International Journal of Biological Macromolecules最新文献

Scrophularia ningpoensis Hemsl. is a traditional Chinese medicine used to regulate blood sugar levels, immunity, etc. We previously isolated polysaccharides from S. ningpoensis Hemsl. (SNPS) and innovatively observed that SNPS exhibit antidepressant properties; however, the underlying mechanism is still unclear. Here, we employed network pharmacology to predict the potential targets and antidepressant mechanism of SNPS. Accordingly, we detected the effects of SNPS on monoamine neurotransmitter synthesis, metabolism, receptor expression and signal transduction in reserpine (RES)-treated mice using ELISA, HPLC-electrochemistry, metabonomics, Golgi-Cox staining and Western blotting. Finally, the mechanism of SNPS on key targets (HTR2A and HTR2C) was verified in vivo and in vitro. Results showed that SNPS ameliorated depression by restoring monoamine neurotransmitter homeostasis and hippocampal neurogenesis. SNPS reversed the depletion of 5-HT, NE and DA by activating the tryptophan (Trp)/5-HT and tyrosine (Tyr)/DA/NE metabolic pathways. SNPS decreased HTR2A and HTR2C contents, leading to the phosphorylation of AKT and GSK3β, followed by increases in β-catenin, CBP and BDNF levels. Mechanistically, SNPS reduced the levels of HTR2A and HTR2C proteins by inhibiting their mRNA transcription, rather than inducing protein degradation. In conclusion, by inhibiting the transcription of HTR2A and HTR2C, SNPS activated the AKT/GSK3β/β-catenin/CBP/BDNF pathway, thereby exerting dose-dependent antidepressant effects.

Hydrogel microneedles (MNs) gained more attentions for diabetes treatments owing to their biocompatibility and versatility. However, the inherent fragility and instability of hydrogels pose limitations on their efficacy in biomedical applications. To overcome this limitation, we developed interpenetrating network hydrogels (IPNs) by incorporating silk fibroin (SF) and methacrylated hyaluronic acid (HAMA). These hydrogels exhibit rapid formation, structural stability, mechanical robustness, and sustainability through photo-crosslinking without the need for crosslinking agents. The hydrogels demonstrated an average formation time of 86 ± 8 s and exhibited favorable elasticity, along with a high compressive stress at break of 70.9 ± 8.2 kPa. Additionally, the extensive proliferation and well-distributed network of human umbilical vein endothelial cells (hUVECs) on the microneedles' (MNs) surface underscored the high cytocompatibility and cell viability of the MNs. In a diabetic mouse model, the MNs were able to maintain normal blood glucose levels for approximately 6 h. The administration of insulin-loaded microneedles to diabetic mice resulted in glucose tolerance levels comparable to those of non-diabetic mice, indicating the efficacy of microneedle therapy in improving the glycemic condition of diabetic subjects. These hydrogel MNs possess a stable structure, can be rapidly fabricated, are sustainable, and hold significant potential for the clinical management of patients with diabetes mellitus.

Despite zinc-based electrochemical energy storage being considered a safe and efficient energy storage system, problems such as uncontrolled dendrite growth, hydrogen precipitation reactions, and corrosion have seriously hindered its commercialization. Mitigating dendrite growth and other associated issues is crucial for the successful commercialization of these systems. Sodium lignosulfonate is an excellent dopant for conductive polymers, which can endow conductive polymers with abundant functional groups. Herein, we propose a sodium lignosulfonate-doped polypyrrole protective layer for zinc anodes with good hydrophilicity, electrical conductivity, and a porous structure, which can effectively inhibit the growth of zinc dendrites and side reactions. The doping of sodium lignosulfonate introduces numerous zincophilic groups. The sulfonate groups enhance zinc ion interaction and regulate flux, while phenolic hydroxyl groups increase zincophilic sites, aiding in the uniform deposition of zinc.

Endometrial fibrosis in sheep reduces reproductive performance with elusive therapeutic targets. The fibrotic endometrium is a complex ecosystem with heterogeneous cells and their interactions. The molecular characterization of key cells and the mechanisms of these interactions are unclear. To uncover the key molecular features of sheep endometrial fibrosis tissue, we used single-nucleus RNA sequencing to profile the transcriptional characterization of sheep endometrial cells from both normal and fibrotic tissues, aiming to clarify the mechanisms of fibrosis development. Histomorphological analysis revealed significant collagen deposition in fibrotic endometrial tissue. The transcription atlas of sheep endometrial cells was created, identifying eight main endometrial cell types. Key findings include the abnormal expression of collagen-related genes in fibrotic cells and the identification of endothelial cells and fibroblasts as major contributors to fibrogenesis with aberrant receptor-ligand interactions involving collagen-related genes. Fibroblasts had a tendency to differentiate into myofibroblasts in fibroblast-mediated fibrosis progression. In vitro experiments demonstrated the role of fibroblasts in fibroblast activation through the PERK/eIF2α/CHOP stress pathway. Additionally, fibrosis disturbs the immune microenvironment. This study highlights that high collagen gene expression in injured endometrial cells leads to abnormal tissue repair and fibrosis, offering valuable insights for understanding endometrial fibrosis at the single-cell level.

The increasing environmental concerns and health risks associated with synthetic chemicals have driven the demand for sustainable and eco-friendly solutions. Biocatalysis, employing enzymes or whole cells as biocatalysts, has emerged as a powerful alternative. This review provides a comprehensive analysis of the applications of biocatalytic enzymes in food packaging, biomedical sciences, and biotechnology. We highlight the potential of enzymes like laccase, glucose oxidase, lysozyme, protease, lipase, cellulase, and asparaginase to replace traditional chemical methods, driving innovation and sustainability. The global enzyme market is also analyzed, including current trends, emerging demands, and the impact of the COVID-19 pandemic. This review aims to bridge knowledge gaps, emphasize recent technological breakthroughs, and showcase the potential of biocatalytic enzymes to address critical industrial challenges while supporting environmental sustainability and economic growth.

Enzymatic hydrolysis approach is commonly employed for preparation of active peptides, while the limited purity and yield of produced peptides hinder further development of action mechanisms. This study presents the biotechnological approach for the efficient production of recombinant angiotensin converting enzyme (ACE) inhibitory peptide LYPVK and investigates its potential antihypertensive action mechanism. DNA encoding sequence of recombinant peptide was designed to form in tandem, which was expressed in Escherichia coli BL21 (DE3). The expressed tandem repeat protein with molecular weight of 13.4 kDa was verified by high performance liquid chromatography (HPLC) and amino acid composition. Subsequently, LYPVK was generated following His-tag removal and trypsin-mediated cleavage of the purified protein, which was performed HPLC and liquid chromatography-mass spectrometry (LC-MS) analysis. LYPVK exhibited an IC₅₀ value of 10.6 ± 0.86 μg/mL, demonstrating a non-competitive mode of action and resistance to gastrointestinal enzyme hydrolysis and heat conditions. Molecular docking results showed that LYPVK interacted with ACE through conventional hydrogen bonds and hydrophobic interactions. Except for ACE, ALB, SRC, PPARG, and MMP9 are identified as potential key targets for its antihypertensive activity by network pharmacological analysis. This study provides a promising biotechnological approach for the preparation of active peptides with high purity and yield.

The HIV/AIDS epidemic poses a severe global health challenge. While antiretroviral therapy is crucial, it has limitations, including high costs and resistance, and requires long-term use. Consequently, novel antiviral agents with unique structures and innovative mechanisms are needed for better management of HIV/AIDS. We previously discovered that Siglec-14 inhibits HIV-1 replication. In this study, we employed homology modeling and AlphaFold 2 to predict the structure of Siglec-14, followed by molecular dynamics simulations to explore its conformational landscape. The MM/GBSA method was used to calculate the binding free energy of selected small molecules. Among them, Forsythoside B (FTS·B) exhibited the highest binding free energy and enhanced Siglec-14's conformational stability. SPR analysis further confirmed a strong binding affinity between FTS·B and Siglec-14. In vitro experiments demonstrated that FTS·B upregulates Siglec-14 expression and suppresses HIV-1 replication in macrophages. Mechanistically, FTS·B suppresses pro-inflammatory cytokines, increases the expression of interferon-stimulated genes and chemokines, and activates the JAK1/STAT1 pathway in Siglec-14 knockdown macrophages. Our results confirm that FTS·B, as an agonist of Siglec-14, effectively inhibits HIV-1 replication by upregulating Siglec-14 expression and modulating the JAK1/STAT1 signaling pathway, highlighting the potential clinical application value of FTS·B in HIV treatment.

Biorefining sugarcane molasses to produce polyhydroxyalkanoates (PHAs) is an anticipated paradigm for replacing petroleum-based plastics. Nevertheless, there exists a deficiency in excellent chassis and genome resolution for the synthesis of poly(3-hydroxybutyrate) (PHB), which is a typical representative of PHAs. In this study, successive enrichment domestication was employed to screen PHB producers. The isolated species was defined as Paracoccus sp. P2 through taxonomic analysis. Then, a variety of nutrient substrates and physicochemical parameters were tailored to enhance the fermentation capacity. The maximum production of bio-polyester was 4.4 g·L^-1, corresponding to a yield of 0.37 g-PHB·g^-1-glucose. The concentration of PHB produced from 30 g·L^-1 sugarcane molasses was 3.9 g·L^-1, indicating a comparable fermentation performance. Furthermore, three-step condensation of acetyl-CoA and de novo synthesis of fatty acids were identified as the primary PHB accumulation pathways. The fermentation performance and genome investigation were compared with Paracoccus genus. The effective production of Paracoccus sp. P2 might be attributed to its efficient substrate conversion capacity and abundant PHB metabolic network. This study broadened the germplasm resources available for the bioconversion of sugarcane molasses, providing theoretical references for the valorization of high-concentration waste carbon sources.

Osteoarthritis (OA) presents a significant challenge in clinical settings due to the limited self-renewal capability of cartilage tissue. To address this, engineered biomaterials employing biomimetic strategies have been developed to modulate and enhance cell-microenvironment interactions, facilitating cartilage regeneration. Nonetheless, excessive mechanical stress on joint structures can induce inflammatory responses, thereby impeding the process of cartilage repair. In this study, we focus on the OA microenvironment, characterized by the overexpression of matrix metalloproteinases (MMPs), and the mechanical stimuli due to joint movement. We engineered a dual-responsive injectable hydrogel: a blend of MMP-responsive, thermo-sensitive GelMA and mechanically robust, reverse thermo-sensitive F127DA. This hydrogel was designed to deliver TGF-β and KGN in a controlled manner via simple temperature modulation. The hydrophilic properties of GelMA and the hydrophobic nature of F127DA allow for efficient intra-articular delivery of diverse drug types, optimizing their therapeutic effects. Photocrosslinking the hydrogel in situ effectively seals cartilage defects and prevents further degradation. The overexpressed MMP in the OA environment triggers the release of TGF-β, recruiting bone marrow-derived stem cells (BMSCs), while mechanical pressure from joint movements releases KGN, promoting chondrogenic differentiation and mitigating inflammation. In summary, our injectable hydrogel, responsive to both the OA microenvironment and mechanical stress, shows promise in enhancing cartilage regeneration in OA. This approach holds significant potential for advancing the field of OA cartilage tissue engineering.

Neuroinflammation can lead to various neurodegenerative disorders, resulting in irreversible neurological dysfunction. Astragalus membranaceus Bunge polysaccharides (APS) present great potential in alleviating neuroinflammation; however, the specific mechanism underlying its neuroprotective effect remains unclear, leading to uncertain prospects for pharmaceutical applications. This study aims to elucidate the mechanism underlying APS-mediated inhibition of neuroinflammation in mice induced by lipopolysaccharide (LPS) through regulation of metabolic function, intestinal flora composition, and cell signaling transduction. Results indicated that APS pretreatment effectively mitigated LPS-induced brain damage. Metabolomics analysis revealed that APS pretreatment also regulated the metabolic disturbances induced by LPS through targeting five specific metabolic pathways. This regulation was supported by notable alterations in nine metabolite markers. Furthermore, APS pretreatment significantly modulated the abundance of four taxa of gut microbes (i.e., Romboutsia, Rikenella, Dubosiella, Odoribacter) closely associated with regulations in eleven metabolic and signaling pathways. Additionally, transcriptome analysis and Western blotting unveiled that APS pretreatment exerted a neuroprotective effect by modulating the MAPK/NF-κB signaling pathway. Our findings provide insights into the potential mechanisms underlying the neuroprotective effects of APS while establishing a solid foundation for future utilization of APS.