Cinnamaldehyde inhibits Enterococcus faecalis biofilm formation and promotes clearance of its colonization by modulation of phagocytes in vitro.

The nosocomial pathogen, Enterococcus faecalis plays a crucial role in the pathogenesis of variety of infections including endocarditis, urinary tract, and recurrent root canal infections. Primary virulence factors of E. faecalis such as biofilm formation, gelatinase production and suppression of host innate immune response can severely harm host tissue. Thus, novel treatments are needed to prevent E. faecalis biofilm development and pathogenicity due to the worrisome rise in enterococcal resistance to antibiotics. The primary phytochemical in cinnamon essential oils, cinnamaldehyde, has shown promising efficacy against a variety of infections. Here, we looked into how cinnamaldehyde affected the growth of biofilms, the activity of the enzyme gelatinase, and gene expression in E. faecalis. In addition, we looked at the influence of cinnamaldehyde on RAW264.7 macrophages' interaction with biofilm and planktonic E. faecalis in terms of intracellular bacterial clearance, NO generation, and macrophage migration in vitro. According to our research, cinnamaldehyde attenuated the biofilm formation potential of planktonic E. faecalis and gelatinase activity of the biofilm at non-lethal concentrations. The expression of the quorum sensing fsr locus and its downstream gene gelE in biofilms were also found to be significantly downregulated by cinnamaldehyde. Results also demonstrated that cinnamaldehyde treatment increased NO production, intracellular bacterial clearance, and migration of RAW264.7 macrophages in presence of both biofilm and planktonic E. faecalis. Overall these results suggest that cinnamaldehyde has the ability to inhibit E. faecalis biofilm formation and modulate host innate immune response for better clearance of bacterial colonization.

Biocidal activity of Ba2+-doped CeO2 NPs against Streptococcus mutans and Staphylococcus aureus bacterial strains.

Mishandling of antibiotics often leads to the development of multiple drug resistance (MDR) among microbes, resulting in the failure of infection treatments and putting human health at great risk. As a response, unique nanomaterials with superior bioactivity must be developed to combat bacterial infections. Herein, CeO2-based nanomaterials (NMs) were synthesized by employing cerium(iii) nitrate and selective alkaline ions. Moreover, the influence of alkaline ions on CeO2 was investigated, and their characteristics, viz.: biochemical, structural, and optical properties, were altered. The size of nano Ba-doped CeO2 (BCO) was ∼2.3 nm, relatively smaller than other NMs and the antibacterial potential of CeO2, Mg-doped CeO2 (MCO), Ca-doped CeO2 (CCO), Sr-doped CeO2 (SCO), and Ba-doped CeO2 (BCO) NMs against Streptococcus mutans (S. mutans) and Staphylococcus aureus (S. aureus) strains was assessed. BCO outperformed all NMs in terms of antibacterial efficacy. In addition, achieving the enhanced bioactivity of BCO due to reduced particle size facilitated the easy penetration into the bacterial membrane and the presence of a sizeable interfacial surface. In this study, the minimum quantity of BCO required to achieve the complete inhibition of bacteria was determined to be 1000 µg mL-1 and 1500 µg mL-1 for S. mutans and S. aureus, respectively. The cytotoxicity test with L929 fibroblast cells demonstrated that BCO was less toxic to healthy cells. Furthermore, BCO did not show any toxicity and cell morphological changes in the L929 fibroblast cells, which is similar to the control cell morphology. Overall, the results suggest that nano BCO can be used in biomedical applications, which can potentially help improve human health conditions.

Inhibitory potential of EGCG on Streptococcus mutans biofilm: A new approach to prevent Cariogenesis.

Dental caries is a common cause for tooth loss and Streptococcus mutans is identified as the etiologic pathogen. This study evaluates the inhibitory potential of Epigallocatechin gallate (EGCG) on S.mutans glucansucrase enzyme and its biofilm. Glucansucrase binding and the inhibitory potential of EGCG was validated using AutoDock tool and enzyme inhibitory assay. Biofilm inhibitory potential was also confirmed using Scanning Electron Microscopic (SEM) analysis in human tooth samples. Molecular docking revealed that EGCG interacted with GLU 515 and TRP 517 amino acids and binds to glucansucrase. SEM analysis revealed inhibition of S.mutans biofilm by various concentrations of EGCG on surfaces of tooth samples. Bioinformatics and biological assays confirmed that EGCG potentially binds to the S. mutans glucansucrase and inhibits its enzymatic activity. Enzymatic inhibition of glucansucrase attenuated biofilm formation potential of S. mutans on tooth surface. Thus, we conclude that EGCG inhibitory potential of S. mutans biofilm on the tooth surface is a novel approach in prevention of dental caries.

Anticancer potential of NF-κB targeting apoptotic molecule "flavipin" isolated from endophytic Chaetomium globosum.

BACKGROUND: Anticancer compounds from natural sources have drawn attention due to their structural diversity and relatively lesser side effects. Endophytic fungi are one such natural resource from, which plethoras of anticancerous compounds have been isolated. PURPOSE: The objective of the study was to isolate and characterize the bioactive metabolite from Chaetomium globosum that exhibits astonishing antiproliferative activity against cancerous cell lines. METHODS: Flavipin was isolated by bioassay-guided fractionation and identified using FT-IR, EI-MS and NMR studies. MTT assay was used to determine the cytotoxicity. Fluorescent staining (AO/EB) and DNA fragmentation studies confirmed the occurrence of apoptosis. Real time PCR and Western blotting were used to analyze the expression of apoptosis related genes and its proteins, respectively. RESULTS: Flavipin inhibited proliferation of A549, HT-29 and MCF-7 cancer cells in dose dependent manner with an IC50 concentration of 9.89 µg/ml, 18 µg/ml and 54 µg/ml, respectively, whereas it was comparatively less sensitive (IC50 = 78.89 µg/ml) against normal cell line (CCD-18Co). At IC50 concentration cancerous cells exhibited cell shrinkage and fragmentation of DNA, which indicated that flavipin induced apoptotic cell death. In treated cells there is an up-regulation of p53 gene and its associated protein, whereas reciprocal expression was observed in BCL-2 gene and its protein. Furthermore, western blotting results also showed down-regulation of NFκB. CONCLUSION: This is the first report on the antiproliferative activity of flavipin isolated from endophytic C. globosum and also proposed that interaction of flavipin with NFкB could be a possible mechanism for this activity. Flavipin induced apoptosis at low concentrations in cancer cell lines (A549, HT-29) and exhibited itself as a potential anticancer agent.

Effect of Mg(2+), Ca(2+), Sr(2+) and Ba(2+) metal ions on the antifungal activity of ZnO nanoparticles tested against Candida albicans.

The antifungal ability of pure and alkaline metal ion (Mg(2+), Ca(2+), Sr(2+) and Ba(2+)) doped ZnO nanoparticles (NPs) prepared by the co-precipitation method was tested against the pathogenic yeast, Candida albicans (C. albicans), and the results showed that the Mg-doped ZnO NPs possessed greater effect than the other alkaline metal ion doped ZnO NPs. The impact of the concentration of Mg doped ZnO sample on the growth of C. albicans was also studied. The Minimal Fungicidal Concentration (MFC) of the Mg doped ZnO NPs was found to be 2000 µg/ml for which the growth of C. albicans was completely inhibited. The ZnO:Mg sample (1.5mg/ml) with various concentrations of histidine reduced the fungicidal effect of the nanoparticles against C. albicans, which was deliberately explained by the role of ROS. The ZnO:Mg sample added with 5mM of histidine scavenged the ample amount of generated ROS effectively. The binding of the NPs with fungi was observed by their FESEM images and their electrostatic attraction is confirmed by the zeta potential measurement.

Impact of alkaline metal ions Mg2+, Ca2+, Sr2+ and Ba2+ on the structural, optical, thermal and antibacterial properties of ZnO nanoparticles prepared by the co-precipitation method.

Pure ZnO and alkaline metal ion (Mg2+, Ca2+, Sr2+ and Ba2+)-doped ZnO nanoparticles (NPs) were synthesized by the co-precipitation method. The synthesized nanoparticles retained the wurtzite hexagonal structure, which was confirmed by X-ray diffraction studies. The micro-strain properties were analyzed through Williamson-Hall analysis. The oxidation states of the elements (C (1s), O (1s), Zn (2p), Mg (1s), Ca (2p), Sr (3d) and Ba (3d)) were confirmed by XPS studies. HRSEM studies showed a reduction in the thickness of the ZnO nanoflakes from 63 to 47 nm after doping. EDAX studies determined the amount of dopant (alkaline metals) incorporated into the doped samples. The FT-IR spectra confirmed the Zn-O stretching bands at 432, 416, 414, 426 and 422 cm-1 for the respective ZnO NPs. The photoluminescence measurements revealed that the broad emission was composed of six different bands due to zinc and oxygen vacancies. Thermal analysis revealed that the irreversible structural transition occurred from the cubic phase to the wurtzite phase in the samples. The antibacterial studies performed against a set of bacterial strains showed that the Mg-doped ZnO NPs possessed a greater antibacterial effect than the other alkaline metal ion-doped ZnO NPs.