First-in-class mitogen-activated protein kinase (MAPK) p38α: MAPK-activated protein kinase 2 dual signal modulator with anti-inflammatory and endothelial-stabilizing properties.

We previously identified a small molecule, UM101, predicted to bind to the substrate-binding groove of p38α mitogen-activated protein kinase (MAPK) near the binding site of its proinflammatory substrate, mitogen-activated protein kinase-activated protein kinase (MK)2. UM101 exhibited anti-inflammatory, endothelial-stabilizing, and lung-protective effects. To overcome its limited aqueous solubility and p38α binding affinity, we designed an analog of UM101, GEn-1124, with improved aqueous solubility, stability, and p38α-binding affinity.

Defining obesity in the context of cancer: thinking beyond body mass index.

Obesity is a condition of excess body fat. Although it has been identified as a risk factor for multiple cancers in part because of its 'metainflammatory' state, it has also been paradoxically associated with improved response to immune checkpoint inhibition. To study obesity, one must first understand how best to define it.

Genetic and anatomical determinants of olfaction in dogs and wild canids.

Understanding the anatomical and genetic basis of complex phenotypic traits has long been a challenge for biological research. Domestic dogs offer a compelling model as they demonstrate more phenotypic variation than any other vertebrate species. Dogs have been intensely selected for specific traits and abilities, directly or indirectly, over the past 15,000 years since their initial domestication from the gray wolf.

Hearing threshold quartiles from the 1999-2006 National Health and Nutrition Examination Surveys.

This report extends the development of normative standards for estimating occupational hearing loss using data from the United States National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics. A proposed revision of the International Organization for Standardization (ISO) 1999:2013 standard ("Acoustics-Estimation on noise-induced hearing loss") uses a linear interpolation of hearing threshold data to estimate the 25th and 75th percentiles for men and women at 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz. This paper revisits the NHANES data to provide these estimates, avoiding other types of interpolations that could misrepresent the population data.

Mineral coated microparticles delivering Interleukin-4, Interleukin-10, and Interleukin-13 reduce inflammation and improve function after spinal cord injury in a rat.

After spinal cord injury (SCI) there is excessive inflammation and extensive infiltration of immune cells that leads to additional neural damage. Interleukin (IL)-4, IL-10, and IL-13 are anti-inflammatories that have been shown to reduce several pro-inflammatory species, alter macrophage state, and provide neuroprotection. However, these anti-inflammatories have a short half-life, do not cross the blood-spinal cord barrier, and large systemic doses of ant-inflammatory cytokines can cause increased susceptibility to infections.

What's in a name? Memory NK cells for cancer immunotherapy.

The discovery that natural killer (NK) cells can retain features of "memory" from previous stimulation and pathogen exposure was a landmark advance highlighting one of many ways in which NK cells of the innate immune system resemble T cells of the adaptive immune system. This ability to "remember" prior stimulation to bring about enhanced protection of the host sparked significant excitement regarding potential therapeutic applications. Yet, how closely the features of naïve and memory NK cells recapitulate those of T cells remains unclear.

Enhancement of Doxorubicin Efficacy by Bacopaside II in Triple-Negative Breast Cancer Cells.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options and high resistance to chemotherapy. Doxorubicin is commonly used, but its efficacy is limited by variable sensitivity and resistance. Bacopaside II, a saponin compound, has shown anti-cancer potential.

Novel Use and Value of Contrast-Enhanced Susceptibility-Weighted Imaging Morphologic and Radiomic Features in Predicting Extremity Soft Tissue Undifferentiated Pleomorphic Sarcoma Treatment Response.

Purpose: Undifferentiated pleomorphic sarcomas (UPSs) demonstrate therapy-induced hemosiderin deposition, granulation tissue formation, fibrosis, and calcification. We aimed to determine the treatment-assessment value of morphologic tumoral hemorrhage patterns and first- and high-order radiomic features extracted from contrast-enhanced susceptibility-weighted imaging (CE-SWI).

Materials And Methods: This retrospective institutional review board-authorized study included 33 patients with extremity UPS with magnetic resonance imaging and resection performed from February 2021 to May 2023.

Interleukin-6 and Interleukin-8 Gene Expressions Differ Between Male and Female Patients at Time of Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Purpose: To identify key molecular components within the femoroacetabular impingement hip and compare the findings between male and female patients across varying age groups.

Methods: All patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) without hip dysplasia were included. During hip arthroscopy, performed at University of Wisconsin Health, loose articular cartilage, excess synovium, damaged labral tissue, and minimal adipose tissue were debrided only as needed for visualization and tissue repair purposes and collected.

Local delivery of TGF-β1-mRNA decreases fibrosis in osteochondral defects.

Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.

Promoting the Efficacy of Deferiprone-Gallium-Protoporphyrin (IX) against Intracellular Infection with Lipid Liquid Crystalline Nanoparticles.

Nontuberculous mycobacteria (NTM) are among the recalcitrant bacterial strains that cause difficult-to-treat infections for patients with chronic underlying pulmonary conditions. The bacteria's intrinsic resistance to various antibiotics and their ability to infect macrophages enable them to overcome both the host immune response and standard antibiotics. Unconventional approaches to treating NTM-mediated infections are required.

Visceral fat area and subcutaneous fat area as measures of body composition in soft tissue sarcoma.

Background And Objectives: Soft tissue sarcomas (STS) are a heterogenous group of malignancies of mesenchymal origin. Given recent data linking obesity as well as the pattern of fat distribution with cancer outcomes, we sought to investigate the association of visceral fat area (VFA) and subcutaneous fat area (SFA) with oncologic outcomes in patients with STS undergoing surgery.

Methods: We analyzed data from 88 patients with STS diagnosed from 2008 to 2022.

Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus.

Optical redox imaging to screen synthetic hydrogels for stem cell-derived cardiomyocyte differentiation and maturation.

Significance: Heart disease is the leading cause of death in the United States, yet research is limited by the inability to culture primary cardiac cells. Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (iPSCs) are a promising solution for drug screening and disease modeling.

Aim: Induced pluripotent stem cell-derived CM (iPSC-CM) differentiation and maturation studies typically use heterogeneous substrates for growth and destructive verification methods.

Hepatic OATP1B zonal distribution: Implications for rifampicin-mediated drug-drug interactions explored within a PBPK framework.

OATP1B facilitates the uptake of xenobiotics into hepatocytes and is a prominent target for drug-drug interactions (DDIs). Reduced systemic exposure of OATP1B substrates has been reported following multiple-dose rifampicin; one explanation for this observation is OATP1B induction. Non-uniform hepatic distribution of OATP1B may impact local rifampicin tissue concentrations and rifampicin-mediated protein induction, which may affect the accuracy of transporter- and/or metabolizing enzyme-mediated DDI predictions.

Toward telomere-to-telomere cat genomes for precision medicine and conservation biology.

Genomic data from species of the cat family Felidae promise to stimulate veterinary and human medical advances, and clarify the coherence of genome organization. We describe how interspecies hybrids have been instrumental in the genetic analysis of cats, from the first genetic maps to propelling cat genomes toward the T2T standard set by the human genome project. Genotype-to-phenotype mapping in cat models has revealed dozens of health-related genetic variants, the molecular basis for mammalian pigmentation and patterning, and species-specific adaptations.

A comparison between full-length 16S rRNA Oxford nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues.

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification.

Chitogel with deferiprone following endoscopic sinus surgery: improved wound healing and microbiome.

Background: Adhesion formation, sinus ostial narrowing, and presence of pathogenic bacteria are associated with poor outcomes following endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Chitogel has been shown to improve wound healing, restore a healthier microbiome, and reduce post-operative infections post ESS. Deferiprone has antibacterial properties and has been shown to reduce adhesion formation.

Preclinical evaluation and first-in-dog clinical trials of PBMC-expanded natural killer cells for adoptive immunotherapy in dogs with cancer.

Background: Natural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product.

Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity.

Although mesenchymal stromal cell (MSC) based therapies hold promise in regenerative medicine, their clinical application remains challenging due to issues such as immunocompatibility. MSC-derived exosomes are a promising off-the-shelf therapy for promoting wound healing in a cell-free manner. However, the potential to customize the content of MSC-exosomes, and understanding how such modifications influence exosome effects on tissue regeneration remain underexplored.