Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation.

The application of nanoparticles (NPs) in industry is on the rise, along with the potential for human exposure. While the toxicity of microscale equivalents has been studied, nanoscale materials exhibit different properties and bodily uptake, which limits the prediction ability of microscale models. Here, we examine the cytotoxicity of seven transition metal oxide NPs in the fourth period of the periodic table of the chemical elements. We hypothesized that NP-mediated cytotoxicity is a function of cell killing and suppression of cell proliferation. To test our hypothesis, transition metal oxide NPs were tested in a human lung cancer cell model (A549). Cells were exposed to a series of concentrations of TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, or ZnO for either 24 or 48 h. All NPs aside from Cr2O3 and Fe2O3 showed a time- and dose-dependent decrease in viability. All NPs significantly inhibited cellular proliferation. The trend of cytotoxicity was in parallel with that of proliferative inhibition. Toxicity was ranked according to severity of cellular responses, revealing a strong correlation between viability, proliferation, and apoptosis. Cell cycle alteration was observed in the most toxic NPs, which may have contributed to promoting apoptosis and suppressing cell division rate. Collectively, our data support the hypothesis that cell killing and cell proliferative inhibition are essential independent variables in NP-mediated cytotoxicity.

Quantifying Distal Deltoid Disruption With Linear versus Curvilinear Plating of Proximal Humerus Fractures: A Cadaveric Study.

BACKGROUND: Plate fixation of proximal humeral fractures is usually associated with some degree of distal deltoid dissection. The purpose of this study was to quantify deltoid release with standard linear versus curvilinear plates used in the repair of proximal humeral fractures. METHODS: Seven nonpaired, fresh-frozen, clavicle-to-fingertip cadaveric shoulders met the inclusion criteria for this study. Four different proximal humerus implants were tested. One of these plates was curvilinear (89 mm), and the other 3 plates were linear (85, 98, 109 mm in length). Plates were compared based on the amount of deltoid insertion released for proper plate positioning. An analysis of variance with post hoc Tukey tests was conducted to compare mean deltoid disruption across the 3 shortest plate types from each manufacturer. A linear regression analysis was conducted to analyze the effect of plate length on mean deltoid release. RESULTS: The mean deltoid insertion length was 39.6 ± 8.6 mm (n = 7). The curvilinear plate (89 mm) required the least amount of average deltoid release at 4.1 ± 4.5 mm, or 12.1% of the deltoid insertion. Independent analysis of variance, including the 3 shortest plates from each manufacturer, found a significant effect of which plate was used on the amount of deltoid disruption that resulted (F(2, 18) = 18.0, P < 0.001, ω = 0.6). A linear regression including all 4 plates demonstrated a statistically significant direct relationship between the plate length and the mean deltoid released (y = 0.6x - 43.8, r2 = 4). CONCLUSION: This study demonstrates that proximal humerus plate length has a direct relationship with the amount of deltoid released during plating. Although deltoid disruption is length dependent, plate shape (curvilinear vs. linear) could also be contributory. When comparing a curvilinear and a linear plate of similar lengths, the curvilinear plate resulted in less mean deltoid release.

Anatomic variations of the deltoid muscle insertion: a cadaveric study.

Background: The deltoid is a trisegmented muscle with anterior, middle, and posterior components. While the clinical relevance of the presence of anatomic variations of the deltoid origin and insertion continues to be debated, the architecture of the deltoid muscle is more complex than initially believed. This study aimed to evaluate the gross anatomy of the deltoid muscle insertion by qualitatively and quantitatively characterizing the insertion and location of the deltoid muscle's anterior, middle, and posterior components. This information is valuable to surgeons as it raises awareness of potential variants that could be encountered during surgery, promotes mindfulness of neurovascular proximities, and reduces the likelihood of confusion between adjacent muscle fibers. Methods: Eight nonpaired, fresh-frozen clavicle-to-fingertip cadaveric shoulders were acquired for the study (6 left, 2 right). The average age of the cadavers was 79.5 years (range: 64-92). The standard deltopectoral approach was carried out on all specimens. The planes dividing the anterior, middle, and posterior deltoid were identified and marked. Once complete exposure had been achieved, digital calipers were used to record the size of the deltoid insertion. The specimens were qualitatively assessed to characterize the style of insertion they demonstrated. Results: The average length of the deltoid insertion was 39.45 ± 9.33 mm (n = 8). Six of the eight shoulders demonstrated an insertion style previously characterized in the literature. The remaining two shoulders highlighted an insertion pattern not previously described. Conclusion: The current study demonstrates a novel insertion pattern for the deltoid muscle that has not been previously characterized. This "step-off" insertion pattern shows that the anterior, middle, and posterior tendons are inserted superior-medial, directly on, and inferior-lateral to the deltoid tuberosity and was found in 2/8 of our cadaveric specimens.

Dynamic duo - FMRP and TDP-43: Regulating common targets, causing different diseases.

RNA binding proteins play essential roles during development and aging, and are also involved in disease pathomechanisms. RNA sequencing and omics analyses have provided a window into systems level alterations in neurological disease, and have identified RNA processing defects among notable disease mechanisms. This review focuses on two seemingly distinct neurological disorders, the RNA binding proteins they are linked to, and their newly discovered functional relationship. When deficient, Fragile X Mental Retardation Protein (FMRP) causes developmental deficits and autistic behaviors while TAR-DNA Binding Protein (TDP-43) dysregulation causes age dependent neuronal degeneration. Recent findings that FMRP and TDP-43 associate in ribonuclear protein particles and share mRNA targets in neurons highlight the critical importance of translation regulation in synaptic plasticity and provide new perspectives on neuronal vulnerability during lifespan.

Cellulose-Chitosan-Keratin Composite Materials: Synthesis, Immunological and Antibacterial Properties.

Novel composites were synthesized from keratin (KER), cellulose (CEL) and chitosan (CS). The method is recyclable because majority (>88%) of [BMIm+Cl-], an ionic liquid (IL), used as the sole solvent, was recovered for reuse. Experimentally, it was confirmed that unique properties of each component remain intact in the composites, namely bactericide (from KER and CS) and anti-inflammatory property (from KER). Specifically, the composites were examined for their anti-inflammatory influence on macrophages. The cells were imaged and immunophenotyped to determine the quantity using the macrophage marker CD11b. The 75:25 [KER+CS] composite was found to have the least amount of CD11b macrophages compared to other composites. Bactericidal assays indicated that all composites, except the 25:75 [KER+CS], substantially reduce the growth of organisms such as vancomycin resistant Enterococcus (VRE) and Eschericia coli. The results clearly indicate that the composites possess all properties needed for effective use as a wound dressing.

Cytotoxicity in the age of nano: the role of fourth period transition metal oxide nanoparticle physicochemical properties.

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials.