Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice.

TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation in myocardial infarction and thereby attenuates inflammation. Motivated by the concept that heart failure with preserved ejection fraction (HFpEF) is a systemic inflammatory disease, we tested TY1 in a murine model of HFpEF. Intravenous TY1, packaged in a transfection reagent, reversed the cardiac and systemic manifestations of HFpEF in two-hit obese-hypertensive mice, without inducing weight loss.

Augmentation of DNA exonuclease TREX1 in macrophages as a therapy for cardiac ischemic injury.

Unlabelled: Noncoding RNAs (ncRNAs) are increasingly recognized as bioactive. Here we report the development of TY1, a synthetic ncRNA bioinspired by a naturally-occurring human small Y RNA with immunomodulatory properties. TY1 upregulates TREX1, an exonuclease that rapidly degrades cytosolic DNA.

Fabrication and characterization of a new eco-friendly sulfonamide-chitosan derivative with enhanced antimicrobial and selective cytotoxicity properties.

Chitosan (CH) exhibits low antimicrobial activity. This study addresses this issue by modifying the chitosan with a sulfonamide derivative, 3-(4-(N,N-dimethylsulfonyl)phenyl)acrylic acid. The structure of the sulfonamide-chitosan derivative (DMS-CH) was confirmed using Fourier transform infrared spectroscopy and Nuclear magnetic resonance.

Prophylactic common iliac artery temporary clamping versus balloon occlusion for management of placenta accreta spectrum disorders: A prospective clinical trial.

Objective: The present study aims to compare prophylactic common iliac artery (CIA) temporary clamping and preoperative balloon occlusion for managing placenta accreta spectrum (PAS) disorders.

Study Design: Between January 2019 and June 2020, 46 patients with PAS disorders were included. Of them, 26 patients were offered CIA balloon occlusion (Group A), while temporary CIA clamping was done for the other 20 patients (Group B).

Synthesis, characterization, and biological evaluation of new chitosan derivative bearing diphenyl pyrazole moiety.

This work reports the synthesis of a new pyrazole derivative by reacting 5-amino-1,3-diphenyl pyrazole with succinic anhydride and bearing the product chemically on the chitosan chains via amide linkage to achieve a new chitosan derivative (DPPS-CH). The prepared chitosan derivative was analyzed by IR, NMR, elemental analysis, XRD, TGA-DTG, and SEM. As compared with chitosan, DPPS-CH showed an amorphous and porous structure.

Systemic Delivery of Extracellular Vesicles Attenuates Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

Background: Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) patients. To date, treatments for HFpEF-related AF have been limited to anti-arrhythmic drugs and ablation. Here we examined the effects of immortalized cardiosphere-derived extracellular vesicles (imCDCevs) in rats with HFpEF.

TDO2-augmented fibroblasts secrete EVs enriched in immunomodulatory Y-derived small RNA.

Mounting evidence implicates extracellular vesicles (EVs) factors as mediators of cell therapy. Cardiosphere-derived cells are cardiac-derived cells with tissue reparative capacity. Activation of a downstream target of wnt/β-catenin signalling, tryptophan 2,3 dioxygenase (TDO2) renders therapeutically inert skin fibroblasts cardioprotective.

New thiadiazole modified chitosan derivative to control the growth of human pathogenic microbes and cancer cell lines.

The emergence of multidrug-resistant microbes and the propagation of cancer cells are global health issues. The unique properties of chitosan and its derivatives make it an important candidate for therapeutic applications. Herein, a new thiadiazole derivative, 4-((5-(butylthio)-1,3,4-thiadiazol-2-yl) amino)-4-oxo butanoic acid (BuTD-COOH) was synthesized and used to modify the chitosan through amide linkages, forming a new thiadiazole chitosan derivative (BuTD-CH).

Synthesis and characterization of new functionalized chitosan and its antimicrobial and in-vitro release behavior from topical gel.

Recently, chitosan and its derivatives have been gaining more attention due to their high integration into various biomedical applications. Herein, a new chitosan derivative was prepared by linking the chitosan (Cs) with a novel heterocyclic compound, Benzoimidazolyl-thiadiazole (BzimTD) to form Cs-BzimTD. The synthesis of the new chitosan derivative was confirmed by Fourier-Transform Infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (H NMR), thermogravimetric (TGA-DTG) analysis, elemental analysis, and UV-Visible spectrophotometer.

Extracellular Vesicles Secreted by TDO2-Augmented Fibroblasts Regulate Pro-inflammatory Response in Macrophages.

Extracellular vesicles (EVs) are secreted lipid bilayer vesicles that mediate cell to cell communication and are effectors of cell therapy. Previous work has shown that canonical Wnt signaling is necessary for cell and EV therapeutic potency. Tryptophan 2,3-dioxygenase (TDO2) is a target gene of canonical Wnt signaling.

Engineered Fibroblast Extracellular Vesicles Attenuate Pulmonary Inflammation and Fibrosis in Bleomycin-Induced Lung Injury.

Pulmonary fibrosis is a progressive disease for which no curative treatment exists. We have previously engineered dermal fibroblasts to produce extracellular vesicles with tissue reparative properties dubbed activated specialized tissue effector extracellular vesicles (ASTEX). Here, we investigate the therapeutic utility of ASTEX and in a mouse model of bleomycin-induced lung injury.

Methylene blue uptake by gum arabic/acrylic amide/3-allyloxy-2-hydroxy-1-propanesulfonic acid sodium salt semi-IPN hydrogel.

In this study, the capacity of methylene blue (MB) uptake from aqueous solution was investigated using acrylic amide-co-3-Allyloxy-2-hydroxy-1-propanesulfonic acid sodium salt/Gum Arabic semi-IPN hydrogel. The semi-IPN hydrogels were prepared by the classical free radical solution technique. The swelling experiments were carried out gravimetrically and the swelling kinetics parameters were calculated.

Synthesis and characterization of a novel benzothiazole functionalized chitosan and its use for effective adsorption of Cu(II).

Contamination of water with the copper(II) ions leads to serious diseases such as liver damage and cancer. This deadly effect prompted us to target the synthesis of a novel functionalized chitosan (Cs-BT) to be used as an adsorbent for removing the copper(II) ions from the aqueous solution. The functionalization was done by introducing benzothiazole moiety into the chitosan (Cs) chain and confirmed by the full disappearance of the NH band in the FT-IR spectrum of the adsorbent.

Small molecule inhibitors and culture conditions enhance therapeutic cell and EV potency via activation of beta-catenin and suppression of THY1.

Primary cell therapy continues to face significant hurdles to therapeutic translation including the inherent variations that exist from donor to donor, batch to batch, and scale-up driven modifications to the manufacturing process. Cardiosphere-derived cells (CDCs) are stromal/progenitor cells with clinically demonstrated tissue reparative capabilities. Mechanistic investigations have identified canonical Wnt/β-catenin signaling as a therapeutic potency marker, and THY1 (CD90) expression as inversely correlated with potency.

Extracellular Vesicles as Therapeutic Agents for Cardiac Fibrosis.

Heart disease remains an increasing major public health challenge in the United States and worldwide. A common end-organ feature in diseased hearts is myocardial fibrosis, which stiffens the heart and interferes with normal pump function, leading to pump failure. The development of cells for regenerative therapy has been met with many pitfalls on its path to clinical translation.

Synthesis of a hydrogel by grafting of acrylamide-co-sodium methacrylate onto chitosan for effective adsorption of Fuchsin basic dye.

This work was designed to produce effective adsorbent from acrylamide (AAm), sodium methacrylate (SMA), and chitosan (CTS) through free radical grafting polymerization for removing the Fuchsin dye from its solution. The gel fraction and the grafting parameters were studied, and the results showed maximum grafting percentage (1014.3%) and gel fraction (83.

Disease-modifying bioactivity of intravenous cardiosphere-derived cells and exosomes in mdx mice.

Dystrophin deficiency leads to progressive muscle degeneration in Duchenne muscular dystrophy (DMD) patients. No known cure exists, and standard care relies on the use of antiinflammatory steroids, which are associated with side effects that complicate long-term use. Here, we report that a single intravenous dose of clinical-stage cardiac stromal cells, called cardiosphere-derived cells (CDCs), improves the dystrophic phenotype in mdx mice.

Chitosan‑g‑maleic acid for effective removal of copper and nickel ions from their solutions.

Pollution of the environment associated with discharging the toxic heavy metals in water makes us focus the light to solve this problem. In continuation of our efforts, we aim in this work to utilize the graft copolymer (chitosan‑g‑maleic acid) to purify water from copper and nickel ions. The graft copolymer has been synthesized using gamma radiation and the grafting conditions have been optimized by studying the influence of acetic acid concentration (0.

A comprehensive method for identification of suitable reference genes in extracellular vesicles.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is one of the most sensitive, economical and widely used methods for evaluating gene expression. However, the utility of this method continues to be undermined by a number of challenges including normalization using appropriate reference genes. The need to develop tailored and effective strategies is further underscored by the burgeoning field of extracellular vesicle (EV) biology.

Exosomes as critical agents of cardiac regeneration triggered by cell therapy.

The CADUCEUS trial of cardiosphere-derived cells (CDCs) has shown that it may be possible to regenerate injured heart muscle previously thought to be permanently scarred. The mechanisms of benefit are known to be indirect, but the mediators have yet to be identified. Here we pinpoint exosomes secreted by human CDCs as critical agents of regeneration and cardioprotection.

Skills acquisition for trainee urologists: are the Federal Medical Centers in Nigeria suitable?

Background: Surgical training involves acquisition of knowledge and skills. The district hospitals are known to play complementary role in surgical training in many parts of the world; it is time to evaluate for the possible role Federal Medical Centers (FMC) in Nigeria can play to complement the training of urologists. Against this background, we retrospectively reviewed the relative frequency of urologic procedures performed in one of the FMC as a case study.