A natural approach to breast cancer treatment: investigation of chemical features of aerial parts of endemic Onosma sintenisii Hausskn. ex Bornm and its antioxidant properties, in vitro cytotoxic and apoptosis induction on MCF-7 cells.

Onosma sintenisii Hausskn. ex Bornm. (O. sintenisii) belongs to the Boraginaceae family and it is an endemic species from Irano-turanian phytogeographical region (central and eastern Anatolia) that distributes in steppe areas. This study aimed to investigate the chemical composition, antioxidant, in vitro cytotoxic and apoptosis induction of methanol extract of aerial parts of O. sintenisii. As a result of GC/MS analysis, 14 components were identified, and the major compounds of the extracts are retronecine (13.94%), α.-D-Glucopyranosiduronic acid (10.86%), melaniline (7.5%) and 1,2-Butanediol (4.02%), respectively. Antioxidant properties of O. sintenisii were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP) and superoxide radical scavenging activity methods. While the DPPH free radical scavenging activity results of O. sintenisii extract varied between 62.49% and 32.27%, reducing power activity and superoxide radical scavenging activity were found to be low. The result of the MTT assay revealed strong anticancer activity of O. sintenisii extract. The most significant cytotoxic effect was noted at a concentration of 1000 µg/mL after 48 hours. These findings together with flow cytometry analysis suggest that apoptosis can be the main mechanism underlying cell death after O. sintenisii extract treatment.

Recent Strategies for Cancer Therapy: Polymer Nanoparticles Carrying Medicinally Important Phytochemicals and Their Cellular Targets.

Cancer is a leading cause of death in the world today. In addition to the side effects of the chemotherapeutic drugs used to treat cancer, the development of resistance to the drugs renders the existing drugs ineffective. Therefore, there is an urgent need to develop novel anticancer agents. Medicinally important phytochemicals such as curcumin, naringenin, quercetin, epigallocatechin gallate, thymoquinone, kaempferol, resveratrol, genistein, and apigenin have some drawbacks, including low solubility in water, stability and bioavailability issues, despite having significant anticancer effects. Encapsulation of these natural compounds into polymer nanoparticles (NPs) is a novel technology that could overcome these constraints. In comparison to the free compounds, phytochemicals loaded into nanoparticles have greater activity and bioavailability against many cancer types. In this review, we describe the preparation and characterization of natural phytochemical-loaded polymer NP formulations with significant antioxidant and anti-inflammatory effects, their in vitro and in vivo anticancer activities, as well as their possible cellular targets.

Development and characterization of sustainable active pectin films: The role of choline chloride/glycerol-based natural deep eutectic solvent and lavender extracts.

This study aimed to evaluate the potential effects of choline chloride: glycerol-based natural deep eutectic solvent (NADES) as a plasticizer, NADES extract (NADESext) of lavender as both plasticizer and active ingredient, as well as the lyophilized extract (LE) of lavender at different concentrations (0.5 %, 1 %, and 2 %) on the physical, mechanical, optical, thermal, barrier, morphological, and antioxidant properties of pectin films. The properties of the films were compared to those of the neat pectin film and the film plasticized with glycerol. The addition of plasticizers and LE increased thickness, water vapor permeability, and elongation at break values of the films while decreasing tensile strength and young modulus. Pectin films plasticized with glycerol, NADES, and NADESext had a similar color property but a lower opacity. The use of LE decreased lightness and increased opacity compared to the films with plasticizers. The addition of plasticizers revealed a smoother surface than neat pectin film while LE triggered the formation of agglomerates on the films. Changes in the FTIR spectra of the films showed some interactions between pectin and polyphenols in LE. The plasticizers had an insignificant effect on the antioxidant capacity of films whereas LE improved antioxidant capacity depending on the concentration. In conclusion, the results suggested that pectin films with NADES and LE could be beneficially used to improve antioxidant packaging technology along with acceptable mechanical properties.

Protective effect of paricalcitol in rat testicular damage induced by subchronic 1800 MHz radiofrequency radiation.

In the present study, the possible protective effects of paricalcitol (P) were investigated in testicular damage because of 1800 MHz radiofrequency radiation (RFR) exposure. Male Sprague Dawley rats 8-10 weeks old (n = 28) were randomly divided into four groups as control (C) (n = 7), RFR (n = 7, 1800 MHz RFR 1 h/day for 30 days), P (n = 7, 0.2 µg/kg paricalcitol, 3 times a week for 30 days), and RFR + P (n = 7, 1800 MHz RFR 1 h/day for 30 days +0.2 µg/kg paricalcitol, 3 times a week for 30 days). Testicular tissue was evaluated with histological and biochemical methods. No statistically significant differences were detected between the groups in seminiferous tubule diameters and germinal epithelial thicknesses. While ultrastructural changes were observed in the seminiferous tubule and Leydig cells in the RFR group, these changes were decreased in the RFR + P group. It was found that the Johnsen Score, Ki67, and p63 immunoreactivity scores (IRS), superoxide dismutase (SOD), and catalase (CAT) activities in the RFR + P group were statistically increased as compared to the RFR group and the malondialdehyde (MDA) levels were decreased statistically and significantly. These results show that paricalcitol administration may have an ameliorative effect on testicular damage occurring because of 1800 MHz RFR exposure.

Cytotoxic effect of silica nanoparticles on human retinal pigment epithelial cells.

In recent years, the use of nanotechnology-based methods has become widespread in the treatment of ocular diseases. Silica nanoparticles (SiO2 NPs) are most common used NPs in medical field due to their physicochemical properties. SiO2 NPs can easily cross biological membranes and interact with basic biological structures, causing structural and functional changes in cells. In this study, it was aimed to investigate the dose dependent effect of SiO2 NPs on retinal pigment epithelium (RPE) in vitro using electrobiophysical, biochemical and histological methods. A commercially purchased human RPE (hARPE-19) cell line was used in this study. Cells were divided into four groups as control, 50 µg/mL SiO2, 100 µg/mL SiO2 and 150 µg/mL SiO2 groups. Cell index, apoptotic activity, cell cycle and oxidative stress markers were measured in all groups. Findings in the present study showed that SiO2 nanoparticles reduced cell proliferation, increased oxidative stress, apoptosis and arrest in the G0/G1 phase of the cell cycle as dose dependent manner in ARPE-19 cells. In conclusion, SiO2 exposure can induce cytotoxic effects in RPE cell line. The results of this study provide clues that exposure to SiO2 nanoparticles may impair visual function and reduce quality of life. However, further studies are needed in this regard.

Gelatin nanoparticles with tunable mechanical properties: effect of crosslinking time and loading.

Tuning the elastic properties of nanoparticles intended to be used in drug delivery is of great interest. To this end, different potential formulations are developed since the particle elasticity is affecting the in vitro and in vivo performance of the nanoparticles. Here we present a method to determine the elasticity of single gelatin nanoparticles (GNPs). Furthermore, we introduce the possibility of tuning the elastic properties of gelatin nanoparticles during their preparation through crosslinking time. Young's moduli from 5.48 to 14.26 MPa have been obtained. Additionally, the possibility to measure the elasticity of single nanoparticles revealed the influence of loading a macromolecular model drug (FITC-dextran) on the mechanical properties, which decreased with raising amounts of loaded drug. Loaded particles were significantly softer, with Young's moduli between 1.06 and 5.79 MPa for the same crosslinking time, than the blank GNPs. In contrast to this, lysozyme as a crosslinkable macromolecule did not influence the mechanical properties. A good in vitro cell compatibility was found investigating blank GNPs and FITC-dextran-loaded GNPs in viability assays with the cancer cell line A549 and the human primary cell-derived hAELVi cell line.

Protective effect of myricetin, apigenin, and hesperidin pretreatments on cyclophosphamide-induced immunosuppression.

Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats.Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide + myricetin (100 mg/kg), cyclophosphamide + myricetin (200 mg/kg), cyclophosphamide + apigenin (100 mg/kg), cyclophosphamide + apigenin (200 mg/kg), cyclophosphamide + hesperidin (100 mg/kg), and cyclophosphamide + hesperidin (200 mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14 d, while cyclophosphamide application (200 mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups.Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow.Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.

The effect of 4.5 G (LTE Advanced-Pro network) mobile phone radiation on the optic nerve.

PURPOSE: Rapid development in mobile phone technologies increase the average mobile phone usage duration. This increase also triggers exposure to radiofrequency radiation (RF), which is a risk factor for the health. In this study, it was aimed to investigate the effect of mobile phone working with LTE-Advanced Pro (4.5 G) mobile network on the optic nerve, which is responsible for the transmission of visual information. MATERIAL AND METHODS: Thirty-two rats divided into two groups as control (no RF, sham exposure) and experimental (RF exposure using a mobile phone with LTE-Advanced Pro network; 2 hours/day, 6 weeks). The visual evoked potential (VEP) was recorded and determined amplitudes and latencies of VEP waves. Optic nerve malondialdehyde level, catalase and superoxide dismutase activities were determined. Furthermore, ultrastructural and morphometric changes of optic nerve were evaluated. RESULTS: In VEP recordings, the mean VEP amplitudes of experimental group were significantly lower than control group. In ultrastructural evaluation, myelinated nerve fibres and glial cells were observed in normal histologic appearance both in sham and experimental group. However, by performing morphometric analysis, in the experimental group, axonal diameter and myelin thickness were shown to be lower and the G-ratio was higher than in the sham group. In the experimental group, malondialdehyde level was significantly higher and superoxide dismutase and catalase activities were significantly lower than sham group. There was a high correlation between VEP wave amplitudes and oxidative stress markers. CONCLUSION: Findings obtained in this study support optic nerve damage. These results point out an important risk that may decrease the quality of life.

Cytotoxic and apoptotic potential of some coumarin and 2-amino-3-carbonitrile selenophene derivatives in prostate cancer.

3-acetyl coumarin derivatives (1a-d) are formed as a result of condensation of salicylaldehyde derivatives and ethyl acetoacetate and were converted into coumarin-selenophene hybrid compounds (2a-d) in the basic medium by modified Gewald reaction in the presence of malononitrile and selenium. Products are characterized by nuclear magnetic resonance (NMR). The prepared compounds are screened for their anticancer activity against DU-145 cell line. In addition, selected target compounds are evaluated for apoptosis and oxidative stress on DU-145 (prostate carcinoma) cell lines.

Photocytotoxicity of liposomal zinc phthalocyanine in oral squamous cell carcinoma and pharyngeal carcinoma cells.

Aim: Photodynamic therapy utilizes a light-sensitive molecule that produces reactive oxygen species following irradiation. Photodynamic activities of free Zn phthalocyanine (ZnPc) and its liposomal formulations on human oral squamous cell carcinoma and pharyngeal carcinoma cells were assessed. Materials & methods: ZnPc was incorporated in extruded and nonextruded liposomes composed of palmitoyloleoylphosphatidylglycerol (POPG):palmitoyloleoylphosphatidylcholine (POPC) or POPG:dioleoylphosphatidylethanolamine liposomes and incubated with CAL 27 or FaDu cells. Cell viability was assessed following illumination and further incubation. Results: ZnPc incorporated in extruded POPG:POPC liposomes caused extensive cytotoxicity, while ZnPc in extruded or nonextruded POPG:dioleoylphosphatidylethanolamine liposomes or in multilamellar POPG:POPC liposomes were not effective. Conclusion: Extruded POPG:POPC liposomes are a useful delivery vehicle for ZnPc in photodynamic therapy of oral and pharyngeal cancers.

Protective effect of N-acetyl cysteine against radiotherapy-induced cardiac damage.

Purpose: Although radiotherapy (RT) is an important component of cancer treatment, it induces adverse tissue reactions in the around of cancer tissue. Therefore, radioprotectives are needed to protect normal tissues. The aim of this study was to investigate the radioprotective effect of N-acetylcysteine (NAC) on RT-induced cardiac damage in rats for the acute term.Materials and methods: The animals were divided into four groups. The rats in control group were injected with saline for 7 d; the rats in NAC group were injected NAC at dose of 240 mg/kg d for 7 d; the rats in RT group were injected with saline for 7 d plus was irradiated 1 h after the last injection and the rats in NAC + RT group were injected with NAC for 7 d and irradiated 1 h after the last NAC dose. The electrocardiogram was recorded and evaluated PR interval, QRS duration, QT interval, T wave alterations and heart rate. Serum interleukin-4, interleukin-6, tumor necrosis factor-alpha, interleukin 1 beta, galectin-3 levels and creatine kinase and creatine kinase isoenzyme-MB activities were determined in all groups. Also, tissue malondialdehyde (MDA) and nitric oxide levels, superoxide dismutase, catalase and glutathione peroxidase activities were determined. In addition, histological changes of heart were evaluated. All measurements were performed 24 h after RT.Results: In the RT group, findings supporting cardiac injury were observed in the electrocardiogram. Also, cytokine levels and oxidative stress were significantly increased. Pretreatment of rats with NAC ameliorated cardiac injury induced by RT.Conclusions: Our findings suggested that NAC may be a potential radioprotector which is capable of preventing cardiac damage.

Effect of Imipramine on radiosensitivity of Prostate Cancer: An In Vitro Study.

Prostate cancer is the most common cancer and leading cause of cancer death for males. Imipramine (IMI), which is a tricyclic antidepressant, has also been shown to has antineoplastic effect. This study was performed to investigate the radiosensitizing effect of IMI on DU145 prostate cancer cell. Cells were divided into 4 groups. Cell index, apoptotic activity, cell cycle arrest, oxidative stress and EAG1 channel currents were determined in all groups. Our findings showed that combined treatment with IMI and radiotherapy (RAD) did not enhance radiosensitivity of DU145 cells but as unexpected finding, treatment of IMI alone was more effective in DU145 cells.

Primary triple head and neck tumors: Laryngeal squamous cell carcinomas, Kaposi's sarcoma, and non-Hodgkin's lymphoma.

Simultaneously triple head and neck malignancies are extremely rare. We report a case who had epithelial and mesenchymal malignant tumor with lymphoid malignancy in head and neck area. A patient who is 74 year old male patient presented to the otorhinolaryngology department with severe breathing difficulty due to laryngeal mass. The result of laryngeal biopsy was invasive SCCs, so patient underwent total larygectomy and bilateral level 2,3,4 neck disection operation. Primary 3 different type head and neck tumors were observed with histopathological examination. These were orderly invasive SCCs in larynx, B-cell Non-Hodgkin's lymphoma in tongue root and one lymph node of left neck dissection material, Kaposi's sarcoma in one lymph node of right neck dissection material. Although synchronous head and neck tumors occurs very rare with laryngeal carcinoma, the neck dissection materials should be researched for synchronous tumors.

Effect of low-level 1800 MHz radiofrequency radiation on the rat sciatic nerve and the protective role of paricalcitol.

The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 µg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631-643, 2018. © 2018 Wiley Periodicals, Inc.

Single-sided sinonasal mass: A retrospective study.

OBJECTIVE: A unilateral sinonasal mass is a common pathology in ear, nose, and throat clinical practice. However, it may be confused with early stage inflammatory pathologies. The aim of this study was to examine the diagnostic histopathological, clinical, and radiological criteria for a unilateral nasal mass. METHODS: The present study examined the clinical and pathological profiles of unilateral sinonasal masses observed in patients at an ear, nose, and throat clinic in Istanbul between January 2008 and January 2016. During the period of this retrospective study, 195 patients presented with a single-sided sinonasal mass (males: 130, females: 65; age range: 9-93 years). The data analyzed were obtained from patient records. RESULTS: The single-sided sinonasal mass was benign in 187 (95.9%) cases and malignant in 8 (4.1%) cases. Inflammatory polyps (81.03%) were the most frequent benign finding. Squamous cell carcinoma (1.54%) was the most commonly diagnosed malignant lesion. CONCLUSION: A single-sided sinonasal mass is commonly detected by otorhinolaryngologists. Although most often the diagnosis is inflammatory nasal polyposis, the risk of malignancy should not be overlooked. For this reason, careful endoscopic examination should be performed, all lesions should undergo a pathological examination, and it should be kept in mind that neoplastic disease can occur at any age and may be associated with many symptoms.