Sepsis is a heterogeneous syndrome caused by a dysregulated host response during the process of infection. Neutrophils are involved in the development of sepsis due to their essential role in host defense. COVID-19 is a viral sepsis. Disfunction of neutrophils in sepsis has been described in previous studies, however, little is known about the role of microRNA-let-7b (miR-let-7b), toll-like receptor 4 (TLR4), and nuclear factor kappa B (NF-κB) activity in neutrophils and how they participate in the development of sepsis. In this study, we investigated the regulatory pathway of miR-let-7b/TLR4/NF-κB in neutrophils. We also explored the downstream cytokines released by neutrophils following miR-let-7b treatment and its therapeutic effects in cecal ligation and puncture (CLP)-induced septic mice. Six-to-eight-week-old male C57BL/6 mice underwent CLP following treatment with miR-let-7b agomir. Survival (n=10), changes in liver and lungs histopathology (n=4), circulating neutrophil counts (n=4), the liver-body weight ratio (n=4–7), and the lung wet-to-dry ratio (n=5–6) were recorded. We found that overexpression of miR-let-7b could significantly down-regulate the expression of human-derived neutrophilic TLR4 at a post-transcriptional level, a decreased level of proinflammatory factors including interleukin-6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), and an upregulation of anti-inflammatory factor IL-10 in vitro. After miR-let-7b agomir treatment in vivo, neutrophil recruitment was inhibited and thus the injuries of liver and lungs in CLP-induced septic mice were alleviated (p=0.01 and p=0.04, respectively), less weight loss was reduced, and survival in septic mice was also significantly improved (p=0.013). Our study suggested that miR-let-7b could be a potential target of sepsis.
Background and Objectives: Platelet has been linked to thrombosis in several studies. Inflammation is closely intertwined with thrombosis and occurs consecutively; it is therefore conceivable that platelet transfusions perform an increasingly vital role in inflammation. As platelet transfusions have been a significant therapeutic approach in patients for decades, serious risks including viral transmission, bacterial sepsis and acute lung injury have been demonstrated by retrospective studies and randomized clinical trials. Recent data suggest associations among platelet transfusion and pro‐inflammatory responses.Materials and Methods: A systematic review (from 2014 to 2019) on English literatures was conducted. Data on platelet transfusion‐related reactions were abstracted. Preset inclusion and exclusion criteria were applied to identify all eligible articles.Results: All patients abstracted have received platelet transfusion. This new review focuses on recent 5‐year advances (from 2014 to 2019) to have found that the platelet transfusion as pro‐inflammatory process, concerning secretion of platelet microparticles and other inflammatory factors.Conclusion: It can be hypothesized that the platelet microparticles or biological response modifier pathways might be innovative and therapeutic approaches to improving platelet transfusion and pretransfusion manipulations to reduce transfusion‐related adverse reactions and therefore improve the efficacy and safety of this wide‐employed therapy.
Background and Objectives In the absence of a vaccine or specific drug treatment options for coronavirus disease (COVID‐19), attention has been shifted in China to the possible therapeutic use of convalescent plasma. COVID‐19 convalescent plasma (CCP) is currently under investigation. We summarized clinical studies and other research data available as of May 5, 2020, on CCP therapy according to the Clinical Treatment Guideline of COVID‐19 Convalescent Plasma in China, as well as clinical experience at the First Affiliated Hospital of Zhejiang University, as part of a comprehensive anti‐epidemic strategy. Materials and Methods As of May 5, 2020, when the epidemic was well‐controlled in China, healthcare databases and sources of English literature relating to convalescent plasma were searched and reviewed. Sources of clinical and methodological heterogeneity were identified. Results As of May 5, 2020, up to 2,000 samples of CCP had been collected across China and administered to 700 COVID‐19 patients. From donors, 200–400 mL of plasma were collected at each donation, with antibody titers >1:160. We identified three clinical studies for COVID‐19 in China. Analyses showed a statistically significant improvement in clinical outcomes compared with untreated cases (P<0.001). No adverse effects were reported. Conclusion From initial studies, convalescent plasma therapy appears effective and safe for COVID‐19. However, there is clearly a need for well‐designed RCTs (randomized controlled trials) or other formal studies to further evaluate the efficacy and any potential adverse effects of CCP.