Sensitivity reply offers minimal influence on Hematopoietic Stem Tissues

Quantum dots (QDs) are semi-conductor luminescent nanocrystals usually of 2-10 nm diameter, attracting the significant attention in biomedical studies since emerged. Due to their unique optical and electronic properties, i.e. wide absorption spectra, narrow tunable emission bands or stable, bright photoluminescence, QDs seem to be ideally suited for multi-colour, simultaneous bioimaging and cellular labeling at the molecular level as new-generation probes. A highly reactive surface of QDs allows for conjugating them to biomolecules, what enables their direct binding to areas of interest inside or outside the cell for biosensing or targeted delivery. Particularly protein-QDs conjugates are current subjects of research, as features of QDs can be combined with protein specific functionalities and therefore used as a complex in variety of biomedical applications. It is known that QDs are able to interact with cells, organelles and macromolecules of the human body after administration. QDs are reported to cause changes at proteins level, including unfolding and three-dimensional structure alterations which might hamper proteins from performing their physiological functions and thereby limit the use of QD-protein conjugates in vivo. Moreover, these changes may trigger unwanted cellular outcomes as the effect of different signaling pathways activation. In this review, characteristics of QDs interactions with certain human proteins are presented and discussed. Besides that, the following manuscript provides an overview on structural changes of specific proteins exposed to QDs and their biological and biomedical relevance.In this study, we determined the roles of oxidative stress and related signals in mediating transgenerational toxicity of 30 nm polystyrene nanoparticles (PS-NPs) in Caenorhabditis elegans. Using brood size and locomotion behavior as endpoints, exposure to 1-100 μg/L PS-NPs caused transgenerational toxicity. Meanwhile, the activation of reactive oxygen species (ROS) was also observed transgenerationally after exposure to 1-100 μg/L PS-NPs. After exposure to 1 μg/L PS-NPs, the transgenerational toxicity was monitored until F2 generation (F2-G) and recovered at F3-G. At the F1-G of 1 μg/L PS-NPs-exposed nematodes, RNAi knockdown of daf-2 with function to inhibit oxidative stress suppressed the transgenerational toxicity and increased the mitochondrial SOD-3 expression. In contrast, at F3-G of 1 μg/L PS-NPs-exposed nematodes, RNAi knockdown of mev-1 with function to induce oxidative stress promoted locomotion and brood size, and suppressed the SOD-3 expression. Moreover, we observed the dynamic expressions of mev-1, daf-2, and sod-2 transgenerationally after exposure to 1 μg/L PS-NPs at P0-G, which further suggested the involvement of MEV-1, DAF-2, and SOD-3 in affecting induction of transgenerational PS-NP toxicity. Therefore, we provided the evidence to suggest the roles of oxidative stress activation and related molecular signals in mediating induction of transgenerational PS-NP toxicity. Our data highlights the crucial function of oxidative stress-related signals during induction of transgenerational PS-NP toxicity.Two-dimensional (2D) engineered nanomaterials are widely used in consumer and industrial goods due to their unique chemical and physical characteristics. Engineered nanomaterials are incredibly small and capable of being aerosolized during manufacturing, with the potential for biological interaction at first-contact sites such as the eye and lung. The unique properties of 2D nanomaterials that make them of interest to many industries may also cause toxicity towards epithelial cells. Using murine and human respiratory epithelial cell culture models, we tested the cytotoxicity of eight 2D engineered nanomaterials graphene (110 nm), graphene oxide (2 um), graphene oxide (400 nm), reduced graphene oxide (2 um), reduced graphene oxide (400 nm), partially reduced graphene oxide (400 nm), molybdenum disulfide (400 nm), and hexagonal boron nitride (150 nm). Non-graphene nanomaterials were also tested in human corneal epithelial cells for ocular epithelial cytotoxicity. Hexagonal boron nitride was found to be cytotoxic in mouse tracheal, human alveolar, and human corneal epithelial cells. Hexagonal boron nitride was also tested for inhibition of wound healing in alveolar epithelial cells; no inhibition was seen at sub-cytotoxic doses. Nanomaterials should be considered with care before use, due to specific regional cytotoxicity that also varies by cell type. Supported by U01ES027288 and T32HL007013 and T32ES007059.Engineered nanomaterials offer the benefit of having systematically tunable physicochemical characteristics (e.g., size, dimensionality, and surface chemistry) that highly dictate the biological activity of a material. Among the most promising engineered nanomaterials to date are graphene-family nanomaterials (GFNs), which are 2-D nanomaterials (2DNMs) with unique electrical and mechanical properties. Beyond engineering new nanomaterial properties, employing safety-by-design through considering the consequences of cell-material interactions is essential for exploring their applicability in the biomedical realm. In this study, we asked the effect of GFNs on the endothelial barrier function and cellular architecture of vascular endothelial cells. Using micropatterned cell pairs as a reductionist in vitro model of the endothelium, the progression of cytoskeletal reorganization as a function of GFN surface chemistry and time was quantitatively monitored. Here, we show that the surface oxidation of GFNs (graphene, reduced graphene oxide, partially reduced graphene oxide, and graphene oxide) differentially affect the endothelial barrier at multiple scales; from the biochemical pathways that influence the development of cellular protrusions to endothelial barrier integrity. More oxidized GFNs induce higher endothelial permeability and the increased formation of cytoplasmic protrusions such as filopodia. We found that these changes in cytoskeletal organization, along with barrier function, can be potentiated by the effect of GFNs on the Rho/Rho-associated kinase (ROCK) pathway. Specifically, GFNs with higher surface oxidation elicit stronger ROCK2 inhibitory behavior as compared to pristine graphene sheets. Overall, findings from these studies offer a new perspective towards systematically controlling the surface-dependent effects of GFNs on cytoskeletal organization via ROCK2 inhibition, providing insight for implementing safety-by-design principles in GFN manufacturing towards their targeted biomedical applications.As a possible carcinogen, carbon black has threatened public health. However, the evidences are insufficient and the mechanism of carcinogenesis is still not specified. Thirty rats were randomly divided into 3 groups, namely 0, 5 and 30 mg/m3 Carbon Black nanoparticles (CBNPs) groups, respectively. Rats were treated with CBNPs by nose-only inhalation for 28 days, 6 h/day. The human bronchial epithelial (16HBE) cells were treated with 0, 50, 100 and 200 μg/mL CBNPs for 24 h. Polo-like kinase 1 (PLK1) overexpression cell line was established by pcDNA3.1-PLK1 stable transfection. Our results showed that CBNPs exposure could induce DNA damage and genetic changes as well as apoptosis in vivo and in vitro. The DNA repair ability increased after CBNPs exposure. Cell cycle process was retarded at the G2/M phases in 16HBE cells after CBNPs treatment. The PLK1, ChK2 GADD45α and XRCC1 expression levels changed in rat lung and 16HBE cells after CBNPs treatment. Compared with NC 16HBE cells, DNA damage and repair, numbers of apoptotic cells and micronucleus (MN) rates, as well as the ChK2, GADD45α, XRCC1 expression levels decreased, whereas cytokinesis block proliferation index (CBPI) and replicative index (RI) increase in PLK overexpression (PLK+/+) cells after CBNPs treatment. This study highlighted that PLK1 related with the genetic toxicity of CBNPs in vitro and in vivo. Our results provided evidences supporting reclassification of carbon black as a human possible carcinogen.
Hyponatremia and hypernatremia are common electrolyte abnormalities in patients with malignancy and have been independently associated with worse survival outcomes. To date, there are no data on the impact of dysnatremia on survival outcomes in patients with neuroendocrine neoplasms (NENs).
This study involves retrospective cohort analysis from a tertiary care center of NEN patients treated with peptide receptor radionuclide therapy (PRRT) with a cumulative activity of at least 3.7 GBq 177Lu-DOTATATE between the years 2000 and 2015.
Comparison of overall survival of patients with the occurrence of hyponatremia (serum sodium < 135 mmol/L) or hypernatremia (serum sodium > 145 mmol/L) before starting or during PRRT was perfomed.
A total of 649 patients were included. Hyponatremia occurred in 57 patients during the observation period and was associated with a shorter median overall survival (95% CI) of 25 months (14-36) compared to 55 months (48-61) of the 512 normonatremic patients (P < 0.001), adjusted hazard ratio (HR) 1.48 (95% CI 1.04-2.12). Overall survival time was reduced regardless of whether hyponatremia was present at baseline or during PRRT. In contrast, hypernatremia occurred in 80 patients and was associated with a longer median overall survival (95% CI) of 94 months (47-140) compared with the 512 normonatremic patients (P = 0.018), adjusted HR 0.61 (95% CI 0.40-0.92). This association was driven by the patients with hypernatremia during PRRT. No association between dysnatremia and progression-free survival after PRRT was observed.
The occurrence of hypo- or hypernatremia in PRRT-treated NET patients is associated with opposing outcomes with regard to overall survival. Sodium levels might have a prognostic role in these patients.
The occurrence of hypo- or hypernatremia in PRRT-treated NET patients is associated with opposing outcomes with regard to overall survival. Sodium levels might have a prognostic role in these patients.
To determine if A-kinase anchoring protein 13 (AKAP13) interacts with the vitamin D receptor (VDR) to alter vitamin D-dependent signaling in fibroid cells. Uterine leiomyomas (fibroids) are characterized by a fibrotic extracellular matrix and are associated with vitamin D deficiency. Treatment with vitamin D (1,25-dihydroxyvitamin D
) reduces fibroid growth and extracellular matrix gene expression. A-kinase anchoring protein 13 is overexpressed in fibroids and interacts with nuclear hormone receptors, but it is not known whether AKAP13 may interact with the VDR to affect vitamin D signaling in fibroids.
Laboratory studies.
Translational science laboratory.
Human immortalized fibroid or myometrial cells were treated with 1,25-hydroxyvitamin D
(1,25(OH)
D
) and transfected using expression constructs for AKAP13 or AKAP13 mutants, RhoQL, C3 transferase, or small interfering ribonucleic acids (RNAs).
Messenger ribonucleic acid (mRNA) levels of AKAP13, fibromodulin, and versican as measured by quantitative real-time polymerase chain reaction. Glutathione S-transferase-binding assays. Vitamin D-dependent gene activation as measured by luciferase assays.
1,25(OH)
D
resulted in a significant reduction in mRNA levels encoding AKAP13, versican, and fibromodulin. Small interfering RNA silencing of AKAP13 decreased both fibromodulin and versican mRNA levels. Glutathione S-transferase-binding assays revealed that AKAP13 bound to the VDR through its nuclear receptor interacting region. Ponatinib price Cotransfection of AKAP13 and VDR significantly reduced vitamin D-dependent gene activation. RhoA pathway inhibition partially relieved repression of vitamin D-dependent gene activation by AKAP13.
These data suggest that AKAP13 inhibited the vitamin D receptor activation by a mechanism that required, at least in part, RhoA activation.
These data suggest that AKAP13 inhibited the vitamin D receptor activation by a mechanism that required, at least in part, RhoA activation.