Nano Plasma Membrane Vesicle-Lipid Nanoparticle Hybrids for Enhanced Gene Delivery and Expression.

Lipid nanoparticles (LNPs) have emerged as the leading nonviral nucleic acid (NA) delivery system, gaining widespread attention for their use in COVID-19 vaccines. They are recognized for their efficient NA encapsulation, modifiability, and scalable production. However, LNPs face efficacy and potency limitations due to suboptimal intracellular processing, with endosomal escape efficiencies (ESE) below 2.

A refined TTC assay precisely detects cardiac injury and cellular viability in the infarcted mouse heart.

Histological analysis with 2,3,5-triphenyltetrazolium chloride (TTC) staining is the most frequently used tool to detect myocardial ischemia/reperfusion injury. However, its practicality is often challenged by poor image quality in gross histology, leading to an equivocal infarct-boundary delineation and potentially compromised measurement accuracy. Here, we introduce several crucial refinements in staining protocol and sample processing, which enable TTC images to be analyzed with light microscopy.

Comparison of ionizable lipids for lipid nanoparticle mediated DNA delivery.

Lipid nanoparticles (LNPs) are successfully used for RNA-based gene delivery. In the context of gene replacement therapies, however, delivery of DNA expression plasmids using LNPs as a non-viral vector could be a promising strategy for the induction of longer-lasting effects. Therefore, DNA expression plasmids (3 to 4 kbp) coding for fluorescent markers or luciferase were combined with LNPs.

Lipid conjugate dissociation analysis improves the in vivo understanding of lipid-based nanomedicine.

Lipid conjugates have advanced the field of lipid-based nanomedicine by promoting active-targeting (ligand, peptide, antibody), stability (PEGylation), controlled release (lipoid prodrug), and probe-based tracking (fluorophore). Recent findings indicate lipid conjugates dissociating from nanomedicine upon encountering a biological environment. Yet, implications for (pre)clinical outcomes remain unclear.

Insights from an advisory board: Facilitating transition of care into adulthood in brain cancer survivors with acquired pediatric growth hormone deficiency.

Objective: Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition.

Design: An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood.

Zebrafish Larvae as an Model for Antimicrobial Activity Tests against Intracellular .

Introduction: Blood infections from multi-drug-resistant pose a major health burden. This is especially true because can survive and replicate intracellularly, and the development of new treatment strategies is dependent on expensive and time-consuming trials. The aim of this study was to develop a -infection model that makes it possible to directly observe infections of macrophages and to use this model to test the effect of antimicrobials against intra- and extracellular in order to close the gap between and rodent-infection models.

High efficiency preparation of monodisperse plasma membrane derived extracellular vesicles for therapeutic applications.

Extracellular vesicles (EVs) are highly interesting for the design of next-generation therapeutics. However, their preparation methods face challenges in standardization, yield, and reproducibility. Here, we describe a highly efficient and reproducible EV preparation method for monodisperse nano plasma membrane vesicles (nPMVs), which yields 10 to 100 times more particles per cell and hour than conventional EV preparation methods.

Constitutive Activation of gp130 in T Cells Results in Senescence and Premature Aging.

IL-6 family members contribute to host defense through the stimulation of acute-phase signaling, hematopoiesis, immune reactions, and regenerative processes. To investigate essential mechanisms that are linked toward a constitutively activated gp130 signaling, we generated and characterized a mouse model that reflects a constitutive and cytokine-independent activation of JAK/STAT3 signaling by Lgp130 in CD4- and CD8-positive T cells. Lgp130 is an engineered form of gp130 in which dimerization and activation are forced by a leucine zipper.

IL-6 in the infarcted heart is preferentially formed by fibroblasts and modulated by purinergic signaling.

Plasma IL-6 is elevated after myocardial infarction (MI) and is associated with increased morbidity and mortality. Which cardiac cell type preferentially contributes to IL-6 expression and how its production is regulated are largely unknown. Here, we studied the cellular source and purinergic regulation of IL-6 formation in a murine MI model.

Cardiac injection of USSC boosts remuscularization of the infarcted heart by shaping the T-cell response.

Regenerating the injured heart remains one of the most vexing challenges in cardiovascular medicine. Cell therapy has shown potential for treatment of myocardial infarction, but low cell retention so far has limited its success. Here we show that intramyocardial injection of highly apoptosis-resistant unrestricted somatic stem cells (USSC) into infarcted rat hearts resulted in an unprecedented thickening of the left ventricular wall with cTnT/BrdU cardiomyocytes that was paralleled by progressively restored ejection fraction.

Tablets Made from Paper-An Industrially Feasible Approach.

Many orally administrated drugs exhibit poor bioavailability due to their limited solubility. The smartFilm technology is an innovative approach to improve the drug aqueous solubility, where the drug is embedded within the matrix of cellulose-based paper in an amorphous state, hence increasing its solubility. Despite its proven effectiveness, smartFilms, i.

Renewable Beta-Elemene Based Cyclic Carbonates for the Preparation of Oligo(hydroxyurethane)s.

Conversion of β-elemene into new β-elemene dicarbonates through epoxidation and halide salt-catalyzed CO cycloaddition reactions is reported. Step-growth polyaddition of this dicarbonate to five different, commercial diamines was investigated under neat conditions at 150 °C yielding non-isocyanate-based low molecular weight oligo(hydroxyurethane)s with 1.3≤M ≤6.

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells Activating the TLR4 Signaling Pathway.

Beauvericin (BEA), a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on dendritic cells remain unknown so far. Here, we identified effects of BEA on murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms.

Incorporation of phosphatidylserine improves efficiency of lipid based gene delivery systems.

The essential homeostatic process of dead cell clearance (efferocytosis) is used by viruses in an act of apoptotic mimicry. Among others, virions leverage phosphatidylserine (PS) as an essential "eat me" signal in viral envelopes to increase their infectivity. In a virus-inspired biomimetic approach, we demonstrate that PS can be incorporated into non-viral lipid nanoparticle (LNP) pDNA/mRNA constructs to enhance cellular transfection.

Zebrafish () larva as an in vivo vertebrate model to study renal function.

There is an increasing interest in using zebrafish () larva as a vertebrate screening model to study drug disposition. As the pronephric kidney of zebrafish larvae shares high similarity with the anatomy of nephrons in higher vertebrates including humans, we explored in this study whether 3- to 4-day-old zebrafish larvae have a fully functional pronephron. Intravenous injection of fluorescent polyethylene glycol and dextran derivatives of different molecular weight revealed a cutoff of 4.

Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses.

Patients with acute ischemic stroke (AIS) present an increased incidence of systemic inflammatory response syndrome and release of Troponin T coinciding with cardiac dysfunction. The nature of the cardiocirculatory alterations remains obscure as models to investigate systemic interferences of the brain-heart-axis following AIS are sparse. Thus, this study aims to investigate acute cardiocirculatory dysfunction and myocardial injury in mice after reperfused AIS.

Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted murine heart.

In the adult heart, the epicardium becomes activated after injury, contributing to cardiac healing by secretion of paracrine factors. Here, we analyzed by single-cell RNA sequencing combined with RNA in situ hybridization and lineage tracing of Wilms tumor protein 1-positive (WT1) cells, the cellular composition, location, and hierarchy of epicardial stromal cells (EpiSC) in comparison to activated myocardial fibroblasts/stromal cells in infarcted mouse hearts. We identified 11 transcriptionally distinct EpiSC populations, which can be classified into three groups, each containing a cluster of proliferating cells.

Normoxic induction of HIF-1α by adenosine-A R signaling in epicardial stromal cells formed after myocardial infarction.

Myocardial infarction (MI) activates the epicardium to form epicardial stromal cells (EpiSC) that reside in the epicardial hypoxic microenvironment. Paracrine factors secreted by EpiSC were shown to modulate the injury response of the post-MI heart and improve cardiac function. We have previously reported that the expression of the angiogenic cytokines vascular endothelial growth factor A (VEGFA) and IL-6 is strongly upregulated in EpiSC by adenosine acting via the A receptor (A R).

Improving Payment for Collaborative Mental Health Care in Primary Care.

Background: There is strong evidence supporting implementation of the Collaborative Care Model within primary care. Fee-for-service payment codes, published by Current Procedural Terminology in 2018, have made collaborative care separately reimbursable for the first time. These codes (ie, 99492-99494) reimburse for time spent per month by any member of the care team engaged in Collaborative Care, including behavioral care managers, primary care providers, and consulting psychiatrists.

Adult growth hormone deficiency: Optimizing transition of care from pediatric to adult services.

Objective: Most patients with childhood-onset growth hormone deficiency (CO-GHD) receive treatment with exogenous growth hormone (GH) to facilitate the attainment of their full potential adult height. Recent evidence suggests that continuing GH administration during the transition period between the end of linear growth and full adult maturity is necessary for proper body composition and bone and muscle health, and may also have beneficial effects on metabolic parameters, bone mineral density, and quality of life. The timing of this transition period coincides with the transfer of care from a pediatric to an adult endocrinologist, creating the potential for a care gap as a consequence of losing the patient to follow-up.