Biology subjects

Cattaneo, S.

Publications and source records attributed to Cattaneo, S..

5 recordsLinked to original sources

bioRxiv2026

A2 and A1B in vitro milk digests: effects on in vitro leaky gut model and adipose cells

Obesity is associated with chronic low-grade systemic inflammation of adipose tissue and is often linked to intestinal epithelial barrier (IEB) dysfunction. The present study aimed to evaluate the effects of in vitro gastrointestinal digests of bovine milk containing A1B or A2 {beta}-casein variants on leaky IEB and adipocyte inflammation. Digests of A1B (DA1B) and A2 (DA2) milk were administered to an in vitro Caco-2/HT-29 intestinal cell co-culture mimicking a leaky gut. Intestinal absorbed fractions derived from A1B (MA1B) and A2 (MA2) were administered to hMADS adipocytes. DA1B and DA2 did not modify intestinal permeability, either in the absence or the presence of inflammation. DA1B reduced Claudin-1 mRNA, as well as zonula occludens-1 mRNA and protein expression. Both DA1B and DA2 increased interleukin-8 expression, but only DA1B increased tumor necrosis factor-. In human adipocytes, MA1B, and to a lesser extent MA2, increased the expression of pro-inflammatory markers monocyte chemoattractant protein-1 and interleukin-6, while reducing adiponectin levels. DA2 preserved in vitro leaky IEB integrity and exhibited a lower inflammatory potential in both leaky gut and adipocytes compared to DA1B. This study is the first to establish a link among A2 milk, leaky gut syndrome, and obesity.

molecular biology↗

bioRxiv2026

Integrated Single-Fiber Multi-Omics Links an Inflammatory-Associated Myofiber State to Altered Myosin Dynamics in Patients with ICU-acquired weakness

Skeletal muscle dysfunction is a pervasive complication of critical illness that worsens survival and recovery, yet remains poorly explained by current clinical or molecular markers. To directly connect disease-associated molecular states to the contractile machinery, this study combined sequential functional, transcriptomic, and proteomic profiling of the same single human skeletal myofibers from critically ill patients in the intensive care unit with acquired weakness (ICU-AW) and controls. Despite marked donor-level heterogeneity, integrated analysis revealed a subtle yet conserved myofiber state enriched in ICU-AW, characterized by inflammatory and chemotactic gene programs, intracellular structural remodeling, and bioenergetic adaptation. Nineteen features were significantly altered at both RNA and protein levels from the same myofiber, linking an inflammatory transcriptional landscape to a proteomic shift toward mitochondrial and translational machinery and away from membrane-associated signaling. Functionally, fibers in this state displayed selectively disrupted myosin dynamics, evidenced by prolonged ATP turnover time of myosin heads in their super-relaxed conformation, implicating altered myosin energetics as a contributor to muscle dysfunction. These findings define a discrete, disease-associated myofiber state and establish an integrative single-fiber framework for connecting multi-omic heterogeneity to molecular motor function in complex human disease. Graphical AbstractSingle-fiber multi-omic and functional analysis reveals a stress-adapted myofiber state in ICU-AW. Specifically, for the present study, myofibers from ICU-AW donors and control donors were isolated and functionally profiled for myosin dynamics before being split for simultaneous transcriptomic and proteomic analysis. Integrated analysis then identified a reproducible fiber phenotype enriched in ICU-AW, characterized by inflammatory transcriptional signatures coordinated with mitochondrial proteomic remodeling and altered myosin super-relaxed state energetics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/706099v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@95715forg.highwire.dtl.DTLVardef@1462ff8org.highwire.dtl.DTLVardef@f74996org.highwire.dtl.DTLVardef@10055ec_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2024

Biogenic nanoparticles from liquid and solid matrices: biochemical and biophysical properties of Extracellular Vesicles-enriched samples from human plasma and skeletal muscle tissue.

AimStudies on extracellular vesicles (EVs) focused on samples enriched from liquid matrices, such as cell culture media and blood. Recent research highlights the roles of EVs derived from the extracellular matrix of solid tissues, and how investigating these specific EVs offers insights into their microenvironment and potential biological influences on surrounding cells. This study presents a shared method to separate and compare EV enriched from solid (human skeletal muscle biopsy) and liquid (human plasma) matrices, addressing technical challenges and minimizing biases in separation techniques. MethodsPlasma and skeletal muscle-EVs were obtained combining serial centrifugation steps and discontinuous sucrose density gradient. EVs characterization employed advanced analytical techniques such as Western Blot, Colorimetric Nanoplasmonic assay, Atomic Force Miscoscopy, Nanoparticle Tracking Analysis and Dynamic Light Scattering to focus on biomolecular composition, nanomechanical properties, particle yield, size distribution, and colloidal stability. ResultsThe analysis revealed distinct differences between skeletal muscle-EVs and plasma-EVs including: molecular composition, physical and nanomechanical properties, as well as particle size distribution. Skeletal muscle-EVs exhibited unique colloidal behavior compared to their plasma counterparts, suggesting tissue-specific features that may influence their biological activity and stability. ConclusionsThe findings demonstrate that EVs from skeletal muscle tissue possess unique biochemical and biophysical characteristics when compared to those derived from plasma. These differences reflect their diverse biological origins and microenvironments. Understanding these distinctions could advance the development of EV-based diagnostic tools, particularly for muscular disorders, and broaden our knowledge of EV roles across various tissue contexts. HIGHLIGHTSO_LIShared protocol to enrich and compare extracellular vesicles (EVs) from both solid (skeletal muscle biopsy) and liquid (plasma) human samples, reducing methodological bias across matrices. C_LIO_LISkeletal muscle-derived EVs differ significantly from plasma EVs in biochemical and biophysical properties such as molecular composition, size distribution, nanomechanical properties, and colloidal stability. C_LIO_LIEV heterogeneity across microenvironments emerged as a key biological feature, highlighting their potential for specific diagnostic applications. C_LI

cell biology↗

bioRxiv2020

Neural precursor cells contribute to decision-making by tuning striatal connectivity via secretion of IGFBPL-1

The adult brain retains endogenous neural stem/precursors cells (eNPCs) in two major neurogenic niches, the subgranular zone (SGZ) in the hippocampus and the subventricular zone (SVZ). While in humans and rodents the SGZ contributes to memory functions by generating new neurons that integrate into hippocampal circuitry, the role of eNPCs of the SVZ is less clear. SVZ-eNPCs contribute to the generation of new neurons fated to the olfactory bulb (OB) in rodents but not in humans where they are thought to contribute to striatal neurogenesis as a result of tissue damage. Here, we show in mice and humans a novel non-neurogenic physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity. We first provide evidence that GABAergic transmission between parvalbumin-expressing fast-spiking interneurons (FSIs) and medium spiny neurons (MSNs) is tuned by SVZ-eNPCs via secretion of Insulin-Like Growth Factor Binding Protein Like 1 (IGFBPL-1) that, in turn, regulates the Insulin-Like Growth Factor (IGF-1) signalling cascade. Consistently, selective ablation of SVZ-eNPCs and in vivo disruption of the IGF-signalling determine the impairment of intrastriatal coherence. A finding associated with a higher failure rate of GABAergic transmission mediated by FSIs and with striatum-related behavioural dysfunctions impairing decision making. Human validation studies revealed IGFBPL-1 expression in the SVZ and in foetal and induced-pluripotent stem cell-derived NPCs as well as a strong correlation in neurological patients between SVZ pathological damage, reduction of striatum volume and impairment of information processing speed. All in all, our results highlight a novel non-neurogenic homeostatic role exerted by SVZ-eNPCs on striatal GABAergic neurons that might contribute to cognitive processes involving decisions-making tasks.

neuroscience↗

bioRxiv2019

Somatostatin-Expressing Interneurons Co-Release GABA and Glutamate onto Different Postsynaptic Targets in the Striatum.

The functional contribution of somatostatin-expressing interneurons (SST-INs) to the synaptic organization of the striatum is poorly understood. Using electrophysiological recordings, optogenetic stimulation, and single-cell PCR analysis, we investigated functional patterns of synaptic connectivity in striatal SST-INs expressing channelrhodopsin-2. Photostimulation of these cells induced both glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) in striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs). The two synaptic components showed equally fast onset latencies, suggesting a mechanism of co-transmission. Accordingly, single-cell PCR analysis revealed that individual striatal SST-INs expressed mRNAs for both glutamate and GABA vesicular transporters (VGLUT1 and VGAT, respectively). During relatively prolonged optical stimuli (0.5-1s), IPSC arrays consistently outlasted EPSCs. As a result, photostimulation of SST-INs caused a transient burst of action potentials followed by a prolonged inhibition in postsynaptic cells.\n\nThese data suggest that striatal SST-INs are specialized to locally project synapses exerting a composite excitatory and inhibitory effect through GABA/glutamate co-transmission onto different postsynaptic targets.

neuroscience↗