Exosomes and miRNAs in disease pathogenesis and opportunities for molecular targeting

Exosomes/extracellular vesicles (EVs) are cell-derived mixed-populations of vesicles released by almost all cells into the intercellular microenvironment, ending up in the circulation. Exosomes contain proteins, RNAs and lipid molecules reflecting the status of the parental cell at the time of release, making them promising candidates for biomarker discovery. The contents of exosomes are protected by a lipid bilayer, leading to better stability of bio-macromolecules. Recent evidence suggests a novel role for exosomes as conveyors of information among cells and across tissues, through horizontal transfer of proteins, lipids, and nucleic acids. Exosomes have been the subject of numerous research in recent years; however, their roles still have to be identified in the pathogenesis of different diseases. MicroRNAs (miRNAs) are small (18-25 nucleotide long) non-coding RNAs which play pivotal roles in the gene expression process and it is estimated that about one third of the human genome is controlled by miRNAs. miRNA regulatory processes have been found to influence many essential biological pathways, such as cellular development, proliferation, apoptosis, and cellular signaling. A great proportion of miRNAs has been reported to be associated with the exosome function of different biofluids. The aim of this research was to elucidate the role of exosomes/EVs as well as miRNAs in the pathogenesis of different diseases, including alcoholic liver disease, hepatitis C, and cancer. This knowledge may lead to the development of novel molecular diagnostic approaches, as well as innovative drug delivery modalities for small RNA-targeted therapy. My research resulted in a) the establishment of new methods and approaches to the study of exosomes/EVs, as well as comparative literature on the efficacy of several isolation and characterization techniques. b) identification of the role of exosomes and miRNA-122 in the cross talk between hepatocytes and immune cells in alcoholic liver disease c) identification of the role of exosomes in HCV pathogenesis, including the potential of molecular therapies based on miRNA and exosome targeting in vitro and in vivo d) understanding the bio-distribution of exosomes and miRNA in an in vivo murine model and f) exploring the utility of miRNA and exosomes in biofluids in cancer biomarker discovery

Tetrameric DABCO™-Bromine: an Efficient and Versatile Reagent for Bromination of Various Organic Compounds

Tetrameric DABCO™-bromine is a powerful brominating agent but shows reasonable selectivity with certain substrates. The selective bromination for activated aromatic compounds and alkenes is reported. Synthesis of -bromo ketones and nitriles has also been achieved by using this reagent and the results are also reported. All products reported were obtained in good to excellent yields.KEYWORDS: Tetrameric DABCO™-Bromine, TDB, solid supports, bromination, -bromination, 1,2-dibromo compounds, bromohydrin

Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: a Randomized, Double-Blind, Placebo-Controlled Trial

Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for diabetic foot ulcer (DFU). This study was carried out to evaluate the effects of magnesium administration on wound healing and metabolic status in subjects with DFU. This randomized, double-blind, placebo-controlled trial was performed among 70 subjects with grade 3 DFU. Subjects were randomly divided into two groups (35 subjects each group) to receive either 250 mg magnesium oxide supplements or placebo daily for 12 weeks. Pre- and post-intervention wound depth and appearance were scored in accordance with the “Wagner-Meggitt’s” wound assessment tool. Fasting blood samples were taken at baseline and after the 12-week intervention to assess related markers. After the 12-week treatment, compared with the placebo, magnesium supplementation resulted in a significant increase in serum magnesium (+0.3 ± 0.3 vs. −0.1 ± 0.2 mg/dL, P < 0.001) and significant reductions in ulcer length (−1.8 ± 2.0 vs. −0.9 ± 1.1 cm, P = 0.01), width (−1.6 ± 2.0 vs. −0.8 ± 0.9 cm, P = 0.02), and depth (−0.8 ± 0.8 vs. −0.3 ± 0.5 cm, P = 0.003). In addition, significant reductions in fasting plasma glucose (−45.4 ± 82.6 vs. −10.6 ± 53.7 mg/dL, P = 0.04), serum insulin values (−2.4 ± 5.6 vs. +1.5 ± 9.6 μIU/mL, P = 0.04), and HbA1c (−0.7 ± 1.5 vs. −0.1 ± 0.4%, P = 0.03) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. −0.004 ± 0.02, P = 0.01) were seen following supplementation of magnesium compared with the placebo. Additionally, compared with the placebo, taking magnesium resulted in significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (−19.6 ± 32.5 vs. −4.8 ± 11.2 mg/L, P = 0.01) and significant increase in plasma total antioxidant capacity (TAC) concentrations (+6.4 ± 65.2 vs. −129.9 ± 208.3 mmol/L, P < 0.001). Overall, magnesium supplementation for 12 weeks among subjects with DFU had beneficial effects on parameters of ulcer size, glucose metabolism, serum hs-CRP, and plasma TAC levels

Brillouin light scattering studies of aqueous E. coli cell lysate: Viscoelastic properties of a multimacromolecular solution

Brillouin spectroscopy was used to probe the viscoelastic properties of E. coli bacterial cell lysate in aqueous solution at GHz-frequencies over the range -5.0 $^\circ$C $\leq T \leq$ 50.0 $^\circ$C. This work offers a first temperature dependent study on cell lysate by Brillouin light scattering. A single peak was observed in the spectra and attributed to a longitudinal acoustic mode of the solution. The speed of sound, bulk modulus, apparent viscosity and hypersound attenuation were extracted from the frequency shift and FWHM of the spectral peak. This study demonstrate that the behavior of complex multimacromolecular solutions, as shown by \textit{E. coli} lysate, can exhibit viscoelastic properties closely akin to those observed in simple binary aqueous protein solutions. Furthermore, our findings show that by analyzing the raw spectral signature of the Brillouin spectra, it may be possible to identify protein denaturation

Comprehensive thermodynamic and operational optimization of a solar-assisted LiBr/water absorption refrigeration system

Absorption cooling systems have been investigated for many years due to their ability to use low-grade heat instead of electricity as the energy source. The aim of this work is to advance the performance of a single-effect Lithium bromide/water absorption cooling system. Taking the generator and evaporator temperatures as variables, the system is optimized to maximize exergetic and energetic efficiencies at different operational conditions using a multi-objective–multi-variable Genetic Algorithm. The Group Method of Data Handling neural network approach is adopted to derive correlations between the design variables and operational parameters. Finally, the system is coupled to evacuated tube solar collectors and compared to a similar system. The results reflect a maximum improvement in energetic and exergetic efficiencies of about 9.1% and 3.0%, respectively. This translates into savings of 187 dollars for every square meter of solar collector at present time. This improvement is achieved by decreasing the mean temperature of the generator by 6.2 °C and increasing the mean temperature of the evaporator by 1.6 °C. In the case of applying low-grade heat such as solar energy, it brings about both an improvement in the thermodynamic performances and a reduction in the generator temperature

Rapid detection of pathogenic bacteria in whole blood samples using 23S rRNA PCR assays

Purpose: Bloodstream infections are a general cause of death among hospitalized patients. Rapid diagnosis and timely treatment can reduce mortality. The aim of this investigation was to evaluate the 23S rRNA PCR assays as a rapid detection method for diagnose of sepsis in patients with suspected bacteremia. Methods: A cross-sectional study was conducted at Shahid Beheshti University Hospital in Kashan from November 2017 to December 2018. The blood samples of 265 patients with suspected bacteremia were studied by blood culture and 23S rRNA PCR techniques. The results were analyzed using SPSS version 16 and Chi-square test. Results: Eighty (30.2) blood samples of 265 suspected patients, were identified as positive by PCR assays, whereas 27 (10.2) were identified as positive by the blood culture technique. The statistical analysis showed a significant association between the results of PCR assays and blood culture and factors such as prior antibiotic use and underlying diseases (P <0.05). Also a significant correlation was observed between laboratory and clinical criteria and the results of both PCR assays and blood culture (P < 0.05). Conclusion: The 23S rRNA PCR method is a rapid and sensitive technique specially for diagnosing sepsis among patients in whom bacteremia is difficult to diagnose with culture method including neonates and patients who have taken antibiotics before microbial culture. © 2019 Firoozeh et al. All rights reserved

Solvent-free synthesis of xanthene derivatives by Preyssler type heteropolyacid

Dimedone reacted with aromatic aldehydes and 3,4-methylenedioxyphenol or β-naphthol in the presence of a catalytic amount of Preyssler type heteropolyacid, H14[NaP5W30O110], as a green and reusable catalyst under solvent-free conditions to form a variety of  new xanthene derivatives in very good  yields.KEY WORDS: Xanthene derivatives, Solvent-free synthesis, Preyssler type heteropolyacid, 3,4-Methylene dioxyphenol, β-Naphthol, Three-component one-pot reactions Bull. Chem. Soc. Ethiop. 2011, 25(3), 399-406

One-Pot Synthesis of Tetrasubstituted Imidazoles Catalyzed by Preyssler-Type Heteropoly Acid

Abstract: A simple one-pot four-component synthetic method was reported for the preparation of tetrasubstituted imidazole derivatives from benzil, aromatic aldehydes, primary amines and ammonium acetate in the presence of Preyssler-type heteropoly acid catalyst. This method was proved to be ecobenign, easy work-up, convenient, relatively short reaction times and the products were isolated with high yields

Biodistribution and function of extracellular miRNA-155 in mice

Circulating miRNAs can be found in extracellular vesicles (EV) and could be involved in intercellular communication. Here, we report the biodistribution of EV associated miR-155 using miR-155 KO mouse model. Administration of exosomes loaded with synthetic miR-155 mimic into miR-155 KO mice resulted in a rapid accumulation and clearance of miR-155 in the plasma with subsequent distribution in the liver, adipose tissue, lung, muscle and kidney (highest to lowest, respectively). miR-155 expression was detected in isolated hepatocytes and liver mononuclear cells of recipient KO mice suggesting its cellular uptake. In vitro, exosome-mediated restoration of miR-155 in Kupffer cells from miR-155 deficient mice augmented their LPS-induced MCP1 mRNA increase. The systemic delivery of wild type plasma to miR-155 KO mice also resulted in a rapid accumulation of miR-155 in the circulation and distribution to the liver and adipose tissue. In summary, our results demonstrate tissue biodistribution and biologic function of EV-associated miR-155