[Retracted] Effects of nutrients on matrix metalloproteinases in human T­lymphotropic virus type 1 positive and negative malignant T­lymphocytes.

Subsequently to the publication of the above article, a concerned reader drew to the attention of the Editorial Office and the authors that certain pairings of the GAPDH western blotting control bands in Fig. 4 appeared to be strikingly similar to adjacent pairings of bands within the same gel slices; moreover, data bands featured in the HuT­2, C91­PL and Jurkat zymography blots in Fig. 5 also appeared to be remarkably similar, both comparing the bands within a given gel slice (as in the case of the Jurkat cell experiment in Fig. 5) or comparing between gel slices (as in the case of the Hut­2 cells compared with the C910PL cells in Fig. 5). The Editorial Office independently investigated these concerns, and reached the conclusion that the bands did appear strikingly similar; too similar for the appearance of the bands within these figures to have arisen by chance. Moreover, the application of a software analysis program revealed that certain of the data in Fig. 6 had also appeared in another paper published by several of the same authors in another journal at around the same time. As a result of this investigation, the Editor of International Journal of Oncology has decided that this paper should be retracted from the journal on account of a lack of confidence in the authenticity of the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 45: 2159­2166, 2014; DOI: 10.3892/ijo.2014.2638].

Ruthana date extract inhibited proliferation of human hepatocellular carcinoma (HepG2) cells by modulation of BAX gene.

Cancer response to chemotherapeutic agents and its side effects remain a challenge for the development of new anticancer compounds. Dates are consumed worldwide due to their high nutritional value. We investigated the cytotoxicity and expression of the proapoptotic BAX gene in human hepatocellular carcinoma (HepG2) cells treated with Ruthana date ethanolic extract (RDE). The RDE ingredients analyzed by GC/MS and HepG2 cells were treated with different concentrations of RDE for 24, 48, and 72 h. Cytotoxicity, cell viability, DNA fragmentation, and BAX expression were determined. The GC/MS analysis of RDE showed its high content of quercetin, myricetin kaempferol, thymine, and catechol as the most active ingredients. HepG2 treated with RDE showed a significant change in morphological characteristics related to cell death. The antiproliferative activity determined by WST-1 demonstrated that RDE significantly reduced cell viability. Cells treated with RDE (10-60 mg) showed gradual DNA fragmentation in a dose-dependent manner. Gene expression analysis showed upregulation of BAX at 30 mg/ml of RDE (p < 0.001). However, it showed downregulation at (40-60 mg/ml) as compared to control. Our findings indicated that RDE exert cytotoxicity against HepG2 cells due to its high content of flavonoids. This effect through DNA fragmentation and activation of the proapoptotic BAX gene.

Leishmaniasis prevalence, awareness and control in Saudi Arabia.

Background: Leishmaniasis is a widespread skin protozoan infectious disease. It is an intracellular parasitic microorganism that develops in the body of infected female phlebotomine sandflies vector, prior to its transmission to human or animal host by the vector bite. The objective of this review is to highlight the current prevalence of Leishmaniasis in the Kingdom of Saudi Arabia, and the direction in research for its control. Materials: The update literature covered The infection of the host with this trypanosome starts with a skin bite from the infected sand fly, followed by penetration of the parasite into cellular structures of the skin, or its infiltration to the circulatory system, targeting the internal organs. Different research groups are experimenting on construction of recombinant Leishmania antigens, compiled from this protozoa and from antigens recovered from the saliva of sand flies, in an attempt to immunize the host for protection against this disease. Conclusion: The benefits behind such a review is to support the personnel involved in developing evidence-based policy guidelines, strategies and standards for disease prevention and management of their implementation; in addition, it provided a technical support to member states to collaborate on establishment of an effective systems to handle the Leishmaniasis.

Strigol1/albumin/chitosan nanoparticles decrease cell viability, induce apoptosis and alter metabolomics profile in HepG2 cancer cell line.

Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ±â€¯0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P < 0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).

Evaluation in broilers of aerosolized nanoparticles vaccine encapsulating imuno-stimulant and antigens of avian influenza virus/Mycoplasma gallisepticum.

BACKGROUND: The global prevalence of economic primary infection of poultry by H9N2 virus, including the Lineage A, panzootic group ME1, and associated with secondary infection by Mycoplasma gallisepticum (MG), is alarming to the sustainability of the poultry sector. This research evaluated in broilers the immunity and protection induced by aerosolization of liposomal nanoparticles vaccine, encapsulating antigens of H9N2 virus and MG, with or without the incorporation of Echinacea extract (EE) immuno-stimulant. Six different treatments (TRTs) of broilers were included in the experimental design, with three replicate pens/TRT and stocking of 20 day-old birds/replicate. RESULTS: The tracheobronchial washings of birds subjected to aerosolization of liposomal nanoparticles, encapsulating antigens of H9N2 and MG and EE had the highest significant mean levels of each of IgA and IgG specific to H9N2 and MG, associated with lowest tracheal MG colonization, tracheal H9N2 recovery, tracheal histopathologic lesions, mortality, and best performance in body weight and feed conversion compared to all other challenged birds allocated to different treatments (P < 0.05). However, the control broilers, free from challenge with MG and H9N2, had the lowest mortality and tracheal lesions, and the highest production performance. CONCLUSION: The aerosolization of liposomal nanoparticles, encapsulating antigens of H9N2 and MG and EE resulted in enough local immunity for protection of broilers against infection, and in attaining the highest production performance in challenged birds. The potential implication of vaccinating with safe killed nanoparticle vaccines is of utmost importance to the global poultry sector.

Hemorrhagic fever in Saudi Arabia: challenge to public health, effective management and future considerations.

BACKGROUND: Viral hemorrhagic fevers (VHF) refers to a group of febrile illnesses caused by different viruses that result in high mortality in animals and humans. Many risk factors like increased human-animal interactions, climate change, increased mobility of people and limited diagnostic facility have contributed to the rapid spread of VHF. MATERIALS: The history of VHFs in the Saudi Arabian Peninsula has been documented since the 19th century, in which many outbreaks have been reported from the southwestern region of Saudi Arabia. Despite presence of regional network of experts and technical organizations, which expedite support and respond during outbreaks, there are some more challenges that need to be addressed immediately. Gaps in funding, exhaustive and inclusive response plans and improved surveillance systems are some areas of concern in the region which can be dealt productively. This review primarily focusses on the hemorrhagic fevers that are caused by three most common viruses namely, the Alkhurma hemorrhagic fever virus, Rift valley fever virus, and Dengue fever virus. CONCLUSION: In summary, effective vector control, health education, possible use of vaccine and concerted synchronized efforts between different government organizations and private research institutions will help in planning effective outbreak-prevention and response strategies in future.

Encapsulation of 5-Flurouracil into PLGA Nanofibers and Enhanced Anticancer Effect in Combination with Ajwa-Dates-Extract (Phoenix dactylifera L.).

Side effects connected with chemotherapeutic agents used in cancer treatment has led to alternative modalities of combinatorial therapies in an attempt to reduce the drug dosage and associated risks. In the current study we evaluated the potential use of Ajwa Dates Extract (ADE), reported to have anti-cancer effects, as an adjuvant therapy in combination with 5-flurouracil (5FU) against the human-breast-adenocarcinoma cell line (MFC-7) in vitro. The effects of ADE alone and in combination with 5-FU were evaluated in terms of cell viability and cytotoxicity. For drug delivery purpose, we successfully encapsulated 5FU in both presence and absence of ADE through electrospinning together with poly lactic-co-glycolic acid (PLGA) in different combinations. Physicochemical properties of 5FU and ADE incorporated into PLGA nanofibers remained unaltered as confirmed by Fourier-Transform-Infrared (FTIR), Raman-spectroscopies and X-ray Diffraction (XRD) techniques. The morphological characterization of nanofibers was done using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The surface roughness of PLGA and PLGA + ADE nanofibers increased by incorporation of 5FU. PLGA + ADE nanofibers were in hydrophilic range (<90°) while nanofibers prepared from both PLGA + 5FU and PLGA + 5FU + ADE combinations were in hydrophobic range (∼112°). The percentage inhibition of MCF-7 proliferation at 72 hrs showed an enhanced combinatorial anti-cancer effect of 5FU and ADE on the cells seeded on PLGA + 5FU + ADE mat (47% decrease) while PLGA + 5FU and PLGA + ADE demonstrated only 23% and 16% decrease respectively as compared to controls. The hydrophobicity induced by 5FU can further be investigated to get improved cellular adherence and efficient controlled-drug-release.

Effects of Ascorbic Acid on Tax, NF-κB and MMP-9 in Human T-cell Lymphotropic Virus Type 1 Positive Malignant T-Lymphocytes.

BACKGROUND: HTLV1 is a retrovirus that infects CD4-positive cells and leads to Adult T-cell leukemia by constitutive activation of nuclear factor kappa B. Ascorbic acid (AA) is an essential nutrient that possess anti-proliferative and pro-apoptotic activity against a number of malignant cell lines. This study delineates the effect of AA on Tax protein expression as well as NF-κB and MMP9 activity in two HTLV1-positive leukemia cells (HuT-102 and C91-PL). METHODS: The cytotoxic and antiproliferative effect of AA were studied by LDH release and MTT tests, respectively. The proteins expression level was assessed by western blotting. RT-PCR was used to study mRNAs level. Finally, ELISA/EMSA and Zymography were used to evaluate NF-κB and MMP-9 activities, respectively. RESULTS: Cell lines were treated with non-cytotoxic concentrations of AA for 48h and 96h, which resulted in a significant inhibition of proliferation at a concentration of 50µg/ml at 96h in both cell lines. The same concentration inhibited Tax protein expression as well as the NF-κB nuclearization and DNA binding activity. The inhibitory effect of AA on MMP9 protein expression and activity started at 100µg/ml and 50µg/ml in HuT-102 and C91-PL cells respectively, with no effect at the transcriptional levels of MMP-9 in either one of the two cell lines. CONCLUSION: These results indicated that while AA exerted its anti-proliferative effect on the NF- κB activation pathway by suppressing Tax expression, its effects on MMP9 seemed to be independent of this mechanism and follow a different approach.

Antimicrobial effect of different types of honey on Staphylococcus aureus.

Honey exhibits antimicrobial activities against a wide range of bacteria in different milieu. This study aims to compare the effects of five types of honey (both imported and local Saudi honey) against Staphylococcus aureus. The five types of honey (Manuka Honey UMF +20, Manuka Honey UMF +16, Active +10 Manuka Honey, Sidr honey and Nigella sativa honey) were evaluated for their bactericidal/bacteriostatic activities against both methicillin resistant and sensitive S. aureus. The inhibitory effect of honey on bacterial growth was evident at concentrations of 20% and 10% (v/v). Manuka Honey showed the best results. Manuka Honey UMF +20 had a bactericidal effect on both methicillin resistant and sensitive S. aureus. However, Sidr and N. sativa honey exerted only a bacteriostatic effect. The efficacy of different types of honey against S. aureus was dependent on the type of honey and the concentration at which it was administered. Manuka Honey had the best bactericidal activity. Future experiments should be conducted to evaluate the effects of honey on bacterial resistance.

Anti-cancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for major cancer-related deaths despite current advanced therapies. Treatment and prognosis of HCC is better in patients with preserved liver function. Many natural products including ajwa dates (Phoenix dactylifera L.), are claimed to have hepatoprotective and HCC inhibitory effects, but most lack scientific validation. To prove our hypothesis, we attempted to evaluate the HCC inhibitory effects, and other beneficial properties of the aqueous extract of ajwa dates (ADE) in a rat model of diethylnitrosamine (DEN) induced liver cancer. METHODS: Thirty-two male rats were divided into four groups of eight each as follows, Group A: untreated control; Group B: DEN control (180 mg/kg bw), Group C: DEN + ADE 0.5 g/kg bw; and Group D: DEN +1.0 g/kg bw. Rats from all groups were assessed for liver cancer progression or inhibition by evaluating histological, biochemical, antioxidant enzyme status, cytokines and gene expression profiles. RESULTS: DEN treatment Groups (B, C, D) showed histological features of HCC and in rats treated with ADE (Groups C, D) partial to complete reversal of normal liver architecture was observed. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), glutatione peroxidase (GPx) and catalase (CAT) were increased, while the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels and lipid peroxidation were significantly decreased in Group C and Group D compared to Group B. Pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1ß,, GM-CSF) were increased in the serum of rats in Group B while the anti-tumor cytokines (IL-2, IL-12) were increased in ADE treated Groups (C, D). In addition, Alpha-Feto Protein (AFP) and IL-6 gene expression levels were upregulated in Group B, while they were significantly downregulated in ADE treated Groups (C, D). CONCLUSIONS: ADE helped in the reversal of DEN damaged liver towards normal. Restoration of anti-oxidant enzymes, liver enzymes, cytokines balance and gene expression to normal levels following ADE treatment indicates that ADE improves liver function and inhibits HCC. ADE can, therefore, be used together with conventional therapeutics for HCC.

SIGNALING PATHWAYS REGULATED BY BRASSICACEAE EXTRACT INHIBIT THE FORMATION OF ADVANCED GLYCATED END PRODUCTS IN RAT BRAIN.

BACKGROUND: The goal of this study was identification signaling molecules mediated the formation of AGEs in brain of rats injected with CdCl2 and the role of camel whey proteins and Brassicaceae extract on formation of AGEs in brain. METHODS: Ninety male rats were randomly grouped into five groups; Normal control (GpI) and the other rats (groups II-V) were received a single dose of cadmium chloride i.p (5 µg/kg/b.w) for induction of neurodegeneration. Rats in groups III-V were treated daily with whey protein (1g/kg b.w) or Brassicaceae extract (1mg/kg b.w) or combined respectively for 12 weeks. RESULTS: It was found that whey protein combined with Brassicaceae extract prevented the formation of AGEs and enhance the antioxidant activity compared with untreated group (p <0.001). Serum tumor necrosis factor (TNF-α) and interleukine (IL-6) levels were significantly decreased (p<0.01) in rats treated with whey protein and Brassicaceae extract formation compared with untreated. The combined treatment showed a better impact than individual ones (p<0.001). The level of cAMP but not cGMP were lowered in combined treatment than individual (p<0.01). CONCLUSION: It can be postulated that Whey protein + Brassicaceae extract formation could have potential benefits in the prevention of the onset and progression of neuropathy in patients.

Gut Microbiota: A Contributing Factor to Obesity.

Obesity, a global epidemic of the modern era, is a risk factor for cardiovascular diseases (CVD) and diabetes. The pervasiveness of obesity and overweight in both developed as well as developing populations is on the rise and placing a huge burden on health and economic resources. Consequently, research to control this emerging epidemic is of utmost importance. Recently, host interactions with their resident gut microbiota (GM) have been reported to be involved in the pathogenesis of many metabolic diseases, including obesity, diabetes, and CVD. Around 10(14) microorganisms reside within the lower human intestine and many of these 10(14) microorganisms have developed mutualistic or commensal associations with the host and actively involved in many physiological processes of the host. However, dysbiosis (altered gut microbial composition) with other predisposing genetic and environmental factors, may contribute to host metabolic disorders resulting in many ailments. Therefore, delineating the role of GM as a contributing factor to obesity is the main objective of this review. Obesity research, as a field is expanding rapidly due to major advances in nutrigenomics, metabolomics, RNA silencing, epigenetics, and other disciplines that may result in the emergence of new technologies and methods to better interpret causal relationships between microbiota and obesity.

Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest.

INTRODUCTION: Phoenix dactylifera L (Date palm) is a native plant of the Kingdom of Saudi Arabia (KSA) and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD) on human breast adenocarcinoma (MCF7) cells in vitro. METHODS: MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml) of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied. RESULTS: Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h). Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml) for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP). Quantitative real time PCR (qRT-PCR) analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2. CONCLUSIONS: MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.

Prosthetics and Techniques in Repair of Animal's Abdominal Wall.

The management of abdominal wall repair continues to present a challenging problem, especially in the repair of major defects. Many abdominal wall defects can be repaired by primary closure; however, if the defect is large and there is a tension on the closure of the wound, the use of prosthetic materials becomes indispensable. Many studies have been performed with various materials and implant techniques, without the comparison of their degrees of success, based on sound meta-analysis and/or inclusive epidemiologic studies. This review covered the effectiveness of recent advances in prosthetic materials and implant procedures used in repair of abdominal wall, based on biomechanical properties and economic aspects of reconstructed large abdominal wall defects and hernias in animals. The presented results in this review helped to reach treatment algorithms that could maximize outcomes and minimize morbidity.

Metagenomic Analysis of Antibiotic-Induced Changes in Gut Microbiota in a Pregnant Rat Model.

Food and Drug Administration (FDA, USA)-approved category B antibiotics are commonly prescribed to treat infections during pregnancy. The aim of this study was to investigate antibiotic-induced changes in gut microbiota (GM) that occur during pregnancy. The 16S rRNA amplicon deep-sequencing method was used to analyze the effect of category B antibiotics (azithromycin, amoxicillin and cefaclor) on GM during pregnancy using a rat model. The GM composition was substantially modulated by pregnancy and antibiotics administration. Firmicutes, Bacteroidetes, Proteobacteria, Chlamydiae, Actinobacteria, and Cyanobacteria were the dominant phyla. Antibiotic treatment during pregnancy increased the relative abundance of Proteobacteria and reduced Firmicutes. The genera Shigella, Streptococcus, Candidatus Arthromitus, and Helicobacter were significantly (p < 0.05) more abundant during pregnancy. Antibiotics significantly (p < 0.05) reduced the relative abundance of Lactobacillus but increased that of Enterobacter. There was a significant (p < 0.05) decrease in Lactobacillus sp., Lactobacillus gallinarum and Lactobacillus crispatus during pregnancy. Antibiotic treatment reduced bacterial diversity; the lowest number of operational taxonomic units (OTUs) were detected in the cefaclor-treated groups. Antibiotics significantly (p < 0.05) promoted weight gain during pregnancy, and increased relative abundance of Shigella sonnei, Enterococcus hormaechei, and Acinetobacter sp. GM perturbations were accompanied by increases in Proteobacteria abundance and weight gain in pregnancy following antibiotic treatment.

MODULATION OF CARCINOGEN-METABOLIZING ENZYME BY MADINAH MINT (Mentha spp) IN RAT LIVER.

BACKGROUND: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P450 mixed function oxidase system. MATERIALS AND METHODS: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P450 mixed function oxidase) analysis. RESULTS: The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (p<0.001) when compared with the control. However, glutathione S-transferase and glucuronosyl transferase activities were significantly decreased (p<0.001 and p<0.01) respectively compared with control. The mutagenic activity of N-nitrosopiperidine was lower in the mint-treated hepatic microsomal compared with the controls. CONCLUSION: It can be concluded that BWME has the potential to suppress the activity of cytochrome enzymes involved in the bio-activation of chemical carcinogen; hence may display chemo preventive activity.

Oseltamivir activity against avian influenza H9N2 strain with different point mutations in their neuraminidase.

The present study has two aims: to optimize the antiviral activity of oseltamivir in chicken embryos against an avian influenza-H9N2 strain (P0) and to apply the optimized protocol for studying the drug susceptibility of 4 H9N2 mutants (M1, M2, M3, and M4). As for the first aim, oseltamivir antiviral activity was monitored upon its delivery into 9-day-old chicken embryo at a concentration of 0.27 mg/100 µl, against 7 doses of the P0 strain, ranging between 1.2 x 10(-5) and 2.0 Hemagglutination (HA) units. Oseltamivir showed its highest efficacy in reduction of viral propagation (95% reduction in HA titer) (P 〈0.05), when the inoculum level contained a minimum HA units of 1.2 x 10(-5). For the second aim of this study, the application of the 1.2 x 10-(5) HA units of the virus in inocula for the evaluation of oseltamivir-antiviral effect against the 4 H9N2 mutants revealed an emergence of a resistant mutant (M1), associated with 2 adjacent point mutations in its neuraminidase (N) amino acid (aa) sequence at positions 46 and 47. The other 3 mutants maintained a variable sensitivity to oseltamivir, resulting in the following reduction in HA titers: M2 (82.9%), M3 (61.5%), and M4 (100.0%). How the point mutations of the neuraminidase sequences affected the susceptibility of H9N2 virus to oseltamivir is still to be determined and deserve further investigations.