Publications by authors named "Tae-Young Kim"

289 Publications

Predictive Factors for Long-Term Outcomes of Cataract Surgery in Patients Receiving Active Treatment for Neovascular Age-Related Macular Degeneration.

J Clin Med 2021 Jul 15;10(14). Epub 2021 Jul 15.

Department of Ophthalmology, Severance Eye Hospital, Yonsei University College of Medicine, 50-1, Yonseiro, Seodaemun-gu, Seoul 03722, Korea.

Background: the safety and efficacy of cataract surgery in eyes with exudative neovascular age-related macular degeneration (nAMD), receiving active treatment, remain unclear. We evaluated the long-term outcomes and associated predictive factors of cataract surgery in eyes with exudative nAMD.

Methods: this retrospective cohort study included 65 eyes (61 patients) treated with anti-vascular endothelial growth factor (VEGF) injections within six months preoperatively. Changes in best-corrected visual acuity (BCVA) and anti-VEGF treatment patterns from before to up to four years after surgery were assessed. Predictive factors were identified in association with one-year surgical outcomes.

Results: the BCVA improved at six months ( < 0.001) and was maintained for three years postoperatively. The interval between anti-VEGF injections increased 3.4 times postoperatively ( = 0.001). Risk factors for poor BCVA were low preoperative BCVA ( < 0.001) and prolonged nAMD duration ( = 0.003). Prolonged nAMD duration and short exudation-free period were associated with more frequent postoperative anti-VEGF treatments ( = 0.028 and = 0.003, respectively). AMD subtypes were not associated with both vision and injection pattern outcomes.

Conclusions: patients with cataracts receiving nAMD treatment can safely undergo surgery with favorable long-term visual benefits. The preoperative BCVA, nAMD duration, and exudation-free period are potential predictors of surgery outcomes.
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http://dx.doi.org/10.3390/jcm10143124DOI Listing
July 2021

Incidence and Risk of Venous Thromboembolism in Bisphosphonates and Selective Estrogen Receptor Modulators Treatment in Korea.

J Korean Med Sci 2021 Jul 12;36(27):e186. Epub 2021 Jul 12.

Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Background: Selective estrogen receptor modulators (SERMs) were associated with an increased risk of venous thromboembolism (VTE) due to the estrogen effect. In this study, we investigated the effect of SERMs on VTE compared to bisphosphonates (BPs) using the Korean National Health Insurance claims database.

Methods: This was a retrospective cohort study. Women over 50 years old who were first prescribed BPs or SERMs for osteoporosis treatment in 2012 were included. The difference in VTE incidence between the SERMs and BP groups was compared. Both groups were followed up for VTE or PE occurrence, death, or until December 2016. The study population was analyzed by 3:1 matching according to age using a multivariate Cox model.

Results: The hazard ratio (HR) for VTE was 0.72 (95% confidence interval [CI], 0.40-1.28) in the SERMs group compared to BP group. Older age (60-69 vs. 50-59 years: HR, 3.77; 95% CI, 2.07-6.86 and 70-79 vs. 50-59 years: HR, 5.88; 95% CI, 3.14-11.02), major osteoporotic fracture (HR, 1.77; 95% CI, 1.16- 2.70), atrial fibrillation (HR, 3.31; 95% CI, 1.35-8.11), and estrogen replacement (HR, 3.40; 95% CI, 2.01-5.73) all increased VTE risk. In subgroup analysis of the SERMs group, past hospitalization (HR, 2.24; 95% CI, 1.02-4.92), estrogen replacement (HR, 5.75; 95% CI, 2.29-14.39), and glucocorticoid replacement (HR, 2.71; 95% CI, 1.05-7.0) increased VTE risk.

Conclusion: SERMs did not increase the risk of VTE compared to BPs in Koreans with osteoporosis. However, old age and estrogen replacement both increased VTE risk.
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http://dx.doi.org/10.3346/jkms.2021.36.e186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275462PMC
July 2021

Coats-like Exudative Vitreoretinopathy in NMNAT1 Leber Congenital Amaurosis.

Ophthalmol Retina 2021 Jul;5(7):624

Institute of Vision Research, Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

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http://dx.doi.org/10.1016/j.oret.2021.04.010DOI Listing
July 2021

Enzyme-Treated Extract Protects against Alcohol-Induced Liver Injury by Regulating the NRF2 Pathway.

Antioxidants (Basel) 2021 Jun 15;10(6). Epub 2021 Jun 15.

Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Jeonbuk, Korea.

Binge drinking patterns easily produce a state of oxidative stress that disturbs liver function. Eventually, this leads to alcoholic liver disease. A safe and effective therapy for alcoholic liver disease remains elusive. Enzyme-treated extract (ETZL) was studied as a potential agent for treating alcohol-induced liver disease. In addition, its underlying mechanisms were elucidated. In the binge model, ETZL was pretreated with alcohol (5 g/kg) three times at 12-h intervals. Our results showed that ETZL pretreatment decreased the serum levels of ALT, AST, ALP, and TG. ETZL treatment appeared to prevent an increase in hepatic TG and MDA levels, and there was a decrease in total GSH following alcohol treatment. Histopathological examination showed that lipid droplets were significantly reduced in the ETZL group compared to the control group. ETZL also exhibited radical scavenging activity. It significantly reduced -BHP-induced cytotoxicity and the production of reactive oxygen species (ROS) in HepG2 cells. ETZL also enhanced NRF2 nuclear translocation and increased expression of the downstream target genes HO-1, NQO1, and GCLC as an antioxidant defense. Finally, ETZL treatment significantly reduced cell death. Our study suggests that ETZL ameliorates binge ethanol-induced liver injury by upregulating the antioxidant defense mechanism.
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http://dx.doi.org/10.3390/antiox10060960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232714PMC
June 2021

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment.

J Korean Med Sci 2021 Jun 21;36(24):e177. Epub 2021 Jun 21.

Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.
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http://dx.doi.org/10.3346/jkms.2021.36.e177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216992PMC
June 2021

Haplopine Ameliorates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice and TNF-α/IFN-γ-Induced Inflammation in Human Keratinocyte.

Antioxidants (Basel) 2021 May 19;10(5). Epub 2021 May 19.

College of Pharmacy, Pusan National University, Busan 46241, Korea.

This study aimed to investigate the anti-inflammatory, antioxidant, and anti-atopic dermatitis (AD) effects of haplopine, which is one of the active components in Haplopine (12.5 and 25 μM) inhibited the mRNA expressions of inflammatory cytokines IL-6, TSLP, GM-CSF, and G-CSF and the protein expressions of IL-6 and GM-CSF in TNF-α/INF-γ-stimulated HaCaT cells. In HO-induced Jukat T cells, haplopine (25 and 50 μM) suppressed the productions of proinflammatory cytokines (IL-4, IL-13, and COX-2) and increased the mRNA and protein expressions of oxidative stress defense enzymes (SOD, CAT, and HO-1) in a concentration-dependent manner. In vivo, haplopine significantly attenuated the development of AD symptoms in 2,4-dinitrochlorobenzene (DNCB)-stimulated Balb/c mice, as evidenced by reduced clinical dermatitis scores, skin thickness measurements, mast cell infiltration, and serum IgE concentrations. These findings demonstrate that haplopine should be considered a novel anti-atopic agent with the potential to treat AD.
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http://dx.doi.org/10.3390/antiox10050806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161082PMC
May 2021

Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence-Based Clinical Practice Guidelines.

Surg Technol Int 2021 05 27;38. Epub 2021 May 27.

Zhongshan Hospital of Dalian University, Dalian, China.

Introduction: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines.

Materials And Methods: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: 1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; 2) What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and 3) What is the best treatment strategy for patients who have post-collapse disease? The Patient, Intervention, Comparison, and Outcome (PICO) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH.

Discussion: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.
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May 2021

Anti-atherosclerotic vaccination against as a potential comparator of statin in mice.

PeerJ 2021 20;9:e11293. Epub 2021 Apr 20.

Cardiology Division, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: is an oral anaerobe which damages teeth and periodontal tissues. Its body infection is known to cause chronic inflammation, thereby inducing an early stage of atherosclerosis through humoral immune actions. Hence, vaccination by immunizing the proteins of post sonication with heating may prevent atherosclerosis. This study aimed to compare the effect of its vaccination with statin, which effectively prevents atherosclerosis by lowering lipids.

Methods: The vaccine was produced by sonicating through heating, and a total of 32 male APOE-/-mice (8-week old) were subjected Western diet for 8 weeks, in order to induce atherosclerosis in a physiological manner. Then, the mice were grouped to undergo four treatment conditions (i.e., no treatment, pitavastatin, vaccine, or pitavastatin with vaccine). Vaccination was conducted through nasal immunization and confirmed by a Pg-specific humoral immune reaction. Then, half of the mice in each group were orally injected with for the next 5 weeks while the other half remained uninfected, generating a total of eight groups ( = 4/group). The mice were sacrificed at 3 weeks after the last injection. After harvesting the aorta, Oil Red O staining of en face was conducted with imaging and image analysis, and plaque formation was quantitatively determined.

Results: Compared to no treatment, the vaccination through nasal immunization significantly reduced the atherosclerotic plaque sizes in APOE -/- mice under Western diet to the comparable level of statin group. When both vaccine and statin were used, no clear synergistic effect was observed as opposed to expectation.

Conclusions: This study revealed that nasal immunization of heat shock has a significant impact on the prevention of arteriosclerosis and acts as a potential comparator of statin.
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http://dx.doi.org/10.7717/peerj.11293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063868PMC
April 2021

Extract Improved Atopic Dermatitis-Like Skin Lesions via Suppression of Interleukin-4 in 2,4-Dinitrochlorobenzene-Induced SKH-1 Hairless Mice.

Molecules 2021 Apr 1;26(7). Epub 2021 Apr 1.

College of Pharmacy, Pusan National University, Busan 46241, Korea.

Plants of the genus are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that is a potential therapeutic agent for AD.
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http://dx.doi.org/10.3390/molecules26072016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036472PMC
April 2021

Risk of QT prolongation through drug interactions between hydroxychloroquine and concomitant drugs prescribed in real world practice.

Sci Rep 2021 03 25;11(1):6918. Epub 2021 Mar 25.

Department of Biomedical Informatics, Ajou University School of Medicine, 206, World cup-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16499, Republic of Korea.

Hydroxychloroquine has recently received attention as a treatment for COVID-19. However, it may prolong the QTc interval. Furthermore, when hydroxychloroquine is administered concomitantly with other drugs, it can exacerbate the risk of QT prolongation. Nevertheless, the risk of QT prolongation due to drug-drug interactions (DDIs) between hydroxychloroquine and concomitant medications has not yet been identified. To evaluate the risk of QT prolongation due to DDIs between hydroxychloroquine and 118 concurrent drugs frequently used in real-world practice, we analyzed the electrocardiogram results obtained for 447,632 patients and their relevant electronic health records in a tertiary teaching hospital in Korea from 1996 to 2018. We repeated the case-control analysis for each drug. In each analysis, we performed multiple logistic regression and calculated the odds ratio (OR) for each target drug, hydroxychloroquine, and the interaction terms between those two drugs. The DDIs were observed in 12 drugs (trimebutine, tacrolimus, tramadol, rosuvastatin, cyclosporin, sulfasalazine, rofecoxib, diltiazem, piperacillin/tazobactam, isoniazid, clarithromycin, and furosemide), all with a p value of < 0.05 (OR 1.70-17.85). In conclusion, we found 12 drugs that showed DDIs with hydroxychloroquine in the direction of increasing QT prolongation.
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http://dx.doi.org/10.1038/s41598-021-86321-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994840PMC
March 2021

Corrective surgery using a gridiron incision for abdominal pain caused by a folded ovary in the third trimester of pregnancy.

J Int Med Res 2021 Mar;49(3):300060521997743

Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, South Korea.

Introduction: Sonography and magnetic resonance imaging (MRI) may be helpful to obtain an accurate diagnosis of acute abdominal pain in pregnancy. Adnexal torsion presenting in the first or second trimester can be confirmed and treated through laparoscopic surgery; however laparoscopic surgery in the third trimester can be difficult owing to the large uterus, and a gridiron incision can be useful.

Case Report/case Presentation: An 18-year-old gravida 1, para 0 (G1P0) woman at 30 + 4 weeks of gestation presented with sudden-onset cyclic pain in the right lower quadrant. Abdominal ultrasonography showed a normal appendix, and MRI showed a normal appendix and normal ovaries. The patient's prominent tender point was marked and compared with the MR images, which confirmed the mark as the position of the right ovary. Laparotomy was performed through a gridiron incision, and a folded right ovary was identified. The ovary was unfolded, and TachoSil® and Surgicel® were used to maintain the unfolded position. The patient's pain resolved, and her postoperative course was uneventful. She delivered a healthy, 2540-g male baby at 35 weeks' gestation.

Discussion/conclusions: A gridiron incision was useful to treat a folded ovary in the third trimester and to evaluate the adnexa and minimize uterine manipulation.
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http://dx.doi.org/10.1177/0300060521997743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975525PMC
March 2021

Development of an optimized sample preparation method for quantification of free fatty acids in food using liquid chromatography-mass spectrometry.

Sci Rep 2021 Mar 15;11(1):5947. Epub 2021 Mar 15.

School of Earth Sciences and Environmental Engineering, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.

Accurate and precise determination of free fatty acid (FFA) contents is essential for quality control and assurance in food production. Herein, a mass spectrometric study was performed to develop a sample preparation protocol that can minimize exogenous FFA contamination during the quantification of FFA in food. The quantities of exogenous FFAs were measured using various combinations of seven pretreatment methods for a sample tube, three extraction methods, and four types of sample tubes. Methanol washing could effectively reduce exogenous palmitic acid (PA) and stearic acid (SA) by 73 and 64%, respectively, in contrast to furnace baking resulting in a decrease in the amount of PA and SA contaminants by 50 and 37%, respectively. A lower amount of FFA contaminants was extracted from glass tubes during comparative analysis of the four different sample tubes studied. A combination of a methanol-washed glass tube and chloroform extraction solvent was determined to be the optimal method for minimizing the error in FFA quantification. The optimized sample preparation protocol used for FFA quantification can lower the amount of foreign palmitic acid and stearic acid to the sub-nanomolar level in the analysis of FFAs in skimmed milk.
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http://dx.doi.org/10.1038/s41598-021-85288-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961064PMC
March 2021

Mucin degrader accelerates intestinal stem cell-mediated epithelial development.

Gut Microbes 2021 Jan-Dec;13(1):1-20

Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Mucin-degrading bacteria are densely populated in the intestinal epithelium; however, their interaction with intestinal stem cells (ISCs) and their progeny have not been elucidated. To determine whether mucin-degrading bacteria play a role in gut homeostasis, mice were treated with , a specialized species that degrades mucin. Administration of for 4 weeks accelerated the proliferation of Lgr5 ISCs and promoted the differentiation of Paneth cells and goblet cells in the small intestine (SI). We found similar effects of in the colon. The levels of acetic and propionic acids were higher in the cecal contents of -treated mice than in PBS-treated mice. SI organoids treated with cecal contents obtained from -treated mice were larger and could be diminished by treatment with G protein-coupled receptor (Gpr) 41/43 antagonists. Pre-treatment of mice with reduced gut damage caused by radiation and methotrexate. Further, a novel isotype of the strain was isolated from heathy human feces that showed enhanced function in intestinal epithelial regeneration. These findings suggest that mucin-degrading bacteria (e.g., ) may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.
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http://dx.doi.org/10.1080/19490976.2021.1892441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946046PMC
March 2021

Effectiveness of Transfer Learning for Deep Learning-Based Electrocardiogram Analysis.

Healthc Inform Res 2021 Jan 31;27(1):19-28. Epub 2021 Jan 31.

Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.

Objectives: Many deep learning-based predictive models evaluate the waveforms of electrocardiograms (ECGs). Because deep learning-based models are data-driven, large and labeled biosignal datasets are required. Most individual researchers find it difficult to collect adequate training data. We suggest that transfer learning can be used to solve this problem and increase the effectiveness of biosignal analysis.

Methods: We applied the weights of a pretrained model to another model that performed a different task (i.e., transfer learning). We used 2,648,100 unlabeled 8.2-second-long samples of ECG II data to pretrain a convolutional autoencoder (CAE) and employed the CAE to classify 12 ECG rhythms within a dataset, which had 10,646 10-second-long 12-lead ECGs with 11 rhythm labels. We split the datasets into training and test datasets in an 8:2 ratio. To confirm that transfer learning was effective, we evaluated the performance of the classifier after the proposed transfer learning, random initialization, and two-dimensional transfer learning as the size of the training dataset was reduced. All experiments were repeated 10 times using a bootstrapping method. The CAE performance was evaluated by calculating the mean squared errors (MSEs) and that of the ECG rhythm classifier by deriving F1-scores.

Results: The MSE of the CAE was 626.583. The mean F1-scores of the classifiers after bootstrapping of 100%, 50%, and 25% of the training dataset were 0.857, 0.843, and 0.835, respectively, when the proposed transfer learning was applied and 0.843, 0.831, and 0.543, respectively, after random initialization was applied.

Conclusions: Transfer learning effectively overcomes the data shortages that can compromise ECG domain analysis by deep learning.
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http://dx.doi.org/10.4258/hir.2021.27.1.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921576PMC
January 2021

The Global Plastic Toxicity Debt.

Environ Sci Technol 2021 03 17;55(5):2717-2719. Epub 2021 Feb 17.

Science and Technology Center for Sustainability, Federal University of São Carlos, Sorocaba, São Paulo 18052-780, Brazil.

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http://dx.doi.org/10.1021/acs.est.0c07781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931444PMC
March 2021

SILAC-Based Quantitative Proteomic Analysis of Oxaliplatin-Resistant Pancreatic Cancer Cells.

Cancers (Basel) 2021 Feb 10;13(4). Epub 2021 Feb 10.

Center for Bioanalysis, Division of Chemical and Medical Metrology, Korea Research Institute of Standards and Science, Daejeon 34113, Korea.

Oxaliplatin is a commonly used chemotherapeutic drug for the treatment of pancreatic cancer. Understanding the cellular mechanisms of oxaliplatin resistance is important for developing new strategies to overcome drug resistance in pancreatic cancer. In this study, we performed a stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative proteomics analysis of oxaliplatin-resistant and sensitive pancreatic cancer PANC-1 cells. We identified 107 proteins whose expression levels changed (thresholds of 2-fold changes and -value ≤ 0.05) between oxaliplatin-resistant and sensitive cells, which were involved in multiple biological processes, including DNA repair, cell cycle process, and type I interferon signaling pathway. Notably, myristoylated alanine-rich C-kinase substrate (MARCKS) and Wntless homolog protein (WLS) were upregulated in oxaliplatin-resistant cells compared to sensitive cells, as confirmed by qRT-PCR and Western blot analysis. We further demonstrated the activation of AKT and β-catenin signaling (downstream targets of MARCKS and WLS, respectively) in oxaliplatin-resistant PANC-1 cells. Additionally, we show that the siRNA-mediated suppression of both MARCKS and WLS enhanced oxaliplatin sensitivity in oxaliplatin-resistant PANC-1 cells. Taken together, our results provide insights into multiple mechanisms of oxaliplatin resistance in pancreatic cancer cells and reveal that MARCKS and WLS might be involved in the oxaliplatin resistance.
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http://dx.doi.org/10.3390/cancers13040724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916634PMC
February 2021

Implications of the specific localization of YAP signaling on the epithelial patterning of circumvallate papilla.

J Mol Histol 2021 Apr 8;52(2):313-320. Epub 2021 Jan 8.

Department of Oral Medicine, School of Dentistry, IHBR, Kyungpook National University, 2177 Dalgubeol-daero, Joong-gu, Daegu, 41940, Korea.

Circumvallate papilla (CVP) is a distinctively structured with dome-shaped apex, and the surrounding trench which contains over two hundred taste buds on the lateral walls. Although CVP was extensively studied to determine the regulatory mechanisms during organogenesis, it still remains to be elucidated the principle mechanisms of signaling regulations on morphogenesis including taste buds formation. The key role of Yes-associated protein (YAP) in the regulation of organ size and cell proliferation in vertebrates is well understood, but little is known about the role of this signaling pathway in CVP development. We aimed to determine the putative roles of YAP signaling in the epithelial patterning during CVP morphogenesis. To evaluate the precise localization patterns of YAP and other related signaling molecules, including β-catenin, Ki67, cytokeratins, and PGP9.5, in CVP tissue, histology and immunohistochemistry were employed at E16 and adult mice. Our results suggested that there are specific localization patterns of YAP and Wnt signaling molecules in developing and adult CVP. These concrete localization patterns would provide putative involvements of YAP and Wnt signaling for proper epithelial cell differentiation including the formation and maintenance of taste buds.
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http://dx.doi.org/10.1007/s10735-020-09951-zDOI Listing
April 2021

Osteoporosis and Osteoporotic Fracture Fact Sheet in Korea.

J Bone Metab 2020 Nov 30;27(4):281-290. Epub 2020 Nov 30.

Division of Endocrinology, Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.

Background: The socioeconomic burdens of osteoporosis and related fractures have increased in parallel with population aging. The Korea Society of Bone and Mineral Research published fact sheets on these topics in 2017, 2018, and 2019. This study provides complied epidemiological data based on these fact sheets for understanding current status of osteoporosis in Korea.

Methods: Data from the Korea National Health and Nutrition Examination Survey (2008-2011) performed by the Korea Centers for Disease Control and Prevention and from National Health Information database (2008-2016) by National Health Insurance Service of Korea was used for analyzing the prevalence and incidence of osteoporosis and related fractures, respectively, fatality rates after fractures, and prescription status of anti-osteoporotic medications (AOMs).

Results: Among Korean adults aged ≥50 years, 22.4% and 47.9% had osteopenia or osteoporosis, respectively. Incidences of osteoporotic hip, vertebral, humerus, and distal radius fractures plateaued in 2013. The cumulative incidence of subsequent fractures gradually increased over 4 years of follow-up once an osteoporotic fracture occurred. Crude fatality rates in the first 12 months after hip fracture were 14.0% for women and 21.0% for men. Only 33.5% of patients with osteoporosis took AOMs, and even after an osteoporotic fracture, only 41.9% of patients took AOMs within the following 12 months. Despite a steady increase in AOM prescriptions of ~6% per annum, only 33.2% of patients were medication compliant (medication possession ratio ≥80%) at 12 months after treatment initiation.

Conclusions: Continuous efforts are required to diagnose patients at high risk of fracture and ensure proper management in Korea.
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http://dx.doi.org/10.11005/jbm.2020.27.4.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746478PMC
November 2020

Fruit Has Anti-Inflammatory Effect and Induces Osteogenic Differentiation by Regulating Nrf2/HO-1 Signaling Pathway in In Vitro and In Vivo Models of Periodontitis.

Antioxidants (Basel) 2020 Dec 3;9(12). Epub 2020 Dec 3.

College of Pharmacy, Keimyung University, 1095 Dalgubeol-daero, Daegu 42601, Korea.

Periodontitis is an infectious inflammatory disease of tissues around teeth that destroys connective tissues and is characterized by the loss of periodontal ligaments and alveolar bone. A new treatment strategy is needed owing to the limitations of the current surgical treatment method and the side effects of anti-inflammatory drugs. Therefore, here, we assessed whether fruit extract (PGFE) is a new therapeutic agent for periodontitis in vitro and in vivo. According to the results, PGFE suppressed pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, and pro-inflammatory mediators such as inducible nitric oxide synthase and cyclooxygenase-2 through heme oxygenase-1 expression in human periodontal ligament cells stimulated with lipopolysaccharide (PG-LPS). In addition, the osteogenic induction of human periodontal ligament cells was inhibited by PG-LPS, and protein and mRNA levels of osteogenic markers such as alkaline phosphatase, collagen type 1 (COL1), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2) were increased. The efficacy of PGFE for inhibiting periodontitis in vitro was demonstrated in a representative in vitro model of periodontitis induced by ligature and PG-LPS. Subsequently, hematoxylin and eosin staining and micro-computed tomography of the euthanized experimental animal model confirmed suppressed periodontal inflammation, which is an important strategy for treating periodontitis and for recovering the resulting alveolar bone loss. Therefore, PGFE is a potential, novel therapeutic agent for periodontal diseases.
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http://dx.doi.org/10.3390/antiox9121221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761716PMC
December 2020

Donepezil-related inadequate neuromuscular blockade during laparoscopic surgery: A case report.

World J Clin Cases 2020 Nov;8(21):5341-5346

Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju 61469, South Korea.

Background: Donepezil is an acetylcholinesterase inhibitor used to improve cognition and delay disease progression in dementia patients by increasing acetylcholine levels. This drug may potentially interact with neuromuscular blocking agents (NMBAs) that act on muscular acetylcholine receptors during general anesthesia. Herein, we present a case of inadequate neuromuscular blockade with rocuronium, a nondepolarizing NMBA, in a dementia patient who had taken donepezil.

Case Summary: A 71-year-old man was scheduled for laparoscopic gastrectomy. He had been taking donepezil 5 mg for dementia. General anesthesia was induced with propofol and remifentanil. The depth of neuromuscular blockade was monitored by train-of-four (TOF) stimulation. After the administration of rocuronium, the TOF ratio decreased at an unusually slow rate, and a TOF count of 0 was detected 7 min later. After intubation, a TOF count of 1 was detected within 1 min, and a TOF ratio of 12% was detected within 2 min. The TOF count remained at 4 even with an additional bolus and continuous infusion of rocuronium, suggesting resistance to this NMBA. Instead of propofol, an inhalation anesthetic was administered alongside another NMBA (cisatracurium). Then, the quality of neuromuscular blockade improved, and the TOF count remained at 0-1 for the next 70 min. No further problems were encountered with respect to surgery or anesthesia.

Conclusion: Donepezil may be responsible for inadequate neuromuscular blockade during anesthesia, especially when total intravenous anesthesia is used.
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http://dx.doi.org/10.12998/wjcc.v8.i21.5341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674726PMC
November 2020

Facilitation of Bone Healing Processes Based on the Developmental Function of in Tooth Loss Lesion.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 41940, Korea.

In the present study, we examined the bone healing capacity of , a homeobox gene that plays essential roles in the differentiation of a range of developing tissues, and identified its putative function in palatogenesis. We applied the knocking down of in human periodontal ligament fibroblasts to examine the osteogenic potential of . Additionally, we applied in vivo periodontitis induced experiment to reveal the possible application of knockdown for 1 and 2 weeks in bone healing processes. We examined the detailed histomorphological changes using Masson's trichrome staining and micro-computed tomography evaluation. Moreover, we observed the localization patterns of various signaling molecules, including α-SMA, CK14, IL-1β, and MPO to examine the altered bone healing processes. Furthermore, we investigated the process of bone formation using immunohistochemistry of Osteocalcin and Runx2. On the basis of the results, we suggest that the knocking down of via the activation of osteoblast and modulation of inflammation would be a plausible answer for bone regeneration as a gene therapy. Additionally, we propose that the purpose-dependent selection and application of developmental regulation genes are important for the functional regeneration of specific tissues and organs, where the pathological condition of tooth loss lesion would be.
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http://dx.doi.org/10.3390/ijms21228701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698889PMC
November 2020

Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment.

Gut 2020 Nov 18. Epub 2020 Nov 18.

Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

Objective: The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans. The aim of this study was to evaluate the mechanisms underlying serum glucose excretion in the small intestine and its contribution to glucose homeostasis after bariatric surgery.

Design: 2-Deoxy-2-[F]-fluoro-D-glucose (FDG) was measured in RYGB-operated or sham-operated obese diabetic rats. Altered glucose metabolism was targeted and RNA sequencing was performed in areas of high or low FDG uptake in the ileum or common limb. Intestinal glucose metabolism and excretion were confirmed using C-glucose and FDG. Increased glucose metabolism was evaluated in IEC-18 cells and mouse intestinal organoids. Obese or mice were treated with amphiregulin (AREG) to correlate intestinal glycolysis changes with changes in serum glucose homeostasis.

Results: The AREG/EGFR/mTOR/AKT/GLUT1 signal transduction pathway was activated in areas of increased glycolysis and intestinal glucose excretion in RYGB-operated rats. Intraluminal GLUT1 inhibitor administration offset improved glucose homeostasis in RYGB-operated rats. AREG-induced signal transduction pathway was confirmed using IEC-18 cells and mouse organoids, resulting in a greater capacity for glucose uptake via GLUT1 overexpression and sequestration in apical and basolateral membranes. Systemic and local AREG administration increased GLUT1 expression and small intestinal membrane translocation and prevented hyperglycaemic exacerbation.

Conclusion: Bariatric surgery or AREG administration induces apical and basolateral membrane GLUT1 expression in the small intestinal enterocytes, resulting in increased serum glucose excretion in the gut lumen. Our findings suggest a novel, potentially targetable glucose homeostatic mechanism in the small intestine.
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http://dx.doi.org/10.1136/gutjnl-2020-321402DOI Listing
November 2020

Developmental Roles of FUSE Binding Protein 1 () in Tooth Morphogenesis.

Int J Mol Sci 2020 Oct 29;21(21). Epub 2020 Oct 29.

Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, 2177, Dalgubeol-daero, Jung-gu, Daegu 41940, Korea.

FUSE binding protein 1 (), a regulator of the c-Myc transcription factor and a DNA/RNA-binding protein, plays important roles in the regulation of gene transcription and cellular physiology. In this study, to reveal the precise developmental function of , we examined the detailed expression pattern and developmental function of during tooth morphogenesis by RT-qPCR, in situ hybridization, and knock-down study using in vitro organ cultivation methods. In embryogenesis, is obviously expressed in the enamel organ and condensed mesenchyme, known to be important for proper tooth formation. Knocking down at E14 for two days, showed the altered expression patterns of tooth development related signalling molecules, including and . In addition, transient knock-down of at E14 revealed changes in the localization patterns of c-Myc and cell proliferation in epithelium and mesenchyme, related with altered tooth morphogenesis. These results also showed the decreased amelogenin and dentin sialophosphoprotein expressions and disrupted enamel rod and interrod formation in one- and three-week renal transplanted teeth respectively. Thus, our results suggested that plays a modulating role during dentinogenesis and amelogenesis by regulating the expression pattern of signalling molecules to achieve the proper structural formation of hard tissue matrices and crown morphogenesis in mice molar development.
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http://dx.doi.org/10.3390/ijms21218079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663687PMC
October 2020

Antibiotic treatment of amniotic fluid "sludge" in patients during the second or third trimester with uterine contraction.

Int J Gynaecol Obstet 2021 Apr 11;153(1):119-124. Epub 2020 Nov 11.

Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, South Korea.

Objective: To assess the effectiveness of antibiotic treatment in patients with amniotic fluid (AF) "sludge" during the second or third trimester with uterine contractions and intact membranes.

Methods: A retrospective cohort study was conducted of women at 15-32 weeks of pregnancy with uterine contractions and intact membranes. Women with AF "sludge" were treated with an antibiotic regimen of ceftriaxone, clarithromycin, and metronidazole. Based on changes in AF "sludge," patients were divided into group A (disappearance of "sludge") and group B (persistent "sludge").

Results: Women in group A (n=30) delivered later than those in group B (n=28). Group A showed a smaller initial size of "sludge" than group B (all P<0.05). Women in group A had a lower rate of preterm birth within 7 days, and before 28, 32, and 34 weeks of pregnancy, and composite neonatal morbidity and perinatal death than group B (all P<0.05).

Conclusion: The administration of antibiotics may eradicate AF "sludge" in women in the second or third trimester with uterine contractions and intact membranes, which are associated with the initial size of "sludge." Patients with disappearing "sludge" had more favorable pregnancy and neonatal outcomes than those with persistent "sludge."
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http://dx.doi.org/10.1002/ijgo.13425DOI Listing
April 2021

Effects of Different Microplastics on Nematodes in the Soil Environment: Tracking the Extractable Additives Using an Ecotoxicological Approach.

Environ Sci Technol 2020 11 14;54(21):13868-13878. Epub 2020 Oct 14.

Institute of Biology, Freie Universität Berlin, 14195 Berlin, Germany.

With increasing interest in the effects of microplastics on the soil environment, there is a need to thoroughly evaluate the potential adverse effects of these particles as a function of their characteristics (size, shape, and composition). In addition, extractable chemical additives from microplastics have been identified as an important toxicity pathway in the aquatic environment. However, currently, little is known about the effects of such additives on the soil environment. In this study on nematodes (), we adopted an ecotoxicological approach to assess the potential effects of 13 different microplastics (0.001-1% of soil dry weight) with different characteristics and extractable additives. We found that poly(ethylene terephthalate) (PET) fragments and polyacrylicnitrile (PAN) fibers show the highest toxicity, while high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS) fragments induced relatively less adverse effects on nematodes. In addition, low-density polyethylene (LDPE) induced no toxicity within our test concentration range for the acute period. Acute toxicity was mainly attributed to the extractable additives: when the additives were extracted, the toxic effects of each microplastic disappeared in the acute soil toxicity test. The harmful effects of the LDPE films and PAN fibers increased when the microplastics were maintained in the soil for a long-term period with frequent wet-dry cycles. We here provide clear evidence that microplastic toxicity in the soil is highly related to extractable additives. Our results suggest that future experiments consider extractable additives as key explanatory variables.
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http://dx.doi.org/10.1021/acs.est.0c04641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643727PMC
November 2020

Effects of Systemic Glucocorticoid Use on Fracture Risk: A Population-Based Study.

Endocrinol Metab (Seoul) 2020 09 22;35(3):562-570. Epub 2020 Sep 22.

College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Korea.

Background: Long-term glucocorticoid use increases fracture risk by reducing bone mass. This study evaluated the relationship between hip and vertebral fractures and the total amount of systematic glucocorticoid use.

Methods: We randomly selected 1,896,159 people aged 20 to 100 years who participated in the National Health Checkup program in 2006. The amount of glucocorticoids prescribed was calculated based on the defined daily dose (DDD). The total DDD was obtained by adding oral and parenteral glucocorticoids for 6 months from the index date. Subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low users (0< DDDs ≤45), intermediate users (45< DDDs ≤90), and high users (90< DDDs). We followed them for 2 years. A multivariate Cox proportional hazard model was used to evaluate the effects of the total amount of glucocorticoid use on hip and vertebral fractures.

Results: Higher glucocorticoid use was associated with a higher risk of vertebral fracture. Relative to non-users, the vertebral fracture risk was 1.39 times higher in the low-user group, 1.94 times higher in the intermediate-user group, and 2.43 times higher in the highuser group. The risk of hip fracture was 1.72 times higher in intermediate users and 3.28 times higher in high users than in non-users.

Conclusion: As the amount of glucocorticoid use for 6 months increased, the risk of hip and vertebral fractures became higher. In order to prevent fractures, it is necessary for doctors to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.
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http://dx.doi.org/10.3803/EnM.2020.659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520587PMC
September 2020

Incidence of and risk for osteonecrosis of the jaw in Korean osteoporosis patients treated with bisphosphonates: A nationwide cohort-study.

Bone 2021 02 19;143:115650. Epub 2020 Sep 19.

Department of Internal Medicine, Wonkwang University College of Medicine, Sanbon Hospital, Gunpo, Republic of Korea. Electronic address:

Purpose: To estimate the incidence of osteonecrosis of the jaw (ONJ) in patients treated with bisphosphonates (BPs) and to identify clinical risk factors that increase the risk for ONJ in Korean osteoporosis patients.

Methods: We used data acquired from the Korean National Health Insurance Service. Among 2,140,149 participants with osteoporosis in 2012, we selected 164,926 new BP users and 164,926 age- and sex-matched control subjects. The control group included only patients with no prescriptions for BPs between January 1, 2011, and December 31, 2016. Participants were followed for 4 years.

Results: Over the 4-year follow-up period, the cumulative incidence rates of ONJ were 20.9 and 6.9 per 100,000 person-years in the BP and control groups, respectively. The BP group had an increased risk for ONJ compared to the control group after adjusting for multiple variables (hazard ratio [HR] 3.72, 95% CI 2.70-5.11). Advanced age (≥70 years), comorbid diseases such as diabetes, hypertension, and rheumatoid arthritis (RA) were independent risk factors for the development of ONJ. In addition, tooth extraction (HR 9.85), gingivitis, and periodontal disease (HR 4.78) were strongly associated with ONJ.

Conclusions: ONJ incidence was 21 per 100,000 person-years in osteoporosis patients receiving bisphosphonates. Clinical factors including advanced age, diabetes, RA, dental disease, as well as BP use were significantly associated with ONJ.
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http://dx.doi.org/10.1016/j.bone.2020.115650DOI Listing
February 2021

DNA Polymerase Alpha Subunit B Is a Binding Protein for Erlotinib Resistance in Non-Small Cell Lung Cancer.

Cancers (Basel) 2020 Sep 13;12(9). Epub 2020 Sep 13.

Chemical Genomics Global Research Lab, Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Korea.

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas the overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.
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http://dx.doi.org/10.3390/cancers12092613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564424PMC
September 2020

Expanding the Clinical Spectrum of Multiple Evanescent White Dot Syndrome with Overlapping Multifocal Choroiditis.

Ocul Immunol Inflamm 2020 Sep 1:1-9. Epub 2020 Sep 1.

Department of Ophthalmology, Institute of Vision Research, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: To evaluate multifocal evanescent white dot syndrome (MEWDS) patients with and without overlapping multifocal choroiditis (MFC).

Methods: Thirty-four patients diagnosed between November 2008 and August 2018 at 2 hospitals were retrospectively reviewed. Multimodal imaging including optical coherence tomography angiography (OCTA) was assessed.

Results: Twenty-seven (79%) patients were women (overall mean age, 30 years). Five developed MFC lesions in the affected eyes, and one developed MFC in the unaffected fellow eye. Another developed combined MEWDS and MFC in the fellow eye during follow-up. Eyes with MFC had thicker choroids (316.5 and 197.3 µm, respectively; = .001) at presentation, which became thinner after resolution ( = .043). Those with subfoveal MFC had poor visual prognosis ( = .019). Areas of suspected choriocapillaris flow deficit were identified on OCTA.

Conclusion: Some MEWDS patients may develop overlapping MFC in the same or fellow eyes, presenting with increased choroidal thickness which decreased after resolution.
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http://dx.doi.org/10.1080/09273948.2020.1795206DOI Listing
September 2020

Probiotic Properties and Antioxidant Activities of SC28 and KU15151 in Fermented Black Gamju.

Foods 2020 Aug 21;9(9). Epub 2020 Aug 21.

Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Korea.

Black gamju is Korean traditional beverage fermented with molds. The aim of this study was to assess the probiotic properties and antioxidant activities of novel SC28 and KU15151 to develop black gamju with bioactive properties for health. Tolerance against artificial gastric juice and bile salts, adhesion ability on HT-29 cells of strains, and antibiotics susceptibility were evaluated as probiotics, and various enzyme productions were detected. The 2,2-diphenyl-1-picrylhydrazyl assay, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate, and β-carotene bleaching assay were used for antioxidant activity of samples. The tolerance of both strains to artificial gastric juice and bile salts (Oxgall) was more than 90%. Additionally, both strains did not produce β-glucuronidase and were resistant to gentamicin, kanamycin, streptomycin, and ciprofloxacin. After fermentation of black gamju with each strain, the number of viable lactic acid bacteria increased to 8.25-8.95 log colony forming unit/mL, but the pH value of fermented samples decreased more (to pH 3.33-3.41) than that of control (pH 4.37). KU15151 showed higher adhesion activity to HT-29 cells and antioxidant effects than SC28 in three antioxidant assays.
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http://dx.doi.org/10.3390/foods9091154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554914PMC
August 2020
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