Inhibiting Cardiac Autophagy Suppresses Zika Virus Replication

alexandrossfakianakis shared this article with you from Inoreader Inhibiting Cardiac Autophagy Suppresses Zika Virus Replication via Journal of Medical Virology Abstract Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. F urthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV. This article is protected by copyright. All rights reserved. View on Web

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Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in Rhesus macaques against SARS‐CoV‐2

alexandrossfakianakis shared this article with you from Inoreader Needle‐free injection system delivery of ZyCoV‐D DNA vaccine demonstrated improved immunogenicity and protective efficacy in Rhesus macaques against SARS‐CoV‐2 via Journal of Medical Virology Abstract The apprehension of needles related to injection site pain, risk of transmitting the blood borne pathogens and effective mass immunization have led to the development of needle free injection system (NFIS). Here, we evaluated the efficacy of the NFIS and needle injection system (NIS) for the delivery and immunogenicity of DNA vaccine candidate ZyCOV-D in Rhesus macaques against SARS-CoV-2 infection. Briefly, twenty rhesus macaques were divided into five groups (4 animals each) i.e., I (1 mg dose by NIS), II (2mg dose by NIS), III [1mg dose by NFIS], IV (2mg dose by NFIS) and V (phosphate-buffer saline). The macaques were immunized with the vaccine candidates/PBS intradermally on day 0, 28 and 56. Subsequently, the animals were challenged with live SARS-CoV-2 after 15 weeks of the first immunization. Blood, nasal swab, throat swab, and bronchoalveolar lavage fluid specimens were collected on 0, 1, 3, 5 and 7 days post infection from each animal to determine immune response and vira l clearance. Amongst all the five groups, 2mg dose by NFIS elicited significant titers of IgG and neutralizing antibody after immunization with enhancement in their titers post virus challenge. Besides this, it also induced increased lymphocyte proliferation and cytokine response. The minimal viral load post-SARS-CoV-2 challenge and significant immune response in the immunized animals demonstrated efficiency of NFIS in delivering 2mg ZyCOV-D vaccine candidate. This article is protected by copyright. All rights reserved. View on Web

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Association between exposure to combustion-related air pollution and multiple sclerosis risk

alexandrossfakianakis shared this article with you from Inoreader Association between exposure to combustion-related air pollution and multiple sclerosis risk via International Journal of Epidemiology - Advance Access Abstract Background Smoking and occupational pulmonary irritants contribute to multiple sclerosis (MS) development. We aimed to study the association between ambient air pollution and MS risk and potential interaction with the human leukocyte antigen (HLA)-DRB1*15:01 allele. Methods Exposure to combustion-related air pollution was estimated as outdoor levels of nitrogen oxides (NOx) at the participants' residence locations, by spatially resolved dispersion modelling for the years 1990–18. Using two population-based case-control studies (6635 cases, 8880 controls), NOx levels were associated with MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Interaction between high NOx levels and the HLA-DRB1*15:01 allele regarding MS risk was calculated by the attributable proportion due to interaction (AP). In addition, a register study was performed comprising al l MS cases in Sweden who had received their diagnosis between 1993 and 2018 (n = 22 173), with 10 controls per case randomly selected from the National Population register. Results Residential air pollution was associated with MS risk. NOx levels (3-year average) exceeding the 90th percentile (24.6 µg/m3) were associated with an OR of 1.37 (95% CI 1.10–1.76) compared with levels below the 25th percentile (5.9 µg/m3), with a trend of increasing risk of MS with increasing levels of NOx (P <0.0001). A synergistic effect was observed between high NOx levels (exceeding the lower quartile among controls) and the HLA-DRB1*15:01 allele regarding MS risk (AP 0.26, 95% CI 0.13–0.29). Conclusions Our findings indicate that moderate levels of combustion-related ambient air pollution may play a role in MS development. View on Web

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A comprehensive evaluation of an animal model for Helicobacter pylori‐associated stomach cancer: Fact and controversy

alexandrossfakianakis shared this article with you from Inoreader A comprehensive evaluation of an animal model for Helicobacter pylori‐associated stomach cancer: Fact and controversy via Helicobacter Abstract Even though Helicobacter pylori infection was the most causative factor of gastric cancer, numerous in vivo studies failed to induce gastric cancer using H. pylori infection only. The utilization of established animal studies in cancer research is crucial as they aim to investigate the coincidental association between suspected oncogenes and pathogenesis as well as generate models for the development and testing of potential treatments. The methods to establish gastric cancer using infected animal models remain limited, diverse in methods, and showed different results. This study investigates the differences in animal models, which highlight different pathological results in gaster by literature research. Electronic databases searched were performed in PubMed, Science Direct, and Cochrane, without a period filter. A total of 135 articles were used in this study after a full-text assessment was conducted. The most frequent animal models used for gastric ca ncer were Mice, while Mongolian gerbils and Transgenic mice were the most susceptible model for gastric cancer associated with H. pylori infection. Additionally, transgenic mice showed that the susceptibility to gastric cancer progression was due to genetic and epigenetic factors. These studies showed that in Mongolian gerbil models, H. pylori could function as a single agent to trigger stomach cancer. However, most gastric cancer susceptibilities were not solely relying on H. pylori infection, and numerous factors are involved in cancer progression. Further study using Mongolian gerbils and Transgenic mice is crucial to conduct and establish the best models for gastric cancer associated H. pylori. View on Web

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Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway

alexandrossfakianakis shared this article with you from Inoreader <i>Porphyromonas gingivalis</i> bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway via International Journal of Oral Science - Issue International Journal of Oral Science, Published online: 12 January 2023; doi:10.1038/s41368-022-00215-y Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway View on Web

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