In Vivo Bioluminescence Imaging of Nuclear Factor kappaB Activation: A Valuable Model for Studying Inflammatory and Oxidative Stress in Live Mice.

The nuclear factor kappaB (NF-κB) is a redox-sensitive transcription factor that plays a critical role in inflammation among other biological functions. This ROS Protocol article describes an in vivo bioluminescence imaging assay for assessing NF-κB activation using the commercially available transgenic mice carrying NF-κB response element-luciferase reporter gene (NF-κB-RE-Luc). Using the highly sensitive Berthold NightOwl LB981 in vivo bioluminescence imaging system, we are able to visualize the NF-κB activation in live mice under basal conditions, suggesting constitutive activation of NF-κB as a part of its fundamental biology.

Dynamic fMRI networks predict success in a behavioral weight loss program among older adults.

More than one-third of adults in the United States are obese, with a higher prevalence among older adults. Obesity among older adults is a major cause of physical dysfunction, hypertension, diabetes, and coronary heart diseases. Many people who engage in lifestyle weight loss interventions fail to reach targeted goals for weight loss, and most will regain what was lost within 1-2 years following cessation of treatment.

A validation of the low mileage bias using naturalistic driving study data.

Introduction: This paper evaluated the low mileage bias (LMB) phenomenon for senior drivers using data mined from the Second Strategic Highway Research Program (SHRP 2) Naturalistic Driving Study. Supporters of the LMB construct postulate that it is only those seniors who drive the lowest annual mileage who are primarily responsible for the increased crash rates traditionally attributed to this population in general.

Method: The current analysis included 802 participants, all aged 65 or older who were involved in 163 property damage and injury crashes, and deemed to be at-fault in 123 (75%) of those instances.

Head impact exposure measured in a single youth football team during practice drills.

OBJECTIVE This study evaluated the frequency, magnitude, and location of head impacts in practice drills within a youth football team to determine how head impact exposure varies among different types of drills. METHODS On-field head impact data were collected from athletes participating in a youth football team for a single season. Each athlete wore a helmet instrumented with a Head Impact Telemetry (HIT) System head acceleration measurement device during all preseason, regular season, and playoff practices.

Evaluation of the effectiveness of toe board energy-absorbing material for foot, ankle, and lower leg injury reduction.

Objective: Since 2000, numerous improvements have been made to the National Association for Stock Car Auto Racing, Incorporated (NASCAR®) driver restraint system, resulting in improved crash protection for motorsports drivers. Advancements have included seats, head and neck restraints (HNRs), seat belt restraint systems, driver helmets, and others. These enhancements have increased protection for drivers from severe crash loading.

Mesenchymal stem cells support growth and organization of host-liver colorectal-tumor organoids and possibly resistance to chemotherapy.

Despite having yielded extensive breakthroughs in cancer research, traditional 2D cell cultures have limitations in studying cancer progression and metastasis and screening therapeutic candidates. 3D systems can allow cells to grow, migrate, and interact with each other and the surrounding matrix, resulting in more realistic constructs. Furthermore, interactions between host tissue and developing tumors influence the susceptibility of tumors to drug treatments.

Patient-derived glioblastoma stem cells respond differentially to targeted therapies.

The dismal prognosis of glioblastoma is, at least in part, attributable to the difficulty in eradicating glioblastoma stem cells (GSCs). However, whether this difficulty is caused by the differential responses of GSCs to drugs remains to be determined. To address this, we isolated and characterized ten GSC lines from established cell lines, xenografts, or patient specimens.

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease.

Our understanding of the functions of cardiac fibroblasts has moved beyond their roles in heart structure and extracellular matrix generation and now includes their contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts also have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation.

Can heart function lost to disease be regenerated by therapeutic targeting of cardiac scar tissue?

Myocardial infarction results in scar tissue that cannot actively contribute to heart mechanical function and frequently causes lethal arrhythmias. The healing response after infarction involves inflammation, biochemical signaling, changes in cellular phenotype, activity, and organization, and alterations in electrical conduction due to variations in cell and tissue geometry and alterations in protein expression, organization, and function - particularly in membrane channels. The intensive research focus on regeneration of myocardial tissues has, as of yet, only met with modest success, with no near-term prospect of improving standard-of-care for patients with heart disease.

Comparative study of oxidative stress biomarkers in urine of cooks exposed to three types of cooking-related particles.

Objectives: To evaluate how exposure to deep-frying oils, repeated frying oil (RFO) and restaurant waste oil (RWO) affects emission of polycyclic aromatic hydrocarbons (PAHs) and oxidative stress in male restaurant workers.

Methods: The study participants included 236 male restaurant workers in 12 restaurants in Shenzhen. Airborne particulate PAHs were measured over 12h on each of two consecutive work days.

A Highly Sensitive Chemiluminometric Assay for Real-Time Detection of Biological Hydrogen Peroxide Formation.

Hydrogen peroxide (HO) is a major reactive oxygen species (ROS) produced by various cellular sources, especially mitochondria. At high levels, HO causes oxidative stress, leading to cell injury, whereas at low concentrations, this ROS acts as an important second messenger to participate in cellular redox signaling. Detection and measurement of the levels or rates of production of cellular HO are instrumental in studying the biological effects of this major ROS.

Ordered-subset Split-Bregman algorithm for interior tomography.

Inspired by the Compressed Sensing (CS) theory, it has been proved that the interior problem of computed tomography (CT) can be accurately and stably solved if a region-of-interest (ROI) is piecewise constant or polynomial, resulting in the CS-based interior tomography. The key is to minimize the total variation (TV) of the ROI under the constraint of the truncated projections. Coincidentally, the Split-Bregman (SB) method has attracted a major attention to solve the TV minimization problem for CT image reconstruction.

Vitamin C, a Multi-Tasking Molecule, Finds a Molecular Target in Killing Cancer Cells.

Early work in the 1970s by Linus Pauling, a twice-honored Nobel laureate, led to his proposal of using high-dose vitamin C to treat cancer patients. Over the past several decades, a number of studies in animal models as well as several small-scale clinical studies have provided substantial support of Linus Pauling's early proposal. Production of reactive oxygen species (ROS) via oxidation of vitamin C appears to be a major underlying event, leading to the selective killing of cancer cells.

A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening.

Current animal and 2-D cell culture models employed in metastasis research and drug discovery remain poor mimics of human cancer physiology. Here we describe a "metastasis-on-a-chip" system allowing real time tracking of fluorescent colon cancer cells migrating from hydrogel-fabricated gut constructs to downstream liver constructs within a circulatory fluidic device system that responds to environmental manipulation and drug treatment. Devices consist of two chambers in which gut and liver constructs are housed independently, but are connected in series via circulating fluid flow.

The effects of a rotator cuff tear on activities of daily living in older adults: A kinematic analysis.

Rotator cuff tears (RCT) in older individuals may compound age-associated physiological changes and impact their ability to perform daily functional tasks. Our objective was to quantify thoracohumeral kinematics for functional tasks in 18 older adults (mean age=63.3±2.

MitoSOX-Based Flow Cytometry for Detecting Mitochondrial ROS.

MitoSOX-based assays are widely used to detect mitochondrial reactive oxygen species (ROS), especially superoxide. To this end, 5 μM MitoSOX is commonly used. In this ROS Protocols article, we described the flow cytometric protocol involving the use of various concentrations of MitoSOX (1, 2.

Nrf2 Deficiency Promotes Melanoma Growth and Lung Metastasis.

The role of Nrf2, a key regulator of antioxidant and cytoprotective genes, in tumorigenesis remains controversial. Here we showed that Nrf2 deficiency led to increased local tumor growth in mice following subcutaneous injection of B16-F10 melanoma cells, as indicated by increased proportion of animals with locally palpable tumor mass and time-dependent increases in tumor volume at the injection site. In vivo bioluminescence imaging also revealed increased growth of melanoma in Nrf2-null mice as compared with wild-type mice.

Fluorescence-Based Assays for Measuring Doxorubicin in Biological Systems.

Detection and measurement of doxorubicin in biological systems, including body fluids, cells, and tissues, are instrumental in understanding the mechanisms of action of this widely used drug in treating cancer as well as in causing adverse effects. In this article, we, for the first time, characterized the use of fluorescence-based techniques, including fluorescence spectrometry, microscopy, and flow cytometry in measuring and/or detecting doxorubicin in biological systems, including cell lysates and cultured intact cells. We showed that doxorubicin has a maximum excitation and emission wavelength of 470 and 560 nm, respectively.

Nrf2 Signaling in Macrophages.

The nuclear factor E2-related factor 2 (Nrf2) is known as the chief regulator of cellular antioxidant defenses as well as a suppressor of inflammation. Macrophages act as major players in inflammatory responses. Because oxidative stress and inflammation are two intertwined processes, the anti-inflammatory activity of Nrf2 signaling is believed to result from its upregulation of cellular antioxidant defenses via the antioxidant response element-driven transcription.

Innovative Bioluminometric Quantification of Cancer Cell Load in Target Organs: Implications for Studying Anticancer Drugs, Including ROS Enhancers.

Animal models are essential for developing effective drugs for treating human cancer. Examination of the formation of lung surface foci of B16-F10 melanoma cells is a widely used animal model for studying cancer metastasis and drug intervention. This model, however, suffers from several drawbacks, including its non-quantitative nature and inability to yield information on cancer cell load inside the target organ.

Driver Injury Risk Variability in Finite Element Reconstructions of Crash Injury Research and Engineering Network (CIREN) Frontal Motor Vehicle Crashes.

Objective: A 3-phase real-world motor vehicle crash (MVC) reconstruction method was developed to analyze injury variability as a function of precrash occupant position for 2 full-frontal Crash Injury Research and Engineering Network (CIREN) cases.

Method: Phase I: A finite element (FE) simplified vehicle model (SVM) was developed and tuned to mimic the frontal crash characteristics of the CIREN case vehicle (Camry or Cobalt) using frontal New Car Assessment Program (NCAP) crash test data. Phase II: The Toyota HUman Model for Safety (THUMS) v4.

Assessments of Fatty Infiltration and Muscle Atrophy From a Single Magnetic Resonance Image Slice Are Not Predictive of 3-Dimensional Measurements.

Purpose: To (1) determine whether standard clinical muscle fatty infiltration and atrophy assessment techniques using a single image slice for patients with a rotator cuff tear (RCT) are correlated with 3-dimensional measures in older individuals (60+ years) and (2) to determine whether age-associated changes to muscle morphology and strength are compounded by an RCT.

Methods: Twenty older individuals were studied: 10 with an RCT of the supraspinatus (5 men and 5 women) and 10 matched controls. Clinical imaging assessments (Goutallier and Fuchs scores and cross-sectional area ratio) were performed for participants with RCTs.

Robust human body model injury prediction in simulated side impact crashes.

This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments.

Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas.

Object: Irreversible electroporation (IRE) is a novel nonthermal ablation technique that has been used for the treatment of solid cancers. However, it has not been evaluated for use in brain tumors. Here, the authors report on the safety and feasibility of using the NanoKnife IRE system for the treatment of spontaneous intracranial gliomas in dogs.

Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells.

Ideal material characteristics for tissue engineering or regenerative medicine approaches to volumetric muscle loss (VML) include the ability to deliver cells, growth factors, and molecules that support tissue formation from a system with a tunable degradation profile. Two different types of human hair-derived keratins were tested as options to fulfill these VML design requirements: (1) oxidatively extracted keratin (keratose) characterized by a lack of covalent crosslinking between cysteine residues, and (2) reductively extracted keratin (kerateine) characterized by disulfide crosslinks. Human skeletal muscle myoblasts cultured on coatings of both types of keratin had increased numbers of multinucleated cells compared to collagen or Matrigel(TM) and adhesion levels greater than collagen.