Search Results (8)

Cardiac glycosides (CGs) constitute a group of steroid-like compounds renowned for their effectiveness in treating cardiovascular ailments. In recent times, there has been growing recognition of their potential use as drug leads in cancer treatment. In our prior research, we identified three highly promising CG compounds, namely lanatoside C (LC), peruvoside (PS), and strophanthidin (STR), which exhibited significant antitumor effects in lung, liver, and breast cancer cell lines. In this study, we investigated the therapeutic response of these CGs, with a particular focus on the MCF-7 breast cancer cell line. We conducted transcriptomic profiling and further validated the gene and protein expression changes induced by treatment through qRT-PCR, immunoblotting, and immunocytochemical analysis. Additionally, we demonstrated the interactions between the ligands and target proteins using the molecular docking approach. The transcriptome analysis revealed a cluster of genes with potential therapeutic targets involved in cytotoxicity, immunomodulation, and tumor-suppressor pathways. Subsequently, we focused on cross-validating the ten most significantly expressed genes, EGR1, MAPK1, p53, CCNK, CASP9, BCL2L1, CDK7, CDK2, CDK2AP1, and CDKN1A, through qRT-PCR, and their by confirming the consistent expression pattern with RNA-Seq data. Notably, among the most variable genes, we identified EGR1, the downstream effector of the MAPK signaling pathway, which performs the regulatory function in cell proliferation, tumor invasion, and immune regulation. Furthermore, we substantiated the influence of CG compounds on translational processes, resulting in an alteration in protein expression upon treatment. An additional analysis of ligand–protein interactions provided further evidence of the robust binding affinity between LC, PS, and STR and their respective protein targets. These findings underscore the intense anticancer activity of the investigated CGs, shedding light on potential target genes and elucidating the probable mechanism of action of CGs in breast cancer. Full article

Biofilms are population of cells growing in a coordinated manner and exhibiting resistance towards hostile environments. The infections associated with biofilms are difficult to control owing to the chronicity of infections and the emergence of antibiotic resistance. Most microbial infections are contributed by polymicrobial or mixed species interactions, such as those observed in chronic wound infections, otitis media, dental caries, and cystic fibrosis. This review focuses on the polymicrobial interactions among bacterial-bacterial, bacterial-fungal, and fungal-fungal aggregations based on in vitro and in vivo models and different therapeutic interventions available for polymicrobial biofilms. Deciphering the mechanisms of polymicrobial interactions and microbial diversity in chronic infections is very helpful in anti-microbial research. Together, we have discussed the role of metagenomic approaches in studying polymicrobial biofilms. The outstanding progress made in polymicrobial research, especially the model systems and application of metagenomics for detecting, preventing, and controlling infections, are reviewed. Full article

Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management. Full article

This study presents a comparative analysis of halophiles from the global open sea and coastal biosystems through shotgun metagenomes (n = 209) retrieved from public repositories. The open sea was significantly enriched with Prochlorococcus and Candidatus pelagibacter. Meanwhile, coastal biosystems were dominated by Marinobacter and Alcanivorax. Halophilic archaea Haloarcula and Haloquandratum, predominant in the coastal biosystem, were significantly (p < 0.05) enriched in coastal biosystems compared to the open sea. Analysis of whole genomes (n = 23,540), retrieved from EzBioCloud, detected crtI in 64.66% of genomes, while cruF was observed in 1.69% Bacteria and 40.75% Archaea. We further confirmed the viability and carotenoid pigment production by pure culture isolation (n = 1351) of extreme halophiles from sediments (n = 410 × 3) sampling at the Arabian coastline of India. All red-pigmented isolates were represented exclusively by Haloferax, resistant to saturated NaCl (6 M), and had >60% G + C content. Multidrug resistance to tetracycline, gentamicin, ampicillin, and chloramphenicol were also observed. Our study showed that coastal biosystems could be more suited for bioprospection of halophiles rather than the open sea. Full article

Cardiac glycosides (CGs) have a long history of treating cardiac diseases. However, recent reports have suggested that CGs also possess anticancer and antiviral activities. The primary mechanism of action of these anticancer agents is by suppressing the Na⁺/k⁺-ATPase by decreasing the intracellular K⁺ and increasing the Na⁺ and Ca²⁺. Additionally, CGs were known to act as inhibitors of IL8 production, DNA topoisomerase I and II, anoikis prevention and suppression of several target genes responsible for the inhibition of cancer cell proliferation. Moreover, CGs were reported to be effective against several DNA and RNA viral species such as influenza, human cytomegalovirus, herpes simplex virus, coronavirus, tick-borne encephalitis (TBE) virus and Ebola virus. CGs were reported to suppress the HIV-1 gene expression, viral protein translation and alters viral pre-mRNA splicing to inhibit the viral replication. To date, four CGs (Anvirzel, UNBS1450, PBI05204 and digoxin) were in clinical trials for their anticancer activity. This review encapsulates the current knowledge about CGs as anticancer and antiviral drugs in isolation and in combination with some other drugs to enhance their efficiency. Further studies of this class of biomolecules are necessary to determine their possible inhibitory role in cancer and viral diseases. Full article

Antibiotic resistance is a global issue which is magnified by interspecies horizontal gene transfer. Understanding antibiotic resistance in bacteria in a natural setting is crucial to check whether they are multidrug resistant (MDR) and possibly avoid outbreaks. In this study, we have isolated several antibiotic-resistant bacteria (ARB) (n = 128) from the mangroves in Kerala, India. ARBs were distributed based on antibiotics (p = 1.6 × 10⁻⁵). The 16S rRNA gene characterization revealed dominance by Bacillaceae (45%), Planococcaceae (22.5%), and Enterobacteriaceae (17.5%). A high proportion of the isolates were MDR (75%) with maximum resistance to methicillin (70%). Four isolates affiliated to plant-growth promoters, probiotics, food, and human pathogens were resistant to all antibiotics indicating the seriousness and prevalence of MDR. A significant correlation (R = 0.66; p = 2.5 × 10⁻⁶) was observed between MDR and biofilm formation. Antagonist activity was observed in 62.5% isolates. Gram-positive isolates were more susceptible to antagonism (75.86%) than gram-negative (36.36%) isolates. Antagonism interactions against gram-negative isolates were lower (9.42%) when compared to gram-positive isolates (89.85%). Such strong antagonist activity can be harnessed for inspection of novel antimicrobial mechanisms and drugs. Our study shows that MDR with strong biofilm formation is prevalent in natural habitat and if acquired by deadly pathogens may create havoc in public health. Full article

Cardiac glycosides (CGs) are a diverse family of naturally derived compounds having a steroid and glycone moiety in their structures. CG molecules inhibit the α-subunit of ubiquitous transmembrane protein Na⁺/K⁺-ATPase and are clinically approved for the treatment of cardiovascular diseases. Recently, the CGs were found to exhibit selective cytotoxic effects against cancer cells, raising interest in their use as anti-cancer molecules. In this current study, we explored the underlying mechanism responsible for the anti-cancer activity of Lanatoside C against breast (MCF-7), lung (A549), and liver (HepG2) cancer cell lines. Using Real-time PCR, western blot, and immunofluorescence studies, we observed that (i) Lanatoside C inhibited cell proliferation and induced apoptosis in cell-specific and dose-dependent manner only in cancer cell lines; (ii) Lanatoside C exerts its anti-cancer activity by arresting the G2/M phase of cell cycle by blocking MAPK/Wnt/PAM signaling pathways; (iii) it induces apoptosis by inducing DNA damage and inhibiting PI3K/AKT/mTOR signaling pathways; and finally, (iv) molecular docking analysis shows significant evidence on the binding sites of Lanatoside C with various key signaling proteins ranging from cell survival to cell death. Our studies provide a novel molecular insight of anti-cancer activities of Lanatoside C in human cancer cells. Full article

The natural population of the aquatic environment supports a diverse aquatic biota and a robust seafood industry. However, this environment also provides an appropriate niche for the growth of pathogenic bacteria that cause problems for human health. For example, species of the genus Vibrio inhabit marine and estuarine environments. This genus includes species that are pathogenic to aquaculture, invertebrates, and humans. In humans, they can cause prominent diseases like gastroenteritis, wound infections, and septicemia. The increased number of multidrug resistant (MDR) Vibrio strains has drawn the attention of the scientific community to develop new broad-spectrum antibiotics. Hence, in this paper we report the bactericidal effects of compounds derived from Piper betel plants: piperidine, chlorogenic acid, and eugenyl acetate, against various strains of Vibrio species. The different MIC90 values were approximately in a range of 2–6 mg/mL, 5–16 mg/mL, 5–20 mg/mL, and 30–80 mg/mL, for piperidine, chlorogenic acid, and eugenyl acetate, respectively. Piperidine showed the best anti-Vibrio effect against the five Vibrio species tested. Interestingly, combinations of sub-inhibitory concentrations of piperidine, chlorogenic acid, and eugenyl acetate showed inhibitory effects in the Vibrio strains. Furthermore, these compounds showed synergism or partial synergism effects against MDR strains of the Vibrio species when they were incubated with antibiotics (ampicillin and chloramphenicol). Full article