Effects of acute exercise on liver function and blood redox status in heavy drinkers

Excessive alcohol consumption can induce oxidative stress, resulting in the development of several diseases. Exercise has been reported to prevent and/or improve a number of health issues through several mechanisms, including an improvement in redox status. It has also been previously suggested that exercise can help individuals with alcohol use disorders reduce their alcohol intake; however, research in this field is limited. The aim of the present study was to investigage the effects of acute exercise of moderate intensity on the liver function and blood redox status in heavy drinkers. For this purpose, a total of 17 heavy drinkers [age, 31.6±3.2 years; body mass index (BMI), 27.4±0.8 kg/m2; experimental group (EG)] and 17 controls [age, 33.5±1.3 years; BMI, 26.1±1.4 kg/m2; control group (CG), who did not exceed moderate alcohol consumption], underwent one trial of acute exercise of moderate intensity (50-60% of the heart rate reserve) for 30 min on a cycle ergometer, following an overnight fast, and abstaining from smoking and alcohol consumption. Blood samples were obtained before and immediately after exercise for later determination of the indices of liver function and blood redox status. The subjects in the EG had significantly higher (p<0.05) baseline γ-glutamyl transferase (γ-GT) levels compared to the subjects in the CG. Exercise thus resulted in significantly higher γ-GT levels (p<0.005) only in the EG. No significant differences in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) baseline levels were observed between the 2 groups. Following exercise, the AST levels increased significantly (p<0.001) in both groups, whereas the ALT levels increased significantly (p<0.01) only in the EG. The baseline glutathione (GSH) levels were significantly lower (p<0.05) and remained low following exercise in the EG. In addition, we observed a trend for higher (p=0.07) baseline levels of thiobarbituric acid-reactive substances (TBARS), which remained elevated post-exercise in the EG compared to the CG. Significantly increased post-exercise total antioxidant capacity (TAC; p<0.01) and uric acid (UA; p<0.05) levels were noted in the CG, whereas the TAC (p=0.06) and UA (p=0.08) levels increased and approached significance post-exercise in the EG. No significant differences in the baseline levels of total bilirubin and protein carbonyl were observed between the 2 groups, even post-exercise. Thus, the findings of the present study indicate that even though heavy drinkers may be prone to oxidative stress, their exercise-induced antioxidant response is similar to that of individuals who do not drink heavily.Interna

Deregulation of the tumour suppressor genes p14ARF, p15 INK4b, p16INK4a and p53 in basal cell carcinoma

Background Basal cell carcinoma (BCC) is a locally aggressive slowly growing tumour that rarely metastasizes and is mostly seen in older members of the population. Objectives To determine the involvement of the tumour suppressor genes p14ARF, p15INK4b, p16INK4a and p53 in BCC. Methods We investigated the integrity of the CDKN2A locus in 15 BCC samples by analysing the presence of allelic imbalance/loss of heterozygosity (LOH). Moreover, we studied the mRNA expression levels of the tumour suppressor genes p14ARF, p15INK4b, p16INK4a and p53 in the BCC samples and compared them with mRNA levels in the corresponding normal tissue. The presence of mutations was examined by sequencing for exons 1a and 2 of p16INK4a. Results We found LOH in one BCC sample for the marker D9S1748. A polymorphism (G442A) of exon 2 was detected in three cases. p14 ARF, p15INK4b and p53 presented high expression levels, whereas p16INK4a exhibited low mRNA levels compared with the corresponding normal tissue. Significant correlations were detected among the genes studied. Conclusions Our results demonstrate a different expression profile between p16INK4a and p14ARF, p15INK4b and p53 in BCC. Moreover, we found a low percentage of LOH and of a polymorphic sequence variant (Ala148Thr) for the CDKN2A locus. © 2009 British Association of Dermatologists

Gene set enrichment analysis of the NF-κB/Snail/YY1/RKIP circuitry in multiple myeloma

The presence of a dysregulated NF-κB/Snail/YY1/RKIP loop was recently established in metastatic prostate cancer cells and non-Hodgkin&apos;s lymphoma; however, its involvement in multiple myeloma (MM) has yet to be investigated. Aim of the study was to investigate the role of the NF-κB/Snail/YY1/RKIP circuitry in MM and how each gene is correlated with the remaining genes of the loop. Using gene set enrichment analysis and gene neighbours analysis in data received from four datasets included in theMultipleMyeloma Genomics Portal of the Multiple Myeloma Research Consortium, we identified various enriched gene sets associated with each member of the NF-κB/Snail/YY1/RKIP circuitry. In each dataset, the 20 most co-expressed genes with the circuitry genes were isolated subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Among many, we highlighted on FNDC3B, TPD52, BBX, MBNL1 and MFAP2. Many co-expressed genes participated in the regulation of metabolic processes and nucleic acid binding, or were transcription factor binding genes and genes with metallopeptidase activity. The transcription factors FOXO4, GATA binding factor, Sp1 and AP4 most likely affect the expression of the NF- κB/ Snail/YY1/RKIP circuitry genes. Computational analysis of various GEO datasets revealed elevated YY1 and RKIP levels in MM vs. the normal plasma cells, as well as elevated RKIP levels in MM vs. normal B lymphocytes. The present study highlights the relationships of the NF- κB/ Snail/YY1/RKIP circuitry genes with specific cancer-related gene sets in multiple myeloma. © International Society of Oncology and BioMarkers (ISOBM) 2014

The miR-200 family in ovarian cancer

Ovarian cancer (OC) is the most lethal gynecological malignancy. Its insidious nature, manifesting with little to no symptoms until the disease progresses to metastasis, along with a wide diversity of histological subtypes and corresponding clinical behavior, poses significant therapeutic challenges. The genetic profiling of this aggressive tumor and its subtypes has led to the identification of various molecular markers of prognosis. Among these, the miR-200 family of miRNAs appears to play an important role. The deregulated expression of the miR-200 family members has been detected in a variety of OC studies. The present review examines the potential usefulness of the miR-200 family members as prognostic indicators in ovarian cancer and their impact across different OC publications, with a particular focus on prognostic features, such as disease stage, tumor histology, survival and response to chemotherapy. We present the potential usefulness of the miR-200 family genes as prognostic indicators in OC and highlight the tendency that miR-200 overexpression corresponds with an advanced cancer stage. © Koutsaki et al

Genetic detection of bladder cancer by microsatellite analysis of p16, RB1 and p53 tumor suppressor genes

Purpose: We investigated the incidence of genetic alterations in urine specimens from patients with bladder cancer. Materials and Methods: A total of 28 cytological urine specimens were assessed for microsatellite alternations, and 15 microsatellite markers were located on p53, RB1 and p16 regions. In 15 patients DNA from tumor specimens was also available. Results: Loss of heterozygosity was detected in 26 of 28 patients (93%) in at least 1 microsatellite marker. Allelic losses were found in 18 patients (64%) for the p16 locus, in 8 (29%) for the RB1 locus and in 17 (61%) for the p53 region. In contrast, no microsatellite alterations were found in the normal group without evidence of bladder cancer. In 11 cases genetic alterations in the cytological urine specimens were not detectable in the corresponding tumor specimen, suggesting heterogeneity of bladder cancer. Conclusions: The detection of loss of heterozygosity in cytological urine specimens may be a prognostic indicator of early detection of bladder cancer. Our results suggest that microsatellite analysis of urine specimens represents a novel, potentially useful, noninvasive clinical tool to detect bladder cancer

Pterygium concomitant with other ocular surface lesions: Clinical implications and pathogenetic links.

In the present study, we aimed to evaluate the co-existence of ophthalmic pterygium with other ocular surface lesions in a cohort of patients from the Cretan population. This is a retrospective evaluation of all pterygia in patients examined and treated at the Department of Ophthalmology of the University Hospital of Heraklion, Greece during an 8-year period (from June 2006 to June 2014). A total of 158 cases was examined. Ocular surface images and medical history were evaluated in order to detect concomitant ocular surface pathological conditions. Concomitant lesions included conjunctival nevi (5 cases, 3.16%), iris nevi (4 cases, 2.53%), conjunctival papillomas (8 cases, 5.06%), conjunctival intraepithelial neoplasia (CIN; 4 cases, 2.53%) and 6 cases of hypertophy of the plica semilunaris (3.79%). Of note, pterygium was overlying the iris which was occupied by the iris nevus in 2 out of the 4 cases of iris nevus. Overall, our data indicate that ophthalmic pterygium may often co-exist with other clinically significant ocular surface lesions. The association of ophthalmic pterygium with conjunctival papillomas or CIN stresses the potential involvement of human papilloma virus in the pathogenesis of ophthalmic pterygium, whereas the topographical association of pterygium with iris nevus may offer support to the transcameral light pathway pathogenetic mechanism

Evidence for loss of heterozygosity in human psoriatic lesions

Psoriasis, a disease of human skin, is characterized by abnormal differentiation and hyperproliferation of keratinocytes; it has a genetic background. Using 11 highly polymorphic microsatellite markers on eight chromosome arms, we performed an allelotype analysis in 14 psoriatic plaques, in order to reveal any chromosome deletions involved in the development of the disease. We detected loss of heterozygosity (LOH) on at least one microsatellite marker in nine of 14 (64%) cases. We also observed particular genetic loci altered with LOH, on chromosomes 3p, 7p/q and 8p. Our results suggest that LOH is an important phenomenon in the development of psoriatic plaques, providing evidence for deletion of regulatory genes

The spectrum of myocardial homeostasis mechanisms in the settings of cardiac surgery procedures (Review)

Classic cardiac surgery, determined through the function of cardiopulmonary bypass machine and myocardial cardioplegic arrest, represents the most controlled scenario for cardiomyocyte homeostatic disturbances due to systemic inflammatory response and myocardial reperfusion injury. An increasing number of studies have demonstrated that myocardial cell homeostasis in cardiac surgery procedures is a sequence of molecularly interrelated and overlapping mechanisms in the form of apoptosis, autophagy and necrosis, which are activated by a plethora of induced inflammatory mediators and gene-related signaling pathways. In this study, we outline the molecular mechanisms of the cardiomyocyte adaptive homeostatic process and the associated clinical implications, in the settings of classic cardiac surgery procedures. Copyright © 2017 Spandidos Publications. All rights reserved

Benchmarking of next and third generation sequencing technologies and their associated algorithms for de novo genome assembly

Genome assemblers are computational tools for de novo genome assembly, based on a plenitude of primary sequencing data. The quality of genome assemblies is estimated by their contiguity and the occurrences of misassemblies (duplications, deletions, translocations or inversions). The rapid development of sequencing technologies has enabled the rise of novel de novo genome assembly strategies. The ultimate goal of such strategies is to utilise the features of each sequencing platform in order to address the existing weaknesses of each sequencing type and compose a complete and correct genome map. In the present study, the hybrid strategy, which is based on Illumina short paired-end reads and Nanopore long reads, was benchmarked using MaSuRCA and Wengan assemblers. Moreover, the long-read assembly strategy, which is based on Nanopore reads, was benchmarked using Canu or PacBio HiFi reads were benchmarked using Hifiasm and HiCanu. The assemblies were performed on a computational cluster with limited computational resources. Their outputs were evaluated in terms of accuracy and computational performance. PacBio HiFi assembly strategy outperforms the other ones, while Hi-C scaffolding, which is based on chromatin 3D structure, is required in order to increase continuity, accuracy and complete- ness when large and complex genomes, such as the human one, are assembled. The use of Hi-C data is also necessary while using the hybrid assembly strategy. The results revealed that HiFi sequencing enabled the rise of novel algorithms which require less genome coverage than that of the other strategies making the assembly a less computationally demanding task. Taken together, these developments may lead to the democrati- sation of genome assembly projects which are now approachable by smaller labs with limited technical and financial resources. © 2021 Spandidos Publications. All rights reserved