Biology subjects

Jana, P.

Publications and source records attributed to Jana, P..

4 recordsLinked to original sources

bioRxiv2026

A first-in-class multimodal organomercury compound demonstrates preferential blast reduction with hematopoietic and immune restoration in Acute Lymphoblastic Leukemia

Acute leukemia treatment requires effective blast reduction while improving hematopoietic and immune health. As reported previously, we developed a structurally distinct organomercury derivative of curcumin, -Mercurin, having improved aqueous solubility and intravenous applicability. Here we comprehensively evaluated therapeutic efficacy, pharmacological response, systemic toxicity, blood Hg pharmacokinetics (PK), Hg biodistribution and elimination profile for -Mercurin in a N-nitroso-N-ethylurea (ENU)-induced autochthonous Acute lymphoblastic leukemia (ALL) rat model, comparing with clinical standard cytarabine. Results showed recovery in body-weight, along with longer time-to-humane-endpoint from 13 to 39 days. Treatment successfully reduced immature blast count, while promoting erythroid, myeloid, and megakaryocytic compartments and improving immune mediators across peripheral blood, bone marrow, thymus, spleen, and lymph nodes. Histopathology showed reduced leukemic infiltration with preservation of major organ architecture, while cytarabine produced evident myelosuppression, neurotoxicity, and cardiotoxicity. PK study showed blood Hg reached Tmax at 15 min, followed by urinary and fecal elimination with residual retention in kidney tissue and no detectable Hg in brain. Collectively, -Mercurin demonstrated a promising multimodal therapeutic index, combining cytoreductive activity with improvement in hematopoietic and immune health, along with favorable safety profile for future ALL therapy.

cancer biology↗

bioRxiv2026

Gut microbiota-derived indole-3 acetic acid mitigates key hallmarks of metabolic dysfunction-associated steatotic liver disease (MASLD) in an NLRP3-dependent manner in in vitro and diet-induced mouse models

BackgroundMetabolic-dysfunction associated steatotic liver disease(MASLD) is a global epidemic affecting >30 % global population with no approved therapies till date. Recent reports suggest that activation of NLRP3 inflammasome may be involved in the pathogenesis of MASLD. We, therefore, aimed to identify small molecule inhibitor(s) of NLRP3 inflammasome as a potential therapeutic strategy to manage MASLD and validate their efficacy using in vitro and in vivo models of MASLD. MethodologyWe screened an in-house library of natural products using an in vitro phenotypic assay and identified a gut microbiota derived metabolite of dietary Tryptophan; indole-3 acetic acid (I3A) for its ability to inhibit the levels of IL-1{beta} and IL-18, which are elevated as a result of activation of NLRP3 inflammasome in differentiated THP1 cells. Subsequently, we carried out several in vitro and in vivo studies to confirm the mechanism of action of I3A and its ability to mitigate the key hallmarks of MASLD ResultsOur in vitro data suggest that I3A is an inhibitor of NLRP3 inflammasome. I3A was also found to improve the blood glucose level, plasma lipid profile, hepatic fat, and liver function in high-fat-high-fructose diet induced model of MASLD using C57BL/6 mice. ConclusionOur results show that I3A, which has been previously reported to be a gut microbiota-derived metabolite of dietary tryptophan, mitigates the key hallmarks of MASLD in an NLRP3 dependent manner. A dedicated structure-activity-relationship (SAR) study around the I3A chemotype may be carried out in future to identify novel NLRP3 inhibitors with desirable pharmacological profile.

pharmacology and toxicology↗

bioRxiv2024

Subtractive proteomics unravel the potency of D-Alanine-D-Alanine Ligase as the drug target for Burkholderia pseudomallei

Melioidosis, also known as Whitmores disease, is caused by the deadly pathogen Burkholderia pseudomallei and remains a significant global health concern, particularly in South Asia. The disease is contracted through exposure to contaminated soil, water, air, and food. Infected individuals often present with abscesses in internal organs such as the lungs, spleen, and liver, and in soft tissues, with severe cases leading to septic shock and acute pneumonia. The rising incidence and mortality rates, coupled with B. pseudomalleis ability to form biofilms and develop resistance to antibiotics like cephalosporins, make treatment increasingly challenging. This highlights the urgent need for novel therapeutic approaches. D-Alanine-D-Alanine ligase (Ddl), a crucial enzyme involved in the final stage of bacterial cell wall synthesis, which protects the pathogen from the hostile cellular environment of the host. While many bacteria have two isoforms of this enzyme, B. pseudomallei possesses only the DdlB isoform, presenting a significant vulnerability. Our study represents the first successful attempt to target DdlB through a combination of molecular docking and molecular dynamics simulations. These investigations provide strong evidence that Conivaptan acts as an effective inhibitor of DdlB, offering a novel therapeutic approach for combating melioidosis.

bioinformatics↗

bioRxiv2022

Ancestral SARS-CoV-2 driven antibody repertoire diversity in an unvaccinated individual correlates with expanded neutralization breadth

Understanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of humoral immune response in some individuals capable of broadly neutralizing pan SARS-CoV-2 variants. We assessed the diversity of neutralizing antibody responses developed in an unvaccinated individual infected with ancestral SARS-CoV-2 by examining the ability of the distinct B cell germline-derived monoclonal antibodies (mAbs) in neutralizing known and currently circulating Omicron variants by pseudovirus and authentic virus neutralization assays. The ability of the antibodies developed post vaccination in neutralizing Omicron variants was compared to that obtained at baseline of the same individual and to those obtained from Omicron breakthrough infected individuals by pseudovirus neutralization assay. Broadly SARS-CoV-2 neutralizing mAbs representing unique B cell lineages with non-overlapping epitope specificities isolated from a single donor varied in their ability to neutralize Omicron variants. Plasma antibodies developed post vaccination from this individual demonstrated neutralization of Omicron BA.1, BA.2 and BA.4 with increased magnitude and found to be comparable with those obtained from other vaccinated individuals who were infected with ancestral SARS-CoV-2. Development of B cell repertoire capable of producing antibodies with distinct affinity and specificities for the antigen immediately after infection capable of eliciting broadly neutralizing antibodies offers highest probability in protecting against evolving SARS-CoV-2 variants. ImportanceDevelopment of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known, however varies at population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known VOC and currently circulating Omicron variants. This indicated establishment of unique lineages that contributed in forming B cell repertoire in this particular individual immediately following infection giving rise to diverse antibody responses that could compensate each other in providing broadly neutralizing polyclonal antibody response. Individuals who were able to produce such potent polyclonal antibody responses after infection have a higher chance of being protected from evolving SARS-CoV-2 variants.

immunology↗