Pirfenidone ameliorates ANIT-induced cholestatic liver injury via modulation of FXR, NF-кB/TNF-α, and Wnt/GSK-3ß/ß-catenin signaling pathways.

Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.

Protective effect of kaempferol glucoside against lipopolysaccharide-caused acute lung injury via targeting Nrf2/NF-κB/NLRP3/GSDMD: Integrating experimental and computational studies.

The current study explored the protective potential of kaempferol 3-sophoroside-7-glucoside (KSG) against acute lung injury (ALI). Pre-treatment with KSG effectively secured mice from ALI and showed similar efficaciousness to dexamethasone. KSG markedly increased the survival rate and alleviated lung pathological lesions induced by lipopolysaccharide (LPS). Furthermore, KSG attenuated differential and total cell counts in BALF (bronchoalveolar lavage fluid) and MPO (myeloperoxidase) activity. KSG counteracted the NF-κB (nuclear factor-κB) activation and significantly ameliorated the downstream inflammatory cytokine, TNF-α (tumor necrosis factor-α). Simultaneously, KSG suppressed the over-expression of NLRP3 (NOD-like receptor protein 3), caspase-1, and pro-inflammatory cytokine interleukin IL-1ß (interleukine-1ß) and prohibited the elevation of the pyroptotic parameter GSDMD-N (N-terminal domain of gasdermin D) induced by LPS challenge. In addition, KSG significantly enhanced Nrf2 (nuclear-factor erythroid-2-related factor) and HO-1 (heme-oxygenase-1) expression. Meanwhile, KSG mitigated lipid peroxidative markers (malondialdehyde, protein carbonyl and 4-hydroxynonenal) and boosted endogenous antioxidants (superoxide dismutase/reduced glutathione/catalase) in lung tissue. In silico analyses revealed that KSG disrupts Keap1-Nrf2 protein-protein interactions by binding to the KEAP1 domain, consequently activating Nrf2. Specifically, molecular docking demonstrated superior binding affinity of KSG to KEAP1 compared to the reference inhibitor, with docking scores of -9.576 and -6.633 Kcal/mol, respectively. Additionally, the MM-GBSA binding free energy of KSG (-67.25 Kcal/mol) surpassed that of the reference inhibitor (-56.36 Kcal/mol). Furthermore, MD simulation analysis revealed that the KSG-KEAP1 complex exhibits substantial and stable binding interactions with various amino acids over a duration of 100 ns. These findings showed the protective anti-inflammatory and anti-oxidative modulatory efficiencies of KSG that effectively counteracted LPS-induced ALI and encouraged future research and clinical applications of KSG as a protective strategy for ALI.

Development and evaluation of quercetin enriched bentonite-reinforced starch-gelatin based bioplastic with antimicrobial property.

Nowadays novel bio-based materials have been widely employed in food and pharmaceutical industry because of their wide acceptability by the consumers rather than the synthetic materials nevertheless, they possess poor mechanical properties. Reinforcement of biopolymers with intercalation of mineral clays can improve their physicochemical properties; so that such biocomposites possess superior barrier and mechanical properties as well as stability and drug loading efficacy. Thus, this research aimed at formulating quercetin loaded bentonite-reinforced starch-gelatin based novel bioplastic with diverse applicability. The methodology of the study included Box Behnken optimization as well as physical, structural, mechanical and antimicrobial properties evaluation of the proposed reinforced bioplastics. Amount of starch, bentonite and glycerin were the independent variables while the tensile strength, swelling index and elongation percentage were studied as dependent variables. The optimized bioplastic film showed excellent physicochemical and morphological characteristics and also for efficient percentage drug content. The antimicrobial activity showed the highest activity against Escherichia coli followed by Pseudomonas aeruginosa and Staphylococcus aureus. Scanning electron microscopy (SEM) revealed the non-homogenous nature of the film. Generally, the results revealed that quercetin loaded bentonite-reinforced starch-gelatin based could be used as ecological friendly active food packaging as well as pharmaceutical application with significant antimicrobial properties.

Cordycepin- melittin nanoconjugate intensifies wound healing efficacy in diabetic rats.

The current study was designed to develop a nanoconjugate of cordycepin-melittin (COR-MEL) and assess its healing property in wounded diabetic rats. The prepared nanoconjugate has a particle size of 253.5 ± 17.4 nm with a polydispersity index (PDI) of 0.35 ± 0.04 and zeta potential of 17.2 ± 0.3 mV. To establish the wound healing property of the COR-MEL nanoconjugate, animal studies were pursued, where the animals with diabetes were exposed to excision and treated with COR hydrogel, MEL hydrogel, or COR-MEL nanoconjugate topically. The study demonstrated an accelerated wound contraction in COR-MEL nanoconjugate -treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde (MDA) and exhaustion of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Additionally, the nanoconjugate exhibits a strong expression of transforming growth factor (TGF)-ß1, vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGFR)-ß, indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1 (Col 1A1). Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Psammaceratin A: A Cytotoxic Psammaplysin Dimer Featuring an Unprecedented (2Z,3Z)-2,3-Bis(aminomethylene)succinamide Backbone from the Red Sea Sponge Pseudoceratina arabica.

Bioassay-guided partition of the extract of the Red Sea sponge Pseudoceratina arabica and HPLC purification of the active fraction gave a psammaplysin dimer, psammaceratin A (1), along with psammaplysin A (2). The dimer comprises two units of psammaplysin A (2) connected via the terminal amines with an unprecedented (2Z,3Z)-2,3-bis(aminomethylene)succinamide moiety, and it represents the first dimer to be identified among the psammaplysin family. Data from 1D- and 2D-NMR and HRMS supported the chemical structures of the compounds. Psammaceratin A (1) and psammaplysin A (2) exhibited significant growth inhibition of HCT 116, HeLa, and MBA-MB-231 cells down to 3.1 µM.

Magnificines A and B, Antimicrobial Marine Alkaloids Featuring a Tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione Backbone from the Red Sea Sponge Negombata magnifica.

Investigation of the Red Sea sponge Negombata magnifica gave two novel alkaloids, magnificines A and B (1 and 2) and a new ß-ionone derivative, (±)-negombaionone (3), together with the known latrunculin B (4) and 16-epi-latrunculin B (5). The analysis of the NMR and HRESIMS spectra supported the planar structures and the relative configurations of the compounds. The absolute configurations of magnificines A and B were determined by the analysis of the predicted and experimental ECD spectra. Magnificines A and B possess a previously unreported tetrahydrooxazolo[3,2-a]azepine-2,5(3H,6H)-dione backbone and represent the first natural compounds in this class. (±)-Negombaionone is the first ß-ionone of a sponge origin. Compounds 1-3 displayed selective activity against Escherichia coli in a disk diffusion assay with inhibition zones up to 22 mm at a concentration of 50 µg/disc and with MIC values down to 8.0 µM. Latrunculin B and 16-epi-latrunculin B inhibited the growth of HeLa cells with IC50 values down to 1.4 µM.

Chitosan Coated Microparticles Enhance Simvastatin Colon Targeting and Pro-Apoptotic Activity.

This work aimed at improving the targeting and cytotoxicity of simvastatin (SMV) against colon cancer cells. SMV was encapsulated in chitosan polymers, followed by eudragit S100 microparticles. The release of SMV double coated microparticles was dependent on time and pH. At pH 7.4 maximum release was observed for 6 h. The efficiency of the double coat to target colonic tissues was confirmed using real-time X-ray radiography of iohexol dye. Entrapment efficiency and particle size were used in the characterization of the formula. Cytotoxicity of SMV microparticles against HCT-116 colon cancer cells was significantly improved as compared to raw SMV. Cell cycle analysis by flow cytomeric technique indicated enhanced accumulation of colon cancer cells in the G2/M phase. Additionally, a significantly higher cell fraction was observed in the pre-G phase, which highlighted enhancement of the proapoptotic activity of SMV prepared in the double coat formula. Assessment of annexin V staining was used for confirmation. Cell fraction in early, late and total cell death were significantly elevated. This was accompanied by a significant elevation of cellular caspase 3 activity. In conclusion, SMV-loaded chitosan coated with eudragit S100 formula exhibited improved colon targeting and enhanced cytotoxicity and proapoptotic activity against HCT-116 colon cancer cells.

An Efficient Greener Approach for N-Acylation of Amines in Water Using Benzotriazole Chemistry.

A straightforward, mild and cost-efficient synthesis of various arylamides in water was accomplished using versatile benzotriazole chemistry. Acylation of various amines was achieved in water at room temperature as well as under microwave irradiation. The developed protocol unfolds the synthesis of amino acid aryl amides, drug conjugates and benzimidazoles. The environmentally friendly synthesis, short reaction time, simple workup, high yields, mild conditions and free of racemization are the key advantages of this protocol.

In Vitro Antimycobacterial Activity and Physicochemical Characterization of Diaryl Ether Triclosan Analogues as Potential InhA Reductase Inhibitors.

Two sets of diphenyl ether derivatives incorporating five-membered 1,3,4-oxadiazoles, and their open-chain aryl hydrazone analogs were synthesized in good yields. Most of the synthesized compounds showed promising in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv. Three diphenyl ether derivatives, namely hydrazide 3, oxadiazole 4 and naphthylarylidene 8g exhibited pronounced activity with minimum inhibitory concentrations (MICs) of 0.61, 0.86 and 0.99 µg/mL, respectively compared to triclosan (10 µg/mL) and isoniazid (INH) (0.2 µg/mL). Compounds 3, 4, and 8g showed the InhA reductase enzyme inhibition with higher IC50 values (3.28-4.23 µM) in comparison to triclosan (1.10 µM). Correlation between calculated physicochemical parameters and biological activity has been discussed which justifies a strong correlation with respect to the inhibition of InhA reductase enzyme. Molecular modeling and drug-likeness studies showed good agreement with the obtained biological evaluation. The structural and experimental information concerning these three InhA inhibitors will likely contribute to the lead optimization of new antibiotics for M. tuberculosis.

New Source of 3D Chitin Scaffolds: The Red Sea Demosponge Pseudoceratina arabica (Pseudoceratinidae, Verongiida).

The bioactive bromotyrosine-derived alkaloids and unique morphologically-defined fibrous skeleton of chitin origin have been found recently in marine demosponges of the order Verongiida. The sophisticated three-dimensional (3D) structure of skeletal chitinous scaffolds supported their use in biomedicine, tissue engineering as well as in diverse modern technologies. The goal of this study was the screening of new species of the order Verongiida to find another renewable source of naturally prefabricated 3D chitinous scaffolds. Special attention was paid to demosponge species, which could be farmed on large scale using marine aquaculture methods. In this study, the demosponge Pseudoceratina arabica collected in the coastal waters of the Egyptian Red Sea was examined as a potential source of chitin for the first time. Various bioanalytical tools including scanning electron microscopy (SEM), fluorescence microscopy, FTIR analysis, Calcofluor white staining, electrospray ionization mass spectrometry (ESI-MS), as well as a chitinase digestion assay were successfully used to confirm the discovery of α-chitin within the skeleton of P. arabica. The current finding should make an important contribution to the field of application of this verongiid sponge as a novel renewable source of biologically-active metabolites and chitin, which are important for development of the blue biotechnology especially in marine oriented biomedicine.

Fusaripeptide A: new antifungal and anti-malarial cyclodepsipeptide from the endophytic fungus Fusarium sp.

From the culture of the endophytic fungus Fusarium sp. isolated from the roots of Mentha longifolia L. (Labiatae) growing in Saudi Arabia, a new cyclodepsipeptide, namely fusaripeptide A (1), along with three known compounds adenosine (2), 2[(2-hydroxypropionyl)amino]benzamide (3), and cyclopentanol (4), have been isolated. Their structures were determined, using extensive 1D and 2D NMR and HRESI and GC mass spectral data. That is the first report for the isolation of compound 4 from natural source. In addition, compounds 2 and 3 are reported here for the first time from Fusarium sp. The absolute configuration of the amino acid residues of 1 was assigned by chiral GCMS and Marfey's analysis after acid hydrolysis. Fusaripeptide A differs from the reported ones from Fusarium sp. in the length of fatty acidic alkyl chain. Compound 1 was evaluated for its antifungal, anti-malarial, and cytotoxic activities. It exhibited potent antifungal activity toward C. albicans, C. glabrata, C. krusei, and A. fumigates with IC50 values of 0.11, 0.24, 0.19, and 0.14 µM, respectively. Furthermore, it had significant anti-malarial activity toward P. falciparum (D6 clone) with IC50 value of 0.34 µM. However, it showed cytotoxic activity toward the tested cell lines.

Anti-Helicobacter, Antitubercular and Cytotoxic Activities of Scalaranes from the Red Sea Sponge Hyrtios erectus.

The Red Sea specimen of the marine sponge Hyrtios erectus (order Dictyoceratida) was found to contain scalarane-type sesterterpenes. 12-O-deacetyl-12,19-di-epi-scalarin (14), a new scalarane sesterterpenoid, along with fourteen previously-reported scalarane-type sesterterpenes (1⁻13 and 15) have been isolated. The chemical structures of the isolated compounds were elucidated on the basis of detailed 1D and 2D NMR spectral data and mass spectroscopy, as well as by comparison with reported data. The anti-Helicobacter pylori, antitubercular and cytotoxic activities of all fifteen compounds were evaluated to reveal the potency of Compounds 1, 2, 3, 4, 6, 7 and 10. Amongst these, Compounds 1, 3, 4, 6 and 10 displayed a promising bioactivity profile, possessing potent activities in the antitubercular and anti-H. pylori bioassay. Compounds 2 and 7 showed the most promising cytotoxic profile, while Compounds 1 and 10 showed a moderate cytotoxic profile against MCF-7, HCT-116 and HepG2 cell lines.

Saudi plants as a source of potential ß-lactamase inhibitors.

This study was performed to assess the potential ß-lactamase inhibitory properties of nineteen crude Saudi plant extracts belonging to eight families against extended spectrum ß-lactamase (ESßL) strains of Klebsiella pneumoniae and other medically important pathogens. A total of 276 microbial isolates of pathogenic bacteria were used in this study; only 15 of them showed decreased sensitivity to one or several of ceftazidime, aztreonam, cefotaxime or ceftriaxone, which are deemed to be possible producers of ESßL. Antibacterial activities of plant extracts were carried out against ESßL positive isolates by the disc diffusion method. The potential ESßL suppressing activities of plant extracts and prepared fractions, (chloroform and methanol), with or without antibiotic were studied by disc diffusion method. Results revealed that selected plant extracts showed no antibacterial activity against tested strains; meanwhile, only Echinops viscosus, Pulicaria arabica, Tephrosia nubica, Chrozophora oblongifolia, and Clutia myricoides showed pronounced ESßL inhibitory activities. The extracts were quantified for phenolic compounds and their antioxidant properties. Bio-guided fractionation of the active extracts revealed that the chloroform fraction of C. myricoides possess a promising ESßL inhibitory activity. The separation and the structural elucidation of the active compounds from C. myricoides will offer beneficial leads for developing ß-lactamase inhibitors.

Antimicrobial and quorum sensing inhibitory activities of the pericarp of Garcinia mangostana.

A prenylated xanthone, α-mangostin was separated from the alcoholic extract of Garcinia mangostana pericarp. Its structure was established by different spectroscopic analysis. The total methanolic extract (TME) and different fractions of G. mangostana pericarp as well as α-mangostin were assessed for their antimicrobial and quorum sensing inhibitory effects (QSI). The TME, CHCl3 fraction, and α-mangostin exhibited strong activity against all tested strains. While, EtOAc, n-BuOH, and aqueous fractions showed moderate activity against some of the tested organisms. In addition TME, CHCl3, EtOAc, and α-mangostin showed promising QSI, while n-BuOH and aqueous fractions showed moderate activity. Minimal inhibitory concentration (MIC) for TME, CHCl3 fractions, and α-mangostin was also assessed.

L-arginine mitigates bleomycin-induced pulmonary fibrosis in rats through regulation of HO-1/PPAR-γ/ß-catenin axis.

Pulmonary fibrosis is a chronic and progressively deteriorating lung condition that can be replicated in laboratory animals by administering bleomycin, a chemotherapeutic antibiotic known for its lung fibrosis-inducing side effects. L-arginine, a semi-essential amino acid, is recognized for its diverse biological functions, including its potential to counteract fibrosis. This study aimed to evaluate the antifibrotic properties of L-arginine on bleomycin-induced pulmonary fibrosis in rats. The administration of a single intratracheal dose of bleomycin resulted in visible and microscopic damage to lung tissues, an uptick in oxidative stress markers, and an elevation in inflammatory, apoptotic, and fibrotic indicators. A seven-day treatment with L-arginine post-bleomycin exposure markedly improved the gross and histological architecture of the lungs, prevented the rise of malondialdehyde and carbonyl content, and enhanced total antioxidant capacity alongside the activities of antioxidant enzymes. Also, L-arginine attenuated the expression of the pro-fibrotic factors, transforming growth factor-ß and lactate dehydrogenase in bronchoalveolar lavage fluid. In the lung tissue, L-arginine reduced collagen deposition, hydroxyproline concentration, and mucus production, along with decreasing expression of α-smooth muscle actin, tumor necrosis factor-α, caspase-3, matrix metalloproteinase-9, and ß-catenin. Moreover, it boosted levels of nitric oxide and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), heme oxygenase-1 (HO-1), and E-cadherin and downregulating the expression of ß-catenin. These findings suggest that L-arginine has preventive activities against bleomycin-induced pulmonary fibrosis. This effect can be attributed to the increased production of nitric oxide, which modulates the HO-1/PPAR-γ/ß-catenin axis.

Targeting SIRT1/AMPK/Nrf2/NF-кB by sitagliptin protects against oxidative stress-mediated ER stress and inflammation during ANIT-induced cholestatic liver injury.

Intrahepatic cholestasis is a common clinical form of hepatobiliary injury characterized by the intrahepatic accumulation of toxic bile acids. Besides its antidiabetic activity, the dipeptidyl peptidase IV inhibitor sitagliptin (SG) has been recently assigned diverse pharmacological activities and therapeutic potential against different disorders owing to its emerging antioxidant and anti-inflammatory properties. The current study explored the potential hepatoprotective effect of SG on α-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and investigate its possible targeted signaling pathways. Mice received SG (10 and 20 mg/kg) for four consecutive days, two days before and after a single oral administration of ANIT (75 mg/kg). Our results revealed that SG administration remarkably prevented ANIT-induced histopathological lesions in the liver and maintained hepatic functions and oxidative/antioxidant balance. Ultimately, SG counteracted the inflammatory response in the liver, as indicated by the marked suppression of hepatic expression of NF-κB, TNF-α, and IL-6. Moreover, it inhibited the endoplasmic reticulum (ER) stress response in the liver. These beneficial effects of SG were accompanied by upregulation of SIRT1, p-AMPK, and Nrf2 expressions while downregulating keap1 expression in the liver. In conclusion, this study is the first to demonstrate the ability of SG to protect against ANIT-induced CLI through modulating multiple signaling cascades, including SIRT1/AMPK, Nrf2/keap1, and NF-кB, which resulted in enhanced antioxidant capacity and repressed inflammatory and ER stress responses in the liver.

Thymoquinone is a natural antibiofilm and pathogenicity attenuating agent in Pseudomonas aeruginosa.

Pseudomonas aeruginosa belongs to the critical pathogens that represent a global public health problem due to their high rate of resistance as listed by WHO. P. aeruginosa can result in many nosocomial infections especially in individuals with compromised immune systems. Attenuating virulence factors by interference with quorum sensing (QS) systems is a promising approach to treat P. aeruginosa-resistant infections. Thymoquinone is a natural compound isolated from Nigella sativa (black seed) essential oil. In this study, the minimum inhibitory concentration of thymoquinone was detected followed by investigating the antibiofilm and antivirulence activities of the subinhibitory concentration of thymoquinone against P. aeruginosa PAO1. The effect of thymoquinone on the expression of QS genes was assessed by quantitative real-time PCR, and the protective effect of thymoquinone against the pathogenesis of PAO1 in mice was detected by the mouse survival test. Thymoquinone significantly inhibited biofilm, pyocyanin, protease activity, and swarming motility. At the molecular level, thymoquinone markedly downregulated QS genes lasI, lasR, rhlI, and rhlR. Moreover, thymoquinone could protect mice from the pathologic effects of P. aeruginosa increasing mouse survival from 20% to 100%. In conclusion, thymoquinone is a promising natural agent that can be used as an adjunct therapeutic agent with antibiotics to attenuate the pathogenicity of P. aeruginosa.

Cilostazol is a promising anti-pseudomonal virulence drug by disruption of quorum sensing.

Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.

RETRACTED: Fahmy et al. Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation. Pharmaceutics 2020, 12, 485.

This journal retracts the article "Intranasal Niosomal In Situ Gel as a Promising Approach for Enhancing Flibanserin Bioavailability and Brain Delivery: In Vitro Optimization and Ex Vivo/In Vivo Evaluation" [...].

RETRACTED: Alhakamy et al. Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells. Pharmaceutics 2020, 12, 346.

The journal retracts the article, "Optimized Icariin Phytosomes Exhibit Enhanced Cytotoxicity and Apoptosis-Inducing Activities in Ovarian Cancer Cells" [...].