Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has been implicated in bone destruction, tumor survival and metastases during OS. We examined the role of Dkk-1 in OS disease progression and explored strategies for targeting its activity.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys.

Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (Macrophages, Monocytes, and T-cells) infiltration and myofibroblast activation.

Novel Immune Response Evasion Strategy to Redose Adeno-associated Viral Vectors and Prolong Survival in Surfactant Protein-B Deficient Mice.

Surfactant protein-B (SP-B) deficiency is a lethal neonatal respiratory disease with few therapeutic options. Gene therapy using adeno-associated viruses (AAV) to deliver human cDNA (AAV-hSPB) can improve survival in a mouse model of SP-B deficiency. However, the effect of this gene therapy wanes.

Mesenchymal stem cell-derived exosome and liposome hybrids as transfection nanocarriers of Cas9-GFP plasmid to HEK293T cells.

Exosomes are natural membrane-enclosed nanovesicles (30-150 nm) involved in cell-cell communication. Recently, they have garnered considerable interest as nanocarriers for the controlled transfer of therapeutic agents to cells. Here, exosomes were derived from bone marrow mesenchymal stem cells using three different isolation methods.

Scale-Up of Human Amniotic Epithelial Cells Through Regulation of Epithelial-Mesenchymal Plasticity Under Defined Conditions.

Human amniotic epithelial cells (hAECs) have shown excellent efficacy in clinical research and have prospective applications in the treatment of many diseases. However, the properties of the hAECs and their proliferative mechanisms remain unclear. Here, single-cell RNA sequencing (scRNA-seq) is performed on hAECs obtained from amniotic tissues at different gestational ages and passages during in vitro culture.

Restoring bone healing potential.

A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.

Rapid Video Analysis for Contraction Synchrony of Human Induced Pluripotent Stem Cells-Derived Cardiac Tissues.

Background: The contraction behaviors of cardiomyocytes (CMs), especially contraction synchrony, are crucial factors reflecting their maturity and response to drugs. A wider field of view helps to observe more pronounced synchrony differences, but the accompanied greater computational load, requiring more computing power or longer computational time.

Methods: We proposed a method that directly correlates variations in optical field brightness with cardiac tissue contraction status (CVB method), based on principles from physics and photometry, for rapid video analysis in wide field of view to obtain contraction parameters, such as period and contraction propagation direction and speed.

Elevating Dermatology Beyond Aesthetics: Perinatal-Derived Advancements for Rejuvenation, Alopecia Strategies, Scar Therapies, and Progressive Wound Healing.

Dermatologists have been interested in recent advancements in regenerative therapy. Current research is actively investigating the possibility of placental tissue derivatives to decelerate the skin aging process, enhance skin regeneration, reduce scarring, and prevent hair loss. Amniotic membranes (AM) play a crucial role in regenerative medicine as they serve as a suitable means of transporting stem cells, growth hormones, cytokines, and other essential compounds.

Organ injury accelerates stem cell differentiation by modulating a fate-transducing lateral inhibition circuit.

Injured epithelial organs must rapidly replace damaged cells to restore barrier integrity and physiological function. In response, injury-born stem cell progeny differentiate faster compared to healthy-born counterparts, yet the mechanisms that pace differentiation are unclear. Using the adult Drosophila intestine, we find that injury speeds cell differentiation by altering the lateral inhibition circuit that transduces a fate-determining Notch signal.

Modeling tumor dynamics and predicting response to chemo-, targeted-, and immune-therapies in a murine model of pancreatic cancer.

We seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of the response of pancreatic cancer to the NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, and cisplatin), stromal-targeting drugs (calcipotriol and losartan), and an immune checkpoint inhibitor (anti-PD-L1). We developed a set of ordinary differential equations describing changes in tumor size (growth and regression) under the influence of five cocktails of treatments. Model calibration relies on three tumor volume measurements obtained over a 14-day period in a genetically engineered pancreatic cancer model (KrasLSLG12D-Trp53LSLR172H-Pdx1-Cre).

Electrospinning based biomaterials for biomimetic fabrication, bioactive protein delivery and wound regenerative repair.

Electrospinning is a remarkably straightforward and adaptable technique that can be employed to process an array of synthetic and natural materials, resulting in the production of nanoscale fibers. It has emerged as a novel technique for biomedical applications and has gained increasing popularity in the research community in recent times. In the context of tissue repair and tissue engineering, there is a growing tendency toward the integration of biomimetic scaffolds and bioactive macromolecules, particularly proteins and growth factors.

Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes.

Probiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. According to the International Society of Sports Nutrition (ISSN), probiotic supplementation can optimize the health, performance, and recovery of athletes at all stages of their careers. Recent research suggests that probiotics can improve immune system functions, reduce gastrointestinal distress, and increase gut permeability in athletes.

Safety and Efficacy of Autologous Bone Marrow Derived Mononuclear Cell Transplant in the Management of Various Neurological Disorders.

Background: Cerebral palsy (CP), traumatic spinal cord injury (SCI), and muscular dystrophy (MD), among the various other neurological disorders, are major global health problems because they are chronic disorders with no curative treatments at present. Current interventions aim to relieve symptoms alone and therefore emphasize the necessity for new approaches.

Objective: This study aims to assess the safety and efficacy of autologous bone marrow-derived mononuclear cell (BM-MNC) therapy in patients with CP, traumatic SCI, and MD.

Noninvasive Assessment of Vascular Function: From Physiological Tests to Biomarkers.

Vascular function is impaired by conditions such as hypertension, dyslipidemia, and diabetes as well as coronary risk factors including age, smoking, obesity, menopause and physical inactivity. Measurement of vascular function is useful not only for assessment of atherosclerosis itself but also in many other aspects such as understanding the pathophysiology, assessing treatment efficacy, and predicting prognosis of cardiovascular events. It is therefore important to accurately assess the extent of vascular function.

The influence of government-issued lockdowns during the COVID-19 pandemic on traumatic brain injuries in Tyrol, Austria.

Introduction: In February 2020, COVID-19 infections started to spread in Austria. This was followed by governmental actions and constraints such as lockdowns, quarantine protocols, and a ban on outdoor sports. The goal of this study was to investigate the influence of these measures on the number of traumatic brain injuries (TBI) in the state of Tyrol.

A Meta-analysis of Loneliness and Risk of Dementia using Longitudinal Data from >600,000 Individuals.

Loneliness is one critical risk factor for cognitive health. Combining data from ongoing aging studies and the published literature, we provided the largest meta-analysis on the association between loneliness and dementia ( = 21 samples, = 608,561) and cognitive impairment ( = 16, = 103,387). Loneliness increased risk for all-cause dementia (HR = 1.

A standards-based application for improving platelet transfusion workflow.

Objective: Thrombocytopenia is a common complication of hematopoietic stem-cell transplantation (HSCT), though many patients will become immune refractory to platelet transfusions over time. We built and evaluated an electronic health record (EHR)-integrated, standards-based application that enables blood-bank clinicians to match platelet inventory with patients using data previously not available at the point-of-care, like human leukocyte antigen (HLA) data for donors and recipients.

Materials And Methods: The web-based application launches as an EHR-embedded application or as a standalone application.

Germinal Center B Cells are Uniquely Targeted by Antibody-Suppressor CXCR5CD8 T Cells.

Background: Alloprimed antibody-suppressor CXCR5CD8 T cells (CD8 T cells) downregulate alloantibody production, mediate cytotoxicity of IgG B cells, and prolong allograft survival. The purpose of this investigation was to determine which immune-cell subsets are susceptible to CD8 T cell-mediated cytotoxicity or noncytotoxic suppression.

Methods: Alloprimed immune-cell subsets were evaluated for susceptibility to CD8 T cell-mediated in vitro cytotoxicity and/or suppression of intracellular cytokine expression.

Human adipose-derived multipotent stromal cells enriched with IL-10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift.

Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro-inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin-10 (IL-10) chemically modified mRNA (modRNA)-enriched human adipose-derived multipotent stromal cells (hADSCs) in a well-established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1-methylpseudouridine-5'-triphosphate (m1Ψ) by substituting uridine-5-triphosphate.

Activation of Immune Responses Through the RIG-I Pathway Using TRITC-Dextran Encapsulated Nanoparticles.

Pathogen-associated molecular patterns (PAMPs) are highly conserved motifs originating from microorganisms that act as ligands for pattern recognition receptors (PRRs), which are crucial for defense against pathogens. Thus, PAMP-mimicking vaccines may induce potent immune activation and provide broad-spectrum protection against microbes. Dextran encapsulation can regulate the surface characteristics of nanoparticles (NPs) and induces their surface modification.

Optimizations of Placenta Extracellular Matrix-Loaded Silk Fibroin/Alginate 3D-Printed Scaffolds Structurally and Functionally for Bone Tissue Engineering.

Recent interest has been focused on extracellular matrix (ECM)-based scaffolds totreat critical-sized bone injuries. In this study, urea was used to decellularize and solubilize human placenta tissue. Then, different concentrations of ECM were composited with 8% alginate (Alg) and 12% silk fibroin (SF) for printing in order to produce a natural 3D construct that resembled bone tissue.

Overweight, obesity, and cardiovascular disease in heterozygous familial hypercholesterolaemia: the EAS FH Studies Collaboration registry.

Background And Aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear.

Methods: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD.

Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function.

Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, and drug discovery. Effective reprogramming of fibroblasts is limited by their plasticity, that is, their ability to reprogram, and depends on solving several levels of tasks: inducing cardiomyocyte-like cells and obtaining functionally and metabolically mature cardiomyocytes. Currently, in addition to the use of more classical approaches such as overexpression of exogenous transcription factors, activation of endogenous cardiac transcription factors via controlled nucleases, such as CRISPR, represents another interesting way to obtain cardiomyocytes.