Background COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. Methods We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. Results A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4+ T cell (× 106, MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8+ T cell (× 106, MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 106/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 106/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75). Conclusion Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.
Up-regulation of miR-422a attenuated microsphere formation, proliferation and tumor formation of breast cancer stem cells via suppressing the PLP2 expression.
Radioresistance remains a significant therapeutic obstacle in glioblastoma. Reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation and apoptosis. Nox4 NADPH oxidase is abundantly expressed and has proven to be a major source of ROS production in glioblastoma. Here we investigated the effects of Nox4 on GBM tumor cell invasion, angiogenesis, and radiosensitivity. A lentiviral shRNA vector was utilized to stably knockdown Nox4 in U87MG and U251 glioblastoma cells. ROS production was measured by flow cytometry using the fluorescent probe DCFH-DA. Radiosensitivity was evaluated by clonogenic assay and survival curve was generated. Cell proliferation activity was assessed by a cell counting proliferation assay and invasion/migration potential by Matrigel invasion assay. Tube-like structure formation assay was used to evaluate angiogenesis ability in vitro and VEGF expression was assessed by MTT assay. Nox4 knockdown reduced ROS production significantly and suppressed glioblastoma cells proliferation and invasion and tumor associated angiogenesis and increased their radiosensitivity in vitro. Our results indicate that Nox4 may play a crucial role in tumor invasion, angiogenesis, and radioresistance in glioblastoma. Inhibition of Nox4 by lentivirus-mediated shRNA could be a strategy to overcome radioresistance and then improve its therapeutic efficacy for glioblastoma.
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