ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their ...papers. Sheeza Mughal is first author on ‘ Taurine activates the AKT–mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy’, published in DMM. Sheeza is a PhD Student in the lab of Javier Ramón-Azcón at the Institute for Bioengineering of Catalonia (IBEC) in Barcelona, Spain, and is interested in developing disease models to simplify understanding of otherwise complex diseases.
Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro ...skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.
In sensing applications, the preferential adsorption of molecules on selective Co
3
O
4
facets has been explored, yielding high sensitivity and selectivity. This tendency of the molecules can be ...exploited to enhance methane decomposition efficiency in transition metal catalysts other than nickel, which is known to cause acute toxicity. This study fabricated Co
3
O
4
catalysts with and without algal-resourced biogenic agents to calculate the preferential orientations or facets of the catalyst crystals. Henceforth, it evaluated their cytotoxicity and methane decomposition efficiency in a low-pressure chemical vapor deposition reactor from 750 to 850 °C using 0.04% (w/w) Co
3
O
4
/Al
2
O
3
-Si of nanocatalyst loaded on an Al
2
O
3
-coated p-type silicon support at different reaction conditions. Alg-Co
3
O
4
(311) nanocatalysts (0.158 eV/Å
2
), derived from algal biomass containing catalytically active stepped sites and catering efficient chemisorption of carbon atoms, executed 43.4% methane decomposition as opposed to 34% by NaBH
4
-co-precipitated Ch-Co
3
O
4
(111) nanocatalysts (0.132 eV/Å
2
). The Alg-Co
3
O
4
(311) catalysts were nanometric in size; possessed higher ductility, per particle surface area; and were less cytotoxic for erythrocytes, leukocytes and U87 cells than the Ch-Co
3
O
4
(111) nanocatalysts. This state of the art provides a new platform to resource algal metabolites for tailoring catalytic efficiency at the nanoscale.
Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both ...high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.
Organ‐on‐chip platforms combined with high‐throughput sensing technology allow bridging gaps in information presented by 2D cultures modeled on static microphysiological systems. While these ...platforms do not aim to replicate whole organ systems with all physiological nuances, they try to mimic relevant structural, physiological, and functional features of organoids and tissues to best model disease and/or healthy states. The advent of this platform has not only challenged animal testing but has also presented the opportunity to acquire real‐time, high‐throughput data about the pathophysiology of disease progression by employing biosensors. Biosensors allow monitoring of the release of relevant biomarkers and metabolites as a result of physicochemical stress. It, therefore, helps conduct quick lead validation to achieve personalized medicine objectives. The organ‐on‐chip industry is currently embarking on an exponential growth trajectory. Multiple pharmaceutical and biotechnology companies are adopting this technology to enable quick patient‐specific data acquisition at substantially low costs.
Organ‐on‐chip platforms combined with high‐throughput sensing technology allow bridging gaps in information presented by 2D cultures modeled on static microphysiological systems. Miniaturized biosensors systems and advanced tissue fabrication procedures enable researchers to create multiple tissues on a chip with a high degree of control over experimental variables for high‐content screening applications.
PDF