Newly synthesized chitosan nanoparticles loaded with caffeine/moringa leaf extracts Halt Her2, BRCA1, and BRCA2 expressions.

Breast cancer is among the highest morbidity and mortality rates in women around the world. In the present investigation we aimed to synthesis novel nanosystem combining two naturally important anticancer agents with different mechanism of action namely Moringa oleifera and caffeine. Firstly, chemical analysis of Moringa oleifera extract and caffeine was done by gas chromatography-mass spectroscopy (GC-MS) in order to assess the main chemical compounds present and correlate between them and the possible anticancer effect. The novel nanosystem was characterized through dynamic light scattering techniques which revealed the stability and homogeneity of the prepared M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles, while FTIR and transmission electron microscope (TEM) proved the shape and the successful incorporation of M. oleifera leaves extract/Caffeine onto the nanochitosan carrier. Our initial step was to assess the anticancer effect in vitro in cancer cell line MCF-7 which proved the significant enhanced effect of M. oleifera leaves extract/Caffeine nanosystem compared to M. oleifera leaves extract or caffeine loaded nanoparticles. Further studies were conducted in vivo namely tumor biomarkers, tumor volume, bioluminescence imaging, molecular and histopathological investigations. The present study proved the potent anticancer effect of the synthesized M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles. Mo/Caf/CsNPs exhibited a large number of apoptotic cells within the tumor mass while the adipose tissue regeneration was higher compared to the positive control. The prepared nanoparticles downregulated the expression of Her2, BRCA1 and BRCA2 while mTOR expression was upregulated. The aforementioned data demonstrated the successful synergistic impact of Moringa and caffeine in decreasing the carcinoma grade.

Correction: Diad et al. Novel Amoxicillin-Loaded Sericin Biopolymeric Nanoparticles: Synthesis, Optimization, Antibacterial and Wound Healing Activities. Int. J. Mol. Sci. 2022, 23, 11654.

In the original publication [...].

Correction: Elwakil et al. Memory Impairment, Pro-Inflammatory Host Response and Brain Histopathologic Severity in Rats Infected with K. pneumoniae or P. aeruginosa Meningitis. Pathogens 2022, 11, 933.

In the original publication [...].

Potent biological activity of newly fabricated silver nanoparticles coated by a carbon shell synthesized by electrical arc.

Highly effective AgNPs@C was efficiently synthesized by electrical arc powered by single spark unit which was sufficient to ionize the dielectric media (deionized water) through applying strong electric field between the electrodes (silver and carbon). The AgNPs@C shell was characterized in terms of stability, morphology and phase structure. All characterizations showed that the prepared silver nanoparticles were spherical with average size reached 17 nm coated with carbon shell. The antibacterial effect of the synthesized nanoparticles was tested against Pseudomonas aeruginosa in comparison to Ceftazidime (commonly used antibiotic against P. aeruginosa infections). It was revealed that AgNPs@C shell has superior activity with inhibition zone diameter reached 15 mm and minimum inhibitory concentration reached 2 µg/mL. The observed activity was further confirmed by confocal microscope which showed an increased red region, representing the dead cells, correlated with the presence of AgNPs@C. Moreover, transmission electron microscope studies implied the possible AgNPs@C antibacterial mechanism of action was the nanoparticles adherence to the bacterial membrane causing cell lysis. The molecular studies against fimH (virulence adhesion gene), rmpA (mucoid factor encoding gene), and mrkA (biofilm forming gene) proved the inhibition of their genetic expression. The cytotoxic effect of the synthesized AgNPs@C showed CC50 reached 235.5 µg/mL against normal lung cells (L929 cell line).

The first-in-class pyrazole-based dual InhA-VEGFR inhibitors towards integrated antitubercular host-directed therapy.

Several facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhibitors thematic scaffold. Accordingly, new series of 3-(p-chlorophenyl)-1-phenylpyrazole derivatives tethered to substituted ureas and their isosteres were synthesized, evaluated against Mycobacterium tuberculosis virulent cell line H37Rv, and assessed for their InhA inhibitory activities. The urea derivatives 8d and 8g exhibited the most promising antitubercular activity (MIC = 6.25 µg/mL) surpassing triclosan (MIC = 20 µg/mL) with potential InhA inhibition, thus identified as the study hits. Interestingly, both compounds inhibited VEGFR-2 at nanomolar IC50 (15.27 and 24.12 nM, respectively). Docking and molecular dynamics simulations presumed that 8d and 8g could bind to their molecular targets InhA and VEGFR-2 posing essential stable interactions shared by the reference inhibitors triclosan and sorafenib. Finally, practical LogP, Lipinski's parameters and in silico ADMET calculations highlighted their drug-likeness as novel leads in the arsenal against TB.

In vitro and in vivo anti-colorectal cancer effect of the newly synthesized sericin/propolis/fluorouracil nanoplatform through modulation of PI3K/AKT/mTOR pathway.

The present work aimed to assess the potential effect of sericin/propolis/fluorouracil nanoformula against colorectal cancer (CRC) (the fourth most common cause of cancer-related mortalities). A novel anti-cancerous formula of the synthesized sericin/propolis nanoparticles was developed and tested both in vitro (using Caco-2 cell line) and in vivo (in experimentally induced colorectal cancer animal models). The combination index of the prepared nanoformula proved that the combination between sericin/propolis nanoparticles and 5-fluorouracil demonstrated the highest synergistic effect (0.86), with dose reduction index (DRI) of the chemotherapeutic drug reaching 1.49. The mechanism of action of the prepared nanoformula revealed that it acts through the inhibition of the PI3K/AKT/mTOR signaling pathway and consequently inhibiting cancerous cells proliferation. Treatment and prophylactic studies of both sericin and propolis showed increased TBARS (Thiobarbituric Acid Reactive Substance) formation, downregulated BCL2 (B-cell lymphoma 2) and activated BAX, Caspase 9 and Caspase 3 expression. The prepared nanoformula decreased the ROS (Reactive Oxygen Species) production in vivo owing to PI3K/AKT/mTOR pathway inhibition and FOXO-1 (Forkhead Box O1) activation that resulted in autophagy/apoptosis processes stimulation. The potent anticancer effect of the prepared nanoformula was further emphasized through the in vivo histopathological studies of experimentally induced tumors. The newly formulated sericin/propolis/fluorouracil nanoparticles exhibited clear-cut cytotoxic effects toward tumor cells with provided evidence for the prophylactic effect.

Selenium nanoparticles coated bacterial polysaccharide with potent antimicrobial and anti-lung cancer activities.

Bacterial exopolysaccharides are homopolymeric or heteropolymeric polysaccharides with large molecular weights (10-1000 kDa). Exopolysaccharides' functional uses and potential have revolutionized the industrial and medicinal industries. Hence, the aim of the present study was to optimize the production of bacterial exopolysaccharide and apply it as a capping agent for selenium nanoparticles synthesis. Exopolysaccharide (EPS) producing Lactic acid bacteria (LAB) were isolated from dairy products then biochemically characterized and assessed for their potential antimicrobial effect. The most potent EPS producer was identified as Lactiplantibacillus plantarum strain A2 with accession number OP218384 using 16S rRNA sequencing. Overall, FTIR data of the extracted EPS revealed similarity with amylopectin spectrum. 1H NMR spectrum revealed an α-anomeric configuration of the glycosidic linkage pattern in the polysaccharides while the 13C NMR spectrum can also be separated into two main portions, the anomeric carbons region (δ 98-102 ppm) and the non-anomeric carbons region (δ 60-81 ppm). Antimicrobial activity of the produced EPS showed maximum activity against Staphylococcus aureus, MRSA, Enterobacter aerogenes, Klebsiella pneumoniae and Candida albicans respectively. The EPS capsule layer surrounding the bacterial cells was detected by TEM study. Optimization of EPS production was evaluated using Taguchi design, trial 23 reported the highest biomass yield and EPS output (6.5 and 27.12 g/L respectively) with 2.4 and 3.3 folds increase (from the basal media) respectively. The optimized exopolysaccharide was used as a capping and stabilizing agent for selenium nanoparticles (EPS-SeNPs) synthesis. Zeta potential, size and PDI of the synthesized nanoparticles were - 19.7 mV, 45-65 nm and 0.446 respectively with strong bactericidal and fungicidal effect against the tested pathogens. Complete microbial growth eradication was recorded after 6, 8 and 10 h against Staphylococcus aureus, Candida albicans and Klebsiella pneumoniae respectively. EPS-SeNPs showed a potent antioxidant effect reached 97.4% and anticancer effect against A549 lung cancer cell line (IC50 reached 5.324 µg/mL). EPS-SeNPs inhibited cancerous cell growth at S phase. Moreover, molecular studies revealed the anti-apoptotic activity of Bcl2's was inhibited and Bax was activated. The present investigation successfully synthesized selenium nanoparticles through bacterial EPS with significantly high antimicrobial and anticancer activity.

Nanoemulsion of Lavandula angustifolia Essential Oil/Gold Nanoparticles: Antibacterial Effect against Multidrug-Resistant Wound-Causing Bacteria.

Hospitalized patients are severely impacted by delayed wound healing. Recently, there has been a growing focus on enhancing wound healing using suitable dressings. Lavandula angustifolia essential oil (LEO) showed potential antibacterial, anti-inflammatory, and wound healing properties. However, the prepared gold nanoparticles possessed multifunctional properties. Consequently, the present investigation aimed to synthesize a novel nanosystem consisting of nano-Lavandula angustifolia essential oil and gold nanoparticles prepared through ultrasonic nanoemulsifying techniques in order to promote wound healing and combat bacterial infection. LEO showed potent antibacterial activity against Klebsiella pneumoniae, MRSA and Staphylococcus aureus with minimum inhibitory concentration (MIC) values of 32, 16 and 16 µg/mL, respectively, while exhibiting low activity against Proteus mirabilis. Interestingly, the newly formulated nano-gold/nano-Lavandula angustifolia penetrated the preformed P. mirabilis biofilm with a full eradication of the microbial cells, with MIC and MBEC (minimal biofilm eradication concentration) values reaching 8 and 16 µg/mL, respectively. The cytotoxic effect of the novel nanoformula was also assessed against WI-38 fibroblasts vero (normal) cells (IC50 = 0.089 mg/mL) while nano-gold and nano-Lavandula angustifolia showed higher results (IC50 = 0.529, and 0.209 mg/mL, respectively). Nano-gold/nano-Lavandula angustifolia formula possessed a powerful wound healing efficacy with a 96.78% wound closure. These findings revealed that nano-gold/nano-Lavandula angustifolia nanoemulsion can inhibit bacterial growth and accelerate the wound healing rate.

Nanoformulation-Based 1,2,3-Triazole Sulfonamides for Anti-Toxoplasma In Vitro Study.

Toxoplasma gondii is deemed a successful parasite worldwide with a wide range of hosts. Currently, a combination of pyrimethamine and sulfadiazine serves as the first-line treatment; however, these drugs have serious adverse effects. Therefore, it is imperative to focus on new therapies that produce the desired effect with the lowest possible dose. The designation and synthesis of sulfonamide-1,2,3-triazole hybrids (3a-c) were performed to create hybrid frameworks. The newly synthesized compounds were loaded on chitosan nanoparticles (CNPs) to form nanoformulations (3a.CNP, 3b.CNP, 3c.CNP) for further in vitro investigation as an anti-Toxoplasma treatment. The current study demonstrated that all examined compounds were active against T. gondii in vitro relative to the control drug, sulfadiazine. 3c.CNP showed the best impact against T. gondii with the lowest IC50 value of 3.64 µg/mL. Using light microscopy, it was found that Vero cells treated with the three nanoformulae showed remarkable morphological improvement, and tachyzoites were rarely seen in the treated cells. Moreover, scanning and transmission electron microscopic studies confirmed the efficacy of the prepared nanoformulae on the parasites. All of them caused parasite ultrastructural damage and altered morphology, suggesting a cytopathic effect and hence confirming their promising anti-Toxoplasma activity.

Nano-Chitosan/Eucalyptus Oil/Cellulose Acetate Nanofibers: Manufacturing, Antibacterial and Wound Healing Activities.

Accelerated wound healing in infected skin is still one of the areas where current therapeutic tactics fall short, which highlights the critical necessity for the exploration of new therapeutic approaches. The present study aimed to encapsulate Eucalyptus oil in a nano-drug carrier to enhance its antimicrobial activity. Furthermore, in vitro, and in vivo wound healing studies of the novel nano-chitosan/Eucalyptus oil/cellulose acetate electrospun nanofibers were investigated. Eucalyptus oil showed a potent antimicrobial activity against the tested pathogens and the highest inhibition zone diameter, MIC, and MBC (15.3 mm, 16.0 µg/mL, and 256 µg/mL, respectively) were recorded against Staphylococcus aureus. Data indicated a three-fold increase in the antimicrobial activity of Eucalyptus oil encapsulated chitosan nanoparticle (43 mm inhibition zone diameter against S. aureus). The biosynthesized nanoparticles had a 48.26 nm particle size, 19.0 mV zeta potential, and 0.45 PDI. Electrospinning of nano-chitosan/Eucalyptus oil/cellulose acetate nanofibers was conducted, and the physico-chemical and biological properties revealed that the synthesized nanofibers were homogenous, with a thin diameter (98.0 nm) and a significantly high antimicrobial activity. The in vitro cytotoxic effect in a human normal melanocyte cell line (HFB4) proved an 80% cell viability using 1.5 mg/mL of nano-chitosan/Eucalyptus oil/cellulose acetate nanofibers. In vitro and in vivo wound healing studies revealed that nano-chitosan/Eucalyptus oil/cellulose acetate nanofibers were safe and efficiently enhanced the wound-healing process through enhancing TGF-ß, type I and type III collagen production. As a conclusion, the manufactured nano-chitosan/Eucalyptus oil/cellulose acetate nanofiber showed effective potentiality for its use as a wound healing dressing.

Cinnamon Oil-Loaded Nanoliposomes with Potent Antibacterial and Antibiofilm Activities.

Despite recent scientific advances, the global load of bacterial disease remains high and has been established against a backdrop of increasing antimicrobial resistance. Therefore, there is a pressing need for highly effective and natural antibacterial agents. In the present work, the antibiofilm effect provided by essential oils was evaluated. Of these, cinnamon oil extract showed potent antibacterial and antibiofilm activities against Staphylococcus aureus at an MBEC of 75.0 µg/mL. It was revealed that benzyl alcohol, 2-propenal-3-phenyl, hexadecenoic acid, and oleic acid were the major components of the tested cinnamon oil extract. In addition, the interaction between the cinnamon oil and colistin showed a synergistic effect against S. aureus. Cinnamon oil that had been combined with colistin was encapsulated by liposomes to enhance the essential oil's chemical stability, demonstrating a particle size of 91.67 nm, a PDI of 0.143, a zeta potential of -0.129 mV, and an MBEC of 50.0 µg/mL against Staphylococcus aureus. Scanning electron microscopy was employed to observe the morphological changes in the Staphylococcus aureus biofilm that was treated with the encapsulated cinnamon oil extract/colistin. As a natural and safe option, cinnamon oil exhibited satisfactory antibacterial and antibiofilm performance. The application of liposomes further improved the stability of the antibacterial agents and extended the essential oil release profile.

Design and synthesis of novel bis-pyridinium based-ionic liquids as potent antiparasitic agents.

Focused bis-pyridinium based-ionic liquids were successfully synthesized through the quaternization of the selected 1,2-di(pyridin-4-yl)ethane followed by metathetical anion exchange. The synthesized pyridinium derivatives were fully characterized using various NMR-spectroscopic techniques including 1H, 13C, 11B, 31P and 19F NMR. The synthesized compounds were tested for their potential effect against Toxoplasma gondii. It was revealed that compound 5 had higher antiparasitic activity compared to other compounds. Parasitic reduction percentage reached 38, 50, 77 and 79 for groups III, IV, V and VI respectively in the liver with noticed distortion and deformation in tachyzoites' shape. Surprisingly there was no statistically significant difference between the synthesized compound 5 and the known anti-toxoplasmosis drug pyrimethamine. Histopathological study proved the effectiveness of the synthesized compound 5 on liver, spleen and brain tissues with observed better histological features compared to pyrimethamine treated group. The present investigation may pave the way to the possible use of compound 5 to replace the known drug pyrimethamine with better antiparasitic profile and fewer side effects.

Fungal Secondary Metabolites/Dicationic Pyridinium Iodide Combinations in Combat against Multi-Drug Resistant Microorganisms.

The spread of antibiotic-resistant opportunistic microbes is a huge socioeconomic burden and a growing concern for global public health. In the current study, two endophytic fungal strains were isolated from Mangifera Indica roots and identified as Aspergillus niger MT597434.1 and Trichoderma lixii KU324798.1. Secondary metabolites produced by A. niger and T. lixii were extracted and tested for their antimicrobial activity. The highest activity was noticed against Staphylococcus aureus and E. coli treated with A. niger and T. lixii secondary metabolites, respectively. A. niger crude extract was mainly composed of Pentadecanoic acid, 14-methyl-, methyl ester and 9-Octadecenoic acid (Z)-, methyl ester (26.66 and 18.01%, respectively), while T. lixii crude extract's major components were 2,4-Decadienal, (E,E) and 9-Octadecenoic acid (Z)-, and methyl ester (10.69 and 10.32%, respectively). Moreover, a comparative study between the fungal extracts and dicationic pyridinium iodide showed that the combination of A. niger and T. lixii secondary metabolites with dicationic pyridinium iodide compound showed a synergistic effect against Klebsiella pneumoniae. The combined formulae inhibited the bacterial growth after 4 to 6 h through cell wall breakage and cells deformation, with intracellular components leakage and increased ROS production.

Arc discharge rapid synthesis of engineered copper oxides nano shapes with potent antibacterial activity against multi-drug resistant bacteria.

Nowadays Nano metals have received an eminent compromise of attention. Even though different nanostructure of same metal maybe gives different results in wide range applications. Copper oxide (CuO-NPs) and Copper Nano wires (CuO-NWs) were prepared in controlled size via the alternating current Arc discharge process. Deionized water and argon gas were the chosen dielectric medium during the process to obtain 2 different forms of copper oxides. By changing the dielectric material from deionized water to argon gas the shape of CuO nanoparticles changed from spherical (CuO-NPs) to wires (CuO-NWS). The yield prepared depicted the purity of the prepared CuO, and their diameters were about 10 ± 5 nm and 30 ± 3 nm for CuO-NWs and CuO-NPs respectively. In vitro cytotoxic effect of the prepared CuO-NWs & CuO-NPs using human normal lung fibroblast cell line (WI-38 cells) revealed that CuO-NWs & CuO-NPs CC50 values were 458.8 and 155.6 µg/mL respectively. Both yields showed potent antibacterial activity against different multi-drug resistant Acinetobacter baumannii strains. A complete eradication of the bacterial growth was noticed after 4 Hrs incubation with CuO-NWs. Moreover, CuO-NWs showed superior antibacterial activity (with minimum inhibitory concentration reached 1.8 µg/mL) over CuO-NPs. The detailed antibacterial activity mechanism of CuO-NWs was further investigated; data proved the precipitation and adsorption of the nanoparticles on the bacterial cell surface leading to cell deformation with reactive oxygen species increment. The results explicated that the nanoparticles shape plays an essential role in the antibacterial activity. Rotational Arc discharge machine might be a promising tool to obtain various metal nanostructures with low cost and environmentally friendly with potent activity.

Physiotherapeutic Protocol and ZnO Nanoparticles: A Combined Novel Treatment Program against Bacterial Pyomyositis.

Myositis tropicans or pyomyositis is a muscle inflammation resulting from a bacterial infection of skeletal muscle (commonly caused by Staphylococcus aureus) that usually leads to hematogenous muscle seeding. The present study was designed to estimate the role of ZnO-NPs and a physiotherapeutic program in the management of induced biceps femoris atrophy in rats through histological, biochemical, and radiological examinations at different time intervals. At the beginning, several bacterial strains were evaluated through a proteolytic enzyme activity assay and the highest activity was recorded with the Staphylococcus aureus strain. ZnO-NPs were synthesized with the arc discharge method with an average size of 19.4 nm. The antibacterial activity of ZnO-NPs was investigated and it was revealed that the prepared ZnO-NPs showed a minimum inhibitory concentration of 8 µg/mL against the tested bacterium. The cytotoxicity of the prepared ZnO-NPs was tested in C2C12 myoblast cells, and it was elaborated that CC50 was 344.16 µg/mL. Biceps femoris pyomyositis was induced with a potent strain (Staphylococcus aureus); then, a physiotherapeutic program combined with the prepared ZnO-NPs treatment protocol was applied and evaluated. The combined program claimed antibacterial properties, preventing muscle atrophy, and resulted in the most comparable value of muscle mass.

Novel Amoxicillin-Loaded Sericin Biopolymeric Nanoparticles: Synthesis, Optimization, Antibacterial and Wound Healing Activities.

Infected wounds are a major threat among diabetic patients. Technological advancements are currently increasing the number of new adjunctive therapies that may be potent agents for speeding recovery, lowering the amputation rate and limiting infection recurrences. A novel formula with promising antibacterial activity, namely sericin/propolis/Amoxicillin nanoparticles, was assessed as a potent treatment of infected wounds in normal and diabetic rats. Skin wound healing efficiency was assessed through wound healing scorings, bacterial load assessment and histological examinations. It was revealed that upon using sericin/propolis/Amoxicillin nanoparticles, complete wound healing was successfully achieved after 10 and 15 days postinjury for nondiabetic and diabetic rats, respectively. However, the bacterial load in the induced infected wounds was extremely low (0-10 CFU/mL) after 15 days post-treatment. The histological studies revealed that the dermis was more organized with new matrix deposition, and mature collagen fibers were observed among the treated animal groups. The present study is the first preclinical study which reported the importance of silk sericin in the form of nano-sericin/propolis loaded with Amoxicillin as an effective treatment against bacterial wound infections.

Molasses-Silver Nanoparticles: Synthesis, Optimization, Characterization, and Antibiofilm Activity.

Biofilms are matrix-enclosed communities of bacteria that are highly resistant to antibiotics. Adding nanomaterials with antibacterial activity to the implant surfaces may be a great solution against biofilm formation. Due to its potent and widespread antibacterial effect, silver nanoparticles were considered the most potent agent with different biological activities. In the present investigation, silver nanoparticles (AgNPs) were newly synthesized as antibiofilm agents using sugarcane process byproduct (molasses) and named Mo-capped AgNPs. The synthesized nanoparticles showed promising antimicrobial activity against S. aureus ATCC 6538 and C. albicans DAY185. Statistically designed optimization through response surface methodology was evaluated for maximum activity and better physical characteristics, namely the nanoparticles' size and polydispersity index (PDI), and it was revealed that molasses concentration was the main effective factor. Minimal biofilm eradication concentration (MBEC) of Mo-capped AgNPs against S. aureus ATCC 6538 and C. albicans DAY185 was 16 and 32 µg/mL, respectively. Scanning electron microscope study of Mo-capped AgNP-treated biofilm revealed that AgNPs penetrated the preformed biofilm and eradicated the microbial cells. The optimally synthesized Mo-capped AgNPs were spherically shaped, and the average size diameter ranged between 29 and 88 nm with high proportions of Ag+ element (78.0%) recorded. Fourier-transform infrared spectroscopy (FTIR) analysis indicated the importance of molasses ingredients in capping and stabilizing the produced silver nanoparticles.

1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants.

SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need to discover potent compounds that may control the SARS-CoV-2 virus pandemic and the emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies and in vitro enzyme activity revealed that most of the investigated compounds demonstrated promising binding scores against the SARS-CoV-2 and Omicron spike proteins, in comparison to the reference drugs. In particular, compound 9 has the highest scoring affinity against the SARS-CoV-2 and Omicron spike proteins in vitro with its IC50 reaching 75.98 nM against the Omicron spike protein and 74.51 nM against the SARS-CoV-2 spike protein. The possible interaction between the synthesized triazoles and the viral spike proteins was by the prevention of the viral entry into the host cells, which led to a reduction in viral reproduction and infection. A cytopathic inhibition assay in the human airway epithelial cell line (Vero E6) infected with SARS-CoV-2 revealed the effectiveness and safety of the synthesized compound (compound 9) (EC50 and CC50 reached 80.4 and 1028.28 µg/mL, respectively, with a selectivity index of 12.78). Moreover, the antiinflammatory effect of the tested compound may pave the way to reduce the reported SARS-CoV-2-induced hyperinflammation.

Date Fruit (Phoenix dactylifera L.) Cultivar Extracts: Nanoparticle Synthesis, Antimicrobial and Antioxidant Activities.

The pharmaceutical research sector's inability to produce new drugs has made it difficult to keep up with the rate at which microbial resistance is developing. Recently, nanotechnology and its combinations with natural products have been the saviors against multidrug resistant bacteria. In the present investigation, different Egyptian and Saudi date cultivars were extracted and then phytochemically analyzed and tested for possible antimicrobial activities against multidrug resistant (MDR) microbes. The results revealed that extract of the flesh of fresh "Hayany" fruit (Egyptian date) showed the highest antimicrobial activity, with high levels of phenolic, flavonoid, and tannin concentrations (538.578 µg/mL, 28.481 µg/mL, and 20.888 µg/mL, respectively) and high scavenging activity, with an IC50 reaching 10.16 µg/mL. The highest synergistic activity was found between fresh "Hayany" fruit extract and amikacin. Novel nano-fresh fruit of "Hayany" date extract was synthesized using a ball-milling technique. The vesicle size was 21.6 nm, while the PDI and zeta potential were 0.32 and +38.4 mV, respectively. The inhibition zone diameters of nano-fresh fruit of "Hayany" date extract/amikacin reached 38 mm and 34 mm, with complete microbial eradication after 9 h and 6 h, against Candida albicans and Staphylococcus aureus, respectively. In conclusion, date fruit extract could be used as a candidate bioactive compound in the fight against infectious diseases.