Publications by authors named "Mehmet Enes Arslan"

12 Publications

  • Page 1 of 1

Safety and Efficacy Assessments to Take Antioxidants in Glioblastoma Therapy: From In Vitro Experiences to Animal and Clinical Studies.

Neurochem Int 2021 Aug 25;150:105168. Epub 2021 Aug 25.

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, UK; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden. Electronic address:

Glioblastoma (GBM) is considered one of the most common malignant brain tumors, occurring as over 15% of all primary central nervous system and brain neoplasms. The unique and standard treatment option towards GBM involves the combination of surgical resection followed by radiotherapy (RT) and chemotherapy (CT). However, due to the aggressive nature and heterogeneity of GBMs, they remained difficult to treat. Recent findings from preclinical studies have revealed that disruption of the redox balance via using either oxidative or anti-oxidative agents in GBM presented an effective and promising therapeutic approach. A limited number of clinical trials substantially encouraged their concomitant use with RT or CT. Thus, treatment of GBMs may benefit from natural or synthetic antioxidative compounds as novel therapeutics. Despite the presence of variegated in vitro and in vivo studies focusing on safety and efficacy issues of these promising therapeutics, nowadays their translation to clinics is far from applicability due to several challenges. In this review, we briefly introduce the enzymatic and non-enzymatic antioxidant defense systems as well as potential signaling pathways related to the pathogenesis of GBM with a special interest in antioxidant mechanisms. In addition, we describe the advantages and limitations of antioxidant supplementation in GBM cases or disease models as well as growing challenges for GBM therapies with antioxidants in the future.
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http://dx.doi.org/10.1016/j.neuint.2021.105168DOI Listing
August 2021

Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies.

Neurochem Int 2021 Oct 19;149:105137. Epub 2021 Jul 19.

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, UK; Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SE-17121, Sweden. Electronic address:

Glioblastoma (GB) is the most common and aggressive primary malignant astrocytoma correlated with poor patient survival. There are no curative treatments for GB, and it becomes resistant to chemotherapy, radiation therapy, and immunotherapy. Resistance in GB cells is closely related to their states of redox imbalance, and the role of reactive oxygen species and its impact on cancer cell survival is still far from elucidation. Boron-containing compounds, especially boric acid (BA) and borax (BX) exhibited interesting biological effects involving antibacterial, antiviral, anti-cancerogenic, anti-mutagenic, anti-inflammatory as well as anti-oxidative features. Recent studies indicated that certain boron compounds could be cytotoxic on human GB. Nevertheless, there is gap of knowledge in the literature on exploring the underlying mechanisms of anti-GB action by boron compounds. Here, we identified and compared the potential anti-GB effect of both BA and BX, and revealed their underlying anti-GB mechanism. We performed cell viability, oxidative alterations, oxidative DNA damage potential assays, and explored the inflammatory responses and gene expression changes by real-time PCR using U-87MG cells. We found that BA and BX led to a remarkable reduction in U-87MG cell viability in a concentration-dependent manner. We also found that boron compounds increased the total oxidative status and MDA levels along with the SOD and CAT enzyme activities and decreased total antioxidant capacity and GSH levels in U-87MG cells without inducing DNA damage. The cytokine levels of cancer cells were also altered. We verified the selectivity of the compounds using a normal cell line, HaCaT and found an exact opposite condition after treating HaCaT cells with BA and BX. BA applications were more effective than BX on U-87MG cell line in terms of increasing MDA levels, SOD and CAT enzyme activities, and decreasing Interleukin-1α, Interleukin-6 and Tumor necrosis factor- α (TNF- α) levels. We finally observed that anticancer effect of BA and BX were associated with the BRAF/MAPK, PTEN and PI3K/AKT signaling pathways in respect of downregulatory manner. Especially, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes. In conclusion, our analysis indicated that boron compounds may be safe and promising for effective treatment of GB.
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http://dx.doi.org/10.1016/j.neuint.2021.105137DOI Listing
October 2021

Targeted Gene Candidates for Treatment and Early Diagnosis of Age-Related Macular Degeneration.

Biomed Res Int 2021 2;2021:6620900. Epub 2021 Feb 2.

Department of Medical Biology, Faculty of Medicine, Atatürk University, Erzurum, Turkey.

Age-related macular degeneration (AMD) is an eye disease that impairs the sharp and central vision need for daily activities. Recent advances in molecular biology research not only lead to a better understanding of the genetics and pathophysiology of AMD but also to the development of applications based on targeted gene expressions to treat the disease. Clarification of molecular pathways that causing to development and progression in dry and wet types of AMD needs comprehensive and comparative investigations in particular precious biopsies involving peripheral blood samples from the patients. Therefore, in this investigation, dry and wet types of AMD patients and healthy individuals were aimed at investigating in regard to targeted gene candidates by using gene expression analysis for the first time. 13 most potent candidate genes involved in neurodegeneration were selected via in silico approach and investigated through gene expression analysis to suggest new targets for disease therapy. For the analyses, 30 individuals (10 dry and 10 wet types AMD patients and 10 healthy people) were involved in the study. SYBR-Green based Real-Time PCR analysis was performed on isolated peripheral blood mononuclear cells (PBMCs) to analyze differentially expressed genes related to these cases. According to the investigations, only the gene was found to be upregulated for both dry and wet disease types. When the downregulated genes were analyzed, it was found that 11 genes were commonly decreased for both dry and wet types in the aspect of expression pattern. From these genes, , , , and were found to have the most downregulated gene expression properties for both diseases. From these results, it might be concluded that these common upregulated and downregulated genes could be used as targets for early diagnosis and treatment for AMD.
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http://dx.doi.org/10.1155/2021/6620900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872763PMC
May 2021

Tribological, biocompatibility, and antibiofilm properties of tungsten-germanium coating using magnetron sputtering.

J Mater Sci Mater Med 2021 Jan 20;32(1). Epub 2021 Jan 20.

Molecular Biology and Genetics Department, Faculty of Science, Erzurum Technical University, Erzurum, Turkey.

In this study, borosilicate glass and 316 L stainless steel were coated with germanium (Ge) and tungsten (W) metals using the Magnetron Sputtering System. Surface structural, mechanical, and tribological properties of uncoated and coated samples were examined using SEM, X-ray diffraction (XRD), energy-dispersive spectroscopy, and tribometer. The XRD results showed that WGe chemical compound observed in (110) crystalline phase and exhibited a dense structure. According to the tribological analyses, the adhesion strength of the coated deposition on 316 L was obtained 32.8 N, and the mean coefficient of friction was around 0.3. Biocompatibility studies of coated metallic biomaterials were analyzed on fibroblast cell culture (Primary Dermal Fibroblast; Normal, Human, Adult (HDFa)) in vitro. Hoescht 33258 fluorescent staining was performed to investigate the cellular density and chromosomal abnormalities of the HDFa cell line on the borosilicate glasses coated with germanium-tungsten (W-Ge). Cell viabilities of HDFa cell line on each surface (W-Ge coated borosilicate glass, uncoated borosilicate glass, and cell culture plate surface) were analyzed by using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxicity assay. The antibiofilm activity of W-Ge coated borosilicate glass showed a significant reduction effect on Staphylococcus aureus (ATCC 25923) and Pseudomonas aeruginosa (ATCC 27853) adherence compared to control groups. In the light of findings, tungsten and germanium, which are some of the most common industrial materials, were investigated as biocompatible and antimicrobial surface coatings and recommended as bio-implant materials for the first time.
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http://dx.doi.org/10.1007/s10856-020-06477-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817579PMC
January 2021

Safety Assessments of Nickel Boride Nanoparticles on the Human Pulmonary Alveolar Cells by Using Cell Viability and Gene Expression Analyses.

Biol Trace Elem Res 2021 Jul 9;199(7):2602-2611. Epub 2020 Sep 9.

Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 9RT, UK.

Nickel boride is generally used in the steel industry as a melting accelerator due to its feature of creating a protective and stable attribute at high temperatures. It is also used to improve the hardenability of the steel with boron addition in the production. Thus, safety studies and biocompatibility analysis of nickel boride should be performed comprehensively to understand the limitations of use in various areas. In the present study, nickel boride nanoparticles (NiB NPs) were synthesized by a single-step method and molecule characterizations were performed via the use of X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) analyses. Cytotoxicity properties of NiB NPs were identified on human pulmonary alveolar epithelial cells (HPAEpiC) by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR), and lactate dehydrogenase (LDH) assays. Illumina human ht-12 v4.0 whole-genome microarray analysis was conducted to investigate NiB NPs effects on gene expression regulations of HPAEpiC cells. The database for annotation, visualization, and integrated discovery (DAVID) analysis was performed to reveal the relationship between NiB NP application and cellular pathway alterations. According to cytotoxicity analysis, the IC value for NiB NP application was found as 81.99 mg/L concentration. Microarray analysis of NiB NP application was shown for the first time that 693 gene expression changes (FC ≥ 2) occurred significantly over 40.000 gene probes and NiB NPs were observed to affect microtubule regulation, centrosome organization, and phosphoprotein synthesis.
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http://dx.doi.org/10.1007/s12011-020-02374-7DOI Listing
July 2021

Histidyl-Proline Diketopiperazine Isomers as Multipotent Anti-Alzheimer Drug Candidates.

Biomolecules 2020 05 9;10(5). Epub 2020 May 9.

Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden.

Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer's disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 () peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), α- and β-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against -induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.
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http://dx.doi.org/10.3390/biom10050737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277666PMC
May 2020

In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer's disease model of differentiated neuroblastoma cell line.

Int J Neurosci 2021 Aug 19;131(8):745-754. Epub 2020 Apr 19.

Science for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, Sweden.

Objective: To investigate neuroprotective properties of the farnesene sesquiterpene on the experimental Alzheimer's disease model .

Methods: Human neuroblastoma cell line (SHSY-5Y) was differentiated into neuron-like cells by using retinoic acid to constitute the Alzheimer's Disease model. β-amyloid 1-42 protein was applied to the transformed cells for 24 and 48 hours in a wide dose ranges (3.125-200 μM) to establish AD cytotoxicity. Then, farnesene was applied to cell cultures in a wide spectrum dose interval (1.625-100 μg/ml) to investigate neuroprotective effect against β-amyloid for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were executed to determine cytotoxicity in the Alzheimer model. Nuclear DNA integrity of cells was examined under the fluorescent microscope using the Hoechst 33258 staining method. Furthermore, acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were analyzed to understand the protection mechanism of the farnesene application on the cell culture model. Finally, flow cytometry analysis was used to find out the cell death mechanism after beta-amyloid and farnesene application to the cell culture.

Results: Cell viability tests revealed significant neuroprotection against β-amyloid toxicity in both 24 and 48 hours and the Hoechst 33258 fluorescence staining method showed a significant decrease in necrotic deaths after farnesene application in the cell cultures. Finally, flow cytometry analysis put forth that farnesene could decrease necrotic cell death up to 3-fold resulted from beta-amyloid exposure.

Conclusion: According to the investigations, farnesene can potentially be a safe, anti-necrotic and neuroprotective agents against Alzheimer's disease.
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http://dx.doi.org/10.1080/00207454.2020.1754211DOI Listing
August 2021

Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson's disease model against MPP+ induced apoptosis.

Metab Brain Dis 2020 08 25;35(6):947-957. Epub 2020 Mar 25.

Department of Pharmacology, G. D'Annunzio University, Chieti, Italy.

Parkinson's disease (PD) is one of the most aggressive neurodegenerative diseases and characterized by the loss of dopamine-sensitive neurons in the substantia nigra region of the brain. There is no any definitive treatment to completely cure PD and existing treatments can only ease the symptoms of the disease. Boron nitride nanoparticles have been extensively studied in nano-biological studies and researches showed that it can be a promising candidate for PD treatment with its biologically active unique properties. In the present study, it was aimed to investigate ameliorative effects of hexagonal boron nitride nanoparticles (hBNs) against toxicity of 1-methyl-4-phenylpyridinium (MPP) in experimental PD model. Experimental PD model was constituted by application of MPP to differentiated pluripotent human embryonal carcinoma cell (Ntera-2, NT-2) culture in wide range of concentrations (0.62 to 2 mM). Neuroprotective activity of hBNs against MPP toxicity was determined by cell viability assays including MTT and LDH release. Oxidative alterations by hBNs application in PD cell culture model were investigated using total antioxidant capacity (TAC) and total oxidant status (TOS) tests. The impacts of hBNs and MPP on nuclear integrity were analyzed by Hoechst 33258 fluorescent staining method. Acetylcholinesterase (AChE) enzyme activities were determined by a colorimetric assay towards to hBNs treatment. Cell death mechanisms caused by hBNs and MPP+ exposure was investigated by flow cytometry analysis. Experimental results showed that application of hBNs increased cell viability in PD model against MPP application. TAS and TOS analysis were determined that antioxidant capacity elevated after hBNs applications while oxidant levels were reduced. Furthermore, flow cytometric analysis executed that MPP induced apoptosis was prevented significantly (p < 0.05) after application with hBNs. In a conclusion, the obtained results indicated that hBNs have a huge potential against MPP toxicity and can be used in PD treatment as novel neuroprotective agent and drug delivery system.
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http://dx.doi.org/10.1007/s11011-020-00559-6DOI Listing
August 2020

Microarray assisted toxicological investigations of boron carbide nanoparticles on human primary alveolar epithelial cells.

Chem Biol Interact 2019 Feb 24;300:131-137. Epub 2019 Jan 24.

Department of Medical Genetics, Medical Faculty, Atatürk University, Erzurum, Turkey.

It is important to understand the adverse effects of nanoparticles on human health and to prepare risk reports for widely used nanoscale materials. Synthesis, characterization and cytotoxicity evaluation of BC nanoparticles were performed on HPAEpiC since, first encounter with nanoparticles would generally happen through lung by inhaling chemicals. BC nanoparticles were synthesized via chemical vapor deposition techniques and characterized by using transmission electron microscope (TEM), scanning electron microscope (SEM) and X-ray crystallography (XRD). 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and neutral red (NR) tests were used to analyze cell viability and cytotoxicity against nanoparticles exposure. Microarray analysis was used to discover whole genome effects of BC NPs on gene expressions changes of HPAEpiC cells. Then, the database for annotation, visualization and integrated discovery (DAVID) analysis was performed to understand relationships between gene pathways and nanoparticle exposure. Finally, cytotoxicity analysis revealed that IC value for boron carbide (BC) nanoparticles was 202.525 mg/L. According to microarray analysis 32 genes expression change significantly (FC ≥ 2) over 40,000 genes scanning. The gene pathways analysis showed that boron carbide (BC) nanoparticles mostly affect amino acid biosynthesis process, TGF-beta signaling pathway and developmental proteins regulation. In conclusion, our results supported for the first time that boron carbide (BC) nanoparticles could be used as a safe nanomaterial in both pharmacological and medical applications.
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http://dx.doi.org/10.1016/j.cbi.2019.01.021DOI Listing
February 2019

Synthesis, characterization and cytotoxicity of boron nitride nanoparticles: emphasis on toxicogenomics.

Cytotechnology 2019 Feb 14;71(1):351-361. Epub 2019 Jan 14.

Department of Biology, Faculty of Arts and Sciences, Atatürk University, Erzurum, Turkey.

Nanotechnology is increasingly developing area including more than 700 commercial products such as clothing, food preparation, cosmetics, mechanics, electronics and also health industry. People generally contact with nanoparticles by inhaling from air. Thus, it is becoming important issue to understand harmful effects of nanoparticles on human health and prepare risk reports for common nano-sized materials. In this paper, synthesis, characterization and cytotoxicity evaluation of boron nitride (BN) nanoparticles were performed on human primary alveolar epithelial cells (HPAEpiC) since, main exposure to nanoparticles would generally happen through lung via inhalation. Chemically synthetized BN nanoparticles were characterized by using X-ray crystallography, transmission electron microscope, scanning electron microscope and energy-dispersive X-ray spectroscopy techniques. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide, neutral red and lactate dehydrogenase release assays were used to analyze cytotoxicity after nanoparticles exposure. Whole genome microarray analysis was used to find out the effects of BN NPs on gene expressions of HPAEpiC cells. Finally, the database for annotation, visualization and integrated discovery analysis was used to reveal relationships between different cellular pathways and nanoparticle exposure. According to cytotoxicity analysis LC value for BN nanoparticles was 125.051 mg/L. Microarray results showed that 2159 genes expression change (FC ≥ 2) significantly over 40,000 genes analysis. When the gene pathways were analyzed, it was seemed that BN nanoparticles mostly affect cell cycle, cell-cell interactions, cancer affecting genes and signal transduction. In a conclusion, our results supported for the first time that BN nanoparticles could be used as a safe nanomaterial in both pharmacological and medical applications.
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http://dx.doi.org/10.1007/s10616-019-00292-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368500PMC
February 2019

(R)-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester as dual acting agent for the treatment of Alzheimer's disease.

Neuropeptides 2017 Dec 2;66:52-58. Epub 2017 Oct 2.

Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, Chieti Scalo (CH), Italy. Electronic address:

In this study, effects of LA-GPE (R-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Aβ were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase release (LDH assay). Effects of LA-GPE and GPE on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels, and neural cell apoptosis and necrosis were also determined. In addition, biological safety of these novel formulations was evaluated in human blood cells using different cytotoxicity and genotoxicity assays. Our results indicated that both compounds could block Aβ induced cell death. LA-GPE reduced Aβ-induced AChE activity and oxidative stress, suggesting it as a multifunctional compound potentially valuable for the treatment of Alzheimer's disease (AD).
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http://dx.doi.org/10.1016/j.npep.2017.09.001DOI Listing
December 2017

Toxicogenomic responses of human alveolar epithelial cells to tungsten boride nanoparticles.

Chem Biol Interact 2017 Aug 27;273:257-265. Epub 2017 Jun 27.

Department of Biology, Faculty of Arts and Sciences, Atatürk University, Erzurum, Turkey.

During the recent years, microarray analysis of gene expression has become an inevitable tool for exploring toxicity of drugs and other chemicals on biological systems. Therefore, toxicogenomics is considered as a fruitful area for searching cellular pathways and mechanisms including cancer, immunological diseases, environmental responses, gene-gene interactions and chemical toxicity. In this work, we examined toxic effects of Tungsten Borides NPs on gene expression profiling of the human lung alveolar epithelial cells (HPAEpiC). In line with this purpose, a single crystal of tungsten boride (mixture of WB and WB) nanoparticles was synthesized by means of zone melting method, and characterized via using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX) techniques. Cell viability and cytotoxicity were determined by 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and lactate dehydrogenase (LDH) release tests. The whole genome microarray expression analysis was performed to find out the effects of WB and WB NPs mixture on gene expression of the HPAEpiC cell culture. 123 of 40,000 gene probes were assigned to characterize expression profile for WB/W2B NPs exposure. According to results; 70 genes were up-regulated and 53 genes were down-regulated (≥2 fold change). For further investigations, these genes were functionally classified by using DAVID (The Database for Annotation, Visualization and Integrated Discovery) with gene ontology (GO) analysis. In the light of the data gained from this study, it could be concluded that the mixture of WB/W2B NPs can affect cytokine/chemokine metabolism, angiogenesis and prevent migration/invasion by activating various genes.
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http://dx.doi.org/10.1016/j.cbi.2017.06.027DOI Listing
August 2017
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