Brancato, V. | Search bioRxiv

bioRxiv2024

Comparative Analysis of Stain-Free Fourier Ptychographic Microscopy and Traditional Histopathological Light Microscopy in Renal Membranous Nephropathy

BackgroundHistology remains a cornerstone in the diagnosis and prognosis of renal diseases, with histopathological analysis of kidney tissue being crucial for understanding renal pathophysiology. The availability of multiple stained sections is essential for conducting a comprehensive histopathological analysis and achieving an accurate diagnosis. Recently, Fourier Ptychographic Microscopy (FPM) earned a spot among the most promising microscopy techniques. The ability to provide high-resolution, quantitative phase-contrast images over a wide area, particularly in a stain-free mode, makes FPM highly appealing to experts in histopathology. Since renal pathologies are characterized by subtle morphological changes encoded in tissue slides, phase maps obtained using FPM are well-suited for providing detailed, high-contrast images of tissue structures. Thus, FPM provides a quantitative imaging tool that can be descriptive of the sample and/or expressive of the disease. MethodsIn this study, we explore FPM capability to image pathological kidney tissue, enabling pathologists to select regions of interest within the intricate architecture of renal tissue and zoom in to observe minute submicron structures, ranging from overall tissue organization and glomeruli distribution to individual cell membranes. Attention is focused on membranous glomerulonephritis since it is a nephropathy highly dependent on histological examination. ResultsThe comparative analysis between FPM and traditional light microscopy showed a difference in thickness of glomerular basal membranes between healthy kidney tissues and those affected by membranous glomerulonephritis (MG). Moreover, the results reported in our investigation revealed better glomerular membranes contrast in FPM images with respect to the H&E-stained images. ConclusionsOur study shows the broad potential of FPM in characterizing hallmarks of MG disease even in stain-free tissue slides.

pathology↗

bioRxiv2023

PGM3 inhibition Shows cooperative Effects With Erastin inducing Pancreatic cancer cell death via activation of the Unfolded Protein Response

1Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor patient prognosis. Remarkably, PDAC is one of the most aggressive and deadly tumor types and is notorious for its resistance to all types of treatment. PDAC resistance is frequently associated with a wide metabolic rewiring and in particular of the glycolytic branch named Hexosamine Biosynthetic Pathway (HBP). Here we show the effect of the combined treatment between an HBPs Phosphoglucomutase 3 (PGM3) enzyme inhibitor, named FR054, and erastin (ERA), a recognized ferroptosis inducer, on PDAC cell growth and survival. Noteworthy, the combined treatment applied to PDAC cell lines induces a significant decrease in cell proliferation and a concurrent enhancement of cell death. Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death. Our study discloses that HBP inhibition enhances, through UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.

cancer biology↗