β-Carotene Attenuates Angiotensin II-Induced Aortic Aneurysm by Alleviating Macrophage Recruitment in Apoe?/? Mice

Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe^−/− mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (β-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe^−/− mice.     

Risk and Protective Factors for Cigarette Use in Young Adolescents in a School Setting: What Could Be Done Better?

Smoking among Malaysian adolescents remains a public health concern despite concerted efforts in tobacco control. The aims of this study were to examine the prevalence and determinants of current-smoking status in young adolescents. This cross sectional study used the first round of the Malaysian Health and Adolescents Research Team’s prospective cohort study. It was conducted in three States of the Central and Northern regions of Peninsular Malaysia between March and May 2012. The study used the multistage stratified sampling design. A total of 1,342 adolescents of both sexes, aged 12-13 years, were sampled from randomly selected urban and rural national schools. Information on current smoking status and associated factors were collected by a self-administered, pre-tested, validated, structured questionnaire. Seven percent of the samples were current-smokers; the majority (62%) of them started smoking at the age of 11 years or below. The prevalence of current smoking was significantly higher in males (odds ratio [OR] = 2.37; 95% CI: 1.46, 3.84), those who were influenced by smoker friends (OR = 8.35; 95% CI: 4.90, 14.25), who were unaware of the health risks of smoking (OR =1.85; 95% CI: 1.02, 3.36) and who reported a lack of satisfaction about their overall life (OR =3.26; 95% CI: 1.73, 6.12). The study findings provide valuable information to strengthen the existing school-based smoking prevention program through integration of social competence and social influence curricula. The program should empower the young adolescents to refuse tobacco offers, to overcome social influences and to resist peer pressure to avoid starting smoking. Particular focuses to include mental health service to prevent both emotional and behavioural problems are needed.     

Individual and Combined Effects of Arsenic and Lead on Behavioral and Biochemical Changes in Mice

Arsenic (As) toxicity has caused an environmental tragedy affecting millions of people in the world. Little is known about the toxic effects of As on neurobehavioral and biochemical changes in vivo. Along this line of metal toxicity, co-exposure of lead (Pb) could aggravate the situation in the host. The present study was designed to explore the combined effects of As and Pb on behavioral changes like anxiety, spatial memory and learning impairment, and blood indices related to organ dysfunction. Exposure of mice to As (10 mg/kg body weight), Pb (10 mg/kg body weight), and As + Pb via drinking water significantly decreased the time spent exploring the open arms while it increased the time spent in the closed arms compared to control mice in the elevated plus maze. The mean latency time of the control group to find the platform decreased significantly during the learning for 7 days compared to all three treated groups in the Morris water maze test, and the As-exposed group spent significantly less time in the desired quadrant as compared to the control group in the probe trial. Both metals posed an anxiety-like behavior and deficits in spatial memory and learning, and also altered blood indices related to liver and kidney dysfunction, and a combined exposure of these metals inhibited the individual accumulation of As and Pb. Taken together, these data suggest that As has more toxic effects on neurobehavioral and biochemical changes than Pb, and there may be antagonism in the effects and accumulation between these two toxicants.     

Population genetic structure of three major river Populations of rohu,Labeo rohita (Cyprinidae: Cypriniformes) using microsatellite DNA markers

Determining the genetic structure is essential for developing conservation and stock improvement plans. Four dinucleotide microsatellite loci were analysed to reveal population genetic structure of the Indian major carp,Labeo rohita collected from three major rivers namely the Halda, the Jamuna, and the Padma in Bangladesh. The four loci were polymorphic (P ₉₅) in all the populations. The populations varied in the number and frequencies of alleles as well as heterozygosities in the loci analyzed. Population differentiation (F _ST) value between the Halda and the Jamuna population was significant (P<0.05). Relatively high level of gene flow and low level ofF _ST values were found between the Padma and the Jamuna population. The unweighted pair group method with averages (UPGMA) dendrogram based on genetic distance resulted in two clusters: the Halda population was alone in one cluster whereas the Jamuna and the Padma made another cluster. The results revealed a relatively low level of genetic variability in the river populations ofL. rohita in Bangladesh.     

3D QSAR studies,pharmacophore modeling,and virtual screening of diarylpyrazole–benzenesulfonamide derivatives as a template to obtain new inhibitors,using human carbonic anhydrase II as a model protein

A 3D-QSAR modeling was performed on a series of diarylpyrazole-benzenesulfonamide derivatives acting as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The compounds were collected from two datasets with the same scaffold, and utilized as a template for a new pharmacophore model to screen the ZINC database of commercially available derivatives. The datasets were divided into training, test, and validation sets. As the first step, comparative molecular field analysis (CoMFA), CoMFA region focusing and comparative molecular similarity indices analysis (CoMSIA) in parallel with docking studies were applied to a set of 41 human (h) CA II inhibitors. The validity and the prediction capacity of the resulting models were evaluated by leave-one-out (LOO) cross-validation approach. The reliability of the model for the prediction of possibly new CA inhibitors was also tested.     

Investigation of Serum Trace Element,Malondialdehyde and Immune Status in Drug Abuser Patients Undergoing Detoxification

Drug abuser patients (n = 104), age ranging from 19 to 42 years, were randomly recruited to investigate the serum levels of trace elements (Cu, Zn, Fe, and Mg), malondialdehyde (MDA), and immunoglobulin (IgG, IgA, and IgM) before and after clinical intervention. Control group also included 104 healthy individuals. Blood samples were analyzed for determining trace elements, MDA, and immunoglobulin using atomic absorption spectroscopy, Ultraviolet-Visible (UV-VIS) spectroscopy, and turbidimetry method, respectively. For serum level of Zn and Fe, the differences between the groups (before intervention, after intervention, and control) were not significant (p > 0.05). However, significant differences were found in serum copper levels between control group, drug abuser patients, and before and after intervention (p < 0.05). The concentration of Mg was found to be significantly higher (p = 0.007) in drug abuser patients than the controls, and after intervention, the level was restored to control value. A displacement of elemental homeostasis was observed in drug abuser patients compared to control, and it was improved after intervention. An increase in serum concentration of MDA was found in drug abuser patients compared to control subjects (p > 0.05) but was not statistically significant. After intervention, the concentration was restored to control value (p > 0.05). The serum concentrations of IgA and IgM were found to be significantly higher (p < 0.05) in drug abuser patients before intervention than the controls, and the level tended to be restored to control level after clinical intervention. Serum IgG level was found to be lower in drug abuser patients compared to controls and further declined significantly (p < 0.05) after intervention. These findings may suggest a possible imbalance in the levels of micronutrients, antioxidants, and immunoglobulin in drug abuser patients, which tend to be restored to control values after detoxification.     

Determination of lipoprotein lipase activity using a novel fluorescent lipase assay

A novel, real-time, homogeneous fluorogenic lipoprotein lipase (LPL) assay was developed using a commercially available substrate, the EnzChek lipase substrate, which is solubilized in Zwittergent. The triglyceride analog substrate does not fluoresce, owing to apposition of fluorescent and fluorescent quenching groups at the sn-1 and sn-2 positions, respectively, fluorescence becoming unquenched upon release of the sn-1 BODIPY FA derivative following hydrolysis. Increase in fluorescence intensity at 37°C was proportional to LPL concentration. The assay was more sensitive than a similar assay using 1,2-O-dilauryl-rac-glycero-3-glutaric acid-(6-methylresorufin ester) and was validated in biological samples, including determination of LPL-specific activity in postheparin mouse plasma. The simplicity and reproducibility of the assay make it ideal for in vitro, high-throughput screening for inhibitors and activators of LPL, thus expediting discovery of drugs of potential clinical value.     

Evolutionary Origin of Higher-Order Repeat Structure in Alpha-Satellite DNA of Primate Centromeres

Alpha-satellite DNA (AS) is a main DNA component of primate centromeres, consisting of tandemly repeated units of ∼170 bp. The AS of humans contains sequences organized into higher-order repeat (HOR) structures, in which a block of multiple repeat units forms a larger repeat unit and the larger units are repeated tandemly. The presence of HOR in AS is widely thought to be unique to hominids (family Hominidae; humans and great apes). Recently, we have identified an HOR-containing AS in the siamang, which is a small ape species belonging to the genus Symphalangus in the family Hylobatidae. This result supports the view that HOR in AS is an attribute of hominoids (superfamily Hominoidea) rather than hominids. A single example is, however, not sufficient for discussion of the evolutionary origin of HOR-containing AS. In the present study, we developed an efficient method for detecting signs of large-scale HOR and demonstrated HOR of AS in all the three other genera. Thus, AS organized into HOR occurs widely in hominoids. Our results indicate that (i) HOR-containing AS was present in the last common ancestor of hominoids or (ii) HOR-containing AS emerged independently in most or all basal branches of hominoids. We have also confirmed HOR occurrence in centromeric AS in the Hylobatidae family, which remained unclear in our previous study because of the existence of AS in subtelomeric regions, in addition to centromeres, of siamang chromosomes.