Artificial Cells, Nanomedicine, and Biotechnology最新文献

Spaceflight-related bone loss represents a critical health concern for astronauts undertaking prolonged space missions. This study investigated the mechanistic role of macrophage-derived exosomes in microgravity-induced bone loss using a simulated microgravity model. Phenotypic analysis of macrophages demonstrated that simulated microgravity promoted polarization towards the M2 phenotype and markedly suppressed the secretion of most pro-inflammatory cytokines. Exosomes were isolated and purified from macrophages cultured under normal gravity (1 g) and simulated microgravity (μg) conditions via ultracentrifugation. In vitro experiments revealed that exosomes from the μg group significantly inhibited the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, without affecting cell migration. Subsequent in vivo studies involving tail-vein injection of exosomes into mice demonstrated a significant reduction in bone mass and impaired new bone formation in the μg group, exhibiting a distinct osteoporotic phenotype. Collectively, this study provides evidence at both cellular and animal levels that macrophage-derived exosomes play a role in microgravity-induced bone loss by inhibiting the proliferation and osteogenic differentiation of BMSCs and osteoblasts in a simulated microgravity environment. These findings offer a potential strategy for targeting the immune-bone metabolism axis to prevent spaceflight-associated osteoporosis.

Triple-negative breast cancer (TNBC) is a significant global health issue, with high mortality rates. The chemotherapeutic drugs currently used for TNBC have significant side effects, impacting both normal and cancer cells. In this study, we investigated a potential use of fruit peel extract of Psidium guajava (PGP) encapsulated with chitosan nanoparticles (CSNPs) to combat TNBC. The synthesized PGP-CSNPs were characterized using UV-vis spectroscopy, Fourier transform infra-red (FTIR) spectroscopy, TEM and GC-MS. The maximum loading capacity and encapsulation efficacy of PGP-CSNPs were found to be 72.5 ± 0.49% and 92.9 ± 0.10%, respectively. Furthermore, in vitro cytotoxicity was assessed, and the IC₅₀ value for PGP-CSNPs was 50.13 µg/mL. It was observed that PGP-CSNPs could induce apoptosis in MDA-MB-231 cells in dose-dependent manner. Furthermore, molecular docking was performed for bioactive compounds retrieved from PGP-CSNPs against human tumour suppressor proteins Bcl2, and results showed that the PGP-CSNPs had lower binding energy than cisplatin. This suggests that, the synthesized PGP-CSNPs have the potential to serve as a therapeutic agent for tackling TNBC. However, to validate its efficacy in human therapy, furthermore pre-clinical and clinical procedures should be examined, as this is an ongoing and significant step towards developing an effective and safe anticancer drug.

Cartilage repair remains challenging due to limited self-healing, poor biocompatibility, and insufficient mechanical properties of current materials. To overcome these issues, we developed a multifunctional composite hydrogel by integrating gelatine methacrylate (GelMA) with magnesium-doped bioactive glass (Mg-BG) and icariin (ICA). SEM analysis revealed that pure GelMA exhibited a highly porous yet loosely organized structure, whereas the addition of Mg-BG and ICA produced a denser, more interconnected porous network that enhances cell adhesion and nutrient diffusion. In vitro, the ICA/Mg-BG/GelMA hydrogel achieved a swelling ratio up to 430% and maintained cell viability above 80% over 5 days. Moreover, qRT-PCR and immunohistochemical analyses demonstrated that the composite hydrogel upregulated chondrogenic markers (SOX9, ACAN, and COL2A1) compared with GelMA alone. Specifically, it downregulates M1 pro-inflammatory markers (CCR7, iNOS, CD86) and upregulates M2 anti-inflammatory markers (ARG1, CD163, CD206), thereby creating a regenerative microenvironment. These results indicate that the synergistic combination of GelMA, Mg-BG, and ICA not only improves the scaffold's mechanical support but also enhances its biological functionality, offering a promising strategy for cartilage repair. Future studies will focus on in vivo validation to further assess its clinical potential.

Rheumatoid arthritis (RA) is a systemic immune-mediated disease characterized by synovitis and joint cartilage destruction. Although many studies have shown that mitophagy is crucial in the development of bone metabolism disorders, its exact function in rheumatoid arthritis (RA) is still not well understood. This study analysed the GSE77298 dataset from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) between rheumatoid arthritis (RA) patients and healthy controls. Mitophagy-related genes (MRGs) were extracted from the literature and screened using bioinformatics techniques, resulting in differentially expressed MRGs (DE-MRGs). The diagnostic value of these genes was assessed using receiver operating characteristic (ROC) curves, and an ANN model was constructed. In the GSE77298 dataset, 267 differentially expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) identified 2191 key module genes, leading to 63 DE-MRGs. Two MRGs, TMEM45A and ZBTB25, were identified as hub genes with areas under the curve (AUC) of 0.991 and 0.911, respectively. The nomogram model demonstrated high diagnostic value. Mitophagy plays a critical role in the progression of rheumatoid arthritis (RA). Identifying two genes associated with mitophagy may aid in the early diagnosis, mechanistic understanding, and treatment of RA.

A total of 208 metabolites and 223 targets were initially extracted from the gutMGene v1.0 database. In addition, 1,630 and 1,321 targets were identified using the Similarity Ensemble Approach and Swiss Target Prediction databases, respectively, resulting in 921 overlapping targets. By integrating data from gutMGenev1.0, 13 core targets were finally identified. A microbiota-metabolite-target-signal pathway-disease network was constructed using Cytoscape 3.9.1, revealing 15 metabolites associated with the IL-17, TLR, and PI3K-Akt signalling pathways. Among these, five metabolites exhibited favourable drug similarity and acceptable toxicological profiles. Molecular docking confirmed the stable binding of two key metabolites-succinate and phenylacetylglutamine-to their respective targets. The results showed that succinate and phenylacetylglutamine demonstrated strong binding affinities to IL-1β and GSK3B, both involved in the IL-17, TLR, and PI3K-Akt signalling pathways. IL-17 and TLR4, as important pro-inflammatory cytokines, are closely associated with the development of depression, while the PI3K/AKT signalling pathway plays a key role in its pathogenesis. The present study reveals the potential mechanisms by which gut microbiota influence MDD and provides a scientific basis and a comprehensive research framework for future investigations.

Membrane composition is a critical factor for electroporation. Although existing research focuses on pore formation driven by local phospholipid headgroup clusters, the large-scale membrane dynamics post-pore formation remain underexplored. In this study, coarse-grained (CG) molecular dynamics (MD) simulations were employed to investigate the effects of phospholipid headgroups (PC, PE and PS), tail characteristics (DLPC, DPPC, POPC and DOPC) and cholesterol (CHOL) content (0 mol%-50 mol%) on membrane electroporation. The results demonstrate that membrane structural parameters, such as area per lipid, hydrophobic layer thickness and interfacial water penetration depth, significantly influence the electroporation threshold electric field and transmembrane substance flux. Phospholipid headgroups can modulate the area per lipid and hydrophobic layer thickness through their size, hydrogen bonding and charge. Regarding phospholipid tails, increasing their length and unsaturation strengthens the hydrophobic layer, and thereby inhibits electroporation. The incorporation of CHOL into the membrane leads to tighter lipid packing, increased layer thickness and restricted water penetration, all of which elevate the threshold electric field. After electroporation, CHOL reduces transmembrane flux by enhancing line tension, although this inhibitory effect is limited at higher concentrations. The simulation results align well with existing experimental data, suggesting our approach can guide protocol design and highlight membrane composition's critical role in electroporation efficiency.