Publications by authors named "Wen Qiu"

78 Publications

The Sez6 Family Inhibits Complement by Facilitating Factor I Cleavage of C3b and Accelerating the Decay of C3 Convertases.

Front Immunol 2021 15;12:607641. Epub 2021 Apr 15.

Center for Neurotherapeutics Discovery, Department of Neurology, University of Rochester Medical Center, Rochester, NY, United States.

The Sez6 family consists of Sez6, Sez6L, and Sez6L2. Its members are expressed throughout the brain and have been shown to influence synapse numbers and dendritic morphology. They are also linked to various neurological and psychiatric disorders. All Sez6 family members contain 2-3 CUB domains and 5 complement control protein (CCP) domains, suggesting that they may be involved in complement regulation. We show that Sez6 family members inhibit C3b/iC3b opsonization by the classical and alternative pathways with varying degrees of efficacy. For the classical pathway, Sez6 is a strong inhibitor, Sez6L2 is a moderate inhibitor, and Sez6L is a weak inhibitor. For the alternative pathway, the complement inhibitory activity of Sez6, Sez6L, and Sez6L2 all equaled or exceeded the activity of the known complement regulator MCP. Using Sez6L2 as the representative family member, we show that it specifically accelerates the dissociation of C3 convertases. Sez6L2 also functions as a cofactor for Factor I to facilitate the cleavage of C3b; however, Sez6L2 has no cofactor activity toward C4b. In summary, the Sez6 family are novel complement regulators that inhibit C3 convertases and promote C3b degradation.
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http://dx.doi.org/10.3389/fimmu.2021.607641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081827PMC
April 2021

Adiponectin Enhances B-Cell Proliferation and Differentiation Activation of Akt1/STAT3 and Exacerbates Collagen-Induced Arthritis.

Front Immunol 2021 18;12:626310. Epub 2021 Mar 18.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Although B cells have been shown to contribute to the pathogenesis of rheumatoid arthritis (RA), the precise role of B cells in RA needs to be explored further. Our previous studies have revealed that adiponectin (AD) is expressed at high levels in inflamed synovial joint tissues, and its expression is closely correlated with progressive bone erosion in patients with RA. In this study, we investigated the possible role of AD in B cell proliferation and differentiation. We found that AD stimulation could induce B cell proliferation and differentiation in cell culture. Notably, local intraarticular injection of AD promoted B cell expansion in joint tissues and exacerbated arthritis in mice with collagen-induced arthritis (CIA). Mechanistically, AD induced the activation of PI3K/Akt1 and STAT3 and promoted the proliferation and differentiation of B cells. Moreover, STAT3 bound to the promoter of the Blimp-1 gene, upregulated Blimp-1 expression at the transcriptional level, and promoted B cell differentiation. Collectively, we observed that AD exacerbated CIA by enhancing B cell proliferation and differentiation mediated by the PI3K/Akt1/STAT3 axis.
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http://dx.doi.org/10.3389/fimmu.2021.626310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012765PMC
March 2021

Sublytic C5b-9 induces glomerular mesangial cell proliferation via ERK1/2-dependent SOX9 phosphorylation and acetylation by enhancing Cyclin D1 in rat Thy-1 nephritis.

Exp Mol Med 2021 Apr 2;53(4):572-590. Epub 2021 Apr 2.

Department of Immunology, and Key Laboratory of Immunological Environment and Disease, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu, 211166, China.

Glomerular mesangial cell (GMC) proliferation is a histopathological alteration in human mesangioproliferative glomerulonephritis (MsPGN) or in animal models of MsPGN, e.g., the rat Thy-1 nephritis (Thy-1N) model. Although sublytic C5b-9 assembly on the GMC membrane can trigger cell proliferation, the mechanisms are still undefined. We found that sublytic C5b-9-induced rat GMC proliferation was driven by extracellular signal-regulated kinase 1/2 (ERK1/2), sry-related HMG-box 9 (SOX9), and Cyclin D1. Here, ERK1/2 phosphorylation was a result of the calcium influx-PKC-α-Raf-MEK1/2 axis activated by sublytic C5b-9, and Cyclin D1 gene transcription was enhanced by ERK1/2-dependent SOX9 binding to the Cyclin D1 promoter (-582 to -238 nt). In addition, ERK1/2 not only interacted with SOX9 in the cell nucleus to mediate its phosphorylation at serine residues 64 (a new site identified by mass spectrometry) and 181 (a known site), but also indirectly induced SOX9 acetylation by elevating the expression of general control non-repressed protein 5 (GCN5), which together resulted in Cyclin D1 synthesis and GMC proliferation. Moreover, our in vivo experiments confirmed that silencing these genes ameliorated the lesions of Thy-1N rats and reduced SOX9 phosphorylation, acetylation and Cyclin D1 expression. Furthermore, the renal tissue sections of MsPGN patients also showed higher phosphorylation or expression of ERK1/2, SOX9, and Cyclin D1. In summary, these findings suggest that sublytic C5b-9-induced GMC proliferation in rat Thy-1N requires SOX9 phosphorylation and acetylation via enhanced Cyclin D1 gene transcription, which may provide a new insight into human MsPGN pathogenesis.
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http://dx.doi.org/10.1038/s12276-021-00589-9DOI Listing
April 2021

Microwave ablation induces Th1-type immune response with activation of ICOS pathway in early-stage breast cancer.

J Immunother Cancer 2021 Apr;9(4)

Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China

Background: Despite great advances in the treatment of breast cancer, innovative approaches are still needed to reduce metastasis. As a minimally invasive local therapy (not standard therapy for breast cancer), microwave ablation (MWA) has been attempted to treat breast cancer, but the local effect and immune response induced by MWA have seldom been reported.

Methods: The clinical study was performed to determine the complete ablation rate of MWA for early-stage breast cancer. Secondary endpoints included safety and antitumor immune response. 35 subjects from this clinical study were enrolled in the current report, and the local effect was determined by pathological examinations or follow-up. To investigate MWA-induced immune response, patients treated with surgery (n=13) were enrolled as control, and blood samples were collected before and after MWA or surgery. The immune cell populations, serum cytokines, secretory immune checkpoint molecules, and T-cell receptor sequencing were analyzed.

Results: Of 35 enrolled patients, 32 (91.4%) showed complete ablation. Compared with surgery, MWA induced significantly increased levels of inducible co-stimulator (ICOS)+ activated CD4+ T cells and serum interferon gamma, indicating a shift in the Th1/Th2 balance toward Th1. The activated ICOS pathway was involved in the MWA-induced adaptive immune response. T-cell receptor sequencing revealed MWA of primary tumor activated T lymphocytes expansion and recognized some cancer-specific antigens. Moreover, CD4+ effector memory T-cell response was induced by MWA, and the immune response still existed after surgical resection of the ablated tumor.

Conclusions: MWA may not only be a promising local therapy but also a trigger of antitumor immunity for breast cancer, opening new avenues for the treatment of breast cancer. Combinatorial strategy using additional agents which boost MWA-induced immune response could be considered as potential treatment for clinical study for early breast cancer therapy.
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http://dx.doi.org/10.1136/jitc-2021-002343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021888PMC
April 2021

Circadian clock protein CRY1 prevents paclitaxel‑induced senescence of bladder cancer cells by promoting p53 degradation.

Oncol Rep 2021 Mar 30;45(3):1033-1043. Epub 2020 Dec 30.

Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen, Guangdong 518122, P.R. China.

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first‑line treatment is cisplatin‑based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy‑induced senescence can act as a 'back‑up' response to chemotherapy in cancer types that are resistant to apoptosis‑based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)‑induced senescence in cisplatin‑resistant bladder cancer cells. Cisplatin‑resistant bladder cancer cells were established via long‑term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA‑β‑Gal staining, but this was not observed in the cisplatin‑resistant cells. The cisplatin‑resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin‑resistant cells, and that CRY1 knockdown restored PTX‑induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto‑oncogene. These data suggested that the accumulated CRY1 in cisplatin‑resistant cells could prevent PTX‑induced senescence by promoting p53 degradation.
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http://dx.doi.org/10.3892/or.2020.7914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860017PMC
March 2021

Pharmacokinetics and Safety of Dapoxetine Hydrochloride in Healthy Chinese Men: Impact of Dose and High-Fat Meal.

Clin Pharmacol Drug Dev 2021 Feb 2. Epub 2021 Feb 2.

School of Pharmacy Lanzhou University, Lanzhou, China.

Dapoxetine is the first oral medication specifically developed for the on-demand treatment of premature ejaculation. The pharmacokinetics and safety of 30 mg (n = 40) and 60 mg (n = 38) dapoxetine in healthy Chinese under fasted and fed states were assessed in 2 studies. Both studies are random, single-center, 2-period, open-label, 2-way crossover designs. Plasma concentration of dapoxetine was determined by high-performance liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated using noncompartmental analysis. Dapoxetine was quickly absorbed and reached maximum concentration 1 to 3 hours after oral administration. Elimination was biphasic, and the plasma concentration decreased to 3% to 7% of maximum concentration by 24 hours while half-life was 15 to 18 hours. Meantime, high-fat meals slightly increased its exposure. Both doses of dapoxetine were well tolerated. The adverse events in the high-dose group under fasted and fed states were 37.9% and 19.0%, respectively.
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http://dx.doi.org/10.1002/cpdd.919DOI Listing
February 2021

Bioequivalence Analysis of 2 Dapoxetine Hydrochloride Formulations in Healthy Chinese Male Volunteers Under Fed and Fasting Conditions: A Randomized, Open-Label, 2-Sequence, 2-Period, 2-Way Crossover Study.

Clin Pharmacol Drug Dev 2021 Apr 1;10(4):384-392. Epub 2021 Jan 1.

Phase I Clinical Unit, Lanzhou University Second Hospital, Lanzhou, Gansu, PR China.

This study assessed whether the reference and test formulations of dapoxetine hydrochloride were bioequivalent under fed and fasting conditions postadministration of a single dose as well as evaluated the safety profile of these 2 formulations. This study was a randomized, single-center, 2-period, open-label, 2-way crossover design study with a washout period of 7 days between each period. The study included 80 subjects, 40 under fed and 40 under fasting conditions. During each study period, the subjects were administered a single oral dose of either the reference or the test formulation, followed by collection of plasma samples 70 hours postdose. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was performed to determine the concentrations of dapoxetine in plasma samples along with the calculation of C , AUC and AUC . In addition, adverse events were monitored to determine the safety of these formulations. The geometric mean ratio (90%CI) for the reference and test formulations was 86% to 100%, 89% to 103%, and 89% to 103% under fasting conditions and 92% to 107%, 91% to 100%, and 92% to 101% under fed conditions for C , AUC , and AUC , respectively. The 90%CIs for the test/reference ratio for AUC and C were within the acceptable limits of bioequivalence, thus demonstrating bioequivalence for these 2 dapoxetine hydrochloride formulations.
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http://dx.doi.org/10.1002/cpdd.866DOI Listing
April 2021

The Bio-Synthesis of Three Metal Oxide Nanoparticles (ZnO, MnO, and MgO) and Their Antibacterial Activity Against the Bacterial Leaf Blight Pathogen.

Front Microbiol 2020 4;11:588326. Epub 2020 Dec 4.

State Key Laboratory of Rice Biology, Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

pv. () is the most infectious pathogen of rice, which causes bacterial leaf blight (BLB) disease. However, the accumulation of chemical or antibiotic resistance of necessitate the development of its alternative control. In this study, we biologically synthesize three metal oxide nanoparticles (ZnO, MnO, and MgO) using rhizophytic bacteria strain Sx3 as reducing agent. The biosynthesis of nanoparticles was confirmed and characterized by using UV-vis spectroscopy, XRD, FTIR, EDS, SEM, and TEM analysis. The UV Vis reflectance of the nanoparticle had peaks at 385, 230, and 230 nm with an average crystallite particle size 62.8, 18.8, and 10.9 nm for ZnO, MnO, and MgO, respectively. Biogenic ZnO, MnO, and MgO nanoparticles showed substantial significant inhibition effects against strain GZ 0006 at a concentration of 16.0 μg/ml, for which the antagonized area was 17, 13, and 13 mm and the biofilm formation was decreased by 74.5, 74.4, and 80.2%, respectively. Moreover, the underlining mechanism of nanoparticles was inferred to be in relation to the reactive oxygen species based on their antibacterial efficiency and the deformity in the cell wall phenomenon. Overall, an attractive and eco-friendly biogenic ZnO, MnO, and MgO nanoparticles were successfully produced. Altogether, the results suggest that the nanoparticles had an excellent antibacterial efficacy against BLB disease in rice plants, together with the increase in growth parameter and rice biomass. In conclusion, the synthesized nanoparticles could serve as an alternative safe measure in combatting the antibiotic-resistant of Xoo.
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http://dx.doi.org/10.3389/fmicb.2020.588326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746657PMC
December 2020

Clinical significance and functional role of transmembrane protein 47 (TMEM47) in chemoresistance of hepatocellular carcinoma.

Int J Oncol 2020 Oct 28;57(4):956-966. Epub 2020 Jul 28.

Department of Surgery, The University of Hong Kong Shenzhen Hospital and LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.

Chemoresistance is the main cause of chemotherapy failure in patients with hepatocellular carcinoma (HCC). The gene encoding transmembrane protein 47 (TMEM47) was previously identified to be significantly upregulated in HCC cell lines with acquired chemoresistance. The aim of the present study was to characterize the clinical significance and function of TMEM47 in HCC chemoresistance. The results demonstrated that the TMEM47 expression levels in the tumors of patients not responding to cisplatin‑based transarterial chemoembolization (TACE) treatment was significantly higher compared with those in patients who responded to TACE treatment. Moreover, analyses from clinical samples and HCC cell lines indicated that TMEM47 expression may be upregulated in HCC in response to cisplatin treatment. Furthermore, the TMEM47 mRNA expression levels were positively correlated with the degree of cisplatin resistance of HCC cells. Overexpression of TMEM47 in HCC cells significantly promoted cisplatin resistance. The present study also demonstrated that targeted inhibition of TMEM47 could significantly reduce cisplatin resistance of cisplatin‑resistant HCC cells via enhancing caspase‑mediated apoptosis. In addition, targeted inhibition of TMEM47 enhanced the sensitivity of cisplatin‑resistant cells to cisplatin via suppressing cisplatin‑induced activation of the genes involved in drug efflux and metabolism. The present study also validated that TMEM47 expression was significantly correlated with multidrug resistance‑associated protein 1 in patients with HCC who received TACE treatment. In conclusion, the findings of the present study demonstrated that TMEM47 may be a useful biomarker for predicting the response to chemotherapy and a potential therapeutic target for overcoming HCC chemoresistance.
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http://dx.doi.org/10.3892/ijo.2020.5104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473756PMC
October 2020

Phosphopeptide enrichment for phosphoproteomic analysis - A tutorial and review of novel materials.

Anal Chim Acta 2020 Sep 28;1129:158-180. Epub 2020 Apr 28.

School of Engineering, Faculty of Science, Agriculture and Engineering, Newcastle University, Newcastle Upon Tyne, NE1 7RU, United Kingdom. Electronic address:

Significant technical advancements in phosphopeptide enrichment have enabled the identification of thousands of p-peptides (mono and multiply phosphorylated) in a single experiment. However, it is still not possible to enrich all p-peptide species in a single step. A range of new techniques and materials has been developed, with the potential to provide a step-change in phosphopeptide enrichment. The first half of this review contains a tutorial for new potential phosphoproteomic researchers; discussing the key steps of a typical phosphoproteomic experiment used to investigate canonical phosphorylation sites (serine, threonine and tyrosine). The latter half then show-cases the latest developments in p-peptide enrichment including: i) Strategies to mitigate non-specific binding in immobilized metal ion affinity chromatography and metal oxide affinity chromatography protocols; ii) Techniques to separate multiply phosphorylated peptides from monophosphorylated peptides (including canonical from non-canonical phosphorylated peptides), or to simultaneously co-enrich other post-translational modifications; iii) New hybrid materials and methods directed towards enhanced selectivity and efficiency of metal-based enrichment; iv) Novel materials that hold promise for enhanced phosphotyrosine enrichment. A combination of well-understood techniques and materials is much more effective than any technique in isolation; but the field of phosphoproteomics currently requires benchmarking of novel materials against current methodologies to fully evaluate their utility in peptide based proteoform analysis.
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http://dx.doi.org/10.1016/j.aca.2020.04.053DOI Listing
September 2020

Chemical-potential multiphase lattice Boltzmann method with superlarge density ratios.

Phys Rev E 2020 Jul;102(1-1):013303

Department of Mechanics and Aerospace Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

The liquid-gas density ratio is a key property of multiphase flow methods to model real fluid systems. Here, a chemical-potential multiphase lattice Boltzmann method is constructed to realize extremely large density ratios. The simulations show that the method reaches very low temperatures, at which the liquid-gas density ratio is more than 10^{14}, while the thermodynamic consistency is still preserved. Decoupling the mesh space from the momentum space through a proportional coefficient, a smaller mesh step provides denser lattice nodes to exactly describe the transition region and the resulting dimensional transformation has no loss of accuracy. A compact finite-difference method is applied to calculate the discrete derivatives in the mesh space with high-order accuracy. These enhance the computational accuracy of the nonideal force and suppress the spurious currents to a very low level, even if the density ratio is up to tens of thousands. The simulation of drop splashing verifies that the present model is Galilean invariant for the dynamic flow field. An upper limit of the chemical potential is used to reduce the influence of nonphysical factors and improve the stability.
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http://dx.doi.org/10.1103/PhysRevE.102.013303DOI Listing
July 2020

KLF6 Acetylation Promotes Sublytic C5b-9-Induced Production of MCP-1 and RANTES in Experimental Mesangial Proliferative Glomerulonephritis.

Int J Biol Sci 2020 20;16(13):2340-2356. Epub 2020 Jun 20.

Department of Laboratory Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.

Rat Thy-1 nephritis (Thy-1N) is an experimental mesangial proliferative glomerulonephritis (MsPGN) for studying human MsPGN. Although sublytic C5b-9 complex formation on glomerular mesangial cells (GMCs) and renal MCP-1 and RANTES production in rats with Thy-1N have been proved, the role and mechanism of MCP-1 or RANTES synthesis in GMCs induced by sublytic C5b-9 are poorly elucidated. In this study, we first found the expression of transcription factor (KLF6), co-activator (KAT7) and chemokines (MCP-1 and RANTES) was all up-regulated both in renal tissue of Thy-1N rats () and in sublytic C5b-9-induced GMCs (). Further experiments revealed that KLF6 bound to MCP-1 promoter (-297 to -123 nt) and RANTES promoter (-343 to -191 nt), leading to MCP-1 and RANTES gene transcription. Meanwhile, KAT7 also bound to the same region of MCP-1 and RANTES promoter in a KLF6-dependent manner, and KLF6 was acetylated by KAT7 at lysine residue 100, which finally promoted MCP-1 and RANTES expression. Moreover, our experiments discovered that knockdown of renal KAT7 or KLF6 gene obviously reduced MCP-1 and RANTES production, GMCs proliferation, ECM accumulation, and proteinuria secretion in Thy-1N rats. Collectively, our study indicates that sublytic C5b-9-induced MCP-1 and RANTES synthesis is associated with KAT7-mediated KLF6 acetylation and elevated KLF6 transcriptional activity, which might provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.
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http://dx.doi.org/10.7150/ijbs.46573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378648PMC
June 2020

Evaluation of Bioequivalency and Pharmacokinetic Parameters for Two Formulations of Glimepiride 1-mg in Chinese Subjects.

Drug Des Devel Ther 2020 6;14:2637-2644. Epub 2020 Jul 6.

Phase I Clinical Unit, Lanzhou University Second Hospital, Lanzhou, People's Republic of China.

Purpose: Glimepiride, an FDA-approved oral hypoglycemic drug, is a long-acting sulfonylurea (SU), used for treating type 2 diabetes. The study aimed to evaluate the bioequivalence and safety profiles of two different formulations of glimepiride 1 mg from two different manufactures in healthy Chinese subjects in the fasting and fed state in order to acquire adequate pharmacokinetic evidence for registration approval of the test formulation.

Patients And Methods: This study is an open-label, two-period, two-sequence, randomized, two-way crossover pharmacokinetic study in healthy Chinese subjects in the fasting and fed state. Seventy-two subjects were randomly assigned to the fasting group and the fed group (n=36 each). We collected blood samples, 24-h post drug administration. The plasma concentration of glimepiride was assessed using HPLC coupled with mass spectrometry. The following parameters were evaluated: AUC, AUC, C, t, T, and λ. Safety was determined based on the occurrence of adverse events (AEs) and laboratory examinations (biochemistry, hematology, and urinalysis) throughout the entire study period.

Results: The geometric mean ratios (GMR) amongst the two glimepiride formulations for the primary pharmacokinetic parameters, ie, AUC, AUC, and C as well as the corresponding 90% CIs, were all within the range of 80.00-125.00% in the fasting and fed state. The safety profile for both treatments was comparable.

Conclusion: PK analysis revealed that the test and reference formulations of glimepiride were bioequivalent and well tolerated in healthy Chinese subjects. Chinese Clinical Trials Registry identifier: CTR20171121.

Clinical Trial Registration Number: CTR20171121.
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http://dx.doi.org/10.2147/DDDT.S249355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351633PMC
July 2020

A fluorescence signal amplification strategy for modification-free ratiometric determination of tyrosinase in situ based on the use of dual-templated copper nanoclusters.

Mikrochim Acta 2020 03 20;187(4):240. Epub 2020 Mar 20.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, Eel farming and processing, Fuzhou University, Fuzhou, 350108, Fujian, China.

A fluorescence resonance energy transfer (FRET)-based in situ fluorescence signal amplification strategy is described for the determination of tyrosinase (TYR). In this assay, a dual-templated copper nanocluster (CuNCs) stabilized by bovine serum albumin (BSA) and glycylglycine (Gly-Gly) was used as an energy donor. Metyrosine was employed as a TYR substrate because its enzyme catalytic product (methyldopa) was able to function as a monomer molecule to form fluorescent polymethyldopa (PMeDP) with the assistance of BSA/Gly-Gly CuNCs. In this process, PMeDP can combine with BSA/Gly-Gly CuNCs without extra modification and then acts as an energy receptor, which leads to a remarkable FRET from BSA/Gly-Gly CuNCs to PMeDP. Interestingly, the fluorescence intensity of PMeDP was strengthened greatly in the FRET-based sensor compared to the separate excitation, which provided good sensitivity for TYR sensing. Illuminated under a UV light source, the fluorescence signal change is observed from dark violet to bright green. Therefore, the present sensing system affords a reliable ratiometric assay for TYR determination. Also, the ratio of fluorescence intensity between PMeDP (λ at 505 nm, F505) and BSA/Gly-Gly CuNCs (λ at 415 nm, F415) was used for quantitative determination of TYR. The sensing system was easily operated in aqueous media with an exciting detection limit of 44.0 U L. This sensing strategy has been applied to the screening of inhibitors. Graphical abstract Schematic representation of the strategy for the determination of tyrosinase.
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http://dx.doi.org/10.1007/s00604-020-4186-yDOI Listing
March 2020

Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis.

Brain Behav Immun 2020 07 6;87:739-750. Epub 2020 Mar 6.

Center for Neurotherapeutics Discovery, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA; Department of Neuroscience, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA; Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the CNS characterized by both grey and white matter injury. Microglial activation and a reduction in synaptic density are key features of grey matter pathology that can be modeled with MOG experimental autoimmune encephalomyelitis (EAE). Complement deposition combined with microglial engulfment has been shown during normal development and in disease as a mechanism for pruning synapses. We tested whether there is excess complement production in the EAE hippocampus and whether complement-dependent synapse loss is a source of degeneration in EAE using C1qa and C3 knockout mice. We found that C1q and C3 protein and mRNA levels were elevated in EAE mice. Genetic loss of C3 protected mice from EAE-induced synapse loss, reduced microglial activation, decreased the severity of the EAE clinical score, and protected memory/freezing behavior after contextual fear conditioning. C1qa KO mice with EAE showed little to no change on these measurements compared to WT EAE mice. Thus, pathologic expression and activation of the early complement pathway, specifically at the level of C3, contributes to hippocampal grey matter pathology in the EAE.
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http://dx.doi.org/10.1016/j.bbi.2020.03.004DOI Listing
July 2020

Green-Synthesization of Silver Nanoparticles Using Endophytic Bacteria Isolated from Garlic and Its Antifungal Activity against Wheat Head Blight Pathogen .

Nanomaterials (Basel) 2020 Jan 27;10(2). Epub 2020 Jan 27.

State Key Laboratory of Rice Biology and Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China.

Nanoparticles are expected to play a vital role in the management of future plant diseases, and they are expected to provide an environmentally friendly alternative to traditional synthetic fungicides. In the present study, silver nanoparticles (AgNPs) were green synthesized through the mediation by using the endophytic bacterium strain CO, which was isolated from garlic plants (). Following a confirmation analysis that used UV-Vis, we examined the in vitro antifungal activity of the biosynthesized AgNPs with the size of 19.8-44.9 nm, which showed strong inhibition in the mycelium growth, spore germination, the length of the germ tubes, and the mycotoxin production of the wheat head blight pathogen . Furthermore, the microscopic examination showed that the morphological of mycelia had deformities and collapsed when treated with AgNPs, causing DNA and proteins to leak outside cells. The biosynthesized AgNPs with strong antifungal activity were further characterized based on analyses of X-ray diffraction, transmission electron microscopy, scanning electron microscopy, EDS profiles, and Fourier transform infrared spectroscopy. Overall, the results from this study clearly indicate that the biosynthesized AgNPs may have a great potential in protecting wheat from fungal infection.
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http://dx.doi.org/10.3390/nano10020219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074875PMC
January 2020

Effect of high energy ball milling on organic pollutant adsorption properties of chitosan.

Int J Biol Macromol 2020 Apr 18;148:543-549. Epub 2020 Jan 18.

State Key Joint Laboratory of Environment Simulation and Pollution Control (SKJLESPC), Beijing Key Laboratory of Emerging Organic Contaminants Control (BKLEOCC), School of Environment, Tsinghua University, Beijing 100084, China.

In the present work, chitosan physicochemical transformations that occur during high energy ball milling are investigated and correlated with adsorption capacity of organic pollutants (using azo-dye reactive red 2 as molecular probe). Experimental results reveal that chitosan ball milled for 1 h shows a 70% increase of adsorption capacity, compared to unmilled one, while longer milling time causes a sensible reduction of such capacity. This trend correlates with specific surface area evolution under milling, thus suggesting the primary role of particle comminution in augmenting chitosan adsorption properties. Amorphization of particle surface was found to be marginally relevant for adsorption capacity enhancement. Maximum adsorption capacity (estimated by isothermal equilibrium study) and adsorption rate are augmented by ball milling, with an optimal value found at 1 h milling. Finally, the milled materials were tested to adsorb perfluorooctane sulfonate, obtaining 1.54 mmol g uptake with 1 h milled chitosan. This suggests that chitosan could be used as a cheap expendable material to remove those pollutants, like perfluorooctane sulfonate and the other perfluoroalkyl substances, that deserves destruction and cannot be removed by conventional degradation technologies.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.171DOI Listing
April 2020

Sublytic C5b-9 induces proliferation of glomerular mesangial cells via ERK5/MZF1/RGC-32 axis activated by FBXO28-TRAF6 complex.

J Cell Mol Med 2019 08 11;23(8):5654-5671. Epub 2019 Jun 11.

Department of Immunology, Nanjing Medical University, Nanjing, People's Republic of China.

Mesangioproliferative glomerulonephritis (MsPGN) is characterized by the proliferation of glomerular mesangial cells (GMCs) and accumulation of extracellular matrix (ECM), followed by glomerulosclerosis and renal failure of patients. Although our previous studies have demonstrated that sublytic C5b-9 complex formed on the GMC membrane could trigger GMC proliferation and ECM expansion of rat Thy-1 nephritis (Thy-1N) as an animal model of MsPGN, their mechanisms are still not fully elucidated. In the present studies, we found that the levels of response gene to complement 32 (RGC-32), myeloid zinc finger 1 (MZF1), phosphorylated extracellular signal-regulated kinase 5 (phosphorylated ERK5, p-ERK5), F-box only protein 28 (FBXO28) and TNF receptor-associated factor 6 (TRAF6) were all markedly up-regulated both in the renal tissues of rats with Thy-1N (in vivo) and in the GMCs upon sublytic C5b-9 stimulation (in vitro). Further in vitro experiments revealed that up-regulated FBXO28 and TRAF6 could form protein complex binding to ERK5 and enhance ERK5 K63-ubiquitination and subsequent phosphorylation. Subsequently, ERK5 activation contributed to MZF1 expression and MZF1-dependent RGC-32 up-regulation, finally resulting in GMC proliferative response. Furthermore, the MZF1-binding element within RGC-32 promoter and the functions of FBXO28 domains were identified. Additionally, knockdown of renal FBXO28, TRAF6, ERK5, MZF1 and RGC-32 genes respectively markedly reduced GMC proliferation and ECM production in Thy-1N rats. Together, these findings indicate that sublytic C5b-9 induces GMC proliferative changes in rat Thy-1N through ERK5/MZF1/RGC-32 axis activated by the FBXO28-TRAF6 complex, which might provide a new insight into MsPGN pathogenesis.
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http://dx.doi.org/10.1111/jcmm.14473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6653533PMC
August 2019

Biosynthesis and characterization of magnesium oxide and manganese dioxide nanoparticles using L. extract and its inhibitory effect on strain RS-2.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):2230-2239

a State Key Laboratory of Rice Biology and Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University , Hangzhou , China.

Bacterial brown stripe (BBS) is one of the most economically important diseases of rice caused by (Ao). In order to ensure food security and safe consumption, the use of non-chemical approach is necessary. In this study, MgO and MnO were synthesized using chamomile flower extract. The synthesized MgO and MnO nanoparticles were characterized by UV-Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission/scanning electron microscopy. The sizes were 18.2 and 16.5 nm for MgO and MnO nanoparticles, respectively. The MgO and MnO nanoparticles reduced the growth of Ao strain RS-2 by 62.9 and 71.3%, respectively. Also, the biofilm formation and swimming motility were significantly reduced compared to the control. The antibacterial mechanisms of MgO and MnO nanoparticles against RS-2 reveals that MgO and MnO nanoparticles penetrated the cells and destroyed the cell membrane leading to leakage of cytoplasmic content. Also, the flow cytometry observation reveals that the apoptotic cell ratio of RS-2 increased from 0.97% to 99.52 and 99.94% when treated with MgO and MnO nanoparticles, respectively. Altogether, the results suggest that the synthesized MgO and MnO nanoparticles could serve as an alternative approach method for the management of BBS.
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http://dx.doi.org/10.1080/21691401.2019.1622552DOI Listing
December 2019

Biogenic Synthesis of Silver Nanoparticles Using Fruit Extract and Its Inhibitory Action Against the Pathogen Strain RS-2 of Rice Bacterial Brown Stripe.

Front Microbiol 2019 26;10:820. Epub 2019 Apr 26.

State Key Laboratory of Rice Biology and Key Lab of Molecular Biology of Crop Pathogens and Insects, Institute of Biotechnology, Zhejiang University, Hangzhou, China.

Biogenic synthesis of silver nanoparticles (AgNPs) using plants has become a promising substitute to the conventional chemical synthesis method. In this study, we report low-cost, green synthesis of AgNPs using fresh fruit extract of . The biosynthesized AgNPs was confirmed and characterized by analysis of spectroscopy profile of the UV-visible and Energy dispersive spectrophotometer, Fourier transform infrared, X-ray diffraction pattern, and electron microscopy images examination. UV-visible spectra showed a surface resonance peak of 430 nm corresponding to the formation of AgNPs, and FTIR spectra confirmed the involvement of biological molecules in AgNPs synthesis. In spherical AgNPs, the particle size ranged from 19.8 to 92.8 nm and the average diameter was 39 nm. Synthesized nanoparticles at 20 μg/ml showed remarkable antimicrobial activity against the pathogen strain RS-2 of rice bacterial brown stripe, while 62.41% reduction in OD value was observed compared to the control. Moreover, the inhibitory efficiency of AgNPs increased with the increase of incubation time. Furthermore, AgNPs not only disturbed biofilm formation and swarming ability but also increased the secretion of effector Hcp in strain RS-2, resulting from damage to the cell membrane, which was substantiated by TEM images and live/dead cell staining result. Overall, this study suggested that AgNPs can be an attractive and eco-friendly candidate to control rice bacterial disease.
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http://dx.doi.org/10.3389/fmicb.2019.00820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501729PMC
April 2019

IL-17 induces the proliferation and migration of glioma cells through the activation of PI3K/Akt1/NF-κB-p65.

Cancer Lett 2019 04 18;447:93-104. Epub 2019 Jan 18.

Department of Neurosurgery, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou, Jiangsu, 215300, PR China. Electronic address:

Interleukin 17 (IL-17), as a pro-inflammatory cytokine, is up-regulated in the sera and tumor tissues of glioma patients; however the effects of IL-17 on glioma proliferation and migration remain unclear. In this study, the roles of IL-17 in the proliferation and migration of glioma cells and their potential mechanisms were determined. The results showed that IL-17 could not only enhance the proliferation and migration of cultured glioma cells (in vitro), but also promote the tumor formation of glioma cells in BALB/c nude mice (in vivo). Mechanical exploration revealed that IL-17 stimulation could increase the phosphorylation levels of Akt1 and NF-κB-p65 in glioma cells, and knockdown or inhibition of PI3K, Akt1 and NF-κB-p65 could also reduce the IL-17-induced proliferation and migration of the glioma cells. Moreover, PI3K/Akt1 was the upstream regulator of NF-κB-p65 activation in IL-17-incubated glioma cells. Furthermore, the inhibition of PI3K, Akt1 and NF-κB-p65 markedly suppressed the tumor formation of glioma cells induced by IL-17. Together, these data indicate that IL-17 can promote the proliferation and migration of glioma cells via PI3K/Akt1/NF-κB-p65 activation, and these findings might provide a new insight into glioma pathogenesis.
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http://dx.doi.org/10.1016/j.canlet.2019.01.008DOI Listing
April 2019

Role of type IV secretion system genes in virulence of rice bacterial brown stripe pathogen Acidovorax oryzae strain RS-2.

Microb Pathog 2019 Jan 20;126:343-350. Epub 2018 Nov 20.

State Key Laboratory Breeding Base for Zhejiang Sustainable Pest and Disease Control, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, 310021, Hangzhou, China.

Type IV secretion system (T4SS) is a specialized nanomachine that is utilized for the pathogenicity of gram-negative bacteria. However, the role of T4SS genes in virulence of rice bacterial brown stripe pathogen Acidovorax oryzae (Ao) strain RS-2 is not clear, which contains T4SS gene cluster based on genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type strain RS-2 and nine T4SS mutants, which were constructed in this study. Results indicated that mutation of pilT, pilM, pilQ, or pilZ3 genes not only significantly reduced bacterial virulence, but also caused a reduction of 20.4-62.0% in biofilm formation and 37.7-47.7% reduction in motility, but had no effect on exopolysaccharide (EPS) production or extracellular enzymatic activities when compared to the wild type. The four T4SS genes had a differential effect on bacterial growth after 24 h post-incubation. The complemented strains of the four T4SS mutants restored similar virulence symptom as the wild type. In addition, no change was observed in bacterial virulence by mutation of the other five T4SS genes. Totally, these results demonstrated that T4SS played vital roles in bacterial virulence, motility and biofilm formation in plant pathogen Ao strain RS-2.
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http://dx.doi.org/10.1016/j.micpath.2018.11.017DOI Listing
January 2019

Sublytic C5b-9 Induces IL-23 and IL-36a Production by Glomerular Mesangial Cells via PCAF-Mediated KLF4 Acetylation in Rat Thy-1 Nephritis.

J Immunol 2018 12 7;201(11):3184-3198. Epub 2018 Nov 7.

Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, People's Republic of China;

Sublytic C5b-9 formation on glomerular mesangial cells in rat Thy-1 nephritis (Thy-1N), a model of human mesangioproliferative glomerulonephritis, is accompanied by the production of proinflammatory cytokines, but the relationship between sublytic C5b-9 and cytokine synthesis and the underlying mechanism remains unclear. To explore the problems mentioned above, in this study, we first examined the levels of proinflammatory ILs (e.g., IL-23 and IL-36a) as well as transcription factor (KLF4) and coactivator (PCAF) in the renal tissues of Thy-1N rats and in the glomerular mesangial cell line (HBZY-1) stimulated by sublytic C5b-9. Then, we further determined the role of KLF4 and PCAF in sublytic C5b-9-induced IL-23 and IL-36a production as well as the related mechanism. Our results showed that the levels of KLF4, PCAF, IL-23, and IL-36a were obviously elevated. Mechanistic investigation revealed that sublytic C5b-9 stimulation could increase IL-23 and IL-36a synthesis through KLF4 and PCAF upregulation, and KLF4 and PCAF could form a complex, binding to the IL-23 or IL-36a promoter in a KLF4-dependent manner, causing gene transcription. Importantly, KLF4 acetylation by PCAF contributed to sublytic C5b-9-induced IL-23 and IL-36a transcription. Besides, the KLF4 binding regions on IL-23 or IL-36a promoters and the KLF4 lysine site acetylated by PCAF were identified. Furthermore, silencing renal KLF4 or PCAF gene could significantly inhibit IL-23 or IL-36a secretion and tissue damage of Thy-1N rats. Collectively, these findings implicate that the KLF4/PCAF interaction and KLF4 acetylation by PCAF play a pivotal role in the sublytic C5b-9-mediated IL-23 and IL-36a production of Thy-1N rats.
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http://dx.doi.org/10.4049/jimmunol.1800719DOI Listing
December 2018

HIV Tat causes synapse loss in a mouse model of HIV-associated neurocognitive disorder that is independent of the classical complement cascade component C1q.

Glia 2018 12 16;66(12):2563-2574. Epub 2018 Oct 16.

Center for Neurotherapeutics Discovery, University of Rochester Medical Center, Rochester, New York.

Microglial activation, increased proinflammatory cytokine production, and a reduction in synaptic density are key pathological features associated with HIV-associated neurocognitive disorders (HAND). Even with combination antiretroviral therapy (cART), more than 50% of HIV-positive individuals experience some type of cognitive impairment. Although viral replication is inhibited by cART, HIV proteins such as Tat are still produced within the nervous system that are neurotoxic, involved in synapse elimination, and provoke enduring neuroinflammation. As complement deposition on synapses followed by microglial engulfment has been shown during normal development and disease to be a mechanism for pruning synapses, we have tested whether complement is required for the loss of synapses that occurs after a cortical Tat injection mouse model of HAND. In Tat-injected animals evaluated 7 or 28 days after injection, levels of early complement pathway components, C1q and C3, are significantly elevated and associated with microgliosis and a loss of synapses. However, C1qa knockout mice have the same level of Tat-induced synapse loss as wild-type (WT) mice, showing that the C1q-initiated classical complement cascade is not driving synapse removal during HIV1 Tat-induced neuroinflammation.
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http://dx.doi.org/10.1002/glia.23511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309507PMC
December 2018

Effect of purple grape juice on the pharmacokinetics of digoxin: Results of a food-drug interaction study
.

Int J Clin Pharmacol Ther 2019 Feb;57(2):101-109

Objective: Digoxin is a glycosidic, cardiotonic plant extract with a narrow therapeutic window. The purpose of the study was to investigate the effects of purple grape juice on the pharmacokinetics of digoxin in rats.

Materials And Methods: A randomized, controlled, single- and multiple-dose study was conducted to evaluate the pharmacokinetic profiles of orally and intravenously administered digoxin. The plasma concentration of digoxin was determined by radioimmunoassay using a gamma counter, and a Caco-2 cell transport model was used to investigate the potential mechanism by which purple grape juice affects the pharmacokinetics of digoxin.

Results: The results show that multiple-dose purple grape juice caused a remarkable increase in the AUC, C, and Ka of orally administered digoxin (p < 0.05); only a single dose increased the digoxin AUC by 72.80% (p < 0.05). Other parameters were not significantly affected. The study of intravenously administered digoxin found no significant difference in the pharmacokinetic characteristics of the two dosing groups (p > 0.05). The Caco-2 transwell experiments indicated that both the pure purple grape juice and its ethyl acetate extract significantly inhibited digoxin basolateral-to-apical (B→A) transport at concentrations of 10%, 30%, and 50% with dose dependency. These results confirmed that the improvement in bioavailability of digoxin resulted from the inhibition of P-gp by purple grape juice at the level of the gastrointestinal wall.

Conclusion: Purple grape juice can increase the bioavailability of orally administered digoxin, especially with multiple doses. This information suggests that co-administration of oral digoxin and purple grape juice may require a dose adjustment.
.
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http://dx.doi.org/10.5414/CP203273DOI Listing
February 2019

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis.

Cell Physiol Biochem 2018 20;49(5):1898-1917. Epub 2018 Sep 20.

Department of Immunology, Nanjing Medical University, Nanjing, China.

Background/aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism.

Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry.

Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription.

Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN.
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http://dx.doi.org/10.1159/000493652DOI Listing
October 2018

Combination of procalcitonin, C-reaction protein and carcinoembryonic antigens for discriminating between benign and malignant pleural effusions.

Oncol Lett 2018 Aug 1;16(2):1727-1735. Epub 2018 Jun 1.

Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Pleural effusion (PE) is a common manifestation associated with certain chest diseases. However, there is no effective diagnostic marker with high sensitivity and specificity. The aim of the present study was to evaluate the diagnostic performance of several biomarkers in the use of detecting malignant pleural disorder. One hundred and fifty patients with a specific diagnosis of exudative PE were enrolled in this study and were divided into the benign PE group (n=93) and the malignant PE group (n=57). Thoracoscopy was conducted to identify the reasons for the PE. Biomarkers in pleural fluid and in sera were determined either by microparticle enzyme immunoassay [carcinoembryonic antigen (CEA)], fluorescence immunoassay [procalcitonin (PCT)] or light-scattering turbidimetric immunoassay [C-reaction protein (CRP)]. Then, correlation analysis and receiver-operating characteristic (ROC) curve analysis individually or in combination were performed. The CRP and PCT levels were higher in benign PE than they were in malignant PE (PCT: P=0.017, P=0.032; CRP: P=0.001, P<0.001, respectively), while CEA levels were lower in benign PE than in malignant PE (CEA: P=0.001, P=0.001, respectively). During the ROC curve analysis, an optimal discrimination was identified by combining pleural CRP, pleural CEA and serum (s)PCT with an area under the curve of 0.973 (sensitivity, 98.9%; specificity, 89.5%). In the diagnosis of PE, there was no single biomarker that appeared to be adequately accurate. The combination of pleural CRP, pleural CEA and sPCT may represent an efficient diagnostic procedure for guiding the patient towards follow-up clinical treatment.
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http://dx.doi.org/10.3892/ol.2018.8871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036474PMC
August 2018

C5a induces A549 cell proliferation of non-small cell lung cancer via GDF15 gene activation mediated by GCN5-dependent KLF5 acetylation.

Oncogene 2018 08 18;37(35):4821-4837. Epub 2018 May 18.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo. Our results found that the expression of KLF5, GCN5, GDF15, C5aR, and C5a was significantly upregulated in NSCLC patients. Mechanistic exploration in vitro revealed that C5a could facilitate A549 cell proliferation through increasing KLF5, GCN5, and GDF15 expression. Besides, KLF5 and GCN5 could form a complex, binding to GDF15 promoter in a KLF5-dependent manner and leading to GDF15 gene transcription. More importantly, GCN5-mediated KLF5 acetylation contributing to GDF15 gene transcription and cell proliferation upon C5a stimulation, the region (-103 to +58 nt) of GDF15 promoter which KLF5 could bind to, and two new KLF5 lysine sites (K335 and K391) acetylated by GCN5 were identified for the first time. Furthermore, our experiment in vivo demonstrated that the growth of xenograft tumors in BALB/c nude mice was greatly suppressed by the silence of KLF5, GCN5, or GDF15. Collectively, these findings disclose that C5a-driven KLF5-GCN5-GDF15 axis had a critical role in NSCLC proliferation and might serve as targets for NSCLC therapy.
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http://dx.doi.org/10.1038/s41388-018-0298-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117268PMC
August 2018

[Effects of different salinity levels on nitrification processes in sediments of Minjiang River Estuary, China].

Ying Yong Sheng Tai Xue Bao 2018 Apr;29(4):1313-1320

College of Environmental Science and Engineering, Fujian Normal University, Fuzhou 350007, China.

Two estuary wetlands in Minjiang River, Shanyutan and Daoqingzhou, were selected as the research objects. Wetland sediments were collected to examine the effects of different salinity levels on nitrification processes in the wetland with a culture experiment. The results showed that the nitrification rate of sediment in Minjiang River estuary wetland was generally low. The highest nitrification rate of sediment in the Shanyutan wetland was 0.193 mg·kg·d, while that in the Daoqingzhou wetland did not exceed 0.050 mg·kg·d. In the low salinity level (5), the decrease of nitrification rate was attributed to the restraint of nitrifying bacteria activities. The nitrification rate slightly increased with the increases of salinity (10), but was still lower than the initial value. This would be owed to the fact that the inhibitory effect of salinity on the activities of aerobic bacteria was strengthened, which reduced the rate of NH-N production, and thus resulted in a decrease of the contribution of aerobic ammonification bacteria to the apparent nitrification rate. There were regional variations in the responses of sediment nitrifying activity to salinity. In saltwater wetland (Shanyutan wetland), the adaptability of microbes in sediment to salinity was stronger, so that the nitrification activity in high salinity conditions was still higher. While in the freshwater wetland (Daoqingzhou wetland), the adaptability of the sediment to the salinity change was relatively lower, with a lower nitrification activity of the sediment in high salinity than in middle salinity. Acidic condition was the main reason for the low nitrification in the sediments of Minjiang estuary wetland. The nitrification rate and nitrification activity of the two wetlands increased first and then decreased with the duration of the culture experiment, which was driven by combined effects of initial NH-N concentration, oxygen content and denitrifying.
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http://dx.doi.org/10.13287/j.1001-9332.201804.038DOI Listing
April 2018

IL‑17 induces NSCLC A549 cell proliferation via the upregulation of HMGA1, resulting in an increased cyclin D1 expression.

Int J Oncol 2018 May 7;52(5):1579-1592. Epub 2018 Mar 7.

Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Non-small cell lung cancer (NSCLC) is considered to be an inflammation-associated carcinoma. Although interleukin‑17 (IL‑17) production contributes to the proliferation and growth of NSCLC, the mechanisms underlying IL‑17-induced NSCLC cell proliferation have not been fully elucidated. In the present study, by using ELISA and immunohistochemical analyses, we first found that the expression levels of IL‑17, IL‑17 receptor (IL‑17R), high-mobility group A1 (HMGA1) and cyclin D1 were elevated in the samples of patients with NSCLC. Subsequently, by RT-qPCR, western blot analysis and cell proliferation assay in vitro, we revealed that stimulation with recombinant human IL‑17 (namely IL‑17A) markedly induced the expression of HMGA1 and cyclin D1 in the A549 cells (a human lung adenocarcinoma cell line) and promoted cell proliferation. Furthermore, luciferase reporter and ChIP assays confirmed that upregulated HMGA1 directly bound to the cyclin D1 gene promoter and activated its transcription. Notably, the response element of HMGA1 binding to the cyclin D1 promoter was disclosed for the first time, at least to the best of our knowledge. Taken together, our findings indicate that the IL‑17/HMGA1/cyclin D1 axis plays an important role in NSCLC cell proliferation and may provide new insight into NSCLC pathogenesis and may thus aid in the development of novel therapeutic targets for NSCLC.
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http://dx.doi.org/10.3892/ijo.2018.4307DOI Listing
May 2018