Bioassay-guided screening of antibacterial compounds from the cultured marine Streptomyces sp. ICN19 provided Ala-geninthiocin (1), along with its known analogs geninthiocin (2) and Val-geninthiocin (3) and the indolocarbazole staurosporine (4). The structure of 1 was determined on the basis of 1D and 2D NMR spectra and ESI-HRMS. The absolute configurations of the amino acid residues were determined by enantioselective GC-MS analysis. Compound 1 exhibited potent activity against Gram-positive bacteria including Staphylococcus aureus, Bacillus subtilis, Mycobacterium smegmatis, and Micrococcus luteus, as well as cytotoxicity against A549 human lung carcinoma cells with an IC₅₀ value of 6 nM.

Acute Myeloid Leukemia (AML) is a heterogeneous disease with highest mortality compared to other types of leukemia. There is a need to find the gene abnormalities and mechanisms behind them due to their heterogenic nature. The present study is aimed to understand genes, pathways and biomarker proteins influenced by transcriptomic deregulation due to AML. Differentially expressed gene (DEG), protein-protein interaction network, gene ontology, KEGG pathway, variant analysis and secretome analyses were performed using different AML RNAseq datasets. A total of 655 DEGs including 291 up-regulated and 364 down-regulated genes, which were satisfied with a fold change of 1.5 were identified. Top hub genes for AML were identified as TP53, PTPRC and AKT1. This integrative bioinformatics approach revealed the deregulation of T Cell Receptor (TCR) pathway and altered immune response related genes. The survival analysis revealed the associated deregulation of multiple TCR pathway related genes. Variant analysis identified the benign and likely benign nature of many important target genes and markers screened, which were found to have an important role in the progression of AML. DEGs and secretome analysis found out a set of seven molecules represents potential biomarkers for AML. In vitro analytical validation showed overexpression pattern of CD109 and LRP12 in AML cell line and HL-60 cells than the normal human bone marrow-derived stromal cell line HS-5. Here we report first time for CD109 and LRP12 as a possible biomarkers for the diagnostic significance. Amino acid substitutions detected by variant analysis and deregulation of immune checkpoint molecules revealed their role in reducing immune response and inability to fight cancer cells. In conclusion, this study highlights the possibility of new biomarkers for AML and the mechanism of decrease in immune response due to the downregulation of co-stimulatory immune molecules, which needs further clinical validation investigations.

The aim of the present study was to isolate the anti-MRSA (Methicillin Resistant Staphylococcus aureus) molecule from the Mangrove symbiont Streptomyces and its biomedical studies in Zebrafish embryos. MRSA was isolated from the pus samples of Colachal hospitals and confirmed by amplification of mecA gene. Anti-MRSA molecule producing strain was identified by 16s rRNA gene sequencing. Anti-MRSA compound production was optimized by Solid State Fermentation (SSF) and the purification of the active molecule was carried out by TLC and RP-HPLC. The inhibitory concentration and LC50 were calculated using Statistical software SPSS. The Biomedical studies including the cardiac assay and organ toxicity assessment were carried out in Zebrafish. The bioactive anti-MRSA small molecule A2 was purified by TLC with Rf value of 0.37 with 1.389 retention time at RP-HPLC. The Inhibitory Concentration of the purified molecule A2 was 30 µg/mL but, the inhibitory concentration of the MRSA in the infected embryo was 32-34 µg/mL for TLC purified molecule A2 with LC50 mean value was 61.504 µg/mL. Zebrafish toxicity was assessed in 48-60 µg/mL by observing the physiological deformities and the heart beat rates (HBR) of embryos for anti MRSA molecule showed the mean of 41.33-41.67 HBR/15 seconds for 40 µg/mL and control was 42.33-42.67 for 15 seconds which significantly showed that the anti-MRSA molecule A2 did not affected the HBR. Anti-MRSA molecule from Streptomyces sp PVRK-1 was isolated and biomedical studies in Zebrafish model assessed that the molecule was non toxic at the minimal inhibitory concentration of MRSA.