This review introduces the advanced methodologies currently applied in nano-bio interaction studies, specifically omics and systems toxicology, to reveal the molecular-level biological effects of nanomaterials. In our examination of the in vitro biological responses to gold nanoparticles, omics and systems toxicology studies are emphasized to uncover the relevant mechanisms. Gold-based nanoplatforms' considerable promise for improving healthcare will be introduced, followed by a comprehensive discussion of the critical challenges to their clinical translation. Following this, we analyze the present constraints in utilizing omics data for supporting risk assessment of engineered nanomaterials.
In spondyloarthritis (SpA), the inflammatory process affects the musculoskeletal system, the gut, the skin, and the eyes, revealing a diverse spectrum of diseases with a common pathogenetic background. The innate and adaptive immune disruptions in SpA are associated with the emergence of neutrophils, which are essential for orchestrating a pro-inflammatory cascade, impacting both systemic and local tissue environments across different clinical contexts. A proposal exists regarding their activity as pivotal players throughout the disease's timeline, stimulating type 3 immunity and significantly affecting inflammation's onset and amplification, and causing the damage to structures typical of persistent disease. Our review aims to scrutinize neutrophils' involvement across the spectrum of SpA, dissecting their function and dysregulation within each relevant disease area, to understand their increasing significance as potential biomarkers and therapeutic targets.
Rheometric analysis of Phormidium suspensions and human blood samples across various volume fractions under small amplitude oscillatory shear explored the concentration scaling effect on linear viscoelastic properties of cellular suspensions. GSK J1 The time-concentration superposition (TCS) principle is applied to analyze rheometric characterization data, demonstrating a power law scaling of characteristic relaxation time, plateau modulus, and zero-shear viscosity across the concentrations investigated. Phormidium suspensions' elasticity exhibits a considerably stronger concentration dependence than human blood, a result directly linked to their enhanced cellular interactions and a high aspect ratio. Within the studied hematocrit spectrum, no clear phase transition was seen in human blood; only a single scaling exponent for concentration emerged in the high-frequency dynamic context. In a low-frequency dynamic regime, the analysis of Phormidium suspensions highlights three concentration scaling exponents, specifically for the volume fraction regions denoted as Region I (036/ref046), Region II (059/ref289), and Region III (311/ref344). The image's depiction shows that the Phormidium suspension network forms more robustly as the volume fraction rises from Region I to Region II; subsequently, the sol-gel transition transpires between Region II and Region III. The power law concentration scaling exponent, evident in studies of other nanoscale suspensions and liquid crystalline polymer solutions from the literature, is shown to be influenced by colloidal or molecular interactions that involve the solvent. The sensitivity of this exponent demonstrates its connection to the equilibrium phase behavior of complex fluids. A quantifiable estimation is attainable through the unequivocal application of the TCS principle.
Arrhythmogenic cardiomyopathy (ACM), a largely autosomal dominant genetic disorder, is characterized by fibrofatty infiltration and ventricular arrhythmias, most prominently affecting the right ventricle. A heightened risk of sudden cardiac death, especially in young individuals and athletes, is commonly linked to ACM. Genetic factors heavily influence ACM, with over 25 genes identified to harbor genetic variants associated with ACM, representing roughly 60% of ACM cases. Genetic studies on ACM in vertebrate animal models, particularly zebrafish (Danio rerio), which are highly suitable for large-scale genetic and drug screening endeavors, present exceptional opportunities to discover and functionally assess novel genetic variants associated with ACM, along with dissecting the underlying molecular and cellular mechanisms at the entire organism level. GSK J1 We present a concise overview of the key genes underlying the phenomenon of ACM. Zebrafish models, categorized by gene manipulation techniques like gene knockdown, knockout, transgenic overexpression, and CRISPR/Cas9-mediated knock-in, are discussed for investigating the genetic foundation and mechanism of ACM. Insights gleaned from genetic and pharmacogenomic studies conducted on animal models can significantly advance our understanding of disease progression's pathophysiology, as well as guide disease diagnosis, prognosis, and the development of novel therapeutic strategies.
The identification of biomarkers is pivotal in understanding cancer and a multitude of other illnesses; thus, the construction of analytical systems for biomarker recognition stands as a key pursuit within bioanalytical chemistry. Recently, molecularly imprinted polymers (MIPs) have been integrated into analytical systems for the purpose of biomarker quantification. An overview of MIPs for detecting cancer biomarkers, focusing on prostate cancer (PSA), breast cancer (CA15-3, HER-2), epithelial ovarian cancer (CA-125), hepatocellular carcinoma (AFP), and small molecule biomarkers (5-HIAA and neopterin), is offered in this article. Cancer biomarkers can be present in tumors, blood samples, urine, fecal matter, and other tissues and bodily fluids. Accurately identifying trace levels of biomarkers in these complex substances proves to be a demanding technical task. Using MIP-based biosensors, the reviewed studies examined samples of blood, serum, plasma, or urine, which could be either natural or artificial. The fundamental concepts of molecular imprinting technology and MIP-based sensor design are comprehensively examined. Examining both the nature and chemical composition of imprinted polymers, along with the different approaches to determining analytical signals, is the focus of this discussion. Comparing the results from the reviewed biosensors, a discussion of the optimal materials for each biomarker is undertaken.
Wound closure treatments are being advanced through the exploration of hydrogels and extracellular vesicle-based therapies. The skillful integration of these components has yielded positive outcomes in the treatment of both chronic and acute wounds. The hydrogels' intrinsic properties, which house extracellular vesicles (EVs), enable overcoming barriers such as the continuous and regulated release of EVs and the conservation of their appropriate pH levels. Subsequently, electric vehicles can be sourced from varied origins and isolated through multiple procedures. Nonetheless, the transition of this form of therapy to clinical settings is hindered by obstacles, including the creation of hydrogels infused with functional extracellular vesicles and the identification of appropriate long-term storage conditions for these vesicles. In this review, the goal is to describe the documented EV-hydrogel combinations, elaborate on the outcomes observed, and analyze emerging future possibilities.
Inflammatory processes are marked by the ingress of neutrophils into the target areas, enabling them to enact multiple defensive measures. Their (I) consumption of microorganisms is accompanied by cytokine release (II) following degranulation. These cells (III) recruit immune cells via chemokines tailored to specific cell types, then (IV) secrete anti-microbials, including lactoferrin, lysozyme, defensins, and reactive oxygen species, and (V) extrude DNA to form neutrophil extracellular traps. GSK J1 The latter's origin is twofold, stemming from both mitochondria and decondensed nuclei. Cultured cells exhibiting this trait are readily identified through DNA staining with specific dyes. Nevertheless, the intense fluorescence signals originating from the compacted nuclear DNA in tissue sections impede the detection of the pervasive extranuclear DNA in the NETs. In contrast, application of anti-DNA-IgM antibodies demonstrates limited penetration into the densely compacted DNA of the nucleus, but instead produces a robust signal specific to the elongated DNA sections of the NETs. To confirm the presence of anti-DNA-IgM, the tissue sections were further stained for markers of NETs, including histone H2B, myeloperoxidase, citrullinated histone H3, and neutrophil elastase. Our description encompasses a quick, single-step method for the detection of NETs in tissue sections, which offers a fresh perspective on characterizing neutrophil-involved immune responses in disease processes.
Loss of blood in hemorrhagic shock directly results in a fall in blood pressure, a decrease in the heart's pumping action, and, as a consequence, a reduced capacity for oxygen delivery. To prevent the risk of organ failure, especially acute kidney injury, in the event of life-threatening hypotension, the current guidelines advise the administration of vasopressors along with fluids, ensuring the maintenance of arterial pressure. Conversely, the kidneys' response to different vasopressors fluctuates according to the specific agent's characteristics and dose. Norepinephrine, for instance, elevates mean arterial pressure through both alpha-1-mediated vasoconstriction, augmenting systemic vascular resistance, and beta-1-mediated increases in cardiac output. Mean arterial pressure is elevated by the vasoconstriction induced by vasopressin's interaction with V1a receptors. These vasopressors demonstrate varied actions on renal vascular dynamics. Norepinephrine constricts both afferent and efferent arterioles, whereas vasopressin's vasoconstriction principally affects the efferent arteriole. This review of current knowledge examines the renal hemodynamic impacts of norepinephrine and vasopressin during the occurrence of hemorrhagic shock.
Tissue injury management benefits substantially from the use of mesenchymal stromal cells (MSCs). Unfortunately, the low survival rate of transplanted exogenous cells at the site of injury poses a significant obstacle to the effectiveness of MSC therapy.