A main event and multiple introductions of SARS-CoV-2 initiated the COVID-19 epidemic in Greece.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Chains of infections starting from various countries worldwide seeded the outbreak of COVID-19 in Athens, capital city of Greece. A full-genome analysis of isolates from Athens' hospitals and other healthcare providers revealed the variety of SARS-CoV-2 that initiated the pandemic before lockdown and passenger flight restrictions. A dominant variant, encompassing the G614D amino acid substitution, spread through a major virus dispersal event, and sporadic introductions of rare variants characterized the local initiation of the epidemic. Mutations within the genome highlighted the genetic drift of the virus as rare variants emerged. An important variant contained a premature stop codon in orf7a leading to the truncation of a possibly important for viral pathogenesis domain. This study may serve as a reference for resolving future lines of infection in the area, especially after resumption of passenger flight connections to Athens and Greece during summer of 2020.

Augmenter of liver regeneration gene expression in human colon cancer cell lines and clinical tissue samples.

PURPOSE: Augmenter of liver regeneration (ALR) is an hepatotrophic factor responsible for the increased regenerative capacity of mammalian liver and ALR gene expression has been well-documented in liver cirrhosis and hepatocellular carcinoma tissue samples. The present study aimed to quantify and evaluate ALR gene expression in human colon cancer cell lines and tissue samples. METHODS: Total RNA was isolated from 6 colorectal cancer cell lines and 23 primary colorectal tumors, cDNA was prepared and ALR mRNA expression analysis was performed using quantitative real-time PCR. RESULTS: ALR mRNA expression was confirmed in all 6 colorectal cancer cell lines (SW480, SW620, DLD-1, RKO, COLO-205 and HTC-116) and an epithelial one (WISH). DLD-1 cell line showed the highest ALR mRNA levels, followed by RKO, COLO-205, HCT-116, SW480, SW620 and WISH cell lines. ALR gene expression levels were detected in all cancer tissue samples (N=23), being significantly increased in well/moderately compared to poorly differentiated tumors (p=0.0208). ALR gene expression levels were increased in Dukes' stage A/B compared to stage C tumors, at a non significant level (p=0.2842). ALR mRNA levels were slightly higher in colon cancer tissues compared to adjacent non-neoplastic ones (N=19), at a non significant level (p=0.2122). CONCLUSION: The present study verified for the first time the ALR gene expression in both human colon cancer cell lines and clinical samples. Enhanced ALR gene expression was negatively correlated with advanced histopathological grade and stage in both colon cancer cell lines and human tissue samples, implicating ALR participation at the early stage of colon malignant progression.

Dissecting the Species-Specific Virome in Culicoides of Thrace.

Biting midges (Culicoides) are vectors of arboviruses of both veterinary and medical importance. The surge of emerging and reemerging vector-borne diseases and their expansion in geographical areas affected by climate change has increased the importance of understanding their capacity to contribute to novel and emerging infectious diseases. The study of Culicoides virome is the first step in the assessment of this potential. In this study, we analyzed the RNA virome of 10 Culicoides species within the geographical area of Thrace in the southeastern part of Europe, a crossing point between Asia and Europe and important path of various arboviruses, utilizing the Ion Torrent next-generation sequencing (NGS) platform and a custom bioinformatics pipeline based on TRINITY assembler and alignment algorithms. The analysis of the RNA virome of 10 Culicoides species resulted in the identification of the genomic signatures of 14 novel RNA viruses, including three fully assembled viruses and four segmented viruses with at least one segment fully assembled, most of which were significantly divergent from previously identified related viruses from the Solemoviridae, Phasmaviridae, Phenuiviridae, Reoviridae, Chuviridae, Partitiviridae, Orthomyxoviridae, Rhabdoviridae, and Flaviviridae families. Each Culicoides species carried a species-specific set of viruses, some of which are related to viruses from other insect vectors in the same area, contributing to the idea of a virus-carrier web within the ecosystem. The identified viruses not only expand our current knowledge on the virome of Culicoides but also set the basis of the genetic diversity of such viruses in the area of southeastern Europe. Furthermore, our study highlights that such metagenomic approaches should include as many species as possible of the local virus-carrier web that interact and share the virome of a geographical area.

MCM-2 and MCM-5 expression in gastric adenocarcinoma: clinical significance and comparison with Ki-67 proliferative marker.

BACKGROUND: Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful biomarkers for cancer screening, surveillance and prognosis. The aim of the present study was to evaluate the clinical significance of MCM-2 and MCM-5 expression in gastric adenocarcinoma in comparison with Ki-67 proliferative marker. METHODS: MCM-2, MCM-5 and Ki-67 expression was assessed immunohistochemically in 66 tumoral samples of gastric adenocarcinoma patients and was statistically analyzed in relation to clinicopathological characteristics and patient survival. RESULTS: MCM-2 expression did not show significant associations with any clinicopathological parameters, while Ki-67 expression was merely significantly associated with tumor size (P = 0.0150). MCM-2 and Ki-67 expression were more frequently in intestinal (median values: 67.5 and 60%) compared to diffuse-type (median values: 60 and 45%) gastric adenocarcinoma cases without though reaching statistical significance (P > 0.05). MCM-5 expression was significantly associated with tumor size (P = 0.0295), presence of lymph node metastases (P = 0.0216) and tumor histopathological stage (P = 0.0098). Patients presenting high MCM-5 expression had significantly shorter survival times (log-rank test, P = 0.0042), whereas neither MCM-2 nor Ki-67 expression showed significant prognostic value (log-rank test, P = 0.9618 and P = 0.7174, respectively). In multivariate analysis, patient age, histopathological stage and grade of differentiation, but not MCM-5 expression, were identified as independent prognostic factors (Cox regression analysis, P = 0.0097, P = 0.0195, P = 0.0035 and P = 0.3245, respectively). CONCLUSIONS: The present study showed that MCM-5 expression was associated with clinicopathological parameters in gastric adenocarcinoma. However, further studies highlighting the distinct impact of the two histopathological types, intestinal and diffuse, are warranted to delineate whether MCMs could be used as diagnostic and prognostic markers in gastric neoplasia.

Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value < 0.001, and r = 0.738, P-value < 0.001, respectively), as well as between MCM-2 and MCM-5 proteins (r = 0.745, P-value < 0.001). Significant positive relationships were also observed between the expression of MCM-2 or MCM-5 proteins and that of p53 protein; however, they were consistently lower than the corresponding with Ki-67 protein. No significant association was observed between MCM-5 protein expression and the clinicopathological characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.

Genetically transformed world records: a reality or in the sphere of fantasy?

The disclosure of repeated cases of athletes who abuse performance-enhancing drugs is an ordinary phenomenon in the athletic community. In addition, the completion of sequencing of the human genome and the unprecedented advances in molecular biology have enabled the progression from traditional drug enhancement to hypothetical (at present) gene transfer. Scientific, sports, and antidoping authorities fear that gene doping will be the next major challenge. The misuse of gene therapy to improve athletic ability, which is commonly referred to as "gene doping," represents a practice as dangerous and unethical as any type of conventional doping. However, gene doping appears to be more attractive than traditional forms of doping because it is still undetectable and thus much less preventable. This review focuses on gene doping, the risks involved, and the ethical issues that emerge. It also discusses the possible strategies that can be used to detect this new form of doping.

Insights on augmenter of liver regeneration cloning and function.

Hepatic stimulator substance (HSS) has been referred to as a liver-specific but species non-specific growth factor. Gradient purification and sequence analysis of HSS protein indicated that it contained the augmenter of liver regeneration (ALR), also known as hepatopoietin (HPO). ALR, acting as a hepatotrophic growth factor, specifically stimulated proliferation of cultured hepatocytes as well as hepatoma cells in vitro, promoted liver regeneration and recovery of damaged hepatocytes and rescued acute hepatic failure in vivo. ALR belongs to the new Erv1/Alr protein family, members of which are found in lower and higher eukaryotes from yeast to man and even in some double-stranded DNA viruses. The present review article focuses on the molecular biology of ALR, examining the ALR gene and its expression from yeast to man and the biological function of ALR protein. ALR protein seems to be non-liver-specific as was previously believed, increasing the necessity to extend research on mammalian ALR protein in different tissues, organs and developmental stages in conditions of normal and abnormal cellular growth.

Assessment of Tachykinin Receptor 3' Gene Polymorphism rs3733631 in Rosacea.

Background. Rosacea is a chronic skin disease, possibly following the neurogenic skin inflammation model. Neurokinin B, involved in the pathogenesis of Parkinson's disease, frequently coexisting with subsequent onset of rosacea, is an endogenous ligand of the tachykinin receptor 3 (TACR3). Methods. 128 rosacea patients and 121 matched controls were genotyped for rs3733631 by PCR-RFLP and analyzed by chi-square test. Results. We observed statistically significant predominance of the C/G or G/G genotype (p = 0.006) and of the G allele (p = 0.004) in the papulopustular (PP) form of rosacea and statistically marginal significance of the C/G or G/G genotype in erythematotelangiectatic (ET) rosacea (p = 0.052). Significantly higher frequency of the C/G or G/G genotype and G allele in PP rosacea (p = 0.021 and p = 0.008, resp.) was ascertained within male patients. Conclusion. TACR3 rs3733631 G allele possibly predisposes the evolution of the initial phase of rosacea to the PP and not the ET form in male patients.

Assessment of Leptin Gene Polymorphism rs2060713 in Psoriasis Vulgaris.

Psoriasis is a lifelong disorder characterized by approximately 8-fold reduction of the duration of normal skin keratinocyte cell cycle and 2-fold increase of the number of dividing cells. Multiple genes, several environmental factors, and immune system alterations are involved in the pathogenesis of psoriasis. Hyperleptinemia is associated with psoriasis and leptin acts as an angiogenic factor. Angiogenetic processes precede the epidermal hyperplasia in psoriasis, indicating possible involvement of leptin in the pathogenesis of psoriasis. Leptin gene polymorphisms and their association with psoriasis have been given very little attention. We present a study of the rs2060713C/T genetic polymorphism in the pathogenesis of psoriasis vulgaris in 263 vulgaris patients and 252 unrelated matched healthy controls. No statistically significant differences were observed between patients and controls. A statistically nonsignificant trend was observed in males with the early onset type of psoriasis (11.1% C/T in patients versus 5.6% in controls) and in females with the late onset type of the disease (12.8% C/T in patients versus 3.3% in controls). Still, there is no hard evidence on correlation of psoriasis vulgaris with this polymorphism. Possible association with specific forms of the disease and either gender needs further investigation in larger studies.

Expression and clinical significance of FAK and Src proteins in human endometrial adenocarcinoma.

Focal Adhesion Kinase (FAK) is a protein tyrosine kinase, localised in the focal adhesions, which, upon activation interacts with Src, another tyrosine kinase, regulating several cellular signalling pathways. Both enzymes have been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK and Src expression in cases of endometrial adenocarcinoma. The total (t) and the activated, phosphorylated (p) forms of FAK and Src proteins were assessed immunohistochemically in tumour specimens obtained from 43 endometrial adenocarcinoma patients and were statistically analyzed in relation to various clinicopathological parameters and tumour proliferative capacity, reflected by Ki-67 labelling index. t-FAK positivity was significantly correlated with FIGO disease stage (p = 0.031), and t-FAK overexpression with patients' age (p = 0.015). No statistically significant correlation was identified between t-FAK staining intensity, t-Src positivity, overexpression or staining intensity and any of the clinicopathological parameters tested. No significant correlation was found between neither the positivity nor the intensity of staining of either p-FAk or p-Src with any of the parameters under study. Nonetheless, important, but non-significant, trends were identified between t-FAK staining intensity, t-Src positivity and overexpression and patients' survival (log rank, p = 0.122, p = 0.090 and p = 0.057 respectively). Similarly, p-FAK and p-Src staining characteristics seemed to correlate, even though non-significantly, with patients' survival (log rank, p = 0.051 and p = 0.070 for p-FAK and p-Src expression, respectively; log rank, p = 0.134 and p = 0.110 for p-FAK and p-Src staining intensity, respectively). These results support an important potential role of FAK-Src signalling in endometrial malignant disease progress and render further research in this field a necessity.

An epitome of DNA repair related genes and mechanisms in thyroid carcinoma.

Thyroid cancer presents a growing tendency during the last decades, particularly in regions affected by radiation exposure. The present review describes expression alterations and gene polymorphisms of DNA repair related molecules, leading to genomic instability and cell death, being associated with thyroid cancer. The referred variations in DNA repair related genes depict that indirect repair mechanisms are mainly correlated with thyroid gland carcinogenesis. Such abnormalities could participate in thyroid tumor development and progression and could be targeted for future prevention and therapy.

Toxicogenomics: a pivotal piece in the puzzle of toxicological research.

Toxicogenomics, resulting from the merge of conventional toxicology with functional genomics, being the scientific field studying the complex interactions between the cellular genome, toxic agents in the environment, organ dysfunction and disease state. When an organism is exposed to a toxic agent the cells respond by altering the pattern of gene expression. Genes are transcribed into mRNA, which in turn is translated into proteins that serve in a variety of cellular functions. Toxicogenomics through microarray technology, offers large-scale detection and quantification of mRNA transcripts, related to alterations in mRNA stability or gene regulation. This may prove advantageous in toxicological research. In the present review, the applications of toxicogenomics, especially to mechanistic and predictive toxicology are reported. The limitations arising from the use of this technology are also discussed. Additionally, a brief report of other approaches, using other -omic technologies (proteomics and metabonomics) that overcome limitations and give global information related to toxicity, is included.

DNA repair systems as targets of cadmium toxicity.

Cadmium (Cd) is a heavy metal and a potent carcinogen implicated in tumor development through occupational and environmental exposure. Recent evidence suggests that proteins participating in the DNA repair systems, especially in excision and mismatch repair, are sensitive targets of Cd toxicity. Cd by interfering and inhibiting these DNA repair processes might contribute to increased risk for tumor formation in humans. In the present review, the information available on the interference of Cd with DNA repair systems and their inhibition is summarized. These actions could possibly explain the indirect contribution of Cd to mutagenic effects and/or carcinogenicity.