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Introduction: Sustainable agriculture and meeting the world's food needs face considerable obstacles from abiotic stresses such as soil salinity and drought. This critical issue was addressed by our current study, which sought to uncover multi-trait bioinoculants from hostile ecosystems that could help mitigate salinity and drought stresses at the same time., Methods: The Bacillus subtilis ER-08 (BST) strain was isolated from the halotolerant plant Fagonia cretica which was collected from the Little Rann of Kachchh, India. Various biochemical and molecular approaches were applied for the detailed characterization of the BST isolate., Results and Discussion: The BST isolate demonstrated notable plant growth-promoting qualities. Fenugreek seed biopriming was performed using the BST isolate. The effect of BST seed treatment on fenugreek developmental indices as well as abiotic alleviation was examined under greenhouse conditions. The BST produced 83.7 g ml -1 gibberellins (GA 3 ) and 176.1 g ml -1 indole-3 acetic acid. Moreover, hydrogen cyanide, siderophore, exopolysaccharides (EPS), ammonia, cellulase, protease, pectinase, and chitinase were also produced by the BST strain. Interestingly, 52% of Fusarium oxysporum mycelial growth was suppressed by the BST isolate under in vitro conditions. Furthermore, BST isolates functioned well under several abiotic stress conditions, for instance, salinity (4 and 6 ds m -1 ), pH (5, 7, and 9), drought (PEG6000 at 10%, 20%, and 30%), and temperature (25°C, 35°C, 37°C, and 55°C). This study indicates that the BST strain might serve as an effective bio-inoculant for minimizing the detrimental effects of abiotic stresses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Patel, Islam, Husain, Yadav, Park, Yadav, Bagatharia, Joshi, Jeon and Patel.)

Introduction: Alzheimer's disease (AD) is the most studied progressive eurodegenerative disorder, affecting 40-50 million of the global population. This progressive neurodegenerative disease is marked by gradual and irreversible declines in cognitive functions. The unavailability of therapeutic drug candidates restricting/reversing the progression of this dementia has severed the existing challenge. The development of acetylcholinesterase (AChE) inhibitors retains a great research focus for the discovery of an anti-Alzheimer drug., Materials and Methods: This study focused on finding AChE inhibitors by applying the machine learning (ML) predictive modeling approach, which is an integral part of the current drug discovery process. In this study, we have extensively utilized ML and other in silico approaches to search for an effective lead molecule against AChE., Result and Discussion: The output of this study helped us to identify some promising AChE inhibitors. The selected compounds performed well at different levels of analysis and may provide a possible pathway for the future design of potent AChE inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Taehwan, Cho, Scotti, Priscila Barros de Menezes, Husain, Alomar, Baig and Dong.)

In recent years, the demand for novel antifungal therapies has increased several- folds due to its potential to treat severe biofilm-associated infections. Biofilms are made by the sessile microorganisms attached to the abiotic or biotic surfaces, enclosed in a matrix of exopolymeric substances. This results in new phenotypic characteristics and intrinsic resistance from both host immune response and antimicrobial drugs. Candida albicans biofilm is a complex association of hyphal cells that are associated with both abiotic and animal tissues. It is an invasive fungal infection and acts as an important virulent factor. The challenges linked with biofilm-associated diseases have urged scientists to uncover the factors responsible for the formation and maturation of biofilm. Several strategies have been developed that could be adopted to eradicate biofilm-associated infections. This article presents an overview of the role of C. albicans biofilm in its pathogenicity, challenges it poses and threats associated with its formation. Further, it discusses strategies that are currently available or under development targeting prostaglandins, quorum-sensing, changing surface properties of biomedical devices, natural scaffolds, and small molecule-based chemical approaches to combat the threat of C. albicans biofilm. This review also highlights the recent developments in finding ways to increase the penetration of drugs into the extracellular matrix of biofilm using different nanomaterials against C. albicans ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Atriwal, Azeem, Husain, Hussain, Khan, Alajmi and Abid.)

There is grave necessity to counter the menace of drug-resistant biofilms of pathogens using nanomaterials. Moreover, we need to produce nanoparticles (NPs) using inexpensive clean biological approaches that demonstrate broad-spectrum inhibition of microbial biofilms and cytotoxicity against HepG2 cell lines. In the current research work, titanium dioxide (TiO 2 ) NPs were fabricated through an environmentally friendly green process using the root extract of Withania somnifera as the stabilizing and reducing agent to examine its antibiofilm and anticancer potential. Further, X-ray diffraction (XRD), Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron micrograph (TEM), energy-dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) techniques were used for determining the crystallinity, functional groups involved, shape, size, thermal behavior, surface area, and porosity measurement, respectively, of the synthesized TiO 2 NPs. Antimicrobial potential of the TiO 2 NPs was determined by evaluating the minimum inhibitory concentration (MIC) against Escherichia coli , Pseudomonas aeruginosa , methicillin-resistant Staphylococcus aureus , Listeria monocytogenes , Serratia marcescens , and Candida albicans . Furthermore, at levels below the MIC (0.5 × MIC), TiO 2 NPs demonstrated significant inhibition of biofilm formation (43-71%) and mature biofilms (24-64%) in all test pathogens. Cell death due to enhanced reactive oxygen species (ROS) production could be responsible for the impaired biofilm production in TiO 2 NP-treated pathogens. The synthesized NPs induced considerable reduction in the viability of HepG2 in vitro and could prove effective in controlling liver cancer. In summary, the green synthesized TiO 2 NPs demonstrate multifarious biological properties and could be used as an anti-infective agent to treat biofilm-based infections and cancer., (Copyright © 2020 Al-Shabib, Husain, Qais, Ahmad, Khan, Alyousef, Arshad, Noor, Khan, Alam, Albalawi and Shahzad.)

Cancer and the associated secondary bacterial infections are leading cause of mortality, due to the paucity of effective drugs. Here, we have synthesized silver nanoparticles (AgNPs) from organic resource and confirmed their anti-cancer and anti-microbial potentials. Microwave irradiation method was employed to synthesize AgNPs using Pandanus odorifer leaf extract. Anti-cancer potential of AgNPs was evaluated by scratch assay on the monolayer of rat basophilic leukemia (RBL) cells, indicating that the synthesized AgNPs inhibit the migration of RBL cells. The synthesized AgNPs showed MIC value of 4-16 μg/mL against both Gram +ve and Gram -ve bacterial strains, exhibiting the anti-microbial potential. Biofilm inhibition was recorded at sub-MIC values against Gram +ve and Gram -ve bacterial strains. Violacein and alginate productions were reduced by 89.6 and 75.6%, respectively at 4 and 8 μg/mL of AgNPs, suggesting anti-quorum sensing activity. Exopolysaccharide production was decreased by 61-79 and 84% for Gram -ve and Gram +ve pathogens respectively. Flagellar driven swarming mobility was also reduced significantly. Furthermore, In vivo study confirmed their tolerability in mice, indicating their clinical perspective. Collective, we claim that the synthesized AgNPs have anti-metastasis as well as anti-microbial activities. Hence, this can be further tested for therapeutic options to treat cancer and secondary bacterial infections.

In the present study, a facile environmentally friendly approach was described to prepare monodisperse iron oxide (Fe 3 O 4 ) nanoparticles (IONPs) by low temperature solution route. The synthesized nanoparticles were characterized using x-ray diffraction spectroscopy (XRD), Raman spectroscopy, field emission scanning electron microscopy (FESEM) measurements, Fourier-Transform Infrared Spectroscopy (FTIR), and Thermogravimetric analysis (TGA) analyses. XRD patterns revealed high crystalline quality of the nanoparticles. SEM micrographs showed the monodispersed IONPs with size ranging from 6 to 9 nm. Synthesized nanoparticles demonstrated MICs of 32, 64, and 128 μg/ml against Gram negative bacteria i.e., Serratia marcescens, Escherichia coli , and Pseudomonas aeruginosa , respectively, and 32 μg/ml against Gram positive bacteria Listeria monocytogenes . IOPNs at its respective sub-MICs demonstrated significant reduction of alginate and exopolysaccharide production and subsequently demonstrated broad-spectrum inhibition of biofilm ranging from 16 to 88% in the test bacteria. Biofilm reduction was also examined using SEM and Confocal Laser Scanning Microscopy (CLSM). Interaction of IONPs with bacterial cells generated ROS contributing to reduced biofilm formation. The present study for the first time report that these IONPs were effective in obliterating pre-formed biofilms. Thus, it is envisaged that these nanoparticles with broad-spectrum biofilm inhibitory property could be exploited in the food industry as well as in medical settings to curtail biofilm based infections and losses.

The resistance and pathogenesis of bacteria could be related to their ability to sense and respond to population density, termed quorum sensing (QS). Inhibition of the QS system is considered as a novel strategy for the development of antipathogenic agents, especially for combating drug-resistant bacterial infections. In the present study, the anti-QS activity of Onion peel ethylacetate fraction (ONE) was tested against Chromobacterium violaceum CV12472 and Pseudomonas aeruginosa PAO1. ONE inhibit the QS-mediated virulence factors production such as violacein in C. violaceum and elastase, pyocyanin in P. aeruginosa . Further, the treatment with sub-MICs of ONE significantly inhibited the QS-mediated biofilm formation, EPS (Extracellular polymeric substances) production and swarming motility. Further, quercetin 4'- O -β-D glucopyranoside (QGP) was isolated from ONE and its anti-QS potential was confirmed after observing significant inhibition of QS-controlled virulence factors such as violacein, elastase, pyocyanin and biofilm formation in test pathogens. Molecular docking analysis predicted that QGP should be able to bind at the active sites of Vfr and LasR, and if so blocks the entry of active sites in Vfr and LasR.

Quorum sensing (QS) is a global gene regulatory mechanism in bacteria for various traits including virulence factors. Disabling QS system with anti-infective agent is considered as a potential strategy to prevent bacterial infection. Mangifera indica L. (mango) has been shown to possess various biological activities including anti-QS. This study investigates the efficacy of leaf extracts on QS-regulated virulence factors and biofilm formation in Gram negative pathogens. Mango leaf (ML) extract was tested for QS inhibition and QS-regulated virulence factors using various indicator strains. It was further correlated with the biofilm inhibition and confirmed by electron microscopy. Phytochemical analysis was carried out using ultra performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) analysis. In vitro evaluation of anti-QS activity of ML extracts against Chromobacterium violaceum revealed promising dose-dependent interference in violacein production, by methanol extract. QS inhibitory activity is also demonstrated by reduction in elastase (76%), total protease (56%), pyocyanin (89%), chitinase (55%), exopolysaccharide production (58%) and swarming motility (74%) in Pseudomonas aeruginosa PAO1 at 800 μg/ml concentration. Biofilm formation by P. aeruginosa PAO1 and Aeromonas hydrophila WAF38 was reduced considerably (36-82%) over control. The inhibition of biofilm was also observed by scanning electron microscopy. Moreover, ML extracts significantly reduced mortality of Caenorhabditis elegans pre-infected with PAO1 at the tested concentration. Phytochemical analysis of active extracts revealed very high content of phenolics in methanol extract and a total of 14 compounds were detected by GC-MS and UPLC. These findings suggest that phytochemicals from the ML could provide bioactive anti-infective and needs further investigation to isolate and uncover their therapeutic efficacy.

Bacterial quorum sensing (QS) is a density dependent communication system that regulates the expression of certain genes including production of virulence factors in many pathogens. Bioactive plant extract/compounds inhibiting QS regulated gene expression may be a potential candidate as antipathogenic drug. In this study anti-QS activity of peppermint (Mentha piperita) oil was first tested using the Chromobacterium violaceum CVO26 biosensor. Further, the findings of the present investigation revealed that peppermint oil (PMO) at sub-Minimum Inhibitory Concentrations (sub-MICs) strongly interfered with acyl homoserine lactone (AHL) regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Aeromonas hydrophila. The result of molecular docking analysis attributed the QS inhibitory activity exhibited by PMO to menthol. Assessment of ability of menthol to interfere with QS systems of various Gram-negative pathogens comprising diverse AHL molecules revealed that it reduced the AHL dependent production of violacein, virulence factors, and biofilm formation indicating broad-spectrum anti-QS activity. Using two Escherichia coli biosensors, MG4/pKDT17 and pEAL08-2, we also confirmed that menthol inhibited both the las and pqs QS systems. Further, findings of the in vivo studies with menthol on nematode model Caenorhabditis elegans showed significantly enhanced survival of the nematode. Our data identified menthol as a novel broad spectrum QS inhibitor.