Integrated Pangenome Analysis and Pharmacophore Modeling Revealed Potential Novel Inhibitors against Enterobacter xiangfangensis

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for E. xiangfangensis. In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of E. xiangfangensis using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, Adenine, Mollugin, Xanthohumol C, Sakuranetin, and Toosendanin demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand–protein complexes and revealed that these compounds could serve as potential E. xiangfangensis replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against E. xiangfangensis. Future studies should validate these targets experimentally to prove their function in E. xiangfangensis survival and virulence

Cinnamon and ginger extracts attenuate diabetes-induced inflammatory testicular injury in rats and modulating SIRT1 expression

The current study aimed to evaluate the efficacy of simultaneous administration of Zingiber officinale (ginger) and Cinnamomum cassia (cinnamon) extracts in mitigating testicular changes associated with diabetes mellitus in rats and to investigate its molecular mode of action. After induction of diabetes using streptozotocin, 36 male rats were divided to six groups namely control, diabetic, metformin-treated, cinnamon-treated, ginger-treated and combined, each group having 6 rats. Fasting blood glucose, serum insulin, testosterone was measured. Expression of inflammatory mediators; tumor necrosis factor-alpha (TNF-α), Nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) was assessed in the testicular tissue. Histopathological changes in the testis were observed and spermatogenesis and apoptosis were assessed immunohistochemically. The histological and biochemical studies of the untreated group confirmed structural changes in testes induced by diabetes. Oral administration of ginger and cinnamon increased insulin level significantly increased while the blood glucose level significantly decreased in diabetic rats, improving structural testicular changes considerably. Joint intake of ginger and cinnamon increased antihyperglycemic, antioxidant and anti-inflammatory effects markedly improving the testicular injury compared to the administration of either of them. SIRT1 expression in the testis significantly increased in ginger plus cinnamon-treated rats. These results indicate that when administrated together, ginger and cinnamon synergistically enhanced antioxidant, antiapoptotic and anti-inflammatory effects and induced antihyperglycemic effect comparable to metformin. The combination of ginger and cinnamon also upregulated SIRT1 in the testis

Bacterial Endophytes as a Promising Approach to Enhance the Growth and Accumulation of Bioactive Metabolites of Three Species of Chenopodium Sprouts

Sprouts are regarded as an untapped source of bioactive components that display various biological properties. Endophytic bacterium inoculation can enhance plant chemical composition and improve its nutritional quality. Herein, six endophytes (Endo 1 to Endo 6) were isolated from Chenopodium plants and morphologically and biochemically identified. Then, the most active isolate Endo 2 (strain JSA11) was employed to enhance the growth and nutritive value of the sprouts of three Chenopodium species, i.e., C. ambrosoides, C. ficifolium, and C. botrys. Endo 2 (strain JSA11) induced photosynthesis and the mineral uptake, which can explain the high biomass accumulation. Endo 2 (strain JSA11) improved the nutritive values of the treated sprouts through bioactive metabolite (antioxidants, vitamins, unsaturated fatty acid, and essential amino acids) accumulation. These increases were correlated with increased amino acid levels and phenolic metabolism. Consequently, the antioxidant activity of the Endo 2 (strain JSA11)-treated Chenopodium sprouts was enhanced. Moreover, Endo 2 (strain JSA11) increased the antibacterial activity against several pathogenic bacteria and the anti-inflammatory activities as evidenced by the reduced activity of cyclooxygenase and lipoxygenase. Overall, the Endo 2 (strain JSA11) treatment is a successful technique to enhance the bioactive contents and biological properties of Chenopodium sprouts

Preoperative Imaging Modalities to Predict the Risk of Regional Nodal Recurrence in Well-Differentiated Thyroid Cancers

Abstract Introduction Thyroid cancer incidence has increased in the previous 2 decades. Preoperative identification of lymph node metastasis is a suggested risk factor associated with recurrence following thyroidectomy. Objectives We aimed to evaluate the accuracy of preoperative radiologic investigations of nodal status in determining the postoperative risk of regional nodal recurrence in cases of well-differentiated thyroid cancer. Methods This is a case series. We retrospectively reviewed data, including preoperative ultrasonography and/or computed tomography results, on patients who underwent total thyroidectomy for thyroid cancer at our hospital between 2006 and 2012. Prognostic factors for predicting recurrence, including age, sex, tumor diameter, and nodal diameter, were evaluated. Results Total thyroidectomy was performed on 24 male and 74 female patients (median age, 43 years). The median follow-up time was 21 months. Sixty-eight patients had papillary thyroid cancer, and 30 had follicular cancer. Nodal recurrence was evident in 30% of patients, and 4% of patients died. Identification of lymph node involvement during preoperative radiologic investigations was strongly prognostic for recurrence: 35.3% of patients with positive preoperative ultrasonography findings and 62.5% of those with positive preoperative computed tomography findings had recurrence (p = 0.01). Conclusions Preoperative identification of lymph node metastasis on radiologic studies was correlated with an increased risk of regional nodal recurrence in well-differentiated thyroid cancer. Computed tomography was superior to ultrasonography in detecting metastatic nodal involvement preoperatively and is therefore recommended for preoperative assessment and postoperative follow-up

Photocatalytic and Antimicrobial Activities of Biosynthesized Silver Nanoparticles Using <i>Cytobacillus firmus</i>

The toxicity of the ecosystem has increased recently as a result of the increased industrial wastewater loaded with organic contaminants, including methylene blue (MB), which exerts serious damage to the environment. Thus, the present work aims to green the synthesis of silver nanoparticles (Ag-NPs) and to evaluate their degradability of notorious MB dye, as well as their antimicrobial activities. Ag-NPs were synthesized by Cytobacillus firmus extract fully characterized by UV-vis, TEM, DLS, XRD, and FTIR. Ag-NPs showed good antibacterial and antifungal activities against Escherichia coli ATCC 25922, Enterococcus feacalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and Candida albicans ATCC 90028. Moreover, Ag-NPs exhibited a high biodegradability level (98%) of MB dye after 8 h of co-incubation in the presence of sunlight. Additionally, the phytotoxicity of treated MB dye-contaminated water sample showed good germination of Vicia faba as compared with non-treated MB dye-contaminated solution. In conclusion, the herein biosynthesized Ag-NPs demonstrated its feasibility of the purification of contaminated water from microbes and methylene blue dye and the probability of reusing purified water for agricultural purposes

Dynamic Gene Clusters Mediating Carbapenem-Resistant <i>Acinetobacter baumannii</i> Clinical Isolates

Acinetobacter baumanni (A. baumannii), a nonfermenting Gram-negative bacterium, has recently been associated with a broad range of nosocomial infections. To gain more meaningful insight into the problem of nosocomial illnesses caused by the multidrug-resistant (MDR) A. baumannii, as well as the factors that increase the risk of catching these infections, this investigation included a total of 86 clinical A. baumannii infections. Repetitive extragenic palindromic (REP)-PCR was used to investigate imipenem-resistant A. baumannii isolates for dynamic gene clusters causing carbapenem resistance. Four distinct A. baumannii lineages were found in the REP-PCR-DNA fingerprints of all isolates, with 95% of the samples coming from two dominant lineages. Imipenem, amikacin, and ciprofloxacin were less effective against genotype (A) isolates because of enhanced antibiotic tolerance. Lastly, to gain more insight into the mode of action of imipenem, we explored the binding affinity of imipenem toward different Acinetobacter baumannii OXA beta-lactamase class enzymes

Anti-<i>Salmonella</i> and Antibiofilm Potency of <i>Salvia officinalis</i> L. Essential Oil against Antibiotic-Resistant <i>Salmonella enterica</i>

Raw milk is a significant vehicle for the transmission of different infections. In the present study, we focused on Salmonella enterica from raw milk and its resistance to various antibacterial drugs. Furthermore, we have investigated the antimicrobial and antibiofilm effects of essential oil (EO) obtained from Salvia officinalis L. leaves that were collected from the Aljouf region, Saudi Arabia, against S. enterica. One-dozen strains of S. enterica were found in a batch of a hundred milk samples, and those S. enterica strains were shown to be resistant to several antibiotics, particularly the β-lactam group of antimicrobial drugs. Against multidrug-resistant S. enterica, the inhibitory zones for EO from S. officinalis leaves were found to be 21 mm in diameter. S. officinalis EO at 5% concentration showed a remarkable in vitro inhibitory activity toward the biofilm growth of different S. enterica isolates. Analysis of EO by GC–MS identified 21 distinct components, accounting for 89.94% of the total oil component. The most prominent compounds were 1,8-cineole (39.18%), β-caryophyllene (12.8%), and α--terpineol (10.3%). Taken together, our results unequivocally confirm that the S. officinalis EOs exert numerous bioactivities. Thus, the well-deserved attention on S. officinalis EO usage as a food preservative and adjunctive remedy for bacterial food-borne diseases is justified

Incidence of Vancomycin-Resistant <i>Staphylococcus aureus</i> Strains among Patients with Urinary Tract Infections

There has been a substantial rise in the number of vancomycin-resistant Staphylococcus aureus (VRSA) strains during the last several years. The proportion of vancomycin-resistant strains among isolated S. aureus has risen steadily in recent years, with the first spike occurring in critical care units and thereafter in general hospital wards. S. aureus isolates from urinary tract infection patients were studied for their prevalence and antibiotic resistance. From 292 urine samples, 103 bacterial strains (35.3%) were identified as S. aureus. Various antibiotics were used to test the isolates’ antibacterial resistance profiles. Antibiotic resistance to erythromycin was found in most bacterial isolates, whereas tobramycin antibiotic sensitivity was found in most of them. Vancomycin resistance was found in 23 of all S. aureus isolates in this study. Analysis for β-lactamase found that 71% of S. aureus isolates were positive in all isolates. There was a single plasmid with a molecular weight of 39.306 Kbp in five selected VRSA isolates that was subjected to plasmid analysis. There was evidence of vancomycin resistance among the S. aureus isolates collected from UTI patients in this investigation. This vancomycin resistance pretenses a challenge in the treatment of S. aureus infections and the need to precisely recognize persons who require last-resort medication such as tobramycin

Anti-Salmonella and Antibiofilm Potency of Salvia officinalis L. Essential Oil against Antibiotic-Resistant Salmonella enterica

Raw milk is a significant vehicle for the transmission of different infections. In the present study, we focused on Salmonella enterica from raw milk and its resistance to various antibacterial drugs. Furthermore, we have investigated the antimicrobial and antibiofilm effects of essential oil (EO) obtained from Salvia officinalis L. leaves that were collected from the Aljouf region, Saudi Arabia, against S. enterica. One-dozen strains of S. enterica were found in a batch of a hundred milk samples, and those S. enterica strains were shown to be resistant to several antibiotics, particularly the &beta;-lactam group of antimicrobial drugs. Against multidrug-resistant S. enterica, the inhibitory zones for EO from S. officinalis leaves were found to be 21 mm in diameter. S. officinalis EO at 5% concentration showed a remarkable in vitro inhibitory activity toward the biofilm growth of different S. enterica isolates. Analysis of EO by GC&ndash;MS identified 21 distinct components, accounting for 89.94% of the total oil component. The most prominent compounds were 1,8-cineole (39.18%), &beta;-caryophyllene (12.8%), and &alpha;--terpineol (10.3%). Taken together, our results unequivocally confirm that the S. officinalis EOs exert numerous bioactivities. Thus, the well-deserved attention on S. officinalis EO usage as a food preservative and adjunctive remedy for bacterial food-borne diseases is justified

In vitro and in silico biopotentials of phytochemical compositions and antistaphylococcal and antipseudomonal activities of volatile compounds of Argania spinosa (L.) seed oil

Active components in medicinal plants provide unlimited useful and traditional medicines. Antimicrobial activities are found in secondary metabolites in plant extracts such as argan oil. This experimental investigation aims to determine argan oil’s volatile compounds and examine their in vitro antimicrobial properties. In silico simulations, molecular docking, pharmacokinetics, and drug-likeness prediction revealed the processes underlying the in vitro biological possessions. Gas chromatography–mass spectrometry (GC/MS) was used to screen argan oil’s primary components. In silico molecular docking studies were used to investigate the ability of the selected bioactive constituents of argan oil to act effectively against Pseudomonas aeruginosa and Staphylococcus aureus (S. aureus) isolated from infections. The goal was to study their ability to interact with both bacteria’s essential therapeutic target protein. The 21 chemicals in argan oil were identified by GC/MS. Docking results for all compounds with S. aureus and P. aeruginosa protease proteins ranged from −5 to −9.4 kcal/mol and −5.7 to −9.7 kcal/mol, respectively, compared to reference ligands. Our docking result indicates that the 10-octadecenoic acid, methyl ester was the most significant compound with affinity scores of −9.4 and −9.7 kcal/mol for S. aureus and P. aeruginosa proteins, respectively. The minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC) of argan oil were 0.7 ± 0.03 and 0.5 ± 0.01 for S. aureus and 0.4 ± 0.01 and 0.3 ± 0.02 for P. aeruginosa, respectively. We confirmed the antimicrobial properties of argan oil that showed significant growth inhibition for S. aureus and P. aeruginosa