Screening of peptide probe binding to particulate matter with a high metal content

Particulate matter (PM) is becoming an increasing health concern and there is a need to develop detection methods to keep its harmful effects in check. Generation of reactive oxygen species (ROS) by PM is often associated with metal compounds, hence our aim is to screen for a peptide probe towards improved collection and the detection of PM having a high metal content. Peptides are putative recognition molecules due to their versatility and ease of modification to enhance their binding selectivities. PM binding peptides were screened using the peptide array and different binding behaviors in terms of different spot colors (yellow, mixed and gray), indicating the different composition of bound PMs, were observed. The strongest binding peptides were identified as follows: NHVNTNYYPTLH (gray), NGYYPHSHSYHQ (mixed) and HHLHWPHHHSYT (yellow), with relative binding ratios of 125%, 144% and 136%, in comparison with WQDFGAVRSTRS, a peptide screened from a phage display in our previous study. Inductively coupled plasma mass spectrometry (ICPMS) analyses revealed that Co, Ni and Zn content in the PM bound to the HHLHWPHHHSYT peptide spot were respectively 12.5, 15.8 and 7.8 times that of the PM bound to no peptide spot, suggesting this peptide probe is applicable to collect PM with a high metal content.

Using peptide array, peptides binding to particulate matter with high metal content were screened and characterized by focusing on the different spot colors (yellow, mixed and gray).     

Glucocorticoid and mineralocorticoid cross-talk with progesterone receptor to induce focal adhesion and growth inhibition in breast cancer cells

Progesterone receptor (PR), glucocorticoid receptor, and mineralocorticoid receptor belong to a subfamily of nuclear receptor superfamily with similar sequence and structural characteristics. Many reports have documented glucocorticoid-like effects of progesterone in various tissues. This study addresses the issue of cross-talk between corticosteroids and PR using PR-transfected MDA-MB-231 cells ABC28 and vector-transfected control cells CTC15. At physiological concentrations, dexamethasone, cortisol, and aldosterone mimic the effects of progesterone by inducing significant growth inhibition, cell spreading, and focal adhesions in PR-positive ABC28 cells. These hormones also induce progesterone-like effects in increasing the expression of p21(CIP1/WAF1) protein and decreasing the level of phospho-p42/p44 mAPK. Two lines of evidence suggest that these effects are mediated by cross-talk with PR. First, these compounds do not exhibit the same progesterone-like effects in PR-negative CTC15 cells. Second, PR blocker ZK98299 abolishes their effect on cell spreading and focal adhesion in ABC28 cells. The cross-talk is corticosteroid specific because estradiol and thyroid hormone triiodothyronine have no effect on PR-transfected cells ABC28. It is also interesting to note that dexamethasone induces a small but detectable increase of focal adhesions and limited growth stimulation in vector-transfected cells CTC15. In contrast, progesterone exhibits no detectable effect on CTC15 cells. This study provides evidence that glucocorticoid and mineralocorticoid cross-talk with PR to produce progesterone-like effects in breast cancer cells. Glucocorticoid receptor and PR share some overlapping activity in mediating focal adhesion but not in regulating cell proliferation.     

Candesartan Normalizes Changes in Retinal Blood Flow and p22phox in the Diabetic Rat Retina

Angiotensin II has been implicated in the progression of diabetic retinopathy, which is characterized by altered microvasculature, oxidative stress, and neuronal dysfunction. The signaling induced by angiotensin II can occur not only via receptor-mediated calcium release that causes vascular constriction, but also through a pathway whereby angiotensin II activates NADPH oxidase to elicit the formation of reactive oxygen species (ROS). In the current study, we administered the angiotensin II receptor antagonist candesartan (or vehicle, in untreated animals) in a rat model of type 1 diabetes in which hyperglycemia was induced by injection of streptozotocin (STZ). Eight weeks after the STZ injection, untreated diabetic rats were found to have a significant increase in tissue levels of angiotensin converting enzyme (ACE; p < 0.05) compared to non-diabetic controls, a 33% decrease in retinal blood flow rate (p < 0.001), and a dramatic increase in p22phox (a subunit of the NADPH oxidase). The decrease in retinal blood flow, and the increases in retinal ACE and p22phox in the diabetic rats, were all significantly attenuated (p < 0.05) by the administration of candesartan in drinking water within one week. Neither STZ nor candesartan induced any changes in tissue levels of superoxide dismutase (SOD-1), 4-hydroxynonenal (4-HNE), or nitrotyrosine. We conclude that one additional benefit of candesartan (and other angiotensin II antagonists) may be to normalize retinal blood flow, which may have clinical benefits in diabetic retinopathy.     

Fitness levels of middle aged martial art practitioners

OBJECTIVES: To quantify and compare fitness levels of middle aged practitioners of soo bahk do (SBD; a Korean martial art similar to karate) with those of sedentary subjects. METHODS: Eighteen volunteers, 14 men and four women (aged 40-60 years), participated. Nine sedentary subjects (mean age 46.7 years) and nine SBD practitioners (mean age 46.8 years) were matched for sex and age. All subjects participated in a one day battery of fitness tests. The following dependent variables were tested: body composition, balance, flexibility, quadriceps strength, grip strength, muscle endurance, and aerobic capacity. RESULTS: All dependent variables were analysed using paired t tests. Body composition (% body fat) for the SBD group was 18.9% v 30.8% for the sedentary group (p = 0.004). The SBD group was able to balance for 61.8 seconds v 26.2 seconds for the sedentary group (p = 0.02). The result for the sit and reach flexibility test was 22.3 cm for the SBD group v 10.4 cm for the sedentary group (p = 0.01). The number of push ups performed in one minute was 47.0 for the SBD group v 18.6 for the sedentary group (p = 0.0003), and the number of sit ups performed was 66.1 for the SBD group and 37.3 for the sedentary group (p = 0.00006). Aerobic capacity was 41.0 ml/kg/min v 31.1 ml/kg/min for the sedentary group (p = 0.04). Quadriceps strength was 99.5% (peak torque/body weight) v 83.0% for the sedentary group (p = 0.02). Only grip strength was not significantly different. CONCLUSIONS: There were significant differences between the groups for most of the physical fitness tests. The SBD practitioners displayed greater aerobic capacity, balance, flexibility, muscle endurance, and strength, and less body fat than the sedentary controls matched for age and sex. SBD can be considered an excellent form of exercise for the promotion of fitness in adults. Health professionals should be aware that there are alternative methods to traditional exercise that can increase the physical fitness and health of the middle aged population.     

Serum lipoprotein(A) profiles in a Singaporean population.

Lipoprotein(a) [Lp(a)] is formed when apolipoprotein(a) is linked to low density lipoprotein (LDL)-cholesterol via a single disulfide bond. It is an independent risk factor for myocardial infarction and raised concentrations are associated with an increased risk of developing coronary artery disease. Singapore has a multi-racial population of 77% Chinese, 14% Malays and 7% Indians. Studies have shown that the Indians have significantly higher standardised mortality ratios (SMR) compared to the Chinese and the Malays. We measured serum Lp(a) concentrations in 803 healthy individuals recruited from the Multiphasic Health Screening Programme, using the Macra Lp(a) sandwich enzyme immunoassay kit (Strategics Diagnostics, Delaware, USA). Lp(a) concentrations were skewed in all three groups. Our population mean was 9.0 mg/dl, with 50th, 75th and 95th percentile values of 10.2, 19.8 and 43.1 mg/dl, respectively, which are lower than values reported from Caucasian populations (15.0, 29.0 and 60.0 mg/dl, respectively). Males had lower Lp(a) concentrations than females (P < 0.05). The Indian group had significantly higher concentrations (median 12.3 mg/dl) compared to their Chinese (median 9.6 mg/dl) and Malay (median 8.4 mg/dl) counterparts (P < 0.05). This could partly account for the higher SMR seen in the Indian population in Singapore. As serum Lp(a) concentrations are method- and population-dependent, we recommend that laboratories determine their own reference ranges by their method to avoid misclassification of the coronary heart disease (CHD) risk of patients.