Biology subjects

Marinescu, G. C.

Publications and source records attributed to Marinescu, G. C..

3 recordsLinked to original sources

bioRxiv2025

In situ evidence that mast cells release mutant NLRP1 in keratoacanthomas from multiple self-healing palmoplantar carcinoma

NLRP1 is an inflammasome sensor protein expressed in barrier tissues of humans. Its activation in response to microbes or cellular stress triggers a cascade of molecular events, leading up to IL1{beta}-driven inflammation and pyroptosis. Rare germline mutations of NLRP1 cause its persistent activation, resulting in autoinflammatory syndromes. Multiple self-healing palmoplantar carcinoma (MSPC) is one such syndrome, characterized by the appearance of recurrent keratoacanthomas (KAs) on the palms and soles. Here, we aimed to compare the subcellular localization of mutant NLRP1 in MSPC-associated lesions, to wild-type NLRP1 in non-MSPC KAs and in skin from healthy donors. Using mass spectrometry, immunohistochemistry and immunoelectron tomography, we found that NLRP1 localized to mast cell (MC) granules in all samples, a novel finding which implicates MCs in NLRP1-associated responses in human skin. Moreover, we found that MCs expressing the A66V pathogenic variant of NLRP1 overpopulated MSPC-KAs, infiltrated the epidermis and degranulated, a behavior not seen in other lesions from this study. The released granules had the highest NLRP1 protein content and also contained NLRP3 and IL1{beta}, indicating coexistence of inflammasome pathways within MCs. Taken together, our findings establish cutaneous MCs as a NLRP1 reservoir in health and disease, opening a new area of research in NLRP1-related syndromes.

immunology↗

bioRxiv2024

Proteomic Changes in the Cytoplasmatic Fraction of Weaned Piglets Liver and Kidney Under Antioxidants and Mycotoxins Diets

Antioxidants can mitigate some of the effects of mycotoxins due to their ability to scavenge free radicals, reduce oxidative stress, and have anti-inflammatory and immunomodulatory properties. This work investigates the potential of antioxidants derived from grape seed and sea buckthorn meal to mitigate the adverse effects of aflatoxin B1 (AFB1) and ochratoxin A (OTA). As mycotoxins contamination in weaned piglet diets. We used an unbiased Data Independent Acquisition (DIA) approach to analyse the proteomic impact of OTA and AFB1-contaminated diets on liver and kidney cytoplasmic metabolism, particularly focusing on the conjugation phase. Our findings shed light on the effects of mycotoxins that are partial mitigated by the antioxidants enriched diet. Additionally, we show that in kidneys, some of the effects are synergistically amplified, such as proteins involved in the fatty acids degradation, peroxisome, PPAR signaling, translation, TCA cycle and the excretion pathways. Inclusion of antioxidants in the animal diet can have beneficial effects. Nevertheless, caution is advised, synergistic effects can occur with potentially more serious consequences than the effect of mycotoxins alone.

biochemistry↗

bioRxiv2023

NMN Works in HFD-Induced T2DM by Interesting Effects in Adipose Tissue, and not by Mitochondrial Biogenesis

Nicotinamide mononucleotide (NMN) has emerged as a promising therapeutic intervention for age-related disorders, including Type 2 Diabetes. In this study, we investigated the effects of NMN treatment on glucose uptake and its underlying mechanisms in various tissue and cell lines. Through a comprehensive proteomic analysis, we uncovered a series of distinct organ-specific effects that contribute to the observed improvements in glucose metabolism. Notably, we observed the upregulation of thermogenic UCP1, promoting enhanced glucose utilization in muscle tissue. Additionally, liver and muscle cells displayed a unique response, characterized by spliceosome down-regulation and concurrent upregulation of chaperones, proteasomes, and ribosomes, leading to a mildly impaired and energy-inefficient protein synthesis machinery. Adipose tissue exhibited increased protein synthesis and degradation, fatty acid degradation, Lysosome and mTOR cell proliferation signalling up-regulation, while showing a surprising repressive effect on mitochondrial biogenesis. Furthermore, our findings revealed a remarkable metabolic rewiring in the brain, involving increased production of ketone bodies, down-regulation of mitochondrial OXPHOS components and the TCA cycle, and the induction of known fasting-associated effects. Collectively, our data elucidate the multifaceted nature of NMN action, highlighting its organ-specific effects and their role in modulating glucose metabolism. These findings deepen our understanding of NMNs therapeutic potential and pave the way for novel strategies in managing metabolic disorders.

biochemistry↗