Spyridon Champeris Tsaniras

Antiviral Stratagems Against HIV-1 Using RNA Interference (RNAi) Technology

The versatility of human immunodeficiency virus (HIV)-1 and its evolutionary potential to elude antiretroviral agents by mutating may be its most invincible weapon. Viruses, including HIV, in order to adapt and survive in their environment evolve at extremely fast rates. Given that conventional approaches which have been applied against HIV have failed, novel and more promising approaches must be employed. Recent studies advocate RNA interference (RNAi) as a promising therapeutic tool against HIV In this regard, targeting multiple HIV sites in the context of a combinatorial RNAi-based approach may efficiently stop viral propagation at an early stage. Moreover, large high-throughput RNAi screens are widely used in the fields of drug development and reverse genetics. Computer-based algorithms, bioinformatics, and biostatistical approaches have been employed in traditional medicinal chemistry discovery protocols for low molecular weight compounds. However, the diversity and complexity of RNAi screens cannot be efficiently addressed by these outdated approaches. Herein, a series of novel workflows for both wet- and dry-lab strategies are presented in an effort to provide an updated review of state-of-the-art RNAi technologies, which may enable adequate progress in the fight against the HIV-1 virus.

Concise Review: Geminin—A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells

Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self‐renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells. In embryonic as well as somatic stem cells, Geminin has been shown to interact with transcription factors and epigenetic regulators to drive gene expression programs and ultimately guide cell fate decisions. An ever‐growing number of studies suggests that these interactions of Geminin and proteins regulating transcription are conserved among metazoans. Interactions between Geminin and proteins modifying the epigenome, such as members of the repressive Polycomb group and the SWI/SNF proteins of the permissive Trithorax, have long been established. The complexity of these interactions, however, is only just beginning to unravel, revealing key roles on maintaining stem cell self‐renewal and fate specification. In this review, we summarize current knowledge and give new perspectives for the role of Geminin on transcriptional and epigenetic regulation, alongside with its regulatory activity in DNA replication and their implication in the regulation of stem and progenitor cell biology. Stem Cells 2017;35:299–310

Wound healing related agents: Ongoing research and perspectives

ABSTRACT Wound healing response plays a central part in chronic inflammation, affecting millions of people worldwide. It is a dynamic process that can lead to fibrosis, if tissue damage is irreversible and wound resolution is not attained. It is clear that there is a tight interconnection among wound healing, fibrosis and a variety of chronic disease conditions, demonstrating the heterogeneity of this pathology. Based on our further understanding of the cellular and molecular mechanisms underpinning tissue repair, new therapeutic approaches have recently been developed that target different aspects of the wound healing process and fibrosis. Nevertheless, several issues still need to be taken into consideration when designing modern wound healing drug delivery formulations. In this review, we highlight novel pharmacological agents that hold promise for targeting wound repair and fibrosis. We also focus on drug‐delivery systems that may enhance current and future therapies.

Human Emotions on the Onset of Cardiovascular and Small Vessel Related Diseases

Background/Aim: The aim of the present study was to examine the relation between understanding of emotions and cardiovascular related diseases, namely coronary heart disease, diabetes mellitus and obesity. The uniqueness of this study lies in the fact that it examined the relationship between the cardiovascular related diseases named above and the understanding of emotions in the context of Emotional Intelligence (EI). Patients and Methods: The study was conducted in 300 participants during a 3 year period. All participants completed a self-report questionnaire, assessing various aspects of EI, such as self-emotion appraisal, other emotion appraisal, emotion regulation and use of emotions. As hypothesized, coronary heart disease is a prognostic factor of regulation of emotions. Results: The present study is an attempt to examine the relation between emotional understanding and cardiovascular related diseases, namely coronary heart disease, diabetes mellitus and obesity. Establishing which diseases are independent risk factors for the understanding of emotions, could have a significant impact on emotional health, through the treatment of these cardiovascular related diseases. Emotions were studied within the theoretical context of Emotional Intelligence (EI), which affects peoples physical and mental health. Conclusion: The results of this study emphasize on the relationship of cardiovascular related diseases and psychological characteristics, such as anxiety and anger, being aspects of EI. Additionally, this work fills a gap in the relevant Greek literature, as a first attempt to examine the correlation of EI with cardiovascular related diseases.

Carcinogenic Pesticide ControlviaHijacking Endosymbiosis; The Paradigm of DSB-A fromWolbachia pipientisfor the Management ofOtiorhynchus singularis

Background/Aim: Pesticides have little, if any specificity, to the pathogen they target in most cases. Wide spectrum toxic chemicals are being used to remove pestcides and salvage crops and economies linked to agriculture. The burden on the environment, public health and economy is huge. Traditional pestcide control is based on administering heavy loads of highly toxic compounds and elements that essentially strip all life from the field. Those chemicals are a leading cause of increased cancer related deaths in countryside. Herein, the Trojan horse of endosymbiosis was used, in an effort to control pests using high specificity compounds in reduced quantities. Materials and Methods: Our pipeline has been applied on the case of Otiorhynchus singularis, which is a very widespread pest, whose impact is devastating on a repertoire of crops. To date, there is no specific pesticide nor agent to control it. The deployed strategy involves the inhibition of the key DSB-A enzyme of its endosymbiotic Wolbachia pipientis bacterial strain. Results: Our methodology, provides the means to design, test and identify highly specific pestcide control substances that minimize the impact of toxic chemicals on health, economy and the environment. Conclusion: All in all, in this study a radical computer-based pipeline is proposed that could be adopted under many other similar scenarios and pave the way for precision agriculture via optimized pest control.

Geminin ablation in vivo enhances tumorigenesis through increased genomic instability: Geminin ablation in vivo enhances tumorigenesis

Geminin, a DNA replication licensing inhibitor, ensures faithful DNA replication in vertebrates. Several studies have shown that geminin depletion in vitro results in rereplication and DNA damage, whereas increased expression of geminin has been observed in human cancers. However, conditional inactivation of geminin during embryogenesis has not revealed any detectable DNA replication defects. In order to examine its role in vivo, we conditionally inactivated geminin in the murine colon and lung, and assessed chemically induced carcinogenesis. We show here that mice lacking geminin develop a significantly higher number of tumors and bear a larger tumor burden than sham‐treated controls in urethane‐induced lung and azoxymethane/dextran sodium sulfate‐induced colon carcinogenesis. Survival is also significantly reduced in mice lacking geminin during lung carcinogenesis. A significant increase in the total number and grade of lesions (hyperplasias, adenomas, and carcinomas) was also confirmed by hematoxylin and eosin staining. Moreover, increased genomic aberrations, identified by increased ATR and γH2AX expression, was detected with immunohistochemistry analysis. In addition, we analyzed geminin expression in human colon cancer, and found increased expression, as well as a positive correlation with ATM/ATR levels and a non‐monotonic association with γH2AX. Taken together, our data demonstrate that geminin acts as a tumor suppressor by safeguarding genome stability, whereas its overexpression is also associated with genomic instability. Copyright