Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.
The novel coronavirus pneumonia, which was named later as coronavirus disease 2019 , is caused by the severe acute respiratory syndrome coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. In May, over 150,000 cases in Turkey, and 5.5 million cases around the world have been declared. Due to the urgent need for a vaccine and antiviral drug, isolation of the virus is crucial. Here, we report 1 of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology,and cell culture tropism of the virus that will be available to the research communities.
The SARS-CoV-2 virus caused one of the severest pandemic around the world. The vaccine development for urgent use became more of an issue during the pandemic. An inactivated virus formulated vaccines such as Hepatitis A, inactivated polio, and influenza has been proven to be a reliable approach for immunization for long years. In this pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate by modification of the oldest but the most experienced method that can be produced quickly and tested easily rather than the recombinant vaccines. Here, we optimized an inactivated virus vaccine which includes the gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required. Also, we applied the vaccine candidate (OZG-38.61.3) using the intradermal route in mice which decreased the requirement of a higher concentration of inactivated virus for proper immunization unlike most of the classical inactivated vaccine treatments. Thus, the novelty of our vaccine candidate (OZG-38.61.3) is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. We first determined the efficiency and safety dose (either 1013 or 1014 viral copy per dose) of the OZG-38.61.3 in Balb/c mice. Next, to test the immunogenicity and protective efficacy of the OZG-38.61.3, we immunized human ACE2-encoding transgenic mice and infected them with a dose of infective SARS-CoV-2 virus for the challenge test. We showed that the vaccinated mice showed lowered SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. This study encouraged us towards a new promising strategy for inactivated vaccine development (OZG-38.61.3) and the Phase 1 clinical trial for the COVID-19 pandemic.
The COVID-19 outbreak caused by SARS-CoV-2 has created an unprecedented health crisis since there is no coronavirus vaccine in the market due to the novelty of this virus. Therefore, SARS-CoV-2 vaccines have become very important to reduce morbidity and mortality. At this point, inactivated vaccines are important because the straightforward process of existing infrastructure used for several licensed human vaccines can be used for SARS-CoV-2. Inactive vaccines provide an antigenic presentation similar to that when they encounter invasive virus particles of the immune system. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. Our candidate OZG-3861 version 1 (V1) is an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1) is the GM-CSF adjuvant added vaccine candidate. We applied the candidates intradermal to BALB/c mice to assess the toxicity and immunogenicity of the OZG-3861 V1 and SK-01 V1. Here, we report our preliminary results in vaccinated mice. When considered in terms of T and B cell responses, it was observed that especially the vaccine models containing GM-CSF as an adjuvant caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature. Another finding showed that the presence of adjuvant is more important in T cell response rather than B cell. The vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study encouraged us to start the challenge test using infective SARS-CoV-2 viruses and our second version of gamma-irradiated inactivated vaccine candidates in humanized ACE2+ mice.
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