BackgroundNicotinamide is considered to be effective in halting the Alzheimer’s disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful.MethodNicotinamide loaded solid lipid nanoparticles (SLN) were prepared and functionalized with polysorbate 80 (S80), phosphatidylserine (PS) or phosphatidic acid (PA). The acquired particles were characterized and evaluated in respect of their cytotoxicity, biodistribution, and in vivo effectiveness through the different routes of administration.ResultsThe optimum sizes of 112 ± 1.6 nm, 124 ± 0.8 nm, and 137 ± 1.05 nm were acquired for S80-, PS-, and PA-functionalized SLNs, respectively. The in vitro cytotoxicity on SH-SY5Y cell line showed the safety of formulations except for S80-functionalized SLNs. Biodistribution study of SLNs has proved the benefits of functionalization in improving the brain delivery. The results of spatial and memory test, i.e. Morris water maze, and also histopathology and biochemical tests demonstrated the effectiveness of i.p. injection of PS -functionalized SLNs in improving the cognition, preserving the neuronal cells and reducing tau hyperphosphorylation in a rat model of Alzheimer’s disease.ConclusionThe acquired PS-functionalized SLN could be a potential brain delivery system. Loaded with nicotinamide, an HDAC inhibitor, it could ameliorate the cognition impairment of rats more effectively than the conventional administration of nicotinamide, i.e. oral, in the early stage of Alzheimer’s disease. Graphical abstractᅟ

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Recently, remdesivir was approved by the United States Food and Drug Administration for patients with Coronavirus disease 2019 (COVID-19). We herein describe 3 patients with COVID-19 who showed significant bradycardia and QTc prolongation after remdesivir administration. Bradycardia did not respond to atropine treatment in 2 of the patients, one of whom received theophylline and the other required a temporary pacemaker. Fortunately, the patients’ heart rate and rhythm returned to normal after the discontinuation of remdesivir, albeit it lengthened their hospital stays. Careful monitoring during remdesivir infusion may decrease the risk of adverse cardiovascular side effects.

Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention. Results A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073.