Hepatocarcinoma cells (TLT) were incubated in the presence of ascorbate and menadione, either alone or in combination. Cell death was only observed when such compounds were added simultaneously, most probably due to hydrogen peroxide (H2O2) generated by ascorbate-driven menadione redox cycling. TLT cells were particularly sensitive to such an oxidative stress due to its poor antioxidant status. DNA strand breaks were induced by this association but this process did not correspond to oligosomal DNA fragmentation (a hallmark of cell death by apoptosis). Neither caspase-3-like DEVDase activity, nor processing of procaspase-3 and cleavage of poly(ADP-ribose) polymerase (PARP) were observed in the presence of ascorbate and menadione. Cell death induced by such an association was actively dependent on protein phosphorylation since it was totally prevented by preincubating cells with sodium orthovanadate, a tyrosine phosphatase inhibitor. Finally, while H2O2, when administered as a bolus, strongly enhances a constitutive basal NF-kappaB activity in TLT cells, their incubation in the presence of ascorbate and menadione results in a total abolition of such a constitutive activity.
(1) Background: The detection of SARS-CoV-2 RNA in nasopharyngeal samples through real-time reverse transcription-polymerase chain reaction (RT-PCR) is considered the standard gold method for the diagnosis of SARS-CoV-2 infection. Antigen detection (AD) tests are more rapid, less laborious, and less expensive alternatives but still require clinical validation. (2) Methods: This study compared the clinical performance of five AD tests, including four rapid AD (RAD) tests (biotical, Panbio, Healgen, and Roche) and one automated AD test (VITROS). For that purpose, 118 (62.8%) symptomatic patients and 70 (37.2%) asymptomatic subjects were tested, and results were compared to RT-PCR. (3) Results: The performance of the RAD tests was modest and allowed us to identify RT-PCR positive patients with higher viral loads. For Ct values ≤25, the sensitivity ranged from 93.1% (95% CI: 83.3–98.1%) to 96.6% (95% CI: 88.1–99.6%), meaning that some samples with high viral loads were missed. Considering the Ct value proposed by the CDC for contagiousness (i.e., Ct values ≤33) sensitivities ranged from 76.2% (95% CI: 65.4–85.1%) to 88.8% (95% CI: 79.7–94.7%) while the specificity ranged from 96.3% (95% CI: 90.8–99.0%) to 99.1% (95% CI: 95.0–100%). The VITROS automated assay showed a 100% (95% CI: 95.5–100%) sensitivity for Ct values ≤33, and had a specificity of 100% (95% CI: 96.6–100%); (4) Conclusions: Compared to RAD tests, the VITROS assay fully aligned with RT-PCR for Ct values up to 33, which might allow a faster, easier and cheaper identification of SARS-CoV-2 contagious patients.
The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K(3) in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K(3) administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK(3)-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K(3) as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.
Strategies to detect SARS-CoV-2 are increasingly being developed. Among them, serological methods have been developed. Nevertheless, although these may present an interesting clinical performance, they are often directed against only one antigen. This study aims at evaluating the clinical performance of an innovative multiplex immunoassay (i.e., CoViDiag assay) detecting simultaneously the presence of antibodies directed against N, S1, S2, RBD and NTD antigens. Sensitivity was evaluated in 135 samples obtained from 94 rRT-PCR confirmed coronavirus disease 2019 (COVID-19) patients. Non-SARS-CoV-2 sera (n = 132) collected before the COVID-19 pandemic with potential cross-reactions to the SARS-CoV-2 immunoassay were included in the specificity analysis. The antibody signature was also studied in hospitalized and non-hospitalized patients. The specificity of the CoViDiag assay was excellent for all antibodies (99.2 to 100%) using adapted cut-offs. None of the false positive samples were positive for more than one antibody. The sensitivity obtained from samples collected 14 days since symptom onset varied from 92.0 to 100.0% depending on the antibody considered. Among samples collected more than 14 days after symptom onset, 12.8, 66.3, 3.5, 9.3, 5.8 and 2.3% were positive for 5, 4, 3, 2, 1 or 0 antibodies, respectively. A trend toward higher antibody titers was observed in hospitalized patient in the early days since symptom onset. However, no significant difference was observed compared to non-hospitalized patients after 14 days since symptom onset. The clinical performance of the CoViDiag 5 IgG assay is sufficient to recommend its use for the detection and the characterization of the antibody signature following SARS-CoV-2 infection. The combination of several antigens in the same test improves the overall specificity and sensitivity of the test. Further research is needed to investigate whether this strategy may be of interest to identify severe disease outcome in patients with SARS-CoV-2 infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.