Transcriptomics, proteomics, and metabolomics interventions prompt crop improvement against metal(loid) toxicity.

The escalating challenges posed by metal(loid) toxicity in agricultural ecosystems, exacerbated by rapid climate change and anthropogenic pressures, demand urgent attention. Soil contamination is a critical issue because it significantly impacts crop productivity. The widespread threat of metal(loid) toxicity can jeopardize global food security due to contaminated food supplies and pose environmental risks, contributing to soil and water pollution and thus impacting the whole ecosystem. In this context, plants have evolved complex mechanisms to combat metal(loid) stress. Amid the array of innovative approaches, omics, notably transcriptomics, proteomics, and metabolomics, have emerged as transformative tools, shedding light on the genes, proteins, and key metabolites involved in metal(loid) stress responses and tolerance mechanisms. These identified candidates hold promise for developing high-yielding crops with desirable agronomic traits. Computational biology tools like bioinformatics, biological databases, and analytical pipelines support these omics approaches by harnessing diverse information and facilitating the mapping of genotype-to-phenotype relationships under stress conditions. This review explores: (1) the multifaceted strategies that plants use to adapt to metal(loid) toxicity in their environment; (2) the latest findings in metal(loid)-mediated transcriptomics, proteomics, and metabolomics studies across various plant species; (3) the integration of omics data with artificial intelligence and high-throughput phenotyping; (4) the latest bioinformatics databases, tools and pipelines for single and/or multi-omics data integration; (5) the latest insights into stress adaptations and tolerance mechanisms for future outlooks; and (6) the capacity of omics advances for creating sustainable and resilient crop plants that can thrive in metal(loid)-contaminated environments.

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies.

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than -8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.Communicated by Ramaswamy H. Sarma.

Anti-lung Cancer Activity of Synthesized Substituted 1,4-Benzothiazines: An Insight from Molecular Docking and Experimental Studies.

BACKGROUND: Thiazine, a 6-membered distinctive heterocyclic motif with sulfur and nitrogen atoms, is one of the heterocyclic compounds that functions as a core scaffold in a number of medicinally significant molecules. Small thiazine-based compounds may operate simultaneously on numerous therapeutic targets and by employing a variety of methods to halt the development, proliferation, and vasculature of cancer cells. We have, herein, reported a series of substituted 1,4 benzothiazines as potential anticancer agents for the treatment of lung cancer. METHODS: In order to synthesize 2,3-disubstituted-1,4 benzothiazines in good yield, a facile green approach for the oxidative cycloaddition of 2-amino benzenethiol and 1,3-dicarbonyls employing a catalytic amount of ceric ammonium nitrate has been devised. All the molecules have been characterized by spectral analysis and tested for anticancer activity against the A-549 lung cancer cell line using various functional assays. Further in silico screening of compound 3c against six crucial inflammatory molecular targets, such as Il1-α (PDB ID: 5UC6), Il1- ß (PDB ID: 6Y8I), Il6 (PDB ID: 1P9M), vimentin (PDB ID: 3TRT), COX-2 (PDB ID: 5KIR), Il8 (PDB ID: 5D14), and TNF-α (PDB ID: 2AZ5), was done using AutoDock tool. RESULTS: Among the synthesized compounds, propyl 3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazine-2- carboxylate (3c) was found to be most active based on cell viability assays using A-549 lung cancer cell line and was found to effectively downregulate various pro-inflammatory genes, like Il1-α, Il1-ß, Il6, vimentin, COX-2, Il8, and TNF-α in vitro. The ability of the molecule to effectively suppress the proliferation and migration of lung cancer cells in vitro has been further demonstrated by the colony formation unit assay and wound healing assay. Molecular docking analysis showed the maximal binding affinity (- 7.54 kcal/mol) to be exhibited by compound 3c against IL8. CONCLUSION: A green unconventional route for the synthesis of 2,3-disubstituted-1,4 benzothiazines has been developed. All the molecules were screened for their activity against lung cancer and the data suggested that the presence of an additional unbranched alkyl group attached to the thiazine ring increased their activity. Also, in vitro and in silico modeling confirmed the anti-cancer efficiency of compound 3c, encouraging the exploration of such small molecules against cancer.

Network pharmacology and experimental validation for deciphering the action mechanism of Fritillaria cirrhosa D. Don constituents in suppressing breast carcinoma.

Fritillaria cirrhosa D. Don is a well-known medicinal plant of Kashmir Himalaya. Traditionally, it has been used to treat several diseases, including cancer. However, the molecular mechanism behind anticancer activity remains unclear. Therefore, in the present study, we have performed high performance-liquid chromatography-mass spectrometry (HR-LC/MS), network pharmacology, molecular docking and molecular dynamic (MD) simulation methods were used to explore the underlying molecular mechanism of F. cirrhosa for the treatment of breast cancer (BC). The targets of F. cirrhosa for treating BC were predicted using databases like SwissTargetPrediction, Gene Cards and OMIM. Protein-protein interaction analysis and network construction were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins programme, and analysis of Gene Ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was done using the Cytoscape programme. In addition, molecular docking was used to investigate intermolecular interactions between the compounds and the proteins using the Autodock tool. MD simulations studies were also used to explore the stability of the representative AKT1 gene peiminine and Imperialine-3-ß-glucoside. In addition, experimental treatment of F. cirrhosa was also verified. HR-LC/MS detected the presence of several secondary metabolites. Afterward, molecular docking was used to verify the effective activity of the active ingredients against the prospective targets. Additionally, Peiminine and Imperialine-3-ß-glucoside showed the highest binding energy score against AKT-1 (-12.99 kcal/mol and -12.08 kcal/mol). AKT1 with Peiminine and Imperialine-3-ß-glucoside was further explored for MD simulations. During the MD simulation study at 100 nanoseconds, a stable complex formation of AKT1 + Peiminine and Imperialine-3-ß-glucoside was observed. The binding free energy calculations using MM/GBSA showed significant binding of the ligand with protein (ΔG: -79.83 ± 3.0 kcal/mol) between AKT1 + Peiminine was observed. The principal component analysis exhibited a stable converged structure by achieving global motion. Lastly, F. cirrhosa extracts also exhibited momentous anticancer activity through in vitro studies. Therefore, present study revealed the molecular mechanism of F. cirrhosa constituents for the effective treatment of BC by deactivating various multiple gene targets, multiple pathways particularly the PI3K-Akt signaling pathway. These findings emphasized the momentous anti-BC activity of F. cirrhosa constituents.Communicated by Ramaswamy H. Sarma.

Fritillaria cirrhosa D. Don is well-known, the medicinal plant in the Kashmir Himalaya. Traditionally, it has been used to treat various diseases, including cancer.Many secondary metabolites were identified in F. cirrhosa using high performance-liquid chromatography-mass spectrometry technique, and these bioactive components and potential breast cancer (BC) therapy targets were validated using network pharmacology, molecular docking and MD simulation studies.The bioactive components such as Peimine, Imperialine 3-glucoside and other vital phytocompounds of F. cirrhosa have been demonstrated to interact with AKT1 efficiently, indicating their relevance in inhibiting AKT1 and other protein targets in BC.This study overall showed the anticancer activity of F. cirrhosa extracts by integrating network pharmacology, docking analysis and in vitro experiments.

Integrons in the development of antimicrobial resistance: critical review and perspectives.

Antibiotic resistance development and pathogen cross-dissemination are both considered essential risks to human health on a worldwide scale. Antimicrobial resistance genes (AMRs) are acquired, expressed, disseminated, and traded mainly through integrons, the key players capable of transferring genes from bacterial chromosomes to plasmids and their integration by integrase to the target pathogenic host. Moreover, integrons play a central role in disseminating and assembling genes connected with antibiotic resistance in pathogenic and commensal bacterial species. They exhibit a large and concealed diversity in the natural environment, raising concerns about their potential for comprehensive application in bacterial adaptation. They should be viewed as a dangerous pool of resistance determinants from the "One Health approach." Among the three documented classes of integrons reported viz., class-1, 2, and 3, class 1 has been found frequently associated with AMRs in humans and is a critical genetic element to serve as a target for therapeutics to AMRs through gene silencing or combinatorial therapies. The direct method of screening gene cassettes linked to pathogenesis and resistance harbored by integrons is a novel way to assess human health. In the last decade, they have witnessed surveying the integron-associated gene cassettes associated with increased drug tolerance and rising pathogenicity of human pathogenic microbes. Consequently, we aimed to unravel the structure and functions of integrons and their integration mechanism by understanding horizontal gene transfer from one trophic group to another. Many updates for the gene cassettes harbored by integrons related to resistance and pathogenicity are extensively explored. Additionally, an updated account of the assessment of AMRs and prevailing antibiotic resistance by integrons in humans is grossly detailed-lastly, the estimation of AMR dissemination by employing integrons as potential biomarkers are also highlighted. The current review on integrons will pave the way to clinical understanding for devising a roadmap solution to AMR and pathogenicity. Graphical AbstractThe graphical abstract displays how integron-aided AMRs to humans: Transposons capture integron gene cassettes to yield high mobility integrons that target res sites of plasmids. These plasmids, in turn, promote the mobility of acquired integrons into diverse bacterial species. The acquisitions of resistant genes are transferred to humans through horizontal gene transfer.

Exploring the tumor immune microenvironment in ovarian cancer: a way-out to the therapeutic roadmap.

INTRODUCTION: Despite cancer treatment strides, mortality due to ovarian cancer remains high globally. While immunotherapy has proven effective in treating cancers with low cure rates, it has limitations. Growing evidence suggests that both tumoral and non-tumoral components of the tumor immune microenvironment (TIME) play a significant role in cancer growth. Therefore, developing novel and focused therapy for ovarian cancer is critical. Studies indicate that TIME is involved in developing ovarian cancer, particularly genome-, transcriptome-, and proteome-wide studies. As a result, TIME may present a prospective therapeutic target for ovarian cancer patients. AREAS COVERED: We examined several TIME-targeting medicines and the connection between TIME and ovarian cancer. The key protagonists and events in the TIME and therapeutic strategies that explicitly target these events in ovarian cancer are discussed. EXPERT OPINION: We highlighted various targeted therapies against TIME in ovarian cancer, including anti-angiogenesis therapies and immune checkpoint inhibitors. While these therapies are in their infancy, they have shown promise in controlling ovarian cancer progression. The use of 'omics' technology is helping in better understanding of TIME in ovarian cancer and potentially identifying new therapeutic targets. TIME-targeted strategies could account for an additional treatment strategy when treating ovarian cancer.

Network pharmacology combined with molecular docking and in vitro verification reveals the therapeutic potential of Delphinium roylei munz constituents on breast carcinoma.

Delphinium roylei Munz is an indigenous medicinal plant to India where its activity against cancer has not been previously investigated, and its specific interactions of bioactive compounds with vulnerable breast cancer drug targets remain largely unknown. Therefore, in the current study, we aimed to evaluate the anti-breast cancer activity of different extracts of D. roylei against breast cancer and deciphering the molecular mechanism by Network Pharmacology combined with Molecular Docking and in vitro verification. The experimental plant was extracted with various organic solvents according to their polarity index. Phytocompounds were identified by High resolution-liquid chromatography-mass spectrometry (HR-LC/MS) technique, and SwissADME programme evaluated their physicochemical properties. Next, target(s) associated with the obtained bioactives or breast cancer-related targets were retrieved by public databases, and the Venn diagram selected the overlapping targets. The networks between overlapping targets and bioactive were visualized, constructed, and analyzed by STRING programme and Cytoscape software. Finally, we implemented a molecular docking test (MDT) using AutoDock Vina to explore key target(s) and compound(s). HR-LC/MS detected hundreds of phytocompounds, and few were accepted by Lipinski's rules after virtual screening and therefore classified as drug-like compounds (DLCs). A total of 464 potential target genes were attained for the nine quantitative phytocompounds and using Gene Cards, OMIM and DisGeNET platforms, 12063 disease targets linked to breast cancer were retrieved. With Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment, a total of 20 signalling pathways were manifested, and a hub signalling pathway (PI3K-Akt signalling pathway), a key target (Akt1), and a key compound (8-Hydroxycoumarin) were selected among the 20 signalling pathways via molecular docking studies. The molecular docking investigation revealed that among the nine phytoconstituents, 8-hydroxycoumarin showed the best binding energy (-9.2 kcal/mol) with the Akt1 breast cancer target. 8-hydroxycoumarin followed all the ADME property prediction using SwissADME, and 100 nanoseconds (ns) MD simulations of 8-hydroxycoumarin complexes with Akt1 were found to be stable. Furthermore, D. roylei extracts also showed significant antioxidant and anticancer activity through in vitro studies. Our findings indicated for the first time that D. roylei extracts could be used in the treatment of BC.

Artificial intelligence and cheminformatics tools: a contribution to the drug development and chemical science.

In the ever-evolving field of drug discovery, the integration of Artificial Intelligence (AI) and Machine Learning (ML) with cheminformatics has proven to be a powerful combination. Cheminformatics, which combines the principles of computer science and chemistry, is used to extract chemical information and search compound databases, while the application of AI and ML allows for the identification of potential hit compounds, optimization of synthesis routes, and prediction of drug efficacy and toxicity. This collaborative approach has led to the discovery, preclinical evaluations and approval of over 70 drugs in recent years. To aid researchers in the pursuit of new drugs, this article presents a comprehensive list of databases, datasets, predictive and generative models, scoring functions and web platforms that have been launched between 2021 and 2022. These resources provide a wealth of information and tools for computer-assisted drug development, and are a valuable asset for those working in the field of cheminformatics. Overall, the integration of AI, ML and cheminformatics has greatly advanced the drug discovery process and continues to hold great potential for the future. As new resources and technologies become available, we can expect to see even more groundbreaking discoveries and advancements in these fields.Communicated by Ramaswamy H. Sarma.

Putting CRISPR-Cas system in action: a golden window for efficient and precise genome editing for crop improvement.

The daunting task of feeding an ever-growing population is an immense challenge for the contemporary scientific community, especially in view of the rapidly changing climate throughout the world. Amidst these threatening crises, we witness rapid development in genome editing (GE) technologies, revolutionizing the field of applied genomics and molecular breeding. Various GE tools have been developed during the last two decades, but the CRISPR/Cas system has most recently made a significant impact on crop improvement. The major breakthroughs of this versatile toolbox are genomic modifications like single base-substitutions, multiplex GE, gene regulation, screening mutagenesis, and enhancing the breeding of wild crop plants. Previously, this toolbox was used to modify genes related to significant traits such as biotic/abiotic resistance/tolerance, post-harvest traits, nutritional regulation, and to address self-incompatibility analysis-related challenges. In the present review, we have demonstrated the functional dynamics of CRISPR-based GE and its applicability in targeting genes to accomplish novel editing of crops. The compiled knowledge will provide a solid foundation for highlighting the primary source for applying CRISPR/Cas as a toolbox for enhancing crops, to achieve food and nutritional security.

Unravelling diversity, drivers, and indicators of soil microbiome of Trillium govanianum, an endangered plant species of the Himalaya.

In an era of global environmental change, conservation of threatened biodiversity and ecosystem restoration are formidable ecological challenges. The forest understory strata and the belowground soil environment including rhizospheric microbial communities, which are crucial for ecosystem functioning and overall forest biodiversity maintenance, have remained understudied. Here, we investigate the soil microbiome of Trillium govanianum - an endangered Himalayan Forest herb, to unravel the underground diversity, drivers, and potential indicators of the microbial community. We collected rhizospheric and bulk soil samples for microbiome and physicochemical analysis at three sites along an elevation gradient (2500-3300 m) in Kashmir Himalaya. Amplicon sequencing of 16 S rRNA and ITS was used to identify the bacterial and fungal soil microorganisms. We found significant differences in the structure and diversity of microbial community (bacterial and fungal) between the rhizosphere and bulk soil along the altitudinal gradient, and noticeable shifts in the nutrient level in dominant microbial phyla associated with T. govanianum. A significant difference between soil physicochemical parameters and increasing altitude suggests that microbial community structure is determined by altitude and soil type. Similarly, the microbial communities showed a significant (P < 0.05) correlation with soil physicochemical variables along the altitudinal gradient. The moisture content in bacterial and total organic carbon in fungal communities showed the most substantial impact on the physiochemical drivers. We also identify potential bacterial and fungal plant growth promoter indicator species in the soil microbiome of T. govanianum. Overall, our findings provide novel research insights that can be pivotal in designing integrated species recovery programs and long-term restoration plans for T. govanianum, with learnings for biodiversity conservation elsewhere.

Integrating genomics and genome editing for orphan crop improvement: a bridge between orphan crops and modern agriculture system.

Domestication of orphan crops could be explored by editing their genomes. Genome editing has a lot of promise for enhancing agricultural output, and there is a lot of interest in furthering breeding in orphan crops, which are sometimes plagued with unwanted traits that resemble wild cousins. Consequently, applying model crop knowledge to orphan crops allows for the rapid generation of targeted allelic diversity and innovative breeding germplasm. We explain how plant breeders could employ genome editing as a novel platform to accelerate the domestication of semi-domesticated or wild plants, resulting in a more diversified base for future food and fodder supplies. This review emphasizes both the practicality of the strategy and the need to invest in research that advances our understanding of plant genomes, genes, and cellular systems. Planting more of these abandoned orphan crops could help alleviate food scarcities in the challenge of future climate crises.

Antimicrobial resistance: new insights and therapeutic implications.

Antimicrobial resistance has not been a new phenomenon. Still, the number of resistant organisms, the geographic areas affected by emerging drug resistance, and the magnitude of resistance in a single organism are enormous and mounting. Disease and disease-causing agents formerly thought to be contained by antibiotics are now returning in new forms resistant to existing therapies. Antimicrobial resistance is one of the most severe and complicated health issues globally, driven by interrelated dynamics in humans, animals, and environmental health sectors. Coupled with various epidemiological factors and a limited pipeline for new antimicrobials, all these misappropriations allow the transmission of drug-resistant organisms. The problem is likely to worsen soon. Antimicrobial resistance in general and antibiotic resistance in particular is a shared global problem. Actions taken by any single country can adversely or positively affect the other country. Targeted coordination and prevention strategies are critical in stopping the spread of antibiotic-resistant organisms and hence its overall management. This article has provided in-depth knowledge about various methods that can help mitigate the emergence and spread of antimicrobial resistance globally. KEY POINTS: • Overview of antimicrobial resistance as a global challenge and explain various reasons for its rapid progression. • Brief about the intrinsic and acquired resistance to antimicrobials and development of antibiotic resistance in bacteria. • Systematically organized information is provided on different strategies for tackling antimicrobial resistance for the welfare of human health.

The role of plant-associated rhizobacteria in plant growth, biocontrol and abiotic stress management.

The rhizosphere is the region around the plant roots where maximum microbial activities occur. In the rhizosphere, microorganisms' beneficial and harmful activities affect plant growth and development. The mutualistic rhizospheric bacteria which improve plant growth and health are known as plant growth-promoting rhizobacteria (PGPR). They are very important due to their ability to help the plant in diverse ways. PGPR such as Pseudomonas, Bacillus, Azospirillum, Azotobacter, Arthrobacter, Achromobacter, Micrococcus, Enterobacter, Rhizobium, Agrobacterium, Pantoea and Serratia are now very well known. Rhizomicrobiome plays critical roles in nutrient acquisition and assimilation, improved soil texture, secreting and modulating extracellular molecules such as hormones, secondary metabolites, antibiotics and various signal compounds, all leading to the enhancement of plant growth and development. The microbes and compounds they secrete constitute valuable biostimulants and play pivotal roles in modulating plant stress responses. In this review, we highlight the rhizobacteria diversity and cutting-edge findings focusing on the role of a PGPR in plant growth and development. We also discussed the role of PGPR in resisting the adverse effects arising from various abiotic (drought, salinity, heat, heavy metals) stresses.

Molecular docking analysis and evaluation of the antimicrobial properties of the constituents of Geranium wallichianum D. Don ex Sweet from Kashmir Himalaya.

Geranium wallichianum D. Don ex Sweet is a well-known medicinal plant in Kashmir Himalya. The evidence for its modern medicinal applications remains majorly unexplored. The present study was undertaken to elucidate the detailed antimicrobial promises of different crude extracts (methanolic, ethanolic, petroleum ether, and ethyl acetate) of G. wallichainum against common human bacterial and fungal pathogens in order to scientifically validate its traditional use. The LC-MS analysis of G. wallichainum yielded 141 bioactive compounds with the vast majority of them having therapeutic applications. Determination of minimum inhibitory concentrations (MICs) by broth microdilution method of G. wallichainum was tested against bacterial and fungal pathogens with MICs ranging from 0.39 to 400 µg/mL. Furthermore, virtual ligands screening yielded elatine, kaempferol, and germacrene-A as medicinally most active constituents and the potential inhibitors of penicillin-binding protein (PBP), dihydropteroate synthase (DHPS), elongation factor-Tu (Eu-Tu), ABC transporter, 1,3 beta glycan, and beta-tubulin. The root mean square deviation (RMSD) graphs obtained through the molecular dynamic simulations (MDS) indicated the true bonding interactions which were further validated using root mean square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. The effective binding of elatine, kaempferol, and germacrene-A with these proteins provides ground for further research to understand the underlying mechanism that ceases the growth of these microbes.

Natural Therapeutics in Aid of Treating Alzheimer's Disease: A Green Gateway Toward Ending Quest for Treating Neurological Disorders.

The current scientific community is facing a daunting challenge to unravel reliable natural compounds with realistic potential to treat neurological disorders such as Alzheimer's disease (AD). The reported compounds/drugs mostly synthetic deemed the reliability and therapeutic potential largely due to their complexity and off-target issues. The natural products from nutraceutical compounds emerge as viable preventive therapeutics to fill the huge gap in treating neurological disorders. Considering that Alzheimer's disease is a multifactorial disease, natural compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs so far used to treat Alzheimer's disease. A wide range of plant extracts and phytochemicals reported to possess the therapeutic potential to Alzheimer's disease includes curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and other phytochemicals such as huperzine A, limonoids, and azaphilones. Reported targets of these natural compounds include inhibition of acetylcholinesterase, amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc. We tenaciously aimed to review the in-depth potential of natural products and their therapeutic applications against Alzheimer's disease, with a special focus on a diversity of medicinal plants and phytocompounds and their mechanism of action against Alzheimer's disease pathologies. We strongly believe that the medicinal plants and phytoconstituents alone or in combination with other compounds would be effective treatments against Alzheimer's disease with lesser side effects as compared to currently available treatments.

Evaluation of the In Vitro Antimicrobial Activities of Delphinium roylei: An Insight from Molecular Docking and MD-Simulation Studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The burden of antimicrobial resistance demands a continued search for new antimicrobial drugs. The synthetic drugs used clinically have serious side effects. Natural products or compounds derived from natural sources show diversity in structure and play an essential role in drug discovery and development. OBJECTIVE: Delphinium roylei is an important medicinal herb of Kashmir Himalaya, India. Traditionally this medicinal plant treats liver infections, skin problems, and chronic lower back pain. The current study evaluates the antimicrobial potential of various extracts by in -vitro and in -silico studies. METHODS: Three extracts and 168 bioactive compounds analysed through LC-MS data, with the vast majority of them having therapeutic applications. D. roylei have been screened for the antimicrobial activity against bacteria (Escherichai coli, Streptococcus pneumonia, Haemophilus influenzae, Neisseria mucosa) and fungi (Candida albicans, Candida glabrata, Candida paropsilosis) species through molecular docking using autodock Vina, MD simulation and a broth microdilution method for minimum inhibitory concentration (MIC) evaluation. RESULTS: The extracts and the compounds analyzed through the LC-MS technique of Delphinium roylie showed significant antimicrobial activity. CONCLUSION: Our study established that the leaf extracts of Delphinium roylei exhibit antimicrobial activity and thus confirm its importance in traditional medicine.

Metabolite fingerprinting of phytoconstituents from Fritillaria cirrhosa D. Don and molecular docking analysis of bioactive peonidin with microbial drug target proteins.

Fritillaria cirrhosa D. Don (Liliaceae), a valuable and critically endangered medicinal herb of northwest India, including Jammu and Kashmir, grows in temperate to alpine regions of the Himalaya. It is known as the traditional herb for cardiovascular diseases, respiratory diseases, and metabolic disorders. The plant bulbs are precious and are used to cure many other health complications. The current study analysed the phytoconstituents by liquid chromatography-mass spectrometry (LC-MS) of different crude extracts (methanolic, petroleum ether, and ethyl acetate) of F. cirrhosa. The LC-MS analysis from the bulbs of F. cirrhosa yielded 88 bioactive compounds, with the vast majority having therapeutic applications. Further, determination of minimum inhibitory concentrations (MICs) by broth microdilution method of F. cirrhosa against tested bacterial and fungal pathogens showed remarkable results with MICs ranging between 6.25-200 µg/mL and 50-400 µg/mL, respectively. Subsequently, these 88 identified phytocompounds were tested for their bioactivity through ADMET prediction by SwissADME and in silico molecular docking studies. Results revealed that Peonidin might have maximum antibacterial and antifungal activity against various microbial protein drug targets among the phytochemical compounds identified. Furthermore, the highest binding affinity complex was subjected to molecular dynamic simulation (MDS) analysis using Desmond Schrodinger v3.8. The root-mean-square deviation (RMSD) graphs obtained through the molecular dynamic simulations indicated the true bonding interactions, further validated using the root-mean-square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. To our best knowledge, this is the first description of the phytochemical constituents of the bulbs of F.cirrhosa analyzed through LC-MS, which show pharmacological significance. The in silico molecular docking and molecular dynamics study of peonidin was also performed to confirm its broad-spectrum activities based on the binding interactions with the antibacterial and antifungal target proteins. The present study results will create a way for the invention of herbal medicines for several ailments by using F. cirrhosa plants, which may lead to the development of novel drugs.

Multidimensional Role of Silicon to Activate Resilient Plant Growth and to Mitigate Abiotic Stress.

Sustainable agricultural production is critically antagonistic by fluctuating unfavorable environmental conditions. The introduction of mineral elements emerged as the most exciting and magical aspect, apart from the novel intervention of traditional and applied strategies to defend the abiotic stress conditions. The silicon (Si) has ameliorating impacts by regulating diverse functionalities on enhancing the growth and development of crop plants. Si is categorized as a non-essential element since crop plants accumulate less during normal environmental conditions. Studies on the application of Si in plants highlight the beneficial role of Si during extreme stressful conditions through modulation of several metabolites during abiotic stress conditions. Phytohormones are primary plant metabolites positively regulated by Si during abiotic stress conditions. Phytohormones play a pivotal role in crop plants' broad-spectrum biochemical and physiological aspects during normal and extreme environmental conditions. Frontline phytohormones include auxin, cytokinin, ethylene, gibberellin, salicylic acid, abscisic acid, brassinosteroids, and jasmonic acid. These phytohormones are internally correlated with Si in regulating abiotic stress tolerance mechanisms. This review explores insights into the role of Si in enhancing the phytohormone metabolism and its role in maintaining the physiological and biochemical well-being of crop plants during diverse abiotic stresses. Moreover, in-depth information about Si's pivotal role in inducing abiotic stress tolerance in crop plants through metabolic and molecular modulations is elaborated. Furthermore, the potential of various high throughput technologies has also been discussed in improving Si-induced multiple stress tolerance. In addition, a special emphasis is engrossed in the role of Si in achieving sustainable agricultural growth and global food security.

In vitro and in silico evaluation of antimicrobial properties of Delphinium cashmerianum L., a medicinal herb growing in Kashmir, India.

ETHNOPHARMACOLOGICAL RELEVANCE: Microorganisms are developing resistance to synthetic drugs. As a result, the search for novel antimicrobial compounds has become an urgent need. Medicinal plants are commonly used as traditional medicine and Delphinium is one of the prominent genus used in the treatment of several diseases. AIM OF THE STUDY: The present study aimed to determine the in vitro and in silico antimicrobial activities of petroleum ether, ethyl acetate and methanol extracts from the leaf samples of plant (Delphinium cashmerianum L.) against various bacterial and fungal strains. MATERIAL AND METHODS: Three extracts of Delphinium cashmerianum prepared and 88 bioactive compounds were analyzed through LC-MS data with the vast majority of them having therapeutic applications. These extracts have been screened for the antimicrobial activity against various bacterial (Escherichia coli, Micrococcus luteus, Klebsiella pneumoniae, Streptococcus pneumonia, Haemophilus influenzae, Neisseria mucosa) and fungal (Candida albicans, Candida glabrata, Candida paropsilosis) species through in silico molecular docking approach using autodock vina software, molecular dynamic simulation (MDS), in vitro disc diffusion and broth microdilution method for minimum inhibitory concentration (MIC) evaluation. RESULTS: Our results demonstrated that all three extracts were active against the whole set of microorganisms. The ethyl acetate extract was the most active against S.pneumonia, K. pneumoniae and C. albicans with a minimum inhibitory concentration (MIC) value of 6.25, 25 and 50 µg/ml, respectively. The petroleum ether and methanol extracts were active against S.pneumonia and N.mucosa with MIC values of 25 and 50 µg/ml. Furthermore, we also performed the in silico virtual screening of all these compounds obtained from LC-MS data analysis against various known drug targets of bacterium and fungi. Upon analysis, we obtained 5 compounds that were efficiently binding to the drug targets. However, after performing exhaustive molecular docking and molecular dynamic simulation (MDS) analysis, it was observed that Daidzein compound is bound to drug targets more efficiently. CONCLUSION: The results showed that these plant extracts exhibit antimicrobial activity and ethyl acetate extract proved to exhibit the most effective antibacterial and antifungal properties.

Microbiome dysbiosis and epigenetic modulations in lung cancer: From pathogenesis to therapy.

The lung microbiome plays an essential role in maintaining healthy lung function, including host immune homeostasis. Lung microbial dysbiosis or disruption of the gut-lung axis can contribute to lung carcinogenesis by causing DNA damage, inducing genomic instability, or altering the host's susceptibility to carcinogenic insults. Thus far, most studies have reported the association of microbial composition in lung cancer. Mechanistic studies describing host-microbe interactions in promoting lung carcinogenesis are limited. Considering cancer as a multifaceted disease where epigenetic dysregulation plays a critical role, epigenetic modifying potentials of microbial metabolites and toxins and their roles in lung tumorigenesis are not well studied. The current review explains microbial dysbiosis and epigenetic aberrations in lung cancer and potential therapeutic opportunities.