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Sharma, U.

Publications and source records attributed to Sharma, U..

At least 19 recordsLinked to original sources

A Guided AI Framework for Customizable and Efficient Harmonisation to the OMOP Common Data Model

Getting clinical data from different sources to "talk" to each other within the OMOP Common Data Model (CDM) is arguably the most tedious part of multi-center research. While this integration is essential, the transformation process is frequently a manual grind, requiring a rare overlap of deep clinical knowledge and technical expertise. In this paper, we present a framework designed to alleviate some of the burden on the researcher by automating data harmonization through two distinct steps: structural schema mapping and terminological standardization. For the structural piece, we moved away from "black box" logic in favor of a stateful workflow managed by large language models (LLMs) and directed acyclic graphs. By profiling EHR data at the source, our system generates context-aware dictionaries that offer ranked mapping suggestionsalongside confidence scores. While our benchmarking showed a 97.5% agreement rate at the schema level and an 84% agreement rate at the value level when compared with human experts, the system appears most effective when treated as a "co-pilot" rather than a total replacement for human oversight. To handle value-level standardization, we implemented a hybrid search strategy that pairs the semantic depth of SapBERT embeddings with the literal precision of fuzzy string matching. By using FAISS for rapid similarity retrieval, the engine attempts to resolve messy or "noisy" clinical descriptionsto standard OMOP concepts. This approach seems particularly promising for handling the non- standardized labels that often plague smaller, local datasets. Ultimately, our results suggest that this guided approach can shift the timeline for OHDSI-compliant warehousing from weeks of manual curation to a more manageable and scalable pipeline, potentially lowering the barrier to entry for smaller research teams.

bioinformatics↗

α5β1 and αvβ3 integrins employ two distinct adhesion strengthening modes to respond to fibronectin stiffness within seconds of initiating adhesion

The complex interplay between extracellular matrix stiffness and actomyosin contractility regulates long-term integrin-based adhesion and signaling in mammalian cells. However, how cells sense and respond to the stiffness of the environment during the first minutes of initiating adhesion remains elusive. Here, we show that fibroblasts upon initiating adhesion to fibronectin switch between two distinct mechanosensitive adhesion modes. The first mode of "slow" adhesion strengthening, shared between 5{beta}1 and v{beta}3 integrins and depends modestly on fibronectin stiffness. Fibroblasts adapt this slow adhesion strengthening mode, which is independent of actomyosin contractility and intracellular signaling, on soft fibronectin substrates (<5 kPa). On stiff fibronectin substrates (>5 kPa), however, 5{beta}1 integrins but not v{beta}3 integrins switch to a "fast" adhesion strengthening mode that considerably strengthens adhesion within seconds. The switch to the fast mode depends on myosin II-mediated contractility and a mechanosensitive signaling hub that includes the 5{beta}1 integrin-FN catch bond, paxillin, and focal adhesion kinase. The mechanistic findings highlight the similarities and differences of integrin-type specific adhesion strengthening and intracellular regulation, which depend on mechanotransduction in fibroblasts during adhesion initiation.

biophysics↗

Integrin-identity shapes and mechanotemporally encodes the fibroblast transcriptome

Fibroblast transcriptomic states reflect physiological and pathological tissue contexts, yet the upstream determinants that stabilize these states remain poorly defined. Integrins mediate extracellular matrix (ECM) adhesion and biochemical signaling, but whether they encode mechanical constraints into stable transcriptomic programs is unclear. Using engineered mouse fibroblasts, bulk and single-cell transcriptomics, and controlled micromechanical confinement, we show that integrins can shape the transcriptomic landscape. The bulk transcriptome of fibroblasts expressing V- and {beta}1-class indicates a shared mechanosensitive baseline, except when these integrin classes are expressed individually. We also found integrin-specific gene clusters, including {beta}1-class integrin-dependent enrichment of Areg, Epha7, Lhpp and Igf2r, which regulate development, regeneration and disease, and altered YAP1 targeted gene expression. At single-cell resolution under confinement, {beta}1-class integrins sustain a progenitor-associated program, whereas their loss or V-class enrichment promotes a constitutively activated state linked to injury repair and wound healing. Mechanical confinement and confinement duration further reshapes these states in an integrin-identity-dependent manner. Our findings establish integrin-identity as a determinant of how fibroblasts transduce mechanotemporal inputs from the cell surface to the nucleus.

Cell Biology↗

Quantitative CDK2 Dynamics Are Linked to Cell Fate Decisions in Differentiating Trophoblast Stem Cells

During early development of the placenta, a subset of murine trophectoderm stem cells (TSCs) undergo endoreplication, an unusual form of cell division cycle that decouples DNA synthesis from cytokinesis, resulting in physiological polyploidy. Oscillations in CDK2 activity are essential for the orderly progression of the cell cycle to ensure replicated DNA is accurately partitioned into two daughter cells. However, it remains underexplored how the dynamics of CDK2 activity regulate endoreplication in the context of TSCs differentiation. To address this question, we leveraged the variability in cell fate decisions in an established in vitro system of TSCs differentiation that relies on removal of a growth factor, FGF4, to induce endoreplication. Using quantitative single-cell live confocal microscopy of a precise CDK2 biosensor, DHB-Venus, we identified at least three different outcomes upon FG4 removal: self-renewal, endoreplication, and migration. Our quantitative analyses showed high levels of Cdk2 activity in self-renewing cells whereas intermediate DHB-Venus turnover is linked to increased nuclear and cell size, indicating a shift to endoreplication. Importantly, we also characterize a third class of differentiating TSCs with migratory characteristics that correlate with low levels Cdk2 activity without a change in nuclear size. In sum, our results demonstrated a correlation between different fate outcomes and specific thresholds of CDK2 activity. Our findings show that TSCs can distinguish between different outcomes through modulating the central kinase of the cell cycle, CDK2, positioning it as a key regulator of early trophoblast differentiation. Summary StatementThis study investigates the oscillatory behavior of CDK2 activity during murine trophectoderm differentiation and its potential role in guiding cell fate decisions.

developmental biology↗

Attomolar fecal cytokine profiling reveals gut immune dynamics and disease states

The gut modulates systemic health, influencing immune, neurological, and cardiovascular processes. While fecal sequencing of microbial nucleic acids provides a non-invasive view of microbial composition, sensitive measurement of host-derived signals in stool remains limited. Here we introduce DIGEST (Digital Immunoassay for Gut-Environment Single-molecule Targets), an ultrasensitive digital immunoassay that quantifies proteins in fecal extracts to attomolar levels. In mice, longitudinal profiling during a high-fat diet perturbation revealed coordinated host cytokine responses that occurred within 24 hours, with sustained elevation after diet withdrawal, enabling non-invasive tracking of within-subject immune dynamics. Application of DIGEST to quantify a panel of host inflammatory cytokines in patients with inflammatory bowel disease distinguished active ulcerative colitis from quiescent disease and non-IBD controls (AUC=0.98). In advanced melanoma patients receiving PD-1 blockade, pretreatment fecal IL-23 concentrations discriminated responders from non-responders with an AUC of 0.87. Together, these results establish DIGEST as a generalizable platform for sensitive, non-invasive quantification of host protein activity at the gut interface, with broad applications in basic science discovery, disease surveillance, and therapy response prediction.

systems biology↗

The multifaceted role of acetamide derivative of Chalcone: Anti-inflammatory Action and Impact on Osteoclastogenesis, insights on NF-kB and MAPK pathways.

Inflammation serves as a vital physiological process essential for preserving health and countering illness. Yet, persistent inflammation drives osteoclastogenesis and ongoing bone erosion in rheumatoid arthritis (RA), mainly via macrophage activation and overproduction of pro-inflammatory cytokines like TNF-, IL-1{beta}, and IL-6. Limitations of prolonged conventional treatments underscore the need for safer small-molecule inhibitors that address both inflammation and osteoclast formation. Chalcones, natural plant defense compounds, exhibit diverse pharmacological properties including anti-inflammatory, anticancer, antibacterial, antifungal, and antiparasitic actions, owing to their characteristic reactive , {beta}- unsaturated carbonyl moiety. This study assessed chalcone derivative 7a for its anti-inflammatory effects in vitro and in vivo, alongside its capacity to modulate osteoclast differentiation, offering the inaugural demonstration of its dual anti-inflammatory and anti-osteoclastogenic properties. In LPS-stimulated macrophages, 7a substantially curtailed nitric oxide production, curbed pro-inflammatory cytokines (TNF-, IL-1{beta}, IL-6), and concentration-dependently diminished iNOS and COX-2 expression while inhibiting reactive oxygen species levels. In vivo, oral 7a dosing potently alleviated carrageenan-evoked paw swelling and restored serum lactate dehydrogenase and C-reactive protein to normalcy. In LPS-exposed mice, it further lowered systemic cytokines and rectified dysregulated biomarkers such as LDH, ALP, ALT, AST, creatinine, and urea. Moreover, in RANKL-stimulated osteoclast cultures, 7a markedly suppressed osteoclastogenesis by downregulating pivotal markers like tartrate-resistant acid phosphatase (TRAP) and matrix metalloproteinase-9 (MMP-9). Derivative 7a also enhances antioxidant defense--superoxide dismutase and catalase--via blockade of NF-{kappa}B and MAPK pathways. Overall, chalcone derivative 7a displays robust anti-inflammatory and anti-osteoclastogenic activity, positioning it as a compelling candidate for RA therapy.

immunology↗

Load-dependent RGD-context sensing via αV-class integrins reprograms cellular adhesion and mechanics within seconds

The cellular ability to biophysically and biochemically recognize extracellular matrix proteins is fundamental to adhesion, mechanics, migration, and morphogenesis, and influences homeostasis and disease. However, the mechanisms underlying integrin-mediated mechanosensing of the arginine-glycine-aspartic acid (RGD)-motif of vitronectin and fibronectin remain elusive. Here, we discover that within seconds of sensing vitronectin, V-class integrins initiate and strengthen adhesion biphasically through complementary mechanotransduction pathways, which rely on the catch bond behavior of single V{beta}3 integrins. The first adhesion phase requires V{beta}3 and V{beta}5 integrin-associated actomyosin and FAK activity, while V{beta}5 integrin additionally requires clathrin-mediated endocytosis. With elevating mechanical load, the second phase requires V{beta}3 integrin-directed Arp2/3, cSrc, and PI3K signaling that dominates V{beta}5 integrin in organizing the consensus adhesome on vitronectin. Simultaneously, V{beta}5 integrin regulates the mechanical stiffening of fibroblasts. Thus, V-class integrins exhibit rapid RGD-motif- and {beta}-subunit-specific programs to synergistically guide mammalian cell adhesion and mechanics upon encountering diverse extracellular environments.

biophysics↗

Tracking tRNA evolution in closely related mouse strains

Transfer RNAs are conserved RNAs that are essential for translation in all forms of life and are present in multiple variants to allow interpretation of the entire genetic code. Transfer RNA genes in eukaryotes exist in multiple identical and non-identical copies across the genome to contribute to the tRNA repertoire of a cell. While the same tRNAs are conserved across species, their number and conservation vary from genome to genome. The evolution of these tRNA genes, especially in mammals, is poorly understood. To understand what guides tRNA evolution, we examined the tRNA gene complement from 17 closely related mouse strain genomes. Our analysis revealed that although most tRNAs are conserved, a subset shows copy number variation, sequence divergence, and even strain-specific gains or losses. We also identified a group of transcribed single-copy tRNAs that are conserved across multiple mouse strains and other mammals, suggesting specialized or lineage-specific functions. Together, these findings provide new insights into the evolutionary dynamics of the mammalian tRNA repertoire.

evolutionary biology↗

HIV Infection and Opioid Treatment Enable the Engraftment of Kaposi Sarcoma-like Tumors into Immunocompetent Mice

The Kaposi Sarcoma herpesvirus (KSHV) causes Kaposi sarcoma (KS), primary effusion lymphoma, a lymphoproliferative disease (KSHV-multicentric Castlemans disease), and a cytokine inflammatory syndrome (KICS). These diseases occur more frequently, though not exclusively, among people living with HIV or other types of immune dysregulation. While limited KS can regress with immune reconstitution, such as through antiretroviral therapy (ART) in people living with HIV, there are currently no curative treatments for advanced KS. Preventive or therapeutic vaccines targeting KSHV could have a significant clinical impact; however, the development and testing of such strategies have been limited by the lack of preclinical models that faithfully recapitulate KS, including the presence of infected spindle cells and a relevant immune microenvironment. HIV/AIDS is an important cofactor for KS, and globally, the majority of individuals with KS are HIV-infected. Current evidence indicates that HIV-1 may enable KS progression through immunosuppression and promote pathogenesis by inducing inflammatory cytokines and producing secreted regulatory proteins like Tat and Nef. The design and testing of new therapeutic approaches based on pathogenesis are hampered by the lack of models that replicate KSHV oncogenesis in the context of HIV/AIDS. In the present study, we demonstrate that KSHV-infected cells can form tumors in an immunocompetent mouse model, but only when these mice are pretreated with EcoHIV and morphine, both of which have immunomodulatory and pro-inflammatory effects. These tumors exhibit gene expression profiles and immune microenvironments that closely resemble those observed in human KS lesions. This novel KSHV tumor model in immunocompetent mice provides a valuable platform to test immunotherapeutic strategies for KS, including immunomodulatory agents, targeted antibody therapies, checkpoint inhibitors, and vaccines. Author SummaryKaposi sarcoma (KS) is a cancer caused by the Kaposis sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). A vaccine against this virus could prevent or cure this malignancy. However, there are no good animal models with an immune system to test new immunization approaches. The possibility of having KSHV-driven tumors develop in immunocompetent mice due to EcoHIV infection presents a unique opportunity to create an AIDS-KS mouse model suitable for testing immune-based therapies and KSHV vaccines in a scenario that replicates important aspects of AIDS-KS. These first-in-kind murine models incorporating a biologically relevant mouse HIV infection tool make our models unique and original, with the potential to provide novel mechanistic and pathobiological insights.

microbiology↗

A survey of dietary effects on tRNA abundance and modifications

Transfer RNAs (tRNAs) play a central role in protein translation and are increasingly recognized as dynamic regulators of gene expression. Both physiological and environmental signals can modulate tRNA abundance and chemical modifications, yet the impact of dietary cues on the tRNA landscape remains poorly understood. Here, we investigated the effects of two distinct dietary interventions--low-protein and high-fat diets--on tRNA abundance and modification profiles across multiple mouse tissues. We conducted a comprehensive analysis of tRNA abundance and modification changes in response to these nutritional challenges using RNA mass spectrometry and Ordered Two-Template Relay sequencing (OTTR-seq), a modified-base-sensitive tRNA sequencing method. Our results reveal both shared and tissue-specific alterations in abundance and modifications of specific nuclear and mitochondrial genome-encoded tRNAs in response to dietary conditions at isotype, isoacceptor, and isodecoder levels. As many of the tissue-specific or diet-responsive tRNA modifications have been previously reported to affect decoding efficiency or translational fidelity, these results have implications for understanding translational adaptation in response to dietary conditions.

genomics↗

Epididymis-specific RNase A family genes regulate fertility and small RNA processing

Sperm small RNAs are implicated in intergenerational transmission of paternal environmental effects. Small RNAs generated by cleavage of tRNAs, known as tRNA fragments (tRFs), are an abundant class of RNAs in mature sperm, and can be modulated by environmental conditions. The ribonuclease(s) responsible for the biogenesis of tRFs in the male reproductive tract remains unknown. Angiogenin, a member of the Ribonuclease A superfamily (RNase A), cleaves tRNAs to generate tRFs in response to cellular stress. Four paralogs of Angiogenin, namely Rnase9, Rnase10, Rnase11, and Rnase12, are specifically expressed in the epididymis--a long, convoluted tubule where sperm mature and acquire fertility and motility. The biological functions of these genes remain largely unknown. Here, by generating mice deleted for all four genes (Rnase9-12-/-, termed "KO" for Knock Out), we report that these genes regulate fertility and RNA processing. KO mice showed complete male sterility. KO sperm fertilized oocytes in vitro but failed to efficiently fertilize oocytes in vivo, likely due to an inability of sperm to pass through the utero-tubular junction. Intriguingly, there were decreased levels of fragments of tRNAs (tRFs) and rRNAs (rRNA-derived small RNAs or rsRNAs) in the KO epididymis and epididymal luminal fluid, implying that Rnase9-12 regulate the biogenesis and/or stability of tRFs and rsRNAs. Importantly, KO sperm showed a dramatic decrease in the levels of tRFs, demonstrating a role of Rnase9-12 in regulating sperm RNA composition. Together, our results reveal an unexpected role of four epididymis-specific non-canonical RNase A family genes in fertility and RNA processing.

genetics↗

A sperm-enriched 5'fragment of tRNA-Valine regulates preimplantation embryonic transcriptome and development

Sperm small RNAs have been implicated in intergenerational epigenetic inheritance of paternal environmental effects; however, their biogenesis and functions remain poorly understood. We previously identified a 5 fragment of tRNA-Valine-CAC-2 (tRFValCAC) as one of the most abundant small RNA in mature sperm. tRFValCAC is specifically enriched in sperm during post-testicular maturation in the epididymis, and we found that it is delivered to sperm from epididymis epithelial cells via extracellular vesicles. Here, we investigated the mechanistic basis of tRFValCAC delivery to sperm and its functions in the early embryo. We show that tRFValCAC interacts with an RNA binding protein, heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB), in the epididymis, and this interaction regulates the sorting and packing of tRFValCAC into extracellular vesicles. In the embryo, we found that tRFValCAC regulates early embryonic mRNA processing and splicing. Inhibition of tRFValCAC in preimplantation embryos altered the transcript abundance of genes involved in RNA splicing and mRNA processing. Importantly, tRFValCAC-inhibited embryos showed altered mRNA splicing, including alternative splicing of various splicing factors and genes important for proper preimplantation embryonic development. Finally, we find that inhibition of tRFValCAC in zygotes delayed preimplantation embryonic development. Together, our results reveal a novel function of a sperm-enriched tRF in regulating alternating splicing and preimplantation embryonic development and shed light on the mechanism of sperm small RNA-mediated epigenetic inheritance.

developmental biology↗

Pred-AHCP: Robust feature selection enabled Sequence Specific Prediction of Anti-Hepatitis C Peptides via Machine Learning

Every year, an estimated 1.5 million people worldwide contract Hepatitis C (HepC), a significant contributor to liver disease. Although many studies have explored machine learnings potential to predict antiviral peptides, very few have addressed predicting peptides against specific viruses such as Hepatitis C. In this study, we demonstrate the use of machine learning (ML) algorithms to predict peptides that are effective against HepC. We developed an explainable ML model that harnesses the amino acid sequence of a peptide to predict its potential as an anti-HepC (AHC) agent. Specifically, features were computed based on sequence and physicochemical properties, with feature selection performed utilizing a combined scheme of mutual information and variance inflation factor. This facilitated the removal of redundant and multicollinear features from the sequence data, enhancing the models generalizability in predicting AHCPs. The model using the random forest algorithm produced the best performance with an accuracy of about 90%. The feature selection analysis highlights that the distribution of hydrophobicity and polarizability, as well as the frequencies of glycine residues and di-peptide motifs--YXL, LXK, VXXXF, VL, LV, CC, RR, TXXXV, VXXA, CXXXC--emerged as the key predictors for identifying AHCPs targeting different components of the HepC virus. The model developed can be accessed through the Pred-AHCP web server, provided at http://tinyurl.com/web-Pred-AHCP. This resource facilitates the prediction and re-engineering of AHCPs for designing peptide-based therapeutics while also proposing an exploration of similar strategies for designing peptide inhibitors effective against other viruses.

bioinformatics↗

Understanding the mechanism of the SARS CoV-2 coinfection with other respiratory viruses

Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. Rapid diagnostic tests are tools with a paramount impact both on improving patient care. Particularly in the case of respiratory infections, it is of great importance to quickly confirm/exclude the involvement of pathogens. The COVID-19 pandemic has been associated with changes in respiratory virus infections worldwide, which have differed between virus types. In this paper, we systematically searched the percentage of coinfection of various respiratory viruses in COVID-19-positive samples. We included patients of all ages, in all settings. The main outcome was the proportion of patients with viral coinfection. By describing the differences in changes between viral species across different geographies over the course of the COVID-19 pandemic, we may better understand the complex factors involved in the community cocirculation of respiratory viruses.

genomics↗

Propagated circulating tumor cells uncovers the rople of NFκB and COP1 in metastasis

Circulating tumor cells (CTCs), a population of cancer cells that represents the seeds of metastatic nodules, are a promising model system for studying metastasis. However, expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here, we report the development of a combined CTC and CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers. Propagated CTCs yielded a highly aggressive population of cells that could be used to routinely and robustly establish primary tumors and metastatic lesions in CDXs. Differential gene analysis of the resultant CTC models emphasized a role for NF-kB signaling as a pan-cancer signaling pathway involved in metastasis. Furthermore, metastatic CTCs were identified through a prospective 5-gene signature (BCAR1, COL1A1, IGSF3, RRAD, and TFPI2). Whole-exome sequencing of CDX models and metastases further identified mutations in constitutive photomorphogenesis protein 1 (COP1) as a potential driver of metastasis. These findings illustrate the utility of the combined patient-derived CTC model and provide a glimpse of the promise of CTCs in identifying drivers of cancer metastasis.

cancer biology↗

Iron-dependent mutualism between Chlorella sorokiniana and Ralstonia pickettii forms the basis for a sustainable bioremediation system

Mutualism between microalgae and bacteria is ubiquitous, but remains underexplored as a basis for biodegradation of anthropogenic pollutants. In industrial systems, poor iron uptake by microalgae limits growth, bioprocessing efficacy, and bioremediation potential. Iron supplementation is costly and ineffective because iron remains insoluble in aqueous medium and biologically unavailable. In aquatic environments, microalgae develop an association with bacteria that solubilize iron by production of siderophore, which increases the bioavailability of iron as a public good. Algae, in exchange, provides dissolved organic matter to bacteria to sustain such interkingdom associations. Therefore, using a case study of azo dye degradation, we combine environmental isolations and synthetic ecology as a workflow, establishing a microbial community to degrade industrially relevant Acid Black 1 dye. We create a mutualism between previously non-associated chlorophyte alga Chlorella sorokiniana and siderophore-producing bacterium Ralstonia pickettii, based on the eco-evolutionary principle of exchange of iron and carbon. This siderophore-mediated increased iron bioavailability increases reductive iron uptake, growth rate, and azoreductase-mediated dye degradation of microalga. In exchange, C. sorokiniana produces galactose, glucose, and mannose as major extracellular monosaccharides, supporting bacterial growth. We propose a mechanism whereby extracellular ferrireductase is crucial for azoreductase-mediated dye degradation in microalgae. Our work demonstrates that bioavailability of iron, which is often overlooked in industrial bio-designs, governs microalgal growth and enzymatic processes. Our results suggest that algal-bacterial consortia based on the active association are a self-sustainable mechanism to overcome existing challenges of micronutrient availability in bioremediation systems and their industrial translation.

microbiology↗

Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies

BackgroundViral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present. PurposeHerbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach. MethodsWe analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed. ResultsSeveral predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa.

systems biology↗

Traditional use of Cissampelos pareira L. for hormone disorder and fever provides molecular links of ESR1 modulation to viral inhibition

Bioactive fractions or compounds obtained from medicinal plants have been used for the treatment of multiple diseases. This effect could be due to common pathways underlying these conditions that are targeted by such medicines. In this study, we explored the molecular basis of action of one such herbal formulation Cissampelos pareira, used for the treatment of female hormone disorders and fever. Genome-wide expression studies on MCF7 cell lines treated with Cipa extract were carried out using Affymetrix arrays. Transcriptome analysis revealed a downregulation of signatures of estrogen response governed by estrogen receptor (ER). Molecular docking analysis identified 38 constituent molecules in Cipa that potentially bind ({Delta}G< -7.5) with ER at the same site as estrogen. Cipa transcriptome signatures show high positive connectivity (https://clue.io/) scores with protein translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is also an ER coactivator. Cipa exhibits antiviral activity in dengue infected MCF7 cells that is decreased upon ESR1 (estrogen receptor 1) gene knockdown. This approach reveals a novel pathway involving ESR1-RPL7 axis that could be a potential target in dengue viral infection.

genomics↗