Khalid Omer Abualnaja

A comparative assessment of human exposure to tetrabromobisphenol A and eight bisphenols including bisphenol A via indoor dust ingestion in twelve countries.

Tetrabromobisphenol A (TBBPA) and eight bisphenol analogues (BPs) including bisphenol A (BPA) were determined in 388 indoor (including homes and microenvironments) dust samples collected from 12 countries (China, Colombia, Greece, India, Japan, Kuwait, Pakistan, Romania, Saudi Arabia, South Korea, U.S., and Vietnam). The concentrations of TBBPA and sum of eight bisphenols (ƩBPs) in dust samples ranged from <1 to 3600 and from 13 to 110,000 ng/g, respectively. The highest TBBPA concentrations in house dust were found in samples from Japan (median: 140 ng/g), followed by South Korea (84 ng/g) and China (23 ng/g). The highest ∑BPs concentrations were found in Greece (median: 3900 ng/g), Japan (2600 ng/g) and the U.S. (2200 ng/g). Significant variations in BPA concentrations were found in dust samples collected from various microenvironments in offices and homes. Concentrations of TBBPA in house dust were significantly correlated with BPA and ∑BPs. Among the nine target chemicals analyzed, BPA was the predominant compound in dust from all countries. The proportion of TBBPA in sum concentrations of nine phenolic compounds analyzed in this study was the highest in dust samples from China (27%) and the lowest in Greece (0.41%). The median estimated daily intake (EDI) of ∑BPs through dust ingestion was the highest in Greece (1.6-17 ng/kg bw/day), Japan (1.3-16) and the U.S. (0.89-9.6) for various age groups. Nevertheless, in comparison with the reported BPA exposure doses through diet, dust ingestion accounted for less than 10% of the total exposure doses in China and the U.S. For TBBPA, the EDI for infants and toddlers ranged from 0.01 to 3.4 ng/kg bw/day, and dust ingestion is an important pathway for exposure accounting for 3.8-35% (median) of exposure doses in China.

Occurrence of perchlorate in indoor dust from the United States and eleven other countries: Implications for human exposure

Perchlorate is a widespread environmental contaminant and potent thyroid hormone disrupting compound. Despite this, very little is known with regard to the occurrence of this compound in indoor dust and the exposure of humans to perchlorate through dust ingestion. In this study, 366 indoor dust samples were collected from 12 countries, the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China, during 2010-2014. Dust samples were extracted by 1% (v/v) methylamine in water. Analyte separation was achieved by an ion exchange (AS-21) column and analysis was performed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The overall concentrations of perchlorate in dust were in the range of 0.02-104μg/g (geometric mean: 0.41μg/g). The indoor dust samples from China contained the highest concentrations (geometric mean: 5.38μg/g). No remarkable differences in perchlorate concentrations in dust were found among various microenvironments (i.e., car, home, office, and laboratory). The estimated median daily intake (EDI) of perchlorate for toddlers through dust ingestion in the USA, Colombia, Greece, Romania, Japan, Korea, Pakistan, Kuwait, Saudi Arabia, India, Vietnam, and China was 1.89, 0.37, 1.71, 0.74, 4.90, 7.20, 0.60, 0.80, 1.55, 0.70, 2.15, and 21.3ng/kgbodyweight (bw)/day, respectively. Although high concentrations of perchlorate were measured in some dust samples, the contribution of dust to total perchlorate intake was <5% of the total perchlorate intake in humans. This is the first multinational survey on the occurrence of perchlorate in indoor dust.

A survey of cyclic and linear siloxanes in indoor dust and their implications for human exposures in twelve countries.

Siloxanes are used widely in a variety of consumer products, including cosmetics, personal care products, medical and electrical devices, cookware, and building materials. Nevertheless, little is known on the occurrence of siloxanes in indoor dust. In this survey, five cyclic (D3-D7) and 11 linear (L4-L14) siloxanes were determined in 310 indoor dust samples collected from 12 countries. Dust samples collected from Greece contained the highest concentrations of total cyclic siloxanes (TCSi), ranging from 118 to 25,100ng/g (median: 1380), and total linear siloxanes (TLSi), ranging from 129 to 4990ng/g (median: 772). The median total siloxane (TSi) concentrations in dust samples from 12 countries were in the following decreasing order: Greece (2970ng/g), Kuwait (2400), South Korea (1810), Japan (1500), the USA (1220), China (1070), Romania (538), Colombia (230), Vietnam (206), Saudi Arabia (132), India (116), and Pakistan (68.3). TLSi concentrations as high as 42,800ng/g (Kuwait) and TCSi concentrations as high as 25,000ng/g (Greece) were found in indoor dust samples. Among the 16 siloxanes determined, decamethylcyclopentasiloxane (D5) was found at the highest concentration in dust samples from all countries, except for Japan and South Korea, with a predominance of L11; Kuwait, with L10; and Pakistan and Romania, with L12. The composition profiles of 16 siloxanes in dust samples varied by country. TCSi accounted for a major proportion of TSi concentrations in dust collected from Colombia (90%), India (80%) and Saudi Arabia (70%), whereas TLSi predominated in samples collected from Japan (89%), Kuwait (85%), and South Korea (78%). Based on the measured median TSi concentrations in indoor dust, we estimated human exposure doses through indoor dust ingestion for various age groups. The exposure doses ranged from 0.27 to 11.9ng/kg-bw/d for toddlers and 0.06 to 2.48ng/kg-bw/d for adults.

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).

Gingerenone A Attenuates Monocyte-Endothelial Adhesion via Suppression of I Kappa B Kinase Phosphorylation: GINGERENONE A ATTENUATES MONOCYTE -ENDOTHELIAL ADHESION

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.

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.

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.

Synthesis, screening and pro-apoptotic activity of novel acyl spermidine derivatives on human cancer cell lines

The polyamines putrescine, spermidine, and spermine are polycationic, alkyl polyamines which play a significant role in eukaryotic cell proliferation. The polyamine metabolism and function are dysregulated in tumor cells making them an attractive therapeutic target by employing polyamine analogs. These analogs have a high degree of similarity with the structure of polyamines but not with their function. Multidrug resistance is a major factor in the failure of many chemotherapeutic drugs which necessitates further research and exploration of better novel alternatives. In the present study, Twenty-six novel acylspermidine derivatives were synthesized and evaluated for their anti-proliferative and pro-apoptotic activities on human breast cancer cells and T-lymphoblastic leukemia cells. The cell proliferation and apoptosis assays using WST-1 and annexin-V/7AAD staining respectively suggest that Compound 1 (C19H41N3O2), Compound 7(C25H51N3O2) and Compound 8 (C29H59N3O) significantly reduced cancer cell viability in a dose- and time-dependent manner. Interestingly, compounds 7, 8 and 9 had slight or no effect on cell proliferation of non-cancerous cells. These studies speculate that these novel acylspermidine derivatives could be promising candidates in designing an anti-proliferative drug, targeting both solid and blood cancer cells.

Standardization of a Protocol for Quantitative Evaluation of Anti-AerosolizedInfluenza Virus Activity by Vapors of a Chemically-Characterized Essential OilBlend

The aim of this research is to standardize the conditions of a constructed impinger, enabling to evaluate quantitatively the anti-aerosolized H9N2 avian influenza virus (AIV) activity by vapors of a chemically-characterized essential oil blend. The standardization resulted in 100% recovery of the aerosolized H9N2 virus when the impinger’s conditions were set at aerosolized viral particles count of 1.2 × 106/c.c. of Tryptose Phosphate Broth, temperature of 35°C, average micelle diameter of 44.3 μm, negative pressure of 6 mbar, air-suspension time of H9N2 virus of 1.5 min, collection chamber and its transport medium volumes of 250 cc and 25 cc, respectively. The adoption of the above standardized conditions, with an inclusion of vaporized essential oil (EO) at 1.0 × 10-4 μl EO/μl volume of the pulverization chamber, and contact times of 0.5-1.5 min with the H9N2 virus, resulted in 84.6% reduction in viral titer at 1.5 min contact time, compared to the control virus, deprived from contact with vaporized EO (P<0.05). This new finding will help in future investigations related to application of safe essential oils in reduction of air-suspended influenza virus in closed systems harboring domestic animals and human populations.

Spermidine, a polyamine, confers resistance to rice blast

Polyamines are involved not only in fundamental cellular processes such as growth, differentiation, and morphogenesis, but also in various environmental stresses. We demonstrated that spermidine, a polyamine, confers resistance to rice blast accompanied by the up-regulation of marker genes for the salicylic acid-mediated signaling pathway PR1b and PBZ1 and of phytoalexin biosynthesis genes CPS4 and NOMT. This is the first report about the involvement of spermidine in rice disease resistance.