Synthesis and Characterization of Silver Nanoparticles Using Cannonball Leaves and Their Cytotoxic Activity against MCF-7 Cell Line

Cannonball (Couroupita guianensis) is a tree belonging to the family Lecythidaceae. Various parts of the tree have been reported to contain oils, keto steroids, glycosides, couroupitine, indirubin, isatin, and phenolic substances. We report here the synthesis of silver nanoparticles (AgNPs) using cannonball leaves. Green synthesized nanoparticles have been characterized by UV-Vis spectroscopy, SEM, TEM, and FTIR. Cannonball leaf broth as a reducing agent converts silver ions to AgNPs in a rapid and ecofriendly manner. The UV-Vis spectra gave surface plasmon resonance peak at 434 nm. TEM image shows well-dispersed silver nanoparticles with an average particle size of 28.4 nm. FTIR showed the structure and respective bands of the synthesized nanoparticles and the stretch of bonds. Green synthesized silver nanoparticles by cannonball leaf extract show cytotoxicity to human breast cancer cell line (MCF-7). Overall, this environmentally friendly method of biological silver nanoparticles production provides rates of synthesis faster than or comparable to those of chemical methods and can potentially be used in various human contacting areas such as cosmetics, foods, and medical applications

Culturable diversity of bacterial endophytes associated with medicinal plants of the Western Ghats, India

Bacterial endophytes are found in the internal tissues of plants and have intimate associations with their host. However, little is known about the diversity of medicinal plant endophytes (ME) or their capability to produce specialised metabolites that may contribute to therapeutic properties. We isolated 75 bacterial ME from 24 plant species of the Western Ghats, India. Molecular identification by 16S rRNA gene sequencing grouped MEs into 13 bacterial genera, with members of Gammaproteobacteria and Firmicutes being the most abundant. To improve taxonomic identification, 26 selected MEs were genome sequenced and average nucleotide identity (ANI) used to identify them to the species-level. This identified multiple species in the most common genus as Bacillus. Similarly, identity of the Enterobacterales was also distinguished within Enterobacter and Serratia by ANI and core-gene analysis. AntiSMASH identified non-ribosomal peptide synthase, lantipeptide and bacteriocin biosynthetic gene clusters (BGC) as the most common BGCs found in the ME genomes. A total of five of the ME isolates belonging to Bacillus, Serratia and Enterobacter showed antimicrobial activity against the plant pathogen Pectobacterium carotovorum. Using molecular and genomic approaches we have characterised a unique collection of endophytic bacteria from medicinal plants. Their genomes encode multiple specialised metabolite gene clusters and the collection can now be screened for novel bioactive and medicinal metabolites

Long non-coding RNA SNHG8 drives stress granule formation in tauopathies

Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts \u3e200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer\u27s disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels in immortalized cells and in MAPT mutant neurons, suggesting that dysregulation of this non-coding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD

SYNTHESIS AND CHARACTERIZATION OF SILVER NANOPARTICLES USING TABERNAEMONTANA DIVARICATA AND ITS CYTOTOXIC ACTIVITY AGAINST MCF-7 CELL LINE

Objective: Tabernaemontana divaricata a common garden plant on tropical countries has been used as a traditional medicine. There is an increasing commercial demand for nanoparticles due to their wide applicability in various areas such as electronics, catalysis, chemistry, energy, and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. In this work, we describe a cost effective and environment friendly technique for green synthesis of silver nanoparticles (AgNPs) from T. divaricata leaf extract. Methods: Biosynthesized AgNPs were characterized using UV– Vis absorption spectroscopy, TEM, FTIR and SEM analysis. Cytotoxicity of AgNPs was tested in human breast cancer cell line (MCF-7). Results: TEM analysis showed the average particle size of 22.85 nm as revealed in their structure. The qualitative assessment of reducing potential of leaf extract has also been carried out which indicated presence of significant amount of reducing entities. Green synthesized AgNPs by T. divaricata leaf extract show cytotoxicity to human breast cancer cell line (MCF-7). Conclusion: The most important outcome of this work will be the development of value-added products from T. divaricata. The characteristics of the obtained AgNPs were analysed which could be used potentially in various human contacting areas such as cosmetics, foods, and medical applications

Synthesis of some Potential High Energy Materials using Metal Nitrates; An approach towards Environmental Benign Process

485-488A novel and efficient method for the synthesis of various promising high energy materials (HEMs) like nitrotriazolone (NTO), 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20), bis (2,2-dinitropropyl) nitramine (BDNPN), 1,1-diamino-2,2-dinitro ethylene (FOX-7) etc. using metal nitrates/sulphuric acid as nitrating agent has been described successfully. The synthesized materials have been characterized using various spectroscopic techniques as well as thermal studies and the data obtained confirmed their structure.  From the study it was revealed that this method certainly an alternative method of preparation of high energy materials (HEMs) in place of the conventional nitration mixture

GAS5 long non-coding RNA in malignant pleural mesothelioma

BACKGROUND Malignant pleural mesothelioma (MPM) is an aggressive cancer with short overall survival. Long non-coding RNAs (lncRNA) are a class of RNAs more than 200 nucleotides long that do not code for protein and are part of the 90% of the human genome that is transcribed. Earlier experimental studies in mice showed GAS5 (growth arrest specific transcript 5) gene deletion in asbestos driven mesothelioma. GAS5 encodes for a lncRNA whose function is not well known, but it has been shown to act as glucocorticoid receptor decoy and microRNA "sponge". Our aim was to investigate the possible role of the GAS5 in the growth of MPM. METHODS Primary MPM cultures grown in serum-free condition in 3% oxygen or MPM cell lines grown in serum-containing medium were used to investigate the modulation of GAS5 by growth arrest after inhibition of Hedgehog or PI3K/mTOR signalling. Cell cycle length was determined by EdU incorporation assay in doxycycline inducible short hairpinGAS5 clones generated from ZL55SPT cells. Gene expression was quantified by quantitative PCR. To investigate the GAS5 promoter, a 0.77 kb sequence was inserted into a pGL3 reporter vector and luciferase activity was determined after transfection into MPM cells. Localization of GAS5 lncRNA was identified by in situ hybridization. To characterize cells expressing GAS5, expression of podoplanin and Ki-67 was assessed by immunohistochemistry. RESULTS GAS5 expression was lower in MPM cell lines compared to normal mesothelial cells. GAS5 was upregulated upon growth arrest induced by inhibition of Hedgehog and PI3K/mTOR signalling in in vitro MPM models. The increase in GAS5 lncRNA was accompanied by increased promoter activity. Silencing of GAS5 increased the expression of glucocorticoid responsive genes glucocorticoid inducible leucine-zipper and serum/glucocorticoid-regulated kinase-1 and shortened the length of the cell cycle. Drug induced growth arrest was associated with GAS5 accumulation in the nuclei. GAS5 was abundant in tumoral quiescent cells and it was correlated to podoplanin expression. CONCLUSIONS The observations that GAS5 levels modify cell proliferation in vitro, and that GAS5 expression in MPM tissue is associated with cell quiescence and podoplanin expression support a role of GAS5 in MPM biology

Extraction of itaconic acid by endophytic Aspergillus sp., isolated from Garcinia indica: Spectroscopic, structural and quantum computational studies

Endophytic fungi are generally absorbed into the metabolic networks of their hosts, causing changes in metabolite synthesis and higher levels of active compounds in medicinal plants. The primary objective of this research is to study the secondary metabolite profile of Aspergillus sp., BGSm03, a fungal endophyte isolated from a shrub called Garcinia indica grown in the Bisle Ghat region of Karnataka, India. Organic acids were effectively produced during fermentation with the isolate Aspergillus sp., BGSm03. Itaconic Acid (IA) was extracted and purified from them using chromatography. For the chemical structure and characterization of substances, spectroscopic analyses such as ultraviolet (UV), infrared (IR), and mass spectrometry (MS) are carried out. Following that, the single-crystal X-ray diffraction (SC-XRD) technique is used to determine the 3D molecular structure and to identify the various intra and intermolecular interactions responsible for the stability of the crystal structure of IA. The energy and other quantum chemical characteristics of IA were calculated using density functional theory (DFT). Furthermore, the purified IA is evaluated for antimicrobial and anticancer activity.(c) 2022 Elsevier B.V. All rights reserved

Design, synthesis of pyridine coupled pyrimidinone/pyrimidinthione as anti-MRSA agent: Validation by molecular docking and dynamics simulation

Methicillin Resistant Staphylococcus aureus (MRSA) is a major cause of severe hospital and infections acquired by the population and related morbidity and mortality. In this unique situation, there is a need of dynamic strong drug candidates to control MRSA diseases. Thus, the present work focuses on the synthesis and characterization of pyrimidinones and pyrimidinthiones coupled pyridine derivatives as anti-MRSA agent. The synthesized compounds were characterized by different spectroscopic techniques and evaluated against MRSA strain. Among them, 4e and 4g possessed better antibacterial activity with MIC values of 10 mu g and 8 mu g respectively. The key determinant of the wide range beta-lactam resistance in MRSA strains is the Penicillin-Binding Protein 2a (PBP2a) but the gene encodes PBP2a which has a low affinity towards beta-lactam antibiotics. Because of this, the present investigation focused on the mechanism of PBP2a protein binding studies by in-silico studies. The synthesized compounds showed very good interactions with PBP2A compared with standard drug Vancomycin, among them compound 4g showed better interaction with the binding score of 9.8 kcal/mol. Antibacterial activity was validated with molecular docking and molecular dynamic simulation. Simulation results revealed that protein-ligand interactions of 4g compound stably sustained up to 20,000ps