Search bioRxiv⌕ Search

Biology subjects

Amirkhani, A.

Publications and source records attributed to Amirkhani, A..

3 recordsLinked to original sources

Functionalized nanoparticle transforms cold to hot adenoid cystic carcinoma of salivary gland tumour microenvironment in vitro

Adenoid cystic carcinoma (ACC) of salivary gland is a "immune-cold" tumour. Annexin A3 (ANXA3) is an apoptotic protein found to be participating in immune cell infiltration in tumour microenvironment (TME) of various cancer cases. Significant low expressions of ANXA3 protein found in adenoid cystic carcinoma. We hypothesized overexpressing ANXA3 transforms ACC "cold" TME to "hot". We cultured UM-HACC-2A and UFH2 spheroids on extracellular matrix and co cultured them with peripheral blood mononuclear cells. We functionalized FDA (The Food and Drug Administration) approved Poly(lactic-co-glycolic acid) PLGA nanoparticles with anti-cMyb antibody and ANXA3 recombinant protein using streptavidin-biotin conjugation. Upon overexpressing ANXA3 in ACC spheroids in immune coculture model using functionalized nanoparticles, significant increase of tumour infiltrating lymphocytes and decrease in the size of the ACC spheroids observed. Apoptotic profiler assay further confirmed significant upregulation of apoptotic proteins, some of them participate in immune infiltration. Overall, this project exhibits promising results showing potential approach to convert ACC into an immune "hot" tumour.

cancer biology↗

Evaluating the impact of two different diets on the protein profile expression of the brain, liver, and intestine of barramundi

AbstractCommercial feed formulations are increasingly being evaluated for their nutritional impacts on aquaculture species, yet the molecular consequences of commonly used commercial diets remain underexplored. This study investigated the effects of two commercial diets, diet A (higher land animal protein) and diet B (higher fish meal content), on protein expression in the brain, liver, and intestine of barramundi (Lates calcarifer). A 12-week feeding trial was conducted with controlled water quality, and proteomic profiling was performed using data-independent acquisition. Differential analysis revealed consistent changes between diets across all tissues, with a higher percentage of differentially abundant proteins observed in between-diet comparisons (12.99% in brain, 12.73% in liver, and 16.59% in intestine) than within-diet controls (<8%), confirming a measurable dietary effect size. In total, 3,901 proteins in the brain, 3,660 in the liver, and 5,025 in the intestine were quantified. Functional enrichment highlighted upregulation of ferroptosis pathways, downregulation of apelin signaling in the brain, and increased digestive proteases in the liver. ICP-MS confirmed elevated iron concentrations in the brain, liver and intestine of fish fed on diet B. These findings demonstrate that molecular pathways linked to iron metabolism, digestion, and growth regulation are very sensitive to dietary composition, highlighting how proteomics can help identify subtle impacts of compositional differences in aquaculture feeding. Despite the absence of significant differences in physiological parameters, the proteomic alterations observed across tissues likely represent adaptive metabolic adjustments of each organ to the varying nutrient availability between diets.

biochemistry↗

Proteomic Profiling of Mesenchymal Stem Cell-Derived Extracellular Vesicles: Impact of Isolation Methods on Protein Cargo

Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are secreted by cells and play a critical role in cell-to-cell communication. Despite the promising reports regarding their diagnostic and therapeutic potential, the utilization of EVs in the clinical setting is limited due to insufficient information about their cargo and a lack of standardization in isolation and analysis methods. Considering protein cargos in EVs as key contributors to their therapeutic potency, we conducted a tandem mass tag (TMT) quantitative proteomics analysis of three subpopulations of mesenchymal stem cell (MSC)-derived EVs obtained through three different isolation techniques: ultracentrifugation (UC), high-speed centrifugation (HS), and ultracentrifugation on sucrose cushion (SU). Subsequently, we checked EV marker expression, size distribution, and morphological characterization, followed by bioinformatic analysis. The bioinformatic analysis of the proteome results revealed that these subpopulations exhibit distinct molecular and functional characteristics. The choice of isolation method impacts the proteome of isolated EVs by isolating different subpopulations of EVs. Specifically, EVs isolated through the high-speed centrifugation (HS) method exhibited a higher abundance of ribosomal and mitochondrial proteins. Functional apoptosis assays comparing isolated mitochondria with different EV isolation methods revealed that HS-EVs, but not other EVs, induced early apoptosis in cancer cells. On the other hand, EVs isolated using the sucrose cushion (SU) and ultracentrifugation (UC) methods demonstrated a higher abundance of proteins primarily involved in the immune response, cellLJcell interactions, and extracellular matrix interactions. Our analyses unveil notable disparities in proteins and associated biological functions among EV subpopulations, underscoring the importance of meticulously selecting isolation methods and resultant EV subpopulations based on the intended application.

cell biology↗