Biology subjects

Brunt, K. R.

Publications and source records attributed to Brunt, K. R..

4 recordsLinked to original sources

bioRxiv2025

Turmeric Phyto-nanoparticle: enhanced cellular bioavailability and anti-inflammatory effect in human monocyte / macrophage model

The poor bioavailability of curcuminoids remains a major challenge to therapeutic use. This is largely due to their hydrophobicity, poor absorption, rapid metabolism, and short circulating half-life--limitations that are now being addressed through advances in nano- and micro-emulsion technologies. Curcuminoids and other water-insoluble phyto-polyphenols offer significant putative health benefits as anti-inflammatory, antioxidant, anticancer, radioprotective, and neuroprotective agents. Conventional emulsion-based delivery systems, such as liposomes, micelles, or solid lipid particles, rely on various emulsifying surfactants and/or excipients, some of which may themselves pose health risks. Here, we establish a novel class of all-natural, additive-free, oil-free, and emulsion-free Turmeric Phyto-NanoParticles (TPNPs) formulated directly from turmeric rhizomes and tested in a human monocyte/macrophage cell model to assess bioavailability kinetics and the efficacy of antioxidant and anti-inflammatory potential. TPNPs are enriched with curcuminoids (24.85% by mass), form a homogeneous nanoparticle distribution, exhibit higher antioxidant capacity, and demonstrate significantly improved cellular uptake in both monocytes and macrophages compared to conventionally purified curcuminoids. Favourable cellular pharmacodynamic anti-inflammatory effect of TPNPs was shown by increased levels of the cytoprotective enzyme heme oxygenase-1 (HMOX1), and a more effective reduction in lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) secretion compared to conventional curcuminoids. TPNPs could thus serve as a stable, non-synthetic, excipient-free formulation for safe and effective delivery of curcuminoids by nanocarriers for inflammatory conditions.

pharmacology and toxicology↗

bioRxiv2024

ROSLT: An Improved Raspberry-Pi Open-Source Live Voluntary-Wheel Running Tracker Method and Resource

BackgroundExercise promotes health and has therapeutic effects on disease. Over time, the body improves its maximal exercise capacity through training adaptations such as an increase in VO2 max. In mice, voluntary wheel running allows for a natural setting to test spontaneous running behaviour under non-stressed conditions. There is a need to design sensitive animal-based assay that improves resolution for differentiating exercise performance from a regular cyclometer (which presents a single value from a summary of dynamic data collected over time) and offer circadian analyses. The purpose of this work is to examine the exercise behaviours of mice with a focus on circadian rhythm of running. We hypothesize the pi cyclometer (ROSLT) will mirror VDO M2.1 behaviors, enhancing circadian rhythm insights. MethodsUsing a hand-built cyclometer programmed through the Raspberry Pi computer, voluntary wheel running behaviours in CD-1 mice ([~]8-10 weeks) were recorded for 6 consecutive days. This features a Hall Effect sensor and neodymium magnets attached on the running wheels that will detect changes to wheel rotation, speed, acceleration, and distance (continuously) and publish the data to a server in real-time. To compare capabilities, running wheels will also be equipped with the VDO M2.1 WR Cycling Computer to track distance which will be manually recorded once a day. Accuracy from both devices were mechanically validated. ResultsThe main findings include that voluntary wheel running distance over 6 days produces inaccuracies by the VDO. The VDO showed fluctuations in distance over the last 3 days, while ROSLT showed consistent measurements. ConclusionThis comparison shows that ROSLT expands on the running activity of mice each day while maintaining accuracy and precision. This novel dynamic circadian cyclometer will advance our research abilities and can be used in differentiating exercise performance in applications such as doping.

physiology↗

bioRxiv2024

Yap is a Nutrient Sensor Sensitive to the Amino Acid L-Isoleucine and Regulates Expression of Ctgf in Cardiomyocytes.

Myocardial infarction and reperfusion is a complex injury consisting of many distinct molecular stress patterns that influence cardiomyocyte survival and adaptation. Cell signalling that is essential to cardiac development also presents potential disease-modifying opportunities to recover and limit myocardial injury or maladaptive remodelling. Here we hypothesized that Yap signalling could be sensitive to one or more molecular stress patterns associated with early acute ischemia. Yap, not Taz, patterns of expression differ in post-myocardial infarct compared to peri-infarct tissue suggesting cell-specificity that would be challenging to resolve for causation in vivo. Using H9c2 ventricular myotubes in vitro as a model, Yap levels were most sensitive to nutrient deprivation compared to other stress patterns typified by ischemia within the first hour of stress. Moreover, this is mediated by amino acid availability, dominantly L-isoleucine, and influences the expression of Ctgf--a major determinant of myocardial adaptation after injury. These findings present novel opportunities for future therapeutic development and risk assessment for myocardial injury and adaptation.

pharmacology and toxicology↗

bioRxiv2023

Cardiac atrophy, dysfunction, and metabolic impairments: a cancer-induced heart failure phenotype

Muscle atrophy and weakness are prevalent features of cancer. While extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naive cancer. In cell-based models of orthotopic, syngeneic epithelial ovarian cancer (EOC) and pancreatic ductal adenocarcinoma (PDAC), and a patient-derived pancreatic xenograft model (PDX), we evaluated cardiac structure, function, and metabolism. Tumor-bearing mice showed cardiac atrophy and intrinsic systolic and diastolic dysfunction; associated with hypotension and exercise intolerance. In hearts of ovarian tumor-bearing mice, fatty acid-supported mitochondrial respiration decreased and carbohydrate-supported respiration increased, establishing a substrate shift in cardiac metabolism that is characteristic of heart failure. EOC decreased cytoskeletal and cardioprotective gene expression, which was paralleled by downregulation of transcription factors that regulate cardiomyocyte size and function. PDX tumors altered myosin heavy chain isoform expression - a molecular phenotype observed in heart failure. Markers of autophagy and ubiquitin-proteasome system were upregulated with cancer, providing evidence of catabolic signaling that promotes cardiac wasting. Together, metabolic stress, cardiac gene dysregulation, and upregulation of catabolic pathways contribute to cardiac atrophy and failure during cancer. Finally, we demonstrate that pathological cardiac remodeling is induced by human cancer, providing translational evidence of cancer-induced cardiomyopathy.

physiology↗