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      Dexamethasone: Insights into Pharmacological Aspects, Therapeutic Mechanisms, and Delivery Systems

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          Abstract

          Dexamethasone (DEX) has been widely used to treat a variety of diseases, including autoimmune diseases, allergies, ocular disorders, cancer, and, more recently, COVID-19. However, DEX usage is often restricted in the clinic due to its poor water solubility. When administered through a systemic route, it can elicit severe side effects, such as hypertension, peptic ulcers, hyperglycemia, and hydro-electrolytic disorders. There is currently much interest in developing efficient DEX-loaded nanoformulations that ameliorate adverse disease effects inhibiting advancements in scientific research. Various nanoparticles have been developed to selectively deliver drugs without destroying healthy cells or organs in recent years. In the present review, we have summarized some of the most attractive applications of DEX-loaded delivery systems, including liposomes, polymers, hydrogels, nanofibers, silica, calcium phosphate, and hydroxyapatite. This review provides our readers with a broad spectrum of nanomedicine approaches to deliver DEX safely.

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          Is Open Access

          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

            Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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              Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

              Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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                Author and article information

                Journal
                ACS Biomater Sci Eng
                ACS Biomater Sci Eng
                ab
                abseba
                ACS Biomaterials Science & Engineering
                American Chemical Society
                2373-9878
                19 April 2022
                : acsbiomaterials.2c00026
                Affiliations
                []Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science , Jacksonville, Florida 32224, United States
                []Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences , Kerman 7618866749, Iran
                [§ ]Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine , Santariskiu 5, LT-08406 Vilnius, Lithuania
                []Department of Urologic Sciences, Vancouver Prostate Centre , Vancouver, British Columbia, Canada V6H 3Z6
                []Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences , Shiraz 7146864685, Iran
                [# ]Department of Radiology, Division of Translational Nanobiomaterials and Imaging, Leiden University Medical Center , Leiden 2333 ZA, The Netherlands
                [7 ]Department of Polymeric Biomaterials, Biomaterials Center (BIOMAT), University of Havana , Havana 10600, Cuba
                [8 ]Cellular and Molecular Research Center, Iran University of Medical Sciences , Tehran 1417755469, Iran
                [9 ]Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels 1200, Belgium
                [10 ]Istituto Italiano di Tecnologia , Centre for Micro-BioRobotics, Viale Rinaldo Piaggio 34, 56025 Pontedera, Pisa, Italy
                [11 ]Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences , Tehran 14496-14535, Iran
                [12 ]Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences , Kerman 7618866748, Iran
                [13 ]Drug Delivery Research Group, Auckland University of Technology (AUT), School of Science , Auckland 1010, New Zealand
                Author notes
                [* ]Reza Mohammadinejad Email: r.mohammadinejad@ 123456kmu.ac.ir .
                [* ]Ali Seyfoddin Email: ali.seyfoddin@ 123456aut.ac.nz .
                Author information
                https://orcid.org/0000-0001-9883-190X
                https://orcid.org/0000-0003-3511-9282
                https://orcid.org/0000-0002-1105-3891
                https://orcid.org/0000-0002-8531-7650
                https://orcid.org/0000-0002-5337-2903
                https://orcid.org/0000-0003-4343-9905
                Article
                10.1021/acsbiomaterials.2c00026
                9045676
                35439408
                466ca233-e732-456d-beed-5a97cc97effa
                © 2022 American Chemical Society

                This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 09 January 2022
                : 28 March 2022
                Categories
                Review
                Custom metadata
                ab2c00026
                ab2c00026

                dexamethasone,drug delivery,drug repurposing,nanomaterials,tissue engineering

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