Design and synthesis of novel 2-(2-(4-bromophenyl)quinolin-4-yl)-1,3,4-oxadiazole derivatives as anticancer and antimicrobial candidates: in vitro and in silico studies.

Cancer is the second leading cause of death globally, surpassed only by heart disease. Moreover, bacterial infections remain a significant global health burden, contributing substantially to morbidity and mortality, especially among hospitalized patients. EGFR has emerged as a prime therapeutic target due to its pivotal role in driving uncontrolled cell growth and survival across numerous cancer types. In addition, DNA gyrase represents a promising target for the development of novel antimicrobial agents. Therefore, we aimed to design and synthesize new multi-target quinoline hybrids (7-17e) capable of acting as anti-proliferative and antimicrobial agents by inhibiting EGFR and microbial DNA gyrase, respectively. The inhibitory potential of the synthesized compounds was determined using in vitro and in silico approaches. The antiproliferative activity of the synthesized quinoline-oxadiazole derivatives 7-17e was assessed against two cancer cell lines, namely, hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7). The assessed compounds 7-17e showed considerable cytotoxic activity activities against HepG2 and MCF-7 with IC50 values of 0.137-0.332 and 0.164-0.583 µg mL-1, respectively, in comparison to erlotinib as the positive control, which showed an IC50 value of 0.308 and 0.512 µg mL-1, respectively. Moreover, an EGFR tyrosine kinase inhibition assay was conducted on the most prominent candidates. The results showed good IC50 values of 0.14 and 0.18 µM for compounds 8c and 12d, respectively, compared to lapatinib (IC50 value of 0.12 µM). Furthermore, the minimum antimicrobial inhibitory concentration was evaluated for the most prominent candidates with S. aureus, E. coli, and C. albicans. Compounds 17b, 17d and 17e displayed the most potent inhibitory activity, exhibiting 4-, 16- and 8-fold more activity, respectively, than the reference neomycin. Hence, we can conclude that the afforded compounds can be used as lead dual anticancer and antimicrobial candidates for future optimization.

Mangiferin: An effective agent against human malignancies.

Mangiferin is a bioactive substance present in high concentration in mangoes and also in some other fruits. Owing to its potential as a chemopreventive and chemotherapeutic agent against several types of cancer, this unique, significant, and well-researched polyphenol has received a lot of attention recently. It possesses the ability to treat cancers, including rectal cancer, prostate cancer, ovarian cancer, leukemia, gastric cancer, liver cancer, chronic pancreatitis, and lung cancer. It can control/regulate multiple key signaling pathways, such as signal transducer and activator of transcription 3 (STAT3), second mitochondria-derived activator of caspases/direct inhibitor of apoptosis (IAP)-binding protein with low propidium iodide (pl) (Smac/DIABLO) nuclear factor kappa B (NF-κB), phosphatidylinositol 3 kinase/protein 3 kinase (PI3K/Akt), transforming growth factor beta/suppressor of mothers against decapentaplegic (TGF-ß/SMAD), c-jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38-MAPK), and phosphor-I kappa B kinase (p-IκB), which are crucial to the development of cancers. By triggering apoptotic signals and halting the advancement of the cell cycle, it can also prevent some cancer cell types from proliferating and developing. It has been revealed that mangiferin targets a variety of adhesion molecules, cytokines, pro-inflammatory transcription factors, kinases, chemokines, growth factors, and cell-cycle proteins. By means of preventing the onset, advancement, and metastasis of cancer, these targets may mediate the chemopreventive and therapeutic effects of mangiferin. Mangiferin has confirmed potential benefits in lung, cervical, breast, brain, and prostate cancers as well as leukemia whether administered alone or in combination with recognized anticancer compounds. More clinical trials and research investigations are required to completely unleash the potential of mangiferin, which may lower the risk of cancer onset and act as a preventive and therapeutic alternative for a number of cancers.

Synthesis of chitosan/Fe2O3/CuO-nanocomposite and their role as inhibitor for some biological disorders in vitro with molecular docking interactions studies.

The hybrid material between the functional elements particularly with the polymer compounds as a nanocomposites are attractive in numerous fields. In the current work, chitosan/Fe2O3/CuO-nanocomposite has been successfully synthesized in situ via a coprecipitation method and characterized by several apparatuses. The X-ray diffraction cleared that chitosan/Fe2O3/CuO-nanocomposite was crystalline. Transmission Electron Microscopy (TEM) showed that the size of chitosan/Fe2O3/CuO-nanocomposite was of 17-85 nm. Candida albicans, Candida tropicalis, and Geotrichum candidum were inhibited employing the chitosan/Fe2O3/CuO-nanocomposite with inhibition areas of 25 ± 0.1 and 30 ± 0.1, and 23 ± 0.2 mm, respectively. Minimum inhibitory concentration (MIC) of chitosan/Fe2O3/CuO-nanocomposite was 15.62, 31.25, and 62.5 µg/mL for C. tropicalis, C. albicans, and G. candidum, respectively. Biofilm formation of C. albicans, C. tropicalis and G. candidum was inhibited at level of 95.31, 96.65, and 93.63 %, respectively at 75 % MIC of chitosan/Fe2O3/CuO-nanocomposite. The exposed C. tropicalis to chitosan/Fe2O3/CuO-nanocomposite showed severe damag of cytoplasm membrane with cell wall rupture. Chitosan/Fe2O3/CuO-nanocomposite reflected anticancer potential against human skin cancer (A-431) cells with IC50 of 77.79 ± 1.37 µg/mL. Moreover, wound heals was induced by chitosan/Fe2O3/CuO-nanocomposite with closure level 92.76 %. Molecular docking studies suggested strong binding of C. tropicalis (PDB ID: 8BH8) and A-431 (PDB ID: 5JJX) proteins with CuO nanoparticles and FeO nanoparticles.

Improving plant adaptation to soil antimony contamination: the synergistic contribution of arbuscular mycorrhizal fungus and olive mill waste.

BACKGROUND: This study aimed to investigate the alterations in biochemical and physiological responses of oat plants exposed to antimony (Sb) contamination in soil. Specifically, we evaluated the effectiveness of an arbuscular mycorrhizal fungus (AMF) and olive mill waste (OMW) in mitigating the effects of Sb contamination. The soil was treated with a commercial strain of AMF (Rhizophagus irregularis) and OMW (4% w/w) under two different levels of Sb (0 and 1500 mg kg-1 soil). RESULTS: The combined treatment (OMW + AMF) enhanced the photosynthetic rate (+ 40%) and chlorophyll a (+ 91%) and chlorophyll b (+ 50%) content under Sb condition, which in turn induced more biomass production (+ 67-78%) compared to the contaminated control plants. More photosynthesis in OMW + AMF-treated plants gives a route for phenylalanine amino acid synthesis (+ 69%), which is used as a precursor for the biosynthesis of secondary metabolites, including flavonoids (+ 110%), polyphenols (+ 26%), and anthocyanins (+ 63%) compared to control plants. More activation of phenylalanine ammonia-lyase (+ 38%) and chalcone synthase (+ 26%) enzymes in OMW + AMF-treated plants under Sb stress indicated the activation of phenylpropanoid pathways in antioxidant metabolites biosynthesis. There was also improved shifting of antioxidant enzyme activities in the ASC/GSH and catalytic pathways in plants in response to OMW + AMF and Sb contamination, remarkably reducing oxidative damage markers. CONCLUSIONS: While individual applications of OMW and AMF also demonstrated some degree of plant tolerance induction, the combined presence of AMF with OMW supplementation significantly enhanced plant biomass production and adaptability to oxidative stress induced by soil Sb contamination.

Exploring biosurfactant from Halobacterium jilantaiense as drug against HIV and zika virus: fabrication, characterization, cytosafety property, molecular docking, and molecular dynamics simulation.

Biosurfactants are surface-active molecules with unique qualities and various uses. Many microorganisms produce secondary metabolites with surface-active characteristics that serve various antiviral functions. The HIV and Zika viruses were chosen for this study because they can spread from mother to child and result in potentially fatal infections in infants. Halophilic bacteria from the Red Sea solar saltern in Egypt were screened using drop collapse, emulsification activity, and oil displacement assays to produce biosurfactants and emulsifiers. Halobacterium jilantaiense strain JBS1 was the most effective strain of the Halobacteriaceae family. It had the best oil displacement test and emulsification activity against kerosene and crude oil, respectively. Among the ten isolates, it produced the most promising biosurfactant, also recognized by the GC-MASS library. This study evaluated biosurfactants from halophilic bacteria as potential antiviral drugs. Some of the computer methods we use are molecular docking, ADMET, and molecular dynamics. We use model organisms like the HIV reverse transcriptase (PDB: 5VZ6) and the Zika virus RNA-dependent RNA polymerase (ZV-RdRP). Molecular docking and molecular dynamics make the best complexes with 5VZ6 HIV-RT and flavone (C25) and 5wz3 ZV-RdRP and ethyl cholate (C8). Testing for ADMET toxicity on the complex revealed that it is the safest medicine conceivable. The 5VZ6-C25 and 5wz3-C8 complexes also followed the Lipinski rule. They made five hydrogen bond donors and ten hydrogen bond acceptors with 500 Da MW and a 5:1 octanol/water partition coefficient. Finally, extreme settings require particular adaptations for stability, and extremophile biosurfactants may be more stable.

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

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

A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

Chromium(VI) Toxicity and Active Tolerance Mechanisms of Wheat Plant Treated with Plant Growth-Promoting Actinobacteria and Olive Solid Waste.

The present study aimed to assess the potential of plant growth-promoting Actinobacteria and olive solid waste (OSW) in ameliorating some biochemical and molecular parameters of wheat (Triticum aestivum) plants under the toxicity of high chromium levels in the soil. With this aim, a pot experiment was conducted, where the wheat plants were treated with a consortium of four Actinobacterium sp. (Bf treatment) and/or OSW (4% w/w) under two levels of nonstress and chromium stress [400 mg Cr(VI) per kg of soil] to estimate the photosynthetic traits, antioxidant protection machine, and detoxification activity. Both Bf and OSW treatments improved the levels of chlorophyll a (+47-98%), carotenoid (+324-566%), stomatal conductance (+17-18%), chlorophyll fluorescence (+12-28%), and photorespiratory metabolism (including +44-72% in glycolate oxidase activity, +6-72% in hydroxypyruvate reductase activity, and +5-44% in a glycine to serine ratio) in leaves of stressed plants as compared to those in the stressed control, which resulted in higher photosynthesis capacity (+18-40%) in chromium-stressed plants. These results were associated with an enhancement in the content of antioxidant metabolites (+10-117%), of direct reactive oxygen species-detoxifying enzymes (+49-94%), and of enzymatic (+40-261%) and nonenzymatic (+17-175%) components of the ascorbate-glutathione cycle in Bf- and OSW-treated plants under stress. Moreover, increments in the content of phytochelatins (+38-74%) and metallothioneins (+29-41%), as markers of detoxification activity, were recorded in the plants treated with Bf and OSW under chromium toxicity. In conclusion, this study revealed that the application of beneficial Actinobacteria and OSW as biofertilization/supplementation could represent a worthwhile consequence in improving dry matter production and enhancing plant tolerance and adaptability to chromium toxicity.

Molecular Profile and the Effectiveness of Antimicrobials Drugs Against Staphylococcus aureus and Pseudomonas aeruginosa in the Diagnostic Approaches of Otitis Infection.

Background: Otitis externa and otitis media are two types of ear infections that affect people of all ages, although they are more common in newborns and young children. Antibiotic usage, healthcare, and advanced age all play a role in the development of this illness. Methods: Fifty-eight patients with various kinds of infections of the ears were voluntary patients attending the outpatient clinics of the Prince Mutaib Bin Abdulaziz Hospital in Sakaka, Al Jouf, Saudi Arabia, examined to evaluate the role of bacteria and the likely significance of plasmids in their antibiotic resistance as ear infectious agents. Results: Staphylococcus aureus and Pseudomonas aeruginosa are the most prevalent bacteria found in ear infections. The greatest number of major bacterial isolates were S. aureus (54%), followed by P. aeruginosa (13%), whereas a smaller number of isolates (3%) were from Streptococcus pyogenes, Bacillus subtilis, and Proteus vulgaris, respectively. Mixed growth was noted in 3.4% of instances. The isolation rate for Gram-positive organisms was 72%, while the rate for Gram-negative species was 28%. All the isolates had DNA greater than 14 kilobases. Hind III analysis of the plasmid DNA extracted from the resistant strains of ear infection demonstrated that antibiotic-resistance plasmids were extensively dispersed. Exotoxin A PCR amplification indicated 396 pb PCR-positive DNA for all identified samples, with the exception of three strains for which no band was observed. Patients in the epidemiological study ranged in number, but all were linked together for the purposes of the study because of their shared epidemiological characteristics. Conclusion: Vancomycin, linezolid, tigecycline, rifampin, and daptomycin are all antibiotics that have been shown to be effective against S. aureus and P. aeruginosa. Microbiological pattern evaluation and antibiotic sensitivity patterns of the microorganisms providing empirical antibiotics are becoming increasingly crucial to minimize issues and the development of antibiotic-resistant strains.

Avian campylobacteriosis, prevalence, sources, hazards, antibiotic resistance, poultry meat contamination, and control measures: a comprehensive review.

Avian campylobacteriosis is a vandal infection that poses human health hazards. Campylobacter is usually colonized in the avian gut revealing mild signs in the infected birds, but retail chicken carcasses have high contamination levels of Campylobacter spp. Consequently, the contaminated avian products constitute the main source of human infection with campylobacteriosis and result in severe clinical symptoms such as diarrhea, abdominal pain, spasm, and deaths in sensitive cases. Thus, the current review aims to shed light on the prevalence of Campylobacter in broiler chickens, Campylobacter colonization, bird immunity against Campylobacter, sources of poultry infection, antibiotic resistance, poultry meat contamination, human health hazard, and the use of standard antimicrobial technology during the chicken processing of possible control strategies to overcome such problems.

Ameliorative avian gut environment and bird productivity through the application of safe antibiotics alternatives: a comprehensive review.

The avian digestive tract is an important system for converting ingested food into the nutrients their bodies need for maintenance, growth, and reproduction (meat, table eggs, and fertile eggs). Therefore, preserving digestive system integrity is crucial to bird health and productivity. As an alternative to antibiotics, the world has recently turned to the use of natural products to enhance avian development, intestinal health, and production. Therefore, the primary goal of this review is to explain the various characteristics of the avian digestive tract and how to enhance its performance with natural, safe feed additives such as exogenous enzymes, organic acids, photogenic products, amino acids, prebiotics, probiotics, synbiotics, and herbal extracts. In conclusion, the composition of the gut microbiome can be influenced by a number of circumstances, and this has important consequences for the health and productivity of birds. To better understand the connection between pathogens, the variety of therapies available, and the microbiome of the gut, additional research needs to be carried out.

Characterization of Delonix regia Flowers' Pigment and Polysaccharides: Evaluating Their Antibacterial, Anticancer, and Antioxidant Activities and Their Application as a Natural Colorant and Sweetener in Beverages.

In the present study, an attempt was made to investigate the in vitro antioxidant, anticancer, and antibacterial activities of Delonix regia, then in vivo evaluate its safety as a natural colorant and sweetener in beverages compared to synthetic colorant and sweetener in rats, then serve the beverages for sensory evaluation. Delonix regia flowers had high protein, polysaccharide, Ca, Na, Mg, K, and Fe contents. The Delonix regia pigment extract (DRPE) polysaccharides were separated and purified by gel permeation chromatography on Sephacryl S-200, characterized by rich polysaccharides (13.6 g/L). The HPLC sugar profile detected the monosaccharides in the extracted polysaccharides, composed of mannose, galactose, glucose, arabinose, and gluconic acid, and the structure of saccharides was confirmed by FTIR, which showed three active groups: carbonyl, hydrocarbon, and hydroxyl. On the other hand, the red pigment constituents of DRPE were detected by HPLC; the main compounds were delphinidin and cyanidin at 15 µg/mL. The DRPE contained a considerable amount (26.33 mg/g) of anthocyanins, phenolic compounds (64.7 mg/g), and flavonoids (10.30 mg/g), thus influencing the antioxidant activity of the DRPE, which scavenged 92% of DPPH free radicals. Additionally, it inhibited the population of pathogenic bacteria, including Staphylococcus aureus, Listeria monocyogenes, Salmonella typhimurum, and Pseudomonas aeruginosa, in the range of 30-90 µg/mL, in addition to inhibiting 85% of pancreatic cancer cell lines. On the in vivo level, the rats that were delivered a diet containing DRPE showed regular liver markers (AST, ALP, and ALT); kidney markers (urea and creatinine); high TP, TA, and GSH; and low MDA, while rats treated with synthetic dye and aspartame showed higher liver and kidney markers; lowered TP, TA, and GSH; and high MDA. After proving the safety of DRPE, it can be safely added to strawberry beverages. Significant sensorial traits, enhanced red color, and taste characterize the strawberry beverages supplemented with DRPE. The lightness and redness of strawberries were enhanced, and the color change ΔE values in DRPE-supplemented beverages ranged from 1.1 to 1.35 compared to 1.69 in controls, indicating the preservative role of DRPE on color. So, including DRPE in food formulation as a natural colorant and sweetener is recommended for preserving health and the environment.

Antimicrobial Resistance Pattern, Pathogenicity and Molecular Properties of Hypervirulent Klebsiella pneumonia (hvKp) among Hospital-Acquired Infections in the Intensive Care Unit (ICU).

Hypervirulent Klebsiella pneumoniae (hvKp) is a new emerging variant of K. pneumoniae that is increasingly reported worldwide. The variant hvKp is known to cause severe invasive community-acquired infections such as metastatic meningitis, pyogenic liver abscesses (PLA) and endophthalmitis, but its role in hospital-acquired infections (HAIs) is little known. The aim of this study was to evaluate the prevalence of hvKp among hospital-acquired (HA) K. pneumoniae infections in the intensive care unit (ICU) and to compare between hvKp and classical K. pneumoniae (cKP) regarding antimicrobial resistance pattern, virulence and molecular characteristics. The study was cross-sectional and included 120 ICU patients suffering from HA K. pneumoniae infections between January and September 2022. K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and detection of extended-spectrum-ß-lactamase (ESBL) production by the Phoenix 100 automated microbiology system, string test, biofilm formation, serum resistance assay, and detection of virulence-associated genes (rmpA, rmpA2, magA, iucA) and capsular serotype-specific genes (K1, K2, K5, K20, K57) by polymerase chain reaction (PCR). Of 120 K. pneumoniae isolates, 19 (15.8%) were hvKp. The hypermucoviscous phenotype was more significantly detected in the hvKp group than in the cKP group (100% vs. 7.9%, p ≤ 0.001). The rate of resistance to different antimicrobial agents was significantly higher in the cKP group than that in the hvKp group. Fifty-three strains were identified as ESBL-producing strains, which was more frequent in the cKP group than in the hvKp group (48/101 [47.5%] vs. 5/19 [26.3%], respectively, p ≤ 0.001). The hvKP isolates were highly associated with moderate and strong biofilm formation than cKP isolates (p = 0.018 and p = 0.043 respectively). Moreover, the hvKP isolates were highly associated with intermediate sensitivity and re sistance to serum in the serum resistance assay (p = 0.043 and p = 0.016 respectively). K1, K2, rmpA, rmpA2, magA and iucA genes were significantly associated with hvKp (p ≤ 0.001, 0.004, <0.001, <0.001, 0.037 and <0.001, respectively). However, K5, K20 and K57 were not associated with hvKp. The hvKp strains have emerged as a new threat to ICU patients because of their ability to cause more severe and life-threatening infections than cKP. The string test alone as a laboratory test for screening of hvKp has become insufficient. Recently, hvKp was defined as hypermucoviscous- and aerobactin-positive. It is important to improve the awareness towards the diagnosis and management of hvKp infections.

Natural bioactive compounds-doxorubicin combinations targeting topoisomerase II-alpha: Anticancer efficacy and safety.

Cancer is one of the leading causes of death worldwide, so pursuing effective and safe therapeutics for cancer is a key research objective nowadays. Doxorubicin (DOX) is one of the commonly prescribed chemotherapeutic agents that has been used to treat cancer with its antimitotic properties via inhibition of topoisomerase II (TOP2) activity. However, many problems hinder the broad use of DOX in clinical practice, including cardiotoxicity and drug resistance. Research in drug discovery has confirmed that natural bioactive compounds (NBACs) display a wide range of biological activities correlating to anticancer outcomes. The combination of NBACs has been seen to be an ideal candidate that might increase the effectiveness of DOX therapy and decreases its unfavorable adverse consequences. The current review discusses the chemo-modulatory mechanism and the protective effects of combined DOX with NBACs with a binding affinity (pKi) toward TOP2A more than pKi of DOX. This review will also discuss and emphasize the molecular mechanisms to provide a pathway for further studies to reveal other signaling pathways. Taken together, understanding the fundamental mechanisms and implications of combined therapy may provide a practical approach to battling cancer diseases.

Pomegranate Peel Extract Stabilized Selenium Nanoparticles Synthesis: Promising Antimicrobial Potential, Antioxidant Activity, Biocompatibility, and Hemocompatibility.

The green synthesis of selenium nanoparticles (Se NPs) had been synthesized by pomegranate peel extract (PPE). The antimicrobial, antioxidant, and anticancer activities of the synthesized Se NPs, as well as their hemocompatibility, were investigated. Se NPs were characterized by UV-Vis., SEM, XRD, HR-TEM, DLS, EDX, FTIR, and mapping techniques. HR-TEM image represented the spheroidal forms with moderately monodispersed NPs with a mean diameter 14.5 nm. The SEM image of Se NPs, incorporated with PPE, exhibits uniform NP surfaces, and the appearance was clear. The antimicrobial results confirmed the potential of Se NPs to hinder the growth of some tested pathogenic microbes. Results revealed that Se NPs exhibited promising antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Streptococcus mutans where inhibition zones were 29, 16, 41, 22, and 54 mm, respectively. Likewise, it exhibited antifungal activity where the values of inhibition zones were 41, 40, 38, and 36 mm against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and A. niger, respectively. The antioxidant activities of Se NPs at concentrations 250-4000 µg/mL were greater than 90% in all cases. Se NP concentrations of 500 µg/mL or less are safe in usage according to hemocompatibility study. Se NPs had an IC50 of 113.73 µg/mL in a cytotoxicity experiment. Results revealed that Se NPs have promising anticancer activities against MCF7 and Mg63 cancerous cell line, where IC50 was 69.8 and 47.9 µg/mL, respectively. In conclusion, Se NPs were successfully biosynthesized using PPE for the first time; these Se NPs had promising antimicrobial, antioxidant, and anticancer activities.

Valorizing the usage of olive leaves, bioactive compounds, biological activities, and food applications: A comprehensive review.

Olive oil production is a significant source of economic profit for Mediterranean nations, accounting for around 98 percent of global output. Olive oil usage has increased dramatically in recent years, owing to its organoleptic characteristics and rising knowledge of its health advantages. The culture of olive trees and the manufacture of industrial and table olive oil produces enormous volumes of solid waste and dark liquid effluents, involving olive leaves, pomace, and olive oil mill wastewaters. These by-products cause an economic issue for manufacturers and pose major environmental concerns. As a result, partial reuse, like other agronomical production wastes, is a goal to be achieved. Because these by-products are high in bioactive chemicals, which, if isolated, might denote components with significant added value for the food, cosmetic, and nutraceutical sectors, indeed, they include significant amounts of beneficial organic acids, carbohydrates, proteins, fibers, and phenolic materials, which are distributed differently between the various wastes depending on the olive oil production method and table olive agronomical techniques. However, the extraction and recovery of bioactive materials from chosen by-products is a significant problem of their reasonable value, and rigorous detection and quantification are required. The primary aims of this review in this context are to outline the vital bioactive chemicals in olive by-products, evaluate the main developments in extraction, purification, and identification, and study their uses in food packaging systems and safety problems.

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

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

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery.

(1) Background: Chitosan-gelatin-based thermosensitive hydrogel containing 5FU-alginate nanoparticles was formulated for the effective and sustained delivery of 5FU to the skin. (2) Methods: Alginate, a polysaccharide was used for the formulation of nanoparticles using a spray drying technique. Size, zeta potential, and surface morphology were investigated using a zetasizer and scanning electron microscope. The hydrogel was fabricated using chitosan and gelatin. Several important analyses were used to characterize these prepared topical hydrogels. The pH, visual transparency, rheological behavior, and swelling index of the prepared hydrogels were evaluated. The in vitro release studies were performed at different pH (5.5 and 7.4) and temperature (32 and 37 °C) conditions using a Franz diffusion cell. Ex vivo permeation and in vivo studies were performed using Sprague Dawley rats. (3) Results: Results show that spherical nanoparticles were produced at sizes of 202−254 nm and with zeta potentials of −43 to −38 mV. The prepared nanoparticles were successfully incorporated into chitosan-gelatin-based hydrogels using a glycerol 2-phosphate disodium salt hydrates crosslinker. Drug polymers and excipients compatibility and formulation of hydrogels was confirmed by ATR-FTIR results. The pH of the prepared hydrogels was in accordance with the skin pH. The viscosity of prepared hydrogel increased with temperature increase and phase transition (sol-gel transition) occurred at 34 °C. The release of drug was sustained in case of nanoparticles incorporated hydrogels (5FU-Alg-Np-HG) as compared to nanoparticles (5FU-Alg-Np) and simple hydrogels (5FU-HG) (ANOVA; p < 0.05). The premature and initial burst release of 5FU was prevented using 5FU-Alg-Np-HG. The release mechanism of 5FU from the 5FU-Alg-Np-HG diffusion was followed by swelling and erosion, as suggested by Korsmeyer-Peppas model. The prepared hydrogel proved to be non-irritant. Ex vivo permeation study across rat's skin suggests that permeability of nanoparticles (5FU-Alg-Np) was higher than the 5FU-Alg-Np-HG (ANOVA; p < 0.05). However, skin-related drug retention of 5FU-Alg-Np-HG was significantly higher than the 5FU solution, 5FU-Alg-Np, and 5FU-HG (ANOVA; p < 0.05). This was due to swelling of hydrogels in the lower layers of skin where the temperature is 37 °C. The higher concentration of 5FU in the skin is helpful for treatment of local skin cancer, such as melanoma, and actinic keratosis. In vivo results also confirmed maximum AUC, t1/2, and skin-related drug retention of 5FU-Alg-Np-HG. (4) Conclusions: Chitosan-gelatin-based hydrogels containing 5FU-Alg-Np possess exceptional properties, and can be used for the sustained delivery of 5FU for the treatment of local skin cancers.