International Journal of Biological Macromolecules最新文献

Lipid nanoparticles are obtaining significant attention in cancer treatment because of their efficacy at delivering drugs and reducing side effects. These things are like a flexible platform for getting anticancer drugs to the tumor site, especially upon HA modification, a polymer that is known to target tumors overexpressing CD44. HA is promising in cancer therapy because it taregtes tumor cells by binding onto CD44 receptors, which are often upregulated in cancer cells. Lipid nanoparticles are not only beneficial in improving solubility and stability of drugs; they also use the EPR effect, meaning they accumulate more in tumor tissue than in healthy tissue. Adding HA to these nanoparticles expands their biocompatibility and makes them more accurate and specific towards tumor cells. Studies show that HA-modified nanoparticles carrying drugs such as paclitaxel or doxorubicin improve how well cells absorb the drugs, reduce drug resistance, and make tumor shrinking. These nanoparticles can respond to tumor microenvironment stimuli in targeted delivery. This targeted delivery diminishes side effects and improves anti-cancer activity of drugs. Thus, lipid-based nanoparticles conjugated with HA are a promising way to treat cancer by delivering drugs effectively, minimizing side effects, and giving us better therapeutic results.

The creation of polymer composites with better performance is a crucial thing. The cellulosic filler material gain popularity in polymer composites. In this study, aquatic plant Pistia stratiote leaves were used as a raw material for cellulose extraction. The cellulose was extracted via acid hydrolysis method with mild concentration chemicals. The main aim was to assess the cellulose characteristics and its potential as a reinforcement for composites. Surface, thermal, and physicochemical properties of the micro fillers made of cellulose were the primary areas of research. To determine the composition of the cellulose, extensive chemical characterization analyses were conducted. According to X-ray diffraction studies, Pistia stratiotes leaves cellulose have a crystallinity index of 75.9 % and crystalline size of 8.2 nm. Cellulosic functional groups were revealed by examination using a Fourier Transform Infrared Spectrometer. Scanning electron microscopy images revealed smooth surface and distorted shaped particles. The average particle size, which was calculated using the ImageJ software, was 23.253 ± 6.55 μm. The extracted micro cellulose had an acceptable average roughness value of 28.296 μm, as shown by atomic force microscopy images. Surface properties of the Pistia stratiotes leaves cellulose (PSC) were shown to be conducive to the formation of interfacial bonds with other matrices while composites are being built. The BET surface areas are significantly higher as well. The material degrades only at high temperatures 215 °C, which was analysed by TG analysis. The findings demonstrate that Pistia stratiotes, a plant, outperforms more conventional sources of micro cellulose, such as cotton, hemp, and wood. As a greener alternative to synthetic reinforcements, the recovered micro cellulose has potential uses across numerous industries.

Pseudomonas aeruginosa (PA) is a critical pathogen, and its antibiotic resistance is largely driven by the quorum-sensing regulator LasR. Herein, we report the design, synthesis, and characterization of Aqs1C, a mutated peptide derivative of Aqs1, optimized to inhibit LasR and its quorum-sensing pathway. By introducing a targeted mutation, Aqs1C exhibited enhanced stability and binding affinity for LasR protein compared to its predecessor, Aqs1B. Using molecular dynamics simulations (MDS), the Aqs1C-LasR complex demonstrated a marked increase in structural stability, reflected in reduced root mean square deviation (RMSD) values and lower binding free energy. Electrostatic complementarity analysis showed stronger and more favorable interactions between Aqs1C and LasR. Further, GaMD experiments were able to reproduce the binding state between Aqs1C and LasR, indicating the binding mechanism between them. These molecular insights correlated with functional in vitro assays. Aqs1C effectively inhibited quorum-sensing-associated virulence factors in PA, involving biofilm formation (77.6 % inhibition), pyocyanin production (75.7 % inhibition), protease secretion (61.1 % inhibition), and rhamnolipid production (74.1 % inhibition), at a 100 μg/mL concentration, in a comparable or superior pattern to azithromycin (AZM). Molecular modelling, MDS, and GaMD insights and in vitro assays established Aqs1C as a promising candidate for therapeutic development to mitigate PA infections through targeted quorum-sensing disruption.

Fatigue is a pathological state that can impair physical and cognitive performance, making the development of effective therapeutic strategies crucial. In this study, an acid polysaccharide (MHa) was isolated from Mentha haplocalyx. Structural analysis showed that MHa (40.7 kDa) has a backbone consisting of 4-α-GalAp, 6-α-Galp, and 4,6-α-Galp, with branches at the C6 of 4,6-α-Galp linked to four distinct side chains, including 4-α-Galp, 3,6-β-Manp, t-α-Araf, t-α-Rhap, t-α-Glcp, and t-β-Rhap. MHa possesses a triple-helix conformation with a sheet-like appearance, which may contribute to its biological stability and activity. Functionally, MHa exhibited significant antifatigue effects, with the 400 mg/kg dose showing the most potent activity. Compared to the model group, treatment with 400 mg/kg of MHa increased the exhaustive swimming time by 1.89-fold in fatigued mice, reduced blood lactate and urea nitrogen levels by 24.21 % and 35.57 %, respectively, and enhanced liver glycogen, muscle glycogen, and ATP levels by 20.08 %, 46.52 %, and 50.43 %, respectively. MHa improved the activities of Ca²⁺-Mg²⁺-ATPase and Na⁺-K⁺-ATPase, while also enhancing antioxidant defense. Mechanistically, MHa promotes mitochondrial biogenesis and enhances oxidative defense via activating AMPK. These findings highlight the potential of MHa as a promising candidate for developing antifatigue supplements, offering a novel strategy to mitigate fatigue.

Oxidative stress (OS) is a pivotal mechanism driving the progression of cardiovascular diseases, particularly heart failure (HF). However, the comprehensive characterisation of OS-related genes in HF remains largely unexplored. In the present study, we analysed single-cell RNA sequencing datasets from the Gene Expression Omnibus and OS gene sets from GeneCards. We identified 167 OS-related genes potentially linked to HF by applying algorithms, such as AUCell, UCell, singscore, ssgsea, and AddModuleScore, combined with correlation analysis. Subsequently, we used feature selection algorithms, including least absolute shrinkage and selection operator, XGBoost, Boruta, random forest, gradient boosting machines, decision trees, and support vector machine recursive feature elimination, to identify lumican (LUM) and procollagen C-endopeptidase enhancer 2 (PCOLCE2) as key biomarker candidates with significant diagnostic potential. Bulk RNA-sequencing confirmed their elevated expression in patients with HF, highlighting their predictive utility. Single-cell analysis further revealed their upregulation primarily in fibroblasts, emphasising their cell-specific role in HF. To validate these findings, we developed a transverse aortic constriction-induced HF mouse model that showed enhanced cardiac OS activity and significant PCOLCE2 upregulation in the HF group. These results provide strong evidence of the involvement of OS-related mechanisms in HF. Herein, we propose a diagnostic strategy that provides novel insights into the molecular mechanisms underlying HF. However, further studies are required to validate its clinical utility and ensure its application in the diagnosis of HF.

Lignocellulosic nanofibers (LCNF), blending nano-scale cellulose and lignin, were carboxylated and integrated with PVA and baicalin to create a molecularly imprinted membrane (CLCNF-MINM). This innovation, leveraging reactive deep eutectic solvent technology and electrospinning, boosts adsorption capacity by 12.3-21.5 % and resolution by 31.6 %, achieving a max capacity of 142.1 mg·g^-1. The high surface area, layered structure and tunable surface chemistry of carboxyl lignocellulose nanofibers (CLCNF), along with chemisorption and multimolecular adsorption mechanisms, significantly improve adsorption efficiency and selectivity. The membrane's mechanical strength is quadrupled and it retains 96.4 % of its absorption capacity after eight cycles of use. CLCNF-MINM significantly enhances the efficient utilization of biomass resources while exhibiting exceptional performance in the separation and purification of natural products. This study provides valuable insights into the development of advanced materials for improved natural product purification.

α-Glucosidase (α-Glu) is an enzyme that lowers postprandial blood glucose after breaking down complex carbohydrates. Kaempferide is the principal flavonoid active ingredient in plants and is widely found in fruits, vegetables, and beverages. This study found that kaempferide has the potential to inhibit α-Glu activity to treat type 2 diabetes. The results showed that kaempferide (IC₅₀ = 55.35 ± 0.27 μM), serving as a mixed-type inhibitor for α-Glu, exhibited sensibly superior inhibition of α-Glu than acarbose (IC₅₀ = 414.08 ± 10.73 μM). In addition, the outcomes from fluorescence quenching, 3D fluorescence, synchronous fluorescence, CD spectroscopy, and molecular docking analysis showed that kaempferide can not only chelate with α-Glu by hydrogen bonding and Van der Waals forces, but also affect the secondary structure and activity of the enzyme. After oral administration of sucrose in mice, kaempferide effectively reduces postprandial blood glucose (PBG) and without any other adverse symptoms. In summary, this study has the potential to contribute to the development of functional foods for the prevention and management of type 2 diabetes (T2DM).

Glycoprotein Ibα (GPIbα), the initiation protein of arterial thrombosis, was selected as a target for developing new antiplatelet drugs to prevent and treat arterial thrombosis. However, no anti-GPIbα drug is used successfully in clinical. We used human platelets as an antigen to immunize mice and obtained mouse anti-human GPIbα antibody 9C9. The chimeric antibody 1A09 was constructed, and the antibody binding sites were validated, before employing 3D modeling. Following design of a humanized anti-GPIbα, a mouse-derived antibody was mutated into a human sequence to construct the humanized anti-GPIbα antibody SZ003. ELISA, western blot, platelet aggregation, and thrombus model experiments were used to test the specificity, affinity, safety, and thrombus inhibition effects. The experimental results showed that SZ003 bound to GPIbα, inhibited GPIbα-mediated platelet aggregation, and induced in vivo platelet clearance. Furthermore, SZ003-Fab inhibited GPIbα-mediated platelet aggregation and thrombosis but did not induce in vivo platelet clearance, prolong bleeding time in mouse tails, nor have cytotoxic effects on human platelets. The Fab fragment of anti-human GPIbα humanized antibody SZ003 effectively inhibited GPIbα receptor-mediated platelet activation and thrombosis in vivo without leading to thrombocytopenia and bleeding. Therefore, SZ003-Fab has clinical value as a novel antithrombotic drug to treat arterial thrombus-related diseases.

The chitosan-based bone-targeted delivery system was designed to enhance the therapy efficacy of Cyclolinopeptide J (CLJ), a bioactive peptide derived from flaxseed, for the treatment of osteoporosis. The bone-targeting polymer conjugates (CSD8) were prepared via a crosslinking reaction between carboxylated chitosan (CMCS) and functional peptide (ASP8). The CSD8 was then modified on the surface of CLJ-loaded nanoparticles to form novel nanoparticles (JCA/CSD8). The particle size of JCA/CSD8 was 122.40 ± 1.8 nm and the loading capacity of CLJ was 22.7 %. The results showed that the in vitro bone affinity and in vivo bone targeting efficiency of JCA/CSD8 increased 11.7-fold and 13.6-fold, respectively, achieving systemic targeting. Moreover, in vitro studies revealed that JCA/CSD8 could degrade within lysosomes under acidic conditions, thereby releasing CLJ and Ca²⁺ for synergistically promoting osteogenesis to realize the local targeting. The JCA/CSD8 group increased the transcription levels of osteogenic-related markers, including OPG, ColI, OCN, OPN, RUNX2, and ALP. Furthermore, in vivo studies demonstrated the impressive capability of JCA/CSD8 to increase bone density and restore trabecular bone architecture in the OVX mice model, which was superior to the positive control group. In conclusion, using chitosan-based bone-targeted nanoparticles presents a highly promising and efficient clinical therapy for addressing osteoporosis.