Biology subjects

Rosa-Caldwell, M. E.

Publications and source records attributed to Rosa-Caldwell, M. E..

4 recordsLinked to original sources

bioRxiv2026

Palliative Irradiation Affects Temporal Degradation of Rodent Vertebral Bone Mechanics, Architecture, and Composition

BackgroundPalliative radiation therapy (RT) for metastatic spine disease significantly increases the risk of vertebral fractures. However, the temporal mechanisms underlying radiation-induced vertebral bone fragility remain poorly understood. ObjectiveTo evaluate the longitudinal effects of a single high-dose irradiation, simulating palliative RT, on vertebral bone mechanical, architectural, and compositional properties in a healthy, skeletally mature rat model. MethodsThirty-one male Sprague Dawley rats received a single 15 Gy lumbar spine irradiation (IR). L4 vertebrae were assessed across all groups (irradiation: 7, 14, and 28 days post-IR, controls: at 0 and 28 days post-IR) for compressive strength and stiffness, micro-CT-derived bone composition and trabecular indices, serum bone turnover markers (NTX and BAP) and advanced glycation endproducts (AGEs). ResultsIrradiation induced progressive deterioration of vertebral bone mechanical properties, with strength decreasing up to 44% and stiffness up to 38% by 28 days post-IR, compared to 0- day controls. Trabecular bone exhibited reduced BMD, BV/TV, and Tb.N with increased Tb.Sp, a shift toward a more rod-like structure. Early post-IR changes suggested disrupted bone remodeling, characterized by elevated NTX and AGEs, but decreased BAP. Multivariable regression demonstrated that Tb.Th and AGEs were independent predictors of stiffness, collectively explaining 61% of its variance. DiscussionHigh-dose irradiation induces sustained temporal degradation of vertebral mechanical properties driven by both trabecular architectural deterioration and alterations in bone matrix quality. Measures of bone composition and non-enzymatic bone turnover suggest this early damage was driven by disruption of bone cellular homeostasis, favoring increased resorption over formation. These findings support that radiation impairs both structural integrity and pre-yield mechanical behavior, providing mechanistic insight into the elevated fracture risk observed clinically after irradiation for metastatic spine disease. Lay summaryThis study used a rat model to mimic palliative radiation therapy for cancer that has spread to the spine and evaluated the changes in bone quality up to 28 days post-therapy. We found that irradiation progressively weakened the structural integrity and composition of the bones in the spine and disrupted the normal balance of bone breakdown and repair, leading to greater bone loss and fragility. Our findings provide insight into the increased risk of fractures observed in patients receiving radiation therapy to the spine and may support efforts to better protect bone health during treatment.

bioengineering↗

bioRxiv2025

Changes in muscle strength and moderators of protein turnover in a rodent model of anorexia nervosa and recovery

Anorexia nervosa (AN) is a psychiatric disorder characterized by severe caloric restriction, leading to health complications. In addition to fat loss, AN also results in profound skeletal muscle loss, yet molecular pathways underlying these musculoskeletal complications or how long-lasting these musculoskeletal consequences may be are currently unknown. The purpose of this study was to investigate the effects of AN and subsequent weight recovery on muscle strength, size, and moderators of protein turnover in a rat model of AN. Female Sprague Dawley rats (n=11/group, 8 weeks of age) underwent 30 days of simulated AN (50-60% food restriction) followed by varying recovery periods. Muscle mass, strength, and protein synthesis/degradation pathways were assessed. AN led to substantial reductions in muscle mass and strength. While muscle mass recovered within 30 days, muscle strength remained depressed in rats with a prior history of AN, suggesting alterations to muscle quality. Moreover, moderators of protein synthesis (Igf1, Redd1, Deptor) remained altered following 30 days of AN and subsequent recovery. These findings suggest muscle impairments in AN may be longer-lasting than previously thought and may contribute to increased health complications and reduced quality of life in those with a history of AN.

physiology↗

bioRxiv2021

Muscle weakness precedes atrophy during cancer cachexia and is associated with muscle-specific mitochondrial stress

Muscle weakness and wasting are defining features of cancer-induced cachexia. Mitochondrial stress occurs before atrophy in certain muscles, but distinct responses between muscles and across time remains unclear. We aimed to determine the time-dependent and muscle-specific responses to Colon-26 (C26) cancer-induced cachexia in mice. At 2 weeks post-inoculation, the presence of small tumours did not alter body or muscle mass but decreased force production in the quadriceps and diaphragm. Pyruvate-supported mitochondrial respiration was lower in quadriceps while mitochondrial H2O2 emission was elevated in diaphragm. At 4 weeks, large tumours corresponded to lower body mass, muscle mass, and cross-sectional area of fibers in quadriceps and diaphragm. Force production in quadriceps was unchanged but remained lower in diaphragm vs control. Mitochondrial respiration was increased while H2O2 emission was unchanged in both muscles vs control. Mitochondrial creatine sensitivity was compromised in quadriceps. These findings indicate muscle weakness precedes atrophy in quadriceps and diaphragm but is linked to heterogeneous mitochondrial alterations. Eventual muscle-specific restorations in force and bioenergetics highlight how the effects of cancer on one muscle do not predict the response in another muscle. Exploring heterogeneous responses of muscles to cancer may reveal new mechanisms underlying distinct sensitivities, or resistance, to cancer cachexia.

physiology↗

bioRxiv2020

Combined Effects of Standing and Passive Heating on Attenuating Sitting-Induced Vascular Dysfunction

Recent evidence suggests prolonged sitting strains the arteries through angulations that create turbulent blood flow. This turbulent flow reduces flow-mediated dilation (FMD), a key indicator of vascular health. The purpose of this study was to determine if arterial angulations (through sitting or standing), shear stress (through local heating), or a combination of these factors affected vascular function. In addition, we sought examined the impact of biological sex on these responses. MethodsTwenty-six healthy, young (18-40 years old) males (n=13) and females (n=13) participated. Participants completed two experimental trials (2-h sitting and 2-h standing), and, in a randomized fashion, one leg was passively heated. Flow-mediated dilation (FMD) at the superficial femoral artery (SFA), and central and peripheral pulse-wave velocity (PWV) were measured using vascular ultrasound. ResultsThere was a non-significant decrease in FMD (- 1.48%; p = .06) during sitting and the decline in FMD was not different between biological sexes (-1.96% vs -0.93%; p = .49, males and females respectively). Passive heating (1.42%; p < .05) and standing (1.42%; p < .05) both improved FMD in comparison to sitting. However, standing resulted in a significant increase in peripheral PWV (50 cm/s; p < .05). Interestingly, the standing was not well tolerated among female participants with seven participants having to stop their initial trial early due to lightheadedness. ConclusionsBoth interventions appear to be equally effective at mitigating reductions FMD associated with sitting, but standing increased peripheral PWV. In addition, it does not appear that biological sex moderates these physiological responses. New FindingsO_ST_ABSWhat is the central question of this study?C_ST_ABSProlonged sitting can cause acutely vascular dysfunction while interventions such as local heating or standing have been explored they have not been used in combination and the role of biological sex has not been fully explored. What is the main finding and its importance?In this study we demonstrate that either local heating or standing are effective at reducing some of the vascular dysfunction associated with prolonged sitting. Biological sex did not appear appear to play a role in this response. However, standing may also cause some negative effects such as increased arterial stiffness and increase the risk of syncope.

physiology↗