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Bitong Mixture (BM) has shown efficacy in alleviating pain in knee osteoarthritis (OA) in clinical practice; however, the molecular mechanisms underlying its therapeutic effects remain to be fully elucidated. This study aimed to identified BM-related OA biomarkers and explore their functional implications. An integrative strategy combining bioinformatics prediction and experimental validation was used. Biomarkers were screened from public OA transcriptomic data using differential expression analysis, network pharmacology, and machine learning. Their functions were explored via enrichment and immune infiltration analyses. Molecular docking predicted interactions between herbal compounds and targets. Single-cell analysis characterized biomarker expression in chondrocyte subsets. A rat OA model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were employed for validation. Bioinformatic prediction identified three potential biomarkers: MMP9, MMP2, and SPP1. They demonstrated certain diagnostic performance for OA and were implicated in pathways related to extracellular matrix organization and immune regulation. Immune analysis revealed significant correlations, notably between MMP2 and activated dendritic cells (cor = 0.66) and between SPP1 and CD4+ central memory T cells (cor = -0.75). Molecular docking suggested strong binding affinity between luteolin (a BM component) and MMP9. Single-cell analysis indicated high expression of these potential biomarkers in hypertrophic chondrocytes, inflammatory chondrocytes, and fibrochondrocytes. validation confirmed that BM alleviated OA symptoms and histopathological damage in rats. RT-qPCR results showed that BM treatment alleviated the OA-induced upregulation of MMP9, MMP2, and SPP1 expression. MMP9, MMP2, and SPP1 are potential therapeutic biomarkers for BM in OA. The efficacy of BM may be attributed to its regulation of extracellular matrix remodeling and immune responses, which provides a possible mechanistic explanation for its clinical use.

Polysaccharides are gaining increasing attention for their relevance in the production of sustainable materials. In the domain of biomaterials, polysaccharides play an important role as hydrophilic components in the design of amphiphilic block copolymers for the development of drug delivery systems, in particular nanocarriers due to their outstanding biocompatibility, biodegradability, and structural versatility. The presence of a reducing end in polysaccharide chains allows for the synthesis of polysaccharide-based block copolymers. Compared with polysaccharide-based graft copolymers, the structure of block copolymers can be more precisely controlled. In this review, the synthesis methods of polysaccharide-based amphiphilic block copolymers are discussed in detail, taking into consideration the structural characteristics of polysaccharides. Various synthetic approaches, including reductive amination, oxime ligation, and other chain-end modification reactions, are explored. This review also focuses on the advantages of polysaccharides as hydrophilic blocks in polymeric nanocarriers. The structure and unique properties of different polysaccharides such as cellulose, hyaluronic acid, chitosan, alginate, and dextran are described along with examples of their applications as hydrophilic segments in the synthesis of amphiphilic copolymers to construct nanocarriers for sustained drug delivery.

Selenium nanoparticles (SeNPs) attract considerable attention for their promising applications in the biomedical field, driven by their unique properties and antioxidant activities. However, their practical use is often hindered by issues such as instability and aggregation. In this study, a polysaccharide, P2, extracted from Ononis natrix, was used to stabilize SeNPs to address these limitations. P2-SeNPs were prepared through a green synthesis method involving sodium selenite, P2, and ascorbic acid, and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD). P2-SeNPs exhibited a smaller particle size and enhanced stability compared to unmodified SeNPs. UV-Vis spectroscopy and X-ray photoelectron spectroscopy (XPS) demonstrated the presence of Se–O bonds, suggesting effective stabilization by covalent bonding between SeNPs and P2. Stability tests revealed that P2-SeNPs maintained good dispersion under various conditions, with optimal stability observed at refrigerated temperatures and neutral pH. Moreover, P2-SeNPs exhibited better antioxidant activities than unmodified SeNPs, as evidenced by higher DPPH radical scavenging, ABTS radical scavenging, and metal chelation ratios. This difference is attributed to both the reduced aggregation and smaller size of P2-SeNPs. Therefore, it is concluded that P2-SeNPs exhibit significant potential as an effective antioxidant agent for biomedical applications.

A well-defined block copolymer brush poly(glycidyl methacrylate)-graft-(poly(methyl methacrylate)-block- poly(oligo(ethylene glycol) methyl ether methacrylate)) (PGMA-g-(PMMA-b-POEGMA)) is synthesized via grafting from an approach based on a combination of click chemistry and reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting block copolymer brushes were characterized by 1H-NMR and size exclusion chromatography (SEC). The self-assembly of the block copolymer brush was then investigated under selective solvent conditions in three systems: THF/water, THF/CH3OH, and DMSO/CHCl3. PGMA-g-(PMMA-b-POEGMA) was found to self-assemble into spherical micelle structures as analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The average size of the particles was much smaller in THF/CH3OH and DMSO/CHCl3 as compared with the THF/water system. Thin film of block copolymer brushes with tunable surface properties was then prepared by the spin-coating technique. The thickness of the thin film was confirmed by scanning electron microscopy (SEM). Atom force microscopy (AFM) analysis revealed a spherical morphology when the block copolymer brush was treated with poor solvents for the backbone and hydrophobic side chains. The contact angle measurements were used to confirm the surface rearrangements of the block copolymer brushes.

Purpose The aim of this study is to develop novel polylactide/poly(ethylene glycol) (PLA/PEG) micelles as carrier of hydrophobic drug (paclitaxel) by direct dissolution method without using any organic solvents. The in vitro and in vivo release properties were studied in comparison with micelles prepared by dialysis. Methods Drug encapsulation efficiency (EE) and loading content (LC) of the micelles were evaluated by high-performance liquid chromatography. Micelle diameters and structures were determined by dynamic light scattering and transmission electron microscopy. In vitro release was performed in phosphate-buffered saline (pH 7.4) at 37°C, and in vivo experiments were realized in lung cancer-bearing mice. Results Similar EE and LC values were obtained for micelles by direct dissolution method and those by dialysis. L- and D-PLA/PEG mixed micelles present higher drug encapsulation ability than separate micelles due to stereocomplexation. Micelle diameters are enlarged by drug-loading. Faster drug release was obtained for micelles by direct dissolution than those by dialysis. Compared with current clinical formulation and micelles by dialysis, paclitaxel-loaded micelles by direct dissolution showed the highest antitumor ability. Conclusion The L- and D-PLA/PEG mixed micelles by direct dissolution method present many advantages such as easy formulation and absence of toxic organic solvents, which shows great potential as carrier of hydrophobic drugs.

Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro, and Zebrafish embryonic compatibility in vivo. The nanotubes present good cell compatibility and blood compatibility in vitro, and almost no toxicity towards Zebrafish embryos development in vivo. Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.

To find better strategies to enhance the cytotoxic effect of paclitaxel (PTX) and lapatinib (LAP) against breast cancer cells, we analyzed the efficacy of a novel delivery system containing polylactide-co-poly(ethylene glycol) (PLA-PEG) filomicelles of over 100 nm in length and spherical micelles of approximately 20 nm in diameter. The 1H NMR measurements confirmed the incorporation of PTX and LAP into micelles. Analysis of the drug release mechanism revealed the diffusion-controlled release of LAP and anomalous transport of PTX. Drug content analysis in lyophilized micelles and micellar solution showed their good storage stability for at least 6 weeks. Blank micelles, LAP-loaded micelles and free LAP did not affect MCF-7 breast cancer cell proliferation, suggesting that the cytotoxicity of PTX-, PTX/LAP-loaded micelles, and the binary mixture of free PTX and LAP was solely caused by PTX. PTX/LAP-loaded micelles showed greater toxicity compared to the binary mixture of PTX and LAP after 48 h and 72 h. Only free PTX alone induced P-gp activity. This study showed the feasibility of using a LAP and PTX combination to overcome MDR in MCF-7 cells, particularly when co-loaded into micelles. We suggest that PTX/LAP micelles can be applicable not only for the therapy of HER-2-positive, but also HER-2-negative breast cancers.

The present study aims to investigate the properties of biopolymers extracted from a Lebanese onion non edible plant. The extraction was performed under mild conditions by varying the percentage of ultra-sound (US) treatment duration to a total extraction time of 30 min (0, 50, 100% US). The extracts were characterized using FTIR, SEC, GC-MS, TGA, and DSC analyses. The composition of the extracts was determined from the total carbohydrate content and protein content measurements. The thermal analyses indicate that all samples have high thermal stability. The antioxidant activities of the extracts were investigated, using β-carotene bleaching, scavenging activity of ABTS, metal chelating ability, and total antioxidant activity tests. The results indicate that the 50% US treatment leads to the best antioxidant activity. Biocompatibility of the extracts was evaluated using hemolysis and cytotoxicity assays. The results showed that 0 and 50% US samples are not toxic to human cells, in contrary to 100% US.

The morphology and melt crystallization of zinc catalyzed poly(L‐lactide) (PLLA) were investigated by using differential scanning calorimetry (DSC), polarized optical microscopy, and scanning electron microscopy. Isothermal melt crystallization performed at 95–135°C showed that the morphology depends on the degree of supercooling, as illustrated by crystallite perfection and lamellar thickening behaviors. Double melting peak was observed on DSC thermograms and attributed to the melt‐recrystallization mechanism, small and imperfect crystals becoming gradually more stable ones. Circumferential and hexagonal cracks were detected in PLLA spherulites, which were formed during melt‐crystallization at 135°C and quenching in liquid nitrogen. Rhythmic growth and thermal shrinkage are suggested to be the two main factors accounting for the formation of periodic cracks. Spherulite growth rates of PLLA were evaluated by using combined isothermal and nonisothermal procedures, and were analyzed by the secondary nucleation theory. The maximum growth rate reached 9.1 μm/min at 130°C. The temperature range investigated (120–155°C) belongs to the Regime II of crystallization. The value of U* was found to be 1890 cal/mol, instead of 1500 cal/mol commonly used in literature, and Kg and σ were estimated to be 3.03 × 105 K2 and 1.537 × 10−4 J/m2, respectively. As a result, no distinct difference between PLLA catalyzed by zinc metal and those prepared with stannous octoate catalyst exists in this work. POLYM. ENG. SCI., 46:1583–1589, 2006. © 2006 Society of Plastics Engineers.

The present study investigated chitosan nanoparticle (CS-TPP NPs) preparation by ionic gelation process with chitosan (CS) and tripolyphosphate (TPP). The structural characterization of nanoparticles was studied using Dynamic Light Scattering, Nuclear Magnetic Resonance, Fourier Transform Infrared (FTIR) and X-Ray Diffraction spectroscopies. FTIR spectra confirmed that the tripolyphosphoric groups of TPP linked with ammonium groups of CS in the prepared nanoparticles. CS-TPP NPs exhibited higher antioxidant activity and an interesting antimicrobial potential. In fact, there was no report available in literature on using CS nanoparticles for the surimi preservation. Further, data revealed that nanoparticle incorporation in fish surimi effectively inhibited thiobarbituric acid substances and conjugated dienes formation, and thereby, retarding lipid oxidation. Results showed that CS-TPP NPs were able to hinder fish surimi myoglobin oxidation with a significant improvement in the transformation of Heme iron. In addition, CS nanoparticles exhibited a distinguishable antimicrobial activity in the stored surimi during cold storage of 9 days. Thus, nanoparticles could be used as a natural ingredient to prevent lipid oxidation in surimi based food systems for the development of novel healthy fish products and addresses consumer demands for functional fish products.