Abstract Purpose/Background/Objectives Tissue transglutaminase (TG2) is a highly expressed protein especially in endothelial cells. TG2 has several functions including transamidation activity which is important in several processes such as extracellular matrix remodeling [1]. TG2 activity takes place in aortic stiffness regulation and atherosclerotic plaque formation [2]. One of the most effective implementation for atheroprone state and general cardiovascular health is calorie restriction (CR). In addition, lipid accumulation and subsequent metabolic disorders can be regulated by CR and longer lifespan can be achieved [3]. In this study we aimed to determine the effect of different CR application types on liver TG2 levels of female mice fed up to 82 weeks old age. Methods For this purpose, female MMTV-TGF- a mice fed with different dietary regimes; ad libitum (AL), chronic CR (%15 restriction of AL group), intermittent CR (3 weeks AL (ICR-ReFeed)+1 week %60 restriction of AL (ICR-Restricted), between 10-week to 82-week old. Liver tissue was isolated at 10-week old (AL mice as baseline), 50 and 82 weeks. Then, liver tissue samples were homogenized for western blotting. Analysis made by ImageLab software and Glyceraldehyde-3-Phosphate Dehydrogenase used as housekeeping gene. Results TG2 levels were increased in CCR and ICR-R groups, decreased in ICR-RF compared to AL group. In addition, 82-week old AL mice had higher level of TG2 than 10-week old. Conclusion These results may provide future perspectives about TG2 levels depending on feeding protocols and ageing in kidney. TG2 levels in arteries of the same groups will be examined in further studies.
Early diagnosis of cancer clearly reduces morbidity and mortality, and a sizable number of cancers could be prevented at the secondary level with appropriate diagnostic tools. In early detection, biochemical analyses are highly supportive of the cytological and/or histopathological assessments. Among children, cancers probably originate from altered signaling pathways attributable to developmental genetic disorders. In adults, generally preventable risk factors, e.g., cigarette smoking, infections, unhealthy lifestyle and obesity, create a state of inflammation and associated oxidative imbalance, which may progress to ma- lignancy. Pathological mechanisms of cancer are associated with abnormal expressions of various endogenous molecules that can be used as tumor biomarkers. Evaluation of such markers in different phases along the disease course plays a crucial role in clinical management and prognosis. Definitely, the current trend of active research on neoplastic mechanisms will help the clinical biochemistry laboratories to provide a better service.
Abstract Point‐of‐care diagnosis is crucial to control the spreading of viral infections. Here, universal‐modifiable probe‐gated silica nanoparticles (SNPs) based lateral flow assay (LFA) is developed in the interest of the rapid and early detection of viral infections. The most superior advantage of the rapid assay is its utility in detecting various sides of the virus directly from the human swab samples and its adaptability to detect various types of viruses. For this purpose, a high concentration of fluorescein and rhodamine B as a reporting material was loaded into SNPs with excellent loading capacity and measured using standard curve, 4.19 μmol ⋅ g −1 and 1.23 μmol ⋅ g −1 , respectively. As a model organism, severe acute respiratory syndrome coronavirus‐2 (CoV‐2) infections were selected by targeting its nonstructural (NSP9, NSP12) and envelope (E) genes as target sites of the virus. We showed that NSP12‐gated SNPs‐based LFA significantly outperformed detection of viral infection in 15 minutes from 0.73 pg ⋅ mL −1 synthetic viral solution and with a dilution of 1 : 10 3 of unprocessed human samples with an increasing test line intensity compared to steady state (n=12). Compared to the RT‐qPCR method, the sensitivity, specificity, and accuracy of NSP12‐gated SNPs were calculated as 100 %, 83 %, and 92 %, respectively. Finally, this modifiable nanoparticle system is a high‐performance sensing technique that could take advantage of upcoming point‐of‐care testing markets for viral infection detections.
Adropin is a peptide hormone that has been implicated in insulin resistance and as a potential regulator of growth. The aim of this study is to determine the effect of calorie restriction on circulating levels of adropin in the MMTV-TGFα breast cancer mouse model and investigate the effects of adropin peptide on the viability of MCF-7 and MDA-231 breast cancer cells in culture. Ten-week-old mice were assigned to either ad libitum-fed (AL), chronic calorie-restricted, or intermittent calorie-restricted groups. Concentrations of serum adropin were measured using an enzyme-linked immunosorbent assay. Results showed an inverse correlation between serum adropin levels and mouse age that was attenuated by calorie restriction. In the AL group the level of adropin was significantly lower at week 50 compared to levels at week 10. However, among the calorie-restricted groups, serum levels of adropin remained high at week 50. The cell-line-specific effects were observed after treatment of cancer cell lines with a series of adropin concentrations (5, 10, 25, 50 ng/mL). Flow cytometry analysis showed that MCF-7 cells entered the early phase of apoptosis after treatment with 50 ng/mL for 24 h. Adropin may be involved in the protective effects that calorie restriction has on breast cancer risk.
Support for the notion that a carotid intima-media thickness (CIMT) measurement is useful in individual cardiovascular risk prediction in addition to a risk function may come from studies showing that for an individual a high or low CIMT measurement leads to a correct shift from one to another risk category and this shift is followed by different treatment consequences. We set out to systematically review the published evidence by performing a PubMed search (2 March 2009). Out of 50 publications on CIMT and future events, 31 reported on the relation in the correct domain, [i.e. those free from symptomatic vascular disease or diabetes mellitus in which assessment of risk using a risk function (e.g. Framingham or SCORE) to base initiation of drug treatment upon is recommended]. Most studies reported relative risks (or equivalents) for the entire population only, and no information on relative risks within certain risk categories that may be of use to reclassify individuals based on combination of absolute and relative risks. No data on potential shifts of participants was presented. Eight studies specifically focused on the added value of CIMT in risk prediction. In seven studies the area under the curve (AUC) of a receiver operating characteristic was used to assess improvements in risk prediction. These analyses showed that addition of a CIMT measurement to established risk factors led to small and sometimes significant improvements in the AUC. However, change in AUC should not be the only parameter to rely on to judge the appropriateness of CIMT in risk stratification. In one study (n = 242), evidence was presented in participants with an intermediate Framingham risk score, a CIMT measurement above the 60th (men) and 80th (women) percentile of age-specific normal CIMT values, shifted participants above the threshold for initiation of drug therapy. Yet, the study was based on 24 events, and no information was presented on the proportion of participants correctly shifted. At present it seems that the published evidence to quantitatively support the use of a CIMT measurement to help in risk stratification on top of a risk function is limited.
Point-of-care diagnosis is crucial to control the spreading of viral infections. Here, universal-modifiable probe-gated silica nanoparticles (SNPs) based lateral flow assay (LFA) is developed in the interest of the rapid and early detection of viral infections. The most superior advantage of the biosensor is its utility in detecting various sides of the virus directly from the human swab samples and its adaptability to detect various types of viruses. For this purpose, high concentration of fluorescein and rhodamine B as a reporting material was loaded into SNPs with excellent loading capacity 21 µM and 6.2 µM, respectively. As a model organism, severe acute respiratory syndrome coronavirus-2 (CoV-2) infections were selected by targeting its nonstructural (NSP9, NSP12) and envelope (E) genes as target sites of the virus, we showed that NSP12-gated SNPs-based LFA significantly outperformed detection of viral infection in 15 minutes from a dilution of 1:103 of unprocessed human samples with an increasing test line intensity compared to steady state (n=12). Compared to the RT-qPCR method, sensitivity, specificity, and accuracy of NSP12-gated SNPs were calculated as 100%, 83%, and 92%, respectively. Finally, this modifiable nanoparticle system is a high-performance sensing technique that could take advantage of upcoming point-of-care testing markets for detection of viral infection.
The EU-CardioRNA Cooperation in Science and Technology (COST) Action is a European-wide consortium established in 2018 with 31 European country members and four associate member countries to build bridges between translational researchers from academia and industry who conduct research on non-coding RNAs, cardiovascular diseases and similar research areas. EU-CardioRNA comprises four core working groups (WG1-4). In the first year since its launch, EU-CardioRNA met biannually to exchange and discuss recent findings in related fields of scientific research, with scientific sessions broadly divided up according to WG. These meetings are also an opportunity to establish interdisciplinary discussion groups, brainstorm ideas and make plans to apply for joint research grants and conduct other scientific activities, including knowledge transfer. Following its launch in Brussels in 2018, three WG meetings have taken place. The first of these in Lisbon, Portugal, the second in Istanbul, Turkey, and the most recent in Maastricht, The Netherlands. Each meeting includes a scientific session from each WG. This meeting report briefly describes the highlights and key take-home messages from each WG session in this first successful year of the EU-CardioRNA COST Action.
Carotid artery intima-media thickness (CIMT) is widely used in observational and intervention studies. Despite the long history and its frequent use there is little uniformity in the measurement of CIMT. This diversity may have substantial effects on published results of studies and on the interpretation thereof. In this thesis we aimed to study several methodological aspects of CIMT measurements to facilitate an evidence-based decision making with respect to CIMT measurements. In chapter 2, two online techniques to measure CIMT, an automated RF approach and a manual B-mode approach, were compared. CIMT measured with B-mode showed stronger relations with established risk factors and was more strongly associated with risk of future cardiovascular events whereas in individuals with a thin CIMT (<0.9 mm) automated RF provided stronger relations with risk factors and stronger associations with future events, indicating that type of study population and expected presence of local atherosclerotic abnormalities should be considered in the choice of technique. The pros and cons of two different CIMT outcome measures (the mean common CIMT and mean maximum CIMT) were considered in chapter 3. As most parameters (apart from logistics) between both measures were equal, the decisive aspect that remained was the congruency of the result of the outcome measure with event data. The congruency showed a complementary value of both measures, favoring the use of both measures. Since the measurement of the mean maximum CIMT also includes measurement of the mean common CIMT, the balance tips towards the mean maximum CIMT measurement as the choice of outcome. Completeness of CIMT data at different walls, segments and angles of the carotid artery was studied in a population with familial hypercholesterolemia (FH) and in a population with mixed dyslipidemia (MD) in chapter 4. With the current ultrasound protocols and equipment it is possible to obtain high levels of complete CIMT information from nearly all walls, segments and angles. Apart from the study population, the completeness depended on the body mass index and waist circumference. In chapter 5 ultrasound protocols were compared on reproducibility, progression rates of CIMT and treatment effects in four different study populations. Ultrasound protocols that included measurements of both walls at multiple (? 2) angles for both the mean common CIMT and the mean maximum CIMT overall provided the best balance of the parameters mentioned above. In chapter 6, we showed that the quantification of the effect of an intervention did not appear to be affected by the type of reading approach (reading in batch versus reading in consecutive order). However, the absolute observed CIMT progression rates might be biased in a non-batch approach. Finally, all findings were put in perspective and implications of choices on sample size were discussed in chapter 8. If one aims to design a study with a sample size that is large enough to demonstrate a statistically significant effect of the intervention on both the mean maximum CIMT as the mean common CIMT, the differences in magnitude of progression rate and precision of the estimates of both outcome measures should be considered.
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