Background
Germinal matrix‐intraventricular hemorrhage (GMH‐IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the ...primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products.
Purpose/Hypothesis
To evaluate magnetic susceptibility of normal‐appearing white (WM) and gray matter regions in preterm neonates with and without GMH‐IVH.
Study Type
Retrospective case‐control.
Population
A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH‐IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH‐IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks).
Field Strength/Sequence
QSM at 1.5 Tesla.
Assessment
QSM analysis was performed for each brain hemisphere with a region of interest‐based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami).
Statistical Tests
Changes in magnetic susceptibility were explored using a one‐way analysis of covariance, according to GMH‐IVH severity (P < 0.05).
Results
In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH‐IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus ‐0.0014 ppm; P < 0.001), temporal WM (0.0011 versus ‐0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus ‐0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH‐IVH and controls (P = 0.236).
Data Conclusion
Paramagnetic susceptibility changes occur in several normal‐appearing WM regions of neonates with severe GMH‐IVH, likely related to the accumulation of hemosiderin/ferritin iron secondary to diffusion of extracellular hemoglobin from the ventricle into the periventricular WM.
Level of Evidence: 4
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2018;47:1199–1207.
Abstract This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, ...oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa . Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB-231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression.
The ultimate goal of nanomedicine has always been the generation of translational technologies that can ameliorate current therapies. Cancer disease represented the primary target of nanotechnology ...applied to medicine, since its clinical management is characterized by very toxic therapeutics. In this effort, nanomedicine showed the potential to improve the targeting of different drugs by improving their pharmacokinetics properties and to provide the means to generate new concept of treatments based on physical treatments and biologics. In this review, we considered different platforms that reached the clinical trial investigation, providing an objective analysis about their physical and chemical properties and the working mechanism at the basis of their tumoritr opic properties. With this review, we aim to help other scientists in the field in conceiving their delivering platforms for clinical translation by providing solid examples of technologies that eventually were tested and sometimes approved for human therapy.
Protease biology represents a hot topic in biomedical research because of their pivotal role in regulating cell and tissue homeostasis, regeneration and pathogenesis ...
Purpose
The long-term impact of low-grade germinal matrix-intraventricular hemorrhage (GMH-IVH) on brain perfusion has not been fully investigated. We aimed to compare cortical and deep gray matter ...(GM) cerebral blood flow (CBF) obtained with pseudo-continuous arterial spin labeling (pCASL), among preterm neonates with and without low-grade GMH-IVH and full-term controls.
Methods
3T-pCASL examinations of 9 healthy full-term neonates (mean gestational age 38.5 weeks, range 38–39) and 28 preterm neonates studied at term-equivalent age were analyzed. Eighteen preterm neonates presented normal brain MRI (mean gestational age 30.50 weeks, range 29–31) and 10 low-grade GMH-IVH according to Volpe’s grading system (mean gestational age 32 weeks, range 28–34). A ROI-based mean CBF quantification was performed in 5 cortical (frontal, parietal, temporal, insula, occipital), and 4 subcortical GM regions (caudate, putamen, pallidum, thalamus) for each cerebral hemisphere. CBF differences were explored using a nonparametric analysis of covariance.
Results
Low-grade GMH-IVH hemispheres showed consistently lower CBF in all GM regions when compared with healthy preterm neonates, after controlling the confounding effect of gestational age, postmenstrual age, and birth weight
P
< .001, η
2
= .394. No significant differences were observed between neonates with low-grade GMH and full-term controls. Healthy preterm neonates showed significantly higher CBF than full-term controls in parietal (
P
= .032), temporal (
P
= .016), and occipital cortex (
P
= .024), and at level of thalamus (
P
= .023) and caudate nucleus (
P
= .014).
Conclusion
Low-grade GMH-IVH is associated with lower CBF in posterior cortical and subcortical gray matter regions in preterm neonates, suggesting regional vulnerability of these developing brain structures.
Inflammation and Cancer: In Medio Stat Nano Molinaro, Roberto; Corbo, Claudia; Livingston, Megan ...
Current medicinal chemistry,
01/2018, Letnik:
25, Številka:
34
Journal Article
Recenzirano
Odprti dostop
Cancer treatment still remains a challenge due to the several limitations of currently used chemotherapeutics, such as their poor pharmacokinetics, unfavorable chemical properties, as well as ...inability to discriminate between healthy and diseased tissue. Nanotechnology offered potent tools to overcome these limitations. Drug encapsulation within a delivery system permitted i) to protect the payload from enzymatic degradation/ inactivation in the blood stream, ii) to improve the physicochemical properties of poorly water-soluble drugs, like paclitaxel, and iii) to selectively deliver chemotherapeutics to the cancer lesions, thus reducing the off-target toxicity, and promoting the intracellular internalization. To accomplish this purpose, several strategies have been developed, based on biological and physical changes happening locally and systemically as a consequence of tumorigenesis. Here, we will discuss the role of inflammation in the different steps of tumor development and the strategies based on the use of nanoparticles that exploit the inflammatory pathways in order to selectively target the tumor-associated microenvironment for therapeutic and diagnostic purposes.
Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in ...levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.
Cancer is still considered a lethal disease worldwide and the patients' quality of life is affected by major side effects of the treatments including post-surgery complications, chemo-, and radiation ...therapy. Recently, new therapeutic approaches were considered globally for increasing conventional cancer therapy efficacy and decreasing the adverse effects. Bioactive peptides obtained from plant and animal sources have drawn increased attention because of their potential as complementary therapy. This review presents a contemporary examination of bioactive peptides derived from natural origins with demonstrated anticancer, ant invasion, and immunomodulation properties. For example, peptides derived from common beans, chickpeas, wheat germ, and mung beans exhibited antiproliferative and toxic effects on cancer cells, favoring cell cycle arrest and apoptosis. On the other hand, peptides from marine sources showed the potential for inhibiting tumor growth and metastasis. In this review we will discuss these data highlighting the potential befits of these approaches and the need of further investigations to fully characterize their potential in clinics.
Cellular survival hinges on a delicate balance between accumulating damages and repair mechanisms. In this intricate equilibrium, oxidants, currently considered physiological molecules, can ...compromise vital cellular components, ultimately triggering cell death. On the other hand, cells possess countermeasures, such as autophagy, which degrades and recycles damaged molecules and organelles, restoring homeostasis. Lysosomes and their enzymatic arsenal, including cathepsins, play critical roles in this balance, influencing the cell's fate toward either apoptosis and other mechanisms of regulated cell death or autophagy. However, the interplay between reactive oxygen species (ROS) and cathepsins in these life-or-death pathways transcends a simple cause-and-effect relationship. These elements directly and indirectly influence each other's activities, creating a complex web of interactions. This review delves into the inner workings of regulated cell death and autophagy, highlighting the pivotal role of ROS and cathepsins in these pathways and their intricate interplay.
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