ABSTRACT
Coronavirus is a positive-strand RNA virus with the largest genome among all RNA viruses and can affect a wide range of vertebrate in connection, as well as human. Host cell cytoskeletons have been reported to involved in the process of virus entry, intracellular replication transport, assembly and egress of coronavirus, although many detailed mechanisms are still unclear. This article provides a brief overview of the function of the most prominent coronavirus-induced or -hijacked cytoskeletal structures including actin, microtubu1es and intermediate filaments. This article will provide evidence for future research on the interaction between the coronavirus and the host cytoskeleton.
ABSTRACT
Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administered M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EV treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) release in vitro and in vivo, thereby attenuating oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storms. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious disease-related cytokine storms.
Subject(s)
Cytokine Release Syndrome , Extracellular Vesicles , Macrophages , MicroRNAs , Angiotensin-Converting Enzyme 2 , Animals , Cytokine Release Syndrome/drug therapy , Cytokines/metabolism , Endotoxins , Extracellular Vesicles/metabolism , Humans , Interleukin-6/metabolism , Macrophages/metabolism , MicroRNAs/metabolism , NF-kappa B/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tumor Necrosis Factor-alpha/metabolism , p38 Mitogen-Activated Protein Kinases , COVID-19 Drug TreatmentABSTRACT
BACKGROUND: Since the outbreak of COVID-19 in December 2019, it has spread rapidly and widely, bringing great psychological pressure to the public. In order to prevent the epidemic, traffic lockdown was required in many areas of China, which led to inconvenience of treatment for dialysis patients. This study was conducted to explore the psychological distress and the psychological demand induced by CO-VID-19 in the patients undergoing dialysis and compare the difference between hemodialysis (HD) and peritoneal dialysis (PD) patients during the traffic lockdown period. METHODS: Questionnaires were given to the dialysis patients in the West China Hospital of Sichuan University. The Impact of Event Scale (IES) was used to investigate the patients' trauma-related distress in response to COVID-19. RESULTS: 232 eligible respondents were enrolled in this cross-section study, consisting of 156 PD patients and 76 HD patients. The median IES score for all the enrolled patients was 8.00 (2.00-19.00), which belonged to the subclinical dimension of post-traumatic stress symptoms (PTSS). HD patients had a significant higher IES score than PD patients (11.50 vs. 8.00) (p < 0.05). HD patients already got more psychological support from the medical staff. According to IES scores, 22.4% HD patients and 13.4% PD patients were classified as having moderate or severe PTSS, which need psychological support (p < 0.05). But more patients of both groups considered psychological support was necessary (HD: 50%, PD: 45.5%) (p > 0.05). In the multivariate regression analysis, we found that dialysis vintage, the impact of COVID-19 on the severity of illness and daily life, and confidence in overcoming the disease contributed to IES score (p < 0.05). CONCLUSIONS: HD patients had more severe trauma-related stress symptoms than PD patients. When major public healthy events occurred, careful psychological estimate and sufficient psychological support should be provided to the dialysis patients, especially to the HD patients.