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Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography–electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent.

Background: Lead (Pb) is a metal that affects many body systems, primarily the male reproductive system. This study aimed to examine the phytochemical profiling and beneficial effects of Juglans regia oil (JRO) in alleviating lead-induced reprotoxicity-associated oxidative injury in rats. Adult male Wistar rats were randomly divided into four groups as follows: control group received no treatment, Pb group was exposed to 0.344 g kg -1 bw of Pb acetate, Pb + JRO group was co-treated with Pb plus walnut oil (0.9 g kg -1 bw) and JRO group received walnut oil only., Results: Pb-treated rats showed significantly decreased gonado-somatic index, count and viability of sperm. Testosterone levels decreased in Pb-treated animals. Besides, Pb disrupted the oxidative/antioxidative status, the plasmatic lipase activity and testicular Pb content. Furthermore, Pb produced testis histopathological features, especially cell degeneration, atrophy and tubular disarrangement. Co-treatment with JRO was found to be effective for recovering the increased testicular oxidative damage-associated histological features in the Pb group. This was supported by the in silico modeling results., Conclusion: The in silico analyses revealed that JRO compounds bound androgen receptor and RAC-alpha serine/threonine kinase with high affinities, which together with pharmacokinetic properties and molecular interactions satisfactorily support the beneficial in vivo findings in the Pb + JRO group of rats. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

PBDE-47, with lipophilic properties, was found in mussels, clams, and fish where it causes developmental issues, and endocrine and immune disruptions. The current study investigated the effects of PBDE-47 (0.1, 1, and 10 μg.l -1 ) on the clams Ruditapes decussatus and the nematode Metoncholaimus pristiurus. This flame retardant reduced CAT and GST activities in R. decussatus after only 2 days. The AChE activity was similar after 2 days but decreased after 7 days in the digestive gland. In gills, a decrease in AChE activities was observed for both time slots. The clearance rates increased following exposure for 2 days but decreased after one week. The exposure of M. pristiurus to PBDE-47 was accompanied by an increase in CAT and GST activities and a decrease in that of AChE. The microbial descriptors supported the obtained results for this nematode. Finally, the computational analyses supported the ecotoxicity of PBDE-47 for both invertebrate species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The G protein-coupled receptor 40 (GPR40) is known to exert a significant influence on neurogenesis and neurodevelopment within the central nervous system of both humans and rodents. Research findings indicate that the activation of GPR40 by an agonist has been observed to promote the proliferation and viability of hypothalamus cells in the human body. The objective of the present study is to discover new agonist compounds for the GPR40 protein through the utilization of machine learning and pharmacophore-based screening techniques, in conjunction with other computational methodologies such as docking, molecular dynamics simulations, free energy calculations, and investigations of the free energy landscape. In the course of our investigation, we successfully identified five unreported agonist compounds that exhibit robust docking score, displayed stability in ligand RMSD and consistent hydrogen bonding with the receptor in the MD trajectories. Free energy calculations were observed to be higher than control molecule. The measured binding affinities of compounds namely 1, 3, 4, 6 and 10 were -13.9, -13.5, -13.4, -12.9, and -12.1 Kcal/mol, respectively. The identified molecular agonist that has been found can be assessed in terms of its therapeutic efficacy in the treatment of neurological diseases., Competing Interests: The authors declare they have no competing financial interests., (Copyright: © 2024 Siddiqui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Biogenic synthesis of silver nanoparticles (AgNPs) has emerged as an eco-friendly and sustainable approach with diverse biological applications. This study presents synthesis of AgNPs-LS using a probiotic strain Lactobacillus salivarius ( L. salivarius ) and explores their multifaceted biological activities, including antibacterial, antibiofilm, anti-quorum sensing, antifungal, antioxidant, anticancer, anticoagulant and thrombolytic properties. The biosynthesis of AgNPs-LS was successfully achieved using L. salivarius cell free supernatants, resulting in well-characterized nanoparticles as confirmed by UV-Vis spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) and zeta potential analysis. The AgNPs-LS demonstrated potent antibacterial activity against different pathogenic bacteria ( C. violaceum, P. aeruginosa, S. aureus , E. coli and S. marcescens ), emphasizing their potential in combating bacterial infections. Moreover, these AgNPs-LS were effective in inhibiting biofilm formation (>60 % at 1/2 MIC), a key mechanism of bacterial virulence, highlighting their utility in preventing biofilm-related infections. AgNPs-LS exhibited anti-quorum sensing activity, disrupting bacterial communication systems and potentially reducing virulence factor such as, violacein production in C. violaceum, pyocyanin production in P. aeruginosa and prodigiosin production in S. marcescens . Additionally, AgNPs-LS also exhibited notable antifungal activity towards a different pathogenic fungus ( F. proliferatum, P. purpurogenum, A. niger and R. stolonifer ). In terms of health applications, the AgNPs-LS displayed significant antioxidant activity, effectively scavenging DPPH • (IC 50  = 42.65 μg/mL) and ABTS •+ (IC 50  = 53.77 μg/mL) free radicals. Furthermore, AgNPs-LS showed cytotoxicity against breast cancer cells (MCF-7) (IC 50  = 52.29 μg/mL), positioning them as promising candidates for cancer therapy. Moreover, AgNPs-LS were also shown promising anticoagulant and thrombolytic activities under practical conditions. Therefore, the biogenic synthesis of AgNPs-LS using L. salivarius offers a sustainable and cost-effective route for producing AgNPs with an array of biological activities. These AgNPs-LS have the potential to address various challenges in healthcare, ranging from antimicrobial, anticancer applications to biofilm inhibition, antioxidant therapy, anticoagulant and thrombolytic agents., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Two concentrations (6.25 and 1.25 mg/L) were used for two Parkinson's disease medications, Benserazide, and Trihexyphenidyl, to test their effects on the meiobenthic nematofauna. It is predicted that these highly hydrosoluble drugs will end up in marine environments. The results showed that both medications when added alone, induced (i) important changes in the numbers and (ii) taxonomic composition. The impact of Benserazide and Trihexyphenidyl was also reflected in the (iii) functional traits of nematofauna, with the most affected categories following exposure being the trophic group 1B, the clavate tails, the circular amphids, the c-p2 life history, and the body length of 1-2 mm. These results were supported by the molecular interactions of the studied drugs with both GLD-3 and SDP proteins of Caenorhabditis elegans. (iv) The mixtures of both drugs did not show any changes in the nematode communities, suggesting that no synergistic or antagonistic interactions exist between them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial., Methods: Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study., Results: Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control., Conclusion: The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The cactus family plant has been used in folk medicine for a long time. In this work, Opuntia stricta chemical composition and its antioxidative and anti-inflammatory properties were investigated. Our results showed that O. stricta is highly rich in fibers and minerals. The present study assessed the levels of polyphenol contents and antioxidant and in vivo anti-inflammatory activities. The highest phenolic compounds and antioxidant activity were observed in the methanolic extract. Concerning the qualitative analysis, nine phenolic and organic acids were identified and quantified by high-performance liquid chromatography (HPLC). Luteolin-7-Glu (4.25 μg/g), apigenin-7-Glu (3.15 μg/g), and catechin (2.85 μg/g) were identified as major phenolic compounds. The predominant fatty acids detected by gas chromatography (GC) coupled to a flame ionization detector were linoleic and linolenic acids (35.11%). A factorial design plan was used to determine the effect of temperature, agitation speed, and maceration period on phenolic contents. In vivo , the methanol extract from Opuntia stricta showed anti-inflammatory activity. The computational modeling reveals that O. stricta compounds bind VEGF, IL-6, and TNF-α with high binding scores that reach -8.7 kcal/mol and establish significant molecular interactions with some key residues that satisfactorily explain both in vitro and in vivo findings. These data indicate that Opuntia stricta cladode powder could be potentially useful in pharmaceutical and food applications., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The current study aimed to assess the antioxidant and antiproliferative effects of teucrium polium extract: computational and in vivo study in rats. Three groups of animals: Group (i) constitute the control group; Group (ii) HeLa group received an intrafemoral inoculation of HeLa cells and Group (iii) constitue the combination between HeLa + T. polium . The plant was administered by gavage. Our results revealed that HeLa cell injection showed an elevation in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), creatinine, urea, calcium and phosphorus. The pretreatment with the plant extract reduced the level of these parameters. Injection of HeLa cells showed a significant decrease in phosphorus and calcium respectively. However, the pretreatment by T. polium modulated the level of these two minerals. Rats treated with HeLa cells line showed an increase in the level of lipid peroxidation as evaluated by the TBARS substances, at the same time, a significant decreases in SOD, CAT and GPx activities were noted in the HeLa group compared to the control. On the other hand, pretreatment with the plant improved the level of these enzymes. Our results revealed that T.polium has a therapeutic effect on some health problems. HeLa cell line induced a small infiltration in liver and kidney. T. polium reduced the damage in both liver and kidney, but did not reveal any proliferation of tumor cells from trabecular bone tissue. The computational study revealed that T. polium compound bound with high free binding energies and established promising network of molecular interactions with COX-2 and TNF-α macromolecules.

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

In this study, we investigated for the first time the anti-inflammatory and immunomodulatory properties of crude polysaccharide (PSHT) extracted from green marine algae Halimeda tuna . PSHT exhibited anti-oxidant activity in vitro through scavenging 1, 1-diphenyl-2-picryl hydroxyl free radical, reducing Fe 3+ /ferricyanide complex, and inhibiting nitric oxide. PSHT maintained the erythrocyte membrane integrity and prevented hemolysis. Our results also showed that PSHT exerted a significant anti-edematic effect in vivo by decreasing advanced oxidation protein products and malondialdehyde levels and increasing the superoxide dismutase and glutathione peroxidase activities in rat's paw model and erythrocytes. Interestingly, PSHT increased the viability of murine RAW264.7 macrophages and exerted an anti-inflammatory effect on lipopolysaccharide-stimulated cells by decreasing pro-inflammatory molecule levels, including nitric oxide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α). Our findings indicate that PSHT could be used as a potential immunomodulatory, anti-inflammatory, anti-hemolytic, and anti-oxidant agent. These results could be explained by the computational findings showing that polysaccharide building blocks bound both cyclooxygenase-2 (COX-2) and TNF-α with acceptable affinities.

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.

Knowledge of genetic variability within and among types and breeds of dromedary ( Camelus dromedarius L.) can be a valuable asset in selective breeding of desirable characteristics and will shed light on their origin, dynamics of domestication, and dispersion. Variability in an 809 bp segment of the mtDNA genome was measured within and among dromedaries from eight indigenous and one exogenous breed from Ha'il in north-central Saudi Arabia. Sixteen mtDNA haplotypes were identified among 47 camels. Haplotypic diversity among breeds is high ( H d = 0.817); most of the AMOVA variance (55.05%) occurs within breeds. Phylogenetic comparison of these haplotypes with those obtained across their geographic range showed that most haplotypes were placed within the same cluster with ancient wild dromedaries and the two newly identified haplotypes in this study. The most prevalent haplotypes found in dromedaries from this area appear to be ancestral to most other dromedaries and differ from each other by only one SNP. These results support the hypothesis that the Arabian Peninsula is a hub of diversification for dromedaries.

In the face of rising antibiotic resistance and the need for novel therapeutic approaches against cancer, the present study delves into the various facets of biosynthesized silver nanoparticles (AgNPs) derived from the probiotic strain Lactobacillus casei (AgNPs-LC), assessing their efficacy in combating bacterial infections, disrupting biofilm formation, interfering with quorum sensing mechanisms, and exhibiting anti-cancer properties. The results showed that the AgNPs-LC had a spherical shape with an average size of 15 nm. The biosynthesized AgNPs-LC showed a symmetrical absorption spectrum with a peak at 458 nm with a diameter of 5-20 nm. AgNPs-LC exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria and inhibited the biofilm formation (> 50% at sub-MIC) and quorum sensing-mediated virulence factors, such as the production of violacein in C. violaceum (> 80% at sub-MIC), pyocyanin in P. aeruginosa (> 70% at sub-MIC), and prodigiosin in S. marcescens (> 80% at sub-MIC). The exopolysaccharides (EPS) were also found to reduce in the presence of AgNPs-LC. Furthermore, the AgNPs-LC showed anti-cancer and anti-metastasis activity via inhibiting cell migration and invasion of human lung cancer (A-549) cells. Overall, the present study brings out the multifaceted therapeutic capabilities of AgNPs-LC which offer exciting prospects for the development of innovative biomedical and pharmaceutical interventions, making AgNPs-LC a versatile and promising candidate for a wide range of applications in healthcare and medicine. However, further research is essential to fully harness their therapeutic potential., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates ( Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida -associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-β-carotene (-8.5 kJ/mol), CASP1-β-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-βcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.

Plants with medicinal benefits are a crucial source of compounds for developing drugs. This study was designed to determine the chemical composition, antibacterial, antibiofilm, antioxidant, and anti-enzymatic activities of Pulicaria incisa (Lam.) DC. We also reported the molecular interaction between identified molecules and several receptors associated with antimicrobial and antibiofilm activities. A total of seventeen and thirteen compounds were identified in aqueous and methanolic extracts of P. incisa , respectively. The methanolic extract yielded a higher total content of polyphenols and flavonoids of about 84.80 ± 2.8 mg GAE/g and 28.30 ± 1.2 mg QE/g, respectively. Significant antibacterial activity was recorded for both extracts, with minimum inhibitory concentration (MIC) values ranging from 30 to 36 µg/mL, and the result was comparable to the reference antibiotic control. Antibiofilm assays revealed that both extracts were able to reduce the attachment of bacterial cells to 96-well plates, but the highest antibiofilm activity was recorded against Staphylococcus aureus . The methanolic extract also showed anti-enzymatic potency and high antioxidant activity, as demonstrated by all assays used, including DPPH, FRAP, and ABTS. These results were further validated by in silico approaches, particularly the molecular interaction of the identified compounds with the targeted receptors. These findings present P. incisa as a significant source of antibacterial, antibiofilm, antioxidant, and anti-enzymatic molecules.

Staphylococcus aureus strains are a great contributor to both hospital acquired infections as well as community acquired infections. The objective of the present investigation was to compare potential differences in cytoplasmic amino acid levels between clinical and ATCC 29213 strains of S. aureus. The two strains were grown under ideal conditions to mid-exponential and stationary growth phases, after which they were harvested to analyze their amino acid profiles. Initially, the amino acid patterns of both strains were compared at the mid-exponential phase when grown in controlled conditions. At the mid-exponential phase, both strains shared common features in cytoplasmic amino acid levels, with glutamic acid, aspartic acid, proline, and alanine identified as key amino acids. However, the concentration profiles of seven amino acids exhibited major variances between the strains, even though the total cytoplasmic levels of amino acids did not alter significantly. At the stationary phase, the magnitudes of the amino acids abundant in the mid-exponential phase were altered. Aspartic acid became the most abundant amino acid in both strains accounting for 44% and 59% of the total amino acids in the clinical and ATCC 29213 strains, respectively. Lysine was the second most abundant amino acid in both strains, accounting for 16% of the total cytoplasmic amino acids, followed by glutamic acid, the concentration of which was significantly higher in the clinical strain than in the ATCC 29213 strain. Interestingly, histidine was clearly present in the clinical strain but was virtually lacking in the ATCC 29213 strain. This study reveals the dynamic diversity of amino acid levels among strains, which is an essential step toward illustrating the variability in S. aureus cytoplasmic amino acid profiles and could be significant in explaining variances among strains of S. aureus.

Antimicrobial resistance by pathogenic bacteria has become a global risk to human health in recent years. The most promising approach to combating antimicrobial resistance is to target virulent traits of bacteria. In the present study, a biosurfactant derived from the probiotic strain Lactobacillus acidophilus was tested against three Gram-negative bacteria to evaluate its inhibitory potential on their biofilms, and whether it affected the virulence factors controlled by quorum sensing (QS). A reduction in the virulence factors of Chromobacterium violaceum (violacein production), Serratia marcescens (prodigiosin production) and Pseudomonas aeruginosa (pyocyanin, total protease, LasB elastase and LasA protease production) was observed at different sub-MIC concentrations in a dose-dependent manner. Biofilm development was reduced by 65.76%, 70.64% and 58.12% at the highest sub-MIC levels for C. violaceum, P. aeruginosa and S. marcescens, respectively. Biofilm formation on glass surfaces exhibited significant reduction, with less bacterial aggregation and reduced formation of extracellular polymeric materials. Additionally, swimming motility and exopolysaccharides (EPS) production were shown to be reduced in the presence of the L. acidophilus-derived biosurfactant. Furthermore, molecular docking analysis performed on compounds identified through gas chromatography-mass spectrometry (GC-MS) analysis of QS and biofilm proteins yielded further insights into the mechanism underlying the anti-QS activity. Therefore, the present study has clearly demonstrated that a biosurfactant derived from L. acidophilus can significantly inhibit virulence factors of Gram-negative pathogenic bacteria. This could provide an effective method to inhibit the formation of biofilms and QS in Gram-negative bacteria.

Sulfated polysaccharides from seaweed are highly active natural substances with valuable applications. In the present paper, attempts have been made to discuss the physicochemical and structural features of polysaccharides isolated from red marine alga Alsidium corallinum (ACPs) and their protective effect in hepatic impairments induced by tebuconazole (TEB) in male adult rats. Structural features were determined using high-performance liquid chromatography, Fourier-transformed infrared, and solid-state 1 H and 13 C-Nuclear magnetic resonance analysis. ACPs are found to be hetero-sulfated-anionic polysaccharides that contain carbohydrates, sulfate groups, and uronic acids. In vitro biological activities suggested the effective antioxidant and antimicrobial capacities of ACPs. For antioxidant testing in vivo, the biochemical analysis and plasma profiles displayed that oral administration of ACPs could mitigate blood lipid indicators, including total cholesterol, triglyceride, low and high-density lipoprotein cholesterol, and bilirubin. Liver function indexes involving alanine aminotransferase and aspartate aminotransferase showed that ACPs possessed prominent antioxidant activities. Additionally, the intervention of ACPs potentially inhibited lipid peroxidation, protein oxidation, key enzymes of lipid metabolism (<0.001), and improved antioxidant status (<0.05). Histomorphological observation confirmed that ACPs intervention could partially repair liver injuries caused by TEB. The computational results showed that A. corallinum monosaccharides bound 1JIJ, 1HD2, and 1WL4 receptors with acceptable affinities, which, together with deep embedding and molecular interactions, support the antioxidant, antimicrobial, and hypolipidemic outlined effects in the in vitro and in vivo findings. Given their prominent antioxidant effects, ACPs are promising candidates for liver diseases and must be considered in pharmaceutical applications.

The present study aimed to molecularly identify and characterize the hard ticks infesting camels from the northern region (Ha'il province) of Saudi Arabia using the mitochondrial barcoding gene cytochrome oxidase subunit I ( COI ). The sequences of tick samples from camels in three regions of Ha'il were aligned with those previously reported from different geographic regions, revealing nine haplotypes, of which six were newly described in this study for the first time. These haplotypes were used to determine their phylogenetic relationships using the maximum likelihood method, displaying two distinct clades corresponding to Hyalomma dromedarii and H. impeltatum . Moreover, the haplotypes showing the highest homology with those deposited in NCBI-GenBank from different geographic regions, including Saudi Arabia, were obtained and combined to determine their phylogenetic relationships among them. The results showed that the haplotypes belonging to two clades were grouped with those previously determined as H. dromedarii and H. impeltatum . Moreover, the presence of H. scupense (syn. H. detritum ) together with H. impeltatum suggests possible asymmetrical hybridization and mitochondrial introgression between these species. H. scupense infesting different mammal species apart from camels were also clustered in a different clade, indicating the presence of different lineages of this species that show different host specificities.

The glutamate-gated ion channels known as N-methyl-d-aspartate receptors (NMDARs) are important for both normal and pathological brain function. Subunit-selective antagonists have high therapeutic promise since many pathological conditions involve NMDAR over activation, although few clinical successes have been reported. Allosteric inhibitors of GluN2B-containing receptors are among the most potential NMDAR targeting drugs. Since the discovery of ifenprodil, a variety of GluN2B-selective compounds have been discovered, each with remarkably unique structural motifs. These results expand the allosteric and pharmacolog-ical spectrum of NMDARs and provide a new structural basis for the development of next-generation GluN2B antagonists that have therapeutic potential in brain diseases. Small molecule therapeutic inhibitors targeting NMDA have recently been developed to target CNS disorders such as Alzheimer's disease. In the current study, a cheminformatics method was used to discover potential antagonists and to identify the structural requirements for Gly/NMDA antagonism. In this case we have created a useful pharmacophore model with solid statistical values. Through pharmacophore mapping, the verified model was used to filter out virtual matches from the ZINC database. Assessing receptor-ligand binding mechanisms and affinities used molecular docking. To find the best hits, the GlideScore and the interaction of molecules with important amino acids were considered essential features. We found some molecular inhibitors, namely, ZINC13729211, ZINC07430424, ZINC08614951, ZINC60927204, ZINC12447511, and ZINC18889258 with high binding affinity using computational methods. The molecules in our studies showed characteristics such as good stability, hydrogen bonding and higher binding affinities in the solvation-based assessment method than ifenprodil with acceptable ADMET profile. Moreover, these six leads have been proposed as potential new perspectives for exploring potent Gly/NMDA receptor antagonists. In addition, it can be tested in the laboratory for potential therapeutic strategies for both in vitro and in vivo research., 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 Siddiqui, Badraoui, Jahan, Alshahrani, Siddiqui, Khan and Adnan.)

In recent years, bacterial pathogens have developed resistance to antimicrobial agents that have created a global threat to human health and environment. As a novel approach to combating antimicrobial resistance (AMR), targeting bacteria's virulent traits that can be explained by quorum sensing (QS) is considered to be one of the most promising approaches. In the present study, biologically synthesized silver nanoparticles derived from Lactobacillus rhamnosus (AgNPs-LR) were tested against three Gram-negative bacteria to determine whether they inhibited the formation of biofilms and triggered the virulence factors controlled by QS. In C. violaceum and S. marcescens , a remarkable inhibition (>70%) of QS-mediated violacein and prodigiosin production was recorded, respectively. A dose-dependent decrease in virulence factors of P. aeruginosa (pyocyanin, pyoverdine, LasA protease, LasB elastase and rhamnolipid production) was also observed with AgNPs-LR. The biofilm development was reduced by 72.56%, 61.70%, and 64.66% at highest sub-MIC for C. violaceum , S. marcescens and P. aeruginosa , respectively. Observations on glass surfaces have shown remarkable reductions in biofilm formation, with less aggregation of bacteria and a reduced amount of extra polymeric materials being formed from the bacteria. Moreover, swimming motility and exopolysaccharides (EPS) was also found to reduce in the presence of AgNPs-LR. Therefore, these results clearly demonstrate that AgNPs-LR is highly effective in inhibiting the development of biofilms and the QS-mediated virulent traits of Gram-negative bacteria. In the future, AgNPs-LR may be used as an alternative to conventional antibiotics for the treatment of bacterial infections after careful evaluation in animal models, especially for the development of topical antimicrobial agents.

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., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Malaria and schistosomiasis are two major parasitic diseases that remain leading causes of morbidity and mortality worldwide. Co-infections of these two parasites are common in the tropics, where both diseases are endemic. The clinical consequences of schistosomiasis and malaria are determined by a variety of host, parasitic, and environmental variables. Chronic schistosomiasis causes malnutrition and cognitive impairments in children, while malaria can cause fatal acute infections. There are effective drugs available to treat malaria and schistosomiasis. However, the occurrence of allelic polymorphisms and the rapid selection of parasites with genetic mutations can confer reduced susceptibility and lead to the emergence of drug resistance. Moreover, the successful elimination and complete management of these parasites are difficult due to the lack of effective vaccines against Plasmodium and Schistosoma infections. Therefore, it is important to highlight all current vaccine candidates undergoing clinical trials, such as pre-erythrocytic and erythrocytic stage malaria, as well as a next-generation RTS,S-like vaccine, the R21/Matrix-M vaccine, that conferred 77% protection against clinical malaria in a Phase 2b trial. Moreover, this review also discusses the progress and development of schistosomiasis vaccines. Furthermore, significant information is provided through this review on the effectiveness and progress of schistosomiasis vaccines currently under clinical trials, such as Sh28GST, Sm-14, and Sm-p80. Overall, this review provides insights into recent progress in malarial and schistosomiasis vaccines and their developmental approaches.

In recent years, there has been a growing interest in bio-based degradable plastics as an alternative to synthetic plastic. Polyhyroxybutyrate (PHB) is a macromolecule produced by bacteria as a part of their metabolism. Bacteria accumulate them as reserve materials when growing under different stress conditions. PHBs can be selected as alternatives for the production of biodegradable plastics because of their fast degradation properties when exposed to natural environmental conditions. Hence, the present study was undertaken in order to isolate the potential PHB-producing bacteria isolated from the municipal solid waste landfill site soil samples collected from the Ha'il region of Saudi Arabia to assess the production of PHB using agro-residues as a carbon source and to evaluate the growth of PHB production. In order to screen the isolates for producing PHB, a dye-based procedure was initially employed. Based on the 16S rRNA analysis of the isolates, Bacillus flexus ( B. flexus ) accumulated the highest amount of PHB of all the isolates. By using a UV-Vis spectrophotometer and Fourier-transform infrared spectrophotometer (FT-IR), in which a sharp absorption band at 1721.93 cm -1 (C=O stretching of ester), 1273.23 cm -1 (-CH group), multiple bands between 1000 and 1300 cm -1 (stretching of the C-O bond), 2939.53 cm -1 (-CH 3 stretching), 2880.39 cm -1 (-CH 2 stretching) and 3510.02 cm -1 (terminal -OH group), the extracted polymer was characterized and confirmed its structure as PHB. The highest PHB production by B. flexus was obtained after 48 h of incubation (3.9 g/L) at pH 7.0 (3.7 g/L), 35 °C (3.5 g/L) with glucose (4.1 g/L) and peptone (3.4 g/L) as carbon and nitrogen sources, respectively. As a result of the use of various cheap agricultural wastes, such as rice bran, barley bran, wheat bran, orange peel and banana peel as carbon sources, the strain was found to be capable of accumulating PHB. Using response surface methodology (RSM) for optimization of PHB synthesis using a Box-Behnken design (BBD) proved to be highly effective in increasing the polymer yield of the synthesis. With the optimum conditions obtained from RSM, PHB content can be increased by approximately 1.3-fold when compared to an unoptimized medium, resulting in a significant reduction in production costs. Thus, isolate B. flexus is a highly promising candidate for the production of industrial-size quantities of PHB from agricultural wastes and is capable of removing the environmental concerns associated with synthetic plastics from the industrial production process. Moreover, the successful production of bioplastics using a microbial culture provides a promising avenue for the large-scale production of biodegradable and renewable plastics with potential applications in various industries, including packaging, agriculture and medicine.

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., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The current study presents the results of an experiment carried to assess the impact of azithromycin, a COVID-19 drug, probably accumulated in marine sediments for three years, since the start of the pandemic, on benthic marine nematodes. It was explored the extent to which a common macrophyte from the Mediterranean Sea influenced the toxic impact of azithromycin on meiobenthic nematodes. Metals are known to influence toxicity of azithromycin. The nematofauna from a metallically pristine site situated in Bizerte bay, Tunisia, was exposed to two concentrations of azithromycin [i.e. 5 and 10 μg l -1 ]. In addition, two masses of the common macrophyte Posidonia oceanica [10 and 20% Dry Weight (DW)] were considered and associated with azithromycin into four possible combinations. The abundance and the taxonomic diversity of the nematode communities decreased significantly following the exposure to azithromycin, which was confirmed by the toxicokinetic data and behaving as substrate for P-glycoprotein (P-gp). The toxicity of 5 μg l -1 dosage of azithromycin was partially reduced at 10% DW of Posidonia and completely at 20% DW. The results showed that 5 μg l -1 of azithromycin can be reduced by the macrophyte P. oceanica when present in the environment at low masses as 10% DW., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Clinical multi-drug-resistant bacteria continue to be a serious health problem. Plant-derived molecules are an important source of bioactive compounds to counteract these pathogenic bacteria. In this paper, we studied the chemical composition of the methanol (80%) extract from Pithecellobium dulce seed (Hail, Saudi Arabia) and its ability to inhibit the growth of clinically relevant multi-drug-resistant bacteria. Molecular docking analysis was performed to predict the best compounds with low binding energy and high affinity to interact with two Staphylococcus aureus receptors. Data showed that P. dulce extract is a rich source of D-turanose (55.82%), hexadecanoic acid (11.56%), indole-1-acetic acid (11.42%), inositol (5.78%), and octadecanoic acid (4.36%). The obtained extract showed antibacterial activity towards tested clinical bacterial strains with MIC values ranging from 233 mg/mL for Acinetobacter baumannii to 300 mg/mL for S. aureus and Escherichia coli . Turanose interaction has resulted in -7.4 and -6.6 kcal/mol for 1JIJ and 2XCT macromolecules, while inositol showed energy values (-7.2 and -5.4 kcal/mol) for the same receptors. Multiple identified compounds showed desirable bioavailability properties indicating its great potential therapeutic use in human. Overall, current investigation highlights the possible use of P. dulce extract as a valuable source for drug development against pathogenic drug-resistant bacteria., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Abdu Aldarhami et al.)

The proteinaceous compounds produced by lactic acid bacteria are called bacteriocins and have a wide variety of bioactive properties. However, bacteriocin's commercial availability is limited due to short stability periods and low yields. Therefore, the objective of this study was to synthesize bacteriocin-derived silver nanoparticles (Bac10307-AgNPs) extracted from Lactobacillus acidophilus ( L. acidophilus ), which may have the potential to increase the bioactivity of bacteriocins and overcome the hurdles. It was found that extracted and purified Bac10307 had a broad range of stability for both temperature (20-100 °C) and pH (3-12). Further, based on Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis, its molecular weight was estimated to be 4.2 kDa. The synthesized Bac10307-AgNPs showed a peak of surface plasmon resonance at 430 nm λmax. Fourier transform infrared (FTIR) confirmed the presence of biological moieties, and transmission electron microscopy (TEM) coupled with Energy dispersive X-Ray (EDX) confirmed that AgNPs were spherical and irregularly shaped, with a size range of 9-20 nm. As a result, the Bac10307-AgNPs displayed very strong antibacterial activity with MIC values as low as 8 μg/mL for Staphylococcus aureus ( S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa ), when compared to Bac10307 alone. In addition, Bac10307-AgNPs demonstrated promising in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC 50 = 116.04 μg/mL) and in vitro cytotoxicity against human liver cancer cells (HepG2) (IC 50 = 135.63 μg/mL), more than Bac10307 alone (IC 50 = 139.82 μg/mL against DPPH and 158.20 μg/mL against HepG2). Furthermore, a protein-protein molecular docking simulation study of bacteriocins with target proteins of different biological functions was also carried out in order to ascertain the interactions between bacteriocins and target proteins.

The epidermal growth factor receptor (EGFR) has been shown to be extremely important in numerous signaling pathways, particularly those involved in cancer progression. Many therapeutic inhibitors, consisting of both small molecules and monoclonal antibodies, have been developed to target inflammatory, triple-negative and metastatic breast cancer. With the emergence of resistance in breast cancer treatment strategies, there is a need to develop novel drug targets that not only overcome resistance, but also exhibit low toxicity and high specificity. The work presented here focuses on the identification of new inhibitors against the EGFR protein using combined computational approaches. Using a comprehensive machine learning-based virtual screening approach complemented by other computational approaches, we identified six new molecules from the ZINC database. The gold docking score of these six novel molecules is 125.95, 125.38, 123.13, 119.71, 115.64 and 113.73, respectively, while the gold score of the control group is 120.74. In addition, we also analyzed the FEC value of these compounds and found that the values of compounds 1, 2, 3 and 4 (-61.82, -63.98, -67.98 and -63.32, respectively) were higher are than those of the control group (-61.05). Furthermore, these molecules showed highly stable RMSD plots and good interaction of hydrogen bonds. The identified inhibitors provided interesting insights for understanding the electronic, hydrophobic, steric and structural requirements for EGFR inhibitory activity. Distinguishing these novel molecules could lead to the development of new drugs useful in treating breast cancer.Communicated by Ramaswamy H. Sarma.

Polycyclic aromatic hydrocarbons (PAHs) are toxic for humans and marine fauna alike. The current study assessed the impact of PAHs on the migratory behaviour of meiobenthic nematodes collected from the Bizerte lagoon, Tunisia. The experiment lasted for 15 days and was carried in open microcosms, which comprised a lower, contaminated and an upper, uncontaminated compartment. Three treatments were used, for each of them an untreated control was set up: sediment contaminated with chrysene (116 ng g -1 dry weight (DW), with phenanthrene (116 ng g -1 DW) and a mixture of both. The results showed a significant decrease in diversty and abundance in the lower, contaminated compartments compared to the upper zones. The results also highlighted that under an increased stress some species progressively increased in number, these were considered PAH-tolerant species such as Odontophora villoti, some others had an occasionally increased in number were considered as opportunistic species, such as Paracomesoma dubium and the species that showed a progressive decreased in number, such as Metoncholaimus pristiurus and Steineria sp., Terschellingia. longicaudata, and Oncholaimellus sp. were classified as PAH-sensitive. Moreover, an increase in the activity of biochemical biomarkers was observed following the exposure of males and gravid females of T. longicaudata to 29, 58 and 87 ng g -1 DW of chrysene and phenanthrene paralleled by a higher vulnerability of the latter demographic category. Besides, a significant decrease in fertility of females and an increase in pharyngeal sucking power were observed for both types of PAHs considered. The sex ratio was also significantly imbalanced in the favor of males, which suggest that chrysene and phenanthrene affect also the hormone system of T. longicaudata. The high affinities of these PAHs and their molecular interactions with both germ line development protein 3 (GLD-3) and sex-determining protein (SDP) may justify these results and explain the toxicokinetic attributes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the present study, the chemical composition of the volatile oil and methanolic extract from Ducrosia flabellifolia Boiss. was investigated. The antimicrobial, antioxidant, and anticancer activities of the methanolic extract from D. flabellifolia aerial parts were screened using experimental and computational approaches. Results have reported the identification of decanal (28.31%) and dodecanal (16.93%) as major compounds in the essential oil obtained through hydrodistillation. Farnesyl pyrophosphate, Methyl 7-desoxypurpurogallin-7-carboxylate trimethyl ether, Dihydro-Obliquin, Gummiferol, 2-Phenylaminoadenosine, and 2,4,6,8,10-dodecapentaenal, on the other hand, were the dominant compounds in the methanolic extract. Moreover, the tested extract was active against a large collection of bacteria and yeast strains with diameter of growth inhibition ranging from 6.67 ± 0.57 mm to 17.00 ± 1.73 mm, with bacteriostatic and fungicidal activities against almost all tested microorganisms. In addition, D. flabellifolia methanolic extract was dominated by phenolic compounds (33.85 ± 1.63 mg of gallic acid equivalent per gram of extract) and was able to trap DPPH• and ABTS•+ radicals with IC 50 about 0.05 ± 0 mg/mL and 0.105 ± 0 mg/mL, respectively. The highest percentages of anticancer activity were recorded at 500 µg/mL for all cancer cell lines with IC 50 about 240. 56 µg/mL (A-549), 202.94 µg/mL (HCT-116), and 154.44 µg/mL (MCF-7). The in-silico approach showed that D. flabellifolia identified compounds bound 1HD2, 2XCT, 2QZW, and 3LN1 with high affinities, which together with molecular interactions and the bond network satisfactorily explain the experimental results using antimicrobial, antioxidant, and anticancer assays. The obtained results highlighted the ethnopharmacological properties of the rare desertic D. flabellifolia plant species growing wild in Hail region (Saudi Arabia).

The aim of the current study was to assess the multifaceted effects of the polycylic aromatic hydrocarbon phenanthrene, mainly used in the colouring, explosive, and pharmaceutical industries, on the physiology of two bivalve species with economic value as seafood, namely, the Mediterranean mussel Mytilus galloprovincyalis and the European clam Ruditapes decussatus . The current study assessed how the phenanthrene affected several biomarkers and biometric endpoints in both bivalves, based on an in vivo experiment in silico approach. The bivalves were exposed during four time slots (i.e., 7, 15, 21, and 28 days) to two concentrations of phenanthrene in water (50 µg/L and 100 µg/L). For the clam R. decussatus , an additional contamination of sediment was applied due their typical benthic lifestyle (50 µg/kg and 100 µg/kg). The phenanthrene significantly reduced the ability of bivalves to tolerate desiccation and their Median Lethal Time, and also inhibited the activity of the enzyme acetylcholinesterase in a time-dependent manner. The activity of catalase indicated that bivalves also experienced oxidative stress during the first 21 days of the experiment. The significant decline in catalase activity observed during the last week of the experiment for the mussel M. galloprovincyalis supported a depletion of enzymes caused by the phenanthrene. The phenanthrene has also toxicokinetic and toxicodynamic properties, as assessed by the in silico approach. Overall, the results obtained suggest that the bivalves Ruditapes decussatus and M. galloprovincyalis can be used as a sentinel species in monitoring studies to assess the environmental impact of phenanthene in marine ecosystems. The significance of our findings is based on the fact that in ecotoxicology, little is known about the chronic effects, the simultaneous use of multiple species as bioindicators, and the interactions molecular modelling.

Thymus musilii Velen. is a rare plant species cultivated in the Ha'il region (Saudi Arabia) under greenhouse conditions. In this work, we described, for the first time, the phytochemical composition, antimicrobial, antioxidant, anti-quorum sensing, and anticancer activities of T. musilii methanolic extract using both experimental and computational approaches. The obtained results showed the identification of eight small-like peptides and eighteen phyto-compounds by using high-resolution liquid chromatography-mass spectrometry (HR-LCMS) dominated mainly by compounds belonging to isoprenoid, fatty acyl, flavonoid, and alkaloid classes. The tested extracts exhibited high antifungal and antibacterial activity with the mean diameter of growth inhibition zones ranging from 12.33 ± 0.57 mm ( Pseudomonas aeruginosa ATCC 27853) to 29.33 ± 1.15 mm ( Candida albicans ATCC 10231). Low minimal inhibitory concentrations were recorded for the tested micro-organisms ranging from 0.781 mg/mL to 12.5 mg/mL. While higher doses were necessary to completely kill all tested bacterial and fungal strains. Thyme extract was able to scavenge DPPH • , ABTS •+ , β-carotene, and FRAP free radicals, and the IC 50 values were 0.077 ± 0.0015 mg/mL, 0.040 ± 0.011 mg/mL, 0.287 ± 0.012 mg/mL, and 0.106 ± 0.007 mg/mL, respectively. The highest percentage of swarming and swimming inhibition was recorded at 100 µg/mL with 39.73 ± 1.5% and 25.18 ± 1%, respectively. The highest percentage of biofilm inhibition was recorded at 10 mg/mL for S. typhimurium ATCC 14028 (53.96 ± 4.21%) and L. monocytogenes ATCC 7644 (49.54 ± 4.5 mg/mL). The in silico docking study revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of T. musilii are thermodynamically feasible, notably, such as those of the tripeptides (Asn-Met-His, His-Cys-Asn, and Phe-His-Gln), isoprenoids (10-Hydroxyloganin), and diterpene glycosides (4-Ketoretinoic acid glucuronide).

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 β-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.

Listeria monocytogenes ( L. monocytogenes ) is a serious food-borne pathogen that can cause listeriosis, an illness caused by eating food contaminated with this pathogen. Currently, the treatment or prevention of listeriosis is a global challenge due to the resistance of bacteria against multiple commonly used antibiotics, thus necessitating the development of novel green antimicrobials. Scientists are increasingly interested in microbial surfactants, commonly known as "biosurfactants", due to their antimicrobial properties and eco-friendly nature, which make them an ideal candidate to combat a variety of bacterial infections. Therefore, the present study was designed to use a network pharmacology approach to uncover the active biosurfactants and their potential targets, as well as the signaling pathway(s) involved in listeriosis treatment. In the framework of this study, 15 biosurfactants were screened out for subsequent studies. Among 546 putative targets of biosurfactants and 244 targets of disease, 37 targets were identified as potential targets for treatment of L. monocytogenes infection, and these 37 targets were significantly enriched in a Gene Ontology (GO) analysis, which aims to identify those biological processes, cellular locations, and molecular functions that are impacted in the condition studied. The obtained results revealed several important biological processes, such as positive regulation of MAP kinase activity, protein kinase B signaling, ERK1 and ERK2 cascade, ERBB signaling pathway, positive regulation of protein serine/threonine kinase activity, and regulation of caveolin-mediated endocytosis. Several important KEGG pathways, such as the ERBBB signaling pathway, TH17 cell differentiation, HIF-1 signaling pathway, Yersinia infection, Shigellosis, and C-type lectin receptor signaling pathways, were identified. The protein-protein interaction analysis yielded 10 core targets (IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR). Molecular docking was used in the latter part of the study to verify the effectiveness of the active biosurfactants against the potential targets. Lastly, we found that a few highly active biosurfactants, namely lichenysin, iturin, surfactin, rhamnolipid, subtilisin, and polymyxin, had high binding affinities towards IL2, MAPK1, EGFR, PTPRC, TNF, ITGB1, IL1B, ERBB2, SRC, and mTOR, which may act as potential therapeutic targets for listeriosis. Overall, based on the integrated network pharmacology and docking analysis, we found that biosurfactants possess promising anti-listeriosis properties and explored the pharmacological mechanisms behind their effect, laying the groundwork for further research and development.

Diabetes mellitus has become a serious problem associated with health complications, such as metabolism disorders and liver-kidney dysfunction. The inadequacies associated with conventional medicines have led to a determined search for alternative natural therapeutic agents. The present study was conducted to evaluate the hypoglycemic, antilipidemic, and antioxidant effects of EGCG in surviving diabetic mice. Alloxan diabetic mice were treated with EGCG. Their bloods were collected and submitted to various biochemical measurements, including blood glucose, cholesterol, triglycerides, urea, creatinine, and transaminases. Their livers and kidneys were isolated to assess oxidative damage and to perform histological analysis. Both EGCG and insulin treatment of diabetic mice resulted in a significant reduction in fasting blood glucose levels. EGCG supplementation also ameliorated hepatic as well as renal toxicity indices. Moreover, diabetic mice injected with EGCG exhibited significant changes in antioxidant enzyme activities in the liver and kidney. Histological analyses also showed that it exerted an ameliorative action on these organs and efficiently protected the liver-kidney functions of diabetic mice. EGCG was found to bind α-amylase, PTP1B, and α-glucosidase with good affinities ranging from -6.1 to -8.4 kcal/mol. The findings revealed that EGCG administration induced attractive curative effects on diabetic mice, particularly in terms of liver-kidney function. EGCG can, therefore, be considered as a potential strong candidate for future applications to treat and alleviate diabetic burden. Its pharmacokinetics, high affinities, and molecular interactions with the targeted receptors satisfactory explain the in vivo findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Riadh Badraoui reports financial support was provided by University of Hail., (Copyright © 2022 Elsevier B.V. All rights reserved.)

An experiment conducted with 'open microcosm' made by connected sedimentary compartments with different qualities was for 30 days to evaluate the migratory behaviour of nematodes as induced by exposure to pyrene. The nematofauna was collected along with sediment from a reference site in Bizerte lagoon. Following one week acclimatization period, the populated sediments were topped with azoic sediments, with a pyrene concentration of 150 μg kg -1 . The concentration of pyrene from sediments was measured on a weekly basis. A stable status of nematode assemblages was reached between the upper and lower compartments in each microcosm, whatever the treatment type. An upward exploratory phase was observed during the first two weeks within the assemblages, possibly induced by the repellent chemodetection of pyrene. This observation was confirmed by the toxicokinetic properties and molecular interactions of pyrene with the germ-line development Protein 3 and sex-determining protein of Caenorhabditis elegans as nematode model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study reported the fabrication and characterization of gastric dressing, composed of gelatine (GEL), chitosan (CH), and pomegranate peel (PP) extract. The structural changes occurring after γ-irradiation of GEL−CH−PP dressing were reported. The results showed that the electron paramagnetic resonance (EPR) spectroscopy of un-irradiated GEL−CH−PP showed two paramagnetic centers, which corresponded to g = 2.19 and g = 2.002. After irradiation, a new active centre appeared at g = 2.0035 at 10 kGy. The Fourier transform infrared spectroscopy (FTIR) analyses revealed an increase in peak intensity at C−H chains, as well as the C=O carboxyl groups at 10 kGy, due to the cross-linking phenomenon. The X-ray diffraction analysis showed a low change of crystallinity between the range of 2θ (15−30°). Moreover, γ-rays enhanced scavenging DPPH radical activity (51±%) and chelating power activities 79.12%. A significant inhibition of antibacterial and anti-biofilm activities (p < 0.01) was noticed. The hemolysis rates showed 0.42%, suggesting a high hemocompatibility, and exhibited significant anti-inflammatory activity in vitro (48%). In vivo, the healing effects of GEL−CH−PP dressing showed that the incidence and severity of gastric histopathological lesions decreased, compared with the ulcerated group, which could explain the bioavailability and the pharmacokinetic findings. The results highlight the loading of bioactive agents into polymer-based gastric dressings, with promising pharmacokinetics properties and effects on the induced ulcera in rabbits.

In this study, a novel polymeric nanomaterial was synthesized and characterized, and it its potential usability in hypertension treatment was demonstrated. For these purposes, a poly(hydroxyethyl methacrylate-methacryloylamidophenylalanine)-based polymeric nanomaterial (p(HEMPA)) was synthesized using a mini-emulsion polymerization technique. The nanomaterials were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and zeta size analysis. The synthesized p(HEMPA) nanomaterial had a diameter of about 113 nm. Amlodipine-binding studies were optimized by changing the reaction conditions. Under optimum conditions, amlodipine's maximum adsorption value (Qmax) of the p(HEMPA) nanopolymer was found to be 145.8 mg/g. In vitro controlled drug release rates of amlodipine, bound to the nanopolymer at the optimum conditions, were studied with the dialysis method in a simulated gastrointestinal system with pH values of 1.2, 6.8 and 7.4. It was found that 99.5% of amlodipine loaded on the nanomaterial was released at pH 7.4 and 72 h. Even after 72 h, no difference was observed in the release of AML. It can be said that the synthesized nanomaterial is suitable for oral amlodipine release. In conclusion, the synthesized nanomaterial was studied for the first time in the literature as a drug delivery system for use in the treatment of hypertension. In addition, AML-p(HEMPA) nanomaterials may enable less frequent drug uptake, have higher bioavailability, and allow for prolonged release with minimal side effects.

Recently, there has been significant interest in bio-based degradable plastics owing to their potential as a green and sustainable alternative to synthetic plastics due to their biodegradable properties. Polyhydroxybutyrate (PHB) is a biodegradable polymer that is produced by bacteria and archaea as carbon and energy reserves. Due to its rapid degradation in natural environments, it can be considered a biodegradable plastic alternative. In the present study, a dye-based procedure was used to screen PHB-producing bacteria isolated from mangrove soil samples. Among the seven isolates, Agromyces indicus ( A. indicus) , identified by means of 16S rRNA analysis, accumulated the highest amount of PHB. The extracted polymer was characterized by a UV-Vis spectrophotometer, Fourier-transform infrared (FTIR) spectroscopy, and for the presence of the phbB gene, which confirmed the structure of the polymer as PHB. The maximum PHB production by A. indicus was achieved after 96 h of incubation at a pH of 8.0 and 35 °C in the presence of 2% NaCl, with glucose and peptone as the carbon and nitrogen sources, respectively. The strain was found to be capable of accumulating PHB when various cheap agricultural wastes, such as rice, barley, corn, and wheat bran, were used as the carbon sources. The response surface methodology (RSM) through the central composite design (CCD) for optimizing the PHB synthesis was found to be highly efficient at augmenting the polymer yields. As a result of the optimum conditions obtained from the RSM, this strain can increase the PHB content by approximately 1.4-fold when compared with an unoptimized medium, which would substantially lower the production cost. Therefore, the isolate A. indicus strain B2 may be regarded as one of the best candidates for the industrial production of PHB from agricultural wastes, and it can remove the environmental concerns associated with synthetic plastic.

In the present study we focused on the anti-asthmatic and antioxidant effects of Zingiber officinalis roscoe L. (ZO) aqueous extract. This study includes 20 adult male rats, which were grouped into four; Group I: control group; Group II: asthmatic group (Ovalbumin sensitized/challenge model, Oval group); Group III: received ovalbumin sensitized/challenge associated a dose of 207 mg/kg body weight (BW) of ZO (Oval + D1 group); Group IV: received ovalbumin sensitized/challenge associated a dose of 414 mg/k BW of ZO (Oval + D2 group). After 21 days, blood and lung samples were collected for biochemical, hematological, and histopathological analyses. The ameliorative effect of ZO phytochemical compounds was also assessed by in silico approach on transducer and activator of transcription 6 (STAT6) and tumor necrosis factor- α (TNF- α ) receptors. The oxidative/antioxidative status was evaluated in the lung tissues. Our results show that ZO extract alleviated the ovalbumin-induced hematological and biochemical disruptions associated oxidative injury. In fact, white and red blood cells (WBC and RBC, respectively), aspartate aminotransaminase (ASAT), malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase (GPx) were significantly disrupted ( p  < 0.05) in Oval group and alleviated following ZO treatment. Besides, several histopathological features were outlined in lung tissues of Oval group. Interestingly, ZO was found to exert ameliorative effects on tissue level. In silico analyses, particularly the binding affinities, the number of H-bonds, the embedding distance and the molecular interactions of ZO phytochemical compounds with either STAT6 or TNF- α supported the in vivo results. These findings confirm the potential ethno-pharmacological effects of ZO against asthma and its associated complications., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest in the publication., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The effects of microplastics and sorbed polycyclic aromatic hydrocarbons at community levels were rarely assessed in laboratory experiments, despite their obvious advantage in reflecting better the natural conditions compared to traditionally single species-focused toxicological experiments. In the current study, the multifaceted effects of polyvinyl chloride and chrysene, acting alone or combined, on general marine meiobenthos, but with a special focus on free-living marine nematode communities were tested in a laboratory experiment carried in microcosms. The meiobenthos was exposed to two polyvinyl chloride (5 and 10 mg.kg -1 Dry Weight 'DW') and chrysene (37.5 and 75 ng.g -1 DW) concentrations, respectively, as well as to a mixture of both compounds, for 30 days. The results highlighted a significant decrease in the abundance of all meiobenthic generic groups, including nematodes, directly with increasing dosages of these compounds when added alone. The addition of chrysene adheres to microplastics, making the sediment matrix glueyer, hence inducing greater mortality among generic meiobenthic groups. Moreover, the nematofauna went through a strong restructuring phase following the exposure to both compounds when added alone, leading to the disappearance of sensitive nematodes and their replacement with tolerant taxa. However, the similarity in nematofauna composition between control and polyvinyl chloride and chrysene mixtures suggests that the toxicity of the latter could be attenuated by its physical bonding to the former pollutant. Other changes in the functional traits within the nematode communities were a decline in the fertility of females and an increase of the pharyngeal pumping power following exposure to both pollutants for the dominant species. The latter results were also supported by additional toxicokinetics analyses and in silico modeling., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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-IC 50  = 0.670 mg/mL; ABTS-IC 50  = 1.056 mg/mL; β -carotene-IC 50  > 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 IC 50 values of 5.053  μ g/mL, 5.382  μ g/mL, and 6.728  μ g/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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Walid Sabri Hamadou et al.)

The sharp increase in infections due to Staphylococcus aureus is associated with its ability to adapt to changes in its habitat. This study aimed to investigate the differences in the cytoplasmic amino acid profiles of a clinical strain of S. aureus under five combinations of stress-induced conditions representative of a wound site by varying temperature 35-37 °C, adding 0-5% NaCl and adjusting pH 6-8. The results indicated that aspartic acid, lysine, glutamic acid and histidine were the most abundant cytoplasmic amino acids in the control samples grown under optimal growth conditions. However, the magnitudes and levels of these amino acids were altered under the various wound site conditions, which led to differential cytoplasmic amino acid profiles as characterized by multivariate analyses (PLS-DA). The total cytoplasmic amino acid content was significantly reduced in the cells grown with 2.5% NaCl added at pH 7 and 37 °C relative to the control samples and other growth regimes. However, all combinations of enhanced stress conditions showed unique and characteristic changes in the concentration profiles of the cytoplasmic amino acids. These outcomes supported the hypothesis that bacterial cells of S. aureus maintain different metabolic homeostasis under various stress-induced conditions. The potent capability of S. aureus to constantly and rapidly acclimatize to variations within the environment may reflect the crucial feature supporting its virulence as an opportunistic pathogenic bacterium to invade the wound site. Understanding the control systems governing these marked changes in amino acids during the adaptation to the potential wound site conditions of this dangerous bacterium may offer new clinical controls to combat infection.

This study investigated the druggability, pharmacokinetics and ethyl acetate extract of Teucrium polium (EA T. polium ) and the protective effect against carbon tetrachloride (CCl 4 ) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl 4 -induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl 4 in olive oil (0.5 mL/kg); Group III: received the EA T. polium (25 mg/kg) of pretreatment for seven days by gavage then CCl 4 in olive oil by gavage for 15 days. Group IV: received the EA of T. polium for seven days (25 mg/kg). EA T. polium was found to possess significant antioxidant capacity. CCl 4 caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA T. polium pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of T. polium were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of T. polium in this experimental liver cirrhosis model. T. polium phytochemicals are good candidates for further pharmaceutical explorations and drug design.

Methotrexate (MTX) is a chemotherapeutic medicine used in the treatment of several types of cancer and inflammatory diseases. It exhibits several drawbacks especially on highly dividing and developing cells. This study aimed to assess the role of Opuntia ficus indica ethanolic extract on testicular damage induced by MTX in rat. MTX was administrated for 10 days (20 mg/kg). Extract of cactus cladodes ( Opuntia ficus indica ) was given to MTX-treated rats (0.4 g/kg). Spermatozoa were collected from cauda epididymis and analyzed for sperm count and motility. Testis samples were used for histopathological and oxidative stress studies (assessment of malondialdehyde (MDA) levels, protein carbonyls (PCs), catalase (CAT) glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities). Moreover, levels of testosterone were measured in serum by radioimmunoassay. Our results showed that MTX had destructive effects on sperm count and motility associated with significant decrease in testosterone levels in MTX group. This effect was then confirmed by docking results. Testis of MTX group showed increased oxidative stress status. In fact, PCs and MDA were increased and CAT, GPx and SOD were decreased suggesting increased reactive oxygen species and deficiency in enzymatic antioxidant. These findings were associated with disrupted testicular morphology as assessed by histological study. Cladodes extract had protective effects on rat's gonad histology, oxidative stress and improve both sperm parameters (count and motility) and serum testosterone levels. In conclusion, our results suggested that Opuntia ficus indica cladodes extract improved MTX-induced testicular injury and possess potent fertility boosting effects in rats.Communicated by Ramaswamy H. Sarma.