Publications by authors named "Min Ju Kim"

434 Publications

Effect of against Thioacetamide-Induced Acute Liver Injury in Rat.

Can J Gastroenterol Hepatol 2021 13;2021:5581816. Epub 2021 Sep 13.

Department of Herbology, Korean Medicine of College, Daegu Haany University, Deagu 42158, Republic of Korea.

Both oxidative stress (OS) and inflammation are two fundamental pathological processes of acute liver injury (ALI). The current work is to investigate the effect and possible mechanism of (UR) on thioacetamide- (TAA-) induced ALI in rats. UR (100 and 200 mg/kg) was orally administrated with TAA (200 mg/kg of bodyweight, intraperitoneal injection) for 3 consecutive days. ALI was confirmed using histological examination and the factors associated with OS and liver function activity measured in serum. Moreover, expressions of inflammation and collagen-related proteins were measured by the Western blot analysis. Myeloperoxidase (MPO), which mediates OS in the ALI control group, was manifested by a significant rise compared with the normal group. UR significantly reduced AST, ALT, and ammonia levels in serum. The nuclear factor-B (NF-B) activation induced by TAA led to increase both inflammatory mediators and cytokines. Whereas, UR administration remarkably suppressed such an overexpression. UR supplementation improved matrix metalloproteinases (MMPs) such as MMP-1, -2, and -8. In contrast, tissue inhibitors of metalloproteinases- (TIMP-) 1 level increased significantly by UR treatment. In addition, the histopathological analysis showed that the liver tissue lesions were improved obviously by UR treatment. UR may ameliorate the effects of TAA-induced ALI in rats by suppressing both OS through MPO activation and proinflammatory factors through NF-B activation. In conclusion, UR exhibited a potent hepatoprotective effect on ALI through the suppression of OS.
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http://dx.doi.org/10.1155/2021/5581816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455208PMC
September 2021

Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study.

J Immunother Cancer 2021 Sep;9(9)

Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

Background: While some recent studies have reported the development of tuberculosis (TB) in patients exposed to immune checkpoint inhibitors (ICIs), there is limited evidence to date. Therefore, we evaluated the risk of TB in patients with cancer exposed to ICIs using the National Health Insurance claims data in South Korea.

Methods: Patients with diagnostic codes for non-small cell lung cancer, urothelial carcinoma or melanoma between August 2017 and June 2019 were identified. The incidence rate and standardized incidence ratio (SIR) of TB were calculated for both the ICI exposure and non-exposure groups. The risk of TB according to ICI exposure was assessed using a multivariable Cox regression model.

Results: During the study period, 141 550 patients with cancer and 916 new TB cases were identified. Among the 5037 patients exposed to ICIs, 20 were diagnosed with TB at a median of 2.2 months after the ICI was initiated. The crude incidence rate of TB per 100,000 person-years was 675.8 (95% CI 412.8 to 1043.8) for the ICI exposure group and 599.1 (95% CI 560.5 to 639.6) for the non-exposure group. The SIR for TB was 8.1 (95% CI 8.0 to 8.2) in the ICI exposure group. After adjusting for potential confounding factors, ICI treatment was not significantly associated with an increased risk of TB (HR: 0.73; 95% CI 0.47 to 1.14).

Conclusions: While the incidence of TB in cancer patients exposed to ICIs was eightfold higher than in the general population, the risk of patients with cancer developing TB did not significantly differ according to ICI exposure.
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http://dx.doi.org/10.1136/jitc-2021-002960DOI Listing
September 2021

Mining of a novel esterase (est3S) gene from a cow rumen metagenomic library with organosphosphorus insecticides degrading capability: Catalytic insights by site directed mutations, docking, and molecular dynamic simulations.

Int J Biol Macromol 2021 Sep 7;190:441-455. Epub 2021 Sep 7.

Department of Food Science, Gyeongsang National University, Jinju 52725, Republic of Korea. Electronic address:

A novel esterase (est3S) gene, 1026 bp in size, was cloned from a metagenomic library made of uncultured microorganisms from the contents of cow rumen. The esterolytic enzyme (Est3S) is composed of 342 amino acids and shows the highest identity with EstGK1 (71.7%) and EstZ3 (63.78%) esterases from the uncultured bacterium. The Est3S did not cluster in any up-to-date classes (I to XVIII) of esterase and lipase. Est3S protein molecular weight was determined to be 38 kDa by gel electrophoresis and showed optimum activity at pH 7.0 and 40 °C and is partially resistant to organic solvents. Est3S activity was enhanced by K, Na, Mg, and Ca and its highest activity was observed toward the short-chain p-nitrophenyl esters. Additionally, Est3S can degrade chlorpyrifos (CP) and methyl parathion (70% to 80%) in an hour. A mutated Est3S (Ser132-Ala132) did not show any activity toward CP and ester substrates. Notably, the GHS132QG motif is superimposed with the homolog esterase and cutinase-like esterase. Therefore, Ser132 is the critical amino acid like other esterases. The Est3S is relatively stable with ester compounds, and the methyl parathion complex was confirmed by molecular dynamics simulation. NOVELTY STATEMENT: A novel esterase gene (est3S) expressing esters and organophosphorus insecticide degradation traits was isolated from the uncultured bacterium in the contents of cow rumen. The Est3S protein did not cluster in any up-to-date classes (I to XVIII) of esterase/lipase proteins. Est3S was stable with the ligands up to 100 ns during the molecular dynamic simulations.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.224DOI Listing
September 2021

(-)-Loliolide Isolated from Abate UVB-Induced Oxidative Damage in Human Dermal Fibroblasts and Subside ECM Degradation.

Mar Drugs 2021 Jul 30;19(8). Epub 2021 Jul 30.

Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 59626, Korea.

Ultraviolet (UV) B exposure is a prominent cause of skin aging and a contemporary subject of interest. The effects are progressing through the generation of reactive oxygen species (ROS) that alter cell signaling pathways related to inflammatory responses. The present study evaluates the protective effects of (7aR)-6-hydroxy-4,4,7a-trimethyl-6,7-dihydro-5H-1-benzofuran-2-one (HTT) isolated from the edible brown algae Sargassum horneri against UVB protective effects in human dermal fibroblasts (HDFs). HTT treatment dose-dependently suppressed intracellular ROS generation in HDFs with an IC of 62.43 ± 3.22 µM. HTT abated UVB-induced mitochondrial hyperpolarization and apoptotic body formation. Furthermore, UVB-induced activation of key nuclear factor (NF)-κB and mitogen-activated protein kinase signaling proteins were suppressed in HTT treated cells while downregulating pro-inflammatory cytokines (interleukin-1β, 6, 8, 33 and tumor necrosis factor-α). Moreover, HTT treatment downregulated matrix metalloproteinase1, 2, 3, 8, 9 and 13 that was further confirmed by the inhibition of collagenase and elastase activity. The evidence implies that HTT delivers protective effects against premature skin aging caused by UVB exposure via suppressing inflammatory responses and degradation of extracellular matrix (ECM) components. Extensive research in this regard will raise perspectives for using HTT as an ingredient in UV protective ointments.
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http://dx.doi.org/10.3390/md19080435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399698PMC
July 2021

Distribution and antimicrobial resistance of Vibrio parahaemolyticus isolated from fish and shrimp aquaculture farms along the Korean coast.

Mar Pollut Bull 2021 Jul 30;171:112785. Epub 2021 Jul 30.

West Sea Fisheries Research Institute, National Institute of Fisheries Science, Incheon 22383, Republic of Korea.

The present study investigated the distribution and antimicrobial susceptibility patterns of Vibrio parahaemolyticus in water samples and aquatic animals (fish and shrimp) from major aquaculture farms along the Korean coast in 2018. V. parahaemolyticus is the most common pathogen causing seafood-borne illness. The strain was detected in 34.7% of all samples tested, and was detected at higher levels during summer to autumn when the water temperature is higher. Although more than 90.0% of V. parahaemolyticus isolates were sensitive to 13 of the 15 antimicrobials tested, which is useful for treating V. parahaemolyticus infectious disease, the isolates exhibited higher resistance to two antibiotics (colistin and ampicillin), which should be excluded as treatment options for these infections. Koreans typically enjoy consuming raw seafood. To reduce the potential human health risk of raw seafood consumption, the prevalence and antimicrobial resistance of V. parahaemolyticus in aquaculture environments should be continuously valuated.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112785DOI Listing
July 2021

Hot-melt extruded copper sulfate affects the growth performance, meat quality, and copper bioavailability of broiler chickens.

Anim Biosci 2021 Jun 24. Epub 2021 Jun 24.

College of Animal Life Sciences, Kangwon National University, Chuncheon 24341, Korea.

Objective: This study was conducted to evaluate the effects of the supplementation of diets of broiler chickens with hot-melt extruded CuSO4 (HME-Cu) on their growth performance, nutrient digestibility, gut microbiota, small intestinal morphology, meat quality, and copper (Cu) bioavailability.

Methods: A total of 225 broilers (Ross 308), one-day old and initial weight 39.14 g, were weighed and distributed between 15 cages (15 birds per cage) in a completely randomized experimental design with 3 treatments (diets) and 5 replicates per treatment. Cages were allotted to three treatments including control (without supplemental Cu), IN-Cu (16 mg/kg of CuSO4), and HME-Cu (16 mg/kg of HME processed CuSO4).

Results: The HME-Cu treatment tended to increase the overall body weight gain (BWG) (p<0.10). The apparent digestibility of Cu was increased by supplementation of HME-Cu at phase 2 (p<0.05). The Escherichia coli (E. coli) count in cecum tended to decrease with the supplementation with Cu (p<0.10). In addition, the HME-Cu treatment had a higher pH of breast meat than the control and IN-Cu treatments (p<0.05). Significant increases in the cooking loss (CL), water-holding capacity (WHC), and lightness in the breast were observed in the HME-Cu treatment compared to the control (p<0.05). The Cu content of excreta increased with the Cu supplementation (p<0.05). The concentration of excreta Cu in broilers was decreased in the HME-Cu compared to the IN-Cu in phase 2 (p<0.05). The Cu concentration in the liver was increased with the HME-Cu supplementation, compared with the control diets (p<0.05).

Conclusion: This study showed that HME-Cu supplementation at the requirement level (16 mg/kg diets) in broiler diets did not affect the growth performance and the physiological function of Cu in broilers. However, supplementation of Cu in HME form improved the meat quality and the bioavailability of Cu.
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http://dx.doi.org/10.5713/ab.21.0030DOI Listing
June 2021

Psychomotor Speed Predicts Outcome in Patients with Acute Meningitis and Encephalitis: A Prospective Observational Study.

Clin EEG Neurosci 2021 Jul 13:15500594211031137. Epub 2021 Jul 13.

65526Asan Medical Center, Seoul, South Korea.

Although acute meningitis and encephalitis are known to cause cognitive dysfunction, the prognostic values of neuropsychological and neurophysiological tests in predicting clinical outcomes are seldom studied. We investigated specific neurocognitive dysfunction and event-related potentials (ERPs), which can predict functional outcomes in patients with acute meningitis and encephalitis. . We enrolled consecutive adult patients with acute meningitis and encephalitis and performed neuropsychological tests and ERP studies using a passive auditory oddball paradigm at enrollment. Patient functional outcomes were assessed using the Glasgow Outcome Scale at 6 (GOS6) months after discharge. . Twenty-two patients were included in the study. Among 21 patients who performed neuropsychological tests, Korean-Trail Making Test-Elderly's version, Part A time (TMT-A time) correlated with GOS6, which remained significant even after controlling for age. We identified a significant association between TMT-A time and P3a latency. Post-hoc analysis showed that patients with longer TMT-A time (≥23 s) tended to have longer P3a latency than those with shorter TMT-A time. . Decreased psychomotor speed predicted poor clinical outcomes. Because TMT-A time can be performed at the bedside in a relatively short time, this might be a useful neuropsychological biomarker to predict or monitor clinical outcomes. Furthermore, passive oddball P3a may be useful in patients with more severe disease who are unable to perform the TMT task.
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http://dx.doi.org/10.1177/15500594211031137DOI Listing
July 2021

Deep convolution neural networks to differentiate between COVID-19 and other pulmonary abnormalities on chest radiographs: Evaluation using internal and external datasets.

Int J Imaging Syst Technol 2021 May 13. Epub 2021 May 13.

Department of Radiology Korea University Anam Hospital Seoul Republic of Korea.

We aimed to evaluate the performance of convolutional neural networks (CNNs) in the classification of coronavirus disease 2019 (COVID-19) disease using normal, pneumonia, and COVID-19 chest radiographs (CXRs). First, we collected 9194 CXRs from open datasets and 58 from the Korea University Anam Hospital (KUAH). The number of normal, pneumonia, and COVID-19 CXRs were 4580, 3884, and 730, respectively. The CXRs obtained from the open dataset were randomly assigned to the training, tuning, and test sets in a 70:10:20 ratio. For external validation, the KUAH (20 normal, 20 pneumonia, and 18 COVID-19) dataset, verified by radiologists using computed tomography, was used. Subsequently, transfer learning was conducted using DenseNet169, InceptionResNetV2, and Xception to identify COVID-19 using open datasets (internal) and the KUAH dataset (external) with histogram matching. Gradient-weighted class activation mapping was used for the visualization of abnormal patterns in CXRs. The average AUC and accuracy of the multiscale and mixed-COVID-19Net using three CNNs over five folds were (0.99 ± 0.01 and 92.94% ± 0.45%), (0.99 ± 0.01 and 93.12% ± 0.23%), and (0.99 ± 0.01 and 93.57% ± 0.29%), respectively, using the open datasets (internal). Furthermore, these values were (0.75 and 74.14%), (0.72 and 68.97%), and (0.77 and 68.97%), respectively, for the best model among the fivefold cross-validation with the KUAH dataset (external) using domain adaptation. The various state-of-the-art models trained on open datasets show satisfactory performance for clinical interpretation. Furthermore, the domain adaptation for external datasets was found to be important for detecting COVID-19 as well as other diseases.
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http://dx.doi.org/10.1002/ima.22595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239912PMC
May 2021

Luteolin Orchestrates Porcine Oocyte Meiotic Progression by Maintaining Organelle Dynamics Under Oxidative Stress.

Front Cell Dev Biol 2021 15;9:689826. Epub 2021 Jun 15.

Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South Korea.

Increasing evidence has demonstrated that oxidative stress impairs oocyte maturation, but the underlying mechanisms remain largely unknown. Here, for the first time, we examined the antioxidant role of luteolin in meiotic progression and the underlying mechanisms. Supplementation of 5 μM luteolin increased the rates of first polar body extrusion and blastocyst formation after parthenogenetic activation, and the expression levels of oocyte competence ( and )-, mitogen-activated protein kinase ()-, and maturation promoting factor ( and )-related genes were also improved. Luteolin supplementation decreased intracellular reactive oxygen species levels and increased the expression levels of oxidative stress-related genes (, , and ). Interestingly, luteolin alleviated defects in cell organelles, including actin filaments, the spindle, mitochondria, the endoplasmic reticulum, and cortical granules, caused by HO exposure. Moreover, luteolin significantly improved the developmental competence of -fertilized embryos in terms of the cleavage rate, blastocyst formation rate, cell number, cellular survival rate, and gene expression and markedly restored the competencies decreased by HO treatment. These findings revealed that luteolin supplementation during maturation improves porcine meiotic progression and subsequent embryonic development by protecting various organelle dynamics against oxidative stress, potentially increasing our understanding of the underlying mechanisms governing the relationship between oxidative stress and the meiotic events required for successful oocyte maturation.
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http://dx.doi.org/10.3389/fcell.2021.689826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239245PMC
June 2021

Evaluating an In-House Cell-Based Assay for Detecting Antibodies Against Muscle-Specific Tyrosine Kinase in Myasthenia Gravis.

J Clin Neurol 2021 Jul;17(3):400-408

Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.

Background And Purpose: Detecting antibodies against muscle-specific tyrosine kinase (MuSK Abs) is essential for diagnosing myasthenia gravis (MG). We applied an in-house cell-based assay (CBA) to detect MuSK Abs.

Methods: A stable cell line was generated using a lentiviral vector, which allowed the expression of MuSK tagged with green fluorescent protein in human embryonic kidney 293 (HEK293) cells. Serum and anti-human IgG antibody conjugated with red fluorescence were added. The presence of MuSK Abs was determined based on the fluorescence intensity and their colocalization in fluorescence microscopy. Totals of 218 serum samples collected from 177 patients with MG, 31 with other neuromuscular diseases, and 10 healthy controls were analyzed. The CBA results were compared with those of a radioimmunoprecipitation assay (RIPA) and an enzyme-linked immunosorbent assay (ELISA).

Results: The MuSK-HEK293 cell line stably expressed MuSK protein. The CBA detected MuSK Abs in 34 (19.2%) of 177 samples obtained from patients with MG and in none of the participants having other neuromuscular diseases or in the healthy controls. The clinical characteristics of the patients with MuSK MG determined based on the CBA were strongly correlated with known clinical features of MuSK MG. There was an almost perfect agreement between the results of the CBA and those of the RIPA (Cohen's kappa=0.880, <0.001) and ELISA (Cohen's kappa=0.982, <0.001).

Conclusions: The results of the in-house CBA showed excellent agreement with both the RIPA and ELISA. Our in-house CBA can be considered a reliable method for detecting MuSK Abs.
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http://dx.doi.org/10.3988/jcn.2021.17.3.400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242307PMC
July 2021

Interplay among Conformation, Intramolecular Hydrogen Bonds, and Chameleonicity in the Membrane Permeability and Cyclophilin A Binding of Macrocyclic Peptide Cyclosporin O Derivatives.

J Med Chem 2021 06 7;64(12):8272-8286. Epub 2021 Jun 7.

Department of Chemistry, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.

A macrocyclic peptide scaffold with well-established structure-property relationship is desirable for tackling undruggable targets. Here, we adopted a natural macrocycle, cyclosporin O () and its derivatives (-), and evaluated the impact of conformation on membrane permeability, cyclophilin A (CypA) binding, and the pharmacokinetic (PK) profile. In nonpolar media, showed a similar conformation to cyclosporin A (), a well-known chameleonic macrocycle, but less chameleonic behavior in a polar environment. The weak chameleonicity of resulted in decreased membrane permeability; however, the more rigid conformation of was not detrimental to its PK profile. exhibited a higher plasma concentration than , which resulted from minimal CypA binding and lower accumulation in red blood cells and moderate oral bioavailability ( = 12%). Our study aids understanding of , a macrocyclic peptide that is less explored than but with greater potential for diversity generation and rational design.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00211DOI Listing
June 2021

Not all that glitters is cancer: Not all enlarged lateral pelvic mass is a metastasis.

ANZ J Surg 2021 May 28. Epub 2021 May 28.

Department of Colorectal Surgery, Korea University Anam Hospital, Seoul, South Korea.

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http://dx.doi.org/10.1111/ans.16974DOI Listing
May 2021

Totally laparoscopic total gastrectomy using the modified overlap method and conventional open total gastrectomy: A comparative study.

World J Gastroenterol 2021 May;27(18):2193-2204

Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea.

Background: Although several methods of totally laparoscopic total gastrectomy (TLTG) have been reported. The best anastomosis technique for LTG has not been established.

Aim: To investigate the effectiveness and surgical outcomes of TLTG using the modified overlap method compared with open total gastrectomy (OTG) using the circular stapled method.

Methods: We performed 151 and 131 surgeries using TLTG with the modified overlap method and OTG for gastric cancer between March 2012 and December 2018. Surgical and oncological outcomes were compared between groups using propensity score matching. In addition, we analyzed the risk factors associated with postoperative complications.

Results: Patients who underwent TLTG were discharged earlier than those who underwent OTG [TLTG (9.62 ± 5.32) OTG (13.51 ± 10.67), < 0.05]. Time to first flatus and soft diet were significantly shorter in TLTG group. The pain scores at all postoperative periods and administration of opioids were significantly lower in the TLTG group than in the OTG group. No significant difference in early, late and esophagojejunostomy (EJ)-related complications or 5-year recurrence free and overall survival between groups. Multivariate analysis demonstrated that body mass index [odds ratio (OR), 1.824; 95% confidence interval (CI): 1.029-3.234, = 0.040] and American Society of Anaesthesiologists (ASA) score (OR, 3.154; 95%CI: 1.084-9.174, = 0.035) were independent risk factors of early complications. Additionally, age was associated with ≥ 3 Clavien-Dindo classification and EJ-related complications.

Conclusion: Although TLTG with the modified overlap method showed similar complication rate and oncological outcome with OTG, it yields lower pain score, earlier bowel recovery, and discharge. Surgeons should perform total gastrectomy cautiously and delicately in patients with obesity, high ASA scores, and older ages.
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http://dx.doi.org/10.3748/wjg.v27.i18.2193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117731PMC
May 2021

Effects of (-)-Loliolide against Fine Dust Preconditioned Keratinocyte Media-Induced Dermal Fibroblast Inflammation.

Antioxidants (Basel) 2021 Apr 26;10(5). Epub 2021 Apr 26.

Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 59626, Korea.

At present air pollution in parts of East Asia is at an alarming level due to elevated levels of fine dust (FD). Other than pulmonary complications, FD was found to affect the pathogenesis of ROS-dependent inflammatory responses via penetrating barrier-disrupted skin, leading to degradation of extracellular matrix components through the keratinocyte-fibroblast axis. The present study discloses the evaluation of human dermal fibroblast (HDF) responses to FD preconditioned human keratinocyte media (HPM) primed without and with (-)-loliolide (HTT). HPM-FD treatment increased the ROS level in HDFs and activated mitogen-activated protein kinase-derived nuclear factor (NF)-κB inflammatory signaling pathways with a minor reduction of viability. The above events led to cell differentiation and production of matrix metalloproteinases (MMP), increasing collagenase and elastase activity despite the increase of tissue inhibitors of metalloproteinases (TIMP). Media from HTT primed keratinocytes stimulated with FD indicated ameliorated levels of MMPs, inflammatory cytokines, and chemokines in HDFs with suppressed collagenase and elastase activity. Present observations help to understand the factors that affect HDFs in the microenvironment of FD exposed keratinocytes and the therapeutic role of HTT as a suppressor of skin aging. Further studies using organotypic skin culture models could broaden the understanding of the effects of FD and the therapeutic role of HTT.
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http://dx.doi.org/10.3390/antiox10050675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144948PMC
April 2021

Passive Immunity and Antibody Response Induced by VLP Immunization.

Vaccines (Basel) 2021 Apr 23;9(5). Epub 2021 Apr 23.

Department of Medical Zoology, Kyung Hee University School of Medicine, Seoul 02447, Korea.

Passive immunity can provide immediate protection against infectious pathogens. To date, only a few studies have investigated the effect of passive immunization against , and the use of immune sera acquired from VLP-vaccinated mice for passive immunity assessment remains unreported. In this study, immune sera were produced by a single immunization with virus-like particles (VLPs) expressing the inner membrane complex (IMC), rhoptry protein 18 (ROP18), and microneme protein 8 (MIC8) of , with or without a CpG-ODN adjuvant. The passive immunization of immune sera conferred protection in mice, as indicated by their potent parasite-specific antibody response, lessened brain cyst counts, lower bodyweight loss, and enhanced survival. In order to confirm that the immune sera of the VLP-immunized mice were truly protective, the antibody responses and other immunological parameters were measured in the VLP-immunized mice. We found that VLP immunization induced higher levels of parasite-specific IgG, IgG subclass, and IgM antibody responses in the sera and intestines than in the controls. Enhanced Th1 and Th2-associated cytokines in the spleen, diminished brain cyst counts, and lessened body weight loss were found following ME49 challenge infection. These results suggest that passive immunization with the immune sera acquired from VLP-vaccinated mice can confer adequate protection against infection.
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http://dx.doi.org/10.3390/vaccines9050425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146287PMC
April 2021

Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice.

Molecules 2021 Apr 12;26(8). Epub 2021 Apr 12.

Convergence Medical Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul 05505, Korea.

LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1α (HIF-1α), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1α, pharmacokinetics needs to be evaluated to assess its potential as an anti-tumor agent. Here, we investigated the plasma pharmacokinetics and metabolism of LW6 in mice. LW6 exhibited a small volume of distribution (0.5 ± 0.1 L/kg), and a short terminal half-life (0.6 ± 0.1 h). Following intravenous or oral administration, LW6 was rapidly converted to its active metabolite, (4-adamantan-1-yl-phenoxy)acetic acid (APA). Although LW6 was rapidly absorbed, its oral bioavailability, estimated using values, was low (1.7 ± 1.8%). It was slowly degraded in mouse liver microsomes ( > 1 h) and serum ( > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. Thus, our results indicated the need to simultaneously consider the active metabolite as well as the parent compound for successful evaluation during lead optimization.
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http://dx.doi.org/10.3390/molecules26082226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070284PMC
April 2021

Pharmacokinetic Characterization of LW6, a Novel Hypoxia-Inducible Factor-1α (HIF-1α) Inhibitor in Mice.

Molecules 2021 Apr 12;26(8). Epub 2021 Apr 12.

Convergence Medical Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul 05505, Korea.

LW6, an (aryloxyacetylamino)benzoic acid derivative, was recently identified to be an inhibitor of hypoxia-inducible factor-1α (HIF-1α), which is an attractive target for cancer therapeutics. Although LW6 is known to act by inhibiting the accumulation of HIF-1α, pharmacokinetics needs to be evaluated to assess its potential as an anti-tumor agent. Here, we investigated the plasma pharmacokinetics and metabolism of LW6 in mice. LW6 exhibited a small volume of distribution (0.5 ± 0.1 L/kg), and a short terminal half-life (0.6 ± 0.1 h). Following intravenous or oral administration, LW6 was rapidly converted to its active metabolite, (4-adamantan-1-yl-phenoxy)acetic acid (APA). Although LW6 was rapidly absorbed, its oral bioavailability, estimated using values, was low (1.7 ± 1.8%). It was slowly degraded in mouse liver microsomes ( > 1 h) and serum ( > 6 h). About 54% or 44.8% of LW6 was available systemically as APA in the mouse after a single intravenous or oral administration, respectively. Thus, our results indicated the need to simultaneously consider the active metabolite as well as the parent compound for successful evaluation during lead optimization.
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http://dx.doi.org/10.3390/molecules26082226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070284PMC
April 2021

Effects of Fermented Beverage in Subjects with Metabolic Syndrome.

Prev Nutr Food Sci 2021 Mar;26(1):12-20

Bio-Food Research Center, Hurom Co., Ltd., Gyeongnam 50969, Korea.

This study investigated the effects of fermented beverage, kale/apple juice containing 5% vinegar in subjects with metabolic syndrome. Subjects were randomly assigned to receive 250 mL fermented beverage or water containing fructose, glucose, and sucrose twice daily for 10 weeks. Consumption of the fermented beverage significantly decreased plasma triglyceride, thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNF)-α, and high sensitivity C-reactive protein (hs-CRP) levels compared to baseline values (<0.05). Furthermore, consumption of the fermented beverage significantly decreased homeostasis model assessment for insulin resistance (HOMA-IR) values and atherogenic indexes compared with baseline values (<0.05). In the control group, plasma triglyceride, TBARS, TNF-α, and hs-CRP levels, atherogenic indexes, and HOMA-IR values did not significantly differ pre-and post-treatment. The fermented beverage inhibited the activities of α-glucosidase and pancreatic lipase , therefore could be helpful in alleviating metabolic syndrome in subjects with metabolic syndrome.
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http://dx.doi.org/10.3746/pnf.2021.26.1.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027050PMC
March 2021

Impact of Esophagojejunal Reconstruction without Division of the Mesentery for Total Laparoscopic Total Gastrectomy.

J Gastric Cancer 2021 Mar 25;21(1):63-73. Epub 2021 Mar 25.

Department of Stomach Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Purpose: This study aimed to compare the surgical outcomes of total laparoscopic total gastrectomy without mesentery division (LTG without MD) and conventional total laparoscopic total gastrectomy (CLTG), as well as evaluate the appropriate method for esophagojejunostomy (EJ) reconstruction after total laparoscopic total gastrectomy (TLTG).

Materials And Methods: We retrospectively analyzed data from 301 consecutive patients who underwent TLTG for upper or middle third gastric cancer between January 2016 and May 2019. After propensity score matching, 95 patients who underwent LTG without MD and 95 who underwent CLTG were assessed. Data on clinical characteristics and surgical outcomes, including operation time, length of postoperative hospital stay, pathological findings, and postoperative complications were analyzed.

Results: The LTG without MD group showed a shorter time to first flatus (3.26±0.80 vs. 3.62±0.81 days, P=0.003) and a shorter time to soft diet (2.80±2.09 vs. 3.52±2.20 days, P=0.002). The total EJ-related complications in the LTG without MD group were comparable to those in the CLTG group (9.47% vs. 3.16%, P=0.083). EJ-related leakage (6.32% vs. 3.16%, P=0.317) and EJ-related stricture (3.16% vs. 1.05%, P=0.317) rates were not significantly different between the LTG without MD and CLTG groups. No significant differences were found between the two groups in terms of other early surgical outcomes such as early complications, late complications, hospital stay, and readmission rate.

Conclusions: LTG without MD is a safe surgical treatment for upper or middle third gastric cancer. LTG without MD may be an alternative procedure for EJ anastomosis during TLTG.
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http://dx.doi.org/10.5230/jgc.2021.21.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019998PMC
March 2021

Unexpected beta-amyloid production by middle doses of resveratrol through stabilization of APP protein and AMPK-mediated inhibition of trypsin-like proteasome activity in a cell model of Alzheimer's disease.

Food Chem Toxicol 2021 Jun 14;152:112185. Epub 2021 Apr 14.

Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon, Kangwon-do, Republic of Korea; Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chuncheon, Kangwon-do, Republic of Korea. Electronic address:

Resveratrol is a drug candidate used for Alzheimer's disease (AD) and shows beneficial effects in various toxicity and production models, although recent clinical trial data did not show satisfactory results. Here we demonstrated the potential side effects of resveratrol in AD. We demonstrated resveratrol concentration- and time-dependent Aβ production using Aβ secreted cellular model and analyzed resveratrol-related molecular signaling. In Swedish mutant of APP (APPsw) stably expressing cells, treatment with a middle dose of resveratrol for 24 h unexpectedly increased Aβ production, but higher concentrations or shorter treatment durations did not. Resveratrol-mediated Aβ production was caused by an increase in APP protein levels associated with proteasome-dependent regulation of APP stability. Inhibition of AMPK, cAMP production, and epac1 attenuated Aβ production and APP increase by resveratrol, which blocked the inhibition of trypsin-like proteasomal activity. In addition, high-dose resveratrol decreased Aβ secretion and β-secretase activity at any treatment duration. Our data suggest that an appropriate dose of resveratrol can paradoxically increase Aβ production via stabilization of APP protein in an AMPK-proteasome signaling-dependent manner, which provides mechanistic insights into prior unsatisfactory clinical outcomes and the future clinical use of resveratrol.
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http://dx.doi.org/10.1016/j.fct.2021.112185DOI Listing
June 2021

Metabolite Profiling and Characterization of LW6, a Novel HIF-1α Inhibitor, as an Antitumor Drug Candidate in Mice.

Molecules 2021 Mar 30;26(7). Epub 2021 Mar 30.

Asan Medical Center, Asan Institute for Life Sciences, Seoul 05505, Korea.

A novel HIF (hypoxia-inducible factor)-1α inhibitor, the (aryloxyacetylamino)benzoic acid derivative LW6, is an anticancer agent that inhibits the accumulation of HIF-1α. The aim of this study was to characterize and determine the structures of the metabolites of LW6 in ICR mice. Metabolite identification was performed using a predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion (pMRM-IDA-EPI) method in negative ion mode on a hybrid triple quadrupole-linear ion trap mass spectrometer (QTRAP). A total of 12 metabolites were characterized based on their MS/MS spectra, and the retention times were compared with those of the parent compound. The metabolites were divided into five structural classes based on biotransformation reactions: amide hydrolysis, ester hydrolysis, mono-oxidation, glucuronidation, and a combination of these reactions. From this study, 2-(4-((3r,5r,7r)-adamantan-1-yl)phenoxy)acetic acid (APA, M7), the metabolite produced via amide hydrolysis, was found to be a major circulating metabolite of LW6 in mice. The results of this study can be used to improve the pharmacokinetic profile by lowering the clearance and increasing the exposure relative to LW6.
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http://dx.doi.org/10.3390/molecules26071951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037336PMC
March 2021

Pharmacokinetic Characterization of Supinoxin and Its Physiologically Based Pharmacokinetic Modeling in Rats.

Pharmaceutics 2021 Mar 11;13(3). Epub 2021 Mar 11.

Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Korea.

Supinoxin is a novel anticancer drug candidate targeting the Y593 phospho-p68 RNA helicase, by exhibiting antiproliferative activity and/or suppression of tumor growth. This study aimed to characterize the in vitro and in vivo pharmacokinetics of supinoxin and attempt physiologically based pharmacokinetic (PBPK) modeling in rats. Supinoxin has good permeability, comparable to that of metoprolol (high permeability compound) in Caco-2 cells, with negligible net absorptive or secretory transport observed. After an intravenous injection at a dose range of 0.5-5 mg/kg, the terminal half-life (i.e., 2.54-2.80 h), systemic clearance (i.e., 691-865 mL/h/kg), and steady state volume of distribution (i.e., 2040-3500 mL/kg) of supinoxin remained unchanged, suggesting dose-independent (i.e., dose-proportional) pharmacokinetics for the dose ranges studied. After oral administration, supinoxin showed modest absorption with an absolute oral bioavailability of 56.9-57.4%. The fecal recovery following intravenous and oral administration was 16.5% and 46.8%, respectively, whereas the urinary recoveries in both administration routes were negligible. Supinoxin was mainly eliminated via NADPH-dependent phase I metabolism (i.e., 58.5% of total clearance), while UDPGA-dependent phase II metabolism appeared negligible in the rat liver microsome. Supinoxin was most abundantly distributed in the adipose tissue, gut, and liver among the nine major tissues studied (i.e., the brain, liver, kidneys, heart, lungs, spleen, gut, muscles, and adipose tissue), and the tissue exposure profiles of supinoxin were well predicted with physiologically based pharmacokinetics.
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http://dx.doi.org/10.3390/pharmaceutics13030373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998731PMC
March 2021

Epidemiology of congenital upper limb anomalies in Korea: A nationwide population-based study.

PLoS One 2021 9;16(3):e0248105. Epub 2021 Mar 9.

Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

This study aimed to analyze the epidemiology of congenital upper limb anomalies (CULA) in Korea. We evaluated the incidence of each type of CULA, the presence of coexisting anomalies and the surgical treatment status in CULA patients. We conducted a retrospective cohort study of patients aged < 1 year between 2007 and 2016 who were registered with CULA in the Health Insurance Review and Assessment Service of Korea. In total, 10,704 patients had CULA, including 6,174 boys (57.7%) and 4,530 girls (42.3%). The mean annual incidence of CULA was 23.5 per 10,000 live births; it was significantly higher in boys than in girls (26.3 vs. 20.5, p < 0.001). Among the four categories of CULA-polydactyly, syndactyly, limb deficiency, and other anomalies-polydactyly was the most common. In total, 4,149 patients (38.8%) had other congenital anomalies and coexisting anomalies of the circulatory system (24.9%) were the most common. In total 4,776 patients (44.6%) underwent operative treatment for CULA within minimum three years of the diagnosis. The proportion of patients who underwent surgical treatment was significantly higher for polydactyly (73.4% vs. 16.8%, p < 0.001) and syndactyly (65.3% vs. 41.5%, p < 0.001), but it was significantly lower in limb deficiency (27.6% vs. 45.4%, p < 0.001) and other anomalies (10.0% vs. 69.8%, p < 0.001) than rest of CULA patients. Among the patients who had operations, 21.5% underwent multiple operations. The proportion of patients who underwent multiple operations was significantly higher in syndactyly (35.6% vs. 18.1%, p < 0.001), but it was significantly lower in polydactyly (4.0% vs. 95.5%, p < 0.001) and other anomalies (17.9% vs. 21.9%, p < 0.001) than rest of CULA patients. These results could provide a basis for estimating the national healthcare costs for CULA and the required number of CULA specialists.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248105PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943020PMC
March 2021

Selected nasogastric lavage in patients with nonvariceal upper gastrointestinal bleeding.

BMC Gastroenterol 2021 Mar 6;21(1):113. Epub 2021 Mar 6.

Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Korea.

Background: Risk stratification before endoscopy is crucial for proper management of patients suspected as having upper gastrointestinal bleeding (UGIB). There is no consensus regarding the role of nasogastric lavage for risk stratification. In this study, we investigated the usefulness of nasogastric lavage to identify patients with UGIB requiring endoscopic examination.

Methods: From January 2017 to December 2018, patients who visited the emergency department with a clinical suspicion of UGIB and who underwent nasogastric lavage before endoscopy were eligible. Patients with esophagogastric variceal bleeding were excluded. The added predictive ability of nasogastric lavage to the Glasgow-Blatchford score (GBS) was estimated using category-free net reclassification improvement and integrated discrimination improvement.

Results: Data for 487 patients with nonvariceal UGIB were analyzed. The nasogastric aspirate was bloody in 67 patients (13.8 %), coffee-ground in 227 patients (46.6 %), and clear in 193 patients (39.6 %). The gross appearance of the nasogastric aspirate was associated with the presence of UGIB. Model comparisons showed that addition of nasogastric lavage findings to the GBS improved the performance of the model to predict the presence of UGIB. Subgroup analysis showed that nasogastric lavage improved the performance of the prediction model in patients with the GBS ≤ 11, whereas no additive value was found when the GBS was greater than 11.

Conclusions: Nasogastric lavage is useful for predicting the presence of UGIB in a subgroup of patients, while its clinical utility is limited in high-risk patients with a GBS of 12 or more.
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http://dx.doi.org/10.1186/s12876-021-01690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937281PMC
March 2021

Fucoidan Fractionated from via Step-Gradient Ethanol Precipitation Indicate Promising UVB-Protective Effects in Human Keratinocytes.

Antioxidants (Basel) 2021 Feb 26;10(3). Epub 2021 Feb 26.

Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu 59626, Korea.

Fucoidans exhibit a wide range of bioactivities and receive significant attention in functional food and cosmetic research. Industrial applications of fucoidan are limited partially due to high extraction and purification costs. The present study implements an enzyme-assisted extraction and step-gradient ethanol precipitation for fractionating fucoidan from based on its charge and molecular weight and evaluation of ultraviolet B (UVB) protective effects in human keratinocytes (HaCaT). The fucoidan fraction SCOC4 indicated higher fucose and sulfate contents with Fourier-transform infrared and H NMR spectral patterns resembling fucoidans. SCOC4 dose-dependently abated UVB-induced keratinocyte damage via suppressing intracellular reactive oxygen species, apoptotic body formation, DNA damage via suppressing mitochondria-mediated apoptosis. UVB-protective effects of SCOC4 were further attributable to the augmentation of nuclear factor erythroid 2-related factor 2 mediated cellular antioxidant defense enzymes. Step-gradient ethanol precipitation was a convenient approach of fractionating fucoidans based on molecular weight and charge (depend on the degree of sulfation). Further evaluation of seasonal variations, biocompatibility parameters, efficacy, and shelf life may widen the use of fucoidans in developing UVB-protective cosmetics and functional foods.
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http://dx.doi.org/10.3390/antiox10030347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996943PMC
February 2021

Radiofrequency ablation versus stereotactic body radiation therapy for small (≤ 3 cm) hepatocellular carcinoma: A retrospective comparison analysis.

J Gastroenterol Hepatol 2021 Jul 5;36(7):1962-1970. Epub 2021 Mar 5.

Department of Radiation Oncology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background And Aim: We compared the clinical outcomes of radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in small (≤ 3 cm) hepatocellular carcinoma.

Methods: A total of 266 patients treated with RFA (n = 179) or SBRT (n = 87) were reviewed. Local control rates (LCRs), intrahepatic recurrence-free survival (IHRFS) rates, and overall survival (OS) rates were compared. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline characteristics between the two groups.

Results: The median follow-up period was 50.3 months, and treatment method (RFA vs SBRT) was not a significant prognostic factor for LCR, OS, and IHRFS in both multivariate and IPTW-adjusted analyses. The 4-year LCRs after RFA and SBRT were 92.7% and 95.0%, respectively. Perivascular location was a significant prognostic factor for LCR in the entire patients and in the RFA group, but not in the SBRT group. The 4-year OS rates in the RFA and SBRT groups were 78.1% and 64.1%, respectively (P = 0.012). After IPTW adjustment, the 4-year LCRs (90.6% vs 96.3%) and OS rates (71.8% vs 70.2%) were not significantly different between the two groups. The rate of grade ≥ 3 adverse events was 0.6% (n = 1) in the RFA group and 1.1% (n = 1) in the SBRT group.

Conclusions: The two treatment methods showed comparable outcomes in terms of LCR, OS rate, and IHRFS rate after IPTW adjustment. SBRT seems to be a viable alternative method for small hepatocellular carcinomas that are not suitable for RFA due to tumor location.
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http://dx.doi.org/10.1111/jgh.15442DOI Listing
July 2021

Short and Long-Term Mortality Trends for Cancer Patients with Septic Shock Stratified by Cancer Type from 2009 to 2017: A Population-Based Cohort Study.

Cancers (Basel) 2021 Feb 6;13(4). Epub 2021 Feb 6.

Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Korea.

There have been recent advances in both cancer and sepsis management. This study aimed to assess short and long-term mortality trends in cancer patients with septic shock from 2009 to 2017 by cancer type. This nationwide population-based cohort study using data from the National Health Insurance Service of Korea included adult cancer patients who presented to an emergency department (ED) with septic shock from 2009 to 2017. Among 43,466 adult cancer patients with septic shock (90% solid and 10% hematologic cancer cases), the 30-day and 1-year mortality rates were 52.1% and 81.3%, respectively. The overall 30-day mortality showed a marked decrease of 4.8% annually from 2013 to 2017, but the annual decrease in the 1-year mortality over the same period was only 1.9%. Pancreatic cancer cases showed the most significant improvement in 30-day mortality between 2014 and 2019 (11.0% decrease/year). Lung and stomach cancers showed a sustained decrease in 30-day mortality during the whole study period (1.7% and 2.0% decrease/year, respectively). The outcomes of cancer patients with septic shock have improved in recent years across most cancer types. Physicians should have expectations of an improved prognosis in cancer patients admitted to the ED with septic shock.
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http://dx.doi.org/10.3390/cancers13040657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931033PMC
February 2021

Lycopene Improves In Vitro Development of Porcine Embryos by Reducing Oxidative Stress and Apoptosis.

Antioxidants (Basel) 2021 Feb 3;10(2). Epub 2021 Feb 3.

Futuristic Animal Resource & Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do, Cheongju 28116, Korea.

In vitro culture (IVC) for porcine embryo development is inferior compared to in vivo development because oxidative stress can be induced by the production of excessive reactive oxygen species (ROS) under high oxygen tension in the in vitro environment. To overcome this problem, we investigated the effect of lycopene, an antioxidant carotenoid, on developmental competence and the mechanisms involved in mitochondria-dependent apoptosis pathways in porcine embryos. In vitro fertilized (IVF) embryos were cultured in IVC medium supplemented with 0, 0.02, 0.05, 0.1, or 0.2 μM lycopene. The results indicate that 0.1 μM lycopene significantly increased the rate of blastocyst formation and the total cell numbers, including trophectoderm cell numbers, on Day In terms of mitochondria-dependent apoptosis, IVF embryos treated with 0.1 μM lycopene exhibited significantly decreased levels of ROS, increased mitochondrial membrane potential, and decreased expression of cytochrome c on Days 2 and Furthermore, 0.1 μM lycopene significantly decreased the number and percentage of caspase 3-positive and apoptotic cells in Day-6 blastocysts. In addition, Day-2 embryos and Day-6 blastocysts treated with 0.1 μM lycopene showed significantly reduced mRNA expression related to antioxidant enzymes () and apoptosis ( ratio). These results indicate that lycopene supplementation during the entire period of IVC enhanced embryonic development in pigs by regulating oxidative stress and mitochondria-dependent apoptosis.
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http://dx.doi.org/10.3390/antiox10020230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913612PMC
February 2021

Protective Effects of Inflammation of Curcumae Longae Rhizoma 30% EtOH Extract on Acute Reflux Esophagitis Rats.

Biomed Res Int 2021 16;2021:8854945. Epub 2021 Jan 16.

Department of Herbology, College of Korean Medicine, Daegu Haany University, 136, Shinchendong-ro, Suseong-gu, Daegu 42158, Republic of Korea.

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through experiments. Based on the results, we performed experiments . Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-B led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.
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http://dx.doi.org/10.1155/2021/8854945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834798PMC
May 2021
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