MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer: computational and in vitro approaches

The long-lasting inadequacy of existing treatments for prostate cancer has led to increasing efforts for developing novel therapies for this disease. MicroRNAs (miRNAs) are believed to have considerable therapeutic potential due to their role in regulating gene expression and cellular pathways. Identifying miRNAs that efficiently target genes and pathways is a key step in using these molecules for therapeutic purposes. Moreover, computational methods have been devised to help identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are known to have essential roles in cell proliferation and neoplastic transformation in different cancers including prostate cancer. Herein, we tried to identify miRNAs that target these pathways in the context of prostate cancer as therapeutic molecules. Genes involved in these pathways were analyzed with various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b were then selected as the best potential candidates that target a higher number of genes in these pathways with greater predictive scores. We then analyzed the expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate cancer clinical samples. miR-23a and miR-23b showed a significant downregulation in cell line and tissue samples, a finding which is consistent with overactivation of these pathways in prostate cancer. In addition, we overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two miRNAs decreased IL-6R expression which has a critical role in these pathways. These results suggest the probability of utilizing miR-23a and miR-23b as therapeutic targets for the treatment of prostate cancer. © 2015, International Society of Oncology and BioMarkers (ISOBM)

MSC-derived exosomes carrying a cocktail of exogenous interfering RNAs an unprecedented therapy in era of COVID-19 outbreak

Background: The onset of the SARS-CoV-2 pandemic has resulted in ever-increasing casualties worldwide, and after 15 months, standard therapeutic regimens are yet to be discovered. Main body: Due to the regenerative and immunomodulatory function of MSCs, they can serve as a suitable therapeutic option in alleviating major COVID-19 complications like acute respiratory distress syndrome. However, the superior properties of their cognate exosomes as a cell-free product make them preferable in the clinic. Herein, we discuss the current clinical status of these novel therapeutic strategies in COVID-19 treatment. We then delve into the potential of interfering RNAs incorporation as COVID-19 gene therapy and introduce targets involved in SARS-CoV-2 pathogenesis. Further, we present miRNAs and siRNAs candidates with promising results in targeting the mentioned targets. Conclusion: Finally, we present a therapeutic platform of mesenchymal stem cell-derived exosomes equipped with exogenous iRNAs, that can be employed as a novel therapeutic modality in COVID-19 management aiming to prevent further viral spread within the lung, hinder the virus life cycle and pathogenesis such as immune suppression, and ultimately, enhance the antiviral immune response. © 2021, The Author(s)

Efficient inhibition of human immunodeficiency virus replication using novel modified microRNA-30a targeting 3'-untranslated region transcripts

RNA interference (RNAi)-based gene therapy is currently considered to be a combinatorial anti-human immunodeficiency virus-1 (HIV-1) therapy. Although arti­ficial polycistronic microRNAs (miRs) can reduce HIV-1 escape mutant variants, this approach may increase the risk of side effects. The present study aimed to optimize the efficiency of anti-HIV RNAi gene therapy in order to reduce the cell toxicity induced by multi-short hairpin RNA expression. An artificial miR-30a-3'-untranslated region (miR-3'-UTR) obtained from a single RNA polymerase II was used to simultaneously target all viral transcripts. The results of the present study demonstrated that HIV-1 replication was signifi­cantly inhibited in the cells with the miR-3'-UTR construct, suggesting that miR-3'-UTR may serve as a promising tool for RNAi-based gene therapy in the treatment of HIV-1. © 2016, Spandidos Publications. All Rights Reserved

Advanced fabrication techniques for hydrogen-cooled engine structures

Described is a program for development of coolant passage geometries, material systems, and joining processes that will produce long-life hydrogen-cooled structures for scramjet applications. Tests were performed to establish basic material properties, and samples constructed and evaluated to substantiate fabrication processes and inspection techniques. Results of the study show that the basic goal of increasing the life of hydrogen-cooled structures two orders of magnitude relative to that of the Hypersonic Research Engine can be reached with available means. Estimated life is 19000 cycles for the channels and 16000 cycles for pin-fin coolant passage configurations using Nickel 201. Additional research is required to establish the fatigue characteristics of dissimilar-metal coolant passages (Nickel 201/Inconel 718) and to investigate the embrittling effects of the hydrogen coolant

Analysis of microRNA signatures using size-coded ligation-mediated PCR

The expression pattern and regulatory functions of microRNAs (miRNAs) are intensively investigated in various tissues, cell types and disorders. Differential miRNA expression signatures have been revealed in healthy and unhealthy tissues using high-throughput profiling methods. For further analyses of miRNA signatures in biological samples, we describe here a simple and efficient method to detect multiple miRNAs simultaneously in total RNA. The size-coded ligation-mediated polymerase chain reaction (SL-PCR) method is based on size-coded DNA probe hybridization in solution, followed-by ligation, PCR amplification and gel fractionation. The new method shows quantitative and specific detection of miRNAs. We profiled miRNAs of the let-7 family in a number of organisms, tissues and cell types and the results correspond with their incidence in the genome and reported expression levels. Finally, SL-PCR detected let-7 expression changes in human embryonic stem cells as they differentiate to neuron and also in young and aged mice brain and bone marrow. We conclude that the method can efficiently reveal miRNA signatures in a range of biological samples

Effect of Uniform and Non-uniform High-z Nanoparticles Distribution in Tumor Volume on Dose Enhancement Factor During 192Ir Brachytherapy

Introduction: Irradiation of loaded tumor with high-Z nanoparticles with low energy photon of 192Ir source during brachytherapy increases absorbed dose of tumor due to increase in possibility of photoelectric phenomena. Therefore, this study aimed to investigate dose enhancement due to nanoparticles (NPs) with different atomic numbers and concentrations as well as effect of NPs distribution (uniform & non- uniform) on dose enhancement. Methods: Dosimetric parameters of HDR-192Ir source (MicroSelectron model) were calculated by MCNP-4C code on the basis of recommendations of AAPM, TG-43. A tumor (1 cm3) loaded with uniform and non-uniform distribution of 7, 18 and 30 mgr/gr of 79Au, 64Gd, 26Fe and 22Ti in water phantom (30×30×30 cm3) was simulated. Results: DEF of 4.7% to 19.4% and 3.3 to 18.6% were calculated respectively for uniform distribution of 79Au and 64Gd with 7 to 30 mgr/gr concentrations. For non-uniform distribution these values were 0.4%to 1.9% and 0.2% to 1.2%, respectively. Increased dose of the peripheral-health tissue due to presence of 2 to 8.5 mgr/gr of 79Au and 64Gd was estimated from 1.3% to 6.5% and 1.1% to 4.2%, respectively. Conclusion: increase of atomic number and concentrations of NPs enhance the absorbed dose due to increased possibility of photoelectric phenomena. Non-uniform distribution of NPs underestimated dose compared to uniform distribution; therefore, considering accurate NPs distribution inside the tumor volume is crucial to calculation of dose enhancement. Targeted labeling of NPs for the maximum absorption by tumor and for the minimal penetration into peripheral tissues has potential to increase radiation therapeutic ratio

Tumor dose enhancement by nanoparticles during high dose rate 192 Ir brachytherapy

Aims and Objectives: The present study aims to evaluate and compare the dose enhancement factor (DEF) of tumor injected with different nanoparticles (NPs) around high dose rate (HDR) 192 Ir brachytherapy source. Materials and Methods: Monte Carlo calculations were performed with MCNPX code to determine the DEF caused by in tumor injected with 79 Au, 64 Gd, 26 Fe, and 22 Ti NPs during HDR 192 Ir brachytherapy. The uniform and non-uniform distribution of NPs within tumor was modeled with simple NPs-water mixture, and realistic nano-scale-lattice model. Furthermore, a margin of 79 Au and 64 Gd NPs was implemented around the tumor volume. Results: The increased dose caused by uniformly distributed 79 Au and 64 Gd NPs with 7, 18, and 30 mgr/gr concentrations was 4.7, 11.8, 19.4, and 3.3, 8.3, and 18.6, respectively. For non-uniform distribution, it was 0.4, 1.2, 1.9, and 0.2, 0.7, and 1.2, respectively. Increased tumor dose due to 26 Fe and 22 Ti was not significant. The peripheral-healthy tissue dose as margin with 2, 5, and 8.5 mgr/gr of 79 Au and 64 Gd increased by 1.3, 3.6, 6.5, and 1.1, 2.5, and 4.2, respectively. Increase the radial depth of tumor (from 1.5 to 5 cm) increase DEF (up to 22.3). The nano-lattice model underestimated the DEF up to 4 and 3.6 for 79Au and 64 Gd NPs, respectively. Conclusion: Injecting of high-Z gold NPs into tumor increases the absorbed dose of tumor irradiated with 192 Ir HDR brachytherapy source. Size, geometry, concentration, and distribution model of NPs and tumor depth are crucial factors to accurately estimate the DEF. © 2015 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow

Polycarbonate biodegradation by isolated molds using clear-zone and atomic force microscopic methods

The accumulation of dry waste containing synthetic polymers due to their resistance to microorganisms and other environmental factors has posed some serious problems to the environment in recent years. On the other hand, plastics constitute the foundations of economy as they are widely used in agriculture, constructions, packaging, health care and also medicine. The aim of this research was to investigate the role of different isolated fungi in the degradation of polycarbonate polymers. For this purpose, sampling was done using the garden soil and waste leachate from Isfahan Waste Management Organization. Samples were enriched in the liquid mineral salt medium supplemented with polycarbonate and then were transferred to the same medium solidified with agar to isolate and identify different fungi. Finally, their biodegradation activity was investigated with the help of clear- zone and atomic force microscopic (AFM) techniques, and also lipase and amylase production was tested. Among 15 isolated genera of mold fungi, Fusarium , Ulocladium , Chrysosporium and Penicillium showed biodegradation activity. According to the diameter of clear zone around the fungal colonies and also AFM results, the highest rate of degradation was related to Fusarium. Lipase activity of all isolated fungi was positive, but amylase activity of Ulocladium was negative. It can be concluded that some fungal strains such as Fusarium can be used for the biodegrada- tion of plastic materials as it leads to a very eco-friendly biodegradation process