were analyzed and discussed to better understand the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, dates of publication, journal language, authors' affiliations, and methodological characteristics were included in the analysis. All the findings and statements in this review regarding the outbreak are based on published information as listed in the references. Results: Most of the publications were written using the English language (89.2%). The largest proportion of published articles were related to causes (38.5%) and a majority (67.7%) were published by Chinese scholars. Research articles initially focused on causes, but over time there was an increase of the articles related to prevention and control. Studies thus far have shown that the virus' origination is in connection to a seafood market in Wuhan, but specific animal associations have not been confirmed. Reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines have been discussed as ways to reduce transmission. To date, no specific antiviral treatment has proven effective; hence, infected people primarily rely on symptomatic treatment and supportive care. (Continued on next page)Conclusions: There has been a rapid surge in research in response to the outbreak of COVID-19. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies are relevant to control the current public emergency, more high-quality research is needed to provide valid and reliable ways to manage this kind of public health emergency in both the short-and long-term.
Oncogene activation and tumor-suppressor gene inactivation are considered as the main causes driving the transformation of normal somatic cells into malignant tumor cells. Cancer cells are the driving force of tumor development and progression. Yet, cancer cells are unable to accomplish this alone. The tumor microenvironment is also considered to play an active role rather than simply acting as a by-stander in tumor progression. Through different pathways, tumor cells efficiently recruit stromal cells, which in turn, provide tumor cell growth signals, intermediate metabolites, and provide a suitable environment for tumor progression as well as metastasis. Through reciprocal communication, cancer cells and the microenvironment act in collusion leading to high proliferation and metastatic capability. Understanding the role of the tumor microenvironment in tumor progression provides us with novel approaches through which to target the tumor microenvironment for efficient anticancer treatment. In this review, we summarize the mechanisms involved in the recruitment of stromal cells by tumor cells to the primary tumor site and highlight the role of the tumor microenvironment in the regulation of tumor progression. We further discuss the potential approaches for cancer therapy.
Background: The 2019-nCoV has been identified as the cause of an outbreak of respiratory illness in Wuhan, Hubei Province, China beginning in December 2019. This epidemic had spread to 19 countries with 11791 confirmed cases, including 213 deaths, as of January 31, 2020. The World Health Organization declared it as a Public Health Emergency of International Concern.Methods: A scoping review of 65 research articles published until January 31, 2020 were analyzed and discussed for a better understanding of the epidemiology, causes, clinical diagnosis, prevention and control of this virus. The research domains, publishing dates, journal language, and authors’ affiliations, as well as methodological characteristics were analyzed. All findings and statements that are mentioned regarding the outbreak in this review are based on published information as listed in the references.Results: Most of the publications were in English language (89.23%). The largest proportion of articles were related to causes (38.46%) and majority (67.69%), and were published by Chinese scholars. Research articles initially focused on causes while there was an increase of the articles related to prevention and control over time. Studies thus far have shown origination in connection to a seafood market in Wuhan, but specific animal association has not been confirmed. The reported symptoms include fever, cough, fatigue, pneumonia, headache, diarrhea, hemoptysis, and dyspnea. Preventive measures such as masks, hand hygiene practices, avoidance of public contact, case detection, contact tracing, and quarantines are being discussed for reducing the transmission. To date, no specific antiviral treatment is proven effective, hence, infected people primarily rely on symptomatic treatment and supportive care. Conclusions: There has been a rapid surge in research in response to the outbreak of 2019-nCoV. During this early period, published research primarily explored the epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus. Although these studies had relevance to the control of a public emergency, more high-quality research need to be conducted to provide valid and reliable ways to manage this kind of public health emergency in both short-and long-terms.
In a previous whole exome sequencing of patients from 41 families with Hodgkin lymphoma, we identified two families with distinct heterozygous rare coding variants in POT1 (D224N and Y36H), both in a highly conserved region of the gene. POT1 D224N mutant did not bind to a single-stranded telomere oligonucleotide in vitro suggesting the mutation perturbs POT1's ability to bind to the telomeric G-rich overhang. Human HT1080 cells expressing POT1 D224N and lymphoblastoid cells carrying Y36H both showed increased telomere length and fragility in comparison to wild type cells. This strongly suggests that mutant POT1 causes chromosome instability and may play a role in lymphomagenesis in these families.
Short telomeres are a principal defining feature of telomere biology disorders, such as dyskeratosis congenita (DC), for which there are no effective treatments. Here, we report that primary fibroblasts from DC patients and late generation telomerase knockout mice display lower nicotinamide adenine dinucleotide (NAD) levels, and an imbalance in the NAD metabolome that includes elevated CD38 NADase and reduced poly(ADP‐ribose) polymerase and SIRT1 activities, respectively, affecting many associated biological pathways. Supplementation with the NAD precursor, nicotinamide riboside, and CD38 inhibition improved NAD homeostasis, thereby alleviating telomere damage, defective mitochondrial biosynthesis and clearance, cell growth retardation, and cellular senescence of DC fibroblasts. These findings reveal a direct, underlying role of NAD dysregulation when telomeres are short and underscore its relevance to the pathophysiology and interventions of human telomere‐driven diseases.
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