Plasma Extracellular Vesicle-derived MicroRNA Associated with Human Alpha-1 Antitrypsin Deficiency-mediated Liver Disease.

Background And Aims: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with liver disease, ranging from fibrosis to hepatocellular carcinoma. The disease remains asymptomatic until its final stages when liver transplantation is the only available therapy. Biomarkers offer an advantage for disease evaluation.

Diseased Tendon Models Demonstrate Influence of Extracellular Matrix Alterations on Extracellular Vesicle Profile.

Tendons enable movement through their highly aligned extracellular matrix (ECM), predominantly composed of collagen I. Tendinopathies disrupt the structural integrity of tendons by causing fragmentation of collagen fibers, disorganization of fiber bundles, and an increase in glycosaminoglycans and microvasculature, thereby driving the apparent biomechanical and regenerative capacity in patients. Moreover, the complex cellular communication within the tendon microenvironment ultimately dictates the fate between healthy and diseased tendon, wherein extracellular vesicles (EVs) may facilitate the tendon's fate by transporting biomolecules within the tissue.

Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway.

Liver fibrosis associated with increased mortality is caused by activation of hepatic stellate cells and excessive production and accumulation of extracellular matrix in response to fibrotic insults. It has been shown that in addition to liver inflammation, systemic inflammation also contributes to liver fibrogenesis. A deeper understanding of mechanisms that control liver fibrotic response to intra- and extra-hepatic inflammation is essential to develop novel clinical strategies against this disease.

Peptide-based capture-and-release purification of extracellular vesicles and statistical algorithm enabled quality assessment.

Circulating extracellular vesicles (EVs) have gained significant attention for discovering tumor biomarkers. However, isolating EVs with well-defined homogeneous populations from complex biological samples is challenging. Different isolation methods have been found to derive different EV populations carrying different molecular contents, which confounds current investigations and hinders subsequent clinical translation.

CRISPR-Cas9 Engineered Extracellular Vesicles for the Treatment of Dominant Progressive Hearing Loss.

Clinical translation of gene therapy has been challenging, due to limitations in current delivery vehicles such as traditional viral vectors. Herein, we report the use of gRNA:Cas9 ribonucleoprotein (RNP) complexes engineered extracellular vesicles (EVs) for gene therapy. By leveraging a novel high-throughput microfluidic droplet-based electroporation system (μDES), we achieved 10-fold enhancement of loading efficiency and more than 1000-fold increase in processing throughput on loading RNP complexes into EVs (RNP-EVs), compared with conventional bulk electroporation.

Towards artificial intelligence-enabled extracellular vesicle precision drug delivery.

Extracellular Vesicles (EVs), particularly exosomes, recently exploded into nanomedicine as an emerging drug delivery approach due to their superior biocompatibility, circulating stability, and bioavailability in vivo. However, EV heterogeneity makes molecular targeting precision a critical challenge. Deciphering key molecular drivers for controlling EV tissue targeting specificity is in great need.

Nano pom-poms prepared exosomes enable highly specific cancer biomarker detection.

Extracellular vesicles (EVs), particularly nano-sized small EV exosomes, are emerging biomarker sources. However, due to heterogeneous populations secreted from diverse cell types, mapping exosome multi-omic molecular information specifically to their pathogenesis origin for cancer biomarker identification is still extraordinarily challenging. Herein, we introduced a novel 3D-structured nanographene immunomagnetic particles (NanoPoms) with unique flower pom-poms morphology and photo-click chemistry for specific marker-defined capture and release of intact exosome.

Biologically enhanced starch bio-ink for promoting 3D cell growth.

The excellent rheological property has legitimated the suitability of starch hydrogel for extrusion-based 3D printing. However, the inability to promote cell attachment and migration has precluded the non-modified starch hydrogel from direct applications in the biomedical field. Herein, we develop a novel 3D printable nanocomposite starch hydrogel with highly enhanced biocompatibility for promoting 3D cell growth, by formulating with gelatin nanoparticles and collagen.

Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the main pathogens associated with lower respiratory tract infections in infants and young children worldwide. Exosomes secreted by antigen presenting cells (APCs) can elicit immune responses by carrying major histocompatibility complex (MHC) class I molecules complexed with antigenic peptides and other co-stimulating factors. Therefore, we developed novel immunomagnetic nanographene particles to sequentially isolate, surface engineer, and release intact dendritic cell (DC) exosomes for use as a potential vaccine platform against RSV.

Extracellular Vesicles as an Advanced Delivery Biomaterial for Precision Cancer Immunotherapy.

In recent years, cancer immunotherapy has been observed in numerous preclinical and clinical studies for showing benefits. However, due to the unpredictable outcomes and low response rates, novel targeting delivery approaches and modulators are needed for being effective to more broader patient populations and cancer types. Compared to synthetic biomaterials, extracellular vesicles (EVs) specifically open a new avenue for improving the efficacy of cancer immunotherapy by offering targeted and site-specific immunity modulation.

Reducing time to treatment and patient costs with breast cancer: the impact of patient visits.

Background: The purpose of this study was to evaluate the impact of processes aimed at reducing time to treatment initiation (TTI) on minimizing the days spent to complete pretreatment visits and the associated costs for patients with nonmetastatic breast cancer.

Methods: System-wide initiatives were implemented in 2014 to minimize TTI, by incorporating multiple strategies (eg, creation of teams, patient liaisons, process mapping) and enhanced communication to increase coordinated visits. Average number of days spent to complete visits, TTI, and associated patient costs including driving expenses, parking, food, childcare, and lost wages were calculated and compared between the years 2015 and 2018.

The power of one: Evaluating the impact of a single multi-disciplinary treatment visit on time to treatment.

Breast cancer treatment often requires multi-disciplinary evaluation, which can require multiple visits, delaying time to treatment initiation (TTI). The present analysis evaluated the impact of system-wide initiatives to reduce TTI by evaluating TTI for patients completing treatment evaluation in a single visit compared with those having multiple visits. The results demonstrated that patients who completed multi-disciplinary evaluation in a single visit had a reduced median TTI (27 vs 32 days, P = .

Carbodiimide Conjugation of Latent Transforming Growth Factor β1 to Superparamagnetic Iron Oxide Nanoparticles for Remote Activation.

Conjugation of latent growth factors to superparamagnetic iron oxide nanoparticles (SPIONs) is potentially useful for magnetically triggered release of bioactive macromolecules. Thus, the goal of this work was to trigger the release of active Transforming Growth-Factor Beta (TGF-β) via magnetic hyperthermia by binding SPIONs to the latent form of TGF-β, since heat has been shown to induce release of TGF-β from the latent complex. Commercially available SPIONS with high specific absorption rates (SAR) were hydrolyzed in 70% ethanol to create surface carboxylic acid conjugation sites for carbodiimide chemistry.

There is no coherent evidence for a bilingual advantage in executive processing.

Three studies compared bilinguals to monolinguals on 15 indicators of executive processing (EP). Most of the indicators compare a neutral or congruent baseline to a condition that should require EP. For each of the measures there was no main effect of group and a highly significant main effect of condition.