Gastric ulcers have been considered as a major problem worldwide. This study investigated the pro... more Gastric ulcers have been considered as a major problem worldwide. This study investigated the protective synergistic effect of a novel nutrient formulation for the protection and treatment of indomethacin-induced gastric ulcer in rat model. 24, 8 w old male rats with a body weight between 220 and 240 g, were divided into four groups and used for this study. Group 1 consists of healthy controls and group 2 consists of ulcerative animals, group 3 consists of ulcerative+phytobiological formulation treatment (80 mg/kg) and group 4 consists of omeprazole (40 mg/kg). Pre-treatment with 80 mg/kg of phytobiological formulation improved the activities of the measured antioxidant enzymes, decreased lipid peroxidation and inflammation, as evidenced by improved surface and glandular epithelium (white arrows) of phytobiological treated group stained with hematoxylin and eosin and tumor necrosis factor alpha immuno-expression when compared with the ulcer group. In conclusion, the mechanism by which this phytobiological formulation prevents indomethacininduced gastric ulcer may be mediated via improving the homeostasis of enzymatic (superoxide dismutase) and nonenzymatic (glutathione) antioxidants, inhibiting (malondialdehyde) and decreasing the formation of inflammatory cytokines (tumor necrosis factor alpha, C-reactive protein content and interleukin-10). Consequently, this phytobiological formulation may be a beneficial nutrient formulation therapy for patients diagnosed with gastric ulceration.
Thymoquinone nanoparticles protect against cisplatin-induced nephrotoxicity in Ehrlich carcinoma model without compromising cisplatin anti-cancer efficacy
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The influence of antioxidant dietary-derived polyphenolic combination on breast cancer: Molecular study
Biomedicine & Pharmacotherapy, May 1, 2022
Breast cancer remains a leading cause of female mortality worldwide. Therefore, novel complementa... more Breast cancer remains a leading cause of female mortality worldwide. Therefore, novel complementary treatments have been sought. Recently, there has been a growing interest in investigating the possible complementary effects of polyphenolic compounds against various malignancies. In the present study, using MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, the anticancer efficacy of a polyphenolic mixture (PFM) was investigated. PFM is composed of curcumin, resveratrol, epigallocatechin gallate, and quercetin. PFM treatment led to a dose-dependent inhibition of cell proliferation, with IC50 values of 25.9 ± 3 µg/ml and 29.4 ± 0.9 µg/ml for MCF-7 and MDA-MB-231 cells, respectively. In addition, PFM induced apoptosis in MDA-MB-231 cells and cell cycle arrest at the S phase in MCF-7 cells. Using RT-qPCR, PFM treatment was observed to result in significant downregulation of the oncogenic miR-155 (P < 0.05), as well as significant downregulation of the rate-limiting glycolytic enzyme, hexokinase 2 (HK2) (P < 0.05), while upregulating the expression of the zinc finger E-box binding homeobox 2 gene (P < 0.01). PFM was also found to exert an anti-migration effect in breast cancer cells using the wound healing assay, as well as significantly (P < 0.05) increasing the median survival of Ehrlich ascites carcinoma (EAC) tumor-bearing mice. These results suggest that PFM possesses potential antitumor effects against breast cancer. A possible mechanism of action could be due to PFM's effect in modulating the expression of the glycolytic enzyme HK2 through suppression of miR-155 in MCF-7 cells. Combining polyphenolic compounds that interact with one another could result in synergistic effects that potentially target various tumour hallmarks.
Agarwood (Oudh), is often used by people in the Kingdom of Saudi Arabia. The Oudh has been mentio... more Agarwood (Oudh), is often used by people in the Kingdom of Saudi Arabia. The Oudh has been mentioned in the Hadith and is traditionally used for its aroma (perfuming smell) and potential medicinal applications. The aim of the study was to isolate mycotoxigenic fungi that grow on agarwood and the factors and storage conditions that enhance their growth potential. In addition to the detection of associated mycotoxins like: Aflatoxin B1 (AFB 1) and ochratoxin A (OTA) from agarwood. Agarwood samples were collected from local markets of Jeddah governorate, Kingdom of Saudi Arabia. Standard dilution plate method was used for the isolation of fungi. Isolated fungi were identified based on morphological characteristics and confirmed using molecular biology techniques. AFB 1 and OTA were detected by High Performance Liquid Chromatography (HLPC). The results indicated that the most commonly isolated fungal genera were in the following descending order: Aspergillus, Penicillium, Fusarium and Rhizopus. Among Aspergillus genera, A. flavus and A. ochraceus were detected based on their morphology and confirmed by PCR using specific primers. It was also noted that AFB 1 was released by 15.3 and 55.0% of A. flavus and A. parasiticus isolates respectively with levels reaching up to 14.60 mg/L. The moisture content in the samples ranged from 3% to 10% affected fungal growth. AFB 1 was detected in 22 out of 50 of the samples. The maximum level of AFB 1 (50.7 mg/kg) was detected in samples with higher moisture content (12%) stored at a temperature of 32°C. Aspergillus fungi were found to be the most predominant fungal genera found on agarwood. Moisture content (9-10%) and storage temperature (32°C) stimulated fungal growth and their ability to produce mycotoxins. For this reason, storage conditions at the marketing place should be adequate in order not to provide a conducive environment for fungal growth which is associated with the mycotoxin production. In order to prevent fungal growth and mycotoxin production, it would be recommended to store agarwood at temperatures not exceeding 25°C and moisture content of up to a maximum of 5-6%.
Zenodo (CERN European Organization for Nuclear Research), Aug 30, 2021
Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome (ACS). Kounis Syndrome (KS)... more Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome (ACS). Kounis Syndrome (KS) is described as the coincidental occurrence of chest pain and clinical and laboratory findings of ACS. The prognosis depends on the magnitude of the initial allergic response, the patient's sensitivity, comorbidities, the site of antibody antigen reaction, the allergen concentration, and the route of allergen entrance. We report a rare case of KS secondary to antibiotic allergy. This case may suggest that Kounis syndrome should be taught in the differential diagnosis of acute coronary syndromes. Clinicians should be aware of this adverse effect and consider it during diagnostic workup of myocardial injury.
Natural Antioxidants and Colorectal Cancer: A New Approach
The FASEB Journal, Apr 1, 2017
IntroductionColorectal cancer (CRC) is a multifactorial disease; genetic epigenetic and environme... more IntroductionColorectal cancer (CRC) is a multifactorial disease; genetic epigenetic and environmental factors as well as oxidative stress could be responsible for its onset and progression. Several...
Review-Therapeutic implications of Nigella sativa against cancer metastasis
PubMed, Sep 1, 2016
Nigella sativa (N. sativa), remedial usage against different diseases associated with skeleton, c... more Nigella sativa (N. sativa), remedial usage against different diseases associated with skeleton, cardiovascular, digestive and urinary systems has a long-standing history. At present, efforts are underway to study its effects against various cancers at both the cellular and molecular levels. In this review, the role of active constituents like thymoquinone (TQ) on different types of cancer has been explored. TQ putative involvement in metastasis has been assessed by elucidating its effects on cell proliferation, adhesion, invasion and angiogenesis. Up regulation of caspase 3, Smac and down regulation of p-AKT, p65, XIAP, Bcl-2, COX-2 is also influenced by N. sativa. These findings prove a significant positive correlation between TQ concentrations and induction of apoptosis, decrease in motility and a reduction in invasion and angiogenesis in cancerous cells. However, there are still quite a few unaddressed domains, which need to be understood. One of these may include target specificity of N. sativa against cancerous tissues, mode of administration, dosage and downstream regulators in mediating these effects. In reference to earlier findings and low cost availability, N. sativa may, also, be suggested as either a suitable sole remedy for cancer or as a complementary to ongoing conventional therapy based extensive and rigorous in vivo optimization and validation.
Ban or regulate? Costs of dental occupational safety from mercury
PubMed, 2003
Occupational hazard from mercury (Hg) exposure in the dental practice is less well studied than p... more Occupational hazard from mercury (Hg) exposure in the dental practice is less well studied than patient and environmental hazard. Developing country evidence on all dimensions of the problem is sparse, as are analyses of cost tradeoffs from practices that can reduce Hg exposure. A survey was conducted on 99 dentists from Greater Beirut to investigate levels of exposure and factors affecting them. Twenty-five percent of the dentists had hair Hg concentrations above the initially accepted level of 5 microg/g, and 28 percent had levels exceeding 10 microg/g. Gloves and masks had the most significant effect on the reduction of Hg level. Given these results and drawing on previous literature, we estimate and compare the costs of a total ban on amalgam use versus regulatory interventions to reduce exposure. We conclude that regulation constitutes a significantly lower financial burden. This result is consistent with policy conclusions in most industrialized countries. In addition, it serves as a useful benchmark for developing countries with dental sector and socioeconomic characteristics similar to those of Lebanon, such as a range of countries in Latin America, Eastern Europe, Asia, and Africa.
Ascorbate effect on cytokine stimulation of HIV production
PubMed, Sep 1, 1995
We have recently shown that ascorbic acid (AA) suppresses the production of HIV in a latently inf... more We have recently shown that ascorbic acid (AA) suppresses the production of HIV in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus activation following treatment with inflammatory cytokine, we tested tumor necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with HIV/AIDS. ACH-2 cultures, pretreated with various nontoxic concentrations of ascorbate or AZT were stimulated for 2 h with TNF-alpha, and incubated further with fresh supplements of ascorbate or AZT. At 24 to 48 h post-treatment, the RT activity released into culture supernatant was determined. Results showed that TNF-alpha alone caused approximately 13- to 16-fold stimulation in the level of extracellular RT. Pretreatment with ascorbic acid at 200 micrograms/ml caused a little more than about 2- to 4-fold reduction in extracellular RT levels. Most remarkably, exposure to 300 micrograms/ml ascorbate resulted in approximately 5- to 10-fold lowering of the extra-cellular RT titer. In contrast, no significant suppression in extracellular RT levels was seen with concentrations of AZT in the range of 1-5 micrograms/ml.
The retrovirus human T-cell lymphotrophic virus type-1 (HTLV-1) causes adult T-cell leukemia (ATL... more The retrovirus human T-cell lymphotrophic virus type-1 (HTLV-1) causes adult T-cell leukemia (ATL), which remains with no cure. This study evaluates the effects of l-lysine on proliferation and induction of apoptosis using non-cytotoxic concentrations of the test compound against HTLV-1 positive and negative malignant cell lines. The anti-proliferative effect of lysine was established and confirmed by studying the effects of the test compound on the expression of TGF mRNA expression by RT-PCR. To investigate the effect of l-lysine on the induction of apoptosis, DNA flow cytometry analyses was done and the results verified by cell death ELISA. The results indicated that a significant increase in the preG 1 phase and a decrease in the S phase of the cell cycle in all of the ATL cells tested. l-Lysine up-regulated p53, p21, and Bax protein levels and a down-regulation of Bcl-2␣ in all the cell lines tested. l-Lysine was found to exert its effect through the NF-B pathway by inhibiting the p65 subunit specifically. Also l-lysine caused a decrease in the levels MMP-2 and MMP-9 as well as their enzymatic activity.
Ascorbic acid induces apoptosis in adult T-cell leukemia
PubMed, Mar 14, 2007
Background: Adult T-cell leukemia (ATL) is an acute malignancy of activated T-cells caused by the... more Background: Adult T-cell leukemia (ATL) is an acute malignancy of activated T-cells caused by the human T-cell lymphotrophic virus type-1 (HTLV-1). Materials and methods: The effects of non-cytotoxic concentrations of ascorbic acid (AA) were evaluated against HTLV-1 positive and negative cells. The effect of AA on apoptosis and proliferation was evaluated by cell cycle analysis. The role of p53, p21 Bax and Bcl-2a on cell cycle modulation and apoptosis was also assessed. The anti-proliferative effects were tested by determining the changes in the expression of transforming growth factors (TGF-alpha, TGF-beta1 and TGF-beta2). Results: Ascorbic acid was found to reduce the proliferation of cells and induce apoptosis by the modulation of p53, p21, Bcl-2 and Bax. Conclusion: The results of this study show the anti-proliferative effects of AA against leukemic cells.
The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on proliferation and... more The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. EF showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein expression using RT-PCR. EF resulted in the down-regulation of TGFalpha and an up-regulation in TGF-beta2. EF caused a significant increase in apoptotic cells in the preG(1) phase. These results were confirmed using Cell Death ELISA and Annexin V-FITC. Induction of apoptosis was caused by an upregulation of p53, p21 and Bax protein levels and a down-regulation of Bcl-2alpha protein expression level.
Antiviral and Immunomodulatory Activities of Ascorbic Acid
Sub-cellular biochemistry, 1996
It has been known since the early days of ascorbic acid research that the appearance of scurvy, w... more It has been known since the early days of ascorbic acid research that the appearance of scurvy, which is caused by deficiency of this vitamin, is associated with decreased resistance to infection (Reid and Briggs, 1953). Over the years, it has become well recognized that ascorbate can bolster the natural defense mechanisms of the host and provide protection not only against infectious disease, but also against cancer and other chronic degenerative diseases. The functions involved in ascorbate’s enhancement of host resistance to disease include its biosynthetic (hy-droxylating), antioxidant, and immunostimulatory activities. In addition, ascorbate exerts a direct antiviral action that may confer specific protection against viral disease. The vitamin has been found to inactivate a wide spectrum of viruses as well as suppress viral replication abd expression in infected cell. In this article we review the antiviral and immunotimulatory effects of ascorbate and their relevance to control of acute and chronic viral infections. Detailed discussion of thr biosynthetic activities of ascorbate has been presented in a review by England and Seifter (1986). The antinoxidant function of ascorbate has been reviewed recently by Bendich (1988)
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Abstract 4300: Thymoquinone Inhibits Proliferation and induces apoptosis in leukemic cells
Introduction: Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus 1 (HTLV-1)... more Introduction: Adult T-cell leukemia (ATL) is caused by human T-cell lymphotropic virus 1 (HTLV-1) and is an aggressive form of malignancy. So far, there is no effective treatment for ATL. Thymoquinone has been reported to exhibit many useful effects including anti-cancerous properties. Objective: The aim of this study is to investigated the effects of TQ on proliferation, apoptosis induction and the underlying mechanism of action in both HTLV-1 positive (C91-PL and HuT-102) and HTLV-1 negative (CEM and Jurkat) malignant T-lymphocytes. Materials and methods: Cells were treated with various concentrations of thymoquinone for 24h. Cell cytotoxicity was assayed using the CytoTox 96® Non-Radioactive Cytotoxicity Assay Kit. Cell proliferation was determined using CellTiter 96® Non-Radioactive Cell Proliferation. Cell cycle analysis was performed using staining with propidium iodide. Apoptosis was assessed using cell death ELISA kit. The effect of TQ on p53, p21, Bcl-2 protein expression was determined using Western blot analysis while TGF mRNA expression was determined by RT-PCR. Results: At non-cytotoxic concentrations of TQ, it resulted in inhibition of proliferation in a dose dependant manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increased DNA fragmentation. TQ mediated its anti-proliferative effect and apoptosis induction by an up-regulation of TGFβ1, p53 and p21 and a down-regulation of TGF-α and Bcl-2α. Conclusion: Thymoquinone showed antiproliferative and proapoptotic potentials in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL. Citation Format: Steve Harakeh, Josiane Semaan, Marwan El Sabban, Soad K. Al Jaouni, Mona Diab-Assaf, Rania Azar. Thymoquinone Inhibits Proliferation and induces apoptosis in leukemic cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4300. doi:10.1158/1538-7445.AM2017-4300
Antimicrobial-resistance of Streptococcus pneumoniae isolated from the Lebanese environment
Marine Environmental Research, Sep 1, 2006
The aim of this study was to isolate and molecularly characterize Streptococcus pneumoniae in sam... more The aim of this study was to isolate and molecularly characterize Streptococcus pneumoniae in samples collected from the aquatic environment in Lebanon. For this purpose, 57 samples of ground waters, sea water, sediments and crabs were collected. Biochemical tests as well as PCR were used for further identification and molecular characterization of 46 suspected isolates using specific primers for the lytA-gene and protein 2B-gene. The confirmed isolates were evaluated for their antimicrobial resistance, using the minimum inhibitory concentration method. Crab samples exhibited a high contamination level of an average count of 8.2 x 10(4)CFU/g. In water samples, the highest contamination was recorded near a coastal landfill with a bacterial count of 1.8 x 10(3)CFU/ml whereas the lowest bacterial counts (non detectable) were observed in ground water samples. Twenty out of the 46 suspected isolates came from sea water, and 17 out of those were characterized by PCR as S. pneumoniae. Testing the antimicrobial resistance of the 20 isolates to various antimicrobials showed that all sea water isolates were resistant to vancomycin, gentamicin, and oxacillin (100%), whereas 62.5% were resistant to clindamycin, and only 25% were erythromycin resistant. Resistance rates were higher in the case of fresh water samples, with 57% resistance to erythromycin, and 100% resistance to vancomycin, gentamicin, clindamycin and oxacillin. Alternatively, all tested crab isolates were susceptible to erythromycin. However, they showed a high resistance of 80% against vancomycin, gentamicin, clindamycin and 100% against oxacillin.
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