Analysis of microplastics in various foods and assessment of aggregate human exposure via food consumption in korea.

Evidence of microplastics in humans has recently been demonstrated. The primary route of human exposure to microplastics is consumption of contaminated food and water. However, quantitative estimations of exposure to microplastics are limited, which hinders human health risk assessments. In this study, abundances of microplastics were measured in eight food types, comprising 90 products of table salts, soy sauces, fish sauces, salted seafood, seaweed, honey, beer, and beverage. Aggregate human exposure to microplastics via food consumption was assessed based on the number and mass of microplastics, using deterministic calculations and Monte Carlo simulations. The determinations revealed that average adult Koreans likely ingest 1.4 × 10-4 and 3.1 × 10-4 g of microplastics per week, respectively. These results are orders of magnitude smaller than earlier estimates of 0.1-5 g of microplastics per week that likely chose experimental outliers. Therefore, careful selection of literature data and estimation methods is needed to provide more realistic exposure estimations from microplastic counts. This study extends our understanding of MP occurrence in food and provides a more thorough estimate of aggregate microplastic exposure via food consumption.

Growth promotion effect of red ginseng dietary fiber to probiotics and transcriptome analysis of Lactiplantibacillus plantarum.

Background: Red ginseng marc, the residue of red ginseng left after water extraction, is rich in dietary fiber. Dietary fiber derived from fruits or vegetables can promote the proliferation of probiotics, and it is a key technology in the food industry to increase the productivity of probiotics by adding growth-enhancing substances such as dietary fiber. In this study, the effect of red ginseng dietary fiber (RGDF) on the growth of probiotic bacterial strains was investigated at the phenotypic and genetic levels. Methods: We performed transcriptome profiling of Lactiplantibacillus plantarum IDCC3501 in two phases of culture (logarithmic (L)-phase and stationary (S)-phase) in two culture conditions (with or without RGDF) using RNA-seq. Differentially expressed genes (DEGs) were identified and classified according to Gene Ontology terms. Results: The growth of L.plantarum IDCC3501 was enhanced in medium supplemented with RGDF up to 2%. As a result of DEG analysis, 29 genes were upregulated and 30 were downregulated in the RGDF-treated group in the L-phase. In the S-phase, 57 genes were upregulated and 126 were downregulated in the RGDF-treated group. Among the upregulated genes, 5 were upregulated only in the L-phase, 10 were upregulated only in the S-phase, and 3 were upregulated in both the L- and S-phases. Conclusions: Transcriptome analysis could be a valuable tool for elucidating the molecular mechanisms by which RGDF promotes the proliferation of L.plantarum IDCC3501. This growth-promoting effect of RGDF is important, since RGDF could be used as a prebiotic source without additional chemical or enzymatic processing.

Anti-Inflammatory Effects of Limosilactobacillus fermentum KGC1601 Isolated from Panax ginseng and Its Probiotic Characteristics.

We investigated the potential probiotic properties of Limosilactobacillus fermentum KGC1601 isolated from Panax ginseng. Ginseng cultivated in an experimental field of the Korea Ginseng Research Institute was fermented, followed by single colony selection from MRS agar. We performed 16s-rRNA sequencing and whole-genome analysis to identify L. fermentum and evaluate the biosafety parameters of this strain, respectively. We confirmed this strain was susceptible to six antibiotics, as proposed by the European Food Safety Authority, did not produce biogenic amines, and did not exhibit any hemolytic activity. Acid resistance and bile salt tolerance, which are essential properties of a probiotic agent, were investigated. Notably, distinguishing properties of this strain were that it exhibited excellent bile salt tolerance and anti-inflammatory effects. The excellent bile salt tolerance was confirmed by scanning electron microscopy. Through qRT-PCR and ELISA studies, it was revealed that L. fermentum KGC1601 pre-treatment up-regulates anti-inflammatory cytokines and down-regulates pro-inflammatory cytokines in RAW 264.7 cells. Consequently, we suggested that L. fermentum KGC1601 can be safely used as a potential anti-inflammatory functional probiotic agent.

The balance between Bayesian inference and default mode determines the generation of tinnitus from decreased auditory input: A volume entropy-based study.

Along with phantom pain, tinnitus, a phantom auditory perception occurring in the absence of an external acoustic stimulus, is one of the most representative phantom perceptions that develops in subjects with decreased peripheral sensory input. Although tinnitus is closely associated with peripheral hearing loss (HL), it remains unclear why only some individuals with HL develop tinnitus. In this study, we investigated the differences between 65 HL with tinnitus (HL-T) and 104 HL with no tinnitus (HL-NT) using a resting-state electroencephalography data-based volume entropy model of the brain network, by comparing the afferent node capacities, that quantify the contribution of each node to the spread of information, of all Brodmann areas. While the HL-T group showed increased information flow in areas involved in Bayesian inference (the left orbitofrontal cortex, the left subgenual anterior cingulate cortex, and the left ventrolateral prefrontal cortex) and auditory memory storage (the right hippocampus/parahippocampus), the HL-NT group showed increased afferent node capacity in hub areas of the default mode network (DMN; the right posterior cingulate cortex and the right medial temporal gyrus). These results suggest that the balance of activity between the Bayesian inferential network (updating missing auditory information by retrieving auditory memories from the hippocampus/parahippocampus) and DMN (maintaining the "silent status quo") determines whether phantom auditory perception occurs in a brain with decreased peripheral auditory input.

Microplastics in Food: A Review on Analytical Methods and Challenges.

Human exposure to microplastics contained in food has become a significant concern owing to the increasing accumulation of microplastics in the environment. In this paper, we summarize the presence of microplastics in food and the analytical methods used for isolation and identification of microplastics. Although a large number of studies on seafood such as fish and shellfish exist, estimating the overall human exposure to microplastics via food consumption is difficult owing to the lack of studies on other food items. Analytical methods still need to be optimized for appropriate recovery of microplastics in various food matrices, rendering a quantitative comparison of different studies challenging. In addition, microplastics could be added or removed from ingredients during processing or cooking. Thus, research on processed food is crucial to estimate the contribution of food to overall human microplastic consumption and to mitigate this exposure in the future.

Large-scale pharmacogenomics based drug discovery for ITGB3 dependent chemoresistance in mesenchymal lung cancer.

Even when targets responsible for chemoresistance are identified, drug development is often hampered due to the poor druggability of these proteins. We systematically analyzed therapy-resistance with a large-scale cancer cell transcriptome and drug-response datasets and predicted the candidate drugs based on the gene expression profile. Our results implicated the epithelial-mesenchymal transition as a common mechanism underlying resistance to chemotherapeutic drugs. Notably, we identified ITGB3, whose expression was abundant in both drug resistance and mesenchymal status, as a promising target to overcome chemoresistance. We also confirmed that depletion of ITGB3 sensitized cancer cells to conventional chemotherapeutic drugs by modulating the NF-κB signaling pathway. Considering the poor druggability of ITGB3 and the lack of feasible drugs to directly inhibit this protein, we took an in silico screening for drugs mimicking the transcriptome-level changes caused by knockdown of ITGB3. This approach successfully identified atorvastatin as a novel candidate for drug repurposing, paving an alternative path to drug screening that is applicable to undruggable targets.

Multimode-pumped Raman amplification of a higher order mode in a large mode area fiber.

We report the first demonstration of Raman amplification in a fiber of a single Bessel-like higher order mode using a multimode pump source. We amplify the LP08-mode with a 559-µm2 effective mode area at a signal wavelength of 1115 nm in a pure-silica-core step-index fiber. A maximum of 18 dB average power gain is achieved in a 9-m long gain fiber, with output pulse energy of 115 µJ. The Raman pump source comprises a pulsed 1060 nm ytterbium-doped fiber amplifier with V-value ~30, which is matched to the Raman gain fiber. The pump depletion as averaged over the signal pulses reaches 36.7%. The conversion of power from the multimode pump into the signal mode demonstrates the potential for efficient brightness enhancement with low amplification-induced signal mode purity degradation.

Screening of cytotoxic or cytostatic flavonoids with quantitative Fluorescent Ubiquitination-based Cell Cycle Indicator-based cell cycle assay.

The Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) system can be used not only to study gene expression at a specific cell cycle stage, but also to monitor cell cycle transitions in real time. In this study, we used a single clone of FUCCI-expressing HeLa cells (FUCCI-HeLa cells) and monitored the cell cycle in individual live cells over time by determining the ratios between red fluorescence (RF) of RFP-Cdt1 and green fluorescence (GF) of GFP-Geminin. Cytotoxic and cytostatic compounds, the latter of which induced G2 or mitotic arrest, were identified based on periodic cycling of the RF/GF and GF/RF ratios in FUCCI-HeLa cells treated with anti-cancer drugs. With this cell cycle monitoring system, ten flavonoids were screened. Of these, apigenin and luteolin, which have a flavone backbone, were cytotoxic, whereas kaempferol, which has a flavonol backbone, was cytostatic and induced G2 arrest. In summary, we developed a system to quantitatively monitor the cell cycle in real time. This system can be used to identify novel compounds that modulate the cell cycle and to investigate structure-activity relationships.

Quercetin induced ROS production triggers mitochondrial cell death of human embryonic stem cells.

Small molecules to selectively induce cell death of undifferentiated human pluripotent stem cells (hPSCs) have been developed with the aim of lowering the risk of teratoma formation during hPSC-based cell therapy. In this context, we have reported that Quercetin (QC) induces cell death selectively in hESCs via p53 mitochondrial localization. However, the detailed molecular mechanism by which hESCs undergo selective cell death induced by QC remains unclear. Herein, we demonstrate that mitochondrial reactive oxygen species (ROS), strongly induced by QC in human embryonic stem cells (hESCs) but not in human dermal fibroblasts (hDFs), were responsible for QC-mediated hESC's cell death. Increased p53 protein stability and subsequent mitochondrial localization by QC treatment triggered mitochondrial cell death only in hESCs. Of interest, peptidylprolyl isomerase D [PPID, also called cyclophilin D (CypD)], which functions in mitochondrial permeability transition and mitochondrial cell death, was highly expressed in hESCs. Inhibition of CypD by cyclosporine A (CsA) clearly inhibited the QC-mediated loss of mitochondrial membrane potential and mitochondrial cell death. These results suggest that p53 and CypD in the mitochondria are critical for the QC-mediated induction of cell death in hESCs.

BCL2 induced by LAMTOR3/MAPK is a druggable target of chemoradioresistance in mesenchymal lung cancer.

Mesenchymal-type cancers after epithelial mesenchymal transition (EMT) were recently shown to acquire chemoresistance through expressing EMT specific transcription factors. However, druggable (or actionable) target(s) for chemoresistance in mesenchymal-type lung cancers remain unidentified. Here, we used a public clinical genomic database and mesenchymal lung cancer cells (MLCC) model derived from the A549 lung adenocarcinoma cell line to demonstrate that BCL2 expression, which is highly induced in mesenchymal-type lung cancers, as a predictor of poor prognosis in mesenchymal lung cancer patients and association with acquired chemoradioresistance. Thereby, combination treatment with BH3 mimetics, such as ABT-263 and ABT-737, clearly attenuated chemoresistance in MLCCs. BCL2 expression in MLCCs was induced by ERK1 activity through the upregulation of the MEK1/ERK1 scaffold protein MEK partner-1 (MP1). Interfering with the MEK1/MP1/ERK1 axis using a MEK1 inhibitor or MP1 depletion repressed BCL2 expression and sensitized MLCCs to chemoradiotherapy. Taken together, our results suggest that targeting druggable proteins in the MEK1/MP1/ERK1/BCL2 axis, such as MEK1 or BCL2, with currently available FDA approved drugs is a currently feasible approach to improve clinical outcomes of mesenchymal lung cancer patients.

PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells By Enhancing the PI3K/AKT/SOX2 Axis.

Basic fibroblast growth factor (bFGF) supplementation is critical to maintain the pluripotency of human pluripotent stem cells (hPSCs) through activation of PI3K/AKT, rather than MEK/ERK pathway. Thus, elaborate molecular mechanisms that preserve PI3K/AKT signaling upon bFGF stimulation may exist in hPSCs. Protein arginine methyltransferase 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under bFGF-deprived conditions. Direct interaction of membrane-localized PRMT8 with p85, a regulatory subunit of PI3K, was associated with accumulation of phosphoinositol 3-phosphate and consequently high AKT activity. Furthermore, the SOX2 induction, which was controlled by the PRMT8/PI3K/AKT axis, was linked to mesodermal lineage differentiation. Thus, we propose that PRMT8 in hESCs plays an important role not only in maintaining pluripotency but also in controlling mesodermal differentiation through bFGF signaling toward the PI3K/AKT/SOX2 axis. Stem Cells 2017;35:2037-2049.

Induction of integrin ß3 by sustained ERK activity promotes the invasiveness of TGFß-induced mesenchymal tumor cells.

The emerging roles of integrin ß3 in the epithelial-mesenchymal transition (EMT) and drug resistance underline its significance in cancer metastasis and recurrence. However, the molecular mechanism underlying the distinctive expression of integrin ß3 is less understood. In the present report, we demonstrated that repetitive exposure to transforming growth factor ß (TGFß), a potent inducer of the EMT, significantly increased the expression of integrin ß3 in A549 lung cancer cells with distinct mesenchymal properties, such as actin filament reorganization and invasiveness. Notably, integrin ß3 expression was associated to cancer cell invasion and migration, and was determined not by Smad4-dependent pathways but by sustained ERK1/2 activity in the mesenchymal cancer cells. These data suggest that ERK1/2 plays an important role in mediating non-canonical TGFß signal pathways for integrin ß3 expression. Therefore, the targeting of the MEK/ERK activity seems to be a promising therapeutic approach to suppressing EMT-associated cancer progression that potentially occurs in TGFß-enriched microenvironments, which would lead to the suppression of the metastatic potential of integrin ß3-positive cancer cells.

Chronic TGFß stimulation promotes the metastatic potential of lung cancer cells by Snail protein stabilization through integrin ß3-Akt-GSK3ß signaling.

Chronic exposure to TGFß, a frequent occurrence for tumor cells in the tumor microenvironment, confers more aggressive phenotypes on cancer cells by promoting their invasion and migration while at the same time increasing their resistance to the growth-inhibitory effect of TGFß. In this study, a transdifferentiated (TD) A549 cell model, established by chronically exposing A549 cells to TGFß, showed highly invasive phenotypes in conjunction with attenuation of Smad-dependent signaling. We show that Snail protein, the mRNA expression of which strongly correlates with a poor prognosis in lung cancer patients, was highly stable in TD cells after TGFß stimulation. The increased protein stability of Snail in TD cells correlated with elevated inhibitory phosphorylation of GSK3ß, resulting from the high Akt activity. Notably, integrin ß3, whose expression was markedly increased upon sustained exposure to TGFß, was responsible for the high Akt activity as well as the increased Snail protein stability in TD cells. Consistently, clinical database analysis on lung cancer patients revealed a negative correlation between overall survival and integrin ß3 mRNA levels. Therefore, we suggest that the integrin ß3-Akt-GSK3ß signaling axis plays an important role in non-canonical TGFß signaling, determining the invasive properties of tumor cells chronically exposed to TGFß.

Clinical Analysis of Delayed Surgical Epidural Hematoma.

OBJECTIVE: A small epidural hematoma (EDH) that has been diagnosed to be nonsurgical by initial brain computed tomography (CT) can increase in size and need surgical removal, resulting in a poor prognosis. However, there have been few studies, which focused delayed operated EDH. Therefore, we analyzed the clinical factors to determine the predicting factors of delayed operated EDH. METHODS: Between January 2011 and January 2014, 90 patients, who were admitted due to EDH, were enrolled in this study. None of the patients were indicated for operation initially. Based on the presence of surgery, we classified the patients into a delayed-surgery group (DG) and a non-surgical group (NG). Additionally, we analyzed them according to the following: time interval between the trauma and the initial CT, gender, age, medical history, drinking, change of mean arterial pressure (MAP), volume of EDH and other traumatic brain lesion. RESULTS: Among the 90 patients, the DG was 19 patients. Compared with NG, the DG revealed increased MAP, less presence of drinking, and a short time interval (DG vs. NG: +9.684 mm Hg vs. -0.428 mm Hg, 5.26% vs. 29.58%, 1.802 hours vs. 5.707 hours, respectively, p<0.05). Analyzing the time interval with receiver operating characteristic, there was 88.2% sensitivity and 68.3% specificity at the 2.05-hour cut-off value (area under the curve=0.854). CONCLUSION: According to our results, the time interval between the trauma and the initial CT along with blood pressure change are potential predicting factors in the cases of delayed operation of EDH.

Middle Meningeal Artery Embolization in Recurrent Chronic Subdural Hematoma Combined with Arachnoid Cyst.

Chronic subdural hematoma (CSDH) is a collection of old blood and its breakdown products between the surface of the brain parenchyma and the outermost layer called the dura. The most common treatment option for primary CSDH is burr-hole trephination; however, the treatment method for recurrent CSDH is still widely debated. An arachnoid cyst (AC) is a sac filled with cerebrospinal fluid located between the brain or spinal cord and the arachnoid membrane, which is one of the three meninges covering the brain or spinal cord. Although it is rare, the cyst is associated with CSDH in juveniles, and the recurrence rate of CSDH increases in such cases. Much of the literature has supported the preventive role of middle meningeal artery (MMA) embolization in recurrent CSDH. We report a 13-year-old male patient with recurrent CSDH and AC where the early intervention of MMA embolization was proven effective in preventing the further recurrence of CSDH.