The Possible Mechanisms of Cu and Zn in the Treatment and Prevention of HIV and COVID-19 Viral Infection.

Due to their unique properties and their potential therapeutic and prophylactic applications, heavy metals have attracted the interest of many researchers, especially during the outbreak of COVID-19. Indeed, zinc (Zn) and copper (Cu) have been widely used during viral infections. Zn has been reported to prevent excessive inflammatory response and cytokine storm, improve the response of the virus to Type I interferon (IFN-1), and enhance the production of IFN-a to counteract the antagonistic effect of SARS-CoV-2 virus protein on IFN. Additionally, Zn has been found to promote the proliferation and differentiation of T and B lymphocytes, thereby improving immune function, inhibiting RNA-dependent RNA polymerase (RdRp) in SARS- CoV-2 reducing the viral replication and stabilizing the cell membrane by preventing the proteolytic processing of viral polyprotein and proteases enzymes. Interestingly, Zn deficiency has been correlated with enhanced SARS-CoV-2 viral entry through interaction between the ACE2 receptor and viral spike protein. Along with zinc, Cu possesses strong virucidal capabilities and is known to be effective at neutralizing a variety of infectious viruses, including the poliovirus, influenza virus, HIV type 1, and other enveloped or nonenveloped, single- or double-stranded DNA and RNA viruses. Cu-related antiviral action has been linked to different pathways. First, it may result in permanent damage to the viral membrane, envelopes, and genetic material of viruses. Second, Cu produces reactive oxygen species to take advantage of the redox signaling mechanism to eradicate the virus. The present review focused on Zn and Cu in the treatment and prevention of viral infection. Moreover, the application of metals such as Cu and gold in nanotechnology for the development of antiviral therapies and vaccines has been also discussed.

Multilineage Differentiating Stress Enduring (Muse) Cells: A New Era of Stem Cell-Based Therapy.

Stem cell transplantation has recently demonstrated a significant therapeutic efficacy in various diseases. Multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant endogenous pluripotent stem cells that were first reported in 2010. Muse cells can be found in the peripheral blood, bone marrow and connective tissue of nearly all body organs. Under basal conditions, they constantly move from the bone marrow to peripheral blood to supply various body organs. However, this rate greatly changes even within the same individual based on physical status and the presence of injury or illness. Muse cells can differentiate into all three-germ-layers, producing tissue-compatible cells with few errors, minimal immune rejection and without forming teratomas. They can also endure hostile environments, supporting their survival in damaged/injured tissues. Additionally, Muse cells express receptors for sphingosine-1-phosphate (S1P), which is a protein produced by damaged/injured tissues. Through the S1P-S1PR2 axis, circulating Muse cells can preferentially migrate to damaged sites following transplantation. In addition, Muse cells possess a unique immune privilege system, facilitating their use without the need for long-term immunosuppressant treatment or human leucocyte antigen matching. Moreover, they exhibit anti-inflammatory, anti-apoptotic and tissue-protective effects. These characteristics circumvent all challenges experienced with mesenchymal stem cells and induced pluripotent stem cells and encourage the wide application of Muse cells in clinical practice. Indeed, Muse cells have the potential to break through the limitations of current cell-based therapies, and many clinical trials have been conducted, applying intravenously administered Muse cells in stroke, myocardial infarction, neurological disorders and acute respiratory distress syndrome (ARDS) related to novel coronavirus (SARS-CoV-2) infection. Herein, we aim to highlight the unique biological properties of Muse cells and to elucidate the advantageous difference between Muse cells and other types of stem cells. Finally, we shed light on their current therapeutic applications and the major obstacles to their clinical implementation from laboratory to clinic.

Green polymer altered in-situ gel oral liquid sustainable release preparation of vildagliptin suitable for dysphagic diabetic patients: assessment in-vitro & in-vivo.

PURPOSE: This work aimed to fabricate alginate based in-situ gelling matrix of vildagliptin improved by calcium and carboxy methyl cellulose (CMC) for appropriate adjustment of the onset and duration of action. This easy-to-swallow thickened liquid preparation aimed to improve compliance for dysphagic or elderly diabetic patients. METHODS: Vildagliptin dispersions containing alginate were fabricated in the presence or absence of calcium chloride to assess the effect of calcium ion, then a matrix containing 1.5% w/v of sodium alginate with calcium was further examined after the addition of CMC with different concentrations ranging from 0.1% to 0.3%. The viscosity, gelling forming property, Differential scanning calorimetry, and in-vitro drug release were assessed before monitoring the hypoglycemic effect of the selected formulation. RESULTS: In-situ gel matrixes were fabricated at gastric pH with and without calcium ions. The best formula concerning viscosity and the gel-forming property was achieved with higher CMC concentrations, which in turn decreased the rate of vildagliptin release in stimulated gastric pH. In-vivo results confirmed the extended hypoglycemic effect of the vildagliptin in-situ gelling matrix compared to the vildagliptin aqueous solution. CONCLUSION: This study represents a green polymeric-based in-situ gel as a liquid oral retarded release preparation intended for reducing dose frequency, easier administration of vildagliptin, and improving compliance in geriatric and dysphagic diabetic patients.

Exosomes in COVID-19 infection: Focus on role in diagnosis, pathogenesis, immunity, and clinical trials.

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread as a new strain of coronavirus disease (COVID-19) and progressed as a global pandemic. Exosomes are membrane-bound vesicles released from almost all cells and are crucially involved in cell-cell communication. Interestingly, COVID-19 viral particles produce exosomes that moderate communication between infected and uninfected cells. Hence, there is growing evidence highlighting the crucial implications of exosomes in COVID-19 infection, transmission, intercellular spread, and reinfection. On the other hand, clinical trials have demonstrated mesenchymal stem cell-derived exosomes as a promising therapeutic strategy for severely affected COVID-19 patients. Also, convalescent plasma-derived exosomes have been proposed for multiple efficacies in COVID-19 patients. Furthermore, messenger RNAs (mRNA)-loaded exosomes were superior to mRNA-loaded lipid nanoparticles as a delivery system. Hence, exosomes can be used to safely induce SARS-CoV-2 immunity via their loading with mRNAs encoding immunogenic forms of SARS-CoV-2 spike and nucleocapsid proteins. Moreover, exosomes can be used as a nano-delivery system for microRNA to alleviate cytokine storm and prevent the progression of organ failure in COVID-19 patients. The present review summarizes state of the art concerning the role of exosomes in COVID-19 infection and accompanying organ complications as well as the potential use of exosomes in COVID-19 diagnosis, treatment, drug delivery, and vaccination. The review also sheds the light on the common biogenic pathway between the SARS-CoV-2 virus and exosomes. Additionally, the latest and current clinical trials using exosomes for COVID-19 infection are summarized.

Exosomes: Isolation, characterization, and biomedical applications.

Exosomes are nano-sized bioactive vesicles of 30-150 nm in diameter. They are secreted by exocytosis of nearly all type of cells in to the extracellular fluid. Thereby, they can be found in many biological fluids. Exosomes regulate intracellular communication between cells via delivery of their cargo which include lipids, proteins, and nucleic acid. Many desirable features of exosomes made them promising candidates in several therapeutic applications. In this review, we discuss the use of exosomes as diagnostic tools and their possible biomedical applications. Additionally, current techniques used for isolation, purification, and characterization of exosomes from both biological fluids and in vitro cell cultures were discussed.

Umbilical cord stem cells: Background, processing and applications.

Stem cells have currently gained attention in the field of medicine not only due to their ability to repair dysfunctional or damaged cells, but also they could be used as drug delivery system after being engineered to do so. Human umbilical cord is attractive source for autologous and allogenic stem cells that are currently amenable to treatment of various diseases. Human umbilical cord stem cells are -in contrast to embryonic and fetal stem cells- ethically noncontroversial, inexpensive and readily available source of cells. Umbilical cord, umbilical cord vein, amnion/placenta and Wharton's jelly are all rich of many types of multipotent stem cell populations capable of forming many different cell types. This review will focus on umbilical cord stem cells processing and current application in medicine.