gp2, Verrucomicrobiae and Sphingobacteriia decreased with the nitrogen condition. In this work, we introduced evidences of the effect of nitrogen fertilization on microbial community in welsh onion rhizosphere, and the change of microbial community may interfere the growth and development of welsh onion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241371PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678981PMC
December 2020

Parkin enhances sensitivity of paclitaxel to NPC by arresting cell cycle.

Pathol Res Pract 2020 Mar 18;216(3):152755. Epub 2019 Nov 18.

Department of Otolaryngology Head and Neck Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China.

Object: Parkin has been reported as a tumor suppressor gene. The current research found that Parkin expresses abnormally in nasopharynx cancer (NPC).

Materials And Methods: C666-1 and HONE1 NPC cell lines were performed to evaluate the effect of Parkin on cell cycle and apoptosis, the potential mechanisms of paclitaxel resistant based on its relationship with Parkin. Cell viability were determined by Cell counting kit-8 (CCK-8) and was further performed to explore the NPC cell sensitivity for paclitaxel. Cell cycle and cell apoptosis were used by flow cytometry. Corresponding proteins in the biological effects were detected by western blotting.

Results: Overexpression of Parkin conspicuously enhanced paclitaxel sensitivity to NPC cells, whereas depleting of Parkin reduced paclitaxel sensitivity. In addition, overexpression of Parkin significantly delayed the cell cycle progression in G2/M phase. Paclitaxel is an anti-mitotic chemotherapeutic, and inhibition of Parkin reduces the effects of paclitaxel on mitosis.

Conclusions: Loss of Parkin inhibits the NPC cell sensitivity to paclitaxel. Upregulation of Parkin enhances the sensitivity of paclitaxel to NPC which indicates that Parkin can be a potential therapy target for NPC. Parkin may not only participate the paclitaxel resistance, but also exert synergistic effect with paclitaxel on NPC therapy. Thus Parkin may be a potential target for cancer therapy.
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http://dx.doi.org/10.1016/j.prp.2019.152755DOI Listing
March 2020

Bartter syndrome type III with only a synonymous mutation of the gene
.

Clin Nephrol 2019 Dec;92(6):325-328

Bartter syndrome (BS), a rare autosomal recessive disorder affecting renal tubular potassium handling, is characterized by hypokalemia, metabolic alkalosis, and renal salt wasting. In this report, we describe an adult patient with longstanding clinical symptoms of fatigue, polyuria, polydipsia, mental retardation, and physical dysplasia along with hypokalemia and metabolic alkalosis as laboratory findings. With these clinical symptoms, a patient can be diagnosed with BS type III. Renal biopsy and genetic testing were performed for further confirmation of the diagnosis, revealing renin granular deposits in the juxtaglomerular apparatus (JA) with JA hyperplasia. DNA sequencing detected a heterozygous synonymous mutation, c.1140G>A, in exon 12 of the gene, which could be traced back to a heterozygous synonymous mutation in the patient's mother, who does not have BS.
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http://dx.doi.org/10.5414/CN109784DOI Listing
December 2019

ANGPTL2 regulates autophagy through the MEK/ERK/Nrf-1 pathway and affects the progression of renal fibrosis in diabetic nephropathy.

Am J Transl Res 2019 15;11(9):5472-5486. Epub 2019 Sep 15.

Department of Geriatrics, Zhongda Hospital Affiliated with Southeast University Nanjing 210009, Jiangsu, China.

Background: Diabetic nephropathy (DN) is one of the most important microvascular complications of diabetes mellitus. The present study aims to explore whether angiopoietin-like protein 2 (ANGPTL2) can promote renal tissue fibrosis in DN.

Materials And Methods: Models includes diabetic SD rats induced by streptozotocin (STZ) and high glucose (HG)-stimulated HK-2 cells. qRT-PCR, western blot and immunohistochemical analysis were performed to explore ANGPTL2 expression. The renal injury and fibrosis were assessed using hematoxylin-eosin staining (H&E) and Masson trichrome staining. Immunofluorescence was conducted to detect the expression of collagen IV and LC3II. The levels of pro-inflammatory factors IL-6, -1β, TNF-α and ANGPTL2 were assessed by an ELISA, and nitric oxide (NO) production was determined using Griess method. Protein levels of iNOS, PTEN, fibronectin (FN), collagen I, IV, p62, beclin1 and MEK/ERK/Nrf-1 pathway in DN rats and HK-2 cells were determined, respectively.

Results: When compared with normal rats, DN rats experienced severe renal injury and fibrosis and showed decreased LC3II and beclin1, increased PTEN, FN, collagen I and IV, p62, NO, iNOS and ANGPTL2 in kidney. The pro-inflammatory factors and ANGPTL2 were markedly elevated. Again, knockdown of ANGPTL2 caused an increase in MEK, p-ERK, Nrf-1, LC3II, beclin1, and a decrease in PTEN, FN, collagen I and IV, p62, NO, iNOS and pro-inflammatory factors of HK-2 cells. Furthermore, knockdown of MEK/ERK reversed these changes.

Conclusion: ANGPTL2 may serve an important role in the autophagy of DN and activate MEK/ERK/Nrf-1 pathway, which may therefore have potential as a treatment to prevent renal fibrosis in DN.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789235PMC
September 2019

Luteolin inhibits IL-1β-induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model.

Biomed Pharmacother 2019 Jan 26;109:1586-1592. Epub 2018 Nov 26.

Department of Orthopedics, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, Jiangsu, China.

Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. Accumulating evidence has demonstrated that luteolin, a natural flavonoid, has anti-inflammatory and anticatabolic effects. The present study aimed to assess the protective effect of luteolin on interleukin (IL)-1β-stimulated rat chondrocytes and a monosodium iodoacetate (MIA)-induced model of OA. Rat chondrocytes were pretreated with luteolin (0, 25, 50, and 100 μM for 12 h) prior to stimulation with IL-1β (10 ng/ml for 24 h). Nitric oxide (NO) production was determined using the Griess method. Production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-2, -8, and -9 (MMP-2, MMP-8 and MMP-9) was measured by an enzyme-linked immunosorbent assay (ELISA). Protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMP-1, MMP-3, MMP-13, p65, p-p65, IκB, and p-IκB were determined by Western blotting. The OA rats received luteolin (10 mg/kg/day) by gavage in vivo. Morphological and ultrastructural scanning electron microscopy (SEM) observations were performed to assess the severity of OA at 45 days following MIA injection. Collagen II protein expression was determined by immunohistochemistry. In this study, luteolin considerably reduced the IL-1β-induced production of NO, PGE2, TNF-α, MMP-2, MMP-8 and MMP-9 and the expression of COX-2, iNOS, MMP-1, MMP-3 and MMP-13. Luteolin reversed the degradation of collagen II induced by IL-1β. Luteolin also significantly inhibited IL-1β-induced phosphorylation of NF-κB in vitro. Luteolin treatment prevented cartilage destruction and enhanced collagen II expression in OA rats in vivo. Overall, our findings suggest that luteolin may be a useful therapeutic agent for patients with OA.
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http://dx.doi.org/10.1016/j.biopha.2018.09.161DOI Listing
January 2019

Downregulation of ribophorin II suppresses tumor growth, migration, and invasion of nasopharyngeal carcinoma.

Onco Targets Ther 2018 15;11:3485-3494. Epub 2018 Jun 15.

Department of Otolaryngology, Hangzhou First People's Hospital, Hangzhou, China.

Background: It has been reported that ribophorin II (RPN2) expression is increased in many cancers, but the role of RPN2 in nasopharyngeal carcinoma (NPC) remains unclear.

Patients And Methods: This study found that the expression of RPN2 is increased dramatically in NPC tissues of patients compared with that in the adjacent normal tissues. This study attempted at understanding the effect of siRNA-RPN2 treatment on the migration and invasion of NPC cell lines CNE2 and HNE1.

Results: RT-PCR and Western blotting showed that RPN2 was highly expressed in CNE2 and HNE1 cells. siRNA-RPN2 treatment significantly inhibited cell viability at 24 and 48 h compared with the control group. Results of the transwell assay showed that, compared to the control groups, migration and invasion of the cells treated with siRNA-RPN2 decreased markedly. In addition, compared to the control groups, caspase-3, caspase-9, and E-cadherin expression levels increased and MMP 2 expression decreased significantly in the siRNA-RPN2-treated group. Phosphorylation of AKT and PI3K was also inhibited after siRNA-RPN2 treatment.

Conclusion: siRNA-RPN2 can effectively inhibit the invasion and migration of human NPC cells via AKT/PI3K signaling. This can serve as a novel strategy for NPC treatment.
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http://dx.doi.org/10.2147/OTT.S158355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007195PMC
June 2018

[Expression and meaning of T-bet and GATA3 mRNA in T lymphocyte of patients during the operation with cardiopulmonary bypass].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017 Dec;29(12):1107-1111

Department of Cardiac Surgery, the 150th Military Hospital, Luoyang 471031, Henan, China (Ni HF); Department of Cardiac Surgery, the Third Military Medical University Xinqiao Hospital, Chongqing 400037, China (Xiao YB). Corresponding author: Xiao Yingbin, Email:

Objective: To investigate the effects of cardiopulmonary bypass (CPB) on the differentiation of T lymphocyte subsets and the expression of specific transcription regulator T-bet/GATA binding protein 3 (GATA3).

Methods: A prospective double-blind study was conducted. Patients with CPB pulmonary repair of ventricular septal defect (observation group) or off-pump ligation of ductus arteriosus (control group) with 20 cases each in the 150th Military Hospital from February 2015 to February 2016 were enrolled. The blood sampled was collected on the time of before operation, at the end of CPB or operation, 4 hours after operation, and 24 hours after operation. T lymphocytes were isolated, the helper T cell 1 (Th1) specific transcription factor T-bet mRNA, helper T cell 2 (Th2) specific transcription factor GATA3 mRNA expression and cytokine γ-interferon (IFN-γ) mRNA, interleukin-4 (IL-4) mRNA expression were measured by Northern Blot.

Results: Compared with before operation, expression levels of T-bet mRNA [integral gray values: (1.39±0.52)×10 vs. (2.92±0.88)×10], IFN-γ mRNA [integral gray values: (3.68±0.65)×10 vs. (6.10±0.93)×10] were decreased transiently at the end of CPB in the observation group (both P < 0.05), returned to preoperative levels at 24 hours after operation [integral gray values: (2.77±0.74)×10, (6.22±1.25)×10, respectively, both P > 0.05]; expression levels of GATA3 mRNA [integral gray values: (4.96±0.88)×10 vs. (3.21±0.68)×10], IL-4 mRNA [integral gray values: (3.52±1.13)×10 vs. (1.85±0.63)×10] were increased (both P < 0.05), recovered to the preoperative levels at 24 hours after operation [integral gray values: (3.11±0.51)×10, (1.93±0.84)×10, respectively, both P > 0.05]. There were no significant differences in the expressions of T-bet, GATA3, IFN-γ and IL-4 mRNA in the control group at each time points (all P > 0.05).

Conclusions: CPB causes the imbalance of Th1, Tc1/Th2, Tc2 and pro-inflammatory and anti-inflammatory reactions specially, which participate the complication occurrence after CPB. The changing of T-bet/GATA3 may be the internal mechanism for these changes.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2017.12.011DOI Listing
December 2017

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

Int J Mol Med 2017 Sep 27;40(3):673-678. Epub 2017 Jun 27.

Department of Otolaryngology, Affiliated Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China.

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3‑methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.
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http://dx.doi.org/10.3892/ijmm.2017.3044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547962PMC
September 2017

Inactivation of parkin by promoter methylation correlated with lymph node metastasis and genomic instability in nasopharyngeal carcinoma.

Tumour Biol 2017 Mar;39(3):1010428317695025

1 Department of Otolaryngology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, China.

This study aimed to investigate the inactivation of the parkin gene by promoter methylation and its relationship with genome instability in nasopharyngeal carcinoma. Parkin was considered as a tumor suppressor gene in various types of cancers. However, its role in nasopharyngeal carcinoma is unexplored. Genomic instabilities were detected in nasopharyngeal carcinoma tissues by the random amplified polymorphic DNA. The methylation-specific polymerase chain reaction, semi-quantitative reverse transcription polymerase chain reaction, and immunohistochemical analysis were used to detect methylation and mRNA and protein expression of parkin in 54 cases of nasopharyngeal carcinoma tissues and 16 cases of normal nasopharyngeal epithelia tissues, and in 5 nasopharyngeal carcinoma cell lines (CNE1, CNE2, TWO3, C666, and HONE1) and 1 normal nasopharyngeal epithelia cell line (NP69). mRNA expression of parkin in CNE1 and CNE2 was analyzed before and after methyltransferase inhibitor 5-aza-2-deoxycytidine treatment. The relationship between promoter methylation and mRNA expression, demethylation and mRNA expression, and mRNA and protein expression of the gene and clinical factors and genomic instabilities were analyzed. The mRNA and protein expression levels were significantly reduced in 54 cases of human nasopharyngeal carcinoma compared with 16 cases of normal nasopharyngeal epithelia. Parkin-methylated cases showed significantly lower mRNA and protein expression levels compared with unmethylated cases. After 5-aza-2-deoxycytidine treatment, parkin mRNA expression was restored in CNE1 and CNE2; 92.59% (50/54) of nasopharyngeal carcinoma demonstrated genomic instability. Parkin is frequently inactivated by promoter methylation, and its mRNA and protein expression correlate with lymph node metastasis and genomic instability. Parkin deficiency probably promotes tumorigenesis in nasopharyngeal carcinoma.
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http://dx.doi.org/10.1177/1010428317695025DOI Listing
March 2017

Chemosensitizing Effect of Astragalus Polysaccharides on Nasopharyngeal Carcinoma Cells by Inducing Apoptosis and Modulating Expression of Bax/Bcl-2 Ratio and Caspases.

Med Sci Monit 2017 Jan 26;23:462-469. Epub 2017 Jan 26.

Department of Otolaryngology Head and Neck Surgery, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang, China (mainland).

BACKGROUND Platinum-based chemotherapy is the most effective regimen for nasopharyngeal carcinoma, which presents highly invasive and metastatic activity. However, the dose-related toxicity of chemotherapy agents limits the dose administration. Astragalus polysaccharide (APS) is the major active ingredient extracted from Chinese herb Radix Astragali and is proven to be active against carcinomas. We aimed to assess the chemosensitizing effects of Astragalus polysaccharides on nasopharyngeal carcinoma in vitro and in vivo and to explore the underlying mechanism. MATERIAL AND METHODS We used BALB/c nu/nu mice and human nasopharyngeal carcinoma cell lines CNE-1, CNE-2, and SUNE-1. MTT, Annexin V/PI, Western blot analysis, and TUNEL assay were carried out. RESULTS APS significantly promoted anti-proliferative and apoptotic effects of cisplatin on nasopharyngeal carcinoma cells. APS also enhanced the anti-tumor effects and cisplatin-induced apoptosis in the xenograft model. The level of Bcl-2 decreased, while the levels of Bax, caspase-3, and caspase-9 increased in cisplatin combined with APS treatment compared to cisplatin only treatment. The ratio of Bax to Bcl-2 was significantly enhanced by the APS to cisplatin. CONCLUSIONS APS enhanced the anti-proliferative and apoptotic effect of cisplatin by modulating expression of Bax/Bcl-2 ratio and caspases on nasopharyngeal carcinoma cells and in the xenograft model.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291085PMC
http://dx.doi.org/10.12659/msm.903170DOI Listing
January 2017

Sphingosine-1-phosphate receptor agonist, FTY720, restores coronary flow reserve in diabetic rats.

Circ J 2014 15;78(12):2979-86. Epub 2014 Oct 15.

Department of Cardiology, The fourth Affiliated Hospital, China Medical University.

Background: Impairment of coronary flow reserve (CFR) has been generally demonstrated in diabetic patients and animals with microvascular complications but without obvious obstructive coronary atherosclerosis. There have been few studies investigating CFR in cases of relatively well-controlled therapy. The purpose of this study is to evaluate the effect of treatment with a Sphingosine-1-phosphate (S1P) receptor potent agonist, FTY720, on early diabetic rats in terms of CFR. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were divided into 3 groups: (1) streptozotocin-uninjected rats (control rats); (2) streptozotocin-injected hyperglycemic rats (diabetic group); and (3) FTY720-fed and streptozotocin-injected hyperglycemic rats. FTY720 (1.25 mg/kg per day orally) was administrated for 9 weeks in SD rats (from 6 weeks old to 15 weeks old). CFR was evaluated by (13)NH3-positron emission tomography. No obvious pathological changes of macrovascular atherosclerosis were observed in each group. Diabetic rats had impaired CFR compared with the control group (1.39±0.26 vs. 1.94±0.24, P<0.05). Treatment with FTY720 for 9 weeks attenuated the heart histological changes and improved CFR in 32% of diabetic rats (1.84±0.36 vs. 1.39±0.26, P<0.05).

Conclusions: In summary, long-term therapy with the Sphingosine-1-phosphate receptor agonist, FTY720, improved CFR by attenuating the heart histological changes, and it might have a beneficial effect on coronary microvascular function in diabetic rats.
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http://dx.doi.org/10.1253/circj.cj-14-0521DOI Listing
July 2015

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells.

Int J Nanomedicine 2014 12;9:4317-30. Epub 2014 Sep 12.

School of Medicine, Southeast University, Nanjing, People's Republic of China ; Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.

Background: Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.

Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet-visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death.

Conclusion/significance: Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use-especially for the potential GNP-related therapies in chronic kidney disease patients.
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http://dx.doi.org/10.2147/IJN.S68685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168869PMC
May 2015

FTY720 prevents progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease.

J Mol Histol 2013 Dec 2;44(6):693-703. Epub 2013 Aug 2.

Institute of Nephrology, Zhong Da Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.

Recent studies have shown that chronic endothelial dysfunction can impair multiple aspects of renal physiology and, in turn, contribute to renal fibrosis. Sphingosine 1-phosphate (S1P) has been highlighted as an endothelial barrier-stabilizing mediator. The aim of our study was to investigate the effect of FTY720, an S1P analog, on the progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease. Thirty male Sprague-Dawley rats were used in this study. Seven days after surgery, we placed the animals into three groups: sham surgery; 5/6 nephrectomized (Nx) rats; and 5/6Nx + FTY720 (1 mg/kg/day). All of the animals were sacrificed 12 weeks after surgery. We obtained and analyzed blood and kidney tissue samples from all of the groups. Glomerular capillary density and peritubular capillary (PTC) density were determined by CD31 immunostaining. The expression of transforming growth factor beta 1 (TGF-β1), collagen IV, fibronectin, endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were analyzed by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. The 5/6Nx group exhibited increased blood urea nitrogen and serum creatinine, visible renal histological changes, pro-fibrotic molecule (TGF-β1) and production of extracellular matrix proteins such as collagen IV and fibronectin and decreased glomerular and PTC density, compared to the sham controls (P < 0.01). We observed that treatment with FTY720 reduced these abnormalities. Furthermore, the level of NO, the expression levels of eNOS and VEGF were downregulated in the kidney tissue in 5/6Nx rats, FTY720 treatment significantly attenuated this decrease. FTY720 prevents the progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease.
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http://dx.doi.org/10.1007/s10735-013-9521-8DOI Listing
December 2013

Ion redistribution in an electric double layer.

J Colloid Interface Sci 2003 Apr;260(2):344-8

Department of Engineering, University of Denver, Denver, CO 80208, USA.

The structure of a single flat electric double layer (EDL) is studied by grounding a symmetric electrolyte (NaCl), which is in contact with a planar positively corona-treated polypropylene film. Because the profiles of the electrostatic potential distribution and ion distribution in the solution are altered when the solution is grounded, some mobile counterions in the diffuse layer of the electrolyte solution will go into the Helmholtz layer and thus decrease the electric potential psi(a/2) at the Stern plane in order to obtain a new equilibrium. After the system is grounded for a long time, the representation of the electric double layer changes from a Stern model to a Helmholtz model. Theoretical and experimental analyses are given in this study.
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http://dx.doi.org/10.1016/s0021-9797(02)00229-1DOI Listing
April 2003