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1.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38256924

ABSTRACT

We investigated the immune-stimulating and anti-diabetic effects of Allium hookeri leaves grown in a plant factory with artificial lights. The immunomodulatory effects of A. hookeri leaves' ethanol extracts were evaluated with immune-related hematological factors in blood, the proliferation of splenocytes, NK cell activity, IgG and cytokine levels, and their mechanisms in immunosuppressed obese mice. Anti-diabetic effects were determined by the inhibitory activity against α-amylase and α-glucosidase in vitro and fasting blood glucose levels and biochemical factors in the serum of immunosuppressed obese mice. A. hookeri leaf extracts increased WBC and LYM counts, the proliferation of splenocytes, and serum IgG and IL-1ß concentrations compared to those of the NC group, which was used as a negative control. A. hookeri leaf extracts also improved serum HDL levels while they decreased the activities of digestive enzymes, fasting blood glucose, and biochemical factors (ALT, AST, T-Chol, TG, LDL, and GLU). The expressions of IL-1ß, JNK, c-Jun, p65, and iNOS in the thymus of immunosuppressed mice were activated by the treatment of A. hookeri leaf extracts. The results suggest that A. hookeri leaves grown in a plant factory with artificial lights also have immune-stimulatory and anti-diabetic effects and can be used as novel functional supplements to control related diseases and to improve public health.

3.
Plant Pathol J ; 37(6): 580-595, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34897250

ABSTRACT

Although late blight is an important disease in eco-friendly potato cultivation in Korea, it is highly dependent on the use of eco-friendly agricultural materials and the development of biological control technology is low. It is a necessary to develop an effective biocontrol agent to inactivate late blight in the field. AFB2-2 strain is a gram-positive with peritrichous flagella. It can utilize 20 types of carbon sources, like L-arabinose, and D-trehalose at 35°C. The optimal growth temperature of the strain is 37°C. It can survive at 20-50°C in tryptic soy broth. The maximum salt concentration tolerated by AFB2-2 strain is 7.5% NaCl. AFB2-2 strain inhibited the mycelial growth of seven plant pathogens by an average inhibitory zone of 10.2 mm or more. Among the concentrations of AFB2-2, 107 cfu/ml showed the highest control value of 85.7% in the greenhouse. Among the three concentrations of AFB2-2, the disease incidence and severity of potato late blight at 107 cfu/ml was lowest at 0.07 and 6.7, respectively. The nucleotide sequences of AFB2-2 strain were searched in the NCBI GenBank; Bacillus siamensis strain KCTC 13613, Bacillus velezensis strain CR-502, and Bacillus amyloliquefaciens strain DSM7 were found to have a genetic similarity of 99.7%, 99.7%, and 99.5%, respectively. The AFB2-2 strain was found to harbor the biosynthetic genes for bacillomycin D, iturin, and surfactin. Obtained data recommended that the B. velezensis AFB2-2 strain could be considered as a promising biocontrol agent for P. infestans in the field.

4.
Stem Cells Int ; 2021: 9886877, 2021.
Article in English | MEDLINE | ID: mdl-34712335

ABSTRACT

BACKGROUND: This study is aimed at investigating the safety and tolerability of the intra-arterial administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with multiple system atrophy- (MSA-) cerebellar type (MSA-C). METHODS: This was a single-center, open-label phase I clinical trial in patients with MSA-C. A three-stage dose escalation scheme (low-dose, 3.0 × 105 cells/kg; medium-dose, 6.0 × 105 cells/kg; high-dose, 9.0 × 105 cells/kg) was applied to determine the maximum tolerated dose of intra-arterial administration of BM-MSCs based on the no-observed-adverse-effect level derived from the toxicity study. The occurrence of adverse events was evaluated 1 day before and 1, 14, and 28 days after BM-MSC therapy. Additionally, we assessed changes in the Unified MSA Rating Scale (UMSARS) score 3 months after BM-MSC treatment. RESULTS: One serious adverse drug reaction (ADR) of leptomeningeal enhancement following the intra-arterial BM-MSC administration occurred in one patient in the low-dose group. The safety review of the Internal Monitoring Committee interpreted this as radiological evidence of the blood-brain barrier permeability for MSCs. No other ADRs were observed in the medium- or high-dose groups. In particular, no ischemic lesions on diffusion-weighted images were observed in any of the study participants. Additionally, the medium- and high-dose groups tended to show a slower increase in UMSARS scores than the low-dose group during the 3-month follow-up. CONCLUSION: The present study confirmed that a single intra-arterial administration of autologous BM-MSCs is a safe and promising neuroprotective strategy in patients with MSA-C.

5.
Orthop Traumatol Surg Res ; 107(8): 103091, 2021 12.
Article in English | MEDLINE | ID: mdl-34601158

ABSTRACT

INTRODUCTION: Historically, cerclage wires were not used in the treatment of clavicle fractures because of their invasiveness. The purpose of this study was to evaluate the radiologic results and the incidence of complications following cerclage wire application and plate fixation in the treatment of comminuted mid-shaft clavicle fractures. MATERIALS AND METHODS: A total of 116 patients with comminuted mid-shaft clavicle fractures who underwent open reduction and internal fixation were reviewed. We analyzed the postoperative length ratio and bone union period according to the fracture classification, patient age, the number of fragments and the number of applied wires. The thickness of the fracture site was compared with the normal contralateral clavicle shaft. RESULTS: Bone union was confirmed in all enrolled patients at an average of 14.9±4.67 weeks. There are no significant differences in the length ratio or bone union period among the subgroups (including the fracture types, age, number of fragments and applied wires). The diameter at the occupied area was not significantly from that on the normal side (p=.505). CONCLUSIONS: The application of a single cerclage or multiple cerclage wires around the fracture site did not hamper the clavicle shaft fracture healing. This result suggests that cerclage wires should not be avoided, but can be used as a viable treatment option for clavicle shaft fractures. LEVEL OF EVIDENCE: IV.


Subject(s)
Fractures, Bone , Fractures, Comminuted , Bone Plates , Clavicle/surgery , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Fracture Healing , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Fractures, Comminuted/diagnostic imaging , Fractures, Comminuted/surgery , Humans , Retrospective Studies , Treatment Outcome
6.
Tissue Eng Regen Med ; 18(5): 775-785, 2021 10.
Article in English | MEDLINE | ID: mdl-34491556

ABSTRACT

BACKGROUND: For stem cell applications in regenerative medicine, it is very important to produce high-quality stem cells in large quantities in a short time period. Recently, many studies have shown big potential of graphene oxide as a biocompatible substance to enhance cell growth. We investigated if graphene oxide-coated culture plate can promote production efficiency of stem cells. METHODS: Three types of graphene oxide were used for this study. They are highly concentrated graphene oxide solution, single-layer graphene oxide solution, and ultra-highly concentrated single-layer graphene oxide solution with different single-layer ratios, and coated on cell culture plates using a spray coating method. Physiochemical and biological properties of graphene oxide-coated surface were analyzed by atomic force microscope (AFM), scanning electron microscope (SEM), cell counting kit, a live/dead assay kit, and confocal imaging. RESULTS: Graphene oxide was evenly coated on cell culture plates with a roughness of 6.4 ~ 38.2 nm, as measured by SEM and AFM. Young's Modulus value was up to 115.1 GPa, confirming that graphene oxide was strongly glued to the surface. The ex vivo stem cell expansion efficiency was enhanced as bone marrow-derived stem cell doubling time on the graphene oxide decreased compared to the control (no graphene oxide coating), from 64 to 58 h, and the growth rate increased up to 145%. We also observed faster attachment and higher affinity of stem cells to the graphene oxide compared to control by confocal microscope. CONCLUSION: This study demonstrated that graphene oxide dramatically enhanced the ex vivo expansion efficiency of stem cells. Spray coating enabled an ultra-thin coating of graphene oxide on cell culture plates. The results supported that utilization of graphene oxide on culture plates can be a promising mean for mass production of stem cells for commercial applications.


Subject(s)
Graphite , Cell Proliferation , Stem Cells
7.
Hip Pelvis ; 33(2): 78-86, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34141694

ABSTRACT

PURPOSE: This study aimed to investigate the relationship between femoral offset (FO) and clinical outcomes of patients with femoral neck fracture following bipolar hip arthroplasty (BHA). MATERIALS AND METHODS: Records for a total of 520 patients who underwent BHA for a femoral neck fracture between December 1, 2003, and September 30, 2018, were reviewed retrospectively. Patients with unclear medical records, a congenital deformity and preoperative trauma history of the hip, high-energy multiple trauma, or a history of neurodegenerative disease or cerebrovascular disease were excluded. The remaining 77 patients included in the analysis had a minimum follow-up period of one year. For clinical assessment, the postoperative pain visual analogue scale (VAS) and Harris hip score (HHS) were analyzed at each follow-up period. For radiological assessment, the difference in leg length discrepancy (LLD) and FO were measured. RESULTS: The difference in mean FO postoperatively was 6.7±4.8 mm, and the difference in mean postoperative LLD was 4.9±3.4 mm. The mean HHS was 77.1±7.7, 82.3±8.6, 83.4±7.7, and 86.4±6.7 at 1, 3, 6, and 12 months postoperative, respectively. The correlation coefficient between FO and HHS in 1-year follow-up was -0.38, and a statistically significant outcome was found (P=0.001). For the HHS domain, the correlation coefficient for function at 1-year follow-up was -0.42, revealing a statistically significant outcome (P=0.0001). CONCLUSION: There was a statistically significant correlation between clinical outcomes and FO difference at 1 year after BHA in patients over 65 years of age with femoral neck fractures.

8.
Psychosom Med ; 83(7): 787-794, 2021 09 01.
Article in English | MEDLINE | ID: mdl-33938504

ABSTRACT

OBJECTIVE: Older adults are at increased risk for depression and poor asthma outcomes. We examined whether depressive symptoms are associated with overperception of airflow obstruction and a pattern of worse asthma control, but not pulmonary function. METHODS: We recruited a cohort of adults with asthma 60 years and older in East Harlem and the Bronx, New York. Baseline measures included the Geriatric Depression Scale, Asthma Control Questionnaire, and Mini Asthma Quality of Life Questionnaire. Spirometry was conducted at baseline to assess pulmonary function. Perception of airflow obstruction was assessed for 6 weeks following baseline by participants entering estimates of peak expiratory flow (PEF) into a programmable peak flow meter followed by PEF blows. Participants were blinded to actual PEF values. The percentage of time that participants were in the overperception zone was calculated as an average. RESULTS: Among the 334 participants (51% Hispanic, 25% Black), depressive symptoms were associated with overperception of airflow obstruction (ß = 0.14, p = .029), worse self-reported asthma control (ß = 0.17, p = .003), and lower asthma-related quality of life (ß = -0.33, p < .001), but not with lung function (ß = -0.01, p = .82). Overperception was also associated with worse self-reported asthma control (ß = 0.14, p = .021), but not lung function (ß = -0.05, p = .41). CONCLUSIONS: Depressive symptoms were associated with greater perceived impairment from asthma, but not pulmonary function. Overperception of asthma symptoms may play a key role in the relationship between depression and asthma outcomes in older adults.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Aged , Depression/epidemiology , Forced Expiratory Volume , Humans , Lung , Peak Expiratory Flow Rate , Quality of Life
9.
J Microbiol Biotechnol ; 30(5): 708-716, 2020 May 28.
Article in English | MEDLINE | ID: mdl-32482936

ABSTRACT

The purpose of this study was to identify strawberry wilt pathogens and evaluate the efficacy of Chlorella fusca CHK0059 for improving plant growth and suppressing Fusarium wilt. We identified 10 isolates of wilt pathogens of non-pesticide Seolhyang strawberry plant, including Fusarium oxysporum f. sp. fragariae, using morphological and molecular analysis. On the 15th day after 0.4% CHK0059 treatment, the plant height of the untreated control strawberry plants was significantly greater than that of the CHK0059-treated strawberry plants. After 85 days, both treatments showed a similar tendency regarding the height of the strawberry plants. However, the thickness of strawberry leaves treated with the CHK0059 was found to be 1 mm thicker than that of the untreated control. The flowering percentage of the CHK0059 plants was also 40.2% higher on average than that of the untreated control. The chlorophyll content of strawberry leaves treated with the CHK0059 was also, on average, 6.63% higher than that of the untreated control. After 90 days of the CHK0059 treatment, the incidence of Fusarium wilt in the CHK0059-treated plants had reduced by 9.8% on average compared to the untreated control. The population density of F. oxysporum f. sp. fragariae was also reduced by approximately 86.8% in the CHK0059-treated plants by comparison to the untreated control at 70 days after treatment. The results indicate that the microalga C. fusca CHK0059 is an efficient biological agent for improving strawberry plant growth and suppressing Fusarium wilt disease in organic strawberries.


Subject(s)
Biological Control Agents/pharmacology , Chlorella/chemistry , Fragaria/microbiology , Fusarium/drug effects , Microalgae/chemistry , Hydroponics , Plant Diseases/microbiology , Soil Microbiology
10.
Plant Signal Behav ; 15(6): 1763005, 2020 06 02.
Article in English | MEDLINE | ID: mdl-32408798

ABSTRACT

Plant tissues naturally senesce over time. Attempts to improve plant robustness and increase longevity have involved genetic modification, application of synthetic chemicals, and use of beneficial microbes. Recently, culture supernatant from a microalga Chlorella fusca was found to prime innate immunity against Pseudomonas syringae in Arabidopsis thaliana. However, the capacity of Chlorella culture supernatants to prevent or delay aging in higher plants has not been elucidated. In this study, roots of the ornamental flowering plant Erinus alpinus L. were drenched with cell-free supernatants from three Chlorella species. Flower and leaf senescence in E. alpinus was significantly reduced and delayed with all three Chlorella supernatants. Investigations of the mode of action underlying delayed senescence showed that the Chlorella supernatants did not act as a chemical trigger to elicit plant immunity or as a growth-promoting fertilizer in E. alpinus. The mechanisms underlying the anti-aging effects remain undetermined, and several possible hypotheses are discussed. Several Chlorella species are industrially cultivated, and disposal of cell-free supernatant can be economically and environmentally challenging. This study provides a novel method for extending plant lifespan through use of Chlorella supernatant and discusses the potential of using industrial waste supernatants in agriculture and horticulture to reduce reliance on chemical pesticides and genetic modification.


Subject(s)
Chlorella/metabolism , Flowers/metabolism , Plant Leaves/metabolism , Cellular Senescence/physiology , Chlorella/physiology , Flowers/physiology , Plant Leaves/physiology
11.
Structure ; 28(3): 314-323.e3, 2020 03 03.
Article in English | MEDLINE | ID: mdl-31948726

ABSTRACT

Arrestins desensitize and/or internalize G-protein-coupled receptors by interacting with phosphorylated receptors. A few studies have reported that arrestins themselves can be phosphorylated, and the phosphorylation status modulates their cellular functions. However, the effects of phosphorylation on arrestin structure have not been studied. Here, we investigated the conformational changes in ß-arrestin-1 and -2 upon incorporation of phospho-mimetic mutations into the known phosphorylation sites (i.e., S412D for ß-arrestin-1 and S14D, T276D, S14D/T276D, S361D, T383D, and S361D/T383D for ß-arrestin-2) by using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS analysis suggested that ß-arrestin-2 S14D/T276D shows an HDX profile similar to the pre-active states, resulting in increased interaction with receptors. Phospho-mimetic mutation at corresponding residues of ß-arrestin-1 (i.e., S13D/T275D) induced similar conformational and functional consequences, and the detailed structural changes related to ß-arrestin-1 S13D/T275D were investigated further by X-ray crystallography.


Subject(s)
Mutation , beta-Arrestin 1/chemistry , beta-Arrestin 1/metabolism , beta-Arrestin 2/chemistry , beta-Arrestin 2/metabolism , Amino Acid Sequence , Animals , Crystallography, X-Ray , Hydrogen Deuterium Exchange-Mass Spectrometry , Models, Molecular , Phosphorylation , Protein Binding , Protein Conformation , Rats , beta-Arrestin 1/genetics , beta-Arrestin 2/genetics
12.
Biosensors (Basel) ; 9(3)2019 Jul 10.
Article in English | MEDLINE | ID: mdl-31295893

ABSTRACT

This paper compares the structural design of two organic biosensors that minimize power consumption in wireless photoplethysmogram (PPG) waveform monitoring. Both devices were fabricated on the same substrate with a red organic light-emitting diode (OLED) and an organic photodiode (OPD). Both were designed with a circular OLED at the center of the device surrounded by OPD. One device had an OLED area of 0.06 cm2, while the other device had half the area. The gap distance between the OLED and OPD was 1.65 mm for the first device and 2 mm for the second. Both devices had an OPD area of 0.16 cm2. We compared the power consumption and signal-to-noise ratio (SNR) of both devices and evaluated the PPG signal, which was successfully collected from a fingertip. The reflectance-based organic pulse meter operated successfully and at a low power consumption of 8 µW at 18 dB SNR. The device sent the PPG waveforms, via Bluetooth low energy (BLE), to a PC host at a maximum rate of 256 kbps data throughput. In the end, the proposed reflectance-based organic pulse meter reduced power consumption and improved long-term PPG wireless monitoring.


Subject(s)
Biosensing Techniques , Photoplethysmography/instrumentation , Photoplethysmography/methods , Pulse , Wireless Technology , Equipment Design , Heart Rate , Humans , Optical Devices , Signal-To-Noise Ratio
13.
Biosensors (Basel) ; 9(2)2019 Mar 29.
Article in English | MEDLINE | ID: mdl-30934921

ABSTRACT

This paper demonstrated a new design structure for minimizing the power consumption of a pulse meter. Monolithic devices composed of a red (625 nm) organic light-emitting diode (OLED) and an organic photodiode (OPD) were fabricated on the same substrate. Two organic devices were designed differently. One had a circle-shaped OLED in the center of the device and was surrounded by the OPD, while the other had the opposite structure. The external quantum efficiency (EQE) of the OLED and the OPD were 7% and 37%, respectively. We evaluated and compared the signal-to-noise ratio (SNR) of the photoplethysmogram (PPG) signal on different parts of the body and successfully acquired clear PPG signals at those positions, where the best signal was obtained from the fingertip at a SNR of about 62 dB. The proposed organic pulse meter sensor was operated successfully with a power consumption of 0.1 mW. Eventually, the proposed organic biosensor reduced the power consumption and improved the capability of the pulse meter for long-term use.


Subject(s)
Biosensing Techniques , Photoplethysmography/instrumentation , Equipment Design , Humans
14.
Plant Pathol J ; 34(6): 567-574, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30588229

ABSTRACT

This study was conducted to investigate the efficacy of freshwater alga, Chlorella fusca on the improvement of growth and qualities in organic spinach and Chinese chives farm. The average height of Chinese chives treated with the chlorella was 3.7 cm smaller than that of the untreated. The leaf width and fresh weight of Chinese chives treated with the chlorella was 0.5 mm wider and 30.3 g heavier than that of the untreated. The commercialization and yield of Chinese chives treated with the chlorella was 11.9% and 18.3%, respectively higher than that of the untreated. Also, the disease severity of gray mold disease of Chinese chives treated with the chlorella was reduced by more than 24.2% when compared with the untreated. The thickness and number of spinach leaves treated with chlorella was 27.9% and 41.8%, respectively higher than that of the untreated. The fresh weight and yield of the spinach treated with the chlorella was 63.6% and 31.5%, respectively higher than that of the untreated. Moreover, the mineral content of K, Ca, Mg, P, Fe, and Mn were recorded higher in the spinach treated with chlorella compared with that of untreated. The results indicated that the freshwater alga, Chlorella fusca is efficient and economical biostimulant in improving plant growth and quality of Chinese chives and spinach in organic farm.

15.
Cutis ; 102(4): 283-286, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30489553

ABSTRACT

Trametinib, a mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor, has demonstrated great promise in treating metastatic melanoma associated with BRAF V600E and V600K mutations; however, it also is highly associated with cutaneous adverse events (AEs). As both BRAF and MEK inhibitors become increasingly used to treat malignant melanoma, it is important to better characterize these AEs so that we can manage them. Herein, we present a case of a 66-year-old man who developed erythematous scaly papules on the face and bilateral upper extremities after beginning therapy with trametinib. The severity of the reaction worsened on trametinib monotherapy compared to combination therapy with a BRAF inhibitor. Biopsy revealed a xanthogranulomatous reaction.


Subject(s)
Acrylonitrile/analogs & derivatives , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Granuloma/diagnosis , Pyridones/therapeutic use , Pyrimidinones/therapeutic use , Xanthomatosis/diagnosis , Acrylonitrile/administration & dosage , Acrylonitrile/adverse effects , Acrylonitrile/therapeutic use , Aged , Aniline Compounds/administration & dosage , Aniline Compounds/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Diagnosis, Differential , Granuloma/chemically induced , Humans , Male , Melanoma/drug therapy , Melanoma/secondary , Neoplasm Staging , Pyridones/administration & dosage , Pyridones/adverse effects , Pyrimidinones/administration & dosage , Pyrimidinones/adverse effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Xanthomatosis/chemically induced
16.
Int J Mol Sci ; 19(4)2018 Apr 09.
Article in English | MEDLINE | ID: mdl-29642532

ABSTRACT

The in vivo relevance of ursodeoxycholate (UDCA) treatment (100 mg/kg/day, per oral tid for 5 days before cholestasis induction followed by the same dosing for 5 days) on hepatic function was investigated in rats with 17α-ethinylestradiol (EE, 10 mg/kg, subcutaneous for 5 days)-induced experimental cholestasis. The bile flow rate and the expression level of hepatic multidrug resistance-associated protein 2 (Mrp 2) that were decreased in cholestasis were restored after UDCA treatment. Consistent with this, the biliary excretion clearance (CLexc,bile) of a representative Mrp2 substrate-methotrexate (MTX)-was decreased in cholestatic rats but was restored after UDCA treatment. Consequently, the plasma concentrations of MTX, which were increased by cholestasis, were decreased to control levels by UDCA treatment. Thus, the restoration of CLexc,bile appears to be associated with the increase in Mrp2 expression on the canalicular membrane by UDCA treatment followed by Mrp2-mediated biliary excretion of MTX. On the other hand, the hepatic uptake clearance (CLup,liver) of MTX was unchanged by cholestasis or UDCA treatment, suggestive of the absence of any association between the uptake process and the overall biliary excretion of MTX. Since UDCA has been known to induce the expression of canalicular MRP2 in humans, UDCA treatment might be effective in humans to maintain or accelerate the hepatobiliary elimination of xenobiotics or metabolic conjugates that are MRP2 substrates.


Subject(s)
Bile Acids and Salts/chemistry , Cholestasis/prevention & control , Ethinyl Estradiol/adverse effects , Methotrexate/blood , Ursodeoxycholic Acid/administration & dosage , ATP-Binding Cassette Transporters/metabolism , Administration, Oral , Animals , Cholestasis/blood , Cholestasis/chemically induced , Cholestasis/metabolism , Down-Regulation , Drug Administration Schedule , Male , Multidrug Resistance-Associated Protein 2 , Rats , Treatment Outcome , Ursodeoxycholic Acid/pharmacology
17.
J Pharm Biomed Anal ; 151: 61-70, 2018 Mar 20.
Article in English | MEDLINE | ID: mdl-29306735

ABSTRACT

We previously reported that MDR-1339, an inhibitor of ß-amyloid protein aggregation, was likely to be eliminated by biotransformation in rats. The objective of this study was to determine the chemical identity of metabolites derived from this aggregate inhibitor and to characterize the kinetics of formation of these metabolites in rats. Using high performance liquid chromatography coupled with mass spectrometry with a hybrid triple quadrupole-linear ion trap, 7 metabolites and 1 potential metabolic intermediate were identified in RLM incubations containing MDR-1339. In addition to these, 3 glucuronide metabolites were detected in urine samples from rats receiving a 10 mg/kg oral dose of MDR-1339. When the kinetics of the formation of two major metabolites, M1 and M2, were analyzed assuming simple Michaelis-Menten kinetics, the Vmax and Km values were found to be 0.459 ±â€¯0.0196 nmol/min/mg protein and 28.3 ±â€¯3.07 µM for M1, and 0.101 ±â€¯0.00537 nmol/min/mg protein and 14.7 ±â€¯2.37 µM for M2, respectively. When chemically synthesized M1 and M2 were individually administered to rats intravenously at the dose of 5 mg/kg respectively, the volume of distribution and elimination clearance were determined to be 4590 ±â€¯709 mL/kg and 68.4 ±â€¯5.60 mL/min/kg for M1 and 15300 ±â€¯8110 mL/kg and 98.0 ±â€¯19.5 mL/min/kg for M2, respectively. When MDR-1339 was intravenously administered to rats at a dose of 5 mg/kg, the parent drug and M1 were readily detected for periods of up to 6 h after the administration, but M2 was observed only from 2 to 4 h. A standard moment analysis indicates that the formation clearance of M1 is 6.01 mL/min/kg, suggesting that 19.7% of the MDR-1339 dose was eliminated in rats. These observations indicate that the hepatic biotransformation of MDR-1339 results in the formation of at least 10 metabolites and that M1 is the major metabolite derived from this aggregation inhibitor in rats.


Subject(s)
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Benzofurans/metabolism , Microsomes, Liver/metabolism , Protein Aggregates/drug effects , Animals , Benzofurans/pharmacology , Dose-Response Relationship, Drug , Male , Microsomes, Liver/drug effects , Protein Aggregates/physiology , Rats , Rats, Sprague-Dawley
18.
Therap Adv Gastroenterol ; 10(7): 529-536, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28804513

ABSTRACT

BACKGROUND: Although hepatocellular carcinoma (HCC) usually develops in cirrhotic livers, a minority of cases occur in noncirrhotic livers (NCLs). We investigated etiology, clinicopathological features, and occult hepatitis B virus (HBV) infection (OBI) in patients with NCL HCC in an HBV-endemic area. METHODS: A total of 710 patients who underwent resection or transplantation for HCC at the National Cancer Center (NCC), Korea, were enrolled. HCC and fibrosis stage were diagnosed pathologically. RESULTS: A total of 178 patients (25%) did not have cirrhosis (NCL group). The main cause of HCC was HBV infection (77.2%), followed by cryptogenic disease (11.0%). The prevalence of NCL was 19.2%, 32.5%, 50.0%, and 48.7% among patients with HBV, hepatitis C virus (HCV), alcoholic, and cryptogenic disease, respectively (p < 0.05); corresponding nonfibrosis rates were 8.1%, 0%, 19.0%, and 24.3%, respectively. The NCL group was significantly older, with a larger tumor size, smaller tumor number, lower tumor stage, and more frequent non-HBV etiology. Among non-HBV HCC cases, 130 (80.2%) had antibodies against HBV core (HBc) and 55 (38.5%) had OBI. OBI-positive rates of 0%, 31.8%, and 52.6% were detected among HCV, alcoholic, and cryptogenic HCC cases, respectively. OBI did not correlate with advanced fibrosis. The NCL and liver cirrhosis (LC) groups did not differ in median overall survival. CONCLUSION: Regardless of etiology, a significant number of HCC patients, including half of nonviral cases, did not have LC. Half of cryptogenic HCC cases had OBI. This study promotes an understanding of fibrosis and OBI among patients with HCC in an HBV-endemic area.

19.
Plant Pathol J ; 33(1): 1-8, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28167883

ABSTRACT

Seed dehiscence of ginseng (Panax ginseng C. A. Mayer) is affected by moisture, temperature, storage conditions and microbes. Several microbes were isolated from completely dehisced seed coat of ginseng cultivars, Chunpoong and Younpoong at Gumsan, Korea. We investigated the potential of five Talaromyces flavus isolates from the dehiscence of ginseng seed in four traditional stratification facilities. The isolates showed antagonistic activities against fungal plant pathogens, such as Cylindrocarpon destructans, Fusarium oxysporum, Rhizoctonia solani, Sclerotinia nivalis, Botrytis cinerea, and Phytophthora capsici. The dehiscence ratios of ginseng seed increased more than 33% by treatment of T. flavus GG01, GG02, GG04, GG12, and GG23 in comparison to control (28%). Among the treatments, the reformulating treatment of T. flavus isolates GG01 and GG04 showed the highest of stratification ratio of ginseng seed. After 16 weeks, the reformulating treatment of T. flavus isolates GG01 and GG04 significantly enhanced dehiscence of ginseng seed by about 81% compared to the untreated control. The candidate's treatment of T. flavus GG01 and GG04 showed the highest decreasing rate of 93% in seed coat hardness for 112 days in dehiscence period. The results suggested that the pre-inoculation of T. flavus GG01 and GG04 found to be very effective applications in improving dehiscence and germination of ginseng seed.

20.
Nanoscale ; 9(7): 2442-2448, 2017 Feb 16.
Article in English | MEDLINE | ID: mdl-28165105

ABSTRACT

We have successfully demonstrated a graphene-ZnO:N Schottky barristor. The barrier height between graphene and ZnO:N could be modulated by a buried gate electrode in the range of 0.5-0.73 eV, and an on-off ratio of up to 107 was achieved. By using a nitrogen-doped ZnO film as a Schottky contact material, the stability problem of previously reported graphene barristors could be greatly alleviated and a facile route to build a top-down processed graphene barristor was realized with a very low heat cycle. This device will be instrumental when implementing logic functions in systems requiring high-performance logic devices fabricated with a low temperature fabrication process such as back-end integrated logic devices or flexible devices on soft substrates.

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