Biology subjects

Nicola, F.

Publications and source records attributed to Nicola, F..

3 recordsLinked to original sources

bioRxiv2026

Sobetirome, a thyroid hormone receptor beta agonist, is a potential therapeutic agent for pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with limited treatment options. Our group previously identified the antifibrotic potential of thyroid hormone, triiodothyronine (T3); however, clinical translation of thyroid hormone therapy is limited by its systemic adverse effects. In this study, we investigate whether sobetirome, a selective and well tolerated thyroid hormone receptor beta (THRB) agonist, offers antifibrotic benefits of thyroid hormone while minimizing systemic toxicity. Our study reveals that sobetirome, administered via intraperitoneal or inhalational routes, effectively mitigates bleomycin-induced pulmonary fibrosis in mice, with no evidence of toxicity. We identified that sobetirome restores mitochondrial homeostasis via activating the THRB-PPARGC1a axis. This protects alveolar type II epithelial cells from injury-induced apoptosis while selectively inducing apoptosis and metabolic reprogramming in apoptosis resistant IPF fibroblasts. Cell-specific deletion of Ppargc1a in either alveolar epithelial cells or fibroblasts abolishes sobetirome-mediated protection, establishing PPARGC1a as an essential mediator of therapeutic response. Importantly, sobetirome reverses fibrosis-associated transcriptional programs in human IPF lung tissue, reducing expression of key fibrosis-associated genes, including collagen I alpha 1 (COL1A1), collagen III alpha 1 (COL3A1), periostin (POSTN), cathepsin K (CTSK), and Chitinase 3 Like 1 (CHI3L1), while promoting extracellular matrix remodeling, epithelial restoration, and tissue homeostasis. Collectively, our findings identify THRB activation as a novel metabolic strategy for reversing pulmonary fibrosis. Across complementary in vitro, in vivo, and human ex vivo models, sobetirome restores mitochondrial function, modulates apoptotic pathways in pathogenic cells, and promotes fibrosis resolution, highlighting its potential as a lung-targeted therapeutic approach for IPF and other fibrotic lung diseases.

systems biology↗

bioRxiv2026

A spinal substrate for modular control of natural behavior

Natural behavior unfolds as coordinated sequences of body movements. This organization suggests that behavior may be built from discrete motor patterns, yet how such arrangements are implemented by neural circuits remains unknown. Here, we combined kinematic analysis, muscle recordings, genetically identified cell types, and closed-loop optogenetic perturbations to examine the organizational logic of natural gap-crossing jumps in mice. Jumping was characterized by a series of precisely defined phases and their associated modular motor patterns. The core phases, propulsion and flight, exhibited distinct signatures of neural control, including unique bursts of coordinated hindlimb muscle activity, differential tuning strategies for jump distance, and active requirements for spinal neural drive. Mapping activity across lumbar interneuron populations and functionally screening candidate cell types for their ability to drive coordinated movement revealed that a population of dorsal excitatory dILB6 neurons can autonomously evoke coordinated multi-joint hindlimb flexion characteristic of the jumping flight phase, across behavioral contexts. These findings provide a specific cellular substrate for the long-standing concept of spinal modular motor control: a flexible, preconfigured motor template that the mammalian CNS can recruit and modulate to meet the demands of natural behavior. Highlights- Jumping behavior is organized into discrete phases with stereotyped motor patterns - Each phase contains a distinct signature of body-wide, joint, and muscle coordination - dILB6 spinal interneurons autonomously evoke a triple-flexion hindlimb motor module - dILB6 neurons can shape active jumping behavior

neuroscience↗

bioRxiv2024

Dual host-bacterial gene expression to study pathogenesis and the regulation of virulence factors in tissue during respiratory infections

Co-localization of spatial transcriptome information of host and pathogen can revolutionize our understanding of microbial pathogenesis. Here, we aimed to demonstrate that customized bacterial probes can be successfully used to identify host-pathogen interactions in formalin-fixed-paraffin-embedded (FFPE) tissues by probe-based spatial transcriptomics technology. We analyzed the spatial gene expression of bacterial transcripts with the host transcriptomic profile in murine lung tissue chronically infected with Mycobacterium abscessus embedded in agar beads. Customized mycobacterial probes were designed for the constitutively expressed rpoB gene (an RNA polymerase {beta} subunit) and the virulence factor precursor lsr2, modulated by oxidative stress. We found a correlation between the rpoB expression, bacterial abundance in the airways, and an increased expression of lsr2 virulence factor in lung tissue with high oxidative stress. Overall, we demonstrate the potential of dual bacterial and host gene expression assay in FFPE tissues, paving the way for the simultaneous detection of host and bacterial transcriptomes in pathological tissues.

microbiology↗