Efficacy and safety of a novel antiviral herbal preparation in ICU-admitted patients with COVID-19: A phase III double-blinded controlled trial

Objective: Despite an increasing number of studies, there is as yet no definite treatment developed for the coronavirus disease 2019 (COVID-19). In this clinical trial, we examined the efficacy of a novel herbal antiviral preparation in critically ill COVID-19 patients.Materials and Methods: A total number of 120 ICU-admitted patients with a diagnosis of COVID-19 pneumonia were recruited to the trial. Participants were equally randomized to receive either the novel antiviral preparation sublingually, for up to two consecutive weeks or till discharge, or placebo. Clinical and laboratory parameters as well as survival rates were compared between the two groups.Results: The cumulative incidence of death throughout the study period was 8.33% in the intervention group and 60% in the placebo group (risk ratio: 0.14; 95% confidence interval [CI], 0.05 to 0.32; p<0.001). On day 7, several parameters including white blood cells (WBCs) count, C-reactive protein, and SpO2 were improved for the treatment group compared with the placebo group (p-values of 0.05, 0.01, and <0.001, respectively).Conclusion: This preparation might be suggested as a potentially promising COVID-19 treatment

LncRNAs roles in Chemoresistance of Cancer cells

Cancer is an important health issue worldwide. Cancer therapy is multifaceted, and drug resistance is still the major limiting factor in treatment of patients with this disease. Although the mechanisms of anticancer drug resistance have been broadly investigated, a massive biological signal pathway of Non-coding RNAs (ncRNAs) involved in this process has not been completely understood. Long noncoding RNAs (lncRNAs) are a kind of transcripts with a minimum length of 200 nucleotides in size which have a limited potential for coding proteins. The roles of these RNA molecules have been evaluated in relation to several pathological processes including tumor formation and progression. Increasing evidence haverecently reported that non-coding RNAs (ncRNAs), particularly long non-coding RNAs have significant roles in many cellular and genomic processes, and because of their potential in regulation specific genes, they are also involved in drug resistance. In this review, we review the literature on the features oflncRNA, their regulation roles in the gene expression related to chemoresistance and the potential of these RNAs as targeted therapies for personalized treatment in cancers. Keywords: Drug resistance; Long non-coding RNAs; Non-coding RNAs; cancer; epithelial to mesenchymal transition; personalized treatment

Designing a Humanized Immunotoxin Based on HER2 Specific scFv and DFF40 Toxin Against Breast Cancer: An In-Silico Study

Breast cancer is the most frequent cancer in women worldwide. Human epidermal growth factor receptor 2 (HER2) is a receptor which is overexpressed in breast cancer cells. Targeting this receptor could be a key factor for treatment of breast cancer patients. Herceptin is an antibody which can bind to HER2 receptor, in addition Herceptin derived single chain fragment V (scFv) can be used in designing immunotoxin for targeting HER2 positive cancer cells. DFF40 is a nuclease activated by caspase-3 and responsible for genomic DNA fragmentation during apoptosis. In this study, we used bioinformatics tools to design an immunotoxin containing HER2 specific scFv and DFF40 toxin. An immunotoxin construct was designed by linking scFv and DFF40 amino acids sequence via a peptide linker. The secondary structure, physicochemical features, solubility, and allergenicity of construct were predicted. The tertiary structure was built, refined, and evaluated. Protein-protein docking, and molecular dynamics studies were carried out for evaluation of immunotoxin-receptor binding, and the stability of the immunotoxin, respectively. The results indicated that the designed construct could be a stable protein with appropriate solubility, which is not an allergen and has a suitable structure which can bind to HER2 appropriately. Finally, this construct could be a promising candidate for producing an HER2 targeting immunotoxin. However, different in vitro and in vivo immunological assays should be performed to confirm the efficacy of the designed construct

Nattokinase: Structure, applications and sources

Nattokinase (NK) as a serine protease enzyme has a strong fibrinolytic activity that is found in bacteria. In comparison to other fibrinolytic enzymes (plasmin, urokinase, and t-PA), NK has the advantages of a long lifespan, low cost, and no side effects. As a food supplement, it could be utilized as a substance to treat cardiovascular disease. As a result, NK has high commercial value and therapeutic applications. The current study provides a brief description of the properties of this important enzyme. Also, some of the most notable applications of NK are discussed. Eventually, different microbial, plant and animal sources of this enzyme are summarized in the last par

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis

Abstract:Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring

Liposomal delivery system/adjuvant for tuberculosis vaccine

Abstract As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next‐generation TB vaccines

Insights into the Function of Regulatory RNAs in Bacteria and Archaea

Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals