Novel 3D printed bioactive SiC orthopedic screw promotes bone growth associated activities by macrophages, neurons, and osteoblasts.

Ceramic additive manufacturing currently relies on binders or high-energy lasers, each with limitations affecting final product quality and suitability for medical applications. To address these challenges, our laboratory has devised a surface activation technique for ceramic particles that eliminates the necessity for polymer binders or high-energy lasers in ceramic additive manufacturing. We utilized this method to 3D print bioactive SiC orthopedic screws and evaluated their properties.

REV7-p53 interaction inhibits ATM-mediated DNA damage signaling.

REV7 is an abundant, multifunctional protein that is a known factor in cell cycle regulation and in several key DNA repair pathways including Trans-Lesion Synthesis (TLS), the Fanconi Anemia (FA) pathway, and DNA Double-Strand Break (DSB) repair pathway choice. Thus far, no direct role has been studied for REV7 in the DNA damage response (DDR) signaling pathway. Here we describe a novel function for REV7 in DSB-induced p53 signaling.

Heterodimers Are an Integral Component of Chemokine Signaling Repertoire.

Chemokines are a family of signaling proteins that play a crucial role in cell-cell communication, cell migration, and cell trafficking, particularly leukocytes, under both normal and pathological conditions. The oligomerization state of chemokines influences their biological activity. The heterooligomerization occurs when multiple chemokines spatially and temporally co-localize, and it can significantly affect cellular responses.

Promoting Bone Formation and Healing in Segmental Defects Through Ectopic Induced Membrane.

We aimed to determine whether addition of an in vivo ectopic induced membrane (EM) to the Masquelet Technique enhanced angiogenesis and bone formation in a segmental defect. After generating and stabilizing a diaphyseal femur defect, 10 rats received a polymethylmethacrylate (PMMA) spacer within the defect (control); 10 received another PMMA spacer implanted subcutaneously (EM). We removed the spacers and added autograft; the excised EM was added to their autograft (EM group).

A new obligate CXCL4-CXCL12 heterodimer for studying chemokine heterodimer activities and mechanisms.

Chemokines form a family of proteins with critical roles in many biological processes in health and disease conditions, including cardiovascular, autoimmune diseases, infections, and cancer. Many chemokines engage in heterophilic interactions to form heterodimers, leading to synergistic activity enhancement or reduction dependent on the nature of heterodimer-forming chemokines. In mixtures, different chemokine species with diverse activities coexist in dynamic equilibrium, leading to the observation of their combined response in biological assays.

Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention .

The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a "kill-switch" mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers.

Nanoparticle combination for precise stroma modulation and improved delivery for pancreatic cancer.

Therapeutic success in the treatment of pancreatic ductal adenocarcinoma (PDAC) is hindered by the extensive stroma associated to this disease. Stroma is composed of cellular and non-cellular components supporting and evolving with the tumor. One of the most studied mediators of cancer cell-stroma crosstalk is sonic hedgehog (SHh) pathway leading to the intense desmoplasia observed in PDAC tumors.

Structure and Function of Porcine Arteries Are Preserved for up to 6 Days Using the HypoRP Cold-storage Solution.

Background: Maintaining functional vessels during preservation of vascularized composite allografts (VCAs) remains a major challenge. The University of Wisconsin (UW) solution has demonstrated significant short-term benefits (4-6 h). Here we determined whether the new hypothermic resuscitation and preservation solution HypoRP improves both structure, survival, and function of pig arteries during storage for up to 6 days.

CXCL12-CXCL4 heterodimerization prevents CXCL12-driven breast cancer cell migration.

Despite improvements in cancer early detection and treatment, metastatic breast cancer remains deadly. Current therapeutic approaches have very limited efficacy in patients with triple negative breast cancer. Among the many mechanisms associated that contribute to cancer progression, signaling through the CXCL12-CXCR4 is an essential step in cancer cell migration.

Overcoming Immunological Resistance Enhances the Efficacy of A Novel Anti-tMUC1-CAR T Cell Treatment against Pancreatic Ductal Adenocarcinoma.

Chimeric antigen receptor (CAR) T cells have shown remarkable success in treating hematologic cancers. However, this efficacy has yet to translate to treatment in solid tumors. Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy with poor prognosis and limited treatment options.

Combining the Specific Anti-MUC1 Antibody TAB004 and Lip-MSA-IL-2 Limits Pancreatic Cancer Progression in Immune Competent Murine Models of Pancreatic Ductal Adenocarcinoma.

Immunotherapy regimens have shown success in subsets of cancer patients; however, their efficacy against pancreatic ductal adenocarcinoma (PDA) remain unclear. Previously, we demonstrated the potential of TAB004, a monoclonal antibody targeting the unique tumor-associated form of MUC1 (tMUC1) in the early detection of PDA. In this study, we evaluated the therapeutic benefit of combining the TAB004 antibody with Liposomal-MSA-IL-2 in immune competent and human MUC1 transgenic (MUC1.

A 3D human triculture system modeling neurodegeneration and neuroinflammation in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by beta-amyloid accumulation, phosphorylated tau formation, hyperactivation of glial cells, and neuronal loss. The mechanisms of AD pathogenesis, however, remain poorly understood, partially due to the lack of relevant models that can comprehensively recapitulate multistage intercellular interactions in human AD brains. Here we present a new three-dimensional (3D) human AD triculture model using neurons, astrocytes, and microglia in a 3D microfluidic platform.

3D Miniaturization of Human Organs for Drug Discovery.

"Engineered human organs" hold promises for predicting the effectiveness and accuracy of drug responses while reducing cost, time, and failure rates in clinical trials. Multiorgan human models utilize many aspects of currently available technologies including self-organized spherical 3D human organoids, microfabricated 3D human organ chips, and 3D bioprinted human organ constructs to mimic key structural and functional properties of human organs. They enable precise control of multicellular activities, extracellular matrix (ECM) compositions, spatial distributions of cells, architectural organizations of ECM, and environmental cues.

Mucin-1-Antibody-Conjugated Mesoporous Silica Nanoparticles for Selective Breast Cancer Detection in a Mucin-1 Transgenic Murine Mouse Model.

Mucin-1 (MUC1), a transmembrane glycoprotein is aberrantly expressed on ~90% of breast cancer and is an excellent target for nanoparticulate targeted imaging. In this study, the development of a dye-doped NIR emitting mesoporous silica nanoparticles platform conjugated to tumor-specific MUC1 antibody (ab-tMUC1-NIR-MSN) for optical detection of breast adenocarcinoma tissue is reported. The structural properties, the and performance of this nanoparticle-based probe were evaluated.

Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors.

Background: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1). We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo.

Bioengineered silk scaffolds in 3D tissue modeling with focus on mammary tissues.

In vitro generation of three-dimensional (3D) biological tissues and organ-like structures is a promising strategy to study and closely model complex aspects of the molecular, cellular, and physiological interactions of tissue. In particular, in vitro 3D tissue modeling holds promises to further our understanding of breast development. Indeed, biologically relevant 3D structures that combine mammary cells and engineered matrices have improved our knowledge of mammary tissue growth, organization, and differentiation.

Influence of pistachios on performance and exercise-induced inflammation, oxidative stress, immune dysfunction, and metabolite shifts in cyclists: a randomized, crossover trial.

Objectives: Pistachio nut ingestion (3 oz./d, two weeks) was tested for effects on exercise performance and 21-h post-exercise recovery from inflammation, oxidative stress, immune dysfunction, and metabolite shifts.

Methods: Using a randomized, crossover approach, cyclists (N = 19) engaged in two 75-km time trials after 2-weeks pistachio or no pistachio supplementation, with a 2-week washout period.

Mammary epithelial cell adhesion, viability, and infiltration on blended or coated silk fibroin-collagen type I electrospun scaffolds.

Interactions between cells and the extracellular matrix (ECM) play a crucial role in regulating biological tissue function. Silk biomaterials from Bombyx mori (B. mori) silkworm silk are widely used in tissue engineering.

Pancreatic Cancer Cells Isolated from Muc1-Null Tumors Favor the Generation of a Mature Less Suppressive MDSC Population.

Mucin 1 (MUC1) is a transmembrane mucin glycoprotein that is over-expressed and aberrantly glycosylated in >80% of human pancreatic ductal adenocarcinoma (PDA) and is associated with poor prognosis. To understand the role of MUC1 in PDA, we have recently developed two mouse models of spontaneous PDA, one that expresses full-length human MUC1 transgene (KCM mice) and one that is null for MUC1 (KCKO mice). We have previously reported that KCM mice express high levels of myeloid derived suppressor cells (MDSCs) in their tumors and develop highly aggressive PDA.

Breast tumor cell TACE-shed MCSF promotes pro-angiogenic macrophages through NF-κB signaling.

Most deaths associated with breast cancer, the most common malignancy in women, are caused by metastasis. Tumor associated macrophages significantly contribute to breast cancer progression and development of metastasis through the promotion of angiogenesis which involves a central regulator of macrophage functions: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Macrophages are activated by macrophage colony stimulating factor (MCSF) and chemokine (C-C motif) ligand 2 (CCL2) to secrete angiogenic factors including vascular endothelial growth factor (VEGF).

Tumor necrosis factor-alpha-converting enzyme activities and tumor-associated macrophages in breast cancer.

The role of the tumor microenvironment especially of tumor-associated macrophages (TAMs) in the progression and metastatic spread of breast cancer is well established. TAMs have primarily a M2 (wound-healing) phenotype with minimal cytotoxic activities. The mechanisms by which tumor cells influence TAMs to display a pro-tumor phenotype are still debated although the key roles of immunomodulatory cytokines released by tumor cells, including colony-stimulating factor 1, tumor necrosis factor (TNF) and soluble TNF receptors 1/2, soluble vascular cell adhesion molecule 1, soluble interleukin 6 receptor and amphiregulin, have been demonstrated.

Immune and inflammation responses to a 3-day period of intensified running versus cycling.

Functional overreaching has been linked to alterations in immunity and host pathogen defense, but little is known as to whether or not running and cycling evoke different responses. This study compared inflammation, muscle damage and soreness, and innate immune function responses to a 3-day period of intensified exercise in trained long distance runners (N=13, age 34.4±2.

Breast epithelial cell infiltration in enhanced electrospun silk scaffolds.

In the present study, the effects of air-flow impedance electrospinning and air-flow rates on silk-based scaffolds for biological tissues were investigated. First, the properties of scaffolds obtained from 7% and 12% silk concentrations were defined. In addition, cell infiltration and viability of MCF-10A breast epithelial cells cultured onto these scaffolds were used to determine the biological suitability of these nanostructures.