Biology subjects

Parihar, V. C.

Publications and source records attributed to Parihar, V. C..

3 recordsLinked to original sources

bioRxiv2026

Multiscale, Survey-and-Target Optical Super-Resolution Histology

Super-resolution microscopy reveals fine subcellular tissue architecture, yet extending this capability to histological screening requires balancing spatial resolution with imaging area, axial access, throughput, and instrumental complexity. Here we present multiscale optical super-resolution histology (MOSH), an integrated optical-computational platform that combines tissue-scale, extended-depth-of-focus super-resolution surveys with coordinate-guided three-dimensional interrogation of selected targets. MOSH leverages stationary multifocal excitation, continuous sample translation, tunable axial refocusing, and parallelized reconstruction within a shared spatial-coordinate framework in a conventional epi-fluorescence setting. This survey-and-target strategy preserves tissue-scale context, directs volumetric acquisition to selected subcellular structures, and generates virtual H&E images that retain resolution-enhanced structural information. Across cultured cells, cytological preparations, conventional tissue sections, and intact unsectioned biopsies, MOSH achieved approximately twofold resolution enhancement, continuous lateral coverage beyond the native field of view, and tunable axial survey ranges up to 20 m. Bridging tissue-scale histological screening and targeted, quantitative nanoscale interrogation, MOSH establishes a scalable framework for multiscale analysis of biological and clinical specimens.

bioengineering↗

bioRxiv2026

Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer

Leuprolide, a widely used androgen-deprivation therapy (ADT) for prostate cancer (PC), has been associated with increased cardiovascular events (CVE), although the underlying mechanisms remain unclear. Through integrated spatial transcriptomic analyses of murine heart and immune-stromal profiling in patient blood, we identified immune programs linked to leuprolide-associated CVE risk. Spatial analyses revealed the distinct organization of lymphoid (T+B cells) aggregates and inflammatory macrophages in the plaque following leuprolide exposure that accompanied by ventricular hypertrophy, relative to normal vasculature. Parallel profiling of circulatory soluble and cellular components in patients demonstrated CD8+T cell enriched pattern in ~44% of patients, including memory and type 1 cytotoxic subsets that linked to treatment-induced CVE, such as ventricular dysfunctions, but no contribution of adipocytokines. These translational findings highlight the stratification of leuprolide-associated CVE risk in PC patients based on circulating T cell profiling and could guide the risk mitigation with alternative ADT agents.

immunology↗

bioRxiv2025

High-Dimensional Protein Analysis Uncovers Distinct Immunological and Stromal Signatures Between Primary and Metastatic Pancreatic Ductal Adenocarcinoma

Our understanding of the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) primarily stems from murine models or primary patient tumors. While metastatic tumors have generally less immune infiltration compared to primary tumors, the specific cellular features of metastatic PDAC remain understudied. This knowledge gap is impactful as most patients present with metastatic disease and are most often enrolled in clinical trials. We hypothesized PDAC tumors harbor distinct immunologic and stromal features depending on their anatomical site. Using multiplex immunohistochemistry (mIHC), spatial analysis, and single-cell mass cytometry (CyTOF), we uncover dominant immune and stromal cell populations in tumors derived from 27 primary and 26 liver metastases. Metastatic liver tumors from PDAC patients contained fewer T cells and alpha-smooth muscle actin (-SMA+) activated fibroblasts than primary lesions, while CD68+ cells were more abundant. Spatial analyses revealed distinct immune cell communities in primary and metastatic PDAC, whereby CK19+ cells clustered differentially with -SMA+, CD3+, and CD68+ cells, depending on tumor site. When comparing tumor-associated regions, the proportion of peritumoral CK19- cells remained consistent, but their composition varied by disease site. CD8+ T cells were significantly less frequent in metastatic tumors, while both CD4+ and CD8+ T cells present in primary tumors expressed more transcription factors (TFs) associated with suppressive properties, including FoxP3 and ROR{gamma}t. CyTOF revealed that T cells co-expressed multiple inhibitory checkpoint receptors, with LAG-3 and PD-1 predominating. This report reveals that primary and metastatic tumors from PDAC patients harbor vastly distinct immunologic and stromal features at the protein level. Statement of SignificanceProtein level analysis reveals distinct immunological and stromal features between primary and metastatic PDAC tumors, offering a rationale for immunotherapies that target myeloid cells and increase T cell abundance in metastatic disease.

cancer biology↗