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The use of precision medicine for chemotherapy requires the individualization of the therapeutic regimen for each patient. This approach improves treatment efficacy and reduces the probability of administering ineffective drugs. To ensure accurate decision-making in a timely manner, anticancer drug efficacy tests must be performed within a short timeframe using a small number of cancer cells. These requirements can be satisfied via microfluidics-based drug screening platforms, which are composed of complex fluidic channels and closed systems. Owing to their complexity, skilled manipulation is required. In this study, we developed a microfluidic platform, to accurately perform multiple drug efficacy tests using a small number of cells, which can be conducted via simple manipulation. As it is a small, open-chamber system, a minimal number of cells could be loaded through simple pipetting. Furthermore, the extracellular matrix gel inside the chamber provides an in vivo-like environment that enables the localized delivery of the drugs to spontaneously diffuse from the channels underneath the chamber without a pump, thereby efficiently and robustly testing the efficacy and resistance of multiple drugs. We demonstrated that this platform enabled the rapid and facile testing of multiple drugs using a small number of cells (~ 10,000) over a short period of time (~ 2 days). These results provide the possibility of using this powerful platform for selecting therapeutic medication, developing new drugs, and delivering personalized medicine to patients. [ABSTRACT FROM AUTHOR]

• A full-scale WWTP treating PRW was monitored to evaluate pollutant removal. • Removal efficiencies of SCOD and benzene in influent were achieved more than 70%. • Sulfuritalea and Azoarcus were mainly responsible for degradation of benzene. • Ottowia and Thauera were possibly involved in phenol degradation as well. This research investigated the process efficiency and microbial communities and their diversity in a full-scale wastewater treatment plant (WWTP) fed with petroleum refining wastewater (PRW) that contained toxic hydrocarbon contaminants and carcinogens. Process parameters and bacterial community structures were monitored for six months to create a link between microbial dynamics and influent characteristics of petrochemical wastewater. The WWTP showed a stable process with efficiencies >70% for both soluble chemical oxygen demand (SCOD) and benzene removal. More than 30 genera were identified by metagenomic analysis, and the bacterial populations changed significantly during the operation period. Among them, genera Sulfuritalea (11.9 ± 3.5%) , Ottowia (4.3 ± 2.2%) , Thauera (3.1 ± 7.2%) and Hyphomicrobium (1.3 ± 0.7%) were dominant and important bacterial genera that may have been responsible for the degradation of aromatic compounds such as benzene and phenol. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the major causes of therapeutic failure in breast cancer patients. In this study, the mechanism of chemoresistance in human triple-negative breast cancer (TNBC) cells (MDA-MB-231) induced by doxorubicin (DOX) gradient was investigated. These DOX-resistant cells showed higher drug efflux rate, increased anchorage-independent growth when cultured in suspension, and increased tumor-forming ability in nude mice, compared to the wild-type MDA-MB-231 cells. RNA sequencing analysis showed an increase in the expression of genes involved in membrane transport, antiapoptosis, and histone regulation. Kaplan-Meier plot analysis of TNBC patients who underwent preoperative chemotherapy showed that the relapse free survival (RFS) of patients with high HIST1H2BK (histone cluster 1 H2B family member k) expression was significantly lower than that of patients with low HIST1H2BK expression. Quantitative real-time PCR confirmed that the level of HIST1H2BK expression was increased in resistant cells. The cytotoxicity analysis showed that the DOX resistance of resistant cells was reduced by treatment with a histone deacetylase (HDAC) inhibitor. Our results suggest that, in DOX-resistant cells, HIST1H2BK expression can be rapidly induced by the high expression of genes involved in membrane transport, antiapoptosis, and histone regulation. In conclusion, chemoresistance in MDA-MB-231 cells can occur in a relatively short period by DOX gradient via this previously known mechanism of resistance, and DOX resistance is dependent on the specificity of resistant cells to HDAC. [ABSTRACT FROM AUTHOR]

Spheroids are recognized for replicating the physiological microenvironment of tumours. However, because of the lack of controllability of the spheroid size, the response to anticancer drugs is variable in conventional spheroid culture methods. In this paper, we describe a method to generate several hundreds of spheroids of various types of cancer cells including patient derived cancer cells (PDCs) using a microfluidic device with pillars (diameter: 40 μm, height: 70 μm, center-to-center distance: 140 μm), called a microfluidic pillar array (μFPA) device. About three hundred glioma (U87) spheroids were obtained in the μFPA device within 3 days, and about 90% of them ranged from 175 to 225 μm. These spheroids were more resistant to doxorubicin at 10 μM than U87 cells in a monolayer. The former showed higher expression of CD133, a cancer stem cell marker, than the latter. Hypoxia inducible factor-1α (HIF-1α), another cancer stem cell marker, was found in the nucleus of the former, but found in the cytoplasm of the cells in a monolayer. Drug responses of spheroids of another glioma cell line (U251) and triple negative breast cancer (TNBC) primary cells were also easily quantified by measuring changes in spheroid size at different concentrations of their respective drug on the μFPA device. The μFPA device can be a powerful platform for obtaining uniform spheroids and monitoring the drug response of cancer cells including PDCs. [ABSTRACT FROM AUTHOR]

Purpose: To report successful endovascular treatment of a previously implanted balloon-expandable stent bursting fracture with concomitant large pseudoaneurysm formation in the left common iliac artery (LCIA). Case Report: A 72-year-old man had been previously treated with balloon-expandable stents for severe stenotic lesion in the LCIA and left external iliac artery. Seven years later, the patient complained pain in both lower legs and back. Angiography demonstrated a 3.5-cm-sized pseudoaneurysm in the LCIA with embedded metal fragments around the lesion. An endovascular treatment was selected using a limb extension graft for endovascular aortic aneurysm repair. The device was successfully deployed, and no endoleak was observed. At 1-month follow-up, computed tomography scan confirmed patency of the implanted stent graft devices in the LCIA and the absence of any endoleak. Conclusion: Endovascular approach using a limb extension graft stent for endovascular aortic aneurysm repair can be used for treating stent fracture-related pseudoaneurysm in the common iliac artery. [ABSTRACT FROM AUTHOR]

Background: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA+/L444P) mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a selective dopaminergic mitochondrial neurotoxin. Method: We used GBA+/L444P mice, α-synuclein knockout (SNCA-/-) mice at 8 months of age, and adeno-associated virus (AAV)-human GBA overexpression to investigate the rescue effect of DA neuronal loss and susceptibility by MPTP. Mitochondrial morphology and functional assay were used to identify mitochondrial defects in GBA+/L444P mice. Motor behavioral test, immunohistochemistry, and HPLC were performed to measure dopaminergic degeneration by MPTP and investigate the relationship between GBA mutation and α-synuclein. Mitochondrial immunostaining, qPCR, and Western blot were also used to study the effects of α-synuclein knockout or GBA overexpression on MPTP-induced mitochondrial defects and susceptibility. Results: L444P GBA heterozygous mutation reduced GBA protein levels, enzymatic activity and a concomitant accumulation of α-synuclein in the midbrain of GBA+/L444P mice. Furthermore, the deficiency resulted in defects in mitochondria of cortical neurons cultured from GBA+/L444P mice. Notably, treatment with MPTP resulted in a significant loss of dopaminergic neurons and striatal dopaminergic fibers in GBA+/L444P mice compared to wild mice. type (WT) mice. Levels of striatal DA and its metabolites were more depleted in the striatum of GBA+/L444P mice. Behavioral deficits, neuroinflammation, and mitochondrial defects were more exacerbated in GBA+/L444P mice after MPTP treatment. Importantly, MPTP induced PD-like symptoms were significantly improved by knockout of α-synuclein or augmentation of GBA via AAV5-hGBA injection in both WT and GBA+/L444P mice. Intriguingly, the degree of reduction in MPTP induced PD-like symptoms in GBA+/L444P α-synuclein (SNCA)-/- mice was nearly equal to that in SNCA-/- mice after MPTP treatment. Conclusion: Our results suggest that GBA deficiency due to L444P GBA heterozygous mutation and the accompanying accumulation of α-synuclein render DA neurons more susceptible to MPTP intoxication. Thus, GBA and α-synuclein play dual physiological roles in the survival of DA neurons in response to the mitochondrial dopaminergic neurotoxin, MPTP. [ABSTRACT FROM AUTHOR]

Aberrant interleukin-1 beta (IL-1β) expression is associated with cancer development, metastasis, and poor prognosis. Here, we have investigated the regulatory mechanism of IL-1β expression, and the inhibitory effect of zerumbone (ZER) on IL-1β expression and IL-1β-induced signatures, including cell invasion and signaling activation in triple negative breast cancer (TNBC) cells. The basal IL-1β and cell invasiveness levels were significantly higher in TNBC cells, compared with non-TNBC cells. The invasiveness of TNBC cells was also increased following IL-1β treatment. In contrast, the invasiveness of TNBC cells was decreased following IL-1 receptor antagonist (IL-1RA) treatment. Additionally, the basal IL-1β level and the invasiveness of TNBC cells were decreased by Bay11-7085. In contrast, overexpression of NF-κB (p65) caused an increase in IL-1β expression in TNBC cells. Our results showed that treatment with ZER decreased the basal IL-1β expression level, and the phosphorylation level of NF-κB, in TNBC cells. Furthermore, we found that ZER completely suppressed IL-1β-induced NF-κB phosphorylation, but did not suppress IL-1β-induced Akt phosphorylation, in TNBC cells. Our results also demonstrate that IL-1β-induced cell invasion is suppressed by ZER in TNBC cells. Taken together, we demonstrated that IL-1β expression is regulated by the NF-κB-dependent pathway, and that elevated IL-1β is directly influencing the invasiveness of TNBC cells. ZER down-regulates IL-1β expression through the inhibition of NF-κB activity, and then suppresses cell invasiveness of TNBC. [ABSTRACT FROM AUTHOR]

Fibronectin (FN), an extracellular matrix ligand, plays a pivotal role in cell adhesion, migration, and oncogenic transformation. Aberrant FN expression is associated with poor prognoses in various types of cancer, including breast cancer. In the current study, we investigated the relationship between FN induction and HER2 expression in breast cancer cells. Our results showed that the level of FN expression increased in response to HER family ligands, EGF and TGF-α in a time- and dose-dependent manner. On the other hand, EGF-induced FN expression decreased in response to trastuzumab, which is a HER2-targeted monoclonal antibody. However, EGF-induced FN expression was not affected by trastuzumab in JIMT-1 breast cancer cells, which are trastuzumab insensitive cells. Next, we introduced the HER2 gene into MDA-MB231 cells to verify the relationship between FN and HER2. The level of FN expression significantly increased in HER2-overexpressed MDA-MB231 cells. In contrast, the induction of FN by HER2 was significantly decreased in response to trastuzumab treatment. In addition, the induction of FN by HER2 was down-regulated by the MEK 1/2 specific inhibitor, U0126. Using conditioned culture media of vec- and HER2-overexpressed MDA-MB231 cells, we observed the cell morphology, adhesion, and invasion of MDA-MB231 cells. Interestingly, in conditioned culture media of HER2-overexpressed MDA-MB231 cells, the cell morphology was altered, and adhesion and invasion of MDA-MB231 cells significantly increased. In addition, our results showed that recombinant human FN augmented cell adhesion and invasion of MDA-MB231 cells while these inductions decreased in response to an FN inhibitor. Therefore, we demonstrated that the induction of FN by HER2 triggers cell adhesion and invasion capacities. [ABSTRACT FROM AUTHOR]

Abstract: The as-built building information model (BIM) has a huge potential for enhancing the efficiency of building and maintenance operations. To facilitate existing-structure data acquisition for the as-built BIM, a terrestrial laser scanner, which is fast, simple to use, and yet highly accurate, is widely employed. However, as-built BIM creation of building interiors using scanned point clouds incurs critical difficulties: the complex design of indoor structures, not to mention obstacles, necessitates time-consuming manual operation and resultantly huge data sizes, which often leads to system slow-down or failure. To manage this problem, most of the recent and current research has looked to full automation; yet facility management personnel still rely on traditional field measurements because their qualitative results can only be obtained under ideal conditions or with some errors. Alternatively, in this paper, a more practical semi-automatic methodology for improved productivity of as-built BIM creation with respect to large and complex indoor environments is proposed. The proposed approach produces three-dimensional (3D) geometric drawings through three steps: segmentation for plane extraction, refinement for removal of noisy points, and boundary tracing for outline extraction. The experimental results for two test sites, a relatively simple corridor and a complex atrium, showed a high data-size reduction rate: to 3.8 and 4.3% of the original sizes, out of 51.5 and 111.5million points, respectively. Based on the automatically produced geometric drawings and the remaining points, manual as-built BIM creation was conducted. Using the extracted lines as guides, each object and its relationship were more easily identified and modeled. At the same time, the great reduction in the point clouds' data sizes enabled the modeler, using the BIM software, to efficiently manipulate the geometric drawing without system slow-down or failure. The proposed approach was shown to be a potentially effective means of improving productivity and reliability in complex indoor as-built BIM production. [Copyright &y& Elsevier]

Abstract: Students’ learning has been the center of schooling. This study examined the contribution of situational interest motivation and cognitive engagement in workbooks to student achievement in learning health-related fitness knowledge. Situational interest, performance on solving workbook problems, and knowledge gain in cardio-respiratory fitness and benefits were measured in 670 third-grade students from 13 randomly selected urban elementary schools. Structural equation modeling and regression curve estimation analyses revealed that situational interest contributed little to workbook performance and knowledge gain. Performance on solving workbook problems contributed significantly to knowledge gain. The results also show that skipping workbook tasks had stronger negative impact on knowledge gain than performing the tasks incorrectly, suggesting the importance of engaging students in the learning process by attempting the workbook tasks. The findings reinforced the value of using workbooks to facilitate cognitive knowledge learning in physical education, but raised questions about the direct function of situational interest on engaging students in cognitive learning. [Copyright &y& Elsevier]

Background: The biological effects of CD24 (FL-80) cross-linking on breast cancer cells have not yet been established. We examined the impact of CD24 cross-linking on human breast cancer cell line MCF-7. Methods: MCF-7 and MDA-MB-231 cells were treated with anti-rabbit polyclonal IgG or antihuman CD24 rabbit polyclonal antibodies to induce cross-linking, and then growth was studied. Changes in cell characteristics such as cell cycle modulation, cell death, survival in threedimensional cultures, adhesion, and migration ability were assayed after CD24 cross-linking in MCF-7. Results: Expression of CD24 was analyzed by flow cytometry in MDA-MB-231 and MCF-7 cells where 2% and 66% expression frequencies were observed, respectively. CD24 cross-linking resulted in time-dependent proliferation reduction in MCF-7 cells, but no reduction in MDA-MB- 231 cells. MCF-7 cell survival was reduced by 15% in three-dimensional culture after CD24 crosslinking. Increased MCF-7 cell apoptosis was observed after CD24 cross-linking, but no cell cycle arrest was observed in that condition. The migration capacity of MCF-7 cells was diminished by 30% after CD24 cross-linking. Conclusion: Our results showed that CD24 cross-linking induced apoptosis and inhibited migration in MCF-7 breast cancer cells. We conclude that CD24 may be considered as a novel therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC. [ABSTRACT FROM AUTHOR]

Atmospheric aerosols, from both natural and anthropogenic, are known to be major air pollutants affecting climate, environment and human health. The importance of monitoring air pollution on the Korean peninsula has been growing due to deteriorating air quality. Recently, there has been an increase in the ground air pollution observation network on the Korean peninsula because of the concern about the serious high concentration particulate matters (PMs) cases. However, these point-based observations are costly and they have limitations in analyzing temporal and spatial changes such as long-range transport of PMs. To overcome these limitations, studies have been progressed to estimate the ground concentration of particulate matter (PM) using satellite-based aerosol optical depth (AOD). The AOD, which represents the integral value of the aerosol extinction coefficient on the atmospheric optical path, and the PM, which collects the air from the ground and measures the concentration, can be expressed empirically. In order to improve the performance of the PM concentration estimation, a vertical correction method using a planetary boundary layer and a humidity correction method considering hygroscopic growth of an aerosol have been used.In this study, a multiple linear regression model was used to estimate PM2.5 and PM10 (PMs with aerodynamic diameters less than 2.5 and 10 μm, respectively) in the Korean Peninsula. Factors for estimating the PM include the AOD and the altitude of the planetary boundary layer to consider the vertical correction, the hygroscopic growth coefficient for the humidity correction, and the wind speed and surface pressure to take into account the vertical mixing and horizontal diffusion of the aerosol. In addition, seasonal modeling and air pollutants such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide were introduced as factors to improve PMs estimation performance. [ABSTRACT FROM AUTHOR]

Melatonin suppresses tumor development. However, the exact relationship between melatonin and cancer stem cells (CSCs) is poorly understood. This study found that melatonin inhibits colon CSCs by regulating the PrPC‐Oct4 axis. In specimens from patients with colorectal cancer, the expressions of cellular prion protein (PrPC) and Oct4 were significantly correlated with metastasis and tumor stages. Co‐treatment with 5‐fluorouracil (5‐FU) and melatonin inhibited the stem cell markers Oct4, Nanog, Sox2, and ALDH1A1 by downregulating PrPC. In this way, tumor growth, proliferation, and tumor‐mediated angiogenesis were suppressed. In colorectal CSCs, PRNP overexpression protects Oct4 against inhibition by 5‐FU and melatonin. In contrast, Nanog, Sox2, and ALDH1A1 have no such protection. These results indicate that PrPC directly regulates Oct4, whereas it indirectly regulates Nanog, Sox2, and ALDH1A1. Taken together, our findings suggest that co‐treatment with anticancer drug and melatonin is a potential therapy for colorectal cancer. Furthermore, PrPC maintains cancer stemness during tumor progression. Therefore, targeting the PrPC‐Oct4 axis may prove instrumental in colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Heterozygous mutations in glucocerebrosidase 1 (GBA1) are a major genetic risk factor for Parkinson's disease and Dementia with Lewy bodies. Mutations in GBA1 leads to GBA1 enzyme deficiency, and GBA1-associated parkinsonism has an earlier age of onset and more progressive parkinsonism. To investigate a potential influence of GBA1 deficiency caused by mutations in GBA1 on the disease progression of PD, GBA1 mice carrying D409H knock-in mutation were crossbred with the human A53T (hA53T) α-synuclein transgenic mice. Here, we show that GBA1 enzyme activity plays a significant role in the hA53T α-synuclein induced α-synucleinopathy. The expression of D409H GBA1 markedly shortens the lifespan of hA53T α-synuclein transgenic mice. Moreover, D409H GBA1 expression exacerbates the formation of insoluble aggregates of α-synuclein, glial activation, neuronal degeneration, and motor abnormalities in the hA53T α-synuclein transgenic mice. Interestingly, the expression of D409H GBA1 results in the loss of dopaminergic neurons in the substantia nigra pars compacta of hA53T transgenic mice. Taken together, these results indicate that GBA1 deficiency due to D409H mutation affects the disease onset and course in hA53T α-synuclein transgenic mice. Therefore, strategies aimed to maintain GBA1 enzyme activity could be employed to develop an effective novel therapy for GBA1 linked-PD and related α-synucleinopathies. [ABSTRACT FROM AUTHOR]

Background: The biological effects of CD24 (FL-80) cross-linking on breast cancer cells have not yet been established. We examined the impact of CD24 cross-linking on human breast cancer cell line MCF-7.Methods: MCF-7 and MDA-MB-231 cells were treated with anti-rabbit polyclonal IgG or anti-human CD24 rabbit polyclonal antibodies to induce cross-linking, and then growth was studied. Changes in cell characteristics such as cell cycle modulation, cell death, survival in three-dimensional cultures, adhesion, and migration ability were assayed after CD24 cross-linking in MCF-7.Results: Expression of CD24 was analyzed by flow cytometry in MDA-MB-231 and MCF-7 cells where 2% and 66% expression frequencies were observed, respectively. CD24 cross-linking resulted in time-dependent proliferation reduction in MCF-7 cells, but no reduction in MDA-MB-231 cells. MCF-7 cell survival was reduced by 15% in three-dimensional culture after CD24 cross-linking. Increased MCF-7 cell apoptosis was observed after CD24 cross-linking, but no cell cycle arrest was observed in that condition. The migration capacity of MCF-7 cells was diminished by 30% after CD24 cross-linking.Conclusion: Our results showed that CD24 cross-linking induced apoptosis and inhibited migration in MCF-7 breast cancer cells. We conclude that CD24 may be considered as a novel therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]