Biology subjects

N, S. R.

Publications and source records attributed to N, S. R..

3 recordsLinked to original sources

bioRxiv2025

Targeted disruption of Oncogenic Biosphere: A Paradigm Shift Beyond Cancer Cell-Centric Therapies

Traditional cancer therapies have primarily focused on directly targeting malignant cells, yet this paradigm has consistently fallen short in addressing therapeutic resistance and metastasis1. These persistent challenges suggest that the tumors surrounding environment--not just the cancer cells themselves--plays a decisive role in treatment failure. In this study, we present an ecosystem-oriented strategy that targets the pathological microenvironment sustaining cancer progression. We repurposed niclosamide, an FDA-approved anthelmintic agent2,3, and enhanced its bioavailability by formulating Penetrium an orally deliverable nanotherapeutic composed of niclosamide, magnesium oxide, and hydroxypropyl methylcellulose. In syngeneic and xenograft models of triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC), Penetrium showed robust antitumor synergy when combined with standard therapies including anti-PD-1, paclitaxel, and anti-VEGF agents. Notably, Penetrium markedly blocked metastatic spread. Mechanistic analyses revealed that Penetrium remodels the tumor extracellular matrix (ECM), downregulates MMP-9, restores E-cadherin, and enhances immune infiltration-- thereby converting immune-excluded tumors into immune-permissive niches. Furthermore, in patient-derived pancreatic tumor organoids co-cultured with cancer-associated fibroblasts (CAFs), we demonstrated that tumor cell survival is critically dependent on the stromal context. Importantly, Penetrium selectively eliminated CAFs without affecting normal fibroblasts. These findings validate the oncogenic biosphere, and especially the CAF-rich stroma, as a critical therapeutic target. Our results underscore a shift from the conventional cancer cell-centric model to an oncogenic biosphere-disruption strategy that dismantles the structural and immunological defenses of desmoplastic cancers, offering a promising avenue for overcoming resistance and metastasis.

cancer biology↗

bioRxiv2022

Orally administered niclosamide-based organic/inorganic hybrid suppresses SARS-CoV-2 infection

The COVID-19 pandemic is a serious global health threat mainly due to the surging cases along with new variants of COVID-19. Though global vaccinations have indeed some effects on the virus spread, its longevity is still unknown. Therefore an orally administrable anti-viral agent against SARS-CoV-2 would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we repurposed niclosamide (NIC), an FDA approved anthelmintic drug in to MgO, which was further coated with hydroxyl propyl methyl cellulose (HPMC) to get the de-sired product called NIC-MgO-HPMC, which has improved anti-SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of NIC-MgO-HPMC on SARS-CoV-2 replication leads to the prevention of inflammation as well as lung injury. These data strongly support that repurposed NIC-MgO-HPMC could be highly beneficial for controlling the ongoing pandemic thereby achieving an endemic phase.

pharmacology and toxicology↗

bioRxiv2020

Refinement of Genome assemblies of Pigeonpea (Cajanus cajan)

Genome assembly of short reads from large plant genomes remains a challenge in computational biology despite major developments in Next Generation sequencing. Of late multiple draft assemblies of plant genomes are reported in many organisms. The draft assemblies of Cajanus cajan are with different levels of genome completeness; contain large number of repeats, gaps and segmental duplications. Draft assemblies with portions of genome missing, are shorter than the referenced original genome. These assemblies come with low map accuracy affecting further functional annotation and prediction of gene component as desired by crop researchers. Genome coverage i.e. number of sequenced raw reads mapped on to certain locations of the genome is an important quality indicator of completeness and assembly quality in draft assemblies. Present work was aimed at improvement of coverage in reported de novo sequenced draft genomes (GCA_000340665.1 and GCA_000230855.2) of Pigeonpea, a legume widely cultivated in India. The two assemblies comprised 72% and 75% of estimated coverage of genome respectively. We employed assembly reconciliation approach to compare draft assemblies and merged them to generate a high quality near complete assembly with enhanced contiguity. Finished assembly has reduced number of gaps than reported in draft assemblies and improved genome coverage of 82.4%. Quality of the finished assembly was evaluated using various quality metrics and for presence of specific trait related functional genes. Employed pair-end and mate-pair local library data sets enabled to resolve gaps, repeats and other sequence errors yielding lengthier scaffolds compared to two draft assemblies. We report prediction of putative host resistance genes from improved sequence against Fusarium wilt disease and evaluated them in both wet laboratory and field phenotypic conditions.

genomics↗