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Background: This study was performed to determine antifungal activity of silver nanoparticles (nano-Ag) compared to voriconazole on clinical and standard strains of Aspergillus fumigatus.
Materials and Methods: Inhibitory potency of nano-Ag was determined using microtiter broth dilution method. Susceptibility tests were performed against A. fumigatus isolated from BAL (bronchoalveolar lavage) of patients who suffered from respiratory problems and compared with the strain (ATCC: 204305) by broth dilution antifungal susceptibility test of filamentous fungi approved by the Clinical and Laboratory Standards Institute M38-A. In addition, cytotoxicity effect of silver nanoparticles was studied on epithelial cell line by MTT assay.
Results: From 60 BAL samples the following strains were isolated; A. flavus (n=21), A. niger (n=3), and A. fumigatus (n=1). The minimum inhibitory concentration (MIC₉₀) values of nano-Ag were 0.25 and 0.5 μg.mL^-1 for standard strain and clinical isolates respectively. The  Minimum Fungicidal Concentration (MFC) values of nano-Ag were 0.5 and 1 μg.mL^-1for standard strain and clinical isolates respectively. MIC90 values of voriconazole were 0.125 and 0.25 μg.mL^-1 for standard strain and clinical isolate respectively. The MFC values of voriconazole were 0.25 and 0 μg.mL^-1 for standard strain and clinical isolates respectively. Silver nanoparticles exhibited low cytotoxicity in 0.25 μg.mL^-1 concentration.
Conclusion: Our results showed high antifungal activity of silver nanoparticles against Aspergillus isolates. Furthermore, the availability of a wide form of nano-Ag structures can be considered as novel agents to decrease fungal burden in medical application.

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In this study, phenolic compounds-coated ZnO@HAP nanocomposite (Ph.ZnO@HAP) was synthesized and used to improve the physical and chemical properties of chitosan hydrogel for biological application. At first, the phenolic compounds were extracted from walnut green hulls. The synthesis of Ph.ZnO@HAP nanocomposite was performed with the assistance of extracted phenols using a hydrothermal method. Chitosan hydrogel was also prepared using NaHCO₃ at 37°C. Hybrid hydrogels based on chitosan and Ph.ZnO@HAP nanocomposite were prepared in a similar way and then characterized by fourier-transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). The antioxidant property, cytotoxicity, and osteogenesis of hybrid hydrogels were measured using DPPH radical scavenging method, MTT, and alkaline phosphatase enzyme assay, respectively. The FTIR spectra, FESEM images, EDX spectrum, and Zeta potential data showed that Ph.ZnO@HAP nanocomposites synthesized successfully with rod-like morphology, phenolic compounds coated on the surface and a negative particle surface charge. The results of DPPH experiment showed that the antioxidant property of the nanocomposite material increased in a concentration-dependent manner. The FESEM images of chitosan hybrid hydrogels with different concentrations of embedded Ph.ZnO@HAP nanocomposite showed that hybrid hydrogels have a more uniform porous structure, compared to the chitosan hydrogel. Moreover, by an increase in the nanocomposite concentration in the structure of hybrid hydrogels, the antioxidant property augmented. The results of the biological studies showed that the cytotoxicity of hybrid hydrogels on osteoblast-like cells (Saos-2) is lower than that of chitosan hydrogel. Also, hybrid hydrogels showed the higher potential in induction of osteogenesis than chitosan hydrogels.
 

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Backgrounds: Green synthesis of nanoparticles (NPs) is a simple, fast, and eco-friendly method which could be performed by various microorganisms or plant extracts. Silver NPs are well-known as antimicrobial and anti-fungal materials. They play an essential role in the control of tumors via their cytotoxic effects. Therefore, they have attracted significant attention for developing an effective treatment solution for cancer cells. This study aimed to investigate the potential of Penicillium chrysogenum for the synthesis of silver NPs and to evaluate their toxicity on liver cancer cell line (HepG2).
Materials & Methods: After synthesis of NPs usingP. chrysogenum, characterization of the synthesized NPs was performed by UV–Vis spectroscopy, X-ray diffraction (XRD), and transmission electron microscopy (TEM). Fourier transform infrared spectroscopy (FTIR) was carried out to detect biomolecules that may be responsible for the synthesis and stabilization of NPs. The cytotoxic activity of the synthesized AgclNPs on HepG2 cell line was evaluated using MTT assay.
Findings: UV–Vis spectroscopy and XRD analysis confirmed the synthesis of AgclNPs using P. chrysogenum. TEM analysis revealed the spherical shape of AgclNPs with an average crystalline size of 15 to 45 nm. FTIR spectroscopy indicated the possible functional groups that could be responsible for the reduction of metal ions and the capping process. These nanoparticles showed a dose-dependent anticancer activity against HepG2 cells.
Conclusion: The results suggest that biosynthesized silver chloride nanoparticles could offer potential applications in cancer therapy.
 

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Background: A promising strategy in cancer therapy involves the production of fusion proteins, which entail the fusion of two distinct proteins. This study aimed to produce and assess the cytotoxic effects of the Nisin-arginine deiminase (ADI) fusion protein on the SW480 cell lines, a common model for studying colorectal cancer (CRC).
Materials & Methods: The designed Nisin-ADI gene fragment sequence was sent to Biomatik Company for synthesis in pET-28a vectors between SacI and HindIII restriction enzyme sites. Escherichia coli (E. coli) DH5α and BL21 were utilized for cloning and protein expression, respectively. The recombinant fusion protein expression was induced by Isopropyl ß-D-1-thiogalactopyranoside (IPTG) and purified using Ni2+-nitrilotriacetic acid (1) resin affinity chromatography. Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting were conducted to analyze the purified protein. The cytotoxic effect of the purified recombinant fusion protein on SW480 and NIH3T3 cells, as a control, was evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay.
Findings: The results of this study showed that the fusion protein had a significant impact on the SW480 cell lines. The Half-maximal inhibitory concentration (IC50) of the fusion protein was 30 µg/mL, indicating that it effectively inhibited the growth of cancer cells. However, the fusion protein did not significantly affect the control group.
Conclusion: This study provides helpful insights into the potential application of recombinant Nisin-ADI fusion proteins as a potential treatment option for colorectal cancer. The potential for selective targeting of cancer cells is promising as normal cells are unaffected by this fusion protein.

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Aims: Recently, polymer-based nanofibrous scaffolds have attracted great attention due to their significant antibacterial properties in the field of dermatological applications. In this study, a polycaprolactone-based nanofibrous scaffold has been fabricated using the electrospinning method. The aim of this study was to evaluate the antibacterial effect of electrospun nanofibrous structures. Materials and Methods: In this experimental study, the structure and bacterial attachment on polymeric nanofibrous scaffolds were studied by Scanning Electron Microscopy (SEM). In addition, antibacterial properties of nanofibrous scaffolds were studied on two gram-negative bacteria of Escherichia coli and Pseudomonas aeruginosa and two gram-positive bacteria of Staphylococcus aureus and Streptococcus mutans, using microdilution method and biofilm assay. Moreover, MTT assay was performed on HeLa and human fibrosarcoma cell line (HT1080) cancerous cell lines to evaluate the cell viability.
Findings: The results of this study showed that nanofibrous scaffold revealed a significant antimicrobial and anti-biofilm formation effect on all of the studied bacterial strains, but in microscopic observations and microdilution assay was observed on Pseudomonas aeruginosa in 1mg/ml of nanofibrous scaffold extract concentration, while the major effect in biofilm assay was observed in 8µg/ml of extract concentration. Moreover, the cell viability studies showed that the most significant effect was shown on HT1080 cell line which has drastically decreased by 40% after 48 hours in comparison with the control.
Conclusion: These results show that electrospun nanofibrous PCL-based scaffolds are potentially promising for dermal tissue engineering applications, due to anti-biofilm effects and capability of reducing the number of cancerous cells in the wound site.

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Since one of the main problems in bone tissue repair is the bacterial infections, recently the development of drug-eluting nanocomposite scaffolds for bone regenerative medicine applications has attracted significant attention. In this study Polycaprolactone (PCL)-based composite scaffolds containing 10vol% of titanium dioxide nanoparticles (~21nm), and bioactive glass particles (~6µm), were prepared without drug and also loaded by Tetracycline hydrochloride (TCH) antibiotic (0.57, 1.15 mg/mL) through solvent casting method for bone tissue engineering applications. Structural characterizations based on Scanning Electron Microscopy (SEM), and FTIR analysis were utilized to study the chemical bonds of glass/ceramic particles, and antibiotic crystals on the surface. In addition, in vitro cytotoxicity, and antibacterial analysis were performed by MTT, and Agar well-diffusion assays, respectively. In this study polymeric and composite scaffolds were fabricated with TCH clusters decorated on the surface. It was shown that the bioactive glass/PCL scaffolds loaded by 0.57 mg/mL of TCH revealed significant antibacterial effect, despite the acceptable cell viability. These scaffolds seem to be of interest as a potential candidate in drug-eluting scaffolds for bone tissue engineering applications.

 

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Objective: The use of bacterial plasmids carrying specific genes of pathogens as genetic vaccines is a relatively new technique for induction of cellular immune responses against microbial pathogens. Mechanisms of production of specific immune responses against these vaccines are not still completely understood. Therefore, it is necessary to examine various routes of inoculation to find the best way of immunization for specific antigens. In this research, intramuscular method of inoculation of influenza vaccine nucleoprotein (NP) encoding vector was compared with that of intra-dermal method. Materials and Methods: In this study, the ability of two different methods of immunization (intramuscular and intra-dermal) in induction of CTL responses as well as their efficiency in clearance of influenza virus from the lung of BALB/c mice was compared. Female BALB/c mice were immunized with influenza virus NP expressing plasmids on days 0, 14 and 28. CTL activity of mice was evaluated by lactate dehydrogenase technique two weeks after the last inoculation. In addition, the mice were challenged by live influenza virus and the viral titer was measured 4 days post-challenge in the lungs of animals. The results of experiments demonstrated that intramuscular immunization of mice induces a stronger CTL response. Mice immunized by intramuscular route also showed a higher ability in virus clearance from the lungs. Conclusion: Results of this study showed that different routes of immunization of influenza NP genetic vaccine induce different levels of cell-mediated immune responses and protection from the live virus.

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Immunotoxins are an attractive way to treat cancer; in this method, high-cytotoxic protein toxins target cancer cells specifically. An immunotoxin consists of a targeting component (an antibody, cytokine, or other protein that binds to the cell), that is chemically conjugated or fused in DNA level to a cytotoxic cargo (a bacterium, plant or cytotoxic human protein). Immunotoxin, with the help of specific receptors, recognizes the target cell and enters the cell by endocytosis. After entering the cytocell, it kills the target cancer cell with the help of a toxic component. Although various immunotoxins with different structures have been studied and tested in recent decades, only three immunotoxins Denileukin Diftitox, Tagraxofusp and Moxestumomab Pasudotox - have been clinically approved for the treatment of leukemia. In this article, we review important research and two challenges in production and development of immunotoxins that have limited their clinical success. Further, we highlight methods to overcome these obstacles. These challenges include target and non-target cell toxicity and immunization.

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Iron oxide nanocomposites with lanthanides, due to their unique magnetic properties and biocompatibility, are recognized as attractive agents for the detection and treatment of cancerous tumors. Therefore, understanding the interaction of these nanocomposites with biological systems is important for their efficient design. In this study, samarium-doped magnetite iron oxide nanocomposite was synthesized chemically based on polyethylene glycol and triethanolamine. The nanocomposite w::::::::as char::::::::acterized using XRD, SEM, EDX, and DLS techniques. The crystal size of the nanocomposite was calculated to be approximately 12 nanometers using XRD. SEM image showed the synthetic nanocomposite as an agglomeration of fine particles with a spherical morphology. Subsequently, by incubating the nanocomposite in human blood plasma, the formation of a protein complex called corona protein on the surface of nanoparticles when exposed to biological systems was investigated and confirmed by gel electrophoresis. Cellular uptake results in the interaction of nanoparticles with cells showed that incubating the nanocomposite in human blood plasma led to a decrease in nanoparticle uptake in MDA-MB231 cancer cells and an increase in uptake in RAW 264.7 macrophages, indicating the binding of blood opsonin proteins on the nanoparticle surface. Furthermore, the results indicated that the formation of corona protein had no significant effect on the cellular toxicity of nanoparticles on MDA-MB231 cells at different nanoparticle concentrations up to 200 micrograms per milliliter, and no significant toxicity was reported.
 

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Due to the extensive use of chemical preservatives to increase the shelf life of foods and the prevalence of colorectal cancer, the demand for natural and safe pharmaceuticals and preservatives has increased. Thus, this study aimed to evaluate the antioxidant and cytotoxic potentials of Foeniculum vulgare essential oil, which has vast applications in the traditional medicine. In this study, the essential oil of F. vulgare was extracted by hydrodistillation method and its chemical constituents were identified quantitatively and tentatively using gas chromatography coupled to mass spectrometry and fourier transform infrared spectroscopy. The total phenol and flavonoid contents of the essential oil and its antioxidant activity (DPPH and ABTS free radicals scavenging activity and β-carotene/linoleic acid bleaching inhibition) were also investigated. The cytotoxic effect of F. vulgare essential oil was evaluated on colon cancer cell lines (HT29) using MTT assay. Anethole (75.61%) was the main chemical compound of F. vulgare essential oil and its absorption peaks were appeared at 1244 and 840 cm^-1. The total phenol and flavonoid contents of F. vulgare essential oil were 12.87 mg GAE/g and 39.67 mg QE/g, respectively. The antioxidant capacity of the essential oil, based on DPPH radical scavenging activity, ABTS radical scavenging activity, and β-carotene/linoleic acid bleaching inhibition, were 26.68, 39.57, and 32.38%, respectively. The cytotoxic effect of the essential oil on the colon cancer cells was depended on its concentration. The F. vulgare essential oil could be used as a natural compound to inhibit the oxidation of foods and the prevalence of colorectal cancers.

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Objective: Generation 5 poly (amidoamine) dendrimers are promising multipotent gene delivery vectors that provide favorable DNA condensation properties; however, their high toxicity limits their applications. Toxicity of PAMAM dendrimers depends on their type, generation and applied dosage in a way that lower generations (lower than G5 dendrimers) and anionic dendrimers have lower toxicity than higher generations and cationic dendrimers. The aim of this study is to evaluate the effect of PEGylation on toxicity of G5 PAMAM dendrimers. Methods: In this study, to improve their characteristics as gene delivery carriers, G5 PAMAM dendrimers were conjugated to polyethylene glycol molecules (PEG, molecular weight 3500) at three different molar ratios of 10, 20 and 30. Also the number of conjugated PEG chains was quantified using TNBSA and Ellman assays. The effect of different degrees of PEGylation on cytotoxicity and transfection efficiency of modified PAMAM dendrimers toward BT-474 and MCF-10A cell lines were assessed. Results: Compared to unconjugated, PEG conjugated PAMAM dendrimers had lower in vitro cytotoxicity, particularly at higher PEG to PAMAM molar ratios. Among all prepared PEG-PAMAM dendrimers, G5 PAMAM dendrimers that conjugated to PEG at a molar ratio of 10/1 had the highest in vitro transfection rate in both cell lines. Conclusion: Our results showed that these PEG-conjugated PAMAM dendrimers possess a great potential for in vitro gene delivery.

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Objective: Despite significant advances in radiation therapy and cancer treatments in the past 30 years, resistance to chemotherapy is a major obstacle in the recovery of patients with cancer. Resistance to chemotherapy drugs inhibits the recovery process. This study aims to evaluate the anticancer activity of the methanolic extract of rosemary alone and in conjunction with gamma rays on growth inhibition of MCF-7,SKBR3 and Huo2 cell lines.
Methods: We examined cytotoxicity of different concentrations (1, 5, 10, 50, 100, 500 μg/ml) of rosemary extract and various doses of gamma rays (1.5, 3, and 7.5 Gy) on MCF-7, SKBR3, and fibroblast (HU02) cell lines. All three cell lines were obtained from the Iranian Biological and Genetics Reserve Center. The cell lines were grown in DMEM supplemented with 10% FBS, 1% penicillin and streptomycin. The cells were allowed to incubate at 37ºC in an atmosphere that contained 5% CO2 and 100% humidity. The standard MTT assay was performed to estimate cell viability after treatment with gamma rays and rosemary extract.
Results: The results of the MTT assay showed that rosemary extract had time- and concentration-dependent anticancer activities on the MCF-7 and SKBR3 cell lines (p<0.01). Rosemary extract had no remarkable cytotoxicity on the normal HU02 cell line. Gamma rays along with rosemary extract had more cytotoxic activity in a time-dependent manner on viability in the cancer call lines (p<0.03).
Conclusion: Our results, along with results from other studies, have suggested that rosemary extract is a potential candidate, either alone at pre-determined doses or in combination with gamma rays, for the treatment of chemotherapy resistant breast cancer.

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Silver Nanoparticles (AgNPs) are widely used in medical and pharmaceutical applications due to their antimicrobial properties. In this study, Ag-NPs were synthesized using Viola tricolor aqueous extract as a reducing and capping agent. The presence of synthesized Ag-NPs was first confirmed with UV-Visible, SEM, TEM, XRD, and FTIR analyses, and then their antimicrobial characteristics were studied based on the Minimum Inhibitory Concentration (MIC). The SEM analysis showed that the synthesized AgNPs were spherical in shape. The particle size histogram revealed that the average particle size of the AgNPs was 49.45 nm. Findings from the FTIR and UV-Vis spectra showed the successful formation of Ag-NPs because the functional groups involved in the synthesis process and adsorption peaks were well developed. Furthermore, the Ag-NPs had a peak absorption at 420 nm in the spectrometry. MIC results showed the strong antimicrobial effects of the synthesized Ag-NPs. Results of the Minimum Bactericidal Concentration (MBC) revealed the dose-dependent cytotoxicity of the Ag-NPs. Nanoparticles could exert the inhibitory effect of DDPH free radicals in a dose-dependent manner. Methyl tetrazolium (MTT) results showed that silver nanoparticles had a dose-dependent cytotoxic effect and significantly reduced cell survival. The IC50 values for Ag-NPs and the extract were 11.83 and 204.4 μg mL^-1, respectively. This study showed a higher cytotoxic effect of the green synthesized nanoparticles on hepatocellular carcinoma cells than the extract. Consequently, the biosynthesis of Ag-NPs using aqueous extract of V. tricolor is clean, inexpensive, and has antibacterial, anticancer and antioxidant activities. Hence, it can be used as a drug candidate.

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This research investigated the effects of extraction processes on phenolic compound extractions and evaluated the antioxidant and cytotoxicity properties of Nigella sativa seed. The most abundant phenolic compound, namely, Epigallocatechin Gallate (EgCg), was identified in free flavan-3-ol extract (127.85±4.73 µg g^-1 DWE), which exhibited considerable ferrous-ion chelation and cytotoxicity on HepG2 cancer cells. Epigallocatechin (EgC) was the second and recognized in the bound flavan-3-ol extract [(113.31±3.49 µg g^-1 DWE (dry weight extract)], which showed the largest 2,2-Diphenyl-1-Picrylhydrazyl Radical (DPPH^•) scavenging activity and ferric-ion reducing power, as well as the most cytotoxic on HepG2 (IC₅₀= 24.91±1.45 µg mL^-1). Caffeic, sinapic, and p-hydroxybenzoic acids were found in Bound Phenolic acid from Basic-Hydrolysis extract (BPBH), which had the highest Hydroxyl radical (^•OH) and Nitric Oxide radical (NO^•) scavenging activity and appreciable cytotoxicity on HepG2. Ferulic and p-coumaric acids were detected in Acid-Hydrolysable Phenolic Acid extract (AHPA) and Bound Phenolic acid from Acid-Hydrolysis extract (BPAH), respectively. The two extracts demonstrated higher Ferric-ion Reducing Antioxidant Power (FRAP) values and were also cytotoxic to HeLa and HepG2 cell lines. To the best of our knowledge, EgC, EgCg and rosmarinic acid were identified in N. sativa seed for the first time. Our study indicates N. sativa seeds as a promising source of phenolic compounds with antioxidant and anticancer properties.

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ABSTRACT
Introduction. Bleeding in neurosurgery presents a significant challenge due to the brain's dense network of blood vessels. This project aimed to design a biocompatible and biodegradable hemostatic agent based on chitosan hydrogel to rectify disadvantages such as neural compression for use in the control of bleeding in nerve injuries.
Methods. The injury was made in the lambda region, which has a dense network of blood vessels. Using an electric drill, a hole with a diameter of 2 mm was created. Bleeding in control group was examined by  a sterile gauze pad. In other groups, hydrogel dressing and commercial hemostasis such as surgical were used to control bleeding. The main parameters including volume of blood lost and the time of the bleeding, were measured. 
Results. The results demonstrated that chitosan similar to surgical, has an improved hemostatic property.  In addition, chitosan hydrogel was non-cytotoxic, obtaining cell viability values ≥ 89% for the L929 cells.
Conclusion. The results of the present study indicate that the safety and enhanced efficacy of chitosan-based hemostats, make them a potentially suitable option for use in neurological surgery.