Despite the known interplay between blood flow and function, there is currently no minimally invasive method to monitor diaphragm hemodynamics. We used contrast-enhanced ultrasound (CEUS) to quantify ...relative diaphragm blood flow (Q˙DIA) in humans and assessed the technique’s efficacy and reliability during graded inspiratory pressure threshold loading. We hypothesized that: (1) Q˙DIA would linearly increase with pressure generation: and (2) that there would be good test-retest reliability and interanalyzer reproducibility.
Can the first minimally invasive method to measure relative diaphragm blood flow be validated in humans?
Quantitative contrast-enhanced ultrasound of the costal diaphragm was performed in healthy participants (10 male subjects, 6 female subjects; mean age 28 ± 5 years; BMI 22.8 ± 2.0 kg/m) during unloaded breathing and three stages of loaded breathing on two separate days. Gastric and esophageal balloon catheters measured diaphragmatic pressure. Ultrasonography was performed during a constant-rate IV infusion of lipid-stabilized microbubbles following each stage. Ultrasound images were acquired after a destruction-replenishment sequence and diaphragm specific time-intensity data were used to determine Q˙DIA by two individuals.
Transdiaphragmatic pressure for unloaded and each loading stage were 15.2 ± 0.8, 26.1 ± 0.8, 34.6 ± 0.8, and 40.0 ± 0.8 percentage of the maximum, respectively. Q˙DIA increased with each stage of loading (3.1 ± 3.1, 6.9 ± 3.6, 11.0 ± 4.9, and 13.5 ± 5.4 AU/s; P < .0001). The linear relationship between diaphragmatic flow and pressure was reproducible from day to day. Q˙DIA had good to excellent test-retest reliability (0.86 0.77, 0.92; P < .0001) and excellent interanalyzer reproducibility (0.93 0.90, 0.95; P < .0001) with minimal bias.
Relative Q˙DIA measurements have valid physiological underpinnings, are reliable day to day, and reproducible analyzer-to-analyzer. Contrast-enhanced ultrasound is a viable, minimally invasive method for assessing costal Q˙DIA in humans and may provide a tool to monitor diaphragm hemodynamics in clinical settings.
All that melts is not Mooren's Natarajan, Radhika; Kulkarni, Shridhar; Priyanka, Maria
Indian journal of ophthalmology,
07/2022, Letnik:
2, Številka:
3
Journal Article
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Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The physicochemical properties of nanoparticles play critical roles in regulating nano-bio interactions. Whereas the effects of the size, shape, and surface charge of nanoparticles on their ...biological performances have been extensively investigated, the roles of nanoparticle mechanical properties in drug delivery, which have only been recognized recently, remain the least explored. This review article provides an overview of the impacts of nanoparticle mechanical properties on cancer drug delivery, including (1) basic terminologies of the mechanical properties of nanoparticles and techniques for characterizing these properties; (2) current methods for fabricating nanoparticles with tunable mechanical properties; (3) in vitro and in vivo studies that highlight key biological performances of stiff and soft nanoparticles, including blood circulation, tumor or tissue targeting, tumor penetration, and cancer cell internalization, with a special emphasis on the underlying mechanisms that control those complicated nano-bio interactions at the cellular, tissue, and organ levels. The interesting research and findings discussed in this review article will offer the research community a better understanding of how this research field evolved during the past years and provide some general guidance on how to design and explore the effects of nanoparticle mechanical properties on nano-bio interactions. These fundamental understandings, will in turn, improve our ability to design better nanoparticles for enhanced drug delivery.
Molecular oxygen (O
) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen ...concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP-consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best-studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine-tuning the responses to hypoxic stress.
Colorectal cancer is one of the most common cancers worldwide usually is associated with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific ...circulating exosomal miRNAs could act as biomarkers for early diagnosis of colorectal cancer.
A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using qRT-PCR and ROC curve analysis in subsequent training phase, validation phase, and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan-Meier method.
The expression of exosomal miR-27a and miR-130a in plasma significantly increased in colorectal cancer. The area under ROC curves (AUC) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for colorectal cancer (AUCs = 0.846, 0.898, and 0.801 for the training, validation, and external validation phases, respectively). Patients with colorectal cancer with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis.
We identified a circulating exosomal miRNAs panel for the detection of colorectal cancer.
The exosomal miR-27a and miR-130a panel in plasma may act as a noninvasive biomarker for early detection and predicting prognosis of colorectal cancer.
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Stealth and pseudo-stealth nanocarriers Wen, Panyue; Ke, Wendong; Dirisala, Anjaneyulu ...
Advanced drug delivery reviews,
July 2023, 2023-07-00, 20230701, Letnik:
198
Journal Article
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The stealth effect plays a central role on capacitating nanomaterials for drug delivery applications through improving the pharmacokinetics such as blood circulation, biodistribution, ...and tissue targeting. Here based on a practical analysis of stealth efficiency and a theoretical discussion of relevant factors, we provide an integrated material and biological perspective in terms of engineering stealth nanomaterials. The analysis surprisingly shows that more than 85% of the reported stealth nanomaterials encounter a rapid drop of blood concentration to half of the administered dose within 1 h post administration although a relatively long β-phase is observed. A term, pseudo-stealth effect, is used to delineate this common pharmacokinetics behavior of nanomaterials, that is, dose-dependent nonlinear pharmacokinetics because of saturating or depressing bio-clearance of reticuloendothelial system (RES). We further propose structural holism can be a watershed to improve the stealth effect; that is, the whole surface structure and geometry play important roles, rather than solely relying on a single factor such as maximizing repulsion force through polymer-based steric stabilization (e.g., PEGylation) or inhibiting immune attack through a bio-inspired component. Consequently, engineering delicate structural hierarchies to minimize attractive binding sites, that is, minimal charges/dipole and hydrophobic domain, becomes crucial. In parallel, the pragmatic implementation of the pseudo-stealth effect and dynamic modulation of the stealth effect are discussed for future development.
Oxidative stress has been defined as an imbalance between oxidants and antioxidants and more recently as a disruption of redox signaling and control. It is generally accepted that oxidative stress ...can lead to cell and tissue injury having a fundamental role in vascular dysfunction. Physiologically, reactive oxygen species (ROS) control vascular function by modulating various redox-sensitive signaling pathways. In vascular disorders, oxidative stress instigates endothelial dysfunction and inflammation, affecting several cells in the vascular wall. Vascular ROS are derived from multiple sources herein discussed, which are prime targets for therapeutic development. This review focuses on oxidative stress in vascular physiopathology and highlights different strategies to inhibit ROS production.
A unique biomimetic drug‐delivery system composed of 4T1‐breast‐cancer‐cell membranes and paclitaxel‐loaded polymeric nanoparticles (PPNs) (cell‐membrane‐coated PPNs), demonstrates superior ...interactions to its source tumor cells and elongated blood circulation, and displays highly cell‐specific targeting of the homotypic primary tumor and metastases, with successful inhibition of the growth and lung metastasis of the breast cancer cells.
Flow cytometry has proven its capability for rapid and quantitative analysis of individual cells and the separation of targeted biological samples from others. The emerging microfluidics technology ...makes it possible to develop portable microfluidic diagnostic devices for point-of-care testing (POCT) applications. Microfluidic flow cytometry (MFCM), where flow cytometry and microfluidics are combined to achieve similar or even superior functionalities on microfluidic chips, provides a powerful single-cell characterisation and sorting tool for various biological samples. In recent years, researchers have made great progress in the development of the MFCM including focusing, detecting, and sorting subsystems, and its unique capabilities have been demonstrated in various biological applications. Moreover, liquid biopsy using blood can provide various physiological and pathological information. Thus, biomarkers from blood are regarded as meaningful circulating transporters of signal molecules or particles and have great potential to be used as non (or minimally)-invasive diagnostic tools. In this review, we summarise the recent progress of the key subsystems for MFCM and its achievements in blood-based biomarker analysis. Finally, foresight is offered to highlight the research challenges faced by MFCM in expanding into blood-based POCT applications, potentially yielding commercialisation opportunities.
This review summarises the recent major developments of the key subsystems for microfluidic flow cytometry and its achievements in blood-based biomarker analysis.
Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical ...application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano‐based systems coated with immune cells‐derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.
Biocompatibility and targeting potential are the main features of immune cell membranes, which have rendered them the potential of being used as coating platforms for biomimetic nanoparticles for drug delivery, cancer therapy, and bioimaging. Herein, an overview of requirements for the successful coating of nanomedicines with cell membranes and the most recent progresses in their biomedical applications are discussed.
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