Impact of calcium ions at physiological concentrations on the adsorption behavior of proteins on silica nanoparticles.

The adsorption of proteins on nanoparticles (NPs) largely decides the fate and bioeffects of NPs in vivo. However, bio-fluids are too complicated to directly study in them to reveal related mechanisms, and current studies on model systems often ignore some important biological factors, such as metal ions. Herein, we evaluate the effect of Ca2+ at physiological concentrations on the protein adsorption on negatively-charged silica NP (SNP50). It is found that Ca2+, as well as Mg2+ and several transition metal ions, significantly enhances the adsorption of negatively-charged proteins on SNP50. Moreover, the Ca2+-induced enhancement of protein adsorption leads to the reduced uptake of SNP50 by HeLa cells. A double-chelating mechanism is proposed for the enhanced adsorption of negatively-charged proteins by multivalent metal ions that can form 6 (or more) coordinate bonds, where the metal ions are chelated by both the surface groups of NPs and the surface residues of the adsorbed proteins. This mechanism is consistent with all experimental evidences from metal ions-induced changes of physicochemical properties of NPs to protein adsorption isotherms, and is validated with several model proteins as well as complicated serum. The findings highlight the importance of investigating the influences of physiological factors on the interaction between proteins and NPs.

Exocytosis of Nanoparticles: A Comprehensive Review.

Both biomedical applications and safety assessments of manufactured nanomaterials require a thorough understanding of the interaction between nanomaterials and cells, including how nanomaterials enter cells, transport within cells, and leave cells. However, compared to the extensively studied uptake and trafficking of nanoparticles (NPs) in cells, less attention has been paid to the exocytosis of NPs. Yet exocytosis is an indispensable process of regulating the content of NPs in cells, which in turn influences, even decides, the toxicity of NPs to cells. A comprehensive understanding of the mechanisms and influencing factors of the exocytosis of NPs is not only essential for the safety assessment of NPs but also helpful for guiding the design of safe and highly effective NP-based materials for various purposes. Herein, we review the current status and progress of studies on the exocytosis of NPs. Firstly, we introduce experimental procedures and considerations. Then, exocytosis mechanisms/pathways are summarized with a detailed introduction of the main pathways (lysosomal and endoplasmic reticulum/Golgi pathway) and the role of microtubules; the patterns of exocytosis kinetics are presented and discussed. Subsequently, the influencing factors (initial content and location of intracellular NPs, physiochemical properties of NPs, cell type, and extracellular conditions) are fully discussed. Although there are inconsistent results, some rules are obtained, like smaller and charged NPs are more easily excreted. Finally, the challenges and future directions in the field have been discussed.

Endocytosis, Distribution, and Exocytosis of Polystyrene Nanoparticles in Human Lung Cells.

Nanoplastics, one component of plastic pollution, can enter human bodies via inhalation and thus threaten human health. However, the knowledge about the uptake and exocytosis of nanoplastics in cells of human lung organs is still very limited. Herein, we investigated the endocytosis, distribution, and exocytosis of polystyrene nanoparticles (PS NPs) of 50 nm (G50PS) and 100 nm (R100PS) in A549 cells and BEAS-2B cells. We found that both the cellular uptake of PS NPs increased positively with exposure time and dose, and A549 cells ingested more PS NPs than BEAS-2B cells did. In addition, the intracellular content of G50PS was higher than that of R100PS except at a higher dose and longer time. The ingested PS NPs were distributed mainly in lysosomes, while many G50PS appeared around the cell membrane, and R100PS also accumulated in mitochondria in BEAS-2B cells. As for the exocytosis, R100PS was more difficult to excrete than G50PS. Lysosomes in A549 cells and actin and microtubule in BEAS-2B cells were involved in the exocytosis of the PS NPs. These findings provide detailed information about the translocation of nanoplastics in lung cells, which is valuable for the safety assessment of nanoplastics in the environment.

Phenotypic characterization of CADASIL patients with the Arg332Cys mutation in the NOTCH3.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular disease caused by mutations in NOTCH3, that are primarily localized in exons 4, 3, and 11. The Arg332Cys mutation in exon 6 has been rarely reported in patients with CADASIL. METHODS: A case study and the results of a comprehensive systemic search of the PubMed database, using the keywords "CADASIL", "Arg332Cys", "R332C", and "exon 6", are reported. The results obtained, combined with the data obtained from the largest published case series on CADASIL, the clinical and imaging characteristics of patients with the Arg332Cys mutation, were compared and analyzed. RESULTS: A 48-year-old woman with a rare Arg332Cys mutation in exon 6 of NOTCH3, who presented with rapidly developing dementia and recurrent ischemic stroke, was investigated herein. Magnetic resonance imaging (MRI) revealed abnormal signals in the cerebral white matter, bilateral thalamus, internal and external capsules, basal ganglia, corpus callosum, and brainstem. Literature review identified an additional 21 individuals, comprising 11 Europeans and 10 Asians, with the Arg332Cys mutation; of these identified individuals, clinical data was available for 2 Italian and 9 Asian patients. Analysis of the clinical characteristics of the 11 patients and the patient we reported showed that their mean age at disease onset was 37.82±9.36 years, much earlier than 57.0±9.36 years reported in literature. The most frequent manifestations were transient ischemic stroke or stroke (83.3%), followed by cognitive impairment (58.3%), psychiatric symptoms (50%), and migraine (33.3%). Among the 10 Asian patients with available imaging data, the characteristic high signals for the external capsule and brainstem accounted for 90% and 71.43% respectively, and anterior temporal high signal took proportion of 60% (higher than 34.5% reported for Asian patients in literature). None of the 6 patients with available gradient echo imaging data had cerebral microbleeding. CONCLUSIONS: CADASIL patients with the Arg332Cys mutation in exon 6 have been reported in Europe and Asia. The majority of patients had early disease onset. Diffuse high signals involving the external capsule, brainstem, and bilateral temporal pole are the main neuroimaging characteristics.

A case report of paravertebral low-grade malignant fibrous myxoid sarcoma.

RATIONALE: Low-grade malignant fibrous myxoid sarcoma (LGFMS) is a malignant tumor that originates from soft tissues and has specific clinical and histopathological characteristics. Paravertebral LGFMS is rarely reported. PATIENT CONCERNS: A 60-year-old woman had pain in the lower back and right anterior thigh for more than 3 years. DIAGNOSIS: Paravertebral LGFMS. INTERVENTIONS: Tumor resection, vertebral canal decompression and pedicle screw fixation. OUTCOMES: The tumor was excised, and the vertebral arch was fixed with pedicle screws at the root. Chemoradiotherapy was not performed. Her postoperative visual analogue scale (VAS) score decreased from 7 points at admission to 2 points at follow-up. The patient was discharged at postoperative day 13, and no recurrence was observed at the 6-month follow-up. LESSONS: Although LGFMS is rare, it should be considered in differential diagnosis of other soft tissue tumors to avoid misdiagnosis and inappropriate treatment.