Titanium dioxide (TiO2) nanoparticles are one of the most highly manufactured and employed nanomaterials in the world with applications in copious industrial and consumer products. The liver is a ...major accumulation site for many nanoparticles, including TiO2, directly through intentional exposure or indirectly through unintentional ingestion via water, food or animals and increased environmental contamination. Growing concerns over the current usage of TiO2 coupled with the lack of mechanistic understanding of its potential health risk is the motivation for this study. Here we determined the toxic effect of three different TiO2 nanoparticles (commercially available rutile, anatase and P25) on primary rat hepatocytes. Specifically, we evaluated events related to hepatocyte functions and mitochondrial dynamics: (1) urea and albumin synthesis using colorimetric and ELISA assays, respectively; (2) redox signaling mechanisms by measuring reactive oxygen species (ROS) production, manganese superoxide dismutase (MnSOD) activity and mitochondrial membrane potential (MMP); (3) OPA1 and Mfn-1 expression that mediates the mitochondrial dynamics by PCR; and (4) mitochondrial morphology by MitoTracker Green FM staining. All three TiO2 nanoparticles induced a significant loss (p < 0.05) in hepatocyte functions even at concentrations as low as 50 ppm with commercially used P25 causing maximum damage. TiO2 nanoparticles induced a strong oxidative stress in primary hepatocytes. TiO2 nanoparticles exposure also resulted in morphological changes in mitochondria and substantial loss in the fusion process, thus impairing the mitochondrial dynamics. Although this study demonstrated that TiO2 nanoparticles exposure resulted in substantial damage to primary hepatocytes, more in vitro and in vivo studies are required to determine the complete toxicological mechanism in primary hepatocytes and subsequently liver function.
OBJECTIVES: To determine the percentage of and the most prevalent moderate to severe symptoms and to analyze longitudinal patterns and co-occurrence of symptoms during the first three cycles of ...chemotherapy. SAMPLE & SETTING: A secondary analysis of 26 women with gynecologic cancer who reported daily symptoms. METHODS & VARIABLES: Moderate to severe symptom presence and severity levels were calculated as proportions. Symptoms for each patient were graphed during three cycles and analyzed for patterns of onset, duration, and clustering. RESULTS: Patients completed 1,562 calls to the remote symptom monitoring system. The most commonly reported moderate to severe symptoms were pain, fatigue, and trouble sleeping. Pain and fatigue co-occurred with trouble sleeping in one symptom pattern. Patterns included no moderate to severe symptoms, moderate to severe symptoms during one cycle, moderate to severe symptoms during two cycles, and moderate to severe symptoms during all cycles. IMPLICATIONS FOR NURSING: Nurses should consistently assess symptoms across cycles. To verify distinct classes of symptoms and better target interventions, further study is warranted.
Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems ...to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study the uptake pathway in key cells in the brain including primary astrocytes, microglia, and human GBM cells. We observed that the HALNPs specifically target GBM cells over other brain cells due to higher expression of CD44 in tumor cells. Furthermore, CD44 driven HALNP uptake into GBM cells resulted in lysosomal evasion and increased efficacy of Doxorubicin, a model anti-neoplastic agent, while the astrocytes and microglia cells exhibited extensive HALNP-lysosome co-localization and decreased antineoplastic potency. In summary, novel CD44 targeted lipid based nanocarriers appear to be proficient in mediating site-specific delivery of drugs via CD44 receptors in GBM cells, with an improved therapeutic margin and safety.
Young Man With Unilateral Vision Loss Wilson, Christina N.; Fried, Andrew
Annals of emergency medicine,
November 2020, 2020-11-00, 20201101, Letnik:
76, Številka:
5
Journal Article
Abstract Negative symptoms (e.g., asociality and anhedonia) are a distinct symptomatic domain that has been found to significantly affect the quality of life in patients diagnosed with schizophrenia. ...Additionally, the primary negative symptom of asociality (i.e., withdrawal from social contact that derives from indifference or lack of desire to have social contact) is a major contributor to poor psychosocial functioning and has been found to play an important role in the course of the disorder. Nonetheless, the pathophysiology underlying these symptoms is unknown and currently available treatment options (e.g., antipsychotics and cognitive-behavioral therapy) fail to reliably produce efficacious benefits. Utilizing rodent paradigms that measure social behaviors (e.g., social withdrawal) to elucidate the neurobiological substrates that underlie social dysfunction and to identify novel therapeutic targets may be highly informative and useful to understand more about the negative symptoms of schizophrenia. Accordingly, the purpose of this review is to provide an overview of the behavioral tasks for assessing social functioning that may be translationally relevant for investigating negative symptoms associated with schizophrenia.
Hexagonal boron nitride (h-BN) sheets possess an exclusive set of properties, including wide energy band gap, high optical transparency, high dielectric breakdown strength, high thermal conductivity, ...UV cathodoluminescence, and pronounced thermochemical stability. However, functionalization of large h-BN layers has remained a challenge due to their chemical resistance and unavailable molecular-binding sites. Here we report on the protonation of h-BN via treatment with chlorosulfonic acid that not only exfoliates “large” h-BNs (up to 10 000 μm2) at high yields (∼23%) but also results in their covalent functionalization by introducing four forms of aminated nitrogen (N) sites within the h-BN lattice: sp2-delocalized and sp3-quaternary protonation on internal N sites (>N+ and >NH+−) and pyridinic-like protonation on the edge N sites (NH+– and −NH−). The presence of these groups transforms the chemically passive h-BN sheets to their chemically active form, which as demonstrated here can be used as scaffolds for forming composites with plasmonic gold nanoparticles and organic dye molecules. The dispersion of h-BNs exhibits an optical energy band gap of 5.74 eV and a zeta potential of ζ = +36.25 mV at pH = 6.1 (ζmax = +150 mV), confirming high dispersion stability. We envision that these two-dimensional nanomaterials with an atomically packed honeycomb lattice and high-energy band gap will evolve next-generation applications in controlled-UV emission, atomic-tunneling-barrier devices, ultrathin controlled-permeability membranes, and thermochemically resistive transparent coatings.
Objectives
Maternal posttraumatic stress disorder (PTSD) is a risk factor for negative child adjustment, but it is unclear whether this association is direct (e.g., a mother's PTSD symptoms are ...observed, learned, and internalized by children which results in behavioral and emotional problems) or indirect, through parent–child relationship difficulties or parenting stress. We hypothesized that parenting stress and maternal emotional availability would exhibit indirect effects on relationships between maternal PTSD and children's functioning.
Method
Participants were 52 trauma‐exposed mothers and their children (aged 7–12 years). Mothers completed measures of PTSD and parenting stress and reported on their children's functioning. Emotional availability was assessed through observer‐rated mother–child interactions.
Results
Emotional availability was not related to PTSD or child outcomes. Parenting stress had a substantial indirect effect on the relationships between maternal PTSD and child emotion regulation, internalizing, and externalizing behaviors.
Conclusions
Results highlight the need to target parenting stress in interventions with trauma‐exposed families.
Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal ...studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 ± 10.56 ppm, 136.0 ± 31.73 ppm and 62.37 ± 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.
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