A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in 217 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokinesecreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b mid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2and TMPRSS2which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.
Graphene-like two-dimensional materials (2DMats) show application potential in optoelectronics and biomedicine due to their unique properties. However, environmental and biological influences of these 2DMats remain to be unveiled. Here we reported the antibacterial activity of two-dimensional (2D) chemically exfoliated MoS2 (ce-MoS2) sheets. We found that the antibacterial activity of ce-MoS2 sheets was much more potent than that of the raw MoS2 powders used for the synthesis of ce-MoS2 sheets possibly due to the 2D planar structure (high specific surface area) and higher conductivity of the ce-MoS2. We investigated the antibacterial mechanisms of the ce-MoS2 sheets and proposed their antibacterial pathways. We found that the ce-MoS2 sheets could produce reactive oxygen species (ROS), different from a previous report on graphene-based materials. Particularly, the oxidation capacity of the ce-MoS2 sheets toward glutathione oxidation showed a time and concentration dependent trend, which is fully consistent with the antibacterial behaviour of the ce-MoS2 sheets. The results suggest that antimicrobial behaviors were attributable to both membrane and oxidation stress. The antibacterial pathways include MoS2-bacteria contact induced membrane stress, superoxide anion (O2(˙-) induced ROS production by the ce-MoS2, and the ensuing superoxide anion-independent oxidation. Our study thus indicates that the tailoring of the dimension of nanomaterials and their electronic properties would manipulate antibacterial activity.
Highlights Covered broad fields of ageing in China: statistics, basic and translational research, long-term care, policy and social networks. Provided more detailed numerical updates of the ageing challenges in China. New features of the aging-related challenges, e.g., oral ageing and STDs in the elderly in China. A new and independent section on immune ageing. We also mentioned the COVID-19-induced death in the Chinese elderly.
The infusion of coronavirus disease 2019 (COVID-19) patients with mesenchymal stem cells (MSCs) potentially improves clinical symptoms, but the underlying mechanism remains unclear. We conducted a randomized, single-blind, placebo-controlled (29 patients/group) phase II clinical trial to validate previous findings and explore the potential mechanisms. Patients treated with umbilical cord-derived MSCs exhibited a shorter hospital stay (P = 0.0198) and less time required for symptoms remission (P = 0.0194) than those who received placebo. Based on chest images, both severe and critical patients treated with MSCs showed improvement by day 7 (P = 0.0099) and day 21 (P = 0.0084). MSC-treated patients had fewer adverse events. MSC infusion reduced the levels of C-reactive protein, proinflammatory cytokines, and neutrophil extracellular traps (NETs) and promoted the maintenance of SARS-CoV-2-specific antibodies. To explore how MSCs modulate the immune system, we employed single-cell RNA sequencing analysis on peripheral blood. Our analysis identified a novel subpopulation of VNN2+ hematopoietic stem/progenitor-like (HSPC-like) cells expressing CSF3R and PTPRE that were mobilized following MSC infusion. Genes encoding chemotaxis factors — CX3CR1 and L-selectin — were upregulated in various immune cells. MSC treatment also regulated B cell subsets and increased the expression of costimulatory CD28 in T cells in vivo and in vitro. In addition, an in vivo mouse study confirmed that MSCs suppressed NET release and reduced venous thrombosis by upregulating kindlin-3 signaling. Together, our results underscore the role of MSCs in improving COVID-19 patient outcomes via maintenance of immune homeostasis.
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