Showing papers by "Hye Jin Lee published in 2021"

STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer.

Abstract: Background Peritoneal carcinomatosis is a fatal clinical presentation of colon cancer, characterized by unresponsiveness to conventional anticancer therapies, including immune checkpoint inhibitors. Here, we elucidated the immune-evasion mechanisms during the peritoneal carcinomatosis of colon cancer and developed a novel immunotherapy by activating the stimulator of interferon genes (STING) pathway. Methods We generated a syngeneic peritoneal carcinomatosis model of colon cancer. Mice were intraperitoneally treated with either STING agonist (MIW815, also known as ADU-S100) or PD-1 blockade or both. The tumor microenvironment was comprehensively analyzed using multiplexed immunofluorescence imaging, flow cytometry, and NanoString immune profiling. Results Intraperitoneal colon cancer cells induce a massive influx of immunosuppressive M2-like macrophages, upregulate immune checkpoints, and impair effector T cell functions during peritoneal dissemination; these collectively create a highly angiogenic and immunosuppressive milieu that is resistant to anti-PD-1 monotherapy. Intraperitoneal administration of a STING agonist suppressed aberrant angiogenesis, increased pericyte coverage, and normalized tumor vessels, thereby facilitating the infiltration of activated CD8+ T cells into peritoneal tumor nodules. Moreover, STING activation reprogramed tumor-associated macrophages toward the M1 phenotype. STING activation converted immunologically cold peritoneal tumors into T-cell-inflamed tumors in a type-I interferon-dependent manner. Lastly, the STING agonist synergistically cooperated with PD-1 and/or COX2 blockade to further suppress the peritoneal dissemination of colon cancer, resulting in complete eradication of tumor and ascites, and inducing durable antitumor immunity. Conclusions STING activation can normalize the peritoneal vascular and immune microenvironment, providing a rationale for a novel combination therapeutic strategy for peritoneal carcinomatosis in colon cancer.

Application of Metal-Organic Frameworks in Adsorptive Removal of Organic Contaminants from Water, Fuel and Air.

Abstract: Currently, our environment is contaminated with various toxic substances. Removal of such hazardous materials from water, air and fuel is important for sustainability. In this minireview, adsorptive removal of organic substances, by using metal-organic frameworks (MOFs), for our safe environment will be discussed. For example, removal of (i) pharmaceuticals/personal care products, pesticides, and dyes from water; (ii) S- or N-containing compounds from liquid fuel; and (iii) volatile organic compounds from air will be summarized. Moreover, plausible mechanisms to explain the observation will also be discussed. Finally, prospects in the field will be suggested for further research and development.

A serotonin voltammetric biosensor composed of carbon nanocomposites and DNA aptamer.

Abstract: A sensitive and selective voltammetric biosensor composed of layer-by-layer (LbL) self-assembly of positively charged poly(diallyldimethylammonium)-wrapped oxidized single-walled carbon nanotubes (PDDA-oSWCNTs), negatively charged serotonin (5-hydroxytryptamine, 5-HT)-specific aptamer, and tyrosinase on Au nanoparticles deposited screen printed carbon electrode was developed for measurement of 5-HT. Surface characteristics of 5-HT biosensor were explored using scanning electron microscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The respective effects of 5-HT-specific aptamer and oSWCNTs on the detection of 5-HT were investigated by differential pulse voltammetry (DPV). The peak current at the potential of 0.29 V (vs. Ag/AgCl) increased with respect to 5-HT concentration resulting in two dynamic ranges from 0.05 to 0.5 and 1 to 20 μM with a limit of detection of 2 nM from the LbL biosensor in buffer solution, which were better than those without the LbL of aptamer and oSWCNTs. The developed biosensor was applied to the direct determination of 5-HT concentrations in undiluted healthy control and Internet gaming disorder serum samples. The results were verified by comparison with those from liquid chromatography-mass spectrometric analyses.

MTF1 Is Essential for the Expression of MT1B, MT1F, MT1G, and MT1H Induced by PHMG, but Not CMIT, in the Human Pulmonary Alveolar Epithelial Cells.

Abstract: The inhalation of humidifier disinfectants (HDs) is linked to HD-associated lung injury (HDLI). Polyhexamethylene guanidine (PHMG) is significantly involved in HDLI, but the correlation between chloromethylisothiazolinone (CMIT) and HDLI remains ambiguous. Additionally, the differences in the molecular responses to PHMG and CMIT are poorly understood. In this study, RNA sequencing (RNA-seq) data showed that the expression levels of metallothionein-1 (MT1) isoforms, including MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, and MT1X, were increased in human pulmonary alveolar epithelial cells (HPAEpiCs) that were treated with PHMG but not in those treated with CMIT. Moreover, upregulation of MT1B, MT1F, MT1G, and MT1H was observed only in PHMG-treated HPAEpiCs. The protein expression level of metal regulatory transcription factor 1 (MTF1), which binds to the promoters of MT1 isoforms, was increased in PHMG-treated HPAEpiCs but not in CMIT-treated HPAEpiCs. However, the expression of early growth response 1 (EGR1) and nuclear receptor superfamily 3, group C, member 1 (NR3C1), other transcriptional regulators involved in MT1 isomers, were increased regardless of treatment with PHMG or CMIT. These results suggest that MTF1 is an essential transcription factor for the induction of MT1B, MT1F, MT1G, and MT1H by PHMG but not by CMIT.

Understanding the effect of co-reactants on ketonization of carboxylic acids in the aqueous-phase pyrolysis oil of wood

Abstract: Ketonization of carboxylic acids is one of the crucial reactions to produce sustainable bio-fuel and bio-chemicals from the pyrolysis oil of wood. Ketonization using different mixed solutions of carboxylic acids, furfural, and hydroxyacetone has been explored to understand the influence of co-feed reactants on the performance of ketonization of carboxylic acid over the selected CeZrOx catalyst. Furfural (7% in water) inhibited the catalytic activity for ketonization of acetic acid (20% solution) with reversible blocking of active sites, but for a mixed solution of hydroxyacetone (7%) and acetic acid (20%), both reactants influenced each other, resulting in very low conversions and slow and uncompleted recovery to 50% after removing hydroacetone from the mixture. For the mixed solution (20% acetic acid + 7% furfural + 7% hydroxyacetone in water), hydroxyacetone was the most reactive compound on CeZrOx and the conversions of reactants reached below 10%, due to the inhibition of co-existing carbonyl components. This work provides guidance for ketonization of carboxylic acids in the aqueous-phase pyrolysis oil.

Fluorescent paper strip immunoassay with carbon nanodots@silica for determination of human serum amyloid A1.

Abstract: A fluorescent paper strip immunoassay in conjunction with carbon nanodots@silica (CND@SiO2) as a label was developed for the quantitative measurements of human serum amyloid A1 (hSAA1) in serum at clinically significant concentrations for lung cancer diagnosis. Monodispersed CND@SiO2 was prepared by cohydrolysis between silane-crosslinked carbon nanodots and silica precursors via the Strober method and further attached covalently to anti-hSAA1 (14F8) monoclonal antibody [anti-hSAA1(14F8)] specific to the hSAA1 target. The hSAA1 concentrations were then determined by quantifying the blue fluorescence intensity upon 365 nm excitation of the captured hSAA1 with anti-hSAA1(14F8)-CND@SiO2 conjugates in the test line on a paper strip where anti-hSAA1 (10G1) monoclonal antibody was physisorbed. The developed fluorescent paper strip with CND@SiO2 can detect hSAA1 at concentrations ranging from 0.1 to 5 nM (R2 = 0.995), with a limit of detection of 0.258 nM in 10 mM phosphate buffer pH 7.4 containing human serum albumin. The performance of recovery (90.98–109.17%) and repeatability (coefficients of variation < 8.46%) obtained was also acceptable for quantitative determinations. The platform was employed for direct determination of hSAA1 concentrations in undiluted serum samples from lung cancer patients (relative standard deviation (RSD) < 7.46%) and healthy humans (RSD < 3.96%). The results were compared with those obtained using a commercially available enzyme-linked immunosorbent assay alongside liquid chromatography with tandem mass spectrometry measurements.

A short PEG linker alters the in vivo pharmacokinetics of trastuzumab to yield high-contrast immuno-PET images

Abstract: The prolonged blood circulation of the radiolabeled antibody conjugates is problematic when using immuno-PET imaging due to the increased radiation exposure and longer hospitalization required until sufficient contrast develops. In contrast to the prevailing belief that PEGylation prolongs blood retention time, we observed that a PEGylated antibody with a short PEG8 linker cleared much faster from the blood while maintaining tumor uptake compared to its non-PEGylated counterpart. Breast tumors were clearly visualized with a very high tumor-to-background ratio as early as 24 h after injection in immuno-positron emission tomography (PET) imaging.

Deep learning model enables the discovery of a novel immunotherapeutic agent regulating the kynurenine pathway.

Abstract: Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). Although indoleamine 2,3-dioxygenase (IDO)-selective inhibitors have been developed to suppress the Kyn pathw...

High prevalence and variable fitness of fluoroquinolone-resistant avian pathogenic Escherichia coli isolated from chickens in Korea.

Abstract: Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is the most common bacterial disease in poultry, resulting in significant economic losses. Resistance to fluoroquinolones has been ...

Gold-silver core-shell nanodumbbells in solution state as a highly sensitive and reproducible assay platform for bacterial genome detection

Abstract: Surface-enhanced Raman scattering (SERS) has been investigated as a promising spectroscopic tool for various assay platforms. However, key challenges, such as the reproducibility and sensitivity of this tool should be addressed to enable it to become a reliable and practical method for future clinical applications. Although the single-molecule sensitivity of SERS has already been proven in dry state analysis, its signal reproducibility remains a key challenge in developing a real assay platform. The signal reproducibility of SERS can be significantly improved by obtaining the Raman signal from the solution state; however, the sensitivity of this method is not satisfactory. In this study, we demonstrate a method to overcome both key challenges by using a solution-state formation of gold-silver core-shell nanodumbbells (GSNDs) with target nucleic acid and nanoscale Ag shell formation, which was proven to exhibit single-molecule sensitivity in dry state analysis. To utilize the concept of a reliable assay platform in solution, diverse parameters such as the length of the target sequences, hybridization conditions, number density of probe sequences, and the Ag shell thickness are investigated. The hybridization yield of Au dimer reaches up to 79.36% for E. faecalis, indicating that the hybridization yields are target sequence dependent. It is strongly correlated with detection limit for the target bacteria. The solution-state GSND-based assay shows a highly sensitive results for bacterial target DNA with no mutual interference and excellent reproducibility. The method can identify extremely low concentrations of bacteria (4.5 cfu mL−1), which is much superior to the conventional PCR (4500 cfu mL−1) and culture-based assays (45 cfu mL−1). The results envision the current GSND-based assay as a promising assay platform for future clinical applications.

Vascular reactivity contributes to adipose tissue remodeling in obesity.

Abstract: Vascular reactivity of adipose tissue (AT) is hypothesized to play an important role in the development of obesity. However, the exact role of vascular reactivity in the development of obesity remains unclear. In this study, we investigated the chronological changes in vascular reactivity and the microenvironments of the visceral AT (VAT) and subcutaneous AT (SAT) in lean and obese mice. Changes in blood flow levels induced by a β-adrenoceptor agonist (isoproterenol) were significantly lower in the VAT of the mice fed a high-fat diet (HFD) for 1 and 12 weeks than those in the VAT of the mice fed a low-fat diet (LFD) for the same period; no significant change was observed in the SAT of any mouse group, suggesting depot-specific vascular reactivity of AT. Moreover, the hypoxic area and the expression of genes associated with angiogenesis and macrophage recruitment were increased in the VAT (but not in the SAT) of mice fed an HFD for 1 week compared with mice fed an LFD. These changes occurred with no morphological changes, including those related to adipocyte size, AT vessel density, and the diameter and pericyte coverage of the endothelium, suggesting a determinant role of vascular reactivity in the type of AT remodeling. The suppression of vascular reactivity was accompanied by increased endothelin1 (Edn1) gene expression and extracellular matrix (ECM) stiffness only in the VAT, implying enhanced contractile activities of the vasculature and ECM. The results suggest a depot-specific role of vascular reactivity in AT remodeling during the development of obesity.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

Abstract: Aim To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists. Methods We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model. Results Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis. They also increased thermogenesis in brown adipose tissue, and lipolysis and β-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells. Conclusion Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.

Estimation of Evapotranspiration and Water Requirements of Strawberry Plants in Greenhouses Using Environmental Data

Abstract: Farmers routinely determine irrigation requirements from visual observations and cultivation experience, but this can lead to under- or over-irrigation. To establish precise irrigation technology for strawberry cultivation, the average daily evapotranspiration and water requirements were estimated according to the amount of solar radiation. Environmental data was collected; air temperature and humidity from the center of the greenhouses and solar radiation from outside greenhouses. Makkink FAO24 equations (temperature and cloudiness) were used to estimate the evapotranspiration and water requirements. The temperature method showed higher correlation coefficients in solar radiation (R2 = 0.60), evapotranspiration (R2 = 0.76), and water requirements (R2 = 0.69) than other tested methods. The daily irrigation, calculated from the estimated evapotranspiration, was 3.8 tons/10a. It is possible to develop a precision irrigation system from estimated evapotranspiration during the cultivation of strawberries.

Profiles of Environmental Parameters in a Plant Factory with Artificial Lighting and Evaluation on Growth of Cucumber Seedlings

Abstract: Due to the climate change such as high temperature in summer and low sunlight in winter, vegetable seedling growers have been facing difficulties to produce uniform seedlings in all four seasons. A plant factory with an artificial lighting (PFAL) would be considered as an effective alternative tool in that it can control environment conditions and produce uniform seedlings without outside weather conditions. Therefore, this study investigated changes of environment parameters, such as light uniformity, temperature and the relative humidity and uniformity of seedlings cultivated in a PFAL to evaluate plant factory transplant production system with an artificial lighting. Cucumber seedlings were grown in a PFAL at the light intensity 250 μmol·m -2 ·s -1 , the photoperiod 16/8h, the temperature 25/2 0°C and the relative humidity 70/85%. In the light intensity uniformity, as closer to the light source from 255 to 105mm, the amount of light increased by 11 and 23%, respectively, but the standard deviation increased by 1.8 times. For the temperature and the relative humidity by four different height positions (615, 980, 1,345, 1,710 mm distance from the floor), temperature did not show much difference at each location, 24.7/19.5, 24.6/19.5, 24.7/19.4 and 24.7/19.6°C, respectively. Also, the relative did not differ by locations (71/84%). Additionally, cucumber seedling characteristics of plant height, leaf area, fresh weight and dry weight of cucumber seedlings 8 days after sowing showed highly uniform quality, 4.1 ± 0.1 cm, 24.1 ± 3.7 cm 2 , 0.7 ± 0.13 g and 0.05 ± 0.008 g, respectively. Considering the results of environment parameter profiling and cucumber seedling uniformity, vegetable seedling production in a PFAL can be a promise tool in the era of climate change. Additional key words : PPFD, scion, sturdy transplants, plug tray *Corresponding author: skkim76@knu.ac.kr Received April 14, 2021; Revised April 20, 2021; Accepted April 20, 2021 Journal of Bio-Environment Control, Vol. 30, No. 2:126-132, April (2021) DOI https://doi.org/10.12791/KSBEC.2021.30.2.126 pISSN 1229-4675 eISSN 2765-3641

Machine learning algorithms in big data analyses identify determinants of insulin gene transcription

Abstract: Machine learning (ML) workflows enable unprejudiced/robust evaluation of complex datasets and are increasingly sought in big data analyses. Here, we analyzed over 490,000,000 data points to compare 10 different ML algorithms in a large (N=11,652) training dataset of human pancreatic single-cell transcriptomes to identify features (genes) associated with the presence or absence of insulin transcript(s). Prediction accuracy/sensitivity of models were tested in a separate validation dataset (N=2,913) and the performance of each ML-workflow assessed. Overall, Ensemble ML workflows, and in particular, Random Forest ML algorithm delivered high predictive power in a receiver operator characteristic (ROC) curve analysis (AUC=0.83) at the highest sensitivity (0.98), compared to other algorithms. The top-10 features, (including IAPP, ADCYAP1, LDHA and SST) common to the three Ensemble ML workflows were significantly dysregulated in scRNA-seq datasets from Ire-1{beta}-/- mice that demonstrate de-differentiation of pancreatic {beta}-cells as well as in pancreatic single cells from individuals with Type 2 Diabetes. Our findings provide a direct comparison of ML workflows in big data analyses, identify key determinants of insulin transcription and provide workflows for other regulatory analyses to identify/validate novel genes/features of endocrine pancreatic gene transcription. Significance statementsO_LIA comparative analysis of 10 different machine learning (ML) approaches identifies most accurate and sensitive algorithms in big data (>490 million datapoints) analyses; C_LIO_LIEnsemble ML (Random Forest, ADA Boost and Gradient boost) models trained on 392,684,052 datapoints from human pancreatic scRNA-seq studies, identify features (genes) that predict insulin transcription in a separate (N=2,913) dataset; C_LIO_LIIn silico validation of identified features confirmed predictors of insulin gene transcription; C_LIO_LIKnown and novel key variables associated with insulin transcription are dysregulated in a Type 1 diabetes mouse model that shows transient {beta}-cell dedifferentiation and in {beta}-cells of individuals with type 2 diabetes. C_LI

Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice.

Abstract: Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.

NGSpop: A desktop software that supports population studies by identifying sequence variations from next-generation sequencing data

Abstract: Next-generation sequencing (NGS) is widely used in all areas of genetic research, such as for genetic disease diagnosis and breeding, and it can produce massive amounts of data. The identification of sequence variants is an important step when processing large NGS datasets; however, currently, the process is complicated, repetitive, and requires concentration, which can be taxing on the researcher. Therefore, to support researchers who are not familiar with bioinformatics in identifying sequence variations regularly from large datasets, we have developed a fully automated desktop software, NGSpop. NGSpop includes functionalities for all the variant calling and visualization procedures used when processing NGS data, such as quality control, mapping, filtering details, and variant calling. In the variant calling step, the user can select the GATK or DeepVariant algorithm for variant calling. These algorithms can be executed using pre-set pipelines and options or customized with the user-specified options. NGSpop is implemented using JavaFX (version 1.8) and can thus be run on Unix like operating systems such as Ubuntu Linux (version 16.04, 18.0.4). Although there are several pipelines and visualization tools available for NGS data analysis, most integrated environments do not support batch processes; thus, variant detection cannot be automated for population-level studies. The NGSpop software, developed in this study, has an easy-to-use interface and helps in rapid analysis of multiple NGS data from population studies.

Should We Delay Urodynamic Study When Patients With Spinal Cord Injury Have Asymptomatic Pyuria

Abstract: Objective To assess the incidence of urinary tract infection (UTI) with post-urodynamic study (post-UDS) in patients with spinal cord injury (SCI) and study its relationship with pre-UDS pyuria. Methods Patients with SCI who were hospitalized and underwent UDS during a 4-year period were reviewed. Patients with pre-test lower urinary tract symptoms were excluded. Urinalysis and urine culture were performed before and 24 hours after UDS. Prophylactic antibiotics were administered for 5 days starting from the morning of the UDS. UTI was defined as bacteriuria with accompanying symptoms. Results Of 399 patients reviewed, 209 (52.4%) had pyuria in pre-UDS urinalysis, and 257 (64.4%) had bacteriuria in pre-UDS culture. Post-UDS UTI occurred in 6 (1.5%) individuals who all complained of fever: 5 (2.4%) of the post-UDS UTI cases occurred in patients with pre-UDS pyuria, and 1 (0.5%) in a person without. The differences between groups were not statistically significant (p=0.218). Of 221 patients with bacteriuria (gram-negative isolates) on pre-UDS culture, resistance to ciprofloxacin, cephalosporin, and trimethoprim/sulfamethoxazole (TMP/SMT) was noted in 52.9% (117 cases), 57.0% (126 cases), and 38.9% (86 cases), respectively. Conclusion No difference was found in the prevalence of post-UDS UTI based on the presence of pyuria in pre-UDS urinalysis. UDS may be performed even in SCI cases of pre-UDS pyuria without increasing the prevalence of post-UDS UTI if prophylactic antibiotics are administered. TMP/SMT could be used as a first-line antibiotic for the prevention of post-UDS UTI in Korea.