Computational Approaches to Evaluate the Acetylcholinesterase Binding Interaction with Taxifolin for the Management of Alzheimer's Disease.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.

Green Synthesis of Chitosan-Capped Gold Nanoparticles Using Salvia officinalis Extract: Biochemical Characterization and Antimicrobial and Cytotoxic Activities.

Increasing antimicrobial resistance to the action of existing antibiotics has prompted researchers to identify new natural molecules with antimicrobial potential. In this study, a green system was developed for biosynthesizing gold nanoparticles (BAuNPs) using sage (Salvia officinalis L.) leaf extract bioconjugated with non-toxic, eco-friendly, and biodegradable chitosan, forming chitosan/gold bioconjugates (Chi/BAuNPs). Characterization of the BAuNPs and Chi/BAuNPs conjugates takes place using transmission electron microscopy (TEM), X-ray spectra, Fourier transform infrared (FT-IR) spectroscopy, and zeta potential (Z-potential). The chemical composition of S. officinalis extract was evaluated via gas chromatography/mass spectrometry (GC/MS). This study evaluated the antioxidant and antimicrobial activities of human pathogenic multidrug-resistant (MDR) and multisensitive (MS) bacterial isolates using the agar diffusion method. Chi/BAuNPs showed inhibition of the MDR strains more effectively than BAuNPs alone as compared with a positive standard antibiotic. The cytotoxicity assay revealed that the human breast adenocarcinoma cancer cells (MCF7) were more sensitive toward the toxicity of 5-Fu + BAuNPs and 5-Fu + Chi/BAuNPs composites compared to non-malignant human fibroblast cells (HFs). The study shows that BAuNPs and Chi/BAuNPs, combined with 5-FU NPs, can effectively treat cancer at concentrations where the free chemical drug (5-Fu) is ineffective, with a noted reduction in the required dosage for noticeable antitumor action.

Application of a novel lytic Jerseyvirus phage LPSent1 for the biological control of the multidrug-resistant Salmonella Enteritidis in foods.

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including milk, water, apple juice, and chicken breasts. One lytic phage (LPSent1) was selected based on its robust and stable lytic activity. Phage LPSent1 belonged to the genus Jerseyvirus within the Jerseyvirinae subfamily. The lysis time of phage LPSent1 was 60 min with a latent period of 30 min and each infected cell burst about 112 plaque-forming units. Phage LPSent1 showed a narrow host range. Furthermore, the LPSent1 genome did not encode any virulence or lysogenic genes. In addition, phage LPSent1 had wide pH tolerance, prolonged thermal stability, and was stable in food articles lacking its susceptible host for 48 h. In vitro applications of phage LPSent1 inhibited free planktonic cells and biofilms of Salmonella Enteritidis EG.SmE1 with a lower occurrence to form phage-resistant bacterial mutants which suggests promising applications on food articles. Application of phage LPSent1 at multiplicities of infections of 100 or 1000 showed significant inhibition in the bacterial count of Salmonella Enteritidis EG.SmE1 by 5 log10/sample in milk, water, apple juice, and chicken breasts at either 4°C or 25°C. Accordingly, taken together these findings establish phage LPSent1 as an effective, promising candidate for the biocontrol of MDR Salmonella Enteritidis in ready-to-eat food.

Isolation and Characterization of a Novel Lytic Phage, vB_PseuP-SA22, and Its Efficacy against Carbapenem-Resistant Pseudomonas aeruginosa.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a serious public health threat in multiple clinical settings. In this study, we detail the isolation of a lytic bacteriophage, vB_PseuP-SA22, from wastewater using a clinical strain of CRPA. Transmission electron microscopy (TEM) analysis identified that the phage had a podovirus morphology, which agreed with the results of whole genome sequencing. BLASTn search allowed us to classify vB_PseuP-SA22 into the genus Bruynoghevirus. The genome of vB_PseuP-SA22 consisted of 45,458 bp of double-stranded DNA, with a GC content of 52.5%. Of all the open reading frames (ORFs), only 26 (44.8%) were predicted to encode certain functional proteins, whereas the remaining 32 (55.2%) ORFs were annotated as sequences coding functionally uncharacterized hypothetical proteins. The genome lacked genes coding for toxins or markers of lysogenic phages, including integrases, repressors, recombinases, or excisionases. The phage produced round, halo plaques with a diameter of 1.5 ± 2.5 mm on the bacterial lawn. The TEM revealed that vB_PseuP-SA22 has an icosahedral head of 57.5 ± 4.5 nm in length and a short, non-contractile tail (19.5 ± 1.4 nm). The phage showed a latent period of 30 min, a burst size of 300 PFU/infected cells, and a broad host range. vB_PseuP-SA22 was found to be stable between 4-60 °C for 1 h, while the viability of the virus was reduced at temperatures above 60 °C. The phage showed stability at pH levels between 5 and 11. vB_PauP-SA22 reduced the number of live bacteria in P. aeruginosa biofilm by almost five logs. The overall results indicated that the isolated phage could be a candidate to control CRPA infections. However, experimental in vivo studies are essential to ensure the safety and efficacy of vB_PauP-SA22 before its use in humans.

Evaluation of phage-antibiotic combinations in the treatment of extended-spectrum ß-lactamase-producing Salmonella enteritidis strain PT1.

Foodborne infections caused by Salmonella spp. are among the most common foodborne diseases in the world. We isolated a lytic phage against extended-spectrum beta-lactam producing S. Enteritidis strain PT1 derived from chicken carcass. Results from electronmicrography indicated that phiPT1 belonged to the family, Siphoviridae, in the order, Caudovirales. Phage phiPT1 was stable at temperatures from 4 °C to 60 °C and inactivated at 90 °C. phiPT1 retained a high titer from pH 4 to pH 10 for at least 1 h. Nevertheless, it displayed a significant decrease (p < 0.05) in titer at pH 11 and 12, with phage titers of 5.5 and 2.4 log10 PFU/mL, respectively. The latent time and burst size of phiPT1 were estimated to be 30 min and 252 PFU/infected cell, respectively. The virulence of phage phiPT1 was evaluated against S. Enteritidis strain PT1 at different MOIs. phiPT1 reduced Salmonella proliferation relative to the negative control (MOI 0) at all MOIs (P < 0.05). However, there is no significant difference among the MOIs (P > 0.05). The phage-antibiotic combination analysis (PAS) indicated that synergism was not detected at higher phiPT1 titer (1012 PFU/mL) with all tested antibiotics at all subinhibitory concentrations. However, synergistic activities were recorded at 0.25 × MIC of four tested antibiotics: cefixime, gentamicin, ciprofloxacin, and aztreonam in combination with phage at 104, 106 and 108 PFU/mL (ΣFIC ≤0.5). Synergism was detected for all antibiotics (0.1 × MIC) except meropenem and colistin in combination with phiPT1 at 104, 106 and 108 PFU/mL (ΣFIC ≤0.5). Synergism also displayed at the lowest concentrations of all antibiotics (0.01 MIC) in combination with phiPT1 at all titers except 1012 PFU/mL. Such characteristic features make phiPT1 to be a potential candidate for therapeutic uses.

Isolation and Characterization of Chi-like Salmonella Bacteriophages Infecting Two Salmonella enterica Serovars, Typhimurium and Enteritidis

Salmonella enterica Serovar Typhimurium and Salmonella enterica Serovar Enteritidis are well-known pathogens that cause foodborne diseases in humans. The emergence of antibiotic-resistant Salmonella serovars has caused serious public health problems worldwide. In this study, two lysogenic phages, STP11 and SEP13, were isolated from a wastewater treatment plant in Jeddah, KSA. Transmission electron microscopic images revealed that both phages are new members of the genus "Chivirus" within the family Siphoviridae. Both STP11 and SEP13 had a lysis time of 90 min with burst sizes of 176 and 170 PFU/cell, respectively. The two phages were thermostable (0 °C ≤ temperature < 70 °C) and pH tolerant at 3 ≤ pH < 11. STP11 showed lytic activity for approximately 42.8% (n = 6), while SEP13 showed against 35.7% (n = 5) of the tested bacterial strains. STP11 and STP13 have linear dsDNA genomes consisting of 58,890 bp and 58,893 bp nucleotide sequences with G + C contents of 57% and 56.5%, respectively. Bioinformatics analysis revealed that the genomes of phages STP11 and SEP13 contained 70 and 71 ORFs, respectively. No gene encoding tRNA was detected in their genome. Of the 70 putative ORFs of phage STP11, 27 (38.6%) were assigned to functional genes and 43 (61.4%) were annotated as hypothetical proteins. Similarly, 29 (40.8%) of the 71 putative ORFs of phage SEP13 were annotated as functional genes, whereas the remaining 42 (59.2%) were assigned as nonfunctional proteins. Phylogenetic analysis of the whole genome sequence demonstrated that the isolated phages are closely related to Chi-like Salmonella viruses.

The "Big Six": Hidden Emerging Foodborne Bacterial Pathogens.

Non-O157 Shiga toxin-producing Escherichia coli (STEC) are emerging serogroups that often result in diseases ranging from diarrhea to severe hemorrhagic colitis in humans. The most common non-O157 STEC are O26, O45, O103, O111, O121, and O145. These serogroups are known by the name "big six" because they cause severe illness and death in humans and the United States Department of Agriculture declared these serogroups as food contaminants. The lack of fast and efficient diagnostic methods exacerbates the public impact of the disease caused by these serogroups. Numerous outbreaks have been reported globally and most of these outbreaks were caused by ingestion of contaminated food or water as well as direct contact with reservoirs. Livestock harbor a variety of non-O157 STEC serovars that can contaminate meat and dairy products, or water sources when used for irrigation. Hence, effective control and prevention approaches are required to safeguard the public from infections. This review addresses the disease characteristics, reservoirs, the source of infections, the transmission of the disease, and major outbreaks associated with the six serogroups ("big six") of non-O157 STEC encountered all over the globe.

Study the apoptosis and necrosis inducing of fosfomycin into associated infected urothelial tissue by extended spectrum beta lactamase positive of E. coli.

Urinary tract infection is among the greatest prevalent infections, and it is also one of the most challenging diseases to treat because there are germs that are resistant to several drugs. Antibiotics are typically provided as the treatment; however, there is a disparity in the type of antibiotic that was being prescribed, the amount of the dosage, and the length of time that patients were required to take antibiotics, which led to the creation of multidrug-resistant infections. The objective of this research is to prescribe Fosfomycin treatment for the infection brought by the Escherichia coli bacterium and to determine whether or not it is effective. Throughout the course of this research, the antimicrobial drugs fosfomycin were factored in the equation at various points. The patients who had exhibited symptoms of urinary tract infection provided their urine for the purpose of giving a sample for the studies, which were carried out on them. The results of these studies showed that there were Fosfomycin antimicrobials that were successful in disrupting the E. coli bacteria, and the least inhibitory concentration (MIC) required for the pathogen to be vulnerable was quite low. In addition, administration of fosfomycin intravenously considerably lowers both the bacterial load and the inflammatory infiltration in the kidney and bladder, which helps to preserve the structural integrity of the kidney.

Bacteriophage-Based Biosensors: A Platform for Detection of Foodborne Bacterial Pathogens from Food and Environment.

Foodborne microorganisms are an important cause of human illness worldwide. Two-thirds of human foodborne diseases are caused by bacterial pathogens throughout the globe, especially in developing nations. Despite enormous developments in conventional foodborne pathogen detection methods, progress is limited by the assay complexity and a prolonged time-to-result. The specificity and sensitivity of assays for live pathogen detection may also depend on the nature of the samples being analyzed and the immunological or molecular reagents used. Bacteriophage-based biosensors offer several benefits, including specificity to their host organism, the detection of only live pathogens, and resistance to extreme environmental factors such as organic solvents, high temperatures, and a wide pH range. Phage-based biosensors are receiving increasing attention owing to their high degree of accuracy, specificity, and reduced assay times. These characteristics, coupled with their abundant supply, make phages a novel bio-recognition molecule in assay development, including biosensors for the detection of foodborne bacterial pathogens to ensure food safety. This review provides comprehensive information about the different types of phage-based biosensor platforms, such as magnetoelastic sensors, quartz crystal microbalance, and electrochemical and surface plasmon resonance for the detection of several foodborne bacterial pathogens from various representative food matrices and environmental samples.

Mitigative Potential of Novel Lactobacillus plantarum TISTR 2076 against the Aflatoxins-Associated Oxidative Stress and Histopathological Alterations in Liver and Kidney of Broiler Chicks during the Entire Growth Period.

Aflatoxins are the secondary metabolites produced by Aspergillus flavus and Aspergillus parasiticus and have severe pathological effects on the health of human and animals. The present study was designed to investigate the toxicopathological changes induced by aflatoxins and mitigative potential of Lactobacillus plantarum in broiler birds. One hundred and eighty broiler chicks at one day of age was procured from the local market, and chicks were equally divided into six groups with thirty birds in each group. These birds were treated with aflatoxins (300 and 600 µg/kg) and Lactobacillus plantarum (1 × 108 cfu/kg of feed) in different combinations. The first group was kept as the control, and only a basal diet was provided to birds (BD). In the second group (AF1), the first level of aflatoxins (300 µg/kg) was fed to the birds. In the third group (AF2), the second level of aflatoxins (600 µg/kg) was fed to birds. In the fourth group (AF1LP), Lactobacillus plantarum was given with first level of aflatoxins. In the fifth group (AF2LP), Lactobacillus plantarum was given with the second level of aflatoxins, and in the 6th group (BDLP), Lactobacillus plantarum alone was fed to the chicks. This experimental study was continued for 42 days. Birds were slaughtered after 42 days, and different parameters were assessed. Parameters studied were gain in body weight, organ weight along with some histopathological, hematological, biochemical parameters and residues of aflatoxins in liver and kidney. Lactobacillus plantarum improved the body weight gain and restored the relative organ weight. Hepatic and renal biomarkers returned to normal concentrations, serum proteins were restored in combination group AF1LP, and partial amelioration was observed in the AF2LP group. Red blood cells, white blood cells, hemoglobin centration and packed cell volume became normalized in the AF1LP group, while partial amelioration was observed in the AF2LP group. LP also reduced the concentration of aflatoxin residues in liver kidney and improved the TAC concentrations. The results of this study elucidated the mitigative potential of Lactobacillus plantarum against serum biochemical, histopathological, hematological and toxicopathological changes induced by aflatoxins in the chicks.

Floral markers and biological activity of Saudi honey.

The objectives of this research were to identify certain chemical compounds that may be used as fingerprints of Saudi honey and to evaluate their antioxidant and antibacterial activities. Eleven Saudi 'monofloral' honey samples were analyzed and evaluated. Non-phenolic compounds, such as 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, methyl 3-hydroxyhexanaote and 5-hydroxymethyl-2-furancarboxaldehyde were present in different types of tested honey samples. Glyceraldehyde was only detected in five of the honey samples tested. The most promising result was the detection of an alkaloid (by using GC-MS) in only two types of Saudi honey samples. This alkaloid may be of great importance and has the potential to be used as a fingerprint marker for the botanical sources of the various honey samples tested. This alkaloid was present in Toran and Saha. The detected compound is 2-amino-4-hydroxypteridine-6-carboxylic acid, which may originate from the degradation of folic acid as identified by previous studies. These findings can be used as a gateway to obtain a fingerprint for these two types of honey samples and can potentially be used to track any impurities in honey sold on the market. All of the tested honey samples showed antioxidant and antibacterial activities. The highly effective activity was in Toran honey against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus (MRSA). Shafalah honey was effective against MRSA and Acinetobacter baumannii which showed bactericidal effects at concentrations 70-100%. This study also examined the antioxidant activity of honey samples using the DPPH assay. DPPH values of tested honey samples varied between 53.93 ±â€¯0.21%, as the highest value and 5.89 ±â€¯0.125%, as the lowest value. Significant correlations between the antibacterial and the antioxidant activities of the tested honey samples were noticed. The corresponding total phenolic contents (TPC) values supported the fact that phenolic compounds enhanced the antibacterial activity. The study revealed that some of the locally produced honey samples, specifically Zaitoon, Shaflah, Saha, Rabea Aja and Bareq contained the monosaccharides called glyceraldehydes which was the precursor to produce methylglyoxal (MGO) compound, which has antibacterial effects as documented in several previous studies. There was no clear relationship between these activities and the sum total of phenolic compounds present in Saudi honey.