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.

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.

Identification of key transcription factors and their functional role involved in Salmonella typhimurium infection in chicken using integrated transcriptome analysis and bioinformatics approach.

Salmonella enterica serovar typhimurium is the cause of significant morbidity and mortality worldwide that causes economic losses to poultry and is able to cause infection in humans. Indigenous chicken breeds are a potential source of animal protein and have the added advantage of being disease resistant. An indigenous chicken, Kashmir favorella and commercial broiler were selected for understanding the mechanism of disease resistance. Following infection in Kashmir favorella, three differentially expressed genes Nuclear Factor Kappa B (NF-κB1), Forkhead Box Protein O3 (FOXO3) and Paired box 5 (Pax5) were identified. FOXO3, a transcriptional activator, is the potential marker of host resistance in Salmonella infection. NF-κB1 is an inducible transcription factor which lays the foundation for studying gene network of the innate immune response of Salmonella infection in chicken. Pax5 is essential for differentiation of pre-B cells into mature B cell. The real time PCR analysis showed that in response to Salmonella Typhimurium infection a remarkable increase of NF-κB1 (P˂0.01), FOXO3 (P˂0.01) gene expression in liver and Pax5 (P˂0.01) gene expression in spleen of Kashmir favorella was observed. The protein-protein interaction (PPI) and protein-TF interaction network by STRINGDB analysis suggests that FOXO3 is a hub gene in the network and is closely related to Salmonella infection along with NF-κB1. All the three differentially expressed genes (NF-κB1, FOXO3 and PaX5) showed their influence on 12 interacting proteins and 16 TFs, where cyclic adenosine monophosphate Response Element Binding protein (CREBBP), erythroblast transformation-specific (ETSI), Tumour-protein 53(TP53I), IKKBK, lymphoid enhancer-binding factor-1 (LEF1), and interferon regulatory factor-4 (IRF4) play role in immune responses. This study shall pave the way for newer strategies for treatment and prevention of Salmonella infection and may help in increasing the innate disease resistance.

Metabolic-GWAS provides insights into genetic architecture of seed metabolome in buckwheat.

BACKGROUND: Buckwheat (Fagopyrum spp.), belonging to the Polygonaceae family, is an ancient pseudo-cereal with high nutritional and nutraceutical properties. Buckwheat proteins are gluten-free and show balanced amino acid and micronutrient profiles, with higher content of health-promoting bioactive flavonoids that make it a golden crop of the future. Plant metabolome is increasingly gaining importance as a crucial component to understand the connection between plant physiology and environment and as a potential link between the genome and phenome. However, the genetic architecture governing the metabolome and thus, the phenome is not well understood. Here, we aim to obtain a deeper insight into the genetic architecture of seed metabolome in buckwheat by integrating high throughput metabolomics and genotyping-by-sequencing applying an array of bioinformatics tools for data analysis. RESULTS: High throughput metabolomic analysis identified 24 metabolites in seed endosperm of 130 diverse buckwheat genotypes. The genotyping-by-sequencing (GBS) of these genotypes revealed 3,728,028 SNPs. The Genome Association and Prediction Integrated Tool (GAPIT) assisted in the identification of 27 SNPs/QTLs linked to 18 metabolites. Candidate genes were identified near 100 Kb of QTLs, providing insights into several metabolic and biosynthetic pathways. CONCLUSIONS: We established the metabolome inventory of 130 germplasm lines of buckwheat, identified QTLs through marker trait association and positions of potential candidate genes. This will pave the way for future dissection of complex economic traits in buckwheat.

Scavenger receptor B1 facilitates the endocytosis of Escherichia coli via TLR4 signaling in mammary gland infection.

SCARB1 belongs to class B of Scavenger receptors (SRs) that are known to be involved in binding and endocytosis of various pathogens. SRs have emerging role in regulating innate immunity and host-pathogen interactions by acting in co-ordination with Toll-like receptors.Query Little is known about the function of SCARB1 in milk-derived mammary epithelial cells (MECs). This study reports the role of SCARB1 in infection and its potential association in TLR4 signaling on bacterial challenge in Goat mammary epithelial cells (GMECs). The novelty in the establishment of MEC culture lies in the method that aims to enhance the viability of the cells with intact characteristics upto a higher passage number. We represent MEC culture to be used as a potential infection model for deeper understanding of animal physiology especially around the mammary gland. On E.coli challenge the expression of SCARB1 was significant in induced GMECs at 6 h. Endoribonuclease-esiRNA based silencing of SCARB1 affects the expression of TLR4 and its pathways i.e. MyD88 and TRIF pathways on infection. Knockdown also affected the endocytosis of E.coli in GMECs demonstrating that E.coli uses SCARB1 function to gain entry in cells. Furthermore, we predict 3 unique protein structures of uncharacterized SCARB1 (Capra hircus) protein. Overall, we highlight SCARB1 as a main participant in host defence and its function in antibacterial advances to check mammary gland infections. Video Abstract.

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.

Comparative RNA-Seq analysis reveals insights in Salmonella disease resistance of chicken; and database development as resource for gene expression in poultry.

Salmonella, one of the major infectious diseases in poultry, causes considerable economic losses in terms of mortality and morbidity, especially in countries that lack effective vaccination programs. Besides being resistant to diseases, indigenous chicken breeds are also a potential source of animal protein in developing countries. For understanding the disease resistance, an indigenous chicken line Kashmir faverolla, and commercial broiler were selected. RNA-seq was performed after challenging the chicken with Salmonella Typhimurium. Comparative differential expression results showed that following infection, a total of 3153 genes and 1787 genes were differentially expressed in the liver and spleen, respectively. The genes that were differentially expressed included interleukins, cytokines, NOS2, Avß-defensins, toll-like receptors, and other immune-related gene families. Most of the genes and signaling pathways involved in the innate and adaptive immune responses against bacterial infection were significantly enriched in the Kashmir faverolla. Pathway analysis revealed that most of the enriched pathways were MAPK signaling pathway, NOD-like receptor signaling pathway, TLR signaling pathway, PPAR signaling pathway, endocytosis, etc. Surprisingly some immune-related genes like TLRs were upregulated in the susceptible chicken breed. On postmortem examination, the resistant birds showed small lesions in the liver compared to large necrotic lesions in susceptible birds. The pathological manifestations and RNA sequencing results suggest a balancing link between resistance and infection tolerance in Kashmir faverolla. Here we also developed an online Poultry Infection Database (https://skuastk.org/pif/index.html), the first publicly available gene expression resource for disease resistance in chickens. The available database not only shows the data for gene expression in chicken tissues but also provides quick search, visualization and download capacity.

Mammary epithelial cell transcriptome reveals potential roles of lncRNAs in regulating milk synthesis pathways in Jersey and Kashmiri cattle.

BACKGROUND: Long noncoding RNAs (lncRNAs) are now proven as essential regulatory elements, playing diverse roles in many biological processes including mammary gland development. However, little is known about their roles in the bovine lactation process. RESULTS: To identify and characterize the roles of lncRNAs in bovine lactation, high throughput RNA sequencing data from Jersey (high milk yield producer), and Kashmiri cattle (low milk yield producer) were utilized. Transcriptome data from three Kashmiri and three Jersey cattle throughout their lactation stages were utilized for differential expression analysis. At each stage (early, mid and late) three samples were taken from each breed. A total of 45 differentially expressed lncRNAs were identified between the three stages of lactation. The differentially expressed lncRNAs were found co-expressed with genes involved in the milk synthesis processes such as GPAM, LPL, and ABCG2 indicating their potential regulatory effects on milk quality genes. KEGG pathways analysis of potential cis and trans target genes of differentially expressed lncRNAs indicated that 27 and 48 pathways were significantly enriched between the three stages of lactation in Kashmiri and Jersey respectively, including mTOR signaling, PI3K-Akt signaling, and RAP1 signaling pathways. These pathways are known to play key roles in lactation biology and mammary gland development. CONCLUSIONS: Expression profiles of lncRNAs across different lactation stages in Jersey and Kashmiri cattle provide a valuable resource for the study of the regulatory mechanisms involved in the lactation process as well as facilitate understanding of the role of lncRNAs in bovine lactation biology.

Comparative transcriptomics unravels new genes imparting scab resistance in apple (Malus x domestica Borkh.).

Apple scab is caused by an ascomycete fungus, Venturia inaequalis (Cke.) Wint., which is one of the most severe disease of apple (Malus × Domestica Borkh.) worldwide. The disease results in 30-40% fruit loss annually and even complete loss in some places. Owing to the evolving susceptibility of resistant apple genotypes harboring R-genes to new variants of V. inaequalis, a comparative transcriptome analysis using Illumina (HiSeq) platform of three scab-resistant (Florina, Prima, and White Dotted Red) and three susceptible (Ambri, Vista Bella, and Red Delicious) apple genotypes was carried out to mine new scab resistance genes. The study led to the identification of 822 differentially expressed genes in the tested scab-resistant and scab-susceptible apple genotypes. The most upregulated genes uniformly expressed in resistant varieties compared to susceptible ones were those coding for 17.3 kDa class II heat shock protein-like, chaperone protein ClpB1, glutathione S-transferase L3-like protein, B3 domain-containing protein At3g18960-like, transcription factor bHLH7, zinc finger MYM-type protein 1-like, and nine uncharacterized proteins, besides three lncRNAs. The genes that were downregulated in susceptible and upregulated in resistant cultivars were those coding for non-specific lipid transfer protein GPI-anchored 1, rust resistance kinase Lr10-like, disease resistance protein RPS6-like, and many uncharacterized proteins. DESeq2 analysis too revealed 20 DEGs that were upregulated in scab-resistant cultivars. Furthermore, a total of 361 genes were significantly upregulated in scab-susceptible variety, while 461 were found downregulated (P value < 0.05 and Log2 (FC) > 1). The differentially expressed genes (DEGs) were related to various pathways, i.e., metabolic, protein processing, biosynthesis of secondary metabolites, plant hormone signal transduction, autophagy, ubiquitin-mediated proteolysis, plant-pathogen interaction, lipid metabolism, and protein modification pathways. Real-time expression of a set of selected twelve DEGs further validated the results obtained from RNA-seq. Overall, these findings lay the foundation for investigating the genetic basis of apple scab resistance and defense pathways that might have a plausible role in governing scab resistance in apple against V. inaequalis.

Expression of lncRNAs in response to bacterial infections of goat mammary epithelial cells reveals insights into mammary gland diseases.

Mastitis or inflammation of the mammary gland is a highly economic and deadly alarming disease for the dairy sector as well as policymakers caused by microbial infection. Transcriptomic and proteomic approaches have been widely employed to identify the underlying molecular mechanisms of bacterial infections in the mammary gland. Numerous differentially expressed mRNAs, miRNAs, and proteins together with their associated signaling pathways have been identified during bacterial infection, paving the way for analysis of their biological functions. Long noncoding RNAs (lncRNAs) are important regulators of multiple biological processes. However, little is known regarding their role in bacterial infection in mammary epithelial cells. Hence, RNA-sequencing was performed by infecting primary mammary epithelial cells (pMECs) with both gram-negative (E. coli) and gram-positive bacteria (S. aureus). Using stringent pipeline, a set of 1957 known and 1175 novel lncRNAs were identified, among which, 112 lncRNAs were found differentially expressed in bacteria challenged PMECs compared with the control. Additionally, potential targets of the lncRNAs were predicted in cis- and trans-configuration. KEGG analysis revealed that DE lncRNAs were associated with at least 15 immune-related pathways. Therefore, our study revealed that bacterial challenge triggers the expression of lncRNAs associated with immune response and defense mechanisms in goat mammary epithelial cells.

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.

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.

Insights into decontamination of soils by phytoremediation: A detailed account on heavy metal toxicity and mitigation strategies.

In the current era of rapid industrialization, the foremost challenge is the management of industrial wastes. Activities such as mining and industrialization spill over a large quantity of toxic waste that pollutes soil, water, and air. This poses a major environmental and health challenge. The toxic heavy metals present in the soil and water are entering the food chain, which in turn causes severe health hazards. Environmental clean-up and reclamation of heavy metal contaminated soil and water are very important, and it necessitates efforts of environmentalists, industrialists, scientists, and policymakers. Phytoremediation is a plant-based approach to remediate heavy metal/organic pollutant contaminated soil and water in an eco-friendly, cost-effective, and permanent way. This review covers the effect of heavy metal toxicity on plant growth and physiological process, the concept of heavy metal accumulation, detoxification, and the mechanisms of tolerance in plants. Based on plants' ability to uptake heavy metals and metabolize them within tissues, phytoremediation techniques have been classified into six types: phytoextraction, phytoimmobilization, phytovolatilization, phytodegradation, rhizofiltration, and rhizodegradation. The development of research in this area led to the identification of metal hyper-accumulators, which could be utilized for reclamation of contaminated soil through phytomining. Concurrently, breeding and biotechnological approaches can enhance the remediation efficiency. Phytoremediation technology, combined with other reclamation technologies/practices, can provide clean soil and water to the ecosystem.

Abiotic stress induced miRNA-TF-gene regulatory network: A structural perspective.

MicroRNAs (miRNAs) and transcription factors (TFs) are the largest families of trans-acting gene regulatory species, which are pivotal players in a complex regulatory network. Recently, extensive research on miRNAs and TFs in agriculture has identified these trans-acting regulatory species, as an effective tool for engineering new crop cultivars to increase yield and quality as well tolerance to environmental stresses but our knowledge of regulatory network is still not sufficient to decipher the exact mechanism. In the current work, stress-specific TF-miRNA-gene network was built for Arabidopsis under drought, cold, salt and waterlogging stress using data from reliable publically available databases; and transcriptome and degradome sequence data analysis by meta-analysis approach. Further network analysis elucidated significantly dense, scale-free, small world and hierarchical backbone of interactions. The various centrality measures highlighted several genes/TF/miRNAs as potential targets for tolerant variety cultivation. This comprehensive regulatory information will accelerate the advancement of current understanding on stress specific transcriptional and post-transcriptional regulatory mechanism and has promising utilizations for experimental biologist who are intended to improve plant crop performance under multiple Abiotic stress environments.

A validated restriction enzyme ddPCR cg05575921 (AHRR) assay to accurately assess smoking exposure.

BACKGROUND & METHODS: In this study, a novel restriction enzyme (RE) digestion-based droplet digital polymerase chain reaction (ddPCR) assay was designed for cg005575921 within the AHRR gene body and compared with matching results obtained by bisulfite conversion (BIS) ddPCR and Illumina DNA methylation array. RESULTS: The RE ddPCR cg05575921 assay appeared concordant with BIS ddPCR (r2 = 0.94, P < 0.0001) and, when compared with the Illumina array, had significantly better smoking status classification performance for current versus never smoked (AUC 0.96 versus 0.93, P < 0.04) and current versus ex-smoker (AUC 0.88 versus 0.83, P < 0.04) comparisons. CONCLUSIONS: The RE ddPCR cg05575921 assay accurately predicts smoking status and could be a useful component of 'precision-medicine' chronic disease risk screening tools.

Synthesis, biological profile and computational insights of new derivatives of benzo [B][1,4] diazepines as prospective anticancer agents for inhibiting the CDK-2 protein.

In the current work, a new series of benzo[b][1, 4] diazepines (A-1 to C-4) was synthesized and screened against three different human cancer cell lines, HepG2 (hepatocellular carcinoma), HeLa (cervical cancer) and MCF-7 (breast cancer), by employing MTT (MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. The outcomes of in vitro screening revealed that all the compounds exhibited momentous anticancer activity, most notably against the MCF-7 cell line by B1-4 compounds. Further, network pharmacology, UALCAN analysis, molecular docking, molecular dynamics (MD) simulations and density functional theory calculations were conducted to explore expression analysis, pharmacokinetics, toxicity profiles and binding interactions of the B1-4 compounds. By UALCAN, we explored the expression analysis of CDK-2 in 19 cancers. Through UALCAN, Pan-cancer analysis revealed that the expression of CDK-2 in 19 cancers was statistically significant. Among the 19 cancers, the CDK-2 expression was significantly upregulated in breast cancer (BRCA), cervical cancer (CESC) and lung carcinoma (LUSC) than normal tissues. Enzyme-docking examination revealed that B1-4 compounds exhibited significant binding affinity against the CDK-2 (PDB ID: 5IEV) drug target protein. Furthermore, MD simulations supported the docking results, which confirmed that the ligand + protein complex was in a stable conformation throughout the simulation time of 100 nanoseconds. Therefore, the present study demonstrates the potential of these benzo [b][1,4] diazepines as promising drug candidates against cancer.Communicated by Ramaswamy H. Sarma.

A new series of benzodiazepine molecules were designed and synthesized as CDK-2 inhibitors.In vitro anticancer potential against HepG2, HeLa and MCF-7 cancer cells were assessed.Network pharmacology; expression analysis; in silico docking; molecular dynamics simulation; molecular mechanics­generalized Born and surface area; and absorption, distribution, metabolism, excretion and toxicity studies were carried out.This study overall revealed the anticancer activity of benzodiazepines by integrating network pharmacology, molecular modeling and in vitro experiments.

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.

Comparative transcriptome analysis of E. coli & Staphylococcus aureus infected goat mammary epithelial cells reveals genes associated with infection.

Mastitis, an inflammatory disease of the mammary gland, imposes a significant financial burden on the dairy sector. However, the specific molecular mechanisms underlying their interactions with goat mammary epithelial cells (GMECs) remain poorly understood. This study aimed to investigate the transcriptomic response of GMECs during infection with E. coli and S. aureus, providing insights into the host-pathogen interactions. Differential expression of gene (DEGs) analysis was done to find genes and pathways dysregulated in the wake of infection. E. coli infection triggered a robust upregulation of immune response genes, including pro-inflammatory chemokines and cytokines as well as genes involved in tissue repair and remodeling. Conversely, S. aureus infection showed a more complex pattern, involving the activation of immune-related gene as well as those involved in autophagy, apoptosis and tissue remodeling. Furthermore, several key pathways, such as Toll-like receptor signaling and cytokine-cytokine receptor interaction, were differentially modulated in response to each pathogen. Understanding the specific responses of GMECs to these pathogens will provide a foundation for understanding the complex dynamics of infection and host response, offering potential avenues for the development of novel strategies to prevent and treat bacterial infections in both animals and humans.