Publications

Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, remains one of the major causes of death from infection worldwide, with over a million associated deaths each year. The study of biomarkers for TB is critical for advancing our understanding and management of the disease. Biomarkers, defined as measurable indicators of biological states or conditions, are invaluable for the diagnosis, prognosis and treatment monitoring of TB. Clinical studies have provided critical knowledge on the matter but are also notoriously constrained by economical, ethical and sampling limitations. The use of animal models provides a simpler, more controllable, cost-effective setting with great potential for translation to humans. They also allow the evaluation of biomarkers within the respiratory compartment, when available, which is of particular interest due to the nature of TB pathogenesis. This Review focuses on the current landscape of TB biomarker discovery in several animal models, from invertebrates to large mammals. Here we summarize the basics of host-pathogen immune interaction, describe the main methodological approaches used and highlight the most substantial findings for each animal model studied. Furthermore, we discuss the advantages, challenges and limitations associated with species-specific differences in animal models. We conclude that integrating the data obtained from animal models and human studies is absolutely required to advance the TB field to accelerate the management of this disease.

JTD Keywords: Cd4 t-cells, Drosophila-melanogaster, Experimental airborne tuberculosis, Gamma release assay, Guinea-pig, Host-parasite relationships, Ifn-gamma, Mycobacterium-tuberculosis, Nitric-oxide synthase, Pulmonary tuberculosis

A major challenge in cardiac research is the limited translatability of drug screening and toxicity assays due to the use of in vitro models that poorly mimic the native cardiac environment. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a promising route forward, but conventional 2D culture on rigid substrates hinders their functional maturation and predictive accuracy. This study addresses this problem by investigating the effect of hybrid fibronectin-based hydrogels with tunable stiffness on the mechanical and electrical properties of hiPSC-CMs. We engineered hydrogels with stiffness mimicking the lowest range of neonatal heart tissue stiffness (2-4 kPa) and compared hiPSC-CM behavior on these substrates to that on standard fibronectin-coated glass. Our results demonstrate that hydrogel culture promotes more uniform and stable cardiomyocyte contractions, as evidenced by increased single peak percentages and altered contraction duration. Electrophysiological analysis revealed that hydrogel stiffness influences action potential duration and signal amplitude. Furthermore, hiPSC-CMs on hydrogels exhibited enhanced cell-matrix and cell-cell adhesion, indicating improved structural and functional connectivity. Drug testing with known cardioactive compounds, including isoproterenol and nifedipine, revealed distinct differences in drug responses between hydrogel and glass cultures, suggesting that hydrogels provide a more physiologically relevant platform for assessing drug effects. This work highlights the potential of engineered hydrogel substrates to enhance the functional maturity and predictive accuracy of hiPSC-CMs for cardiac research and drug development.

JTD Keywords: Beat, Cells, Contraction, Guinea-pig, Hydrogels, Ipsc-cardiomyocytes, Maturation, Mechanical properties, Platform, Sensitive dye di-4-anepps