Artificial Cells, Nanomedicine, and Biotechnology最新文献

Cell membrane-derived vesicles play essential roles in intercellular communication, material transport, and waste disposal. Despite their biomedical and industrial potential, isolating extracellular vesicles from natural sources remains technically challenging, limiting purification efficiency and scalability. This study introduces cell membrane extrusion as an alternative approach to optimize the production of cell membrane-derived vesicles (CSMs), from eukaryotic and prokaryotic cells. CSMs, generated from HeLa and SH-SY5Y cells exhibited a distinctive cup-shaped morphology and sizes of 151.36 ± 72.36 nm, and 416.86 ± 108.49 nm at 20 °C by DLS respectively, showing remarkable thermal stability at 4-70 °C range. Furthermore, loaded vesicles interacted with mammalian cells and achieved successful cargo internalization. CSMs were also produced from E. coli membranes, forming unilamellar vesicles of approximately 100 nm, as observed by Cryo-TEM. These vesicles displayed an inverse correlation between vesicle size and thermal stability and efficient cargo incorporation detected in 85% ± 3% of CSMs. However, under tested conditions, no interaction with prokaryotic cells occurred, and consequently, no delivery of the loaded molecule was observed. Overall, thesefindings highlight the potential of generating cell membrane-derived nanovesicles through extrusion, offering a promising strategy to mimic extracellular vesicles for innovative biomedical and industrial applications, including targeted drug delivery system.

An open-level, single-arm, phase-4 clinical trial was carried out to assess the safety and potential benefits of micronized coated ferric pyrophosphate (MEFP) in patients with iron deficiency anaemia (IDA). For 12 weeks, 60 patients between the ages of 18 and 60 with moderate IDA were randomly received MEFP by PO daily. The efficacy endpoints as haemoglobin levels, mean corpuscular haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), packed cell volume (PCV), red blood cell count (RBC), serum ferritin and transferrin saturation (%) were measured. Adverse event reports and physical examinations were performed as a measure of safety assessment. The results revealed that haemoglobin, MCV, MCHC, serum ferritin, transferrin saturation (%), PCV and RBC increased significantly from baseline. Fewer occurrences were observed in a few patients, and their adverse events were minimal. There was no adverse effect on liver or renal functions. Few minor improvements were noticed at the completion of the study. In conclusion, MEFP appears to be effective in IDA and well tolerated, with a favourable safety profile. MEFP is an effective, safe therapeutic alternative in IDA subjects for increasing haemoglobin concentration and iron stores along with improvement of symptoms related to anaemia.

Coriandrum sativum L. (coriander) is a medicinal herb with diverse pharmacological properties, but its molecular mechanism in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to systematically investigate the underlying mechanisms of coriander in ccRCC by multi-omics analysis. Active compounds were screened using Traditional Chinese Medicine Systems Pharmacology (TCMSP) and predicted targets identified via SwissTargetPrediction (STP) and Similarity ensemble approach (SEA). Transcriptomic data from GSE53757 were analysed with WGCNA and intersected with coriander targets. Key genes were selected using LASSO, SVM, and random forest models. NEK6 was further analysed for clinical relevance, methylation, immune association, single-cell expression, molecular docking and molecular dynamics simulation. Fourteen coriander compounds were identified, yielding 22 potential ccRCC-related targets. NEK6 and PYGL were consistently selected by all machine learning algorithms. NEK6 was overexpressed in ccRCC and associated with better prognosis, promoter hypomethylation, and lower mutation rates. NEK6 expression correlated with immune infiltration, particularly macrophages, and was enriched in tumour and myeloid cells at the single-cell level. Molecular docking and molecular dynamics simulation revealed strong and stable binding of luteolin, quercetin, and chryseriol to NEK6. NEK6 may function as a prognostic and immune-regulatory biomarker in ccRCC. Coriander flavonoids could target NEK6 to modulate the immune microenvironment, providing new insight into plant-based therapeutic strategies for ccRCC.

This study investigates the anisotropic properties of three different poly(lactic-co-glycolic acid) (PLGA)-based materials: PLGA with nano-calcium sulphate (nCS), PLGA with fucoidan (fu) and PLGA with both nCS and fu. Using finite element analysis (FEA), the study explores their potential applications in bone tissue engineering. Anisotropy, or the directional dependency of mechanical properties, is critical in designing biomaterials for bone regeneration due to the complex, hierarchical structure of natural bone. The objective was to evaluate the mechanical behaviour of each composite material under simulated physiological conditions, focusing on their anisotropic responses to loading. The findings indicate that PLGA-nCS exhibited the highest degree of anisotropy, with enhanced stiffness and strength along preferred load-bearing directions, making it suitable for applications requiring higher mechanical stability. In contrast, PLGA-nCS-fu demonstrated moderate mechanical strength but displayed isotropic behaviour, ensuring consistent compressive performance across all directions. The study highlights the synergistic effects of incorporating nCS and fu into PLGA-based materials. fu, a natural sulphated polysaccharide derived from brown seaweed, significantly enhances the biological performance of these composites.

Diabetic nephropathy (DN), a major driver of end-stage kidney disease, elevates the risk for osteoporosis (OP) and its clinical precursor, low bone mineral density (low BMD), indicating broader systemic effects. While peripheral blood mononuclear cells (PBMCs) participate in both conditions, their common mechanisms remain poorly understood. This study aimed to identify common biomarkers and pathways linking DN to OP/low BMD by analyzing transcriptomic datasets from patients with these conditions. Using weighted gene co-expression network analysis (WGCNA), machine learning, and differential expression validation, we identified NLRP3 as a central hub gene. Functional analyses connected NLRP3 to pro-inflammatory pathways and immune cell activation. Single-cell data showed specific NLRP3 overexpression in DN patient macrophages, which exhibited heightened osteoclast differentiation capability. Protein analysis confirmed elevated NLRP3 levels in DN cases. In conclusion, PBMCs from DN patients with comorbid osteoporosis show upregulated NLRP3 expression and inflammasome activation, which may drive systemic inflammation and bone loss. These results clarify the pathological link between DN and OP/low BMD and highlight NLRP3 as a potential diagnostic marker and therapeutic target.

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.