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Plants serve as reservoirs of bioactive compounds endowed by nature, rendering them promising subjects for investigating chemical diversity. Despite their potential, much remains untapped, whether in standardized extracts or isolated pure compounds. This unexplored terrain has paved the way for significant discoveries in pharmaceuticals. Notably, research has delved into the medicinal properties of Mallotus philippensis, a prominent plant in South Asia. Employing meticulous extraction techniques such as maceration, the fruit of this plant underwent initial antimicrobial screening, revealing encouraging results. Subsequent fractionation of the plant's extracts via liquid–liquid extractions, utilizing dichloromethane and absolute ethanol, facilitated further analysis. Evaluating these fractions for antibacterial activity demonstrated efficacy against various pathogenic microorganisms, particularly Pseudomonas aeruginosa and Escherichia coli, notably by the ethanolic and dichloromethane extracts. Furthermore, a comprehensive phytochemical analysis unveiled the presence of alkaloids, flavonoids, saponins, glycosides, phenols, and tannins. An assessment of the extracts' antioxidant potential via the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay showcased significant activity, with a radical scavenging rate of 97%. This underscores the significance of utilizing fruit remnants, which are often rich in valuable chemical constituents yet commonly discarded, thereby adding value to both the species and the environment. Further investigation focused on the composition of Mallotus philippensis fruit, encompassing volatile and non-volatile metabolites through HPLC-MS analysis. Additionally, this study introduced the application of ionic liquid-loaded polysulfone microcapsules to enrich target constituents from crude extracts. An exploration of the key separation conditions, results, and recycling performance of these microcapsules provided insights for future research endeavors. Overall, this comprehensive study of Mallotus philippensis fruit extracts establishes a foundation for the ongoing exploration and development of this medicinal plant. [ABSTRACT FROM AUTHOR]

The design and development of a bio-adhesive hydrogel with on-demand removability and excellent antibacterial activities are meaningful to achieve high wound closure effectiveness and post-wound-closure care, which is desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial hydrogels containing peptides from Periplaneta americana (PAP) were prepared through multi-dynamic-bond cross-linking among 3,4-dihydroxybenzaldehyde (DBA) containing catechol and aldehyde groups and chitosan grafted with 3-carboxy-4-fluorophenylboronic acid (CS-FPBA) to enable the effective adhesion of skin tissues and prevention of bacterial infection of wound. PAP was derived from alcohol-extracted residues generated during the pharmaceutical process, aiming to minimize resource wastage and achieve the high-value development of such a medicinal insect. The hydrogel was prepared by freezing-thawing with no toxic crosslinkers. The multi-dynamic-bond cross-linking of dynamic borate ester bonds and dynamic Schiff base bonds can achieve reversible breakage and re-formation and the adhesive strength of CS-FPBA-DBA-P-gel treated with a 20 % glucose solution dramatically decreased from 3.79 kPa to 0.35 kPa within 10 s. Additionally, the newly developed hydrogel presents ideal biocompatibility, hemostasis and antibacterial activity against Staphylococcus aureus and Escherichia coli compared to commercial chitosan gel (approximately 50 % higher inhibition rate), demonstrating its great potential in dealing with infected full-thickness skin wounds. • Multi-dynamic-bond hydrogel of CS, FPBA and DBA was designed for the first time. • The friendly hydrogel was prepared by freezing-thawing with no toxic crosslinkers. • This adhesion enables painless and noninvasive on-demand detachment within 10 s. • Bioactive peptides from Periplaneta americana contributed to antibacterial property. • The high-value development of insect residue was realized to avoid resource waste. [ABSTRACT FROM AUTHOR]

Oxidative stress and intestinal inflammation are main pathological features of ulcerative colitis (UC). Ferroptosis, characterized by iron accumulation and lipid peroxidation, is closely related to the pathologic process of UC. 16S r RNA sequencing for intestinal microbiota analysis and gas chromatography–mass spectrometry (GC–MS) for short-chain fatty acid (SCFA) contents clearly demonstrated lower amounts of butyrate-producing bacteria and butyrate in colitis mice. However, the precise mechanisms of sodium butyrate (NaB) in treating UC remain largely unclear. We found that ferroptosis occurred in colitis models, as evidenced by the inflammatory response, intracellular iron level, mitochondria ultrastructural observations and associated protein expression. NaB inhibited ferroptosis in colitis, significantly rescued weight loss and colon shortening in mice and reduced inflammatory lesions and mitochondrial damage. Furthermore, NaB improved intestinal barrier integrity and markedly suppressed the expression of pro-ferroptosis proteins. Conversely, the protein expression of anti-ferroptosis markers including nuclear factor erythroid-related Factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4), was significantly upregulated with NaB treatment. Moreover, the knockdown of Nrf2 reversed the anti-colitis effect of NaB. Taken together, NaB exhibited a protective effect by ameliorating ferroptosis in experimental colitis through Nrf2/GPX4 signaling and improving intestinal barrier integrity, which provides a novel mechanism for NaB prevention of UC. [Display omitted] • Ferroptosis occurred in the experimental colitis in vivo and in vitro. • Butyrate relieved ferroptosis and improved the gut barrier integrity. • Butyrate exhibited anti-colitis effects through Nrf2/GPX4 signaling pathway. [ABSTRACT FROM AUTHOR]

With the development of health service, animal husbandry, aquaculture and the chemical industry, more and more pollutants are discharged into the water environment, including antibiotics and heavy-metal ions. These hazardous substances pose a great threat to environmental safety and human health. Two new kinds of green solvents, ionic liquids (ILs) and deep eutectic solvents (DESs), are widely utilized in various fields, including separation and environmental engineering, and are attracting much attention from academia and industry. In this study, an optimal ionic liquid and a deep eutectic solvent were selected, and their complex with β-cyclodextrin (β-CD) was first prepared by a process of simple and effective inclusion. After necessary characterization and analysis, two kinds of complexes were applied to prepare a special two-sided sorbent disc by adding a diluent (excipient) and pressing the substance under 5~15 MPa. As a result, the IL and DES were stably immobilized on the disc to play a key role in the selective adsorption of targets. Moreover, the experiments with different hazardous substances achieved the expected results. This study demonstrates that the complex disc, with its easy preparation, good stability, and simple operation, exhibited many merits in its separation performance. We believe it to be a useful tool for water purification and detection of noxious substances. [ABSTRACT FROM AUTHOR]

The microneedle (MN) delivery system presents an attractive administration route for patients with Alzheimer's disease (AD). However, the passive drug delivery mode and low drug loading of MNs often result in unsatisfactory therapeutic efficiency. To address these dilemmas, we developed dual engine-drive bionic MNs for robust AD treatment. Specifically, free rivastigmine (RVT) and RVT particles were co-loaded within the MNs to construct the valve and chambers of the guava, respectively, which can serve as an active engine to promote drug permeation by generating capillary force. K 2 CO 3 and citric acid were introduced as a pneumatic engine into the MNs to promote the permeation of free RVT into deeper skin layers for early intervention in AD. Further, the RVT particles served as a drug depot to provide continuous drug release for prolonged AD treatment. Compared with free RVT-loaded MNs, the dual engine-driven bionic MNs showed an increase in drug loading, cumulative transdermal permeability, and normalized bioavailability of approximately 40%, 22%, and 49%, respectively. Pharmacodynamic studies further confirmed that the dual engine-driven bionic MNs were most effective in restoring memory and recognition functions in mice with short-term memory dysfunction. Therefore, the dual engine-driven bionic MNs hold great promise for highly efficient AD treatment. [Display omitted] • Bionic MNs driven with dual pneumatic and capillary forces significantly enhanced the drug loading and bioavailability of rivastigmine. • Bionic MNs with biphasic drug release behavior provided early intervention and prolonged treatment of Alzheimer's disease. • Bionic MNs effectively restored the memory and recognition functions of mice. [ABSTRACT FROM AUTHOR]

A novel portable conductive system of hydroxylated fullerene (TEGs-C 60) embedded on the deep eutectic solvent (DES, choline chloride/malic acid)-agarose gel was developed for on-demand curation with skin contact. It has been found with better elasticity, conductivity and thermal stability than agarose hydrogel. Especially, the electro-responsive drug releasing amount on the skin of mice and live rabbits through small batteries was proved to be 4–5 times of those without electrical stimulation, which reached the level of clinic daily dosage. Meanwhile, it also showed good biocompatibility and much higher antibacterial rate against S. aureus (78.67 ± 0.80 %) together with E. coli (92.08 ± 1.50 %) than those of commercial chitosan gel. The new electrical "switch" gel system provided an effective and useful development strategy for advanced drug delivery. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] The diabetic wound is a prevalent and serious complication of diabetes, which easily deteriorates due to susceptibility to infection and difficulty in healing, causing a high risk of amputation and economic burden to patients. Bacterial infection, persistent excessive inflammation, and cellular and angiogenesis disorders are the main reasons for the difficulty of diabetic wound healing. In this study, glycerol monooleate (GMO) was used to prepare lyotropic liquid crystal hydrogel (LLC) containing the natural antimicrobial peptide LL37 and carbenoxolone (CBX) to achieve antibacterial, anti-inflammation, and healing promotion for the treatment of diabetic wounds. The shear-thinning properties of the LLC precursor solution allowed it to be administered in the form of a spray, which perfectly fitted the shape of the wound and transformed into a gel after absorbing wound exudate to act as a wound protective barrier. The faster release of LL37 realized rapid sterilization of wounds, controlled the source of inflammation, and accelerated wound healing. The inflammatory signaling pathway was blocked by the subsequently released CBX, and the spread of the inflammatory response was inhibited and then further weakened. In addition, CBX down-regulated connexin (Cx43) to assist LL37 to promote cell migration and proliferation better. Combined with the pro-angiogenic effect of LL37, the healing of diabetic wounds was significantly accelerated. All these advantages made LL37-CBX-LLC a promising approach for the treatment of chronic diabetic wounds. [ABSTRACT FROM AUTHOR]

Dissolving microneedles (DMN) have been studied as a drug delivery system to enhance the transport of drug molecules across the skin with almost no pain. However, the poor dissolving ability of microneedles in the skin and low drug loading have limited their potential application. The aim of this study was to develop a novel dissolving microneedle system with improved dissolving ability for the delivery of poorly water soluble contraception drug, levonorgestrel (LNG). Chitosan and beta-sodium glycerophosphate (β-GP) were incorporated in the formulation of microneedles. It was found that 69.32 ± 4.23% of the microneedles penetrated through the skin and dissolved within the first 2 h, which was almost 2-fold higher than that of the conventional microneedles. In addition, drug loading was significantly increased by packaging LNG into the molecules of hydroxypropyl beta cyclodextrin (HP-β-CD) to form LNG-HP-β-CD inclusion compounds. The use of chitosan and β-GP together with HP-β-CD inclusion compounds was shown to enhance the bioavailability of LNG transdermally. This novel DMN system resulted in a similar pharmacokinetic profile as that following oral administration. In addition to similar C max and AUC values, drug concentrations in the blood were more consistent following the DMN in comparison to oral administration. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that can cause nephrotoxicity. However, the underlying mechanisms are not fully understood and require further investigation. In the present study, we established a PFOS-exposed Sprague-Dawley (SD) rat kidney injury model by intraperitoneal injection of PFOS (1 mg/kg and 10 mg/kg body weight) every alternate day for 15 days and cytotoxicity models of normal rat kidney epithelial (NRK52E) and human renal proximal tubular (HK2) cells exposed to PFOS (20 μM and 60 μM) for 24 h to reveal the mechanisms underlying PFOS-induced nephrotoxicity. Data showed that PFOS increased the kidney index and induced nephrotoxicity in rats. Furthermore, PFOS significantly increased malondialdehyde (MDA) levels, decreased GSH peroxidase (GSH-PX) activity in kidney tissues, and increased intracellular reactive oxygen species (ROS) levels in NRK52E and HK2 cells. Following PFOS treatment, mitochondrial damage in the renal tubular epithelial cells of rats was observed and the mitochondrial membrane potential (ΔΨm) was decreased in NRK52E cells. PFOS upregulated apoptosis of tubular epithelial cells and expression of Connexin 43 (Cx43) in vitro and in vivo. The Cx43 inhibitor gap26 attenuated the apoptosis of tubular epithelial cells. In conclusion, our findings reveal that PFOS may trigger renal tubular cell apoptosis through oxidative stress and upregulation of Cx43, resulting in PFOS-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

The purpose of this research was to prepare emulsions stabilized by mixed proteins to achieve excellent storage stability and superior functional properties. The emulsions (O/W) with uniform nanoscale droplets (∼250 nm, polydispersity index < 0.2) were stabilized by mixed sodium caseinate (SC) and soy protein isolate (SPI) and produced through high pressure homogenization. Characteristics of the emulsions were evaluated by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Transmission Electron Microscopy (TEM), Rheometer and Turbiscan Lab analyzer. The stabilization mechanism was preliminarily investigated by studying the influences of pH, NaCl and SDS solutions on the droplet size, with the application of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). It was found that both flexible protein SC and rigid globular protein SPI were adsorbed on the oil-water interface while some free protein molecules dissolved in the aqueous phase. Electrostatic repulsion and steric stabilization were contributed to the system stability. The retention ratio of vitamin A palmitate was above 93% after three months of storage at room temperature, which demonstrated the protection efficiency of the emulsion was excellent. This work showed a significant promise to develop nutritional products with satisfactory storage stability and physiological benefits. [ABSTRACT FROM AUTHOR]

• A novel flunixin meglumine ODT (Test) was prepared utilizing hot-melt extrusion and D-optimal mixture design. • Test had similar pharmacokinetic behavior to HAIYANSHU® but a better taste-masking effect. • This study provides a new formulation of flunixin meglumine for potential clinical use. Flunixin meglumine (FM) is a nonsteroidal anti-inflammatory drug limited by irritation of the respiratory tract and mucosa in veterinary tissue. This study aimed to develop a taste-masked FM solid dispersion (SD) by hot-melt extrusion (HME) and formulate an orally disintegrating tablet (ODT) with selected excipients by direct compression. Eudragit® E PO was chosen as the matrix, and HME parameters were optimized: extrusion temperature, 135℃; screw speed, 100 rpm; and drug loading, 20%. Characterization techniques proved that FM was rendered amorphous in the HME extrudate. In vitro dissolution studies showed that FM SD released significantly slower than the corresponding physical mixture in artificial saliva. Excipients were selected based on compression formability, disintegration, and solubility. A D-optimal mixture design was used to optimize the composition: 25% FM SD, 18.75% microcrystalline cellulose, 52.5% mannitol, 3.75% low-substituted hydroxypropyl cellulose, and 1% magnesium stearate. Taste-masked FM ODT had a tensile strength of 0.7 ± 0.01 MPa and a disintegration time of 17.6 ± 0.1 s. E-tongue and E-nose analysis showed that FM ODT had a better taste-masked effect than commercial granules. Finally, a pharmacokinetic study proved that the main pharmacokinetic parameters of FM ODT were not significantly different from those of commercial granules, which indicated that these formulations had similar pharmacokinetic behaviours in beagles. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: A method to prepare wide-band reflection cholesteric liquid crystals (CLCs) films by thermally induced diffusion of dye was proposed. Due to the greatly enhanced UV intensity gradient formed by thermal diffusion of dye, the pitch gradient was formed and fixed after the process of photoinduced polymerization and diffusion of CLC monomers. Using this method, the prepared CLCs film can reflect circularly polarized light over a broad wavelength range of 750–2400nm. The pitch gradient of the CLC film was observed by scanning electron microscopy (SEM). In addition, the influence of dye concentration, thermal diffusion time and thermal diffusion temperature on the consequent pitch gradient was systemically studied. [Copyright &y& Elsevier]