Enhanced Wound Healing Potential of Spirulina platensis Nanophytosomes: Metabolomic Profiling, Molecular Networking, and Modulation of HMGB-1 in an Excisional Wound Rat Model.

Excisional wounds are considered one of the most common physical injuries. This study aims to test the effect of a nanophytosomal formulation loaded with a dried hydroalcoholic extract of S. platensis on promoting excisional wound healing. The Spirulina platensis nanophytosomal formulation (SPNP) containing 100 mg PC and 50 mg CH exhibited optimum physicochemical characteristics regarding particle size (598.40 ± 9.68 nm), zeta potential (-19.8 ± 0.49 mV), entrapment efficiency (62.76 ± 1.75%), and Q6h (74.00 ± 1.90%). It was selected to prepare an HPMC gel (SPNP-gel). Through metabolomic profiling of the algal extract, thirteen compounds were identified. Molecular docking of the identified compounds on the active site of the HMGB-1 protein revealed that 12,13-DiHome had the highest docking score of -7.130 kcal/mol. SPNP-gel showed higher wound closure potential and enhanced histopathological alterations as compared to standard (MEBO® ointment) and S. platensis gel in wounded Sprague-Dawley rats. Collectively, NPS promoted the wound healing process by enhancing the autophagy process (LC3B/Beclin-1) and the NRF-2/HO-1antioxidant pathway and halting the inflammatory (TNF-, NF-κB, TlR-4 and VEGF), apoptotic processes (AIF, Caspase-3), and the downregulation of HGMB-1 protein expression. The present study's findings suggest that the topical application of SPNP-gel possesses a potential therapeutic effect in excisional wound healing, chiefly by downregulating HGMB-1 protein expression.

Molecular docking and dynamic simulations of Cefixime, Etoposide and Nebrodenside A against the pathogenic proteins of SARS-CoV-2.

The catastrophe of the coronavirus continues from one part of the world to another, and hardly a country is left without its devastations. Millions of people were infected and several hundred thousand died of the COVID-19 pandemic across the world. There is no clear targeted drug therapy available for the treatment of the patients. The discovery of vaccines is not enough to curtail its spread and disastrous implications. An instantly qualifying approach is needed to utilize the current drugs and isolated compounds. The purpose of this work is to determine potent inhibitors against the target proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, molecular docking study of pathogenic spike glycoproteins (S), nucleocapsid phosphoprotein (N), an envelope protein (E), two drugs i.e., cefixime, etoposide, and a previously isolated compound nebrodenside A is performed. Promising results were obtained via complimentary analysis of molecular dynamics (MD) simulations performed for the complexes of three proteins with etoposide drug. Minimum values were recorded for the docking scores and binding energies of the complexes. These results were further supported by the RMSD, RMSF data for the stability of proteins and ligands. Additionally, ligand properties and ligand-protein contacts were also explained with histograms of every simulation trajectory. The computational studies confirmed that cefixime, etoposide, and nebrodenoside A can be used as potent inhibitors of COVID-19. Nevertheless, additional experimental investigations and validation of the selected candidates are mandatory to confirm their applicability for clinical trials.

Co-delivery of hesperidin and clarithromycin in a nanostructured lipid carrier for the eradication of Helicobacter pylori in vitro.

Effective and precise eradication of Helicobacter pylori (H. pylori) is the most promising approach to avoid H. pylori-related gastrointestinal disorders. The present study was conducted to demonstrate the efficacy of the co-delivery of hesperidin (Hesp) and clarithromycin (CLR) in nanostructured lipid carriers (NLCs) against H. pylori. We have produced a new delivery system by combining bioflavonoid Hesp and CLR NLCs to address the failure in single antibiotic therapies. Briefly, a blend of solid lipid, liquid lipid, and surfactant was used. Homogeneous NLCs with all the formulations showed a nano size and surface-negative charge and presented high in vitro stability and slow release of the drug even after 24 h. Bioimaging studies by scanning electron microscopy, transmission electron microscopy, and imaging flow cytometry indicated that NLCs interacted with the membrane by adhering to the outer cell membrane and disrupted the membrane that resulted in the leakage of cytoplasmic contents. The prepared NLCs provide sustained and controlled drug release that can be used to increase the rate of H. pylori eradication.

Plectrabarbene, a New Abietane Diterpene from Plectranthus barbatus Aerial Parts.

A new abietane diterpene namely plectrabarbene (2), together with two known compounds: sugiol (1) and 11,14-dihydroxy-8,11,13-abietatrien-7-one (3) have been isolated from the aerial parts of Plectranthus barbatus Andr. (Labiatae). The structures of these compounds were determined by various spectral techniques (e.g., UV, IR, NMR, and FAB) and by comparison with the literature data. A molecular docking study of the isolated diterpenes (1-3) was performed with AChE to gain an insight into their AChE inhibition mechanism. The results of docking experiments revealed that the all tested compounds showed binding affinity at the active site of AchE in comparison to donepezil.

New Antiproliferative Cembrane Diterpenes from the Red Sea Sarcophyton Species.

The combination of liquid chromatography coupled to high resolution mass spectrometry (LC-HRESMS)-based dereplication and antiproliferative activity-guided fractionation was applied on the Red Sea-derived soft coral Sarcophyton sp. This approach facilitated the isolation of five new cembrane-type diterpenoids (1-5), along with two known analogs (6 and 7), as well as the identification of 19 further, known compounds. The chemical structures of the new compounds were elucidated while using comprehensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional (2D) NMR and HRMS. All of the isolated cembranoids (1-7) showed moderate in vitro antiproliferative activity against a human breast cancer cell line (MCF-7), with IC50 ranging from 22.39-27.12 µg/mL. This class of compounds could thus serve as scaffold for the future design of anticancer leads.

Marine phospholipid nanoliposomes: A promising therapeutic approach for inflammatory bowel disease: Preparation, safety, and efficacy evaluation.

Promising findings have been emerged from studies utilizing n3 polyunsaturated fatty acids (PUFA) supplementation in animal models of inflammatory bowel disease (IBD). Introduction of marine phospholipids which combine n3 PUFA with phosphatidylcholine in a nanoliposome formulation offers enhanced pharmacological efficacy due to physical stability, improved bioavailability, and specific targeting to inflamed colitis tissues. In the present study, a marine phospholipid-based nanoliposome formulation was developed and optimized, resulting in nanovesicles of approximately 107.7 ± 1.3 nm in size, 0.18 ± 0.01 PDI, and - 32.03 ± 3.16 mV ZP. The nanoliposomes exhibited spherical vesicles with stable properties upon incubation at SGF as shown by the TEM, DLS, and turbidity measurements over 3 h. MPL nanoliposomes were cytocompatible until the concentration of 500 µg/mL as per MTT assay and taken by macrophages through macropinocytosis and caveolae pathways, and demonstrated significant inhibitory activity against reactive oxygen species (ROS) in LPS-stimulated macrophages. They were also shown to be blood-compatible and safe for administration in healthy mice. In a colitis mouse model, the nanoliposomes displayed preferential distribution in the inflamed gut, delaying the onset of colitis when administered prophylactically. These findings highlight the potential of marine phospholipid nanoliposomes as a promising therapeutic approach for managing inflammatory bowel disease.

Phytochemical profile and antimicrobial activity of essential oils from two Syzygium species against selected oral pathogens.

BACKGROUND: The genus Syzygium (Myrtaceae) comprises several essential oil-rich species that are utilized traditionally for treating tooth infections and toothache. The current study aimed to extract essential oils (EOs) from the leaves of Syzygium samarangense and Syzygium malaccense cultivated in Egypt for the first time and screen their antimicrobial potential against oral-related pathogens. METHODS: The intended EOs were extracted using hydrodistillation (HD) by boiling fresh leaves with distilled water; supercritical fluid (SF) by extracting the dried leaves using supercritical CO2 at 40 °C and 150 bar; and the headspace (HS) in which the fresh leaves were heated in a glass vial and the vaporized aroma were analyzed. The volatile constituents were analyzed using GC/MS and identified by comparing the experimental Kovats' retention indices with the literature. The antimicrobial activity was assessed against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Candida albicans using agar diffusion, microwell dilution, and biofilm formation assays. Statistical significance (p < 0.05) was determined by applying one-way ANOVA and Duncan's post hoc test. RESULTS: The yield of the extracted EOs differs between the applied methods, and the SF approach harvested the maximum (0.52-0.46%). The GC-MS analysis of SF EOs revealed a discrepancy between the two species. Since S. malaccense showed an abundance of hydrocarbons represented mainly by squalene (60.60%), S. samarangense was deemed to have oxygenated sesquiterpenes exemplified in globulol (52.09%). On the other side, the HD and HS EOs were sequentially comparable, while differed in the percentage of their majors. γ-terpinene (33.06%) pioneered the HS-derived aroma of S. malaccense, while S. samarangense was abundant with α-pinene (30.18%). Concurrently, the HD EOs of S. malaccense and S. samarangense were commonly denoted by caryophyllene oxide (8.19%-18.48%), p-cymene (16.02%- 19.50%), and γ-terpinene (12.20%-17.84). Ultimately, both species EOs exhibited broad-spectrum antimicrobial potential, although the HD EO was more potent than the SF EO. The HD EOs of both species potently inhibited the growth of E. coli (MIC 3.75 µL/mL) and suppressed C. albicans biofilm formation by 83.43 and 87.27%, respectively. The SF-EOs efficiently suppressed the biofilm formation of Gram-positive bacteria by 76.45%-82.95%. CONCLUSION: EOs extracted from both species by different methods possessed a unique blend of volatile components with broad-spectrum antimicrobial activity. They were promoted as bioactive hits for controlling oral infections, however further investigations concerning their safety in clinical settings are needed.

Adaptive Aquila Optimizer with Explainable Artificial Intelligence-Enabled Cancer Diagnosis on Medical Imaging.

Explainable Artificial Intelligence (XAI) is a branch of AI that mainly focuses on developing systems that provide understandable and clear explanations for their decisions. In the context of cancer diagnoses on medical imaging, an XAI technology uses advanced image analysis methods like deep learning (DL) to make a diagnosis and analyze medical images, as well as provide a clear explanation for how it arrived at its diagnoses. This includes highlighting specific areas of the image that the system recognized as indicative of cancer while also providing data on the fundamental AI algorithm and decision-making process used. The objective of XAI is to provide patients and doctors with a better understanding of the system's decision-making process and to increase transparency and trust in the diagnosis method. Therefore, this study develops an Adaptive Aquila Optimizer with Explainable Artificial Intelligence Enabled Cancer Diagnosis (AAOXAI-CD) technique on Medical Imaging. The proposed AAOXAI-CD technique intends to accomplish the effectual colorectal and osteosarcoma cancer classification process. To achieve this, the AAOXAI-CD technique initially employs the Faster SqueezeNet model for feature vector generation. As well, the hyperparameter tuning of the Faster SqueezeNet model takes place with the use of the AAO algorithm. For cancer classification, the majority weighted voting ensemble model with three DL classifiers, namely recurrent neural network (RNN), gated recurrent unit (GRU), and bidirectional long short-term memory (BiLSTM). Furthermore, the AAOXAI-CD technique combines the XAI approach LIME for better understanding and explainability of the black-box method for accurate cancer detection. The simulation evaluation of the AAOXAI-CD methodology can be tested on medical cancer imaging databases, and the outcomes ensured the auspicious outcome of the AAOXAI-CD methodology than other current approaches.

Multifunctional nanoparticles based on marine polysaccharides for apremilast delivery to inflammatory macrophages: Preparation, targeting ability, and uptake mechanism.

Hydrophobic drug encapsulation inside targeted nanoparticles can enhance accumulation in inflamed sites, limit toxicity to healthy tissue, and improve pharmacokinetics compared to free drug dosing. This study reports a functionalized marine polysaccharide nanoparticle with a controlled release, targeting abilities, and in-situ imaging properties. Carbon dots functionalized Enteromorpha polysaccharide/Mannose/Methionine functionalized Chitosan (CDs.EP/Man/Meth.Cs) NPs could deliver apremilast to inflammatory macrophages and Caco-2 intestinal cells as an in vitro model for application in oral drug delivery to cure IBD. The nanoparticles were simply a polyelectrolyte complex between cationic functionalized chitosan and anionic polysaccharide of Enteromorpha prolifera. Functionalized polysaccharides and the prepared NPs were well characterized. The functionalized nanoparticles could overcome the limitation of poor drug bioavailability and showed a high loading capacity of (45 %) with a controlled release of about (74.5 %). Confocal laser scanning imaging showed higher cellular uptake of the modified nanoparticles than that of the unmodified nanoparticles in LPS-activated RAW 264.7 macrophages and Caco-2 cells. The effect of functionalization on the cellular uptake targetability was assessed using spectrofluorometric measurements after mannose competition. Anti-inflammatory activity of apremilast-loaded NPs is more elevated than the free drug. These results suggest the feasibility of using functionalized EP/Cs nanoparticles in IBD oral drug delivery.

Preparation, urease inhibition mechanisms, and anti-Helicobacter pylori activities of hesperetin-7-rhamnoglucoside.

This work investigated the effects of the bioflavonoid hesperetin-7-rhamnoglucoside isolated from Citrus uranium fruit peel on Helicobacter pylori (H. pylori). Separation and purity, crystalline state, and urease inhibition assays were carried out. Then, molecular docking and molecular dynamics (MD) simulations were conducted with urease as the target protein. Hesp was isolated from citrus peel with a purity of 95.14 µg mg-1 of dry raw material. X-ray diffraction analysis, hydrogen-1 nuclear magnetic resonance, Fourier transform infrared spectroscopy, and differential scanning calorimetry revealed that pure Hesp had the same crystallinity rating as the Hesp standard. The kinetic inhibition study demonstrated that Hesp inhibited H. pylori urease in a competitive and concentration-dependent manner with jack bean urease. In addition, bioimaging studies with laser scanning confocal microscopy and scanning electron microscopy illustrated that Hesp interacted with bacterial cells and induced membrane disruption by creating holes in the outer membranes of the bacterial cells, resulting in the leakage of amino acids. Importantly, molecular docking and 20 ns MD simulations revealed that Hesp inhibited the target protein through slow-binding inhibition and hydrogen bond interactions with active site residues, namely, Gly11 (O⋯H distance = 2.2 Å), Gly13 (O⋯H distance = 2.4 Å), Ser12 (O⋯H distance = 3.3 Å), Lys14 (O⋯H distance = 3.3 Å), and Arg179 (O⋯H distance = 2.7 Å). This work presents novel anti- H. pylori agents from natural sources.

Potential utility of nano-based treatment approaches to address the risk of Helicobacter pylori.

INTRODUCTION: Helicobacter pylori (H. pylori) has occupied a significant place among infectious pathogens and it has been documented as a leading challenge due to its higher resistance to the commonly used drugs, higher adaptability, and lower targeting specificity of the available drugs. AREAS COVERED: New treatment strategies are urgently needed in order to improve the current advancement in modern medicine. Nanocarriers have gained an advantage of drug encapsulation and high retention time in the stomach with a prolonged drug release rate at the targeted site. This article aims to highlight the recent advances in nanotechnology with special emphasis on metallic, polymeric, lipid, membrane coated, and target-specific nanoparticles (NPs), as well as, natural products for treating H. pylori infection. We discussed a comprehensive approach to understand H. pylori infection and elicits to rethink about the increasing threat posed by H. pylori and its treatment strategies. EXPERT OPINION: To address these issues, nanotechnology has got huge potential to combat H. pylori infection and has made great progress in the field of biomedicine. Moreover, combinatory studies of natural products and probiotics in conjugation with NPs have proven efficiency against H. pylori infection, with an advantage of lower cytotoxicity, minimal side effects, and stronger antibacterial potential.[Figure: see text].

New phenolic compounds from Calothamnus quadrifidus R.Br. aerial parts and their antioxidant activity.

Two new compounds calothphenone (1) and 6-methoxy kaempferol 3-O-(6″-E-p-coumaroyl)-ß-d-glucopyranoside (6-methoxy tiliroside) (2) along with six known compounds viz gallic acid (3), methyl gallate (4), kaempferol 3-O-(6″-E-p-coumaroyl)-ß-d-glucopyranoside (tiliroside) (5), castalagin (6), kaempferol (7) and quercetin (8) were isolated from the ethyl acetate fraction (EAF) of 80% aqueous methanol extract of Calothamnus quadrifidus aerial parts. Their structure was established based on different chemical and spectroscopic techniques (1H-/13C-NMR and 2D NMR). Antioxidant activity for EAF and compounds 1, 2 and 5 was evaluated using DPPH, superoxide radical and nitric oxide (NO) inhibition methods. EAF exhibited strong activity to inhibit DPPH, superoxide and NO radicals. Moreover, all tested compounds demonstrated a close high ability to inhibit superoxide and NO radicals in comparison to ascorbic acid, but they exerted lower activity towards DPPH radical.[Figure: see text].

Interleukin-6 gene polymorphism in Saudi population with recurrent aphthous stomatitis.

INTRODUCTION: Recurrent aphthous ulcers are common but poorly understood mucosal disorder. Local and systemic conditions, genetic, immunological, and microbial factors may play a role in the pathogenesis of recurrent aphthous ulceration (RAS). Different aetiologies and mechanisms might be involved in the aetiopathogenesis of aphthous ulceration. Cytokines are thought to play an important role and high levels of interleukin (IL)-6, a pro-inflammatory cytokine, have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if polymorphisms of IL-6 gene are associated with RAS in a cohort of specific population. METHODOLOGY: A total of 37 RAS patients and 18 healthy controls were included in the study. The genotypes of IL-6 gene -174G\C polymorphisms were determined using polymerase chain reaction and sequencing. RESULTS: Four SNPs were analyzed, one known mutation which been evaluated as a risk factor for RAS, and three new mutations were investigated. The genotype frequencies of -174G\C polymorphism showed no statistically significant differences between RAS patients and controls (p\ 0.629). Polymorphisms of Rs1800795 heterozygous genotype were found in 21.62% of cases, and 33.33% of controls. Homozygous mutant genotype was found in 5.41% of cases and no homozygous mutant genotype was found in control group. The normal alleles were found in 72.97% of cases and 66.67% of control. CONCLUSION: Thus, according to our study, IL-6 gene polymorphism is not involved in RAS pathogenesis. Further studies should be done on large sample size to detect any association with pathogenesis. However, an alternative reasoning could point out to a complex interactive effect on IL-6 expression that might exist between any of the detected polymorphisms.

Inhibitory activity against urease of quercetin glycosides isolated from Allium cepa and Psidium guajava.

Methanolic extracts of edible plants and seaweeds were tested for their inhibitory activity against Jack bean urease. Quercetin-4'-O-beta-D-glucopyranoside was isolated from Allium cepa as a urease inhibitor with an IC(50) value of 190 microM-. Quercetin and two quercetin glycosides, avicularin and guaijaverin, were isolated from Psidium guajava as urease inhibitors with respective IC(50) values of 80 microM-, 140 microM-, and 120 microM-.

Terezine E, bioactive prenylated tryptophan analogue from an endophyte of Centaurea stoebe.

Fungal endophytes are considered promising sources of new bioactive natural products. In this study, a Mucor sp. has been isolated as an endophyte from the medicinal plant Centaurea stoebe. Through bioactivity-guided fractionation, the isolation of the new bioactive terezine E in addition to the previously reported 14-hydroxyterezine D was carried out. The isolated compounds were fully characterised by HRESIMS and 1D and 2D NMR analyses. Both compounds exhibited potent antiproliferative activity against K-562 and HUVEC cell lines and antifungal efficacy against the tested fungal strains.

Design of γ-AlOOH, γ-MnOOH, and α-Mn2O3 nanorods as advanced antibacterial active agents.

In the current study, γ-AlOOH, γ-MnOOH, and α-Mn2O3 nanorods (NRs) were easily synthesized and applied as advanced antibacterial materials. γ-AlOOH NRs with 20 nm width, [100] crystal plane, and 200 nm length were fabricated through a surfactant-directed solvothermal method. γ-MnOOH NRs with 20 nm width, [101] crystal direction and 500 nm length were fabricated through a hydrothermal method. The prepared γ-MnOOH NRs were calcinated (for 5 h) at 700 °C to produce α-Mn2O3 NRs with 20 nm average width and increased surface area. The NRs' structures were confirmed through FT-IR, XRD, XPS, FESEM, and FETEM. The antibacterial activity of the NRs was studied against different Gram-negative and Gram-positive bacterial strains and yeast. The three NRs exhibited antibacterial activity against all of the used strains. Biological studies indicated that the NRs' antimicrobial activity increased in the order of γ-MnOOH < γ-AlOOH < α-Mn2O3 NRs. The α-Mn2O3 NRs exhibited the lowest MIC value (39 µg mL-1) against B. subtilis, B. pertussis, and P. aeruginosa. The prepared NRs exhibited a higher antimicrobial potential toward Gram-positive bacteria than Gram-negative bacteria. The higher antimicrobial activity of the α-Mn2O3 NRs is highlighted based on their larger surface area and smaller diameter. Consequently, uniform NR architectures, single crystallinity, small nanoscale diameters, and more highly exposed [110] Mn-polar surfaces outwards are promising structures for α-Mn2O3 antibacterial agents. These NRs adhered firmly to the bacterial cells causing cell wrapping and morphology disruption, and microbial death. The designed NRs provide a great platform for microbial growth inhibition.