COVID-19 and post-traumatic stress disorder: The perfect 'storm' for mental health (Review).

Since its outbreak, in December, 2019, in the Chinese city of Wuhan, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an ongoing global pandemic. Due to the novel antigenic properties of this virus, the world population could not develop immunity effectively and this led to the subsequent spread of COVID-19. This caused an unprecedented emergency situation with significant negative effects on health and well-being both on an individual and societal level. Apart from health, economic and social consequences, the impact of this pandemic on mental health is increasingly being reported in the scientific literature. The present review aimed to provide a comprehensive discussion of the possible neurological and neuropsychiatric manifestations of SARS-CoV-2, together with the related underlying molecular pathways. In addition, the present review focused on populations which are at a higher risk of developing psychiatric disturbances due to the COVID-19 pandemic and discussed possible routes of clinical management and therapeutics to minimize the burden associated with psychiatric disorders. Moreover, research findings exploring the prevalence of COVID-19-related post-traumatic stress disorder (PTSD) symptoms across vulnerable groups, including children, adolescents and COVID-19 survivors are presented, with particular emphasis on those with severe disease who required hospitalization and/or intensive care unit admission. Based on the available literature, the identification of potential determinants associated with PTSD across the different populations is underlined. Lessons learnt from the pandemics across the globe together with the ongoing research on COVID-19 and its impact on mental health, highlight the utmost importance for evidence-based, proactive and targeted interventions in high-risk groups aiming to mitigate the risks and manage vulnerabilities

Potential Tumor Suppressor NESG1 as an Unfavorable Prognosis Factor in Nasopharyngeal Carcinoma

BACKGROUND:Recently we identified nasopharyngeal epithelium specific protein 1 (NESG1) as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the involvement of NESG1 in tumor progression and prognosis of human NPC. METHODOLOGY/PRINCIPAL FINDINGS:NESG1 protein expression in NPC was examined. Survival analysis was performed using Kaplan-Meier method. The effect of NESG1 on cell proliferation, migration, and invasion were also investigated. RESULTS:NESG1 expression was downregulated in atypical hyperplasia and NPC samples compared to normal and squamous nasopharynx tissues. Reduced protein expression was negatively associated with the status of NPC progression. Patients with lower NESG1 expression had a shorter overall survival and disease-free time than did patients with higher NESG1 expression. Multivariate analysis suggested NESG1 expression as an independent prognostic indicator for NPC patient survival. Proliferation, migration, and invasion ability were significantly increased in cell lines following lentiviral-mediated shRNA suppression of NESG1 expression. Microarray analysis indicated that NESG1 participated in multiple pathways, including MAPK signaling and cell cycle regulation. Finally, DNA methylation microarray examination revealed a lack of hypermethylation at the NESG1 promoter, suggesting other mechanisms are involved in suppressing NESG1 expression in NPC. CONCLUSION:Our studies are the first to demonstrate that decreased NESG1 expression is an unfavorable prognostic factor for NPC

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido

The progression in the mouse skin carcinogenesis model correlates with ERK1/2 signaling

Background: The ras family of proto-oncogenes encodes for small GTPases that play critical roles in cell-cycle progression and cellular transformation. ERK1/2 MAP kinases are major ras effectors. Tumors in chemically treated mouse skin contain mutations in the Ha-ras protooncogene. Amplification and mutation of Ha-ras has been shown to correlate with malignant progression of these tumors. Cell lines isolated from mouse skin tumors represent the stages of tumor development, such as the PDV:PDVC57 cell line pair and B9 squamous carcinoma and A5 spindle cells. PDVC57 cells were selected from PDV cells, which were transformed with dimethylbenzanthracene (DMBA) in vitro and then transplanted in adult syngeneic mice. The PDV:PDVC57 pair contains ratio of normal:mutant Ha-ras 2:1 and 1:2, respectively. This genetic alteration correlates with more advanced tumorigenic characteristics of PDVC57 compared to PDV. The squamous carcinoma B9 cell clone was isolated from the same primary tumor as A5 spindle cell line. The mutant Ha-ras allele, also present in B9, is amplified and overexpressed in A5 cells. Therefore these cell line pairs represent an in vivo model for studies of Ha-ras and ERK1/2 signaling in mouse tumorigenesis. Materials and Methods: The ERK1/2 status in the above mouse cell lines was examined by using various molecular techniques. For the study of the tumorigenic properties and the role of the ras/MEK/ERK1/2 pathway in the cell lines mentioned, phenotypic characteristics, colony formation assay, anchorage-independent growth, and gelatin zymography were assessed, after or without treatment with the MEK inhibitor, PD98059. Results: ERK1/2 phosphorylation was found to be increased in PDVC57 when compared to PDV. This also applies to A5 spindle carcinoma cells when compared to squamous carcinoma and papilloma cells. The above finding was reproduced when transfecting human activated Ha-ras allele into PDV, thus demonstrating that Ha-ras enhances ERK1/2 signaling. To further test whether ERK1/2 activation was required for growth we used the MEK-1 inhibitor, PD98059. The latter inhibited cell proliferation and anchorage-independent growth of squamous and spindle cells. In addition, PD98059 treatment partially reverted the spindle morphology of A5 cells. Conclusions: These data suggest, for the first time, that oncogenicity and the degree of progression in the mouse skin carcinogenesis model correlates with ERK1/2 signaling

Roles of DNA repair enzyme OGG1 in innate immunity and its significance for lung cancer

Cytokines are pivotal mediators of the immune response, and their coordinated expression protects host tissue from excessive damage and oxidant stress. Nevertheless, the development of lung pathology, including asthma, chronic obstructive pulmonary disease, and ozone-induced lung injury, is associated with oxidant stress; as evidence, there is a significant increase in levels of the modified guanine base 7,8-dihydro-8-oxoguanine (8-oxoG) in the genome. 8-OxoG is primarily recognized by 8-oxoguanine glycosylase 1 (OGG1), which catalyzes the first step in the DNA base excision repair pathway. However, oxidant stress in the cell transiently halts enzymatic activity of substrate-bound OGG1. The stalled OGG1 facilitates DNA binding of transactivators, including NF-κB, to their cognate sites to enable expression of cytokines and chemokines, with ensuing recruitments of inflammatory cells. Hence, defective OGG1 will modulate the coordination between innate and adaptive immunity through excessive oxidant stress and cytokine dysregulation. Both oxidant stress and cytokine dysregulation constitute key elements of oncogenesis by KRAS, which is mechanistically coupled to OGG1. Thus, analysis of the mechanism by which OGG1 modulates gene expression helps discern between beneficial and detrimental effects of oxidant stress, exposes a missing functional link as a marker, and yields a novel target for lung cancer. © 2018 Elsevier Inc

The ideological frame of the genetic basis of cancer: The important role of mirnas

The elucidation of the genetic basis of cancer is the result of the research conducted since the beginning of the previous century, which peaked during the decades of 1960s and 1970s. It has been achieved through two different but convergent routes: the first includes the study of oncogenic viruses in rodents and birds and the second includes the use of chemical carcinogens in cells or in animal model systems (mice). Within this framework, the identification of genes that present mutations, alterations in expression levels, and epigenetic modifications has been facilitated through the development of animal carcinogenesis models. One of these models is the well-characterized mouse multistage skin cancer system discussed in this review. In addition, recent evidence shows the great significance that cancer stem cells seem to have in the emergence and progression of carcinogenesis. Finally, herein we discuss the critical role that miRNAs have emerged to play in cancer progression. miRNAs emerged as molecules with an impact on most cancer-related cellular processes, involving cell proliferation, cell death (apoptosis), angiogenesis, migration/motility,and rearrangement of the cytoskeleton. Their discovery has given rise to studies with a focus on miRNAs as key players in crucial oncogenesis-related processes and thus as potential targets in cancer therapeutics. © 2017 by Begell House, Inc

Homeobox gene involvement in normal hematopoiesis and in the pathogenesis of childhood Leukemias

Homeobox (HOX) genes are a superfamily of highly conserved genes with essential functions in many aspects of mammalian development. Their expression is tightly regulated throughout the duration of definitive hematopoiesis, so the pathogenetic mechanism that leads to leukemia suggests that malignant transformation is directly intertwined with the deregulation of HOX gene expression. Even though HOX gene involvement has been reviewed extensively in adult leukemias, childhood leukemias have received much less attention and mainly in the context of leukemias harboring MLL (mixed-lineage leukemia) gene translocations. In recent years, scientific evidence has highlighted HOX gene involvement in the development of other subtypes of childhood leukemias and added HOX gene family members that were previously unrelated to the pathogenesis of childhood leukemia. This has significant implications when considering both the risk stratification of pediatric patients and potential targets for successful therapy. Through the identification of HOX target genes, their resulting interactions, and the cognate signaling pathways, we hope to gain a better understanding of the molecular mechanism(s) underlying the ectopic activation of these genes in childhood leukemias and subsequently to reveal new molecular targets for successful therapy in cases of poor prognosis or resistant disease. © 2017 by Begell House, Inc

The role of ATF-2 in oncogenesis

Activating Transcription Factor-2 is a sequence-specific DNA-binding protein that belongs to the bZIP family of proteins and plays diverse roles in the mammalian cells. In response to stress stimuli, it activates a variety of gene targets including cyclin A, cyclin D and c-jun, which are involved in oncogenesis in various tissue types. ATF-2 expression has been correlated with maintenance of a cancer cell phenotype. However, other studies demonstrate an antiproliferative or apoptotic role for ATF-2. In this review, we summarize the signaling pathways that activate ATF-2, as well as its downstream targets. We examine the role of ATF-2 in carcinogenesis with respect to other bZIP proteins, using data from studies in human cancer cell lines, human tumours and mouse models, and we propose a potential model for its function in carcinogenesis, as well as a theoretical basis for its utility in anticancer drug design. © 2008 Wiley Periodicals, Inc

The COVID‑19 pandemic as a scientific and social challenge in the 21st century

The coronavirus disease-2019 (coVid-19) pandemic, caused by the new coronavirus SarS-coV-2, has spread around the globe with unprecedented consequences for the health of millions of people. While the pandemic is still in progress, with new incidents being reported every day, the resilience of the global society is constantly being challenged. under these circumstances, the future seems uncertain. SarS-coV-2 coronavirus has spread panic among civilians and insecurity at all socio-political and economic levels, dramatically disrupting everyday life, global economy, international travel and trade. The disease has also been linked to the onset of depression in many individuals due to the extreme restriction measures that have been taken for the prevention of the rapid spreading of coVid-19. First, the socio-economic, political and psychological implications of the coVid-19 pandemic were explored. Substantial evidence is provided for the consequences of the pandemic on all aspects of everyday life, while at the same time we unravel the role and the pursuits of national regimes during this unforeseen situation. The second goal of this review is related to the scientific aspect of the pandemic. Hence, we explain why SarS-coV-2 is not a so-called ‘invisible enemy’, and also attempt to give insight regarding the origin of the virus, in an effort to reject the conspiracy theories that have arisen during the pandemic. Finally, rational strategies were investigated for successful vaccine development. We are optimistic that this review will complement the knowledge of specialized scientists and inform non‑specialized readers on basic scientific questions, and also on the social and economic implications of the coVid-19 pandemic. © 2020 Spandidos Publications. All rights reserved