International Journal of Biological Macromolecules最新文献

Polygonatum cyrtonema Hua has been attracting attention of Asian countries as a traditional herbal medicine. Unveiling the spatial distribution accumulation of key metabolites is of great worth for investigating its nutritional and medicinal values. However, their spatial distribution information during different growth period (four-year-old) in rhizome has not been extensively explored, due to the lack of efficient analytical techniques. In this study, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is employed to visualize the spatial distribution of metabolites in different growth period rhizome sample (Y1, Y2, Y3, Y4). From the mass spectrum imaging, the flavonoids (chalcone, Artemetin, Peganetin, Kaempferol and Icariin) and carbohydrates (Cellobiose, 1-Kestose, Sucrose acetate isobutyrate, D-Galactose, α, β-Trehalose, Raffinose, β-Cyclodextrin were distributed evenly throughout the entire rhizome. Additionally, several flavonoids were down regulated with (27.03 %) in Y2 sample, which indicated that they apparently played protective roles in growth development in response to abiotic and biotic stress. From the collected molecular imaging data, flavonoids were observed toward the edges of rhizome and up-regulated in response to high UV radiation, indicating ability of protection against oxidative stress. Contrarily, polysaccharides dispersed increasing visualization per growth period. Comparative analysis indicated metabolites abundance thoroughly in Y4 sample, due to adopting defense against environmental stress. This study reveals an overview of the spatial distribution and accumulation of key metabolites in four-year-old P. cyrtonema rhizome, that highlight their significant roles in physiological processes as well as their potential medicinal value. Using MALDI-MSI, we characterize differential expression of flavonoids and carbohydrates. The results shows adaptive responses to environmental stress, that revealing new aspects to the nutritional and therapeutic properties.

Dopamine has proven effective in treating conditions such as depression and myocardial infarction. The marine Meyerozyma guilliermondii GXDK6 and Bacillus aryabhattai NM1-A2, both known for their robust nitrogen conversion capabilities, were selected for co-fermentation to synthesize dopamine. The metabolic co-regulation mechanism was further elucidated, demonstrating that the synergistic interaction between GXDK6 and NM1-A2 significantly enhanced dopamine synthesis. Under optimized conditions, dopamine production reached 2019.22 mg/L in a bioreactor. Genome-wide analysis revealed that co-fermentation enriched proteins involved in the conversion of tyrosine to dopamine, including polyphenol oxidase (encoded by gene PPO) and tyrosine decarboxylase (encoded by gene BamfnA) from NM1-A2, as well as cytochrome P450 76AD1 (encoded by gene CYP76AD1) and tyrosine decarboxylase (encoded by gene MgmfnA) from GXDK6. These proteins strengthen the dopamine metabolic pathway, facilitating efficient dopamine expression. Heterologous expression of biosynthetic enzymes indicated that dual-gene expression was more effective in dopamine biosynthesis than individual gene expression, for which the synthesized L-dopa was used to catalyze the synthesis of dopamine. In vitro catalysis with purified PPO showed that 5 mM of tyrosine could be converted to 0.21 mM of L-dopa. This co-fermentation strategy provides a novel theoretical framework for the de novo microbial synthesis of dopamine.

Colorectal cancer is the second leading cause of cancer-related deaths following lung cancer in recent years. Therefore, lung or colorectal cancer therapy is very important for reducing mortality. In this study, we developed and characterized CD47-specific antibody-drug conjugates, namely 7DC-DM1 ADCs, to evaluate their therapeutic effects on lung and colorectal cancer. Both 7DC2-DM1 and 7DC4-DM1 demonstrated good binding affinities of 0.56 nM and 0.49 nM, respectively, and exhibited significant cytotoxicity, though they displayed different penetration effects. These findings suggest that the binding complexes of 7DC2-DM1 and 7DC4-DM1 with CD47 receptors adopt different conformations, leading to variations in their cellular internalized efficiencies. Molecular docking simulations revealed that 7DC2 and 7DC4 bind to CD47 molecules in distinct orientations and epitopes, differing between conserved and non-conserved regions. Furthermore, treatments with 7DC2-DM1 and 7DC4-DM1 displayed notable differences in antitumor effects in murine syngeneic tumor models derived from the MC38 cell line in C57BL/6 mice. In the tumor model treated with 7DC4-DM1, immunofluorescence staining analysis revealed a large area of necrosis in the tumor stroma, accompanied by a significant infiltration of CD11b-expressing immune cells. In summary, these results indicate that 7DC4-DM1 holds promise as a therapeutic agent for colorectal cancer treatment.

Chitosan, derived from the deacetylation of chitin, is the second most widely used natural polymer, valued for its nontoxic, biocompatible, and biodegradable properties. These attributes have driven extensive research into diverse applications of chitosan and various derivatives. The key characteristics of chitosan muco-adhesion, permeability enhancement, drug release modulation, and antimicrobial activity are primarily due to its amino and hydroxyl groups. However, the limited solubility of raw chitosan in water and most organic solvents has posed challenges for broader application. Numerous chemically modified derivatives have been developed to address these inadequacies with improved physical and chemical properties. Among these derivatives, chitosan nanoparticles have emerged as versatile drug carriers with precise release kinetics and the capacity for targeted delivery, greatly enhancing drug efficacy and safety profiles for therapeutic applications. Due to these unique physicochemical properties, chitosan and chitosan nanoparticles are promising for improved drug delivery, vaccine administration, transplantation, gene therapy, and diagnostics. This review examines the physicochemical properties and bioactivities of chitosan and chitosan nanoparticles, emphasizing their broad-ranging biomedical applications.