Artificial Cells, Nanomedicine, and Biotechnology最新文献

Haemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe³⁺ to 11% Fe³⁺). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.

Type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), obesity (OB) and hypertension (HT) are categorized as metabolic disorders (MDs), which develop independently without distinct borders. Herein, we examined the gut microbiota (GM) and Saururus chinensis (SC) to confirm their therapeutic effects via integrated pharmacology. The overlapping targets from the four diseases were determined to be key protein coding genes. The protein-protein interaction (PPI) networks, and the SC, GM, signalling pathway, target and metabolite (SGSTM) networks were analysed via RPackage. Additionally, molecular docking tests (MDTs) and density functional theory (DFT) analysis were conducted to determine the affinity and stability of the conformer(s). TNF was the main target in the PPI analysis, and equol derived from Lactobacillus paracasei JS1 was the most effective agent for the formation of the TNF complex. The SC agonism (PPAR signalling pathway), and antagonism (neurotrophin signalling pathway) by SC were identified as agonistic bioactives (aromadendrane, stigmasta-5,22-dien-3-ol, 3,6,6-trimethyl-3,4,5,7,8,9-hexahydro-1H-2-benzoxepine, 4α-5α-epoxycholestane and kinic acid), and antagonistic bioactives (STK734327 and piclamilast), respectively, via MDT. Finally, STK734327-MAPK1 was the most favourable conformer according to DFT. Overall, the seven bioactives from SC and equol that can be produced by Lactobacillus paracasei JS1 can exert synergistic effects on these four diseases.

Lung cancer is a dangerous disease that is lacking in an ideal therapy. Here, we evaluated the anti-lung cancer effect in nude mice of a fully human single-chain antibody (scFv) against the associated antigen 7 transmembrane receptor (Ts7TMR), which is also called G protein-coupled receptor, between A549 cells and Trichinella spiralis (T. spiralis). Our data showed that anti-Ts7TMR scFv could inhibit lung cancer growth in a dose-dependent manner, with a tumour inhibition rate of 59.1%. HE staining did not reveal any obvious tissue damage. Mechanistically, immunohistochemical staining revealed that the scFv down-regulated the expression of PCNA and VEGF in tumour tissues. Overall, this study found that anti-Ts7TMR scFv could inhibit A549 lung cancer growth by suppressing cell proliferation and angiogenesis, which may provide a new strategy for treating lung cancer.

The various therapeutic drugs that are currently utilized for the management of cancer, especially breast cancer, are greatly challenged by the augmented resistance that is either acquired or de novo by the cancer cells owing to the long treatment periods. So, this study aimed at elucidating the possible anticancer potential of four compounds 7, 4', 7'', 4'''-tetra-O-methyl amentoflavone, hesperidin, ferulic acid, and chlorogenic acid that are isolated from Cycas thouarsii leaves n-butanol fraction for the first time. The MTT assay evaluated the cytotoxic action of four isolated compounds against MDA-MB-231 breast cancer cells and oral epithelial cells. Interestingly, ferulic acid revealed the lowest IC₅₀ of 12.52 µg/mL against MDA-MB-231 cells and a high IC₅₀ of 80.2 µg/mL against oral epithelial cells. Also, using an inverted microscope, the influence of ferulic acid was studied on the MDA-MB-231, which revealed the appearance of apoptosis characteristics like shrinkage of the cells and blebbing of the cell membrane. In addition, the flow cytometric analysis showed that the MDA-MB-231 cells stained with Annexin V/PI had a rise in the count of the cells in the early and late apoptosis stages. Moreover, gel electrophoresis detected DNA fragmentation in the ferulic acid-treated cells. Finally, the effect of the compound was tested at the molecular level by qRT-PCR. An upregulation of the pro-apoptotic genes (BAX and P53) and a downregulation of the anti-apoptotic gene (BCL-2) were observed. Consequently, our study demonstrated that these isolated compounds, especially ferulic acid, may be vital anticancer agents, particularly for breast cancer, through its induction of apoptosis through the P53-dependent pathway.

Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient's quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Gold nanoparticles (AuNPs) were synthesized using three red wine extracts (RW-Es); by varying temperature, pH, concentrations of RW-Es and gold salt. The RW-AuNPs were characterized by UV-vis, transmission electron microscopy (TEM), dynamic light scattering (DLS), and the Fourier Transform Infra-red Spectroscopy (FT-IR). Their stability was evaluated in water, foetal bovine serum (FBS), phosphate-buffered saline (PBS), and Dulbecco's Modified Eagle Medium (DMEM) by UV-Vis. The effect of the RW-Es and RW-AuNPs on KMST-6 cell cell viability was evaluated by MTT assay; and their wound healing effects were monitored by scratch assay. RW-AuNPs synthesis was observed by colour change, and confirmed by UV-Vis spectrum, with an absorption peak around 550 nm. The hydrodynamic sizes of the RW-AuNPs ranged between 10 and 100 nm. Polyphenols, carboxylic acids, and amino acids are some of functional groups in the RW-Es that were involved in the reduction of RW-AuNPs. The RW-AuNPs were stable in test solutions and showed no cytotoxicity to the KMST-6 cells up to 72 h. AuNPs synthesized from Pinotage and Cabernet Sauvignon enhanced proliferation of KMST-6 cells and showed potential as wound healing agents. Further studies are required to investigate the molecular mechanisms involved in the potential wound-healing effect of the RW-AuNPs.

Nanotechnology-based cancer treatment has received considerable attention, and these treatments generally use drug-loaded nanoparticles (NPs) to target and destroy cancer cells. Nanotechnology combined with photodynamic therapy (PDT) has demonstrated positive outcomes in cancer therapy. Combining nanotechnology and PDT is effective in targeting metastatic cancer cells. Nanotechnology can also increase the effectiveness of PDT by targeting cells at a molecular level. Dendrimer-based nanoconjugates (DBNs) are highly stable and biocompatible, making them suitable for drug delivery applications. Moreover, the hyperbranched structures in DBNs have the capacity to load hydrophobic compounds, such as photosensitizers (PSs) and chemotherapy drugs, and deliver them efficiently to tumour cells. This review primarily focuses on DBNs and their potential applications in cancer treatment. We discuss the chemical design, mechanism of action, and targeting efficiency of DBNs in tumour metastasis, intracellular trafficking in cancer treatment, and DBNs' biocompatibility, biodegradability and clearance properties. Overall, this study will provide the most recent insights into the application of DBNs and PDT in cancer therapy.

Acute respiratory distress syndrome (ARDS) is a complication of pulmonary disease that produces life-threatening hypoxaemia. Despite ventilation and hyperoxic therapies, undetected hypoxia can manifest in capillary beds leading to multi-organ failure. Ox66™ is an ingestible, solid-state form of oxygen designed to supplement oxygen deficits. Twenty-four anaesthetized rats underwent a two-hit model of respiratory distress (ARDS), where a single dose (5 mg/kg) of lipopolysaccharide (LPS) was given intratracheally, and then the respiratory tidal volume was reduced by 40%. After 60 min, animals were randomized to receive Ox66™, or normal saline (NS; vehicle control) via gavage or supplemental inspired oxygen (40% FiO₂). A second gavage was administered at 120 min. Cardiovascular function and blood oximetry/chemistry were measured alongside the peripheral spinotrapezius muscle's interstitial oxygenation (P_ISFO₂). ARDS reduced mean arterial pressure (MAP) and P_ISFO₂ compared to baseline (BL) for all treatment groups. Treatment with Ox66 or NS did not improve MAP, but 40% FiO₂ caused a rapid return to BL. P_ISFO₂ improved after treatment with Ox66^™ and 40% FiO₂ and remained elevated for both groups against NS until study conclusion. Both oxygen treatments also suppressed the inflammatory response to LPS, suggesting that Ox66^™ can deliver therapeutically-impactful levels of oxygen in situations of pulmonary dysfunction.

Oral squamous cell carcinoma (OSCC) is a disease of significant concern with higher mortality rates. Conventional treatment approaches have several drawbacks, leading to the opening of new research avenues in the field of nanoparticle-based cancer therapeutics. The study aimed at the synthesis of gold nanoparticles (Pm-AuNPs) from the aqueous bark extract of Pterocarpus marsupium, followed by its characterization and in vitro anticancer evaluation against OSCC. The synthesized Pm-AuNPs were characterized using UV-visible spectroscopy, particle size analyser, zeta potential, FTIR and SEM techniques. The anticancer potential of the Pm-AuNPs was evaluated against OSCC cell lines (SCC29b, SSC154 and OECM-1) through in vitro assays. The IC₅₀ value was found to be 25 ± 1.2, 45 ± 1.5 and 75 ± 2.1 µg/mL for the three OSCC cell lines, elucidating Pm-AuNPs cytotoxic effects and mechanism of action. Intracellular ROS and SOX detection, mitochondrial transmembrane potential analysis and apoptosis detection were used to confirm the activity of Pm-AuNPs against OSCC. Acute toxicity studies on Wistar rats confirmed the non-toxic nature of the Pm-AuNPs at a higher dose concentration up to 2000 mg/kg body weight. The findings underscore Pm-AuNPs as promising candidates for future anticancer therapeutics, providing insights into their mechanism of action and therapeutic efficacy against OSCC.