Epitopes mapping for identification of potential cross-reactive peptide against leptospirosis.

Leptospira, the pathogenic helical spirochetes that cause leptospirosis, is an emerging zoonotic disease with effective dissemination tactics in the host and can infect humans and animals with moderate or severe illnesses. Thus, peptide-based vaccines may be the most effective strategy to manage the immune response against Leptospira to close these gaps. In the current investigation, highly immunogenic proteins from the proteome of Leptospira interorgan serogroup Icterohaemorrhagie serovar Lai strain 56601 were identified using immunoinformatic methods. It was discovered that the conserved and most immunogenic outer membrane Lepin protein was both antigenic and non-allergenic by testing 15 linear B-cells and the ten best T-cell (Helper-lymphocyte (HTL) with the most significant number of HLA-DR binding alleles and the eight cytotoxic T lymphocyte (CTL)) epitopes. Furthermore, a 3D structural model of CTL epitopes was created using the Pep-Fold3 platform. Using the Autodock 4.2 docking server, research was conducted to determine how well the top-ranked CTL peptide models attach to HLA-A*0201 (PDB ID: 4U6Y). With HLA-A*0201, the epitope SSGTGNLHV binds with a binding energy of -1.29 kcal/mol. Utilizing molecular dynamics modeling, the projected epitope-allele docked complex structure was optimized, and the stability of the complex system was assessed. Therefore, this epitope can trigger an immunological response and produce effective Leptospira vaccine candidates. Overall, this study offers a unique vaccination candidate and may encourage additional research into leptospirosis vaccines.Communicated by Ramaswamy H. Sarma.

Genome-Wide Characterization of Fennel (Anethum foeniculum) MiRNome and Identification of its Potential Targets in Homo sapiens and Arabidopsis thaliana: An Inter and Intra-species Computational Scrutiny.

MicroRNAs could be promising biomarkers for various diseases, and small RNA drugs have already been FDA approved for clinical use. This area of research is rapidly expanding and has significant potential for the future. Fennel (Anethum foeniculum) is a highly esteemed spice plant with economic and medicinal benefits, making it an invaluable asset in the pharmaceutical industry. To characterize the fennel miRNAs and their Arabidopsis thaliana and Homo sapience targets with functional enrichment analysis and human disease association. A homology-based computational approach characterized the MiRnome of the Anethum foeniculum genome and assessed its impact on Arabidopsis thaliana and Homo sapience transcriptomes. In addition, functional enrichment analysis was evaluated for both species' targets. Moreover, PPI network analysis, hub gene identification, and MD simulation analysis of the top hub node with fennel miRNA were incorporated. We have identified 100 miRNAs of fennel and their target genes, which include 2536 genes in Homo sapiens and 1314 genes in Arabidopsis thaliana. Functional enrichment analysis reveals 56 Arabidopsis thaliana targets of fennel miRNAs showed involvement in metabolic pathways. Highly enriched human KEGG pathways were associated with several diseases, especially cancer. The protein-protein interaction network of human targets determined the top ten nodes; from them, seven hub nodes, namely MAPK1, PIK3R1, STAT3, EGFR, KRAS, CDC42, and SMAD4, have shown their involvement in the pancreatic cancer pathway. Based on the Blast algorithm, 21 fennel miRNAs are homologs to 16 human miRNAs were predicted; from them, the CSPP1 target was a common target for afo-miR11117a-3p and has-miR-6880-5p homologs miRNAs. Our results are the first to report the 100 fennel miRNAs, and predictions for their endogenous and human target genes provide a basis for further understanding of Anethum foeniculum miRNAs and the biological processes and diseases with which they are associated.

Decoding the mechanism of andrographolide to combat hepatocellular carcinoma: a network pharmacology integrated molecular docking and dynamics approach.

HepatoCellular Carcinoma, being one of the most mortally convoluted malignancy with mounting number of occurrences across the world and being classified as the third most prevalent cause of cancer-associated mortalities and sixth most prevalent neoplasia. The active phytoconstituent andrographolide, derived from Andrographis paniculata is conveyed to reconcile a number of human ailments including various oncologies. However, the molecular mechanism underlying the anti-oncogenic effects of Andrographolide on HCC remains skeptical and unclear, emerging as a budding challenge for researchers and oncologists. The present study intends to analyze the underlying pharmacological mechanism of Andrographolide over HCC, established via assimilated approach of network pharmacology. Herein, the Network pharmacology stratagem was instigated to investigate potential HCC targets. The Andrographolide targets along with HCC targets were extracted from multiple databases. A total of 162 potential overlapping targets among HCC and Andrographolide were obtained and further subjected to gene ontology and Pathway enrichment analysis by employing OmicsBox and DAVID database, respectively. Subsequently, Protein-protein interaction network construction by Cytoscape software identified the top 10 hub nodes which were validated by survival and expression analysis. Further, the results derived from molecular docking and dynamic simulations by CB-Dock2 server and Desmond module (Schrodinger software) indicate ALB, CCND1, HIF1A, TNF, and VEGFA as potential Andrographolide related targets with high binding affinity and promising complex stability. Our findings not only reveal the antioncogenic role of andrographolide but also provide novel insights illuminating the identified targets as scientific foundation for anti-oncogenic clinical application of andrographolide in HCC therapeutics.Communicated by Ramaswamy H. Sarma.

MicroRNAs from Holarrhena pubescens stems: Identification by small RNA Sequencing and their Potential Contribution to Human Gene Targets.

Holarrhena pubescens is an effective medicinal plant from the Apocynaceae family, widely distributed over the Indian subcontinent and extensively used by Ayurveda and ethno-medicine systems without apparent side effects. We postulated that miRNAs, endogenous non-coding small RNAs that regulate gene expression at the post-transcriptional level, may, after ingestion into the human body, contribute to the medicinal properties of plants of this species by inducing regulated human gene expression to modulate. However, knowledge is scarce about miRNA in Holarrhena. In addition, to test the hypothesis on the potential pharmacological properties of miRNA, we performed a high-throughput sequencing analysis using the Next Generation Sequencing Illumina platform; 42,755,236 raw reads have been generated from H. pubescens stems from a library of small RNA isolated, identifying 687 known and 50 new miRNAs led. The novel H. pubescens miRNAs were predicted to regulate specific human genes, and subsequent annotations of gene functions suggested a possible role in various biological processes and signaling pathways, such as Wnt, MAPK, PI3K-Akt, and AMPK signaling pathways and endocytosis. The association of these putative targets with many diseases, including cancer, congenital malformations, nervous system disorders, and cystic fibrosis, has been demonstrated. The top hub proteins STAT3, MDM2, GSK3B, NANOG, IGF1, PRKCA, SNAP25, SRSF1, HTT, and SNCA show their interaction with human diseases, including cancer and cystic fibrosis. To our knowledge, this is the first report of uncovering H. pubescens miRNAs based on high-throughput sequencing and bioinformatics analysis. This study has provided new insight into a potential cross-species control of human gene expression. The potential for miRNA transfer should be evaluated as one possible mechanism of action to account for the beneficial properties of this valuable species.

New molecular insights for 4H-1,2,4-triazole derivatives as inhibitors of tankyrase and Wnt-signaling antagonist: a molecular dynamics simulation study.

Tankyrase (TNKS) enzymes remained central biotargets to treat Wnt-driven colorectal cancers. The success of Olaparib posited the druggability of PARP family enzymes depending on their role in tumor proliferation. In this work, an MD-simulation-based comparative assessment of the protein-ligand interactions using the best-docked poses of three selected compounds (two of the designed and previously synthesized molecules obtained through molecular docking and one reported TNKS inhibitor) was performed for a 500 ns period. The PDB:ID-7KKP and 3U9H were selected for TNKS1 and TNKS2, respectively. The Molecular Mechanics Generalized Born Surface Area (MM-GBSA) based binding energy data exhibited stronger binding of compound-15 (average values of -102.92 and -104.32 kcal/mol for TNKS1 and TNKS2, respectively) as compared to compound-22 (average values of -82.99 and -85.68 kcal/mol for TNKS1 and TNKS2, respectively) and the reported compound-32 (average values of -81.89 and -74.43 kcal/mol for TNKS1 and TNKS2, respectively). Compound-15 and compound-22 exhibited comparable or superior binding to both receptors forming stable complexes when compared to that of compound-32 upon examining their MD trajectories. The key contributors were hydrophobic stacking and optimum hydrogen bonding allowing these molecules to occupy the adenosine pocket by interfacing D-loop residues. The results of bond distance analysis, radius of gyration, root mean square deviation, root mean square fluctuation, snapshots at different time intervals, LUMO-HUMO energy differences, electrostatic potential calculations, and binding free energy suggested better binding efficiency for compound-15 to TNKS enzymes. The computed physicochemical and ADMET properties of compound-15 were encouraging and could be explored further for drug development.Communicated by Ramaswamy H. Sarma.

Small RNA sequencing and identification of Andrographis paniculata miRNAs with potential cross­kingdom human gene targets.

Cross-species post-transcriptional regulatory potential of plant derived small non-coding microRNAs (miRNAs) has been well documented by plenteous studies. MicroRNAs are transferred to host cells via oral ingestion wherein they play a decisive role in regulation of host genes; thus, miRNAs have evolved as the nascent bioactive molecules imparting pharmacological values to traditionally used medicinal plants. The present study aims to investigate small RNA profiling in order to uncover the potential regulatory role of miRNAs derived from Andrographis paniculata, one of the most widely used herb by tribal communities for liver disorders and document the pharmacological properties of A. paniculata miRNAs. In this study, high-throughput sequencing method was used to generate raw data, ~ 60 million sequences were generated from A. paniculata leaves. Using computational tools and bioinformatics approach, analyses of 3,480,097 clean reads resulted in identification of 3440 known and 51 putative novel miRNAs regulating 1365 and 192 human genes respectively. Remarkably, the identified plausible novel miRNAs apa-miR-5, apa-miR-1, apa-miR-26, and apa-miR-30 are projected to target significant host genes including CDK6, IKBKB, TRAF3, CHD4, MECP2, and ADIPOQ. Subsequent annotations revealed probable involvement of the target genes in various pathways for instance p38-MAPK, AKT, AMPK, NF-Kß, ERK, WNT signalling, MYD88 dependant cascade, and pathways in cancer. Various diseases such as human papilloma virus infection, Alzheimer's, Non-alcoholic Fatty Liver, Alcoholic liver diseases, HepatoCellular Carcinoma (HCC), and numerous other cancers were predominantly found to be linked with target genes. Our findings postulate novel interpretations regarding modulation of human transcripts by A. paniculata miRNAs and exhibit the regulation of human diseases by plant-derived miRNAs. Though our study elucidates miRNAs as novel therapeutic agents, however, experimental validations for assessment of therapeutic potential of these miRNAs are still warranted.

MHC2AffyPred: A machine-learning approach to estimate affinity of MHC class II peptides based on structural interaction fingerprints.

Understanding how MHC class II (MHC-II) binding peptides with differing lengths exhibit specific interaction at the core and extended sites within the large MHC-II pocket is a very important aspect of immunological research for designing peptides. Certain efforts were made to generate peptide conformations amenable for MHC-II binding and calculate the binding energy of such complex formation but not directed toward developing a relationship between the peptide conformation in MHC-II structures and the binding affinity (BA) (IC50 ). We present here a machine-learning approach to calculate the BA of the peptides within the MHC-II pocket for HLA-DRA1, HLA-DRB1, HLA-DP, and HLA-DQ allotypes. Instead of generating ensembles of peptide conformations conventionally, the biased mode of conformations was created by considering the peptides in the crystal structures of pMHC-II complexes as the templates, followed by site-directed peptide docking. The structural interaction fingerprints generated from such docked pMHC-II structures along with the Moran autocorrelation descriptors were trained using a random forest regressor specific to each MHC-II peptide lengths (9-19). The entire workflow is automated using Linux shell and Perl scripts to promote the utilization of MHC2AffyPred program to any characterized MHC-II allotypes and is made for free access at https://github.com/SiddhiJani/MHC2AffyPred. The MHC2AffyPred attained better performance (correlation coefficient [CC] of .612-.898) than MHCII3D (.03-.594) and NetMHCIIpan-3.2 (.289-.692) programs in the HLA-DRA1, HLA-DRB1 types. Similarly, the MHC2AffyPred program achieved CC between .91 and .98 for HLA-DP and HLA-DQ peptides (13-mer to 17-mer). Further, a case study on MHC-II binding 15-mer peptides of severe acute respiratory syndrome coronavirus-2 showed very close competency in computing the IC50 values compared to the sequence-based NetMHCIIpan v3.2 and v4.0 programs with a correlation of .998 and .570, respectively.

Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons.

Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights. Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications. Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers. Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances. Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.

A Comprehensive in vitro and in silico Assessment on Inhibition of CYP51B and Ergosterol Biosynthesis by Eugenol in Rhizopus oryzae.

Mucormycosis, also known as Zygomycosis, is a disease caused by invasive fungi, predominantly Rhizopus species belonging to the Order of Mucorales. Seeing from the chemistry perspective, heterocyclic compounds with an "azole" moiety are widely employed as antifungal agent for minimising the effect of mucormycosis as a prescribed treatment. These azoles serve as non-competitive inhibitors of fungal CYP51B by predominantly binding to its heme moiety, rendering its inhibition. However, long-term usage and abuse of azoles as antifungal medicines has resulted in drug resistance among certain fungal pathogens. Hence, there is an unmet need to find alternative therapeutic compounds. In present study, we used various in vitro tests to investigate the antifungal activity of eugenol against R. oryzae/R. arrhizus, including ergosterol quantification to test inhibition of ergosterol production mediated antifungal action. The minimum inhibitory concentration (MIC) value obtained for eugenol was 512 µg/ml with reduced ergosterol concentration of 77.11 ± 3.25% at MIC/2 concentration. Further, the molecular interactions of eugenol with fungal CYP51B were meticulously studied making use of proteomics in silico study including molecular docking and molecular dynamics simulations that showed eugenol to be strongly interacting with heme in an identical fashion to that shown by azole drugs (in this case, clotrimazole was evaluated). This is the first of a kind study showing the simulation study of eugenol with CYP51B of fungi. This inhibition results in ergosterol synthesis and is also studied and compared with keeping clotrimazole as a reference.

Small RNA sequencing and identification of papaya (Carica papaya L.) miRNAs with potential cross-kingdom human gene targets.

Several studies have demonstrated potential role of plant-derived miRNAs in cross-kingdom species relationships by transferring into non-plant host cells to regulate certain host cellular functions. How nutrient-rich plants regulate host cellular functions, which in turn alleviate physiological and disease conditions in the host remains to be explored in detail. This computational study explores the potential targets, putative role, and functional implications of miRNAs derived from Carica papaya L., one of the most cultivated tropical crops in the world and a rich source of phytochemicals and enzymes, in human diet. Using the next-generation sequencing, -Illumina HiSeq2500, ~ 30 million small RNA sequence reads were generated from C. papaya young leaves, resulting in the identification of a total of 1798 known and 49 novel miRNAs. Selected novel C. papaya miRNAs were predicted to regulate certain human targets, and subsequent annotation of gene functions indicated a probable role in various biological processes and pathways, such as MAPK, WNT, and GPCR signaling pathways, and platelet activation. These presumptive target gene in humans were predominantly linked to various diseases, including cancer, diabetes, mental illness, and platelet disorder. The computational finding of this study provides insights into how C. papaya-derived miRNAs may regulate certain conditions of human disease and provide a new perspective on human health. However, the therapeutic potential of C. papaya miRNA can be further explored through experimental studies.

Understanding the Molecular Mechanisms of Betel miRNAs on Human Health.

BACKGROUND: Since ancient times, "betel leaf" (Piper betle) has been revered for its religious, cultural, and medicinal properties. Phytochemicals from the Piper betle are effective in a variety of conditions, including cancer. To date, however, no genomic study or evidence has been found to elucidate the regulatory mechanism that underpins its therapeutic properties. This is the first study of its kind to predict Piper betle miRNAs and also the first genomics source representation of Piper betle. According to previous research, miRNAs from the plants we eat can regulate gene expression. In line with this, our in-silico study revealed that Piper betle and human cross-kingdom control occurs. METHODS: This study demonstrates the prediction and in-silico validation of Piper betle miRNAs from NGS-derived transcript sequences. The cross-kingdom regulation, which can also be understood as inter- species RNA regulation, was studied to identify human mRNA targets controlled by Piper betle miRNAs. Functional annotation and gene-disease association of human targets were performed to understand the role of Piper betle miRNAs in human health and disease. The protein-protein interaction and expression study of targets was further carried out to decipher their role in cancer development. RESULTS: Identified six Piper betle miRNAs belonging to miR156, miR164, miR172, and miR535 families were discovered to target 198 human mRNAs involved in various metabolic and disease processes. Angiogenesis and the cell surface signaling pathway were the most enriched gene ontology correlated with targets, both of which play a critical role in disease mechanisms, especially in the case of carcinoma. In an analysis of gene-disease interactions, 40 genes were found to be related to cancer. According to a protein-protein interaction, the CDK6 gene, which is thought to be a central regulator of cell cycle progression, was found as a hub protein, affecting the roles of CBFB, SAMD9, MDM4, AXIN2, and NOTCH2 oncogenes. Further investigation revealed that pbe-miRNA164a can be used as a regulator to minimise disease severity in Acute Myeloid Leukemia, where CDK6 expression is highest compared to normal cells. CONCLUSION: The predicted pbe-miRNA164a in this study can be a promising suppressor of CDK6 gene involved in tumour angiogenesis. In vivo validation of the pbe-miRNA164a mimic could pave the way for new opportunities to fight cancer and leverage the potential of Piper betle in the healthcare sector.

A core and pan gene map of Leptospira genus and its interactions with human host.

Leptospira species are the etiological agent of an emerging zoonotic disease known as "Leptospirosis" that substantially affects both human health and economy across the globe. Despite the global importance of the disease, pathogenetic features, host-adaptation and proper diagnosis of this bacteria remains lacking. To accomplish these gaps, pan-genome of Leptospira genus was explored in the present study. The pan-genome of Leptospira genus was comprised of core (692) and accessory parts (softcore:1804, shell:6432, cloud:16,600). The functional analysis revealed the abundancy of "Translation, ribosomal structure and biogenesis" COG class in core-genes; whereas in accessory parts, genes involved in signal transduction was the most abundant. Furthermore, pathogen-host interaction (PHI) analysis of core and accessory proteins with human proteins showed the presence of a total of 599 and 510 interactions, respectively. There were eight hubs in core PHI network and five hubs in PHI network of accessory proteins. The human's proteins involved in these interactions were found functionally enriched in metabolic processes, responses to stimulus and immune system processes. Further, pan-genome based phylogeny separated the Leptospira genus in three major clades (belonging to P1, P2 and S) which relates with their pathogenicity level. Additionally, pathogenic and saprophytic clade specific genes of Leptospira have also been identified and functionally annotated for COG, KEGG and virulence factors. The results revealed the presence of 102 pathogenic and 215 saprophytic group specific gene clusters. The COG functional annotation of pathogen specific genes showed that defence mechanism followed by signal transduction mechanisms category were most significantly enriched COG categories; whereas in saprophytic group, signal transduction mechanisms was the most abundant COG, suggesting their role in adaptation and hence important for microbe's evolution and survival. In conclusion, this study provides a new insight of genomic features of Leptospira genus which may further be implemented for development of better control actions of the disease.

Unravelling the antifungal mode of action of curcumin by potential inhibition of CYP51B: A computational study validated in vitro on mucormycosis agent, Rhizopus oryzae.

Like human, fungi too are known to share lot of structural similarities amongst their CYPs (Cytochrome P450 super family of enzymes) which allows antifungal 'azole' compounds to interact with CYPs of human. Clotrimazole, an 'azole' antifungal drug, is a known inhibitor of fungal CYP named CYP51B. Curcumin, a phytochemical obtained from Curcuma longa has the ability to interact with several different human CYPs to induce inhibition. The sequence and the structural similarities amongst both human and fungal CYPs suggest a strong possibility for curcumin to interact with fungal CYP51B to behave like an antifungal agent. To test this hypothesis a study was designed involving mucormycosis agent, Rhizopus oryzae. The ability of curcumin to interact with fungal CYP51B was analysed computationally through molecular docking, MM-GBSA and Molecular Dynamics (MD) simulation assessment. Further, interaction profile for fungal CYP51B-curcumin was compared with human CYP3A4-curcumin, as there are published evidence describing curcumin as an inhibitor of human CYPs. Additionally, to validate in silico findings, an in vitro assay was performed to examine the antifungal potentials of curcumin on the R. oryzae. Conclusive results allow us to determine a plausible mode of action of curcumin to act as an antifungal against a mucormycosis agent.

Whole genome sequencing and de novo assembly of three virulent Indian isolates of Leptospira.

Leptospirosis is a re-emerging bacterial zoonosis caused by pathogenic Leptospira, with a worldwide distribution and becoming a major public health concern. Prophylaxis of this disease is difficult due to several factors such as non-specific variable clinical manifestation, presence of a large number of serovar, species and asymptomatic reservoir hosts, lack of proper diagnostics and vaccines. Despite its global importance and severity of the disease, knowledge about the molecular mechanism of pathogenesis and evolution of pathogenic species of Leptospira remains limited. In this study, we sequenced and analyzed three highly pathogenic species of Indian isolates of Leptospira (interrogans, santarosai, and kirschneri). Additionally, we identified some virulence-related and CRISPR-Cas genes. The virulent analysis showed 232 potential virulence factors encoding proteins in L. interrogans strain Salinem and L. santarosai strain M-4 genome. While the genome of L. kirschneri strain Wumalasena was predicted to encode 198 virulence factor proteins. The variant calling analysis revealed 1151, 19,786, and 22,996 single nucleotide polymorphisms (SNPs) for L. interrogans strain Salinem, L. kirschneri strain Wumalasena and L. santarosai strain M-4, respectively, with a maximum of 5315 missense and 12,221 synonymous mutations for L. santarosai strain M-4. The structural analyses of genomes indicated potential evidence of inversions and structural rearrangment in all three genomes. The availability of these genome sequences and in silico analysis of Leptospira will provide a basis for a deeper understanding of their molecular diversity and pathogenesis mechanism, and further pave a way towards proper management of the disease.

Vaccine Design Against Leptospirosis Using an Immunoinformatic Approach.

Vaccination is the best way to prevent the spread of emerging or reemerging infectious disease. Current research for vaccine development is mainly focused on recombinant-, subunit-, and peptide-based vaccine. At this point, immunoinformatics has been proven as a powerful method for identification of potential vaccine candidates, by analyzing immunodominat B- and T-cell epitopes. This method can reduce the time and cost of experiment to a great extent, by reducing the number of vaccine candidates for experimental testing for their efficacy. This chapter describes the use of immunoinformatics and molecular docking methods to screen potential vaccine candidates by taking Leptospira as a model.

Transcriptome-wide miRNA identification of Bacopa monnieri: a cross-kingdom approach.

Bacopa monnieri known as 'Brahmi' is a well-known medicinal plant belonging to Scrophulariaceae family for its nootropic properties. To the best of our knowledge, no characterization data is available on the potential role of micro RNAs (miRNAs) from this plant till date. We present here the first report of computational characterizations of miRNAs from B. monnieri. Owing to the high conservation of miRNAs in nature, new and potential miRNAs can be identified in plants using in silico techniques. Using the plant miRNA sequences present in the miRBase repository, a total of 12 miRNAs were identified from B. monnieri which pertained to 11 miRNA families from the shoot and root transcriptome data. Furthermore, gene ontology analysis of the identified 68 human target genes exhibited significance in various biological processes. These human target genes were associated with signaling pathways like NF-kB and MAPK with TRAF2, CBX1, IL1B, ITGA4 and ITGB1BP1 as the top five hub nodes. This cross-kingdom study provides initial insights about the potential of miRNA-mediated cross-kingdom regulation and unravels the essential target genes of human with implications in numerous human diseases including cancer.

Computational identification of miRNA and their cross kingdom targets from expressed sequence tags of Ocimum basilicum.

MicroRNAs (miRNAs) are conserved small non coding RNAs, which are typically 22-24 nucleotides long and play an important role in post transcription regulation andin various biological processes in both animals and plants. Ocimum basilicum is an important medicinal plant having different bioactive compounds eugenol and essential oils that possess numerous therapeutic properties. However, only a few miRNAs of Ocimum basilicum and its function have been studied till date. The present study focusses on the identification of miRNA from expressed sequenced tags by carrying out computational approaches based on the homology search method. A total of 10 potential miRNAs with 8 different families were predicted in O.basilicum. Furthermore, the psRNA target server was used to predict cross kingdom target genes on human transcriptome for identification ofpotential miRNAs. Eight miRNA families were found to modulate the 87 human target genes which were associated with RAS/MAPK signalling cascade, cardiomyopathy, HIV, breast cancer, lung cancer, Alzheimer's diseases and several neurological disorders. Moreover, O.basilicum miRNAs regulate the key human target genes having significance in various diseases and important biological networks with 10 hub nodes interactions. Thus this study gives the pave for further studies to explore the potential of miRNA mediated cross kingdom regulation and treatment of various diseases including cancer.

Ocimum basilicum miRNOME revisited: A cross kingdom approach.

O. basilicum is medicinally important herb having inevitable role in human health. However, the mechanism of action is largely unknown. Present study aims to understand the mechanism of regulation of key human target genes that could plausibly modulated by O. basilicum miRNAs in cross kingdom manner using computational and system biology approach. O. basilicum miRNA sequences were retrieved and their corresponding human target genes were identified using psRNA target and interaction analysis of hub nodes. Six O. basilicum derived miRNAs were found to modulate 26 human target genes which were associated `with PI3K-AKTand MAPK signaling pathways with PTPN11, EIF2S2, NOS1, IRS1 and USO1 as top 5 Hub nodes. O. basilicum miRNAs not only regulate key human target genes having a significance in various diseases but also paves the path for future studies that might explore potential of miRNA mediated cross-kingdom regulation, prevention and treatment of various human diseases including cancer.

Publisher Correction: Silibinin, A Natural Blend In Polytherapy Formulation For Targeting Cd44v6 Expressing Colon Cancer Stem Cells.

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