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Cellular Responses to Adenovirus Entry
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Susanna Chiocca, Matthew Cotten
During lytic infection, adenovirus requires the infected cell to survive for only 24 to 48 hours, long enough to complete the synthesis of progeny virions, resulting in a 1000-fold amplification of the virus. Adenovirus has evolved strategies to alter the cellular antiviral responses within this time frame. For example, a translational inhibition due to activation of the interferon pathway occurs during adenovirus infection (55). This is thought to be due to activation of the interferon-inducible kinase p68 by double-stranded RNA molecules generated during the adenovirus life cycle. Kinase activity results in the inactivation of translation initiation factor eIF2α, and can potently downregulate translation. One adenovirus method of blocking this translational block involves the viral-encoded VA RNA molecule, which prevents double-stranded RNA activation of p68 (56-58; reviewed in 59). The adenovirus induction of interferon-responsive genes is also blocked at the transcriptional level by products of the E1A region (60-64). The E1A functions are not included in viral vectors. Furthermore, in the absence of E1A and viral DNA replication, full VA gene expression is not achieved.
Summary and Development of a New Approach to Senescence
Published in Nate F. Cardarelli, The Thymus in Health and Senescence, 2019
Variation in histone activity may arise from acetylation and deacetylation processes. Calf thymus chromatin contains a bound histone deacetylase. Low levels of polyamine cause an increase in activity of this enzyme, whereas at higher levels a decrease is noted.255 Trace metals may play a key role in DNA and RNA activation and synthesis. Magnesium appears to be essential to RNA synthesis, possibly acting by causing conformational changes in DNA. H1 histone inhibits magnesium ion binding to chromatin. Calcium, cobalt, and nickel, as well as magnesium, promote DNA stabilization. Zinc regulates DNA-protein interactions. Low zinc correlates with elevated H1, resulting in Euglena genome repression. Tin compounds, either metalloenzymes or conceivably as hormones, may stimulate RNA transcription. Exogenous alkyl organotins, however, inhibit both RNA and DNA synthesis.
Novel therapeutic drug strategies to tackle immune-oncological challenges faced by cancer patients during COVID-19
Published in Expert Review of Anticancer Therapy, 2021
Anwar Ali, Hafsa Mughal, Nazir Ahmad, Quratulain Babar, Ayesha Saeed, Waseem Khalid, Hasnain Raza, Aizhong Liu
For the treatment of cancer, INF-alpha-2b (IFNα-2b) and INF-gamma (IFNγ) are largely utilized either separately or in combination with other cancer treatments. SARS-CoV-2 compromises the typical antiviral response of type-1 INF [24]. The topical application of INF vapor form or systemic inhalation, alone or in combination with ritonavir/lopinavir, hydroxychloroquine, remdesivir or ribavirin, has become an effective treatment for COVID-19 [25]. It will be meaningful to monitor the virulence of SARS-CoV-2 and the expression of type-1 INF-related genes in the lungs and blood of cancer patients during treatment to determine the usefulness of interferon in the treatment. On the other hand, IFNs type-1 can be increased using agonists that are known as pattern recognition receptor [26]. The anti-proliferative mechanism of human INF α-2b (HIFN2b) not only regulates protein synthesis and translation of proteins responsible for inhibiting proliferation, but also apoptosis of tumor necrosis factor α (TNFα) cells and discharge of cytochrome C from mitochondria that leads to apoptosis [27,28]. Furthermore, HIFN2b can trigger protein kinase RNA-activation (PKR) thus bringing the control of cell division, separation, and apoptosis. PKR delivers FAS, p53, and Bcl-2-associated X (BAX) protein, which can stimulate apoptosis though caspase pathway [29]. IFN is used as antiviral drug in COVID-19 for prophylaxis and cancer as well, for COVID-19. It has increased the effectiveness through immunoregulatory effects [30].
The effect of red-to-near-infrared (R/NIR) irradiation on inflammatory processes
Published in International Journal of Radiation Biology, 2019
Tomasz Walski, Krystyna Dąbrowska, Anna Drohomirecka, Natalia Jędruchniewicz, Natalia Trochanowska-Pauk, Wojciech Witkiewicz, Małgorzata Komorowska
Exposure of lymphocytes to R/NIR resulted in increased proliferation of the cells (Stadler et al. 2000; Wąsik et al. 2007). However, comparing the extent of stimulation, stimulation by R/NIR was markedly lower than that achieved by both light and phytohemagglutinin (PHA), where PHA is a mitogen commonly used to model the immunocyte response to antigen stimulation. This difference can be explained by the fact that R/NIR stimulates relatively short-term changes in cell functions and effects such as increased chromatin remodeling, gene expression, calcium ion influx, increased concentration of c-myc RNA, activation of mitochondria, and synthesis of nucleic acids. R/NIR radiation does not induce the cell to enter the S-phase of the cell cycle, and thus lymphocyte blast transformation is not observed. This is related to the lack of interleukin 2 (IL-2) receptor in the exposed cells (Manteifel et al. 1997; Karu 1998; Karu et al. 1989; Karu 2003; Gulsoy et al. 2006; Wąsik et al. 2007). Of note, all observed effects are dependent on the dose of radiation. ‘Classic’ mitogens, in turn, induce both short-term and long-term (48–72 h) effects, including lymphocyte blast transformation, DNA synthesis and mitosis, and also exhibit phenotypic effects such as IL-2 and IL-2R gene expression (Karu et al. 1989; Manteifel et al. 1997; Karu 1998; Karu 2003; Gulsoy et al. 2006).
Emerging strategies for the noninvasive diagnosis of nosocomial pneumonia
Published in Expert Review of Anti-infective Therapy, 2019
Adamantia Liapikou, Catia Cillóniz, Antoni Torres
Two main technological advances are ongoing. First, the development of point-of-care testing with miniaturized and portable machines that allows rapid testing at the bedside. Second, the development of new methods of analysis for gene expression (genomics), RNA activation (transcriptome), protein production (proteomics), lipids (lipidomics), or metabolites (metabolomics). In addition to accelerating the time to diagnosis of culturable pathogens, real-time metagenomics holds the potential to identify pathogens that cannot be grown in culture [86].