International Journal of Biological Macromolecules最新文献

Self-assembling peptides have been widely used in biomedical fields due to their remarkable advantages including excellent biocompatibility and biodegradable, as well as distinctive physicochemical and biochemical activities. To enabling the further widespread application of self-assembling peptides (SAPs) in clinical cancer therapies, this review summarizes the transmembrane mechanisms and targeted delivery strategies of self-assembling peptides nanomedicines. There are six primary types of transmembrane mechanisms involved in SAPs nanomedicines: classical endocytosis, fluoride-modified transmembrane transport, macropinocytosis-mediated transmembrane transport, flexible cyclic peptide-mediated transmembrane transport, receptor-mediated transmembrane transport, and cell-penetrating peptide-mediated endocytosis. The specific delivery of such systems is mainly determined by the incorporated targeting peptides including three types: tumor cell-targeting peptides, tumor vascular endothelial cell-targeting peptides and tumor microenvironment-targeting peptides. Additionally, in the perspective, we highlight the state-of-the-art design and fabrication of SAPs, and put forward our viewpoints on their future development in cancer therapy and the potential challenges in their clinical translation.

Atherosclerosis, driven by oxidative stress and chronic inflammation, requires advanced localized therapies targeting reactive oxygen species (ROS) and immune dysregulation. Here, we report the development of a bioinspired, phenolic-functionalized, zwitterionic chitosan hydrogel engineered for potent antioxidant therapy and macrophage modulation. The hydrogel, synthesized via a green, aqueous enzymatic crosslinking approach, exhibits strong antioxidant activity (~178 μmol Trolox equivalents/g) and efficient free radical scavenging (ABTS⁺ inhibition ~86%, hydroxyl radical scavenging ~82%). It significantly inhibits lipid peroxidation (~68% reduction in MDA levels) and foam cell formation, while promoting anti-inflammatory M2 macrophage polarization (~2.1-fold increase). Furthermore, treatment with the hydrogel markedly downregulated pro-inflammatory biomarkers including IL-6 (~72% reduction), TNF-α (~65% reduction), and CRP (~60% reduction) compared to untreated controls. The material also demonstrated excellent injectability and self-healing properties, and it maintained >90% antioxidant activity after 3 months of storage and 10 freeze-drying cycles, showing higher storage and lyophilization stability than PON1 under the tested conditions. These results highlight the hydrogel's multifunctional therapeutic potential, stability, and biocompatibility, positioning it as a promising platform for targeted, sustained antioxidant therapy in atherosclerosis management.

Objective: The identification of anti-fatigue compounds from natural resources has become an important research focus. This study investigated the anti-fatigue effects and underlying mechanisms of polysaccharides derived from Panax notoginseng (PPN).

Methods: An exercise-induced fatigue mouse model was established using a non-weight-bearing swimming test. Fatigue-related biochemical markers were analysed to evaluate the pharmacological effects of PPN in vivo. A pathological fatigue model was induced using lipopolysaccharide (LPS). The effects of PPN on toxic metabolites, energy substrates and oxidative stress were further assessed.

Results: PPN was successfully isolated with a weight-average molecular weight of 57,141 Da, and was mainly composed of glucose and galactose monomers. In the exercise-induced fatigue model, PPN administration enhanced exercise endurance through reduction of the accumulation of toxic metabolic by-products, regulation of energy metabolism, and mitigation of oxidative stress. Moreover, PPN significantly increased the protein and mRNA expression levels of p-AMPK/PGC-1α. Comparable anti-fatigue effects were observed in the pathological fatigue model.

Conclusion: PPN improves exercise endurance by modulating the p-AMPK/PGC-1α pathway and demonstrates efficacy against both exercise-induced and pathological fatigue. These findings suggest that PPN may serve as a promising natural therapeutic agent for the management of fatigue.

Cellulose nanocrystals (CNCs) are being recognized as a promising green lubricating additive due to their multiple functional groups and unique structure. However, the strong hydrogen bond interactions between CNCs hinder their dispersion in base oils, significantly limiting their application in tribology. In this study, CNCs were modified with stearamide (SA) using 3-(trihydroxysilyl)-1-propanesulfonic acid (SIT) as a bridging agent to minimize the interactions among CNCs and enhance their compatibility with rapeseed oil (RSO) used as a base oil. The as-prepared CNCs/SA composite was systematically characterized by TEM, FTIR spectroscopy, and TG analysis. The results demonstrated that SA molecules were primarily attached CNCs-SIT through hydrogen bonding, and the modified CNCs/SA exhibited significantly improved dispersion stability and compatibility in RSO. This was attributed to the fact that long chains of grafted SA underwent strong interfacial interactions with the lipid molecules of RSO, resulting excellent colloidal dispersion stability and an effective reduction in the system viscosity. Furthermore, the tribological properties of CNCs/SA@RSO were investigated using a ball-on-disc friction tester. The CNCs/SA content of 0.5 wt% led to significant enhancement in the tribological performance, resulting in a 28.6% reduction in friction coefficient and 73% decrease in wear rate. This improvement was primarily attributed to the excellent dispersion stability of CNCs/SA, enabling it to function as a load-bearing and rolling agent at the sliding interface, while also creating a lubricating composite film that repaired surface roughness and micro-wear grooves. This research aims at promoting the use of CNCs as a green lubricating additive for high-value applications.

The primary challenges in bone tissue engineering include the precise replication of the mechanical anisotropy of natural bone and the facilitation of angiogenesis-driven bone regeneration. In this study, a path-programmable coaxial reactive flow strategy based on radial 3D printing was proposed. By using the hydroxyapatite/sodium alginate (HAP/ALG) composite system, during the extrusion process, it crosslinks and solidifies with Ca²⁺ to form fibers with a hollow structure. Thus, a scaffold mimicking the Haversian canal unit is achieved in a single-step forming process. Among these components, HAP, serving as the inorganic phase, furnishes a bone-mimicking mineralization environment and mechanical support. ALG, acting as a macromolecular regulatory component in the biological context, constructs a flexible 3D network via Ca²⁺ ion crosslinking, thereby providing a moist supportive micro-environment for cells. By modulating the HAP/ALG mass ratio and the fiber arrangement path, the mechanical anisotropy of the scaffold was regulated. Systematic verification of the structural characteristics, anisotropic properties, and angiogenesis-promoting effects of the scaffold was conducted using Micro-CT, SEM, and mechanical testing. In addition, in vitro and in vivo experiments based on adipose-derived stem cells (ADSCs) were also conducted. The results indicated that when the HAP/ALG = 2:1, the axial compressive modulus (193.51 ± 6.82 kPa) of the scaffold with a fully longitudinal arrangement (Path II) was approximately 2.23 times that of its radial compressive modulus (86.82 ± 4.47 kPa). This ratio approaches the upper limit of the anisotropy range (1.6-2.3) of natural cortical bone. Hematoxylin and eosin (H&E) staining observations in animal experiments indicated that, compared with the solid fiber scaffolds, the implanted hollow fiber scaffolds exhibited a stronger tendency for the formation of early vascular-like structures. However, the degradation rate of calcium alginate in the body is relatively rapid in the later stage. Further optimization is still required to match the tissue growth rate. In contrast to conventional extrusion-based 3D printing methods that rely on multi-step shaping or material modification, the methodology employed in this research enables the synchronous construction of hollow structures and the modulation of mechanical anisotropy. This simplifies the fabrication process and improves control over the hollow architecture and fiber alignment. This 3D printing strategy offers a novel design concept and a viable pathway for fabricating bone tissue engineering scaffolds that concurrently exhibit mechanical anisotropy and pro-angiogenic capabilities.

Parkinson's disease, a progressive neurodegenerative disorder, is characterized by the accumulation of toxic α-synuclein aggregates. Molecular chaperones, key to homeostasis, offer a promising mechanism for the clearance of misfolded proteins. Here, we investigated a novel therapeutic approach combining the natural compound resveratrol and lithium chloride in an in vitro model of Parkinson's disease using human LUHMES cells challenged with pre-formed α-synuclein fibrils (PFF). The impact of mono- and co-treatment on α-synuclein levels, aggregation, cell viability, metabolic activity, oxidative stress, aggresome formation, and chaperone activation was assessed. FTIR spectroscopy was employed to analyze cellular biochemical profiles. Our findings demonstrate that the co-treatment of resveratrol and lithium chloride elicits a potent combination effect, significantly reducing both unphosphorylated and phosphorylated α-synuclein levels and decreasing the formation of aggresomes. Notably, this combined treatment robustly activated the cellular molecular chaperone system, a key mechanism for protein quality control. Furthermore, the co-therapy protected cellular viability and maintained metabolic activity, without exacerbating oxidative stress. Biochemical profiling using FTIR spectroscopy further supported the beneficial impact of the co-treatment, indicating a trend towards the restoration of normal cellular molecular signatures. These results underscore the unique and promising potential of combining resveratrol and lithium chloride as a supplementary therapeutic strategy for Parkinson's disease, leveraging their enhanced action to enhance the clearance of neurotoxic α-synuclein aggregates.

Nobiletin, a bioactive flavonoid with promising health benefits, faces challenges in its application due to poor water solubility and limited bioavailability. Here, we prepared Pickering high internal phase emulsions (HIPEs) stabilized by soy protein isolate/pectin (SPI/PE) complexes, optimizing SPI/PE concentration and pH to achieve stable emulsions with improved physicochemical properties. The results showed that SPI/PE complexes formed robust, cohesive interfacial layers that markedly enhanced emulsion stability under a wide range of environmental stresses. The encapsulated nobiletin exhibited significantly improved resistance to UV degradation, extended storage stability, and superior thermal stability relative to conventional carriers. In vitro digestion indicated that SPI/PE HIPEs enhanced nobiletin's bioaccessibility. Cellular uptake studies using Caco-2 cells confirmed enhanced absorption of nobiletin, with SPI/PE HIPEs demonstrating higher cellular uptake and greater overall bioavailability. Furthermore, transport studies suggested potential active transport mechanisms for NOB across Caco-2 monolayers, with higher apparent permeability coefficients in the apical-to-basolateral direction. These findings highlight the efficacy of SPI/PE HIPEs in improving nobiletin's stability and bioavailability, offering a promising strategy to enhance the delivery of hydrophobic compounds in functional food and pharmaceutical applications.

Ribonucleotide reductases (RNRs) are the essential enzymes responsible for synthesizing dNTPs, the building blocks of DNA. In bacteria, the entire RNR network is controlled by the master regulator NrdR. As a regulator of an essential pathway with no eukaryotic equivalent, NrdR is a promising antimicrobial target. Recent structural studies have outlined a mechanism of action for NrdR, in which ATP and dATP induce changes in the protein quaternary structure, regulating RNR repression. However, due to a lack of functional studies linking the known structures to their biological roles, the activation mechanism of NrdR is not yet fully understood. Here, we conducted a comprehensive study of NrdR in Escherichia coli and Pseudomonas aeruginosa. We delimited the NrdR regulon, combining transcriptomics and motif-based sequence analysis. We crystallized E. coli NrdR and identified the protein-protein interfaces involved in its oligomerization, including strong interactions between NrdR dimers to form tetramers, and less stable interfaces connecting such tetramers. We examined the variability of the quaternary structures of NrdR depending on the nucleotides bound by SEC-MALS and atomic force microscopy and correlated structure to function using point mutations, EMSAs, and in vitro transcription assays. Overall, our results demonstrate the mechanism used by NrdR to modulate its quaternary structure and activity, deciphering essential interactions between subunits, and paving the way for targeted antimicrobial therapies.

In our previous study, we identified and characterized a rhamnogalacturonan-I (RG-I)-rich polysaccharide (MP-PE-I) derived from Malus prunifolia (MP), which exhibited notable immunomodulatory activity in IL-1β-stimulated intestinal epithelial cells. This study assessed the protective potential of MP-PE-I in a murine model of intestinal inflammation induced by dextran sulfate sodium (DSS). MP-PE-I was administered orally for three consecutive weeks, during which it was well tolerated and markedly alleviated colitis-related clinical symptoms and pathological features, including colon shortening and splenomegaly. MP-PE-I treatment effectively modulated the DSS-triggered dysregulation of inflammatory cytokines and chemokines, while restoring gene expression related to tight and adherens junctions. Histological evaluation confirmed that MP-PE-I mitigated DSS-induced structural damage in colonic tissue, including preservation of mucin-producing goblet cells. These protective effects were associated with alterations in MAPK- and NF-κB-related signaling pathways. Furthermore, MP-PE-I treatment significantly restored the DSS-induced reduction in short-chain fatty acid levels, accompanied by overall improvements in the gut microenvironment. Collectively, these findings demonstrate the anti-colitic potential of MP-derived RG-I-rich polysaccharides and support their further development as functional agents for intestinal health maintenance.