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Exosome in promoting Cancer Advancement by way of Its Bioactive Cargoes.
Dengue virus (DENV) infection threatens the health and wellbeing of almost 100 million people in the world. Vectored by mosquitoes, DENV may cause severe disease in human hosts called Dengue hemorrhagic fever (DHF)/Dengue shock syndrome (DSS), which are not preventable by any known drug. In the absence of a universally-accepted vaccine, a drug capable of inhibiting DENV multiplication is an urgent and unmet clinical need. Here we summarize inhibitory strategies by targeting either host biochemical pathways or virus-encoded proteins. A variety of approaches have been generated to design Directly-acting antivirals or DAAs targeting different DENV proteins, with mixed success. Among them, DAAs targeting genome replicating viral enzymes have proven effective against many viruses including, Human Immuno-deficiency Virus and Hepatitis C Virus. DAAs may be derived either from existing compound libraries of novel molecules and plant secondary metabolites or devised through Computeraided Drug design (CADD) methods. Here, we focus on compounds with reported DAA-activity against the DENV RNA-dependent RNA polymerase (RdRp), which replicates the viral RNA genome. The structure-activity relation (SAR) and toxicity of the natural compounds, including secondary plant metabolites, have been discussed in detail. We have also tabulated the novel compounds with known anti-RdRp activity. We conclude with a list of DAAs for which a co-crystal structure with RdRp is reported. Promising hit compounds are often discarded due to poor selectivity or unsuitable pharmacokinetics. We hope this review will provide a useful reference for further studies into the development of an anti-DENV drug.Autoimmune diseases are collectively addressed as chronic conditions initiated by loss of one's immunological tolerance, where body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer's, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in fortifying the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross blood brain barrier. MZ-1 This review presents exhaustive yet concise information on potentials of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.Cocrystallization of specific active pharmaceutical ingredients (APIs) in solid-state phase is becoming a feasible way to improve their corresponding physicochemical properties and ultimate bioavailability without making and breaking any covalent bonds within them. Many recent reports deal with the characterization and analysis topics of pharmaceutical APIs-based cocrystals. In this mini-review, we will focus on the recent steady-state and time-dependent spectroscopic investigation into the cocrystallization of specific APIs based on both Raman and emerging terahertz spectroscopy in pharmaceutical fields. Distinctive spectral, structural and also kinetic information of pharmaceutical APIs-based cocrystals are obtained and discussed, which would highlight the potential of vibrational spectroscopy as an attractive technique for various drug research and development during cocrystallization of specific APIs.Background Schizophrenia belongs to mental illnesses affecting 1% of the worldwide population. Its therapy is still unmet; thus, researchers aimed to develop new pharmacological molecules which can improve its management. Methods Moreover, the current typical and atypical antipsychotics should be formulated in more efficacious systems that can deliver the drug in the brain with as few side effects as possible. In further, the development of long acing efficient drug delivery systems could be significant in minimizing frequent dosing which is non-preferred to schizophrenics. Results Herein, authors focused on current developments of antipsychotic medications used in schizophrenia management. Various studies, which include the use of first and second-generation antipsychotics, analyzed according to their efficacy. In fact, in this review, oral, injectable, transdermal and intranasal formulations entrapped antipsychotics are presented to be valuable guidance for scientists to formulate more effective drug delivery systems for schizophrenic patients. Conclusions This review aimed to assist researchers working on schizophrenia management by summarizing current medications and newly synthesized drug delivery systems recently found in the literature.Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.
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