Serum circulating cell free DNA as potential diagnostic and prognostic biomarker in non small cell lung cancer

BackgroundNon-small cell lung cancer (NSCLC) is leading cause of cancer related death and the survival rate for patients with NSCLC remain poor so early diagnosis of NSCLC represents the best opportunity for cure. Cell-free DNA (cf-DNA) is extracellular nucleic acids found in cell-free plasma/serum of humans, given the recent approval of a liquid biopsy in lung cancer, the use of circulating tumor DNA as a novel non-invasive diagnostic and prognostic biomarker is promising.ObjectivesStudying whether the concentrations of circulating Cell Free DNA in serum can be used as a diagnostic and prognostic biomarker for NSCLC patients.MethodThis study was carried out on 140 subjects included 60 patients with non small cell lung cancer,40 patients with Chronic Obstructive Pulmonary Disease (COPD) and 40 healthy controls. Quantitative analysis of serum circulating cf-DNA was done b y AlU-based quantitative real time PCR. Serum level of CEA was measured by ELISA.ResultsNSCLC patients demonstrated significantly higher values of each of ALU 215, ALU 247, and DNA integrity than both COPD patients and controls. On ROC curve analysis, the total accuracy of ALU 247, ALU 115, DNA integrity (92.1%, 83.6%, 56.4%) at cutoff points (325, 565 & 0.48) respectively. On combining both DNA integrity and CEA, improved sensitivity to 93.3% was noted. For NSCLC patients, ALU 115 & ALU 247 increased significantly with more advanced stage and highest level was noticed in metastatic patients. Regarding survival there was better overall survival among patients with low DNA integrity.ConclusionSerum cf-DNA concentrations and integrity index may be valuable tool in early diagnosis of NSCLC and prediction of prognosis of those patients.     

Smaller muscle ATP reduction in women than in men by repeated bouts of sprint exercise.

It was hypothesized that the reduction of high-energy phosphates in muscle after repeated sprints is smaller in women than in men. Fifteen healthy and physically active women and men with an average age of 25 yr (range of 19-42 yr) performed three 30-s cycle sprints (Wingate test) with 20 min of rest between sprints. Repeated blood and muscle samples were obtained. Freeze-dried pooled muscle fibers of types I and II were analyzed for high-energy phosphates and their breakdown products and for glycogen. Accumulation of plasma ATP breakdown products, plasma catecholamines, and blood lactate, as well as glycogen reduction in type I fibers, was all lower in women than in men during sprint exercise. Repeated sprints induced smaller reduction of ATP and smaller accumulation of IMP and inosine in women than in men in type II muscle fibers, with no gender differences in changes of ATP and its breakdown products during the bouts of exercise themselves. This indicates that the smaller ATP reduction in women than in men during repeated sprints was created during recovery periods between the sprint exercises and that women possess a faster recovery of ATP via reamination of IMP during these recovery periods.     

Abstracts of papers read at the Winter Meeting, 1961

Herdmania litoralis is a heterotrophic, sand-dwelling dinoflagellate with morphological characters that do not provide clear evidence for its systematic position in any existing family of dinoflagellates. Protoperidinium minutum is a heterotrophic, planktonic species that has a typical tabulation for the genus Protoperidinium. In order to infer the phylogenetic positions of these two species more confidently, we characterized the thecal plate patterns and determined small-subunit and large-subunit ribosomal DNA sequences (SSU rDNA and LSU rDNA, respectively) from both species. Intraindividual and intraspecific diversity of SSU and LSU rDNA data were characterized in H. litoralis using a combination of single-cell PCR approaches and analyses of PCR clones derived from multi-cell DNA extractions. The results of the molecular phylogenetic analyses demonstrated a novel, well-supported clade comprising both sand-dwelling species (H. litoralis and Thecadinium dragescoi) and planktonic species (P. minutum). Because the establishment of this clade also demonstrated that P. minutum is not a member of Protoperidinium, we reinstated and emended the genus Archaeperidinium Jörgensen 1912 Jörgensen, E. 1912. Bericht über die von der schwedischen hydrographisch-biologischen Kommission in den schwedischen Gewässern in den Jahren 1909–10 eingesammelten Planktonproben. Svenska Hydrograph.-Biol. Komm. Skr., 4: 1–20.  [Google Scholar].     

The effects of pad geometry and material properties on the biomechanical effectiveness of 26 commercially available hip protectors

Wearable hip protectors (padded garments) represent a promising strategy to decrease impact force and hip fracture risk during falls, and a wide range of products are currently marketed. However, little is known about how design features of hip protectors influence biomechanical effectiveness. We used a mechanical test system (simulating sideways falls) to measure the attenuation in femoral neck force provided by 26 commercially available hip protectors at three impact velocities (2, 3, and 4m/s). We also used a materials testing machine to characterize the force-deflection properties of each device. Regression analyses were performed to determine which geometric (e.g., height, width, thickness, volume) and force-deflection properties were associated with force attenuation. At an impact velocity of 3m/s, the force attenuation provided by the various hip protectors ranged between 2.5% and 40%. Hip protectors with lower stiffness (measured at 500N) provided greater force attenuation at all velocities. Protectors that absorbed more energy demonstrated greater force attenuation at the higher impact velocities (3 and 4m/s conditions), while protectors that did not directly contact (but instead bridged) the skin overlying the greater trochanter attenuated more force at velocities of 2 and 3m/s. At these lower velocities, the force attenuation provided by protectors that contacted the skin overlying the greater trochanter increased with increasing pad width, thickness, and energy dissipation. By providing a comparison of the protective value of a large range of existing hip protectors, these results can help to guide consumers and researchers in selecting hip protectors, and in interpreting the results of previous clinical trials. Furthermore, by determining geometric and material parameters that influence biomechanical performance, our results should assist manufacturers in designing devices that offer improved performance and clinical effectiveness.     

The deleterious effect of stress‐induced depression on rat liver: Protective role of resveratrol and dimethyl fumarate via inhibiting the MAPK/ERK/JNK pathway

This study aimed to uncover the protective potentiality of resveratrol and dimethyl fumarate (DMF) in the liver of a chronic unpredictable mild stress (CUMS)‐induced depression animal model. Resveratrol and DMF significantly alleviated CUMS‐induced behavioral abnormalities in stressed rats through improving sucrose preference in sucrose preference test and decreasing immobility time in a forced swimming test. They also mitigated serum corticosterone levels and elevated serum serotonin levels, which were formerly disturbed in CUMS rats. The hepatoprotective effect is evidenced by improvement in hepatic histopathological examinations, as well as normalized serum alanine aminotransferase and aspartate aminotransferase activities. Molecular signaling of resveratrol and DMF was estimated by diminishing hepatic expression of phosphorylated p38 mitogen‐activated protein kinase (MAPK), extracellular signal‐regulated kinase1/2 (ERK1/2), and c‐Jun N‐terminal kinase (JNK). Consequently, they improved the hepatic antioxidant and anti‐inflammatory activities as elaborated by the normalization of total antioxidant capacity, glutathione, malondialdehyde, nuclear factor‐κB, tumor necrosis factor‐α, and myeloperoxidase levels. In addition, they inhibited hepatocyte apoptosis as evidenced by the increased expression of B‐cell lymphoma 2, the decreased expression of Bax, as well as the suppressed activity of caspase‐3. In conclusion, resveratrol and DMF purveyed a significant anti‐depressant effect, which may be mediated, at least in part, via inhibiting the MAPK/ERK/JNK pathway in the CUMS rat model.     

Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy

Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air-exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real-time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function.     

MORPHOLOGY AND MOLECULAR PHYLOGENY OF A NEW MARINE SAND‐DWELLING PROROCENTRUM SPECIES,P. TSAWWASSENENSE (DINOPHYCEAE,PROROCENTRALES), FROM BRITISH COLUMBIA,CANADA1

A new marine benthic, sand‐dwelling Prorocentrum species from the temperate region of the Pacific coast of British Columbia, Canada, is described using LM and EM and molecular phylogenetic analyses. The cells have a broad oval shape, 40.0–55.0 μm long and 30.0–47.5 μm wide, and a wide U‐shaped periflagellar area on the right thecal plate. The left thecal plate consists of a straighter apical outline in the form of a raised ridge. Five to six delicate apical spines in the center of the periflagellar area are present. The nucleus is located in the posterior region of the cell, and a conspicuous pusule is located in the anterior region of the cell. The cells have golden‐brown chloroplasts with a compound, intrachloroplast pyrenoid that lacks a starch sheath. The thecal plates are smooth with round pores of two different sizes. The larger pores are arranged in a specific pattern of radial rows that are evenly spaced around the plate periphery and of irregular rows (or double rows) that form an incomplete “V” at the apical end of the plates. Large pores are absent in the center of the left and right thecal plates. The intercalary band is striated transversely and also has faint horizontal striations. Trichocysts and two types of mucocysts are present. The molecular phylogenetic position of Prorocentrum tsawwassenense sp. nov. was inferred using SSU rDNA sequences. This new species branched with high support in a Prorocentrum clade containing both benthic and planktonic species.