Advances in the application of nanotechnology in reducing cardiotoxicity induced by cancer chemotherapy.

Advances in the development of anti-tumour drugs and related technologies have resulted in a significant increase in the number of cancer survivors. However, the incidence of chemotherapy-induced cardiotoxicity (CIC) has been rising continuously, threatening their long-term survival. The integration of nanotechnology and biomedicine has brought about an unprecedented technological revolution and has promoted the progress of anti-tumour therapy. In this review, we summarised the possible mechanisms of CIC, evaluated the role of nanoparticles (including liposomes, polymeric micelles, dendrimers, and hydrogels) as drug carriers in preventing cardiotoxicity and proposed five advantages of nanotechnology in reducing cardiotoxicity: Liposomes cannot easily penetrate the heart's endothelial barrier; optimized delivery strategies reduce distribution in important organs, such as the heart; targeting the tumour microenvironment and niche; stimulus-responsive polymer nano-drug carriers rapidly iterate; better economic benefits were obtained. Nanoparticles can effectively deliver chemotherapeutic drugs to tumour tissues, while reducing the toxicity to heart tissues, and break through the dilemma of existing chemotherapy to a certain extent. It is important to explore the interactions between the physicochemical properties of nanoparticles and optimize the highly specific tumour targeting strategy in the future.

Real-time imaging and quantitative analysis of internal gap formation in bulk-fill and conventional resin composites: An OCT evaluation.

BACKGROUND: This study used optical coherence tomography (OCT) to observe real-time internal gap formation in both bulk-fill and conventional resin composites. It aimed to provide a quantitative analysis of variations, addressing the inconclusive nature of microleakage assessment caused by differences in testing methods. METHODS: Fifty extracted third molars prepared with Class I cavities, were divided into five groups (n = 10). Conventional resin Filtek Z350 XT (FZX) was applied with a double-layer filling of 2 mm per layer. Bulk-fill resins X-tra fil (XTF), Filtek Bulk Fill Posterior Restorative (FBP), Surefil SDR Flow + (SDR), and Filtek Flowable Restorative (FFR) were applied with a single-layer filling of 4 mm. Real-time OCT imaging was conducted during light curing. Post-curing, the entire sample was OCT-scanned. Following this, ImageJ software was used to measure the gap (G1 %). Subsequently, thermal cycling (TC) (5000 times, 5 °C-55 °C) was applied, followed by OCT scanning to calculate the gap (G2 %) and ΔG%. Data were analyzed using two-way repeated measures ANOVA, Kruskal-Wallis test, and Duncan's test (α=0.05). RESULTS: There was no significant difference in G1 % among the groups (p > 0.05). Following TC, FZX exhibited the highest G2 %, succeeded by FFR, FBP, XTF, and SDR, with SDR demonstrating the lowest G2 % (p < 0.05). FZX showed the highest ΔG% (p < 0.05), while SDR exhibited the lowest ΔG% (p < 0.05). CONCLUSION: OCT proves to be a promising tool for detecting microleakage. TC exerted a more significant negative impact on conventional resin. Surefil SDR Flow + displayed the least microleakage, both before and after TC.

A Mendelian randomization study of the effect of serum 25-hydroxyvitamin D levels on autoimmune thyroid disease.

Objective: The influence of vitamin D on autoimmune thyroid disease (AITD) remains a subject of ongoing debate. This study employs Mendelian randomization (MR) to investigate the causal correlations of serum 25-hydroxyvitamin D (25[OH]D) levels with autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves disease (GD). Methods: Data on single nucleotide polymorphisms related to serum 25(OH)D levels, AIT, AIH, and GD were sourced from UK Biobank and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were employed to test the exposure-outcome causal relationship. Assessments of horizontal pleiotropy, heterogeneity, and stability were performed using the MR-Egger intercept, Cochran's Q test, and leave-one-out sensitivity analysis, respectively. Results: The results of MR analysis showed increased serum 25(OH)D levels was associated with a reduced risk of AIT (OR 0.499, 95% CI 0.289 to 0.860, p = 0.012) but not causal associated with AIH (OR 0.935, 95% CI 0.695 to 1.256, p = 0.654) and GD (OR 0.813, 95% CI 0.635 to 1.040, p = 0.100). Intercept analysis showed no horizontal pleiotropy (p > 0.05), and Cochran's Q test showed no heterogeneity (p > 0.05). Sensitivity analysis suggested that these results were robust. Conclusion: An increased serum 25(OH)D level is associated with AIT risk reduction but unrelated to AIH and GD. This finding suggests that vitamin D supplementation can be valuable for preventing and treating AIT.

Acute impact of salinity and C/N ratio on the formation and properties of soluble microbial products from activated sludge.

The present study investigated the shock of NaCl and C/N ratio on properties of soluble microbial products (SMPs), focusing on their sized fractions. The results indicated that the NaCl stress increased the content of biopolymers, humic substances, building blocks, and LMW substances in SMPs, while the addition of 40 g NaCl L-1 significantly changed their relative abundance in SMPs. The acute impact of both N-rich and N-deficient conditions accelerated the secretion of SMPs, but the characteristics of LMW substances differed. Meanwhile, the bio-utilization of SMPs has been enhanced with the increase of NaCl dosage but decreased with the increase of the C/N ratio. The mass balance of sized fractions in SMPs + EPS could be set up when NaCl dosage <10 g/L and C/N ratio >5, which indicates the hydrolysis of sized fractions in EPS mainly compensated for their increase/reduction in SMPs. Besides, the results of the toxic assessment indicated that the oxidative damage caused by the NaCl shock was an important factor affecting the property of SMPs, and the abnormal expression of DNA transcription cannot be neglected for bacteria metabolisms with the change of C/N ratio.

Polyhydroxyalkanoates: the natural biopolyester for future medical innovations.

Polyhydroxyalkanoates (PHAs) are a family of natural microbial biopolyesters with the same basic chemical structure and diverse side chain groups. Based on their excellent biodegradability, biocompatibility, thermoplastic properties and diversity, PHAs are highly promising medical biomaterials and elements of medical devices for applications in tissue engineering and drug delivery. However, due to the high cost of biotechnological production, most PHAs have yet to be applied in the clinic and have only been studied at laboratory scale. This review focuses on the biosynthesis, diversity, physical properties, biodegradability and biosafety of PHAs. We also discuss optimization strategies for improved microbial production of commercial PHAs via novel synthetic biology tools. Moreover, we also systematically summarize various medical devices based on PHAs and related design approaches for medical applications, including tissue repair and drug delivery. The main degradation product of PHAs, 3-hydroxybutyrate (3HB), is recognized as a new functional molecule for cancer therapy and immune regulation. Although PHAs still account for only a small percentage of medical polymers, up-and-coming novel medical PHA devices will enter the clinical translation stage in the next few years.

Polystyrene microplastic exposure induces insulin resistance in mice via dysbacteriosis and pro-inflammation.

Microplastics (MPs) as emerging contaminants have become a global environmental problem. However, studies on the effects of MPs on metabolic diseases remain limited. Here, we evaluated the effects of polystyrene (PS), one of the most prominent types of MPs, on insulin sensitivity in mice fed with normal chow diet (NCD) or high-fat diet (HFD), and explained the underlying mechanisms. Mice fed with NCD or HFD both showed insulin resistance (IR) after PS exposure accompanied by increased plasma lipopolysaccharide and pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1ß. Exposure to PS also resulted in a significant decrease in the richness and diversity of gut microbiota, particularly an increase in the relative abundance of Gram-negative bacteria such as Prevotellaceae and Enterobacteriaceae. Additionally, PS with a small particle size (5 µm) accumulated in the liver, kidneys and blood vessels of mice. Further analyses showed inhibition of the insulin signaling pathway in the liver of PS exposed mice, such as inhibition of IRS1 and decreased expression of PI3K. Hence, the mechanism of PS exposure to induce IR in mice might be mediated through regulating gut microbiota and PS accumulation in tissues, stimulating inflammation and inhibiting the insulin signaling pathway. In conclusion, PS might be a potential environmental contaminant that causes metabolic diseases associated with IR.

Near-Infrared-Fluorescent Probe for Turn-On Lipopolysaccharide Analysis Based on PEG-Modified Gold Nanorods with Plasmon-Enhanced Fluorescence.

Lipopolysaccharide (LPS), as the major component of the outer membrane of Gram-negative bacteria, can trigger a variety of biological effects such as sepsis, septic shock, and even multiorgan failure. Herein, we developed a near-infrared-fluorescent probe for fluorescent turn-on analysis of LPS based on plasmon-enhanced fluorescence (PEF). Gold nanorods (Au NRs) modified polyethylene glycol (PEG) was used as PEF materials. Au NRs were prepared with different longitudinal surface plasmon resonance (LSPR), and their fluorescence enhancement was investigated. Three kinds of molecular weights (1000, 5000, and 10000) of polyethylene glycol (PEG) were employed to control the distance between the Au NRs and the fluorescence substances of cyanine 7 (Cy7). Experimental analysis showed that the enhancement was related to the spectral overlap between the plasmon resonance of Au NRs and the extinction/emission of fluorophore. The three-dimensional finite-difference time-domain (3D-FDTD) simulation further revealed that the enhancement was caused by local electric field enhancement. Furthermore, the probe was used for the ultrasensitive analysis of LPS with a detection limit of 3.85 ng/mL and could quickly distinguish the Gram-negative bacterium-Escherichia coli (E. coli) (with LPS in the membrane) from Gram-positive bacterium-Staphylococcus aureus (S. aureus) (without LPS), as well as quantitative determination of E. coli with a detection limit of 1.0 × 106 cfu/mL. These results suggested that the prepared probe has great potential for biomedical diagnosis and selective detection of LPS from different bacterial strains.

Synthesis and application of novel silver magnetic amino silicone adhesive particles for preparation of high purity α-linolenic acid from tree peony seed oil under applied magnetic field.

Silver magnetic amino silicone adhesive (Fe3O4@SiO2@NH2@Ag) particles were prepared for the purification of α-linolenic acid from tree peony seed oil under applied magnetic field. First, Fe3O4@SiO2@NH2@Ag particles were prepared and physicochemically characterized, including XRD, TG, FTIR, SEM, magnetic hysteresis curves and elemental analysis. The static process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, including adsorption curve, desorption curve, elution solvent composition and adsorption isotherm. The result indicated that 0-1-4% acetone-n-hexane elution solvent was selected for the gradient elution process, 2 h and 60 min were the time required to reach adsorption and desorption equilibrium, 20 °C was selected as the adsorption temperature, Langmuir model was suitable to fit and explain the equilibrium data, and the adsorption process was spontaneous and exothermic. Under applied magnetic field, the dynamic process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, and the optimum conditions were 20:1 µL/g loading amount, 0.5 mL/min flow rate and 51.73 Oe magnetic field intensity. After purification, the purity and recovery ratio of α-linolenic acid were calculated to be 94% and 74%, respectively. Furthermore, the recycled Fe3O4@SiO2@NH2@Ag particles still achieved better purification result. Therefore, the developed method shows a good application prospect in the field of separation and purification of α-linolenic acid.

Comparative toxicity of silver nanoparticles on oxidative stress and DNA damage in the nematode, Caenorhabditis elegans.

This study examined the effects of polyvinylpyrrolidone (PVP) surface coating and size on the organismal and molecular toxicity of silver nanoparticles (AgNPs) on the nematode, Caenorhabditis elegans. The toxicity of bare AgNPs and 8 and 38 nm PVP-coated AgNPs (PVP8-AgNPs, PVP38-AgNPs) were compared. The toxicity of AgNO3 was also tested because ion dissolution and particle-specific effects are often important characteristics determining Ag nanotoxicity. Comparative toxicity across AgNO3 and the three different types of AgNPs was first evaluated using a C. elegans mortality test by a direct comparison of the LC50 values. Subsequently, mutant screening followed by oxidative stress, mitochondrial toxicity and DNA damage assays were carried out at equitoxic (LC10 and LC50) concentrations to further assess the toxicity mechanism of AgNO3 and AgNPs. AgNO3 and bare AgNPs had similar toxicities, whereas PVP coating reduced the toxicity of the AgNPs significantly. Of the PVP-AgNPs, the smaller NPs were more toxic. Different groups of mutants responded differently to AgNO3 and AgNPs, which indicates that their toxicity mechanism might be different. AgNO3 and bare AgNPs induced mitochondrial membrane damage. None of the silver materials tested caused detectable polymerase-inhibiting DNA lesions in either the nucleus or mitochondria as measured by a quantitative PCR assay, but AgNO3, bare AgNPs and PVP8-AgNPs induced oxidative DNA damage. These results show that coatings on the AgNPs surface and the particle size make a clear contribution to the toxicity of the AgNPs, and oxidative stress-related mitochondrial and DNA damage appear to be potential mechanisms of toxicity.

Intracellular uptake and associated toxicity of silver nanoparticles in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) are frequently used as antimicrobials. While the mechanism(s) by which AgNPs are toxic are unclear, their increasing use raises the concern that release into the environment could lead to environmental toxicity. We characterized the physicochemical behavior, uptake, toxicity (growth inhibition), and mechanism of toxicity of three AgNPs with different sizes and polyvinylpyrrolidone (PVP) or citrate coatings to the nematode Caenorhabditis elegans. We used wild-type (N2) C. elegans and strains expected to be sensitive to oxidative stress (nth-1, sod-2 and mev-1), genotoxins (xpa-1 and nth-1), and metals (mtl-2). Using traditional and novel analytical methods, we observed significant aggregation and extra-organismal dissolution of silver, organismal uptake and, in one case, transgenerational transfer of AgNPs. We also observed growth inhibition by all tested AgNPs at concentrations in the low mg/L levels. A metallothionein-deficient (mtl-2) strain was the only mutant tested that exhibited consistently greater AgNP sensitivity than wild-type. Although all tested AgNPs were internalized (passed cell membranes) in C. elegans, at least part of the toxicity observed was mediated by ionic silver. Finally, we describe a modified growth assay that permits differentiation between direct growth-inhibitory effects and indirect inhibition mediated by toxicity to the food source.