PMID: 

Cancers (Basel). 2019 Sep 18 ;11(9). Epub 2019 Sep 18. PMID: 31540423

Abstract Title: 

Docetaxel Combined with Thymoquinone Induces Apoptosis in Prostate Cancer Cells via Inhibition of the PI3K/AKT Signaling Pathway.

Abstract: 

Toxicity and the development of resistance by cancer cells are impediments for docetaxel (DTX), a primary drug for treating prostate cancer (PCa). Since the combination of DTX with natural compounds can increase its effectiveness by reducing its toxic concentrations, we evaluated a combination of thymoquinone (TQ) with DTX and determined its cytotoxicity against PCa cells (DU145 and C4-2B). This combination, in a concentration-dependent manner, resulted in synergistic cytotoxicity and apoptosis in comparison to either DTX or TQ alone. In addition, inhibition of cell survival pathways by PI3K/AKT inhibitors conferred sensitivity of DU145 and C4-2B cells to the combination as compared to the individual drugs. Moreover, the combined drugs (DTX+TQ) with inhibitors of PI3K/AKT increased the expression of pro-apoptotic markers (BAX and BID) along with caspase-3, PARP and decreased expression of the anti-apoptotic marker, BCL-XL. These data show that, for PCa cells, the cytotoxic effect of the DTX and TQ combination correlates with a block of the PI3K/AKT signaling pathway. These findings indicate that the combination of DTX and TQ, by blocking of the PI3K/AKT pathway, will improve the survival rate and quality of life of PCa patients.

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PMID: 

Drug Discov Today. 2019 Sep 18. Epub 2019 Sep 18. PMID: 31541714

Abstract Title: 

Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics.

Abstract: 

Thymoquinone is a natural product known for its anticancer activity. Preclinical studies indicated numerous mechanisms of action by which thymoquinone exerts its effects on cancer cells. Recent evidence has indicated that thymoquinone can modulate epigenetic machinery, like modifying histone acetylation and deacetylation, DNA methylation and demethylation, which are among the major epigenetic changes that can contribute to carcinogenesis. Moreover, thymoquinone can alter the genetic expression of various noncoding RNAs, such as miRNA and lncRNA, which are the key parts of cellular epigenetics. This review focuses on cellular epigenetic systems, epigenetic changes responsible for cancer and the counteraction of thymoquinone to target epigenetic challenges, which might be among the mechanisms of the thymoquinone effect in cancer cells.

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PMID: 

Microorganisms. 2019 Sep 19 ;7(9). Epub 2019 Sep 19. PMID: 31546941

Abstract Title: 

Bioactive Compounds ofEssential Oil as Antibacterial Agents againstD.

Abstract: 

Urogenital tract infection caused by obligate intracellular bacteriumD (D) is a leading cause of sexually transmitted diseases. Essential oil (EO) ofhas a broad antimicrobial spectrum. The aim of this study was to evaluate the antimicrobial activity of the bioactive compounds (p-cymene, thymoquinone, carvacrol, and thymol) ofEO againstD. The cytotoxic effects of the compounds were determined by MTT assay. In order to quantify the anti-chlamydial activity of the compounds, HeLa cells were infected withD orD treated previously with the compounds. The titer of the infectiousD was determined by indirect immunofluorescence assay. The minimum inhibitory concentrations of the compounds were evaluated by direct quantitative PCR. None of the compounds showed a cytotoxic effect on HeLa cells in the concentrations tested. According to the immunofluorescence assay, all of the compounds significantly inhibited the growth ofD. The quantitative PCR revealed that the minimum concentration that exerted anti-chlamydial activity was 3.12µM in the case of thymoquinone and p-cymene, while that of carvacrol and thymol was 6.25 µM. Therefore, it can be concluded that bioactive compounds ofEO could be used as effective antimicrobial agents againstD.

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PMID: 

Mol Med Rep. 2019 Sep ;20(3):2450-2458. Epub 2019 Jul 2. PMID: 31322211

Abstract Title: 

Ascorbic acid attenuates cell stress by activating the fibroblast growth factor 21/fibroblast growth factor receptor 2/adiponectin pathway in HepG2 cells.

Abstract: 

Increasing prevalence of obesity‑induced non‑alcoholic fatty liver disease (NAFLD) and non‑alcoholic steatohepatitis (NASH) has been reported. Ascorbic acid (AA), also known as vitamin C, an excellent antioxidant, has been shown to exert beneficial effects on NAFLD; however, the underlying mechanisms are yet to be fully elucidated. In the present study, the role of AA on cell stress in tumor necrosis factor α (TNFα)‑treated HepG2 cells was investigated. Our findings revealed that exposure to AA effectively ameliorated TNFα‑induced cell stresses, including hypoxia, inflammation and endoplasmic reticulum (ER) stress by reducing the expression of Hif1α and its target genes (glucose transporter 1), pro‑inflammatory genes (monocyte chemoattractant 1) and ER stress‑related genes (glucose‑regulated protein, 78 kDa). AA also decreased the protein level of HIF1α. Additionally, AA significantly increased the secretion of total adiponectin and high molecular weight (HMW) adiponectin. Mechanistically, AA was determined to increase the expression of fibroblast growth factor 21 (FGF21) and its receptor, fibroblast growth factor receptor 2 (FGFR2). Knockdown of FGFR2 not only decreased the levels of totaladiponectin and HMW adiponectin, but almost abolished the beneficial effects of AA in ameliorating cell stress. Collectively, the findings of our study demonstrated that AA may attenuate hepatocyte stress induced by TNFα via activation of the FGF21/FGFR2/adiponectin pathway. This could a novel mechanism of action of AA, and its potential for the treatment of NAFLD/NASH.

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PMID: 

Mol Hum Reprod. 2019 Aug 8. Epub 2019 Aug 8. PMID: 31393565

Abstract Title: 

Vitamin C protects carboplatin-exposed oocytes from meiotic failure.

Abstract: 

CBP (carboplatin) is a second-generation chemotherapeutic drug of platinum compound commonly applied in the treatment of sarcomas and germ cell tumours. Although it is developed to replace cisplatin, which has been proven to have a variety of side effects during cancer treatment, CBP still exhibits a certain degree of toxicity including neurotoxicity, nephrotoxicity, hematotoxicity and myelosuppression. However, the underlying mechanisms regarding how CBP influences the female reproductive system especially oocyte quality have not yet been fully determined. Here, we report that CBP exposure led to the oocyte meiotic defects by impairing the dynamics of the meiotic apparatus, leading to a remarkably aberrant spindle organisation, actin polymerisation and mitochondrial integrity. Additionally, CBP exposure caused compromised sperm binding and fertilisation potential of oocytes by due to an abnormal distribution of cortical granules and its component ovastacin. More importantly, we demonstrated that vitamin C supplementation prevented meiotic failure induced by CBP exposure and inhibited the increase in ROS levels, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate the toxic effects of CBP exposure on oocyte development, and provide a potential effective way to improve the quality of CBP-exposed oocytes in vitro.

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PMID: 

J Dent Child (Chic). 2019 May 15 ;86(2):125-128. PMID: 31395119

Abstract Title: 

Severe Gingivitis Associated with Ascorbic Acid-Deficiency in a Pediatric Patient.

Abstract: 

Plaque-induced gingivitis, a common condition in children, responds well to proper oral hygiene practices. Persistent severe gingivitis, on the other hand, should prompt investigation of etiological factors. Nutritional elements are implicated in periodontal health. This case report describes a pediatric patient with severe persistent gingivitis caused by vitamin C deficiency. The events that led to a diagnosis of scurvy and a resolution of the systemic and localized manifestations of the disease, after vitamin C administration, are presented. It is recommended that vitamin C deficiency be considered in cases of refractory gingivitis, especially in pediatric patients with special health care needs who have aversion to foods rich in ascorbic acid.

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PMID: 

Electromagn Biol Med. 2012 Mar ;31(1):75-86. Epub 2012 Jan 23. PMID: 22268787

Abstract Title: 

GSM 900 MHz microwave radiation affects embryo development of Japanese quails.

Abstract: 

A wide range of non thermal biological effects of microwave radiation (MW) was revealed during the last decades. A number of reports showed evident hazardous effects of MW on embryo development in chicken. In this study, we aimed at elucidating the effects of MW emitted by a commercial model of GSM 900 MHz cell phone on embryo development in quails (Coturnix coturnix japonica) during both short and prolonged exposure. For that, fresh fertilized eggs were irradiated during the first 38 h or 14 days of incubation by a cell phone in"connecting"mode activated continuously through a computer system. Maximum intensity of incident radiation on the egg's surface was 0.2μW/cm2.The irradiation led to a significant (p

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PMID: 

Okajimas Folia Anat Jpn. 2002 May ;79(1):25-31. PMID: 12199535

Abstract Title: 

The effect of melatonin on morphological changes in liver induced by magnetic field exposure in rats.

Abstract: 

In this study, we aimed to investigate the possible effect of melatonin on morphological changes in liver induced by magnetic fields exposure. Thirty albino young male Wistar Albino rats were used in the study. They were divided into 3 groups. Control group (C) (n: 10) received daily intraperitoneal injections of saline (0.1 ml/100 g) containing 5% ethanol for two weeks. Only magnetic field exposed (MF) group (n: 10); only magnetic field exposed had daily intraperitoneal injections of physiologic saline (0.1 ml/100 g) containing 5% ethanol for two weeks. Magnetic field exposed and melatonin treated (MF+m) group (n: 10); melatonin was dissolved in ethanol with further dilution in physiological saline. The animals in this group were exposed magnetic fields for two weeks. The magnetic fields exposed animals had intraperitoneal single dose of 4 mg/kg melatonin (0.1 ml/100 g) at 10:00 o'clock daily for two weeks following magnetic fields exposure. We used commercial CB handheld portable transceiver, Midland (USA) labelled, of 4 Watts, 40 channel. This channel frequency has been measured 27.17 MHz with frequency counter. According to the IRPA exposure standards; for 27 MHz, for 6 min, exposure limit is 0.2 mW/cm2. This value is for General Public. For occupational exposure limit is 1 mW/cm2. We have to consider General Public exposure limit. Therefore our limit is 0.2 mW/cm2. In other words; in this study; our exposure is always over the recommended limit. All the animals were decapitated. Liver samples were fixed in buffered neutral formalin. Paraffin sections were dyed with hematoxylen-eosin. Sections were examined under light microscopy. In MF group; sinusoidal dilatations, mixed cell infiltrations noticed in the periportal area, necrosis and vacuoler degeneration were determined in liver samples. However, parenchymal and stromal structures were observed to be prevented partially from effects of magnetic fields in melatonin treated group. In conclusion, it is suggested that melatonin has a mild preventive effect on magnetic field exposed changes in liver tissue in the rats.

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PMID: 

Photochem Photobiol Sci. 2014 Jul ;13(7):1082-92. Epub 2014 Jun 2. PMID: 24886806

Abstract Title: 

Effects of 940 MHz EMF on bioluminescence and oxidative response of stable luciferase producing HEK cells.

Abstract: 

The effects of mobile phone frequency electromagnetic field (RF-EMF, 940 MHz) on a stable cell line (HEK293T) harbouring the firefly luciferase gene were evaluated. A waveguide exposure system with 1 W input power provided the mean specific absorption rate of≈0.09 W kg(-1) in 35 mm Petri dishes. The effects of exposure duration (15, 30, 45, 60 and 90 min) on luciferase activity and oxidative response elements were investigated. Endogenous luciferase activity was reduced after 30 and 45 min of continuous exposure, while after 60 min, the exposed cell lysate showed higher luciferase activity compared with the non-exposed control. Reactive oxygen species (ROS) generation was highest in the 30 min exposed cells as studied by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence. The observed boost in ROS was then followed by a sharp risein catalase (CAT) and superoxide dismutase (SOD) activity and elevation of glutathione (GSH) during the 45 min exposure. Decrease in lipid peroxidation (malondialdehyde, MDA) was meaningful for the 45 and 60 min exposed cells. Therefore, it appears that an increase in the activity of luciferase after 60 min of continuous exposure could be associated with a decrease in ROS level caused by activation of the oxidative response. This ability in cells to overcome oxidative stress and compensate the luciferase activity could also be responsible for the adaptive response mechanism detected in ionizing radiation studies with RF-EMF pre-treatments.

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PMID: 

Radiat Res. 1997 May ;147(5):631-40. PMID: 9146709

Abstract Title: 

Lymphomas in E mu-Pim1 transgenic mice exposed to pulsed 900 MHZ electromagnetic fields.

Abstract: 

Whether radiofrequency (RF) fields are carcinogenic is controversial; epidemiological data have been inconclusive and animal tests limited. The aim of the present study was to determine whether long-term exposure to pulse-modulated RF fields similar to those used in digital mobile telecommunications would increase the incidence of lymphoma in E mu-Pim1 transgenic mice, which are moderately predisposed to develop lymphoma spontaneously. One hundred female E mu-Pim1 mice were sham-exposed and 101 were exposed for two 30-min periods per day for up to 18 months to plane-wave fields of 900 MHz with a pulse repetition frequency of 217 Hz and a pulse width of 0.6 ms. Incident power densities were 2.6-13 W/m2 and specific absorption rates were 0.008-4.2 W/kg, averaging 0.13-1.4 W/kg. Lymphoma risk was found to be significantly higher in the exposed mice than in the controls (OR = 2.4. P = 0.006, 95% CI = 1.3-4.5). Follicular lymphomas were the major contributor to the increased tumor incidence. Thus long-term intermittent exposure to RF fields can enhance the probability that mice carrying a lymphomagenic oncogene will develop lymphomas. We suggest that such genetically cancer-prone mice provide an experimental system for more detailed assessment of dose-response relationships for risk of cancer after RF-field exposure.

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