Hepatitis B and Hepatitis C Infections among Female Inmates in a Prison in Jeddah, Saudi Arabia.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major health concerns worldwide. Recent data indicate a decline in prevalence in the Saudi population; however, there are no data on the prevalence in prisoners. This study is the first to investigate the prevalence of viral hepatitis in female inmates in Jeddah, Saudi Arabia. This study aimed to explore the prevalence of HBV and HCV infections and to assess the knowledge and attitudes related to these infections among inmates. METHODS: Inmates were interviewed using a pre-designed questionnaire, and their blood samples were tested for HBV and HCV infections using serology, PCR, and phylogenetic analysis. RESULTS: The overall prevalence of HBV infection in the study population was 4.4%. The age group > 25 years was predominantly affected; 11.1% of the infected cases were Saudi nationals, and 88.9% were non-Saudis. The prevalence of HCV infection was 2.4%. Among the studied variables, age and previous employment were significantly associated with positive HBV PCR, while conviction, knowledge about protection from sexually transmitted infections (STIs), knowledge about condom use for protection against STIs, and condom use for protection against STIs were significantly associated with HCV infection. CONCLUSIONS: This study shows higher HBV and HCV prevalence in the female prisoners in Briman prison compared to the general population. Uneducated prisoners, over 25 years old, and convicted of prostitution are more associated with both HBV and HCV infection. Future preventive plans should include screening new prisoners with these risk factors for HBV and HCV at the time of entry.

An "epitomic" analysis of the specificity of conformation-dependent, anti-Aß amyloid monoclonal antibodies.

Antibodies against Aß amyloid are indispensable research tools and potential therapeutics for Alzheimer's disease. They display several unusual properties, such as specificity for aggregated forms of the peptide, the ability to distinguish polymorphic aggregate structures, and the ability to recognize generic aggregation-related epitopes formed by unrelated amyloid sequences. Understanding the mechanisms underlying these unusual properties and the structures of their corresponding epitopes is crucial for the understanding why antibodies display different therapeutic activities and for the development of more effective therapeutic agents. Here we employed a novel "epitomic" approach to map the fine structure of the epitopes of 28 monoclonal antibodies against amyloid-beta using immunoselection of random sequences from a phage display library, deep sequencing, and pattern analysis to define the critical sequence elements recognized by the antibodies. Although most of the antibodies map to major linear epitopes in the amino terminal 1 to 14 residues of Aß, the antibodies display differences in the target sequence residues that are critical for binding and in their individual preferences for nontarget residues, indicating that the antibodies bind to alternative conformations of the sequence by different mechanisms. Epitomic analysis also identifies discontinuous, nonoverlapping sequence Aß segments that may constitute the conformational epitopes that underlie the aggregation specificity of antibodies. Aggregation-specific antibodies recognize sequences that display a significantly higher predicted propensity for forming amyloid than antibodies that recognize the monomer, indicating that the ability of random sequences to aggregate into amyloid is a critical element of their binding mechanism.

Serum concentrations of perfluoroalkyl substances and their association with osteoporosis in a population in Jeddah, Saudi Arabia.

Human exposure to poly- and perfluoroalkyl substances (PFASs) is widespread and has received considerable attention in recent years due to their link with adverse health outcomes, including bone health. Nevertheless, no earlier studies have reported serum PFAS concentrations, and their association with incident osteoporosis in populations in Saudi Arabia. In this clinical case-control study, serum samples collected from 208 individuals (n = 100 cases and n = 108 controls) aged 40-89 years from Jeddah, Saudi Arabia, were analyzed for 17 PFASs. Unconditional logistic regression was used to calculate odds ratios (ORs) for association between serum PFAS concentrations and osteoporosis, stratified by gender, age, serum calcium and vitamin D, previous history of fractures and thyroid disorders. Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluoro-n-pentanoic acid (PFPeA) and perfluoroundecanoic acid (PFUnDA) were detected in >80% of serum samples analyzed. PFOS (overall median concentration: 5.08 ng/mL), PFHxS (1.49 ng/mL), PFOA (1.33 ng/mL) and PFNA (0.55 ng/mL) accounted for 94% and 80% of the total serum PFASs concentrations in cases and controls, respectively. Serum PFOA, PFNA and PFUnDA concentrations increased with age in Saudi women. Results from the crude models showed that individuals in the 2nd, 3rd and 4th quartiles of serum PFAS concentrations had 2.3-96-fold increase in odds of diagnosis for osteoporosis compared with those in the 1st quartile (rank order: PFUnDA > PFOA > PFNA > PFOS > PFHxS). Our results suggest that exposure to PFOA, PFOS, PFNA, PFHxS and PFUnDA was associated with osteoporosis in this sample of adult Saudi population.

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.

Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.

Gingerenone A Attenuates Monocyte-Endothelial Adhesion via Suppression of I Kappa B Kinase Phosphorylation.

During the early stages of atherosclerosis, monocytes bind and migrate into the endothelial layer, promoting inflammation within the aorta. In order to prevent the development of atherosclerosis, it is critical to inhibit such inflammation. The therapeutic effects of ginger have been investigated in several models of cardiovascular disease. However, although a number of previous studies have focused on specific compounds, the mechanisms of action responsible remain unclear. Here, we investigated five major compounds present in ginger, and observed that gingerenone A exhibited the strongest inhibitory effects against tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS) induced monocyte-endothelial adhesion. Furthermore, gingerenone A significantly suppressed the expression of TNF-α and LPS-induced vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 2 (CCL2), key mediators of the interaction between monocytes, and endothelial cells. Transactivation of nuclear factor-κB (NF-κB), which is a key transcription factor of VCAM-1 and CCL2, was induced by TNF-α and LPS, and inhibited by treatment of gingerenone A. Gingerenone A also inhibited the phosphorylation of NF-κB inhibitor (IκB) α and IκB Kinase. Taken together, these results demonstrate that gingerenone A attenuates TNF-α and LPS-induced monocyte adhesion and the expression of adhesion factors in endothelial cells via the suppression of NF-κB signaling. J. Cell. Biochem. 119: 260-268, 2018. © 2017 Wiley Periodicals, Inc.

Synthetic strigolactone analogues reveal anti-cancer activities on hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

Resin-based dental sealants as a source of human exposure to bisphenol analogues, bisphenol A diglycidyl ether, and its derivatives.

Although studies have examined leaching of bisphenol A (BPA) from dental sealants into saliva, occurrence of BPA, bisphenol A diglycidyl ether (BADGE), and their derivatives in dental sealants themselves has not been investigated. In this study, concentrations of eight bisphenol analogues (BPs), BADGE and its derivatives (BADGEs), including BADGE‧H2O, BADGE‧HCl, BADGE‧2H2O, BADGE‧2HCl, and BADGE‧H2O‧HCl, were determined in 70 dental sealants collected from the U.S. market. Of the 70 dental sealants analyzed, 65 contained at least one of the target chemicals measured. BADGE‧2H2O was the most abundant compound, found at concentrations of up to 1780µg/g. The geometric mean (GM) concentration of total BADGEs was 47.8µg/g, which was two to three orders of magnitude higher than that of total BPs (GM: 539ng/g). BPA was found in 46% of the sealants and BADGEs was found in 87% of the sealants analyzed. Majority of the dental sealants analyzed in this study were manufactured in the United States and Korea; no significant differences were observed in the concentrations of BPs and BADGEs between the two countries. An exposure assessment was made based on the concentrations of BPs and BADGEs measured in sealants and their application rates in dentistry. The worst-case exposure scenario with the highest measured concentration of total BPs and BADGEs and application on 8 teeth at 8mg each yielded an estimated daily intake (EDI) of 1670 and 5850ng/kg·bw/day for adults and children, respectively. Although the EDI is below the specific migration limit set by the European Food Safety Authority, dental sealants are a source of exposure to BPs and BADGEs, especially in children.

Urinary concentrations of environmental phenols and their association with type 2 diabetes in a population in Jeddah, Saudi Arabia.

A few epidemiologic studies suggest that exposure to bisphenol A (BPA) is associated with type 2 diabetes mellitus (T2DM). However, little is known about association between other phenolic endocrine disrupting chemicals (EDCs) and T2DM. In this case-control study, we measured urinary concentrations of 23 phenolic EDCs in 101 individuals from Jeddah, Saudi Arabia, to examine the association of parabens, antimicrobials, bisphenols, benzophenones and bisphenol A diglycidyl ethers with T2DM. Urine samples were collected from 54 T2DM cases and 47 non-diabetic individuals (controls), aged 28-68 years old, during 2015-2016. Unconditional logistic regression was performed to estimate odd ratios (ORs) for the association between diabetes and EDC exposures after adjusting for confounders including age, gender, nationality, smoking status and occupation. Age from 40 to 59 years (OR 5.56, 95% CI 2.20-14.0) and smoking status (OR 2.92, 95% CI 1.25-6.79) showed significant positive associations with T2DM. After adjusting for potential confounders, we found that T2DM cases had high urinary levels of parabens (i.e., methyl- (MeP), ethyl- (EtP), propyl- (PrP) and 4-hydroxy benzoic acid (4-HB)), bisphenols (i.e., bisphenols A (BPA) and F (BPF)), and benzophenone (i.e., 4-hydroxybenzophenone (4-OH-BP)) relative to the controls. Individuals in the 4th quartile for urinary concentrations of MeP, EtP, PrP, 4-HB and BPF and in the 3rd quartile for BPA and 4-OH-BP showed over a 6-fold increase in the odds of having diabetes compared with those in the first quartile. Overall, our study shows that urinary levels of multiple phenolic EDCs were associated with increased risk for diabetes. Further prospective studies are required to verify these associations.

Urinary levels of triclosan and triclocarban in several Asian countries, Greece and the USA: Association with oxidative stress.

Triclosan (TCS) and Triclocarban (TCC) are widely used as antimicrobial preservatives in personal care products (PCPs). Because of their potential for endocrine disrupting effects, human exposure to these chemicals is a concern. Biomonitoring studies of human exposure to TCS and TCC have shown widespread exposure of populations in western European countries and the USA. However, exposure to TCC and TCS by populations in Asian countries is less well known. In this study, concentrations of TCS and TCC were determined in human urine collected from seven Asian countries (China, India, Korea, Kuwait, Japan, Saudi Arabia, and Vietnam), and Greece and the USA. A total of 430 urine samples were analyzed for TCS and TCC, of which 355 (83%) and 82 (19%), respectively, contained measurable levels of these chemicals. The overall geometric mean [GM] concentrations of TCS and TCC, were 1.36 and 0.03ng/mL, respectively. The highest mean concentration of TCS was found in urine from China (100ng/mL) and the lowest concentration was found in urine from Vietnam (2.34ng/mL). We also analyzed urinary 8-OHdG, a marker of oxidative stress, to elucidate the association with TCS and TCC levels for samples from Saudi Arabia (n=130) and a positive correlation between Ln-transformed TCC levels and 8-OHdG was found, although this was not statistically significant. This is the first study to report urinary levels of TCS and TCC in several Asian countries, especially for Vietnam, Kuwait, and Japan.

Chemical screening and development of novel gibberellin mimics.

Gibberellin (GA) plays versatile roles in the regulation of plant growth and development and therefore is widely used as a regulator in agriculture. We performed a chemical library screening and identified a chemical, named 67D, as a stimulator of seed germination that was suppressed by paclobutrazol (PAC), a GA biosynthesis inhibitor. In vitro binding assays indicated that 67D binds to the GID1 receptor. Further studies on the structure-activity relationship identified a chemical, named chemical 6, that strongly promoted seed germination suppressed by PAC. Chemical 6 was further confirmed to promote the degradation of RGA (for repressor of ga1-3), a DELLA protein, and suppress the expression levels of GA3ox1 in the same manner as GA does. 67D and its analogs are supposed to be agonists of GID1 and are expected to be utilized in agriculture and basic research as an alternative to GA.

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.

Diversity, Physiochemical and Phylogenetic Analyses of Bacteria Isolated from Various Drinking Water Sources.

OBJECTIVE: To evaluate the indigenous bacterial strains of drinking water from the most commercial water types including bottled and filtered water that are currently used in Saudi Arabia. METHODS: Thirty randomly selected commercial brands of bottled water were purchased from Saudi local markets. Moreover, samples from tap water and filtered water were collected in sterilized glass bottles and stored at 4°C. Biochemical analyses including pH, temperature, lactose fermentation test (LAC), indole test (IND), methyl red test (MR), Voges-Proskauer test (VP), urease test (URE), catalase test (CAT), aerobic and anaerobic test (Ae/An) were measured. Molecular identification and comparative sequence analyses were done by full length 16S rRNA gene sequences using gene bank databases and phylogenetic trees were constructed to see the closely related similarity index between bacterial strains. RESULTS: Among 30 water samples tested, 18 were found positive for bacterial growth. Molecular identification of four selected bacterial strains indicated the alarming presence of pathogenic bacteria Bacillus spp. in most common commercial types of drinking water used in Saudi Arabia. CONCLUSION: The lack of awareness about good sanitation, poor personal hygienic practices and failure of safe water management and supply are the important factors for poor drinking water quality in these sources, need to be addressed.

Synthetic Phenolic Antioxidants and Their Metabolites in Indoor Dust from Homes and Microenvironments.

Synthetic phenolic antioxidants (SPAs), including 2,6-di-tert-butyl-4-hydroxytoluene (BHT), are extensively used in food, cosmetic and plastic industries. Nevertheless, limited information is available on human exposures, other than the dietary sources, to SPAs. In this study, occurrence of 9 SPAs and their metabolites/degradation products was determined in 339 indoor dust collected from 12 countries. BHT was found in 99.5% of indoor dust samples from homes and microenvironments at concentrations that ranged from < LOQ to 118 µg/g and 0.10 to 3460 µg/g, respectively. This is the first study to measure BHT metabolites in house dust (0.01-35.1 µg/g) and their concentrations accounted for 9.2-58% of the sum concentrations (∑SPAs). 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO), 2,6-di-tert-butyl-4-(hydroxymethyl)phenol (BHT-OH), 2,6-di-tert-butyl-1,4-benzoquinone (BHT-Q) were the major derivatives of BHT found in dust samples. The concentrations of gallic acid esters (gallates) in dust from homes and microenvironments ranged from < LOQ to 18.2 and < LOQ to 684 µg/g, respectively. The concentrations and profiles of SPAs varied among countries and microenvironments. Significantly elevated concentrations of SPAs were found in dust from an e-waste workshop (1530 µg/g). The estimated daily intake (EDI) of BHT via house dust ingestion ranged from 0.40 to 222 ng/kg/d (95th percentile).

Urinary biomarkers of exposure to 57 xenobiotics and its association with oxidative stress in a population in Jeddah, Saudi Arabia.

Oxidative stress arises from excessive free radicals in the body and is a trigger for numerous diseases, such as cancer and atherosclerosis. Elevated exposure to environmental chemicals can contribute to oxidative stress. The association between exposure to xenobiotics and oxidative stress, however, has rarely been studied. In this study, urinary concentrations of 57 xenobiotics (antimicrobials, parabens, bisphenols, benzophenones, and phthalates metabolites) were determined in a population from Jeddah, Saudi Arabia, to delineate association with the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8OHDG). We collected 130 urine samples and analyzed for 57 xenobiotics using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods. The association between unadjusted and creatinine- or specific gravity-adjusted concentrations of xenobiotics and 8OHDG was examined by Pearson correlations and multiple regression analysis. High concentrations of mCPP (a metabolite of di-n-octyl phthalate; DnOP) and mCMHP (a metabolite of diethylhexyl phthalate; DEHP) were found in urine. In addition, the concentrations of bisphenol S (BPS) were higher than those of bisphenol A (BPA). The concentrations of metabolites of DEHP, phthalic acid, BPA, BPS, and methyl-protocatechuic acid were significantly associated with 8OHDG. This is the first biomonitoring study to report exposure of the Saudi population to a wide range of environmental chemicals and provides evidence that environmental chemical exposures contribute to oxidative stress.

Genome wide analysis of novel copy number variations duplications/deletions of different epileptic patients in Saudi Arabia.

BACKGROUND: Epilepsy is genetically complex neurological disorder affecting millions of people of different age groups varying in its type and severity. Copy number variants (CNVs) are key players in the genetic etiology of numerous neurodevelopmental disorders and prior findings also revealed that chromosomal aberrations are more susceptible against the pathogenesis of epilepsy. Novel technologies, such as array comparative genomic hybridization (array-CGH), may help to uncover the pathogenic CNVs in patients with epilepsy. RESULTS: This study was carried out by high density whole genome array-CGH analysis with blood DNA samples from a cohort of 22 epilepsy patients to search for CNVs associated with epilepsy. Pathogenic rearrangements which include 6p12.1 microduplications in 5 patients covering a total region of 99.9kb and 7q32.3 microdeletions in 3 patients covering a total region of 63.9kb were detected. Two genes BMP5 and PODXL were located in the predicted duplicated and deleted regions respectively. Furthermore, these CNV findings were confirmed by qPCR. CONCLUSION: We have described, for the first time, several novel CNVs/genes implicated in epilepsy in the Saudi population. These findings enable us to better describe the genetic variations in epilepsy, and could provide a foundation for understanding the critical regions of the genome which might be involved in the development of epilepsy.

Next generation sequencing of acute myeloid leukemia: influencing prognosis.

Acute myeloid leukemia (AML) is a clonal disorder of the blood forming cells characterized by accumulation of immature blast cells in the bone marrow and peripheral blood. Being a heterogeneous disease, AML has been the subject of numerous studies that focus on unraveling the clinical, cellular and molecular variations with the aim to better understand and treat the disease. Cytogenetic-risk stratification of AML is well established and commonly used by clinicians in therapeutic management of cases with chromosomal abnormalities. Successive inclusion of novel molecular abnormalities has substantially modified the classification and understanding of AML in the past decade. With the advent of next generation sequencing (NGS) technologies the discovery of novel molecular abnormalities has accelerated. NGS has been successfully used in several studies and has provided an unprecedented overview of molecular aberrations as well as the underlying clonal evolution in AML. The extended spectrum of abnormalities discovered by NGS is currently under extensive validation for their prognostic and therapeutic values. In this review we highlight the recent advances in the understanding of AML in the NGS era.

pecific nutrient combination effects on tax, NF- κB and MMP-9 in human T-cell lymphotropic virus -1 positive malignant T-lymphocytes.

BACKGROUND: Adult T-cell Leukemia (ATL) is a disease with no known cure. The disease manifests itself as an aggressive proliferation of CD4+ cells with the human T-cell Lymphotropic virus type 1 (HTLV-1). The leukemogenesis of the virus is mainly attributed to the viral oncoprotein. Tax activates the Nuclear Factor kappa B (NF-κB) which stimulates the activity and expression of the matrix metalloproteinase-9 (MMP-9). The objective of this study was to investigate the efficacy of a specific nutrient synergy (SNS) on proliferation, Tax expression, NF-κB levels as well as on MMP-9 activity and expression both at the transcriptional and translational levels in two HTLV-1 positive cell lines, HuT-102 and C91-PL at 48h and 96h of incubation. Cytotoxicity of Epigallocatechin-3-gallate (EGCG) was assayed using CytoTox 96 Non-radioactive and proliferation was measured using Cell Titer96TM Nonradioactive Cell Proliferation kit (MTT- based assay). Enzyme linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA) were used to assess the effect of SNS on NF-κB mobility. Zymography was used to determine the effects of SNS on the activity and secretion of MMP-9. The expression of MMP-9 was done using RT-PCR at the translational level and Immunoblotting at the transcriptional level. RESULTS: A significant inhibition of proliferation was seen in both cell lines starting at a concentration of 200µg/ml and in a dose dependent manner. SNS induced a dose dependent decrease in Tax expression, which was paralleled by a down-regulation of the nuclearization of NF-κB. This culminated in the inhibition of the activity of MMP-9 and their expression both at the transcriptional and translational levels. CONCLUSIONS: The results of this study indicate that a specific nutrient synergy targeted multiple levels pertinent to the progression of ATL. Its activity was mediated through the NF-κB pathway, and hence has the potential to be integrated in the treatment of this disease as a natural potent anticancer agent.

The relative validity and repeatability of an FFQ for estimating intake of zinc and its absorption modifiers in young and older Saudi adults.

OBJECTIVE: To assess the relative validity and repeatability of a sixty-four-item FFQ for estimating dietary intake of Zn and its absorption modifiers in Saudi adults. In addition, we used the FFQ to investigate the effect of age and gender on these intakes. DESIGN: To assess validity, all participants completed the FFQ (FFQ1) and a 3 d food record. After 1 month, the FFQ was administered for a second time (FFQ2) to assess repeatability. SETTING: Jeddah, Saudi Arabia. SUBJECTS: One hundred males and females aged 20-30 years and 60-70 years participated. RESULTS: Mean intakes of Zn and protein from FFQ1 were significantly higher than those from the food record while there were no detectable differences between tools for measurement of phytic acid intake. Estimated intakes of Zn, protein and phytate by both approaches were strongly correlated (P<0·001). Bland-Altman analysis showed for protein that the difference in intake as measured by the two methods was similar across the range of intakes while for Zn and phytic acid, the difference increased with increasing mean intake. Zn and protein intakes from FFQ1 and FFQ2 were highly correlated (r>0·68, P<0·001) but were significantly lower at the second measurement (FFQ2). Older adults consumed less Zn and protein compared with young adults. Intakes of all dietary components were lower in females than in males. CONCLUSIONS: The FFQ developed and tested in the current study demonstrated reasonable relative validity and high repeatability and was capable of detecting differences in intakes between age and gender groups.

Phytochemical analysis of Convolvulus hystrix Vahl and its biological effects in rats.

"Convolvulus hystrix Vahl" is a plant that has been known to Ancient Egyptians and to Arabs and its root was used traditionally as a purgative. Our attention was directed to the root bark as we observed that the largest part of the plant is deeply impeded underground. The work plan involved testing experimental animals for the influence of aqueous root bark extract on carbohydrate, fat and protein metabolisms as reflected on the growth and relevant laboratory metabolic assessment parameters. Proximate analysis showed high percentages of moisture (85%) and total lipids (7.2%) and surprising amounts of elements such as barium, strontium, rhodium and tellurium (1.7 mg, 3.1 mg, 8 mg and 9.1 mg/g ash, respectively). Random serum glucose value showed a significant decrease in the treated female group (p < 0.05). Serum total proteins of treated female group were found to be increased significantly (p < 0.001), while it was found to be decreased in the relevant treated male group (p < 0.01), together with a significant decrease in blood urea nitrogen (p < 0.05), with a significant increase in the serum creatinine (p < 0.05). Concerning serum fat metabolic parameters, a significant decrease in the serum triglycerides and high-density lipoproteins (p < 0.01 and p < 0.01, respectively) were found. We concluded that the presence of huge amount of polyphenolics such as tannins is responsible for the overall results documented as growth retarding and antinutritional factors. The results were motivating and pointed out to the possible opening of vast areas of research in the field of natural products. We recommend a series of biochemical and pharmacological studies concerning different parts of the plant as well.