Biology subjects

Eslami, S.

Publications and source records attributed to Eslami, S..

4 recordsLinked to original sources

bioRxiv2026

Dual-Lipa: A sequential multi-omic subcellular landscape map of mouse heart

Spatial multi-omics can provide a unique understanding in molecular organisation and heterogeneity of organs including the heart. Heart function is dependent on the abundance and the spatial arrangement of proteins and lipids. Yet, an integrated multi-omics landscape of the heart at subcellular scale remains unknown. Here, we used a sequential lipid-proteomic analytical pipeline applied to the mouse heart to identify, map, and integrate lipid and protein features, revealing coordinated distinct molecular networks within defined subcellular niches. Here, we benchmark this dual extraction workflow for integrated global proteome-lipidome analyses to demonstrate its performance. We developed conserved subcellular proteome of mouse heart across 14 niches and applied the knowledge of subcellular proteome to spatially resolve the heart lipidome, identifying unique lipid features from different subcellular niches, including mitochondria (e.g., cardiolipin, LPC) and plasma membrane-enriched lipids (e.g., plasmalogens). We identified sex-dependent molecular differences in heart subcellular proteome between male and female, including RNA-protein complexes, mitochondrial calcium handling and immune regulatory pathways. We demonstrate that lipid-protein integrated multi-omics analysis of the heart by dual extraction workflow and mass spectrometry could enable previously unidentified discoveries in heart molecular composition and organisation and spatial cardiac biology. HighlightsO_LIResolved tissue-wide subcellular architecture of cardiac tissue through simultaneous high-resolution proteomics and lipidomics profiling. C_LIO_LISystematically evaluated MS-compatible dual extraction strategies for integrated proteome-lipidome recovery and performance. C_LIO_LIProteomics revealed major sex-dependent differences in mouse left ventricles, primarily involving cellular metabolism, immune regulation, detoxification pathways, and signalling responses. C_LIO_LILipidomics identified strong sex-specific lipid signatures, including differences in omega-3 vs omega-6 fatty-acid containing lipid species, triacylglycerides, and acylcarnitines. C_LIO_LIDeveloped supervised machine-learning models to classify 14 subcellular niches from tissue-wide fractionation proteomics and identified a conserved core subcellular proteome. C_LIO_LIApplied the tissue-wide subcellular proteome model to infer lipid subcellular localisation, revealing mitochondria-enriched lipids (e.g., cardiolipin, LPC) and plasma membrane-enriched lipids (e.g., plasmalogens) in the mouse left ventricle. C_LIO_LIMapped sex-specific subcellular distribution in the heart, highlighting pathways linked to RNA-protein complexes, mitochondrial calcium handling, and immune regulatory networks. C_LI

biochemistry↗

bioRxiv2023

Expression of Lanthipeptides in Human Cells

Cyclic peptides represent a burgeoning area of interest in therapeutic and biotechnological research. In opposition to their linear counterparts, cyclic peptides, such as certain ribosomally synthesized and post-translationally modified peptides (RiPPs), are more conformationally constrained and less susceptible to proteolytic degradation. The lanthipeptide RiPP cytolysin L forms a covalently enforced helical structure that may be used to disrupt helical interactions at protein-protein interfaces. Herein, an expression system is reported to produce lanthipeptides and structurally diverse cytolysin L derivatives in mammalian cells. Successful targeting of lanthipeptides to the nucleus is demonstrated. In vivo expression and targeting of such peptides in mammalian cells may allow for screening of lanthipeptide inhibitors of native protein-protein interactions. Table of contents graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/563208v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@aafac8org.highwire.dtl.DTLVardef@13687caorg.highwire.dtl.DTLVardef@10d16caorg.highwire.dtl.DTLVardef@533398_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Protective Effects of Edaravone Against Hypoxia-Induced Lethality in Mice

Edaravone has been recently used for the treatment of acute cerebral infarction. However, there is no data on the protective effects of this drug against hypoxia-induced lethality. Here, we aimed to evaluate the protective effects of edaravone against hypoxia-induced lethality and oxidative stress in mice through three experimental models of hypoxia. Materials and Methodsmale Swiss albino mice were randomly housed in groups of 10. Mice received single i.p. injections of edaravone for four consecutive days. Three experimental models of hypoxia: asphyctic, circulatory, and haemic were applied in this study. Oxidative stress, lipid peroxidation and glutathione content were assessed after hypoxia induction. ResultsSignificant protective activities were observed in all models of hypoxia. Antihypoxic activities were highly significant in asphytic and circulatory hypoxia. These effects were dose-dependent. Edaravone, at 5 mg kg-1, showed statistically significant activities concerning the control groups. Edaravone significantly prolonged the latency for death. At 2.5 mg kg-1, it prolonged survival time (26.08 {+/-} 0.79 min). This effect was statistically significant (P<0.05). Also, edaravone significantly inhibited hypoxia-induced oxidative stress (lipid peroxidation and glutathione oxidation) in three models of hypoxia. ConclusionsEdaravone showed an excellent protective effect against hypoxia in all tested models and decreased the oxidative stress in the brain tissue of hypoxic mice. Notably, results showed significant and dose-dependent effects on the models of asphytic and circulatory hypoxia. The antioxidant activity itself might be a proposed mechanism for the antihypoxic activities of this drug. Impact statementThis study provides a novel proof-of-concept for a FDA approved drug, which will open a new area of research in the field and drug repurposing.

pharmacology and toxicology↗

bioRxiv2020

Magnesium Sulfate Attenuates Lethality and Oxidative Damage Induced by Different Models of Hypoxia in Mice

Mg2+ is an important cation in our body. It is an essential co-factor for many enzymes. Despite many works, nothing is known about the protective effects of MgSO4 against hypoxia-induced lethality and oxidative damage in brain mitochondria. In this study, antihypoxic and antioxidative activities of MgSO4 were evaluated by three experimental models of induced-hypoxia (asphyctic, haemic, and circulatory) in mice. Mitochondria protective effects of MgSO4 were evaluated in mice brain after induction of different models of hypoxia. Antihypoxic activity was especially pronounced in asphyctic hypoxia where MgSO4 at dose 600 mg/kg showed the same activity as phenytoin which used as a positive control (P< 0.001). In the haemic model, MgSO4 at all used doses significantly prolonged latency of death. In circulatory hypoxia, MgSO4 (600 mg/kg) doubles the survival time. MgSO4 significantly decreased Lipid peroxidation, protein carbonyl, and improved mitochondrial function and glutathione content in brain mitochondria compared to control groups. The results obtained in this study showed that MgSO4 administration has protective effects against lethality induced by different models of hypoxia and improves brain mitochondria oxidative damage.Competing Interest StatementThe authors have declared no competing interest.View Full Text

pharmacology and toxicology↗