Per- and polyfluoroalkyl substances (PFAS) exposure in plasma and their blood-brain barrier transmission efficiency-A pilot study.

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.

Enrichment of Circulating Tumor Cells of Lung Cancer and Correlation With Serum Leukomonocyte and Tumor Biomarkers: A Retrospective Study.

STUDY DESIGN: Circulating tumor cells is important in the clinical diagnosis of cancer and there are a number of circulating tumor cell detection systems associated with different isolation strategies being validated. There is a novel platform, the CytoBot 2000, which utilizes a combination of physical and immunological technologies to isolate and capture circulating tumor cells. METHODS: In this retrospective study, 39 lung cancer patients and 11 normal healthy individuals were enrolled and performed circulating tumor cell tests and immunofluorescence staining with CytoBot 2000. The performance of this device was assessed by receiver operating characteristic curve. The clinical relevance of circulating tumor cells was assessed by Chi-square. The correlations between circulating tumor cell number and blood lymphocytes and tumor biomarkers were analyzed by Pearson correlation coefficient. RESULTS: The number of circulating tumor cell is significantly increased in lung cancer patients (3.74 > 0.45, P < .0001). The CytoBot 2000 presented a 100% (39/39) circulating tumor cell detection rate in lung cancer patients and 36% (4/11) in healthy individual blood samples, the sensitivity and specificity were 89.7% and 90.9%, respectively, and with the area under curve of 0.966. Further, there was a positive correlation between circulating tumor cell count and carcinoembryonic antigen 211 (R2 = 0.125, P = .027), but not blood lymphocytes (P = .089). CONCLUSIONS: This automatic platform showed excellent performance of circulating tumor cell detection by clinical sample. The tumor biomarkers increased with the number of circulating tumor cell in the lung cancer patients.

Astragaloside IV improved antioxidative stress capacity and related gene expression of the Keap1-Nrf2 pathway in grass carp (Ctenopharyngodon idella) hepatocytes under heat stress.

This study aims to investigate the protective effects of astragaloside IV (AS-IV) on the hepatocytes of grass carp (Ctenopharyngodon idella) on heat stress. Cultured cells were treated with AS-IV (0, 50, 100 and 200 µg/ml) at 28°C for 24 h and then exposed to heat stress by increasing the culturing temperature (32 ± 0.5°C) for 6 h. The increased temperatures significantly reduced cell viability and superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA) levels in the 0 µg/ml AS-IV treatment group at 32°C, but the grass carp hepatocytes treated with 100 and 200 µg/ml AS-IV had significantly increased cell viability and SOD activity and decreased MDA levels. The mRNA levels of keap1a, keap1b, nrf2, gsh-px, cat, cu-zn sod, mgst1 and il-6 were significantly lower in the 0 µg/ml AS-IV treatment group at 32°C, while those of keap1a, nrf2, gsh-px, cat, cu-zn sod, gstp1, ho-1 and il-6 were significantly higher in cells treated with 100 or 200 µg/ml AS-IV. Our findings indicate that AS-IV could enhance the antioxidative stress capacity of grass carp hepatocytes under heat stress, and its mechanism may be associated with the activation of the Keap1-Nrf2 pathway. Thus, these results provide new insights into how to alleviate heat stress in grass carp.

Emissions of Liquid Crystal Monomers from Obsolete Smartphone Screens in Indoor Settings: Characteristics and Human Exposure Risk.

Liquid crystal monomers (LCMs) have been found to accumulate in indoor environments, but the emission kinetics of LCMs from electronic devices are not well understood. Leakage from damaged liquid crystal displays may be an important mechanism for LCMs to enter the environment and become potential health hazards to humans. To address this issue, we conducted chamber experiments to characterize the emissions of LCMs from obsolete smartphone screens and estimated the doses of residential and occupational exposures to LCMs. The emission rates of the detected LCMs were in the ranges of 0.1-7 µg m-2 h-1 at 80 °C, 0.05-7 µg m-2 h-1 at 60 °C, and 0.002-0.2 µg m-2 h-1 at 25 °C. Liquid crystal monomers with large molecular weights and low volatilities tended to accumulate at screen surfaces and were re-emitted at elevated temperatures, leading to high emission rates of heavy LCMs upon thermal treatment. The estimated doses of residential and occupational exposures to individual LCMs were 0.0001-0.009 and 0.007-2 ng kg-1 d-1, respectively. As LCMs are potentially carcinogenic based on in silico assessments, LCMs emitted from obsolete smartphones in indoor settings may become human health hazards.

Measurement of octanol-air partition coefficients for liquid crystals based on gas chromatography-retention time and its implication in predicting long-range transport potential.

Liquid crystals (LCs) are widely used in the modern society, but their environmental fate and related human health effects remain inadequately recognized. To assist in better understanding the environmental fate of LCs, the octanol-air partition coefficients (KOA) of 21 target LCs were determined with a gas chromatography-retention time (GC-RT) approach. Four classes of traditional organic pollutants, including polycyclic aromatic hydrocarbons, organochlorides, polybrominated diphenyl ethers, and polychlorinated biphenyls were employed as reference or calibration compounds. Cluster analysis indicated that the reference and calibration compounds somewhat influenced the relative and absolute magnitudes of GC-RT results. A quantitative structure-property relationship (QSPR) model was constructed from the experimental results and outperformed a widely-used model, KOAWIN, in estimating log KOA of LCs. This model was used to predict log KOAs for 116 LCs with the same element compositions and similar structures as the target LCs. Overall persistence and long-range transport potential were predicted based on the measured and estimated log KOA values, yielding consistent results. Several LCs were shown to have comparable characteristic travel distances and transport efficiencies as the traditional organic pollutants, suggesting they are potential environmental pollutants and the QSPR model is applicable in predicting the environmental fate of LCs.

Prazosin inhibits the growth and mobility of osteosarcoma cells.

BACKGROUND: Osteosarcoma is a primary malignant bone tumor that frequently occurs in adolescents and children, its high aggressiveness and rapid metastasis often resulting in poor prognoses. In previous studies, Prazosin has been shown to possess anti-proliferative properties against prostate cancer and glioblastoma cells. In our study, we investigated Prazosin's underlying mechanisms and its effects on the biological behaviors of osteosarcoma cells. METHODS: Osteosarcoma cell lines MG63 and 143B were treated with different concentrations of Prazosin, and a CCK8 assay assessed its effect on cell viability. Colony formation, Transwell and flow cytometry assays were used to examine its effects on cell proliferation, cell migration, and cell invasion and apoptosis, respectively. The expression of relevant proteins was then examined using western blotting. RESULTS: Our data showed that Prazosin dose-dependently reduced the viability of MG63 and 143B cells and significantly inhibited their clonogenic ability. Moreover, Prazosin attenuated the cell migration and invasion abilities of MG63 and 143B cells when compared with the NC group. It also accelerated cell apoptosis in mitochondrial pathways by regulating Bcl-2/Bax axis and caspase 3. Furthermore, Prazosin treatment inactivated the Akt/mTOR pathway by down-regulating Akt and mTOR phosphorylation (p-Akt, p-mTOR) and the expression of P70 and cyclin D1. CONCLUSIONS: Our data highlights the fact that Prazosin inhibits cell growth, inhibits the motility of osteosarcoma cells, and promotes apoptosis, suggesting that Prazosin is a potential anti-cancer agent in osteosarcoma therapy.

Effect on Chest Deformation of Simultaneous Correction of Pectus Excavatum with Scoliosis.

Objective: This paper is to understand the effect of simultaneous correction of pectus excavatum with scoliosis and to provide some useful information for clinical orthopedic surgery design. Methods: The method of a three-dimensional reconstruction has been used to the reconstruction of the chest model of pectus excavatum with scoliosis, and the numerical stimulation has been conducted to the process of minimally invasive correction. Three kinds of correction methods have been considered in the numerical simulation, stretch spine, stretch spine and minimally invasive correction at the same time, and release stretch spine after stretch spine and minimally invasive correction of pectus excavatum at the same time. Results: It is found that stretch spine may help to correction of scoliosis but aggravate the sternum collapse, and release stretch spine after stretch spine and minimally invasive correction at the same time could not only be good at scoliosis but also improve the collapse of the sternum, which could help to improve the heartbeat and breath of the patients. Conclusion: Among the three kinds of correction methods, release stretch spine after stretch spine and minimally invasive correction at the same time could help to improve both the scoliosis and the collapse of the sternum.

Label-Free Fluorescent Detection of Trypsin Activity Based on DNA-Stabilized Silver Nanocluster-Peptide Conjugates.

Trypsin is important during the regulation of pancreatic exocrine function. The detection of trypsin activity is currently limited because of the need for the substrate to be labeled with a fluorescent tag. A label-free fluorescent method has been developed to monitor trypsin activity. The designed peptide probe consists of six arginine molecules and a cysteine terminus and can be conjugated to DNA-stabilized silver nanoclusters (DNA-AgNCs) by Ag-S bonding to enhance fluorescence. The peptide probe can also be adsorbed to the surface of graphene oxide (GO), thus resulting in the fluorescence quenching of DNA-AgNCs-peptide conjugate because of Förster resonance energy transfer. Once trypsin had degraded the peptide probe into amino acid residues, the DNA-AgNCs were released from the surface of GO, and the enhanced fluorescence of DNA-AgNCs was restored. Trypsin can be determined with a linear range of 0.0-50.0 ng/mL with a concentration as low as 1 ng/mL. This label-free method is simple and sensitive and has been successfully used for the determination of trypsin in serum. The method can also be modified to detect other proteases.

Abnormal Pupil Finding After an Orbital Floor Fracture in a Child.

PURPOSE: Trauma to the pupillary fibers can occur during repair of orbital floor fracture resulting in a fixed and dilated pupil. The authors report, discuss, and propose an etiology of an abnormal pupil in a child with an orbital floor fracture before surgical repair. METHODS: A case report is described. RESULTS: Although the orbital fracture was repaired, anisocoria persisted 18 months after the initial trauma. CONCLUSIONS: Pupillary function must be assessed before surgical repair of an orbital floor fracture as damage of the pupillary fibers can occur secondary to the orbital floor fracture.

Damage to dopaminergic neurons is mediated by proliferating cell nuclear antigen through the p53 pathway under conditions of oxidative stress in a cell model of Parkinson's disease.

Oxidative stress is widely considered as a central event in the pathogenesis of Parkinson's disease (PD). The mechanisms underlying the oxidative damage-mediated loss of dopaminergic neurons in PD are not yet fully understood. Accumulating evidence has indicated that oxidative DNA damage plays a crucial role in programmed neuronal cell death, and is considered to be at least partly responsible for the degeneration of dopaminergic neurons in PD. This process involves a number of signaling cascades and molecular proteins. Proliferating cell nuclear antigen (PCNA) is a pleiotropic protein affecting a wide range of vital cellular processes, including chromatin remodelling, DNA repair and cell cycle control, by interacting with a number of enzymes and regulatory proteins. In the present study, the exposure of PC12 cells to 1-methyl-4-phenylpyridinium (MPP+) led to the loss of cell viability and decreased the expression levels of PCNA in a dose- and time-dependent manner, indicating that this protein may be involved in the neurotoxic actions of MPP+ in dopaminergic neuronal cells. In addition, a significant upregulation in p53 expression was also observed in this cellular model of PD. p53 is an upstream inducer of PCNA and it has been recognized as a key contributor responsible for dopaminergic neuronal cell death in mouse models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. This indicates that MPP+-induced oxidative damage is mediated by the downregulation of PCNA through the p53 pathway in a cellular model of PD. Thus, our results may provide some novel insight into the molecular mechanisms responsible for the development of PD and provide new possible therapeutic targets for the treatment of PD.

[Clinicopathological analysis of aggressive angiomyxoma].

OBJECTIVE: To explore the clinicopathological characteristics of aggressive angiomyxoma (AAM) so as to boost the level of diagnosis and treatment. METHODS: Seven cases of aggressive angiomyxoma were studied with light microscope and immunohistochemistry. Antibody of Vimentin, Desmin, CD34, smooth muscle actin (SMA), estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), S-100, p53 and Ki67 were used. RESULTS: There were 3 males and 4 females with an average age of 43.1 years. Three patients had urinary compressive complaints while others were symptom-free. All underwent surgical resection. Three patients were recurrent after operation. The tumor was generally nodular and its cut surface appeared jelly-like. Histologically, on myxoid stroma background, it was composed of a mixture of spindle and stellar cells without atypical cell and mitosis. There were various-sized vessels with thin to thick walls. The scattered muscle-like cells had a perivascular distribution. Immunohistochemistry showed that tumor cells were positive for Vimentin(+)7/7, Desmin(+)7/7, CD34(+)3/7, SMA(+)2/7, ER(+)6/7, p53(+)4/7, Ki67(+) 1% - 8% and negative for PR, AR and S-100. CONCLUSIONS: As a rare soft tissue tumor, AAM extremely rare in males. Owing to its local invasion and high recurrence, extensive resection and long-term follow-up are necessary.

[The effects of SV40 PolyA sequence and its AATAAA signal on upstream GFP gene expression and transcription termination].

SV40 PolyA (Simian virus 40 PolyA, also called PolyA) sequence is DNA sequence (240 bp) that possesses the activity of transcription termination and can add PolyA tail to mRNA. PolyA contains AATAAA hexanucleotide polyadenylation signal. Fourteen copies of Alu in sense orientation (Alu14) were inserted downstream of GFP in pEGFP-C1 to construct pAlu14 plasmid, and then HeLa cells were transiently transfected with pAlu14. Northern blot and fluorescence microscope were used to observe GFP RNA and protein expressions. Our results found that Alu tandem sequence inhibited remarkably GFP gene expression, but produced higher-molecular-mass GFP fusion RNA. PolyA and its sequence that was deleted AATAAA signal in sense or antisense orientation were inserted between GFP and Alu tandem sequence in pAlu14. The results showed that all the inserted PolyA sequences partly eliminated the inhibition induced by Alu14. PolyA sequences without AATAAA signal in sense or antisense orientation still induced transcription termination. Antisense PolyA (PolyAas) was divided into four fragments that all are 60 bp long and the middle two fragments were named 2F2R and 3F3R. 2F2R or 3F3R was inserted upstream of Alu tandem sequence in pAlu14. The molecular mass of GFP fusion RNA increased when the copy number of 2F2R increased. 2F2R can support transcription elongation when 2F2R is located upstream of other 2F2R. Nevertheless, 2F2R located upstream of Alu tandem sequence can induce transcription termination. Inserting one copy or 64 copies of 3F3R in upstream of Alu tandem sequence caused the production of lower-molecular-mass GFP RNA.