Artificial Cells, Nanomedicine, and Biotechnology最新文献

This study investigated whether Salvia Miltiorrhiza Injection (SMI) could mitigate acute myocardial injury following resuscitation from severe haemorrhagic shock with the hemoglobin-based oxygen carrier HBOC-CHP01. Network pharmacology was first used to predict SMI's potential mechanisms. In vivo, a 50% severe haemorrhagic shock model was induced in rats, which were then resuscitated with either HBOC-CHP01 alone (n=12) or HBOC-CHP01 plus SMI (8.0 ml/kg, n=12). Subgroups were assessed for 72-hour survival, blood parameters, and myocardial tissue injury at 24 hours post-resuscitation. Network pharmacology identified 189 potential targets, with AKT1, CASP3, and HIF-1α among the core candidates. In vivo, while 72-hour survival was unchanged, SMI significantly reduced plasma cardiac injury markers (AST, LDH, CK, cTnI) at 24 hours post-resuscitation compared to HBOC-CHP01 alone. Histological analysis revealed markedly reduced myocardial inflammation and apoptosis in the SMI-treated group. This cardioprotection was associated with significant upregulation of myocardial Nrf2 and HO-1, alongside reduced reactive oxygen species and myeloperoxidase levels. In conclusion, SMI reduces myocardial injury after HBOC-CHP01 resuscitation in haemorrhagic shock rats, primarily by activating the Nrf2/HO-1 antioxidant pathway, suggesting its potential as an adjunctive therapy to improve the safety of hemoglobin-based oxygen carriers.

Pathogenic variants in the KIDINS220 gene can cause SINO syndrome (OMIM #617296), VENARG syndrome (OMIM #619501), or other neurological and metabolic disorders such as obesity and nystagmus. We identified two novel intronic variants in intron 29 of KIDINS220 gene (NM_020738.4), c.4054-2A > G and c.4054-7T > C, in a female patient presenting with motor dysfunction and developmental delay. Brain MRI revealed delayed myelination. To investigate whether these intronic variants cause aberrant splicing and affect protein expression, we sequenced KIDINS220 cDNA from peripheral blood and concurrently performed a minigene splicing assay. The results indicated that KIDINS220 was not expressed in PBMCs. However, the minigene assay demonstrated that the c.4054-2A > G variant causes an in-frame 336-bp deletion in exon 30, resulting in a 112-amino acid deletion in the C-terminal region of KIDINS220 (p.(Ser1352_Ser1463del)). In contrast, the c.4054-7T > C variant did not disrupt normal splicing. Based on the patient's clinical features and functional validation of the genetic variants, our paediatricians established a diagnosis of mild motor dysfunction and developmental delay. Our findings broaden the spectrum of pathogenic variants underlying KIDINS220-related disorders and provide essential information for genetic counselling.

Alzheimer's disease (AD) remains a major global health challenge, with current therapies offering only symptomatic relief. A significant constraint in the development of effective treatments is the blood-brain barrier (BBB), as it greatly limits the access of therapeutic drugs targeting amyloid-β (Aβ) aggregation, tau hyperphosphorylation and neuroinflammation. Nanobodies, single-domain antibody fragments derived from camelids, have emerged as versatile tools with unique properties such as small size, high stability and the ability to penetrate the BBB. Engineered formats allow for specific targeting of Aβ and tau, receptor-mediated transcytosis, and conjugation with therapeutic or diagnostic substances. Preclinical studies show that nanobody-based strategies can reduce pathological burden, attenuate neuroinflammation and improve cognitive outcomes in AD models. Manufacturing scale-up, long-term safety and regulatory validation are among the remaining challenges, yet nanobody engineering represents a viable path to disease-modifying medicines. Innovative approaches, including artificial intelligence-driven design, i.e. 4-1BB agonist nanobodies, and clustered regularly interspaced short palindromic repeat-facilitated diversification of nanobody libraries - such as targeted complementarity-determining region 3 mutagenesis followed by functional screening against disease-relevant tau or Aβ conformers - alongside half-life extension strategies, are commencing to surmount these obstacles and enhance the potential of nanobody platforms to develop into clinically viable disease-modifying therapies.

The study aimed to optimize and develop novel PEGylated co-loaded nanoliposome entrapped with paclitaxel (PTX) and 6-gingerol (Gn) (PEG-Lipo-PTX-Gn) by response surface methodology (RSM) approach to prevent the diffusion and resistant-related issues of PTX in oncotherapy. Physiochemical characterization studies results revealed that the prepared PEG-Lipo-PTX-Gn attained optimum particle size, shape, charge, polydispersity index (PDI) as well as showed synergistic entrapment of PTX and Gn, sustained drug release, better colloidal stability and structural integrity. PEG-Lipo-PTX-Gn exhibited a noteworthy antiproliferative effect, apoptotic percentage and a higher proportion of G2/M cell cycle arrest in MDA-MB-231 and A549 cell lines. Meanwhile, no significant toxicity was observed in normal cell lines (HEK 293 kidney embryonic cells and L929 fibroblast cells). Another testament to its efficacy is the dramatic decline in Bcl-2 levels in the PEG-Lipo-PTX-Gn-treated group. Hence, optimized PEG-Lipo-PTX-Gn could be a promising novel approach in cancer treatment regimens.

Purinergic signalling pathways play a vital role in the biological functions of the aortic valve (AV) through nucleotide and adenosine-dependent receptor effects. This study focused on characterizing a side-specific purinergic cascade in human non-stenotic and stenotic AVs, ovine native AVs and a novel bacterial nanocellulose (BNC) bio-prosthesis in an ovine model. Human stenotic AVs were collected during replacement surgeries, while non-stenotic AVs came from heart transplant patients. Ovine native AVs were sourced from domestic sheep, and the BNC prosthesis was implanted in the ovine aorta for six months, with hemodynamic monitoring throughout. Biochemical assessments revealed a beneficial ecto-enzyme pattern in non-stenotic and native AVs, contrasting with a detrimental pattern in stenotic valves. The BNC prosthesis demonstrated significantly lower nucleotide conversion activities than native valves and displayed increased peripheral blood mononuclear cell adhesion on its aortic surface. These findings suggest that nucleotide-converting ecto-enzymes could serve as markers for the biological activity of AV prostheses, highlighting the need for further studies to enhance the cellularization of BNC prostheses, potentially through adenosine-releasing scaffold modifications.

Ageing is increasingly recognized as a significant risk factor for RA, yet the molecular mechanisms linking the two remain poorly understood. This study aimed to explore the association between ageing and RA and to identify potential therapeutic targets using multi-omics approaches. By analysing the GBD database, we observed a notable increase in RA incidence and prevalence among individuals aged 55 and older from 1990 to 2021. Through integrative analysis of transcriptomic data and ageing-related gene sets, we identified 145 shared genes between ageing and RA. Machine learning algorithms further refined these to five hub genes, among which STAT1, MCL1, and BCL6 were validated via single-cell RNA sequencing as key players in RA pathogenesis. Immune infiltration analysis revealed distinct immune cell profiles in RA patients compared to controls. These findings underscore the strong molecular link between ageing and RA and highlight STAT1, MCL1, and BCL6 as promising therapeutic targets. This study provides a foundation for developing targeted interventions for RA in the context of ageing.

Cartilage injuries caused by trauma or degenerative conditions such as osteoarthritis have limited intrinsic healing capacity and often require invasive interventions. This study proposes a minimally invasive therapeutic strategy using spheroids of human amniotic fluid-derived mesenchymal stromal cells (AF-MSCs) embedded in a thermosensitive hydrogel composed of 10% (w/v) methylcellulose and 1% (w/v) carboxymethyl chitosan (M10C1). AF-MSCs spheroids, generated in 3D culture under TGF-β3 stimulation, exhibited high viability and robust extracellular matrix production, including type II collagen and aggrecan. Rheological characterisation confirmed that M10C1 displays shear-thinning behaviour and gelation near physiological temperatures (∼30 °C), making it suitable for injection and 3D bioprinting. Importantly, confocal microscopy and fusion assays demonstrated that the hydrogel preserved spheroid bioassembly and viability. Co-culture with human cartilage explants further showed that M10C1 promoted spheroid adhesion without hindering integration into native tissue. These findings highlight the potential of this AF-MSCs spheroid-hydrogel system as an injectable, biocompatible platform for cartilage repair, with promising applications in regenerative medicine and bioengineered tissue therapies.