Menopause-induced 17β-estradiol and progesterone loss increases senescence markers, matrix disassembly and degeneration in mouse cartilage.

Female individuals who are post-menopausal present with higher incidence of knee osteoarthritis (KOA) than male counterparts; however, the mechanisms underlying this disparity are unknown. The most commonly used preclinical models lack human-relevant menopausal phenotypes, which may contribute to our incomplete understanding of sex-specific differences in KOA pathogenesis. Here we chemically induced menopause in middle-aged (14-16 months) C57/BL6N female mice.

Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms.

Pulmonary Artery Vasa Vasorum Damage in Severe COVID-19-Induced Pulmonary Fibrosis.

Background: COVID-19 patients exhibit higher incidence of thrombosis in arteries and veins, including those in lungs. Vasa vasorum, which support large blood vessels, have shown involvement in these pathologic processes.

Methods: To further explore the extent of microvascular damage caused by COVID-19 infection, we examined resected main, right, or left pulmonary artery specimens from patients undergoing bilateral lung transplantation for COVID-19- or non-COVID-19-induced pulmonary fibrosis compared with organ donors by histologic and immunohistologic analyses.

Space exploration and risk of Parkinson's disease: a perspective review.

Systemic mitochondrial dysfunction, dopamine loss, sustained structural changes in the basal ganglia including reduced tyrosine hydroxylase, and altered gait- these effects observed in space-flown animals and astronauts mirrors Parkinson's disease (PD). Evidence of mitochondrial changes in space-flown human cells, examined through the lens of PD, suggests that spaceflight-induced PD-like molecular changes are important to monitor during deep space exploration. These changes, may potentially elevate the risk of PD in astronauts.

The goat as a model for temporomandibular joint disc replacement: Techniques for scaffold fixation.

A state-of-the-art scaffold capable of efficiently reconstructing the temporomandibular joint (TMJ) disc after discectomy remains elusive. The major challenge has been to identify a degradable scaffold that remodels into TMJ disc-like tissue, and prevents increased joint pathology, among other significant complications. Tissue engineering research provides a foundation for promising approaches towards the creation of successful implants/scaffolds that aim to restore the disc.

tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.

Tet enzymes are epigenetic modifiers that impact gene expression via 5mC to 5hmC oxidation. Previous work demonstrated the requirement for Tet and 5hmC during zebrafish retinogenesis. mutants possessed defects in the formation of differentiated retinal neurons, but the mechanisms underlying these defects are unknown.

Development of a method to achieve antegrade in situ fenestration of endovascular stent grafts in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is the focal dilation of the terminal aorta, which can lead to rupture if left untreated. Traditional endovascular aneurysm repair techniques are minimally invasive and pose low mortality rates compared with open surgical repair; however, endovascular aneurysm repair procedures face challenges in accommodating variations in the patient's anatomy. Complex aneurysms are defined when the sac extends past the renal arteries or has an insufficient neck landing zone to deploy a traditional endograft.

Longitudinal changes in electrophysiology and widefield calcium imaging following electrode implantation.

. Intracortical microelectrode arrays often fail to deliver reliable signal quality over chronic recordings, and the effect of an implanted recording array on local neural circuits is not completely understood..

Mission SpaceX CRS-19 RRRM-1 space flight induced skin genomic plasticity via an epigenetic trigger.

Genomic plasticity helps adapt to extreme environmental conditions. We tested the hypothesis that exposure to space environment (ESE) impacts the epigenome inducing genomic plasticity. Murine skin samples from the Rodent Research Reference Mission-1 were procured from the International Space Station (ISS) National Laboratory.

Hypoxia-Inducible Factor-2α Promotes Liver Fibrosis by Inducing Hepatocellular Death.

The activation of hypoxia-inducible factors (HIF)-1α and 2α in the liver is closely linked to the progression of fatty liver diseases. Prior studies indicated that disrupting hepatocyte HIF-2α attenuates diet-induced hepatic steatosis, subsequently decreasing fibrosis. However, the direct role of hepatocyte HIF-2α in liver fibrosis has not been addressed.

Examining the NEUROG2 lineage and associated gene expression in human cortical organoids.

Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated from human embryonic stem cell-derived cortical organoids (COs) to show that NEUROG1 and NEUROG2 are most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating that NEUROG1-derived lineages predominate early and NEUROG2 lineages later.

Cardiac matrix-bound Nanovesicles provide insight into mechanisms of clinical heart disease progression to failure.

Aims: Remodeling of the extracellular matrix (ECM) is critical for effective wound healing and maintaining organ homeostasis. The ECM of soft tissues, including cardiac, contains embedded nanovesicles; or matrix-bound nanovesicles (MBV). The luminal cargo of MBV consists of lipids, microRNAs (miRNAs), and proteins that influence the function of immune and stromal cells.

Synergistic label-free fluorescence imaging and miRNA studies reveal dynamic human neuron-glial metabolic interactions following injury.

Neuron-glial cell interactions following traumatic brain injury (TBI) determine the propagation of damage and long-term neurodegeneration. Spatiotemporally heterogeneous cytosolic and mitochondrial metabolic pathways are involved, leading to challenges in developing effective diagnostics and treatments. An engineered three-dimensional brain tissue model comprising human neurons, astrocytes, and microglia is used in combination with label-free, two-photon imaging and microRNA studies to characterize metabolic interactions between glial and neuronal cells over 72 hours following impact injury.

Exercise Preconditioning of the Donor Liver Decreases Cold Ischemia/Reperfusion Injury in a Mouse Model.

Background: Liver transplantation stands as the primary treatment for end-stage liver disease, with demand surging in recent decades because of expanded indications. However, hepatic ischemia/reperfusion injury can lead to liver transplant failure in both deceased donor and living donor transplantation. This study explored whether preconditioning donor livers through exercise training (ExT) could mitigate cold ischemic injury posttransplantation.

Advanced therapy to cure diabetes: mission impossible is now possible?

Cell and Gene therapy are referred to as advanced therapies that represent overlapping fields of regenerative medicine. They have similar therapeutic goals such as to modify cellular identity, improve cell function, or fight a disease. These two therapeutic avenues, however, possess major differences.

Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.

Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are upregulated in the heart, lung, kidney, and liver, but not mediastinal lymph nodes.

Methodologies for Mitochondrial Omic Profiling During Spaceflight.

To be able to understand how spaceflight can affect human biology, there is a need for maximizing the amount of information that can be obtained from experiments flown to space. Recently there has been an influx of data obtained from astronauts through multi-omics approaches based on both governmental and commercial spaceflight missions. In addition to data from humans, mitochondrial specific data is gathered for other experiments from rodents and other organisms that are flown in space.

A finite element model for biomechanical characterization of ex vivo peripheral nerve dysfunction during stretch.

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury.

Intervening to Preserve Function in Ischemic Cardiomyopathy with a Porous Hydrogel and Extracellular Matrix Composite in a Rat Myocardial Infarction Model.

Multiple hydrogels are developed for injection therapy after myocardial infarction, with some incorporating substances promoting tissue regeneration and others emphasizing mechanical effects. In this study, porosity and extracellular matrix-derived digest (ECM) are incorporated, into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA)) and evaluate whether this biomaterial injectate can abrogate adverse remodeling in rat ischemic cardiomyopathy. After myocardial infarction, rats are divided into four groups: NP (non-porous hydrogel) without either ECM or porosity, PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and PME with porosity and ECM digest added to the synthetic copolymer.

Local Controlled Delivery of IL-4 Decreases Inflammatory Bone Loss in a Murine Model of Periodontal Disease.

Chronic inflammatory diseases are a leading global health problem. In many of these diseases, the consistent presence of systemic low-grade inflammation induces tissue damage. This is true in conditions such as diabetes, arthritis, and autoimmune disorders, where an overactive and uncontrolled host immune response is a major driver of immunopathology.