Antagonistic and enzymatic activities of Bacillus species isolated from the fish gastrointestinal tract as potential probiotics use in Artemia culture.

Probiotics have been used successfully in aquaculture to enhance disease resistance, nutrition, and/or growth of cultured organisms. Six strains of Bacillus were isolated from the intestinal tracts of fish and recognised by conventional biochemical traits. The six isolated strains were Bacillus cereus and Bacillus subtilis using MALDI-TOF-MS technique. The probiotic properties of these Bacillus strains were studied. The tested bacillus strains exhibit antibacterial activity against the different pathogens. The strain S5 gave the important inhibition zones against most pathogens (20.5, 20.33, 23, and 21 mm against Vibrio alginolyticus, Vibrio parahaemolyticus, Staphylococcus aureus, and Salmonella typhimurium, respectively). According to our results, all Bacillus strains have extracellular components that can stop pathogenic bacteria from growing. The enzymatic characterization showed that the tested strains can produce several biotechnological enzymes such as α-glucosidase, naphtol-AS-BI-Phosphohydrolase, esterase lipase, acid phosphatase, alkaline phosphatase, amylase, lipase, caseinase, and lecithinase. All Bacillus strains were adhesive to polystyrene. The adding Bacillus strains to the Artemia culture exerted significantly greater effects on the survival of Artemia. The challenge test on Artemia culture showed that the protection against pathogenic Vibrio was improved. These findings allow us to recommend the examined strains as prospective probiotic options for the Artemia culture, which will be used as food additives to improve the culture conditions of crustacean larvae and marine fish.

Improving the anti-diabetic and anti-hyperlipidemic activities of extra virgin olive oil by the incorporation of diallyl sulfide.

Development of novel functional foods is trending as one of the hot topics in food science and food/beverage industries. In the present study, the anti-diabetic, anti-hyperlipidemic and histo-protective effects of the extra virgin olive oil (EVOO) enriched with the organosulfur diallyl sulfide (DAS) (DAS-rich EVOO) were evaluated in alloxan-induced diabetic mice. The ingestion of EVOO (500µL daily for two weeks) attenuated alloxan-induced elevated glucose, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), urea and creatinine. It also normalized the levels of triglycerides (TG), total cholesterols (TC), low-density lipoprotein-cholesterol (LDL-c) and their consequent atherogenic index of plasma (AIP) in diabetic animals. Additionally, EVOO prevented lipid peroxidation (MDA) and reduced the level of hydrogen peroxide (H2O2) in diabetic animals. Concomitantly, it enhanced the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), reducing thereby tissue oxidative stress injury. The overall histologic (pancreas, liver, and kidney) alterations were also improved after EVOO ingestion. The manifest anti-diabetic, lipid-lowering and histo-protective properties of EVOO were markedly potentiated with DAS-rich EVOO suggesting possible synergistic interactions between DAS and EVOO lipophilic bioactive ingredients. Overall, EVOO and DAS-rich EVOO show promise as functional foods and/or adjuvants for the treatment of diabetes and its complications.

Green synthesis and characterization of silver nanoparticles from Ducrosia flabellifolia Boiss. aqueous extract: Anti-quorum sensing screening and antimicrobial activities against ESKAPE pathogens.

Biosynthesis of silver nanoparticles using natural compounds derived from plant kingdom is currently used as safe and low-cost technique for nanoparticles synthesis with important abilities to inhibit multidrug resistant microorganisms (MDR). ESKAPE pathogens, especially MDR ones, are widely spread in hospital and intensive care units. In the present study, AgNPs using Ducrosia flabellifolia aqueous extract were synthesized using a reduction method. The green synthesized D. flabellifolia-AgNPs were characterized by UV-Vis spectrophotometer, Scanning electron microscopy (SEM), and X-ray diffraction assays. The tested D. flabellifolia aqueous extract was tested for its chemical composition using Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS). Anti-quorum sensing and anti-ESKAPE potential of D. flabellifolia-AgNPs was also performed.  Results from LC-ESI-MS technique revealed the identification of chlorogenic acid, protocatechuic acid, ferulic acid, caffeic acid, 2,5-dihydroxybenzoic acid, and gallic acid as main phytoconstituents. Indeed, the characterization of newly synthetized D. flabellifolia-AgNPs revealed spherical shape with mean particle size about 16.961±2.914 nm. Bio-reduction of silver was confirmed by the maximum surface plasmon resonance of D. flabellifolia-AgNPs at 430 nm. Newly synthetized D. flabellifolia-AgNPs were found to possess important anti-ESKAPE activity with low minimal inhibitory concentrations (MICs) ranging from 0.078 to 0.312 mg/mL, and low minimal bactericidal concentrations (MBCs) varying from 0.312 to 0.625 mg/mL. Moreover, D. flabellifolia-AgNPs were active against Candida utilis ATCC 9255, C. tropicalis ATCC 1362, and C. albicans ATCC 20402 with high mean diameter of growth inhibition at 5 mg/mL, low MICs, and minimal fungicidal concentrations values (MFCs). The newly synthetized D. flabellifolia-AgNPs were able to inhibit violacein production in Chromobacterium violaceum, pyocyanin in Pseudomonas aeruginosa starter strains.  Hence, the newly synthesized silver nanoparticles using D. flabellifolia aqueous extract can be used as an effective alternative to combat ESKAPE microorganisms. These silver nanoparticles can attenuate virulence of Gram-negative bacteria by interfering with the quorum sensing system and inhibiting cell-to-cell communication.

GC-MS screening of the phytochemical composition of Ziziphus honey: ADME properties and in vitro/in silico study of its antimicrobial activity.

A revival interest has been given to natural products as sources of phytocompounds to be used as alternative treatment against infectious diseases. In this context, we aimed to investigate the antimicrobial potential of Ziziphus honey (ZH) against twelve clinical bacterial strains and several yeasts and molds using in vitro and computational approaches. The well-diffusion assay revealed that ZH was able to induce growth inhibition of most Gram-positive and Gram-negative bacteria. The high mean growth inhibition zone (mGIZ) was recorded in E. coli (Clinical strain, 217), S. aureus followed by E. coli ATCC 10536 (mGIZ values: 41.00 ± 1 mm, 40.67 ± 0.57 mm, and 34.67 ± 0.57 mm, respectively). The minimal bactericidal concentrations (MBCs) and minimal fungicidal concentration values (MFCs) from approximately 266.33 mg/mL to over 532.65 mg/mL. Molecular docking results revealed that the identified compounds maltose, 2-furoic acid, isopropyl ester, 2,4-imidazolidinedione, 5-(2-methylpropyl)-(S)- and 3,4,5-trihydroxytoluene, S-Methyl-L-Cysteine, 2-Furancarboxylic acid, L-Valine-N-ethoxycarbonyl, Hexanoic acid, 3,5,5-trimethyl-, Methyl-beta-D-thiogalactoside, gamma-Sitosterol, d-Mannose, 4-O-Methylmannose, 2,4-Imidazolidinedione, 5-(2-methylpropyl)- (S) were found to have good affinity for targeted receptor, respectively. Through a 100-ns dynamic simulation research, binding interactions and stability between promising phytochemicals and the active residues of the studied enzymes were confirmed. The ADMET profiling of all identified compounds revealed that most of them could be qualified as biologically active with good absorption and permeation. Overall, the results highlighted the efficiency of ZH against the tested clinical pathogenic strains. The antimicrobial potential and the potency displayed by the identified compounds could imply their further pharmacological applications.Communicated by Ramaswamy H. Sarma.

Methicillin-Resistant Staphylococcus aurous: Epidemiology, Transmission and New Alternative Therapies: A Narrative Review.

Over the last decade, we were facing medical struggle by the emergence of multi-resistant bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA). MRSA infections are still causing a growing global concern due to the rapid adaptive multidrug resistance to conventional antibiotics in human, community and veterinary medicine. Here we provide an overview about MRSA epidemiology, transmission and alternative potential treatments particularly new discovered phytochemicals with biological activity. In this narrative review, bibliographic data was collected from literature search databases: Google Scholar, web of science and PubMed/MEDLINE during recent years (2016 to 2021). MRSA is responsible of wide spectrum life threatening infections such us septicemia, endocarditis, and wound infections. It has epidemic potential in hospitals, that is responsible of most nosocomial infections leading to mortality and constitute a real burden for the healthcare systems. Effective preventive strategies for management of MRSA are highly required moreover, the identification and development of novel drugs or active biomolecules through phytochemicals are time challenging to face new resistant strains.

Therapeutic Role of ELOVL in Neurological Diseases.

Fatty acids play an important role in controlling the energy balance of mammals. De novo lipogenesis also generates a significant amount of lipids that are endogenously produced in addition to their ingestion. Fatty acid elongation beyond 16 carbons (palmitic acid), which can lead to the production of very long chain fatty acids (VLCFA), can be caused by the rate-limiting condensation process. Seven elongases, ELOVL1-7, have been identified in mammals and each has a unique substrate specificity. Researchers have recently developed a keen interest in the elongation of very long chain fatty acids protein 1 (ELOVL1) enzyme as a potential treatment for a variety of diseases. A number of neurological disorders directly or indirectly related to ELOVL1 involve the elongation of monounsaturated (C20:1 and C22:1) and saturated (C18:0-C26:0) acyl-CoAs. VLCFAs and ELOVL1 have a direct impact on the neurological disease. Other neurological symptoms such as ichthyotic keratoderma, spasticity, and hypomyelination have also been linked to the major enzyme (ELOVL1). Recently, ELOVL1 has also been heavily used to treat a number of diseases. The current review focuses on in-depth unique insights regarding the role of ELOVL1 as a therapeutic target and associated neurological disorders.

Computational insight into structural basis of human ELOVL1 inhibition.

Very long-chain fatty acids (VLCFAs) play a direct role in the development of a neurological disorder, X-linked adrenoleukodystrophy (X-ALD). Since ELOVL1 catalyzes the rate-limiting step of the synthesis of VLCFAs, it has emerged as an attractive target for the treatment of X-ALD. Recently two potent inhibitors, compound 22 (C22) and compound 27 (C27) have been reported to specifically inhibit human ELOVL1 but their structural basis of inhibition has not been explored. In the present study, we have used a homology model of human ELOVL1 to deduce the binding site and binding modes of C22 and C27. We have employed computational approaches to characterize the binding of C22 and C27. Initially, binding of hexacosanoyl-CoA (C26:0-CoA) to ELOVL1 was modelled and further validated by molecular dynamics (MD) simulation. We observed that the fatty acid tail of C26: CoA protrudes from a unique opening located at the occluded end of ELOVL1. Structural comparison of ELOVL1 with the crystal structure of ELOVL7 revealed that the unique opening was not present in human ELOVL7. Combined blind and focused molecular docking approaches revealed that C22 and C27 exhibit favourable binding in the same unique opening. Further, MD simulations and free binding energy calculations confirmed that C22 and C27 maintain the favourable binding in the unique opening of ELOVL1. Overall, our findings suggest that selective human ELOVL1 inhibitors block the binding of long tails of VLCFAs near the occluded end of ELOVL1. Present study will be helpful in the discovery and design of novel, selective and potent inhibitors of human ELOVL1.

Molecular Identification of Bacteria Isolated from Marketed Sparus aurata and Penaeus indicus Sea Products: Antibiotic Resistance Profiling and Evaluation of Biofilm Formation.

BACKGROUND: Marketed fish and shellfish are a source of multidrug-resistant and biofilm-forming foodborne pathogenic microorganisms. METHODS: Bacteria isolated from Sparus aurata and Penaeus indicus collected from a local market in Hail region (Saudi Arabia) were isolated on selective and chromogenic media and identified by using 16S RNA sequencing technique. The exoenzyme production and the antibiotic susceptibility patterns of all identified bacteria were also tested. All identified bacteria were tested for their ability to form biofilm by using both qualitative and quantitative assays. RESULTS: Using 16S RNA sequencing method, eight genera were identified dominated by Vibrio (42.85%), Aeromonas (23.80%), and Photobacterium (9.52%). The dominant species were V. natrigens (23.8%) and A. veronii (23.80%). All the identified strains were able to produce several exoenzymes (amylases, gelatinase, haemolysins, lecithinase, DNase, lipase, and caseinase). All tested bacteria were multidrug-resistant with a high value of the multiple antibiotic index (MARI). The antibiotic resistance index (ARI) was about 0.542 for Vibrio spp. and 0.553 for Aeromonas spp. On Congo red agar, six morphotypes were obtained, and 33.33% were slime-positive bacteria. Almost all tested microorganisms were able to form a biofilm on glass tube. Using the crystal violet technique, the tested bacteria were able to form a biofilm on glass, plastic, and polystyrene abiotic surfaces with different magnitude. CONCLUSIONS: Our findings suggest that marketed S. aurata and P. indicus harbor various bacteria with human interest that are able to produce several related-virulence factors.

Multifunctional Derivatives of Spiropyrrolidine Tethered Indeno-Quinoxaline Heterocyclic Hybrids as Potent Antimicrobial, Antioxidant and Antidiabetic Agents: Design, Synthesis, In Vitro and In Silico Approaches.

To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with 5d being the most potent (MIC 3.95 mM against Staphylococcus aureus ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly 5c, exhibiting the strongest activity with IC50 of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their α-amylase inhibitory effect, the examined analogues display a variable degree of α-amylase activity with IC50 ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC50 1.19 ± 0.02 mM), with the most active compounds being 5d, followed by 5c and 5j, affording IC50 of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure-activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.

Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties of Acacia Honey from the Hail Region: The in vitro and in silico Investigation.

In consideration of the emergence of novel drug-resistant microbial strains and the increase in the incidences of various cancers throughout the world, honey could be utilized as a great alternative source of potent bioactive compounds. In this context, this study pioneers in reporting the phytochemical profiling and the antimicrobial, antioxidant, and anticancer properties of Acacia honey (AH) from the Hail region of Saudi Arabia, assessed using in vitro and molecular docking approaches. The phytochemical profiling based on high-resolution liquid chromatography-mass spectrometry (HR-LCMS) revealed eight compounds and three small peptide-like proteins as the constituents. The honey samples exhibited promising antioxidant activities (DPPH-IC50 = 0.670 mg/mL; ABTS-IC50 = 1.056 mg/mL; ß-carotene-IC50 > 5 mg/mL). In the well-diffusion assay, a high mean growth inhibition zone (mGIZ) was observed against Staphylococcus aureus (48.33 ± 1.53 mm), Escherichia coli ATCC 10536 (38.33 ± 1.53 mm), and Staphylococcus epidermidis ATCC 12228 (39.33 ± 1.15 mm). The microdilution assay revealed that low concentrations of AH could inhibit the growth of almost all the evaluated bacterial and fungal strains, with the minimal bactericidal concentration values (MBCs) ranging from 75 mg/mL to 300 mg/mL. On the contrary, high AH concentrations were required to kill the tested microorganisms, with the minimal bactericidal concentration values (MBCs) ranging from approximately 300 mg/mL to over 600 mg/mL and the minimal fungicidal concentration values (MFCs) of approximately 600 mg/mL. The AH exhibited effective anticancer activity in a dose-dependent manner against breast (MCF-7), colon (HCT-116), and lung (A549) cancer cell lines, with the corresponding IC50 values of 5.053 µg/mL, 5.382 µg/mL, and 6.728 µg/mL, respectively. The in silico investigation revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of AH are thermodynamically feasible, particularly those of the tripeptides (Asp-Trp-His and Trp-Arg-Ala) and aminocyclitol glycoside. The overall results highlighted the potential of AH as a source of bioactive compounds with significant antimicrobial, antioxidant, and anticancer activities, which could imply further pharmacological applications of AH.

The "Molecular Biodiversity of Bacteria Isolated from Medicago sativa Rhizosphere in Hail District, Saudi Arabia.

Global biodiversity is affected remarkably by global climate change, which in turn its effect reflected on all life aspects. Identifying microorganisms in environmental samples, particularly soil could be a valuable interest to study their effect on soil quality and plant growth. Through this study, we conducted a molecular characterization of bacteria found in the rhizosphere of Medico sativa plants grown in Hail soil and we highlighted their main properties. The sequences analyses revealed that the main bacterial isolates Pseudarthrobacter, Metabacillus, Priestia, and Massilia species. According to the sequences analysis and the phylogeny tree results, some of the identified bacteria were classified at the species level: Pseudarthrobacter was identified clearly as Pseudarthrobacter phenanthrenivorans; Metabacillus isolates grouped with Metabacillus sediminilitoris and the two Priestia isolates closely related to Priestia aryabhattai. We concluded that Hail soil is a niche of diverse bacteria with a high interest in soil environment and ecosystems. Further studies are required for further classification of all identified bacteria and to define their specific role in the environment.

Lactiplantibacillus plantarum-Derived Biosurfactant Attenuates Quorum Sensing-Mediated Virulence and Biofilm Formation in Pseudomonas aeruginosa and Chromobacterium violaceum.

Quorum sensing (QS) controls the expression of diverse biological traits in bacteria, including virulence factors. Any natural bioactive compound that disables the QS system is being considered as a potential strategy to prevent bacterial infection. Various biological activities of biosurfactants have been observed, including anti-QS effects. In the present study, we investigated the effectiveness of a biosurfactant derived from Lactiplantibacillus plantarum on QS-regulated virulence factors and biofilm formation in Pseudomonas aeruginosa and Chromobacterium violaceum. The structural analogues of the crude biosurfactant were identified using gas chromatography-mass spectrometry (GC-MS). Moreover, the inhibitory prospects of identified structural analogues were assessed with QS-associated CviR, LasA, and LasI ligands via in silico molecular docking analysis. An L. plantarum-derived biosurfactant showed a promising dose-dependent interference with the production of both violacein and acyl homoserine lactone (AHL) in C. violaceum. In P. aeruginosa, at a sub-MIC concentration (2.5 mg/mL), QS inhibitory activity was also demonstrated by reduction in pyocyanin (66.63%), total protease (60.95%), LasA (56.62%), and LasB elastase (51.33%) activity. The swarming motility and exopolysaccharide production were also significantly reduced in both C. violaceum (61.13%) and P. aeruginosa (53.11%). When compared with control, biofilm formation was also considerably reduced in C. violaceum (68.12%) and P. aeruginosa (59.80%). A GC-MS analysis confirmed that the crude biosurfactant derived from L. plantarum was a glycolipid type. Among all, n-hexadecanoic acid, oleic acid, and 1H-indene,1-hexadecyl-2,3-dihydro had a high affinity for CviR, LasI, and LasA, respectively. Thus, our findings suggest that the crude biosurfactant of L. plantarum can be used as a new anti-QS/antibiofilm agent against biofilm-associated pathogenesis, which warrants further investigation to uncover its therapeutic efficacy.

Kidney injury and oxidative damage alleviation by Zingiber officinale: pharmacokinetics and protective approach in a combined murine model of osteoporosis.

Ginger (Zingiber officinale) is considered as a nutraceutical spice, which possesses several health promotion and benefits. This study was carried out to investigate the phyto-chemical composition, the antioxidant capacities, the drug-likeness, and pharmacokinetic properties of ginger extract on kidney injury-associated osteoporosis in rats. Phenolic and flavonoid contents were assessed by standard chemical analysis methods and HPLC. In vivo protective effect was based on the use of female rats to evaluate the effect on renal injury as a result of combined osteoporosis using biochemical markers, oxidative status, and histological analyses. Results showed that ZO contained appreciable amounts of phenolics and flavonoids and it exhibited high scavenging activity. Ovariectomy-associated corticotherapy induced severe renal injury marked by altered biochemical markers (creatinine, urea, and uric acid), reduced GFR, significative oxidative damage signs, and disrupted antioxidant status in the combined osteoporotic rats. The histopathological examination revealed structural modifications of kidney tissues. However, all these changes were reversed following the use of ZO. These results confirm the renoprotective and antioxidant potential of ginger against renal injuries in osteoporotic rats.

Antiviral Effects of Artemisinin and Its Derivatives against SARS-CoV-2 Main Protease: Computational Evidences and Interactions with ACE2 Allelic Variants.

Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action-specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between -5.2 and -8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin-Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein.

Impact of chemoprophylaxis immunisation under halofantrine (CPS-HF) drug cover in Plasmodium yoelii Swiss mice malaria model.

In the present study, we have investigated the role of antimalarial drug halofantrine (HF) in inducing the sterile protection against challenges with sporozoites of the live infectious Plasmodium yoelii (Killick-Kendrick, 1967) in Swiss mice malaria model. We observed that during the first to third sequential sporozoite inoculation cycles, blood-stage patency remains the same in the control and chemoprophylaxis under HF drug cover (CPS-HF) groups. However, a delayed blood-stage infection was observed during the fourth and fifth sporozoite challenges and complete sterile protection was produced following the sixth sporozoite challenge in CPS-HF mice. We also noticed a steady decline in liver stage parasite load after 3th to 6th sporozoite challenge cycle in CPS-HF mice. CPS-HF immunisation results in a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-12 and iNOS) and down-regulation of anti-inflammatory cytokines (IL-10 and TGF-ß) mRNA expression in hepatic mononuclear cells (HMNC) and spleen cells in the immunised CPS-HF mice (after 6th sporozoite challenge) compared to control. Overall, our study suggests that the repetitive sporozoite inoculation under HF drug treatment develops a strong immune response that confers protection against subsequent challenges with sporozoites of P. yoelii.

Expression Profiling of Selected Immune Genes and Trabecular Microarchitecture in Breast Cancer Skeletal Metastases Model: Effect of α-Tocopherol Acetate Supplementation.

Breast cancer bone metastases (BCBM) result in serious skeletal morbidity. Although there have been important advances in cancer treatment methods such as surgery and chemotherapy, the complementary treatments, such as α-tocopherol acetate (ATA), still remain of key role via complementary and/or synergistic effects. The aim of this work was to study immune response in a rat model of BCBM due to Walker 256/B cells inoculation and the effect of ATA alone. Compared to the control group (CTRL), rat injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group) showed osteolytic damages with marked tumor osteolysis of both cancellous and trabecular bone as assessed by X-ray radiology, micro-computed tomography, and histology. Rats inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW, W256ATA group) presented marked less tumor osteolysis, less disturbance of Tb.Th and Tb.Sp associated with conversion of rods into plates, and increased structure model index and trabecular pattern factor (Tb.Pf). Elsewhere, 3D frequency distributions of Tb.Th and Tb.Sp were highly disturbed in metastatic W256 rats. Overexpression of some genes commonly associated with cancer and metastatic proliferation: COX-2, TNF-α, and pro-inflammatory interleukins 1 and 6 was outlined. ATA alleviated most of the Walker 256/B cells-induced microarchitectural changes in the target parameters without turning back to normal levels. Likewise, it alleviates the BCSM-induced overexpression of COX-2, TNF-α, IL-1, and IL-6. In silico approach showed that ATA bound these proteins with high affinities, which satisfactory explain its beneficial effects. In conclusion, BCBM is associated with bone microarchitectural disorders and an immune response characterized by an overexpression of some key role genes in cancer proliferation and invasion. ATA exerted favorable effects on trabecular bone distribution and morphology, which may involve the COX-2, TNF-α, and ILs pathways.

Phytochemical Composition, Antioxidant, and Anticancer Activities of Sidr Honey: In Vitro and In Silico Computational Investigation.

Cancer is one of the major causes of death worldwide. The repercussions of conventional therapeutic approaches present a challenge in the delivery of new effective treatments. Thus, more attention is being awarded to natural products, mainly honey. Honey could be the basis for the development of new therapies for cancer patients. The aim of this study is to assess the phytochemical profiling, antioxidant, drug-likeness properties, and anticancer activity of Ziziphus honey (ZH) derived from the Hail region of Saudi Arabia. The phytochemical profiling using high resolution-liquid chromatography mass spectrometry (HR-LCMS) revealed 10 compounds belonging to several familial classes and one tripeptide. Potential antioxidant activity was noted as assessed by DPPH (IC50 0.670 mg/mL), ABTS (IC50 3.554 mg/mL), and ß-carotene (IC50 > 5 mg/mL). The ZH exerted a notable cytotoxic effect in a dose-dependent manner against three cancer cell lines: lung (A549), breast (MCF-7), and colon (HCT-116), with respective IC50 values of 5.203%, 6.02%, and 7.257%. The drug-likeness investigation unveiled that most of the identified compounds meet Lipinski's rule. The molecular docking analysis revealed interesting antioxidant and anticancer activities for most targeted proteins and supported the in vitro findings. The Miraxanthin-III compound exhibited the most stabilized interaction. This study provides deeper insights on ZH as prominent source of bioactive compounds with potent antioxidant and anticancer effects.

Inhibition of Bacterial Adhesion and Antibiofilm Activities of a Glycolipid Biosurfactant from Lactobacillus rhamnosus with Its Physicochemical and Functional Properties.

Biosurfactants derived from different microbes are an alternative to chemical surfactants, which have broad applications in food, oil, biodegradation, cosmetic, agriculture, pesticide and medicine/pharmaceutical industries. This is due to their environmentally friendly, biocompatible, biodegradable, effectiveness to work under various environmental conditions and non-toxic nature. Lactic acid bacteria (LAB)-derived glycolipid biosurfactants can play a major role in preventing bacterial attachment, biofilm eradication and related infections in various clinical settings and industries. Hence, it is important to explore and identify the novel molecule/method for the treatment of biofilms of pathogenic bacteria. In the present study, a probiotic Lactobacillus rhamnosus (L. rhamnosus) strain was isolated from human breast milk. Firstly, its ability to produce biosurfactants, and its physicochemical and functional properties (critical micelle concentration (CMC), reduction in surface tension, emulsification index (% EI24), etc.) were evaluated. Secondly, inhibition of bacterial adhesion and biofilm eradication by cell-bound biosurfactants from L. rhamnosus was performed against various biofilm-forming pathogens (B. subtilis, P. aeruginosa, S. aureus and E. coli). Finally, bacterial cell damage, viability of cells within the biofilm, exopolysaccharide (EPS) production and identification of the structural analogues of the crude biosurfactant via gas chromatography-mass spectrometry (GC-MS) analysis were also evaluated. As a result, L. rhamnosus was found to produce 4.32 ± 0.19 g/L biosurfactant that displayed a CMC of 3.0 g/L and reduced the surface tension from 71.12 ± 0.73 mN/m to 41.76 ± 0.60 mN/m. L. rhamnosus cell-bound crude biosurfactant was found to be effective against all the tested bacterial pathogens. It displayed potent anti-adhesion and antibiofilm ability by inhibiting the bacterial attachment to surfaces, leading to the disruption of biofilm formation by altering the integrity and viability of bacterial cells within biofilms. Our results also confirm the ability of the L. rhamnosus cell-bound-derived biosurfactant to damage the architecture of the biofilm matrix, as a result of the reduced total EPS content. Our findings may be further explored as a green alternative/approach to chemically synthesized toxic antibiofilm agents for controlling bacterial adhesion and biofilm eradication.

Chemoprophylaxis under sporozoites-lumefantrine (CPS-LMF) immunization induce protective immune responses against Plasmodium yoelii sporozoites infection in mice.

Malaria represents one of the major life-threatening diseases that poses a huge socio-economic impact, worldwide. Chemoprophylaxis vaccination using a relatively low number of wild-type infectious sporozoites represents an attractive and effective vaccine strategy against malaria. However, the role of immune responses to pre-erythrocytic versus blood-stage parasites in protection against different antimalarial drugs remains unclear. Here, in the present study, we explored the immune responses against the repetitive inoculation of live Plasmodium yoelii (P. yoelii) sporozoites in an experimental Swiss mouse model under antimalarial drug lumefantrine chemoprophylaxis (CPS-LMF). We monitored the liver stage parasitic load, pro/anti-inflammatory cytokines expression, and erythrocytic stage patency, following repetitive cycles of sporozoites inoculations. It was found that repetitive sporozoites inoculation under CPS-LMF results in delayed blood-stage infection during the fourth sporozoites challenge, while sterile protection was produced in mice following the fifth cycle of sporozoites challenge. Intriguingly, we observed a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and iNOS response and down-regulation of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) in the liver HMNC (hepatic mononuclear cells) and spleen cells after 4th and 5th cycle of sporozoites challenge in the CPS-LMF mice. Meanwhile, we also noticed that the liver stage parasites load under CPS-LMF immunization has gradually reduced after 2nd, 3rd, 4th and 5th sporozoites challenge. Overall, our study suggests that chemoprophylaxis vaccination under LMF drug cover develops strong immune responses and confer superior long-lasting protection against P. yoelii sporozoites. Furthermore, this vaccination strategy can be used to study the protective and stage-specific immunity against new protective antigens. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03022-0.

Functional and Structural Characterization of Pediococcus pentosaceus-Derived Biosurfactant and Its Biomedical Potential against Bacterial Adhesion, Quorum Sensing, and Biofilm Formation.

Biosurfactants are surface-active molecules of microbial origin and alternatives to synthetic surfactants with various applications. Due to their environmental-friendliness, biocompatibility, biodegradability, effectiveness to work under various environmental conditions, and non-toxic nature, they have been recently recognized as potential agents with therapeutic and commercial importance. The biosurfactant produced by various probiotic lactic acid bacteria (LAB) has enormous applications in different fields. Thus, in vitro assessment of biofilm development prevention or disruption by natural biosurfactants derived from probiotic LAB is a plausible approach that can lead to the discovery of novel antimicrobials. Primarily, this study aims to isolate, screen, and characterize the functional and biomedical potential of biosurfactant synthesized by probiotic LAB Pediococcus pentosaceus (P. pentosaceus). Characterization consists of the assessment of critical micelle concentration (CMC), reduction in surface tension, and emulsification index (% EI24). Evaluation of antibacterial, antibiofilm, anti-QS, and anti-adhesive activities of cell-bound biosurfactants were carried out against different human pathogenic bacteria (B. subtilis, P. aeruginosa, S. aureus, and E. coli). Moreover, bacterial cell damage, viability of cells within the biofilm, and exopolysaccharide (EPS) production were also evaluated. As a result, P. pentosaceus was found to produce 4.75 ± 0.17 g/L biosurfactant, which displayed a CMC of 2.4 ± 0.68 g/L and reduced the surface tension from 71.11 ± 1.12 mN/m to 38.18 ± 0.58 mN/m. P. pentosaceus cells bound to the crude biosurfactant were found to be effective against all tested bacterial pathogens. It exhibited an anti-adhesion ability and impeded the architecture of the biofilm matrix by affecting the viability and integrity of bacterial cells within biofilms and reducing the total EPS content. Furthermore, the crude biosurfactant derived from P. pentosaceus was structurally characterized as a lipoprotein by GC-MS analysis, which confirms the presence of lipids and proteins. Thus, our findings represent the potent anti-adhesion and antibiofilm potential of P. pentosaceus crude biosurfactant for the first time, which may be explored further as an alternative to antibiotics or chemically synthesized toxic antibiofilm agents.