Biology subjects

Kumari, B.

Publications and source records attributed to Kumari, B..

5 recordsLinked to original sources

bioRxiv2026

Antiviral Potential of Lauric Acid against Dengue Virus 2: Evidence from a Luciferase-Based Replicon Assay

Dengue virus (DENV) infection generates a significant health burden throughout the world, and there are no clinically approved antiviral drugs, as of now. The virus also depends on lipid metabolism in the host to conduct effective replication and this makes lipid-directed compounds promising as therapeutic options. We assessed the antiviral effect of lauric acid, a 12-carbon medium-chain fatty acid, against DENV serotype 2 (DV2) in the presence of a stable cell line, DV2-replicon, expressing all the non-structural proteins (NS1-NS5) and a luciferase reporter. Active viral replication in replicon cells was established by morphological examination and immunofluorescence of cells. The MTT assay was used to determine the cytotoxicity of lauric acid revealing the LD50 of 2.52 uM, so higher concentrations were toxic as the effect of the drug is dose-related. The antiviral effect was tested through replicon inhibition (luciferase) assay which showed an incredible inhibition of viral RNA replication with a IC50 of 1.70 uM and this is equivalent to antiviral mycophenolphycic acid. The cytopathic effects, as well as a decrease in the activity of luciferase, proved the presence of viral translation and replication inhibition within the process of the treatment of the lauric acid. These results propose that lauric acid has cytotoxic and antiviral dual effect and can be a possible inhibitor of DENV replication. The toxicity needs to be reduced and future research is necessary to explain its molecular pathway and also to come up with the best delivery methods. IMPORTANCEDengue virus (DENV) remains a significant health challenge to the world since there are no effective antiviral agents. This work will recognize lauric acid as a possible dengue virus replication inhibitor in a model of a DV2 replicon, exhibiting antiviral action that is similar to that of mycophenolic acid. These results support lipid-directed compounds as potential dengue antiviral targets, but more research is needed to minimize toxicity and better understand the molecular mechanism of action.

molecular biology↗

bioRxiv2025

Spontaneous cancer regression as inversion of spontaneous cancer progression: Malignant melanoma remission as a case-study towards clinical applicability

The spontaneous cancer regression process (SCR) a rather rare paradoxical natural phenomenon, shows that malignant tumors can episodically undergo complete permanent elimination without treatment, and thus may be used for gaining clues to incisive therapeutic innovations. SCR of malignant breast tumors occurs subclinically across human populations ([~]22% rate), according to Scandinavian and Wisconsin Screening Registries (monitoring 0.33million and 2.95million population respectively). SCR occurs in discoid melanomas ([~]12% rate). SCR process has high novelty with no toxicity nor recurrence, and duplicating SCR process is indeed clinically desirable. We aim to probe SCR using melanoma as illustrative pilot-study, and identify candidate leads that may mimic SCR on the tumor. We investigated molecular biological of melanoma, finding two reciprocal phases: spontaneous-progression and spontaneous-regression, and showed driver genes for melanoma SCR. Then, we pursued network pharmaco-informatics analysis. We found that spontaneous melanoma eradication shows an unexpected finding, in distinct contrast to the prevalent view that immunological processes and immunotherapy are critical for melanoma regression, than targeting DNA. We found that in contradistinction, it is DNA interference process that is primary route for melanoma regression, while anti-tumor immune activation is only secondarily needed. We observed that targeting two pathways (kinase-system, inositide-system) by inhibiting two genes, arrested melanoma-progression phase, and activated the reverse phase, melanoma-regression. We investigated the interactions of possible candidate leads, indicating significant therapeutic potency. Our findings underscore the high impact possibility for leveraging the anomalous phenomenon of spontaneous cancer regression as a general oncological principle for probing targeted therapeutic interventions, with substantial clinical potentials.

cancer biology↗

bioRxiv2025

Deciphering a common code: Unitary gene profile factor enabling Spontaneous Tumor Regression

Spontaneous-remission of Cancer (SRC), well documented in humans, is the paradoxical process of natural permanent tumor elimination by host-tissue system without any toxicity, recurrence or cancer stem-cell formation. This rare biological phenomenon is usually associated with immune activation, apoptosis, tumor microenvironment as well as oncogenic suppression. Thus, to understand this strikingly complex event, it is utmost important to look into the genetic and molecular landscape in-depth. Majorly, cancer mortalities occur due to epithelial tumors, hence, to find out the contributing pathways involved we interrogated epithelial malignancies: Neuroblastoma (neural-crest tissue), and Melanoma (skin tissue). Neuroblastoma, the most prevalent tumor type in newborns, arises from embryonic nerve cells and have a very diverse clinical trajectory. Similarly, Melanoma another common skin tumor, developed from malignant transformation of melanocytes (cells producing melanin pigment). It is well-known that in numerous patients, both these malignant tumors spontaneously regress permanently, while in others, these tumors escalate to fatality. We investigated microarray expression of spontaneous regression of malignant neuroblastoma tumors (n=498), the patients having 4 temporal stages (S1-S2-S3-S4), and malignant melanoma tumors (n=22) having 4 time points (T1-T2-T3-T4) [i.e. total 520 patients, each 8 remission-route steps]. We studied differentially expressed genes (DEGs) common in both regressing Neuroblastoma and Melanoma, and analyzed the protein-protein interactions (PPI) as well as protein-miRNA networks. One crucial ubiquitous gene factor was found across each stage of both the regressing tumors. This focal gene codes for a spectrin-repeat protein which acts as a linker between nucleus-cytoskeleton, and aids in maintaining normal cells nuclear and cellular integrity (demarcated as a significant morphological change in tumor cells) by abetting the formation of Mut-S complex, which is a significant player in mis-match repair pathway. Strikingly, both this protein and miRNA were found to be commonly targeting PIK3CA protein through separate paths. We endeavor to unravel the mechanism of action and decipher the common gene factors across the entire tumor regression process in both Neuroblastoma and Melanoma. We meticulously identified the underlying biological pathways responsible for spontaneous regression. These results provide insights into the molecular genetics and underlying pathophysiology of SCR in Neuroblastoma and Melanoma, suggesting a role for precision therapeutics in the future that can help mimic this extraordinary prodigy by targeting the uniform factors mentioned in this study.

cancer biology↗

bioRxiv2025

RNA-coupled CRISPR Screens Reveal ZNF207 as a Regulator of LMNA Aberrant Splicing in Progeria

Despite progress in understanding pre-mRNA splicing, the regulatory mechanisms controlling most alternative splicing events remain unclear. We developed CRASP-Seq, a method that integrates pooled CRISPR-based genetic perturbations with deep sequencing of splicing reporters, to quantitively assess the impact of all human genes on alternative splicing from a single RNA sample. CRASP-Seq identifies both known and novel regulators, enriched for proteins involved in RNA splicing and metabolism. As proof-of-concept, CRASP-Seq analysis of an LMNA cryptic splicing event linked to progeria uncovered ZNF207, primarily known for mitotic spindle assembly, as a regulator of progerin splicing. ZNF207 depletion enhances canonical LMNA splicing and decreases progerin levels in patient-derived cells. High-throughput mutagenesis further showed that ZNF207s zinc finger domain broadly impacts alternative splicing through interactions with U1 snRNP factors. These findings position ZNF207 as a U1 snRNP auxiliary factor and demonstrate the power of CRASP-Seq to uncover key regulators and domains of alternative splicing. Main PointsO_LICRASP-Seq: RNA-coupled CRISPR screen quantifying gene and domain impact on splicing C_LIO_LIProfiling of five events identified 370 genes influencing alternative splicing C_LIO_LIZNF207 regulates splicing by interacting with U1 snRNP via its zinc-finger domains C_LIO_LIZNF207 depletion corrects LMNA aberrant splicing causing progeria C_LI

genetics↗

bioRxiv2018

Japanese Encephalitis Virus Infected Microglial Cells Secrete Exosomes Containing let-7a/b that Facilitate Neuronal Damage via Caspase Activation

Extracellular microRNAs (miRNAs) are essential for the cell to cell communication in the healthy and diseased brain. MicroRNAs released from the activated microglia upon neurotropic virus infection may exacerbate CNS damage. Here, we identified let-7a and let-7b (let-7a/b) as the overexpressed miRNAs in Japanese Encephalitis virus (JEV) infected microglia and assessed their role in JEV pathogenesis. We measured the let-7a/b expressions in JEV infected post-mortem human brains, mice brains and in mouse microglial N9 cells by the qRT-PCR and in situ hybridization assay. The interaction between let-7a/b and NOTCH signaling pathway further examined in Toll-like receptor 7 knockdown (TLR7 KD) mice to assess the functions. Exosomes released from JEV infected or let-7a/b mimic transfected N9, and HEK-293 cells were isolated and evaluated their function. We observed an upregulation of let-7a/b in the infected brains as well as in microglia. Knockdown of TLR7 or Inhibition of let-7a/b suppressed the JEV induced NOTCH activation possibly via NF-{kappa}B dependent manner and subsequently, attenuated JEV induced TNF production in microglial cells. Further, exosomes secreted from JEV-infected microglial cells specifically contained let-7a/b. Exosomes overexpressed with let-7a/b were injected into BALB/c mice as well as co-incubated with mouse neuronal (Neuro2a) cells, or primary cortical neuron resulted in caspase activation leading to neuronal damage in the brain. Thus, our results provide evidence for the multifaceted role of let-7a/b miRNAs and unravel the exosomes mediated mechanism for JEV induced pathogenesis.

neuroscience↗