Discovery of antibacterial biogenic magnetosome nanoparticles from Providencia sp. MTBPRB-1: Screening, purification and characterization.

Bacterial species referred to as magnetotactic bacteria (MTB) biomineralize iron oxides and iron sulphides inside the cell. Bacteria can arrange themselves passively along geomagnetic field lines with the aid of these iron components known as magnetosomes. In this study, magnetosome nanoparticles, which were obtained from the taxonomically identified MTB isolate Providencia sp. PRB-1, were characterized and their antibacterial activity was evaluated. An in vitro test showed that magnetosome nanoparticles significantly inhibited the growth of Staphylococcus sp., Pseudomonas aeruginosa, and Klebsiella pneumoniae. Magnetosomes were found to contain cuboidal iron crystals with an average size of 42 nm measured by particle size analysis and scanning electron microscope analysis. The energy dispersive X-ray examination revealed that Fe and O were present in the extracted magnetosomes. The extracted magnetosome nanoparticles displayed maximum absorption at 260 nm in the UV-Vis spectrum. The distinct magnetite peak in the Fourier transform infrared (FTIR) spectroscopy spectra was observed at 574.75 cm-1. More research is needed into the intriguing prospect of biogenic magnetosome nanoparticles for antibacterial applications.

Identification of apigenin-4'-glucoside as bacterial DNA gyrase inhibitor by QSAR modeling, molecular docking, DFT, molecular dynamics, and in vitro confirmation studies.

CONTEXT: It is well known that antibiotic resistance is a major health hazard. To eradicate antibiotic-resistant bacterial infections, it is essential to find a novel antibacterial agent. Hence, in this study, a quantitative structure-activity relationship (QSAR) model was developed using 43 DNA gyrase inhibitors, and 700 natural compounds were screened for their antibacterial properties. Based on molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, the top three leads viz., apigenin-4'-glucoside, 8-deoxygartanin, and cryptodorine were selected and structurally optimized using density functional theory (DFT) studies. The optimized structures were redocked, and molecular dynamic (MD) simulations were performed. Binding energies were calculated by molecular mechanics/Poisson-Boltzmann surface area solvation (MM-PBSA). Based on the above studies, apigenin-4'-glucoside was identified as a potent antibacterial lead. Further in vitro confirmation studies were performed using the plant Lawsonia inermis containing apigenin-4'-glucoside to confirm the antibacterial activity. METHODS: For QSAR modeling, 2D descriptors were calculated by PaDEL-Descriptors v2.21 software, and the model was developed using the DTClab QSAR tool. Docking was performed using PyRx v0.8 software. ORCA v5.0.1 computational package was used to optimize the structures. The job type used in optimization was equilibrium structure search using the DFT hybrid functional ORCA method B3LYP. The basis set was 6-311G (3df, 3pd) plus four polarization functions for all atoms. Accurate docking was performed for optimized leads using the iGEMDOCK v2.1 tool with a genetic algorithm by 10 solutions each of 80 generations. Molecular dynamic simulations were performed using GROMACS 2020.04 software with CHARMM36 all-atom force field.

Microstructure, Mechanical Characteristics, and Wear Performance of Spark Plasma Sintered TiB2-Si3N4 as Affected by B4N Doping.

This study aims to analyze the effect of boron nitride (B4N) additive (3-6%) on the densification, microstructure, mechanical properties, and wear performance of TiB2-15%Si3N4 and TiB2-30%Si3N4 sintered composites. When the B4N (3%) was added to the TiB2-30Si3N4 composite, the density increased to 99.5%, hardness increased to 25.2 MPa, and the fracture toughness increased to 4.62 MPam1/2. Microstructural analysis shows that in situ phases such as TiB2 help to improve the relative mechanical characteristics. However, raising the B4N additive to 6% in the above-sintered composite reduces the composites' relative density and hardness. The tested sintered composites demonstrated that their superior wear resistance can be attributed to their increased density and hardness.

4a-methyl-dodecahydro-1H-pyrrolo[3,4-b]quinoline-6-one produced by Endophytic Fungi Aspergillus niger E12 obtained from Dodonaea viscosa Plant Leaves as a Novel Antibacterial Compound.

Endophytic fungi were isolated from forty plant leaf samples from Gudiyam forest. The potent antibacterial strain Aspergillus niger E12 isolated from the plant Dodonaea viscosa showed maximal antibacterial activity against all the test organisms, viz., Staphylococcus aureus, Bacillus coagulans, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The production of the antibacterial compound was optimized using the yeast extract sucrose medium (2% YES) using response surface methodology (RSM). For the production, the optimal parameters were carbon/nitrogen (C:N) ratio, 9:1; temperature, 25 °C; pH, 5.7; incubation time, 240 h; and rpm, 30. A zone of inhibition of 19.33 mm was observed as maximal bioactivity against Pseudomonas aeruginosa. The antibacterial compound was purified by extraction with ethyl acetate, activity-guided fractionation, and preparative high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) studies showed that the Aspergillus niger E12 bioactive substance is 4a-methyl-dodecahydro-1H-pyrrolo [3,4-b] quinoline-6-one.

A novel colorimetric technique for estimating iron in magnetosomes of magnetotactic bacteria based on linear regression.

Magnetotactic bacteria (MTB) use iron from their habitat to create magnetosomes, a unique organelle required for magnetotaxis. Due to a lack of cost-effective assay methods for estimating iron in magnetosomes, research on MTB and iron-rich magnetosomes is limited. A systemized assay was established in this study to quantify iron in MTB using ferric citrate colorimetric estimation. With a statistically significant R2 value of 0.9935, the iron concentration range and wavelength for iron estimation were optimized using linear regression. This colorimetric approach and the inductively coupled plasma optical emission spectrometry (ICP-OES) exhibited an excellent correlation R2 value of 0.961 in the validatory correlative study of the iron concentration in the isolated magnetotactic bacterial strains. In large-scale screening studies, this less-expensive strategy could be advantageous.

Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of Scopoletin.

OBJECTIVES: Scopoletin (6-methoxy-7-hydroxycoumarin) is a naturally occurring coumarin belonging to the category of secondary metabolites. Coumarins are commonly found in several herbs and play a prominent role in the defense mechanism of plants. Beneficial effects of scopoletin including antioxidant, anti-diabetic, hepatoprotective, neuroprotective and anti-microbial activity induced via numerous intracellular signalling mechanisms have been widely studied. However, anti-inflammation and anti-tumorigenesis properties of scopoletin are not well documented in the literature. Therefore, the primary focus of the present review was to highlight the plethora of research pertaining to the signalling mechanisms associated with the prevention of the progression of disease condition by scopoletin. KEY FINDINGS: Multiple signalling pathways like nuclear erythroid factor-2 (NEF2)-related factor-2 (NRF-2), apoptosis/p53 signalling, nuclear factor-κB (NF-κB) signalling, autophagy signalling, hypoxia signalling, signal transducer and activator of transcription-3 (STAT3) signalling, Wnt-ß signalling, Notch signalling are coupled with the anti-inflammation and anti-tumorigenesis potential of scopoletin. SUMMARY: Understanding crucial targets in these molecular signalling pathways may support the role of scopoletin as a promising naturally derived bioactive compound for the treatment of several diseases.

Production and characterization of naturally occurring antibacterial magnetite nanoparticles from magnetotactic Bacillus sp. MTB17.

AIMS: This study envisaged the isolation and characterization of magnetite nanoparticles (MNPs) from magnetotactic bacteria (MTB) and the evaluation of their antibacterial efficacy. METHODS AND RESULTS: MNPs were extracted from 20 motile but morphologically different MTB, and they were subjected to antibacterial activity assay. These MNPs were found to be highly effective against Vibrio cholerae. MTB17 was considered as the potent MTB strain based on the antibacterial activity. The MNPs of MTB17 were isolated and validated by UV-Visible spectroscopy, particle size analysis, FTIR analysis, and PXRD. CONCLUSIONS: Isolation and characterization of ~85 nm MNPs from MTB is reported, and it is highly active against all the gram-positive and gram-negative strains tested. SIGNIFICANCE AND IMPACT OF THE STUDY: This study focuses on a novel use of biogenic magnetite MNPs as an antibacterial agent, which can be further explored using in vivo studies.

1,2,4 triazolo[1,5-a] pyrimidin-7-ones as novel SARS-CoV-2 Main protease inhibitors: In silico screening and molecular dynamics simulation of potential COVID-19 drug candidates.

Discovery of a potent SARS-CoV-2 main protease (Mpro) inhibitor is the need of the hour to combat COVID-19. A total of 1000 protease-inhibitor-like compounds available in the ZINC database were screened by molecular docking with SARS-CoV-2 Mpro and the top 2 lead compounds based on binding affinity were found to be 1,2,4 triazolo[1,5-a] pyrimidin-7-one compounds. We report these two compounds (ZINC000621278586 and ZINC000621285995) as potent SARS-CoV-2 Mpro inhibitors with high affinity (<-9 kCal/mol) and less toxicity than Lopinavir and Nelfinavir positive controls. Both the lead compounds effectively interacted with the crucial active site amino acid residues His41, Cys145 and Glu166. The lead compounds satisfied all of the druglikeness rules and devoid of toxicity or mutagenicity. Molecular dynamics simulations showed that both lead 1 and lead 2 formed stable complexes with SARS-CoV-2 Mpro as evidenced by the highly stable root mean square deviation (<0.23 nm), root mean square fluctuations (0.12 nm) and radius of gyration (2.2 nm) values. Molecular mechanics Poisson-Boltzmann surface area calculation revealed thermodynamically stable binding energies of -129.266 ± 2.428 kJ/mol and - 116.478 ± 3.502 kJ/mol for lead1 and lead2 with SARS-CoV-2 Mpro, respectively.

Effect of Extremely Low Power Time-Varying Electromagnetic Field on Germination and Other Characteristics in Foxtail Millet (Setaria italica) Seeds.

The ability of extremely low, time-varying electromagnetic field (EMF) to improve germination efficacy was studied in Foxtail millet (Setaria italica) seeds using response surface methodology. An optimal factorial central composite design was chosen to optimize the EMF with three critical factors, viz. frequency, intensity, and duration. The adequacy of the model and fitness was evaluated by analysis of variance and regression coefficients. This model suggested that the factors, frequency, and intensity had a significant impact on germination. Optimal conditions for germination were observed to be 10 Hz frequency, 30,007 nT intensity, and 30-min duration with an observed germination percentage of 93.0, and a predicted germination percentage of 92.92. Magneto-priming was found to increase the germination efficacy (15.66%), shoot length (27.78%), total seedling length (20.30%), seedling dry mass (26.49%), and water uptake (34.48% at 80 min) showing significant output when compared with the control and positive controls. Remarkable improvements were observed in germination parameters such as vigor index-1 (39.14%), vigor index-2 (46.28%), speed of germination (27.52%), and emergence index (12.50%). Magneto-priming was found to reduce the levels of germination-specific enzymes, viz. α-amylase, protease, and dehydrogenase, while it enhanced the levels of antioxidant enzymes, viz. catalase (114.63%) and superoxide dismutase (19.62%), triggering fast germination and early vigor of seedlings. This study clearly showed that EMF priming significantly improved the germination effect and other characteristics of Foxtail millet seeds. Bioelectromagnetics. © 2020 Bioelectromagnetics Society.

Superintendence of antimicrobial resistance observed in bacterial flora isolated from human faecal carriage in Vellore, India.

A frequent cross-sectional study was conducted to determine the patterns of antimicrobial resistance in 296 bacterial strains isolated from in-patient faecal samples of Government Vellore Medical College and Hospital, Vellore. Isolation and identification of bacterial strains were done using enrichment media, selective media, and biochemical tests. Antimicrobial susceptibility testing by the disc diffusion method and minimal inhibitory concentration method was conducted and the strains were subjected to extended spectrum beta-lactamases screening. Antibiotic sensitivity pattern of Staphylococcus spp. showed oxacillin resistance. Almost all the strains were sensitive to linezolid, vancomycin, gentamycin and chloramphenicol. In gram negative isolates ciprofloxacin and tobramycin showed better sensitivity and ceftazidime showed a higher percentage of resistance by MIC. Out of 250 isolates, Enterobacteriaceae showed positive for 86/250, 82/250 and 94/250 isolates and 3/10, 4/10 and 4/10 non-Enterobacteriaceae isolates were found to be positive for CTX-M gene, TEM gene and SHV gene, respectively. This study helps to assess/analyse the relation between the spectrum of microorganisms present in various grades of faecal carriage and their susceptibility pattern in this part of the Vellore town.

Green synthesis of silver nanoparticles using Delphinium denudatum root extract exhibits antibacterial and mosquito larvicidal activities.

Green synthesis of silver nanoparticles (AgNPs) using aqueous root extract of Delphinium denudatum (Dd) by reduction of Ag(+) ions from silver nitrate solution has been investigated. The synthesized DdAgNPs were characterized by using UV-Vis spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectroscopy (FTIR). The prepared DdAgNPs showed maximum absorbance at 416nm and particles were polydispersed in nature, spherical in shape and the size of the particle obtained was⩽85nm. The DdAgNPs exhibited antibacterial activity against Staphylococcus aureus ATCC 6538, Bacillus cereus NCIM 2106, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027. The DdAgNPs showed potent larvicidal activity against second instar larvae of dengue vector Aedes aegypti with a LC50 value of 9.6ppm.

Fisetin modulates mitochondrial enzymes and apoptotic signals in benzo(a)pyrene-induced lung cancer.

The present study was aimed to delineate in vivo mechanisms of orally administered fisetin with special reference to mitochondrial dysfunction in lung tissues employing benzo(a)pyrene (B(a)P) as the model lung carcinogen. The recent revival of interest in the study of mitochondria has been stimulated by the evidence that genetic and/or metabolic alterations in this organelle lead to a variety of human diseases including cancer. These alterations could be either causative or contributing factors. Hence, the activities of mitochondrial-specific enzymes of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase and tumor marker, carcinogenic embryonic antigen were analyzed in control and experimental groups of mice. The induction of apoptotic and anti-apoptotic proteins such as Bcl-2/Bax, cytochrome c, caspase-9 and caspase-3 was confirmed by the immunohistochemistry and Western blot analyses. Furthermore, transmission electron microscopy study of lung sections of B(a)P-induced mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. All the aberrations were alleviated when the mice were treated with fisetin (25 mg/kg body weight). The results proved fisetin to be a very successful drug in combating the mitochondrial dysfunction in an experimental model of lung carcinogenesis induced by B(a)P.

Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice.

Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring flavonoid is found in vegetables and fruits possesses anti-oxidative, anti-inflammatory and anti-proliferative effects in a wide variety of cancer. In the present study it is hypothesized that fisetin may provide chemopreventive as well as chemotherapeutic effects against experimental lung carcinogenesis. The present study was designed to investigate whether fisetin confers anti-cancer action against benzo(a)pyrene [B(a)P] induced lung carcinogenesis. Treatment with fisetin significantly reduced the degree of histological lesions, restored the levels of lipid peroxidation (LPO), enzymic and non-enzymic anti-oxidants in B(a)P-induced mice. Anti-proliferative efficacy of fisetin was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) in B(a)P induced mice showed increased PCNA expression which is restored upon fisetin administration. Together, our results depicts that fisetin can be used as chemopreventive agent against lung cancer.