Biology subjects

Arora, P.

Publications and source records attributed to Arora, P..

At least 19 recordsLinked to original sources

bioRxiv2026

Paternal cardiac injury elicits an inflammatory signal relay to the gonads with intergenerational cardiac effects in vertebrates

The blood-gonadal barrier protects the germline from parental exposures. A phenomenon known as intergenerational inheritance suggests that, exceptionally, this barrier can be surpassed with consequences for the subsequent generation. Specific diet regimes and early traumatic experiences have been among the chronic stressors shown to be able to lead to intergenerational inheritance in mammals. Less is known about how acute stress can affect the germline. Cardiac damage leads to several alterations in peripheral organs and, overall, affects blood flow, metabolism, and the immune response. Whether cardiac damage can also affect the reproductive system is not known and might offer new insights into the potential inheritance of cardiovascular disease. Here, we used zebrafish and mouse models to explore the intergenerational role of cardiac damage and repair. In the first week after a cardiac cryolesion, male zebrafish gonads and gametes activated responses associated with inflammation. In sperm, chromatin accessibility was found altered in response to cardiac cryolesion. Offspring of cryoinjured zebrafish males revealed changes in cardiac function and cardiac gene expression. Induction of systemic sterile inflammation in the paternal generation mimicked cardiac injury effects in the following generation, while anti-inflammatory treatments in the injured paternal generation partially recovered F1 cardiac features. Similar features were found in mouse testis after a neonatal injury, and in the hearts of their offspring, suggesting a conserved role of sterile inflammation as a vector for intergenerational transmission of cardiac injury.

developmental biology↗

bioRxiv2026

A distribution-aware and functionally relevant novel framework for generation and discovery of bioactive peptides

Recent advances in artificial intelligence have accelerated the discovery of bioactive peptides by enabling computational exploration of the vast peptide sequence space. However, existing peptide generation approaches generally rely on either distribution-learning models, which generate biologically realistic sequences but do not consistently optimize functional activity, or optimization-based methods, which maximize prediction confidence while often deviating from the underlying distribution of experimentally validated peptides. To address this limitation, a two-phase generative-evolutionary framework is proposed that integrates distribution learning with evolutionary optimization. In the first phase, Variational Autoencoders (VAE), Autoregressive Transformers (ART), and Token Diffusion Transformers (TDT) are used to generate biologically plausible seed peptides. In the second phase, these peptides were used as initial seed for Hill Climbing optimization procedure that iteratively improves fitness function score. The proposed two-phase framework was evaluated using a dataset of experimentally validated IL-2-inducing peptides. Evaluation using independent IL-2 prediction models showed that Autoregressive Transformer combined with Hill Climbing achieved the best overall performance, achieving the mean IL-2 induction confidence score of 0.96 while reducing KL divergence from 2.26 for standalone Hill Climbing to 0.75. A case study on an independent IL-13 inducing peptide dataset showed similar trends, with ART initialized Hill Climbing achieving the mean IL-13 induction score of 0.99 while reducing KL divergence from 1.76 to 0.59. Overall, the framework provides a generalizable approach for balancing functional optimization and distributional realism and can be applied to peptide discovery and data augmentation in imbalanced biological datasets thereby generating high confidence peptides for wet lab validation. HighlightsO_LIProposed a two-phase framework for bioactive peptide generation with potential to address class imbalance in peptide classification tasks. C_LIO_LIPerformed a systematic comparison of distribution-learning and optimization-based approaches for peptide generation. C_LIO_LICombined distribution-learning models for sequence generation with optimization algorithms for improving peptide functional properties. C_LIO_LIDemonstrated the applicability of the proposed framework across multiple bioactive peptide datasets. C_LI

bioinformatics↗

bioRxiv2025

Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development

Congenital heart disease (CHD), the most common human birth defect, often results from disruptions in gene regulatory networks (GRNs) that control cardiac lineage specification and cell type identity during heart development. A conserved core set of cardiac transcription factors (TFs) orchestrates these processes through combinatorial interactions that are cell type-specific and tightly regulated across space and time. However, the genomic enhancer architecture that integrates upstream effectors to establish precise cardiac TF dosage and downstream transcriptional output remains largely unresolved. Here, we assessed the functional necessity of five developmental heart enhancer modules previously linked to the regulation of Gata4 and Hand2, core cardiac TFs exhibiting overlapping roles in myocardial and endocardial development. While individual enhancer deletions in mouse embryonic hearts revealed a surprising degree of transcriptional resilience, a subset of Gata4 enhancers proved indispensable for embryonic progression in a genetically compromised background. To achieve higher precision in cardiac cell type-specific enhancer prediction, we applied single-nucleus multiome profiling, enabling the delineation of cardiac cistromes underlying heart morphogenesis. By integrating this resource with deep learning applications, site-directed transgenesis, and chromatin conformation modeling, we mapped the cardiac enhancer repertoire and regulatory signatures that orchestrate Hand2 dynamics across distinct cardiac compartments and lineages. Genome editing further revealed an essential role for the Hand2-upstream regulatory interval (H2-URI) in transcriptional control of endocardial lineage effectors and, consequently, trabecular network formation and cardiac cushion patterning. Together our findings highlight substantial resilience in the cis-regulatory architectures governing cardiac TF dynamics and demonstrate that combinatorial integration of upstream lineage identities across modular enhancer landscapes establishes the cardiac cell type-specific programs driving heart morphogenesis. These results advance the reconstruction of cardiac GRNs and enhance the functional interpretation of CHD-associated variants.

developmental biology↗

bioRxiv2025

A dividing cell model for stable propagation and curing of bona fide human sporadic Creutzfeldt-Jakob Disease prions

Prions are assemblies of misfolded proteins that cause transmissible, progressive neurodegenerative disease in humans and other mammals. Human prion diseases have particular public health and biological significance, both due to their transmissibility between hosts, and the mechanisms they share with many other neurodegenerative conditions. However, their study has been considerably impeded by the absence of a cell-based system capable of reproducibly propagating and quantifying bona fide human prion infectivity, which has been a goal for several decades. Here, we describe the first robust, cell-based assay of human prion infectivity in dividing cells. We found that CAD5 cells expressing human prion protein instead of the endogenous mouse prion protein, replicate human prion infectivity from brain samples of patients with sporadic Creutzfeldt-Jakob disease (sCJD) expressing valine at codon 129 of the prion protein gene. Moreover, these cells quantify human prion infectivity with similar sensitivity to the current gold standard animal bioassay, at a fraction of the cost and time, maintain persistent infection that can be cured with an anti-prion treatment, and can be adapted for therapeutic screening. This novel system permits direct cell-based quantification and investigation of human prion infectivity for the first time.

neuroscience↗

bioRxiv2025

RNA polymerase II-TFIIE-TFIIH interface functions in transcription start site selection in Saccharomyces cerevisiae

During transcription initiation in Saccharomyces cerevisiae, RNA polymerase II (Pol II) and general transcription factors (GTFs) assemble upstream of transcription start sites (TSSs) to form the pre-initiation complex (PIC). In this model organism, yeast, the PIC selects TSSs through a unidirectional scanning mechanism referred to as promoter scanning. Previous studies have shown that the TFIIH subunit Tfb3 connects TFIIH to the rest of the PIC through interactions with Pol II and the GTF TFIIE. Activities within the PIC that influence TSS selection can do so by control of initiation efficiency at individual TSSs or by control of TSS scanning (either rate of scanning or scanning processivity). To understand how this critical interface withing the PIC participates in scanning, we used genetic screens to identify tfb3 and tfa1 mutants that alter initiation using initiation-linked phenotypes. We found mutations within the TFIIH-Pol II-TFIIE interface able to alter promoter scanning in either upstream or downstream directions, suggesting that changes to this interface can fine-tune scanning. Subsets of alleles were analyzed using TSS sequencing approaches, showing that tested tfb3 and tfa1 alleles shift TSS distributions across most genomic promoters. Genetic interaction and genomic analysis revealed that the Tfb3 interfaces with Rpb7 and Tfa1 separately contribute to promoter scanning, and that tfb3 alleles exhibit additive effects with scanning processivity mutants in, consistent with Tfb3-PIC interactions modulating scanning processivity. The ability of this interface to easily modulate scanning in both directions is consistent with the types of changes that might incrementally allow promoter scanning to have evolved.

molecular biology↗

bioRxiv2025

Genetic dissection of transcription start site selection by RNA polymerase II in Saccharomyces cerevisiae

Transcription initiation by RNA Pol II is driven by a preinitiation complex (PIC) comprising Pol II and general transcription factors (GTFs): TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH. In Saccharomyces cerevisiae, transcription start site (TSS) selection proceeds by a promoter scanning mechanism where the PIC scans downstream for TSSs. To determine which factors participate in TSS selection by promoter scanning, we designed and implemented forward genetic selections using initiation-sensitive genetic reporters. These reporters were of two types, either being sensitive to upstream or downstream TSS shifts, allowing detection of alleles that affect promoter scanning in different directions. From >1000 candidates, we identified three primary classes of mutants: existing and novel mutants within known PIC components, including novel alleles of multiple TFIIH subunits; mutants that alter promoter scanning indirectly through cellular conditions (GTP levels and Mn2+ levels); and mutants in chromatin and transcription elongation-related factors. Genome-wide analysis using TSS mapping shows that tested PIC mutants alter TSS usage globally across promoters while tested chromatin and transcription elongation mutants had much more limited effects. These studies expand the spectrum of mutants able to perturb initiation by promoter scanning and suggest potential plasticity in the TFIIH structure that may be part of the evolution of this initiation mechanism.

molecular biology↗

bioRxiv2025

LFA-1 Interaction with GBP-130 on Plasmodium falciparum-infected Red Blood Cells mediates NK Cell Activation and Parasite Control

Natural Killer (NK) cells contribute to early immunity against Plasmodium falciparum by recognizing and eliminating infected red blood cells (iRBCs), a process mediated in part by the integrin LFA-1. However, the cognate parasite ligand for LFA-1 has remained unknown. Here, we identify Glycophorin Binding Protein-130 (PfGBP-130) as a surface-expressed ligand on iRBCs that binds the I-domain of LFA-1 (LFA-1 I). Using an LFA-1 I-Fc fusion protein, we demonstrate stage-specific binding to iRBCs, and LC-MS/MS analysis of immunopreciptates of I-Fc bound to iRBC revealed PfGBP-130 as a high-confidence interactor. Recombinant PfGBP-130 binds NK and THP-1 cells in an LFA-1-dependent manner. Co-culture assays show that PfGBP-130 promotes NK cell activation, degranulation, and facilitates contact-dependent killing of iRBCs. Neutralizing antibodies against PfGBP-130 significantly impair these responses. Our findings establish PfGBP-130 as the LFA-1 ligand on iRBCs, providing new insight into NK cell-mediated immunity in malaria and identifying a potential target for host-directed interventions.

immunology↗

bioRxiv2025

Dietary fibre promotes chronic whipworm infection through direct and time-dependent modulation of innate immunity

Dietary fibre regulates the microbiome and gut health but increases murine whipworm (Trichuris muris) infection through unclear mechanisms. We show that mice fed inulin-supplemented diets exhibit dysregulated innate antimicrobial defences and altered tryptophan metabolism during T. muris infection. Inhibiting tryptophan catabolism or neutralizing IL-27 and IL-18 in inulin-fed mice restored infection resistance. Notably, inulin led to chronic infection even in microbiota-depleted mice. Removing inulin within a critical immune development window rapidly restored anti-helminth immunity, indicating direct, time-dependent modulation of mucosal immune responses. Our findings reveal a previously unrecognized, direct influence of dietary fibre on mucosal immunity to parasitic infection, independent of the microbiome, highlighting the complex interplay between diet timing and host defence.

microbiology↗

bioRxiv2025

Substitutions in RNA-binding protein Hrp1 map a potential interaction surface with the yeast RNA polymerase II elongation complex

Anti-termination factors for eukaryotic RNA polymerase II (RNAP II) that are released upon binding sequences in the terminator of nascent transcripts were proposed almost 40 years ago but few candidates have been found. Here we report genetic evidence that the yeast nuclear RNA-binding protein Hrp1, also known as Nab4 and CF1B, acts as an RNAP II anti-termination factor. A Lys to Glu substitution at residue 9 (K9E) of the Rpb3 subunit of RNAP II causes readthrough of Nrd1-Nab3-Sen1-dependent (NNS) terminators and cold-sensitive growth, as does Asp but not Ala, Met, Arg, or Gln substitution. These allele-specific phenotypes and the location of Rpb3-K9 suggests substitution with Glu or Asp stabilizes binding of an anti-termination factor via a salt bridge. A genome-wide selection for suppressors of the cold-sensitivity of Rpb3-K9E yielded an Arg to Gly substitution at residue 317 of Hrp1 in RNA recognition motif 2 (RRM2), consistent with the hypothesis. A targeted selection for suppressors of Rpb3-K9E in HRP1 yielded substitutions in RRMs 1 and 2, an essential Met- and Gln-rich region C-terminal to the RRMs, and other mutations. We propose that Hrp1 binds to the RNAP II elongation complex via these regions to promote elongation and, in the presence of Rpb3-K9E, is less rapidly released upon binding terminator sequences in the nascent transcript, resulting in terminator readthrough. The Rpb3-K9E-suppressor substitutions in Hrp1 likely weaken binding to the RNAP II elongation complex, compensating for Rpb3-K9E.

molecular biology↗

bioRxiv2025

Effective prediction of IL-17 inducing peptides using hybrid approach: iIL17pred

BackgroundInterleukin 17 (IL-17) plays a crucial role in regulating the immune system and is associated with numerous diseases. Modulating IL-17 levels has demonstrated potential in mitigating disease symptoms, positioning it as a compelling target for drug development. Therefore, identifying and characterizing novel drug molecules capable of influencing IL-17 levels is critical. Recent advances in therapeutic peptides underscore their promise as attractive drug candidates, inspiring the development of IL-17 modulating peptides. ResultsThis study aimed to enhance existing methods for efficiently classifying IL-17 inducing peptides. Positive and negative datasets were obtained from the Immune Epitope Database, and peptide features were extracted using the pfeature algorithm. A three-stage hybrid approach combining BLAST, MERCI, and machine learning techniques was employed to accurately classify IL-17-inducing peptides. ConclusionsExtensive benchmarking experiments revealed that our proposed method outperforms existing techniques i.e IL17eScan, across key performance metrics, including sensitivity, accuracy, and area under the curve-receiver operating characteristics (AUC-ROC). Our algorithm achieved an accuracy of 88.08% and a Matthews Correlation Coefficient (MCC) of 0.68 on an external dataset, significantly surpassing the accuracy of 78.57% and MCC of 0.57 achieved by existing methods under comparable conditions. This demonstrates a substantial improvement in IL-17 peptide classification. The results are accessible via a user-friendly web server (http://www.soodlab.com/iil17pred/). These findings hold significant potential for predicting IL-17-inducing peptides, which can be further validated experimentally.

bioinformatics↗

bioRxiv2024

Impact of JN.1 booster vaccination on neutralisation of SARS-CoV-2 variants KP.3.1.1 and XEC

The SARS-CoV-2 KP.3.1.1 lineage is currently the dominating lineage on several continents. In parallel, the XEC lineage, a recombinant of KS.1.1 and KP.3.3, is on track of becoming the next dominant lineage in Europe and North America. Here we performed a rapid virological characterisation of the XEC lineage and studied the impact of JN.1 mRNA booster vaccination on KP.3.1.1 and XEC neutralisation.

molecular biology↗

bioRxiv2024

AutoTA: Galaxy Workflows for Reproducible and Automated Taxonomic Analysis using Qiime2

Metagenomic sequencing allows systematic characterization of microbial populations isolated from various environments of interest by bypassing the culturing of the isolates. Concomitant to advancement in sequencing techniques, analysis methods and softwares have also grown to be sophisticated and efficient. Qiime2 is a collection of python scripts which enables end-to-end analysis of metagenomic data. However, usage of latest and more complex databases for classification is hindered by requirement of high compute power. To aid cloud-based analysis, we present workflows for diversity analysis and taxonomic assignment which are the two most common and initial steps in a metagenomics experiments. The workflows are made in Galaxy which makes testing and analysing multiple datasets faster, in parallel, reproducible and flexible. The workflows can be integrated into a local Galaxy instance or used completely on the web which is of great importance to non-bioinformaticians and bench scientists.

bioinformatics↗

bioRxiv2024

Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling.

Autophagy-lysosomal degradation is an evolutionarily conserved process key to cellular homeostasis, differentiation, and stress survival, which is particularly important for the cardiovascular system. Furthermore, experimental and clinical observations indicate it affects cardiac morphogenesis, including valve development. However, the cell-specificity and functional role of autophagic processes during heart development remain unclear. Here, we introduce novel zebrafish models to visualize autophagic vesicles in vivo and follow their temporal and cellular localization in the larval heart. We observed a significant accumulation of lysosomal vesicles in the developing atrioventricular and bulboventricular regions and their respective valves. Next, we addressed the role of lysosomal degradation using a Spinster homolog 1 (spns1) mutant. spns1 mutants displayed morphological and functional cardiac defects, including abnormal endocardial organization, impaired valve formation and retrograde blood flow. Single-nuclear transcriptome analysis revealed endocardial-specific differences in the expression of lysosome-related genes and alterations of notch1-signalling in the mutant. Endocardial-specific overexpression of spns1 and notch1 rescued features of valve formation and function. Altogether, our study reveals a cell-autonomous role of lysosomal processing during cardiac valve formation upstream of notch1-signalling.

developmental biology↗

bioRxiv2024

A dynamin-like protein in the human malaria parasite plays an essential role in mitochondrial homeostasis and fission during asexual blood stages

Malaria parasite harbors a single mitochondrion and its proper segregation during the parasite multiplication is crucial for propagation of the parasite within the host. Mitochondrial fission machinery consists of a number of proteins that associate with mitochondrial membrane during segregation. Here, we have identified a dynamin-like protein in P. falciparum, PfDyn2, and deciphered its role in mitochondrial division, segregation and homeostasis. GFP targeting approach combined with high resolution microscopy studies showed that the PfDyn2 associates with mitochondrial membrane to form a clip/hairpin loop like structure around it at specific sites during mitochondrial division. The C-terminal degradation tag mediated inducible knock-down (iKD) of PfDyn2 resulted in significant inhibition of parasite growth. PfDyn2-iKD hindered mitochondrial development and functioning, decreased mtDNA replication, and induced mitochondrial oxidative-stress, ultimately causing parasite death. Further, treatment of parasites with dynamin specific inhibitors disrupted the recruitment of PfDyn2 on the mitochondria, blocked mitochondrial development, and induced oxidative stress. Regulated overexpression of a phosphorylation mutant of PfDyn2 (Ser-612-Ala) had no effect on the recruitment of PfDyn2 on the mitochondria; normal mitochondrial division and parasite growth showed that phosphorylation/dephosphorylation of this conserved serine residue (Ser612) may not be responsible for regulating recruitment of PfDyn2 to the mitochondrion. Overall, we show essential role of PfDyn2 in mitochondrial dynamics and fission as well as in maintaining its homeostasis during asexual cycle of the parasite.

cell biology↗

bioRxiv2024

A paternal cardiac lesion induces cardiac adaptation in offspring

BackgroundFollowing cardiac injury, whether the heart is permanently damaged or regenerating, distal organs are subjected to changes in physiological function. It remains largely unknown whether a cardiac lesion can affect gametes and transmit heritable changes to subsequent generations. Here, we report the influence of paternal cardiac injury on the following generation. MethodsWe studied the intergenerational influence of neonatal cardiac injury in the mouse, an animal model capable of regenerating the heart after early life injury. Neonatal male mice were subjected to ventricular cryoinjury, crossed at adulthood, and their sires were compared with litters derived from uninjured male mice. We used echocardiography, histology, and single nuclei RNA-sequencing to thoroughly characterize cardiac morphology, composition, function, and response to cardiac insult. ResultsWe show that paternal cardiac injury affects the heart morphology of offspring under physiological conditions. Furthermore, in response to the same injury, the F1 generation derived from injured fathers shows better systemic and cardiac recovery, with non-pathological left ventricular enlargement and improved cardiac function during the regenerative process. This is accompanied by the activation of the immune system healing program at 3 weeks post-injury, together with enhanced transcription of genes associated with physiological hypertrophy. ConclusionsThe memory of a paternal neonatal lesion can be transmitted to offspring and improve their recovery from a cardiac insult.

developmental biology↗

bioRxiv2024

Gut microbial-mediated polyphenol metabolism is restrained by parasitic whipworm infection and associated with altered immune function in mice

Polyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundworm Heligmosomoides polygyrus, and induced a type-1, interferon-driven mucosal immune response during infection with the large intestinal whipworm Trichuris muris. PAC also induced alterations in mesenteric lymph node T-cell populations that were dependent on infection model, with a Th2/Treg bias during H. polygyrus infection, and a Th1 bias during T. muris infection. In the absence of infection, PAC intake promoted the expansion of Turicibacter sp. within the gut microbiota, increased faecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-{gamma}-valerolactones in the caecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected with T. muris, suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the caecum dwelling T. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals.

microbiology↗

bioRxiv2023

Upregulated GRP78 and sFlt-1 in preeclampsia induces IRE1 and ATF6 arms of UPR leading to ER stress in placental cells

IntroductionAmongst vivid and diversified stresses which placenta in preeclampsia undergoes, ER stress has been a hal of the fame which is an insinuation of ill-fated UPR. In our previous study, we have already reported activation of PERK arm due to sFlt-1 present in preeclamptic mothers. The present study is an attempt to interpret rest of the two arms (IRE1 and ATF6) of UPR and ER stress subsequently by in vitro study using BeWo cells after upregulation of master regulator of UPR (GRP78) in placental tissue. Materials and MethodsPart I: Serum analysis of circulating levels of GRP78 and sFlt-1 [in 50 pairs of preeclamptic and normotensive, non-proteinuric (control) pregnant women)] using ELISA. Part II: Correlation analysis of levels of GRP78 and sFlt-1 in preeclamptic and control groups. Part III: Status of expression of GRP78 in placentae (n=10 each, preeclamptic and control groups) was reported using immunofluorescence. Part IV: In vitro experiments using BeWo cells were carried out to analyse the effect of GRP78 and sFlt-1 on IRE1 and ATF6 arms of UPR at protein (immunofluorescence and western blot) and transcript (qRT-PCR) levels. ResultsProtein expressions of GRP78 and sFlt-1 were found significantly elevated in preeclamptic patients as compared to controls. Enhanced expression of master regulator of UPR (GRP78) in placental tissue of preeclamptic women was reported. Up-regulated expression of XBP1 (IRE1 arm) and ATF6 markers of UPR was observed in trophoblast cells. ConclusionThe upregulated expression of GRP78 in preeclamptic placentae and enhanced expression of XBP1 and ATF6 markers in BeWo cells at both protein and transcript levels connote role played by raised circulating levels of GRP78 and sFlt-1 in preeclampsia.

developmental biology↗

bioRxiv2023

Abnormal trophoblast invasion in early onset preeclampsia: involvement of cystathionine β-synthase, specificity protein 1 and miR-22

IntroductionImpaired trophoblast invasion has been observed in early onset Preeclampsia patients (EOPE). Trophoblast cell invasion during human placentation is majorly regulated by the balance between MMPs 2, 9 and their inhibitors [tissue inhibitors of matrix metalloproteinases (TIMPs 1, 2)]. Exogenous NaHS (hydrogen sulphide donor) treatment was shown to significantly increase the expression levels of matrix metalloproteinases (MMPs 2, 9) in human bladder cancer EJ cells. Epigentically, the gene expression of hydrogen sulphide synthesising enzyme CBS (cystathionine {beta}-synthase) could be further regulated by various mi-RNAs via the transcription factors like Sp1. Specificity protein 1 (Sp1) has been identified as a target gene for miR-22 to regulate the invasion and metastasis of gastric cancer cells. However, the mechanism of MMPs regulation by either CBS, Sp1 and miRNA-22 in the pregnancies having EOPE is not known. Aims and ObjectivesTo determine and compare the expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 in EOPE patients and normotensive, non-proteinuric controls. Materials and methods100 pregnant women were enrolled from Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. EOPE women (n=50) after clinical diagnosis as per ACOG guidelines were enrolled as cases and normotensive, non-proteinuric pregnant women (n=50) were enrolled as controls. Protocol of the study was approved by Institute Ethics Committee, AIIMS, New Delhi. 5 ml of venous blood was collected from all the recruited women (2.5 ml in each EDTA and sera vial) followed by plasma and sera separation. Plasma samples were used subsequently to determine gene expression of MMPs 2, 9, TIMPs 1, 2, CBS, Sp1 and miRNA-22 by qRT-PCR and sera samples were used to estimate their protein levels by ELISA. Data were analyzed by STATA 14 and Graph Pad Prism 8. ResultsSignificantly down regulated expression of MMPs 2, 9, CBS and Sp1 whereas up regulated expression for that of TIMPs 1, 2 was observed in EOPE patients as compared to healthy pregnant women at both transcription and translation levels. Expression of miR-22 (pre miR-22 and miR-22-3p) was found to be significantly elevated in EOPE patients as compared to normotensive, non-proteinuric controls. ConclusionThis is the very first study of its kind which implicates that down regulated MMPs 2, 9, CBS, Sp1 levels and simultaneously upregulation of miR-22 expression in EOPE patients could have some association. In vitro experiments are needed to prove their association which if proven may provide a new, potential therapeutic target to treat early onset Preeclampsia.

developmental biology↗