Citrus peel pectin and alginate-based emulgel particles for small intestine-targeted oral delivery of curcumin.

Polysaccharides are a prominent choice in the realm of food-grade oral delivery systems due to their resistance to degradation by digestive enzymes in the oral, gastric, and small intestinal environments, as well as their ease of production, cost-effectiveness, and potential health benefits as prebiotics. Furthermore, their ability to respond to pH-induced dissolution, along with their emulsifying properties, can be strategically employed to achieve precise targeting of lipophilic bioactives to the small intestine. In this study, citrus peel pectin and alginate served as stabilizers for emulgel particles without supplementary emulsifiers or gelling agents. Within this system, pectin functioned as an emulsifier, while alginate acted as a gelling agent, facilitated by Ca2+-induced ionic crosslinking. The synergistic interplay between pectin and alginate efficiently protected curcumin in gastric conditions and controlled dissolution in the small intestine, depending on the pectin/alginate ratio. These controlled phenomena facilitated lipolysis, curcumin release, and ultimately enhanced curcumin bioaccessibility. Furthermore, once the emulgel particle released all the entrapped curcumin in the small intestine, residual polysaccharides underwent facile degradation by pectinase and alginate lyase, yielding fermentable monosaccharides. This confirms the potential of the emulgel particles for use as a prebiotic in the colon. These findings offer significant promise for enhancing the systematic design of food-grade delivery systems that encapsulate lipophilic bioactives, achieving controlled release, enhanced stability, and improved bioaccessibility. Importantly, this system can comprise components that undergo complete digestion, absorption, and utilization in the human body, encompassing materials such as oil, nutraceuticals, and prebiotics, all without presenting health risks.

Cr(VI) immobilization by FeS-coated alumina and silica: Effects of pH and surface coating density.

We investigated the feasibility of using FeS-coated alumina and silica for permeable reactive barrier (PRB) applications. By both coated materials, Cr(VI) was reduced to Cr(III), which was immobilized via surface complexation/precipitation at acidic pH, and bulk precipitation at neutral to basic pH. Both pH and surface coating density (the amount of FeS deposits per unit surface area of a supporting matrix) controlled Cr(VI) reduction capacity and [Cr,Fe](OH)3 composition. The reduction was higher at acidic pH due to lower passivation, as evidenced by the increased production of Fe(III) (oxyhydr)oxides over Fe(II)-Fe(III) phases. The coated alumina, despite the lower amount of FeS deposits than the coated silica, showed greater reduction capacities due to its higher surface coating density, which made Fe(III) closer together to favor Fe(III) (oxyhydr)oxide formation. Since Cr(III) was preferentially substituted for Fe(III) in Fe(III) (oxyhydr)oxides, lower pH and higher surface coating density led to lower Cr fractions in [Cr,Fe](OH)3 because of the increased production of Fe(III) (oxyhydr)oxides. Given that Cr-poor [Cr,Fe](OH)3 is more resistant to re-oxidation, FeS-coated alumina is better for PRB applications. This study reveals the significance of the surface coating density when evaluating the effectiveness of coated materials in redox-based treatments.

Discovery of Novel Pyrimidine-Based Capsid Assembly Modulators as Potent Anti-HBV Agents.

Core assembly modulators of viral capsid proteins have been developed as an effective treatment of chronic hepatitis B virus (HBV) infection. In this study, we synthesized novel potent pyrimidine derivatives as core assembly modulators, and their antiviral effects were evaluated in in vitro and in vivo biological experiments. One of the synthesized derivatives, compound 23h (R1 = MeSO2, R2 = 1-piperidin-4-amine, R3 = 3-Cl-4-F-aniline) displayed potent inhibitory effects in the in vitro assays (52% inhibition in the protein-based assay at 100 nM and an IC50 value of 181 nM in the serum HBV DNA quantification assay). Moreover, treatment with compound 23h for 5 weeks significantly decreased serum levels of HBV DNA levels (3.35 log reduction) in a human liver-chimeric uPA/SCID mouse model, and these effects were significantly increased when 23h was combined with tenofovir, a nucleotide analogue inhibitor of reverse transcriptase used for the treatment of HBV infection.

Ulmusakidian, a new coumarin glycoside and antifungal phenolic compounds from the root bark of Ulmus davidiana var. japonica.

Bioactivity-driven LC/MS-based phytochemical analysis of the root bark extract of Ulmus davidiana var. japonica led to the isolation of 10 compounds including a new coumarin glycoside derivative, ulmusakidian (1). The structure of the new compound was elucidated using extensive spectroscopic analyses via 1D and 2D NMR spectroscopic data interpretations, HR-ESIMS, and chemical transformation. The isolated compounds 1-10 were tested for their antifungal activity against human fungal pathogens Cryptococcus neoformans and Candida albicans. Compounds 9 and 10 showed antifungal activity against C. neoformans, with the lowest minimal inhibitory concentration (MIC) of 12.5-25.0 µg/mL, whereas none of the compounds showed antifungal activity against C. albicans.

Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly.

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly.

In Vitro Anti-Malassezia Activity of Castanea crenata Shell and Oil-Soluble Glycyrrhiza Extracts.

BACKGROUND: A new shampoo with anti-Malassezia properties obtained from various plants is required to provide seborrheic dermatitis patients with a wider range of treatment options. OBJECTIVE: The aim of this study was to obtain in vitro susceptibility profiles of Malassezia restricta and M. globosa, the most important pathogenic organisms in the development of seborrheic dermatitis, to the plant extracts used in commercial anti-dandruff shampoos. METHODS: Minimal inhibitory concentrations (MICs) were determined for eight candidate plant extracts and two plant-derived natural products diluted with Leeming and Notman medium to final concentrations of 0.016 to 1 mg/ml. RESULTS: Castanea crenata shell, Camellia sinensis leaf, and oil-soluble Glycyrrhiza extracts presented relatively low MIC values (≤0.5 mg/ml) against both strains. The C. crenata shell and oil-soluble Glycyrrhiza extracts demonstrated especially high anti-Malassezia activity, suggesting their potential use in the treatment of seborrheic dermatitis. The extracts also showed fungistatic activity against other common facultative pathogenic yeasts, Cryptococcus and Candida. CONCLUSION: C. crenata shell and oil-soluble Glycyrrhiza extracts could potentially be used as active ingredients in anti-seborrheic and anti-dandruff shampoo formulations. They could be helpful for repeated treatments and regular prophylaxis of scalp seborrheic dermatitis.

Comparison of treatment with preservative-free versus preserved sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops after cataract surgery in patients with preexisting dry-eye syndrome.

PURPOSE: To compare treatment with preservative-free and preserved sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops after cataract surgery in patients with preexisting dry-eye syndrome. SETTING: Bucheon St. Mary's Hospital, Catholic University of Korea, Seoul, Korea. DESIGN: Randomized controlled study. METHODS: Patients with cataract and dry-eye syndrome were randomly divided into 2 groups. Group 1 patients were treated with preservative-free sodium hyaluronate 0.1% and preservative-free fluorometholone 0.1% eyedrops 4 times a day in the first month and twice a day in the second month. Group 2 patients were treated with preserved eyedrops using the same schedule. Ocular Surface Disease Index (OSDI) score, tear-film breakup time (TBUT), Schirmer I test, corneal fluorescein staining, impression cytology, and antioxidant and inflammatory cytokine activities in tears were evaluated. RESULTS: Both groups comprised 40 patients. At 2 months, the OSDI score, TBUT, Schirmer I score, fluorescein staining score, impression cytology findings, and goblet cell count were significantly better in Group 1 than in Group 2 (P<.05). The interleukin-1ß and tumor necrosis factor-α concentrations were significantly less in the tears of Group 1 patients than in the tears of Group 2 patients, and catalase and superoxide dismutase 2 fluorescence intensities were significantly greater in the tears of Group 1 patients than in the tears of Group 2 patients (P<.05). CONCLUSIONS: Preservative-free sodium hyaluronate 0.1% and fluorometholone 0.1% eyedrops can improve the symptoms and signs of dry-eye syndrome after cataract surgery. Preservative-free fluorometholone eyedrops may have antiinflammatory and antioxidant effects in tears of patients with dry-eye syndrome. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.