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1.
Heliyon ; 10(8): e30105, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38699715

In this study, green synthesis of gold nanoparticles (AuNPs) using aqueous extract from Hymenaea courbaril resin (HCR) is reported. The successful formation, functional group involvement, size, and morphology of the subject H. courbaril resin mediated gold nanoparticles (HCRAuNPs) were confirmed by Ultra Violet-Visible (UV-vis) spectroscopy, Fourier-Transform Infrared spectroscopy (FTIR), and Transmission Electron Microscopy (TEM) techniques. Stable and high yield of HCRAuNPs was formed in 1:15 (aqueous solution: salt solution) reacted in sunlight as indicated by the visual colour change and appearance of surface Plasmon resonance (SPR) at 560 nm. From the FT-IR results, the phenolic hydroxyl (-OH) functional group was found to be involved in synthesis and stabilization of nanoparticles. The TEM analysis showed that the particles are highly dispersed and spherical in shape with average size of 17.5 nm. The synthesized HCRAuNPs showed significant degradation potential against organic dyes, including methylene blue (MB, 85 %), methyl orange (MO, 90 %), congo red (CR, 83 %), and para nitrophenol (PNP, 76 %) up to 180 min. The nanoparticles also demonstrated the effective detection of pharmaceutical pollutants, including amoxicillin, levofloxacin, and azithromycin in aqueous environment as observable changes in color and UV-Vis spectral graph.

2.
Children (Basel) ; 10(12)2023 Nov 27.
Article En | MEDLINE | ID: mdl-38136062

Pediatric anesthesia requires the rapid creation, communication, and execution of anesthesia orders, and there is a risk of human error. The authors developed an order-assisted mobile application (app) to reduce human error during pediatric anesthesia preparation. The authors conducted an observational study that compared the effects of the application by comparing anesthesiologists' errors, nurses' errors, nurses leaving the operating room, and delays in surgery, between the Conventional group (n = 101) and the App group (n = 101). The app was associated with reduced human error by anesthesiologists and nurses, and it lowered the frequency and duration of nurses leaving the operating room during anesthesia. In addition, the authors surveyed anesthesia nurses regarding the effectiveness of the app. The nurses confirmed that the app was convenient and reduced human error. This study revealed that the order-assisted mobile app developed by a pediatric anesthesiologist could reduce human errors by anesthesiologists and nurses during pediatric anesthesia preparation.

3.
Korean J Intern Med ; 38(6): 879-892, 2023 11.
Article En | MEDLINE | ID: mdl-37867139

BACKGROUND/AIMS: Although the incidence of nontuberculous mycobacteria pulmonary disease (NTM-PD), a chronic infectious disease, is increasing, lung and gut microbiota dysbiosis in NTM patients has rarely been studied and was therefore the focus of this study. METHODS: We analyzed the microbiota diversity in sputum and stool samples from 10 healthy subjects and 10 patients with NTM-PD through sequencing of the V3 and V4 regions of the 16S rRNA gene. In NTM-PD patients, we comparatively evaluated the microbiota diversity according to the body mass index (BMI), with BMI ≤ 18.5 kg/m2 defined as "underweight" and BMI > 18.5 kg/m2 as "others." RESULTS: The sputum microbiota from NTM-PD patients tended to have lower index values of amplicon sequence variant richness, Shannon evenness, and beta diversity than those from the control group. Furthermore, NTM-PD patients with a low BMI had a lower microbiota diversity than patients with high BMI. Fecal samples from NTM-PD patients also significantly differed in alpha and beta diversity compared with the control group and exhibited a diversity pattern similar to that found in sputum samples. CONCLUSION: Our results reveal that the lung and gut microbiota of patients with NTM-PD exhibit an altered distribution and reduced richness and diversity.


Gastrointestinal Microbiome , Lung Diseases , Mycobacterium Infections, Nontuberculous , Humans , RNA, Ribosomal, 16S/genetics , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/epidemiology , Lung , Nontuberculous Mycobacteria/genetics
4.
Pharmaceutics ; 15(9)2023 Aug 27.
Article En | MEDLINE | ID: mdl-37765187

(1) Background: Milnacipran is a typical serotonin-norepinephrine reuptake inhibitor and has been shown to have analgesic effects in several pain models. However, its antihyperalgesic effect in cisplatin-induced neuropathy remains unknown. We examined the effects of intraperitoneal (IP) milnacipran on allodynia in cisplatin-induced peripheral neuropathic mice. (2) Methods: Peripheral neuropathy was induced by injecting cisplatin (2.3 mg/kg/day, IP) six times, on every other day. Saline or milnacipran (10, 30, 50 mg/kg, IP) were then administered to the neuropathic mice. We examined mechanical allodynia using von Frey hairs at preadministration and at 30, 60, 90, 120, 180, 240 min and 24 h after drug administration. We also measured the dorsal root ganglion (DRG) activating transcription factor 3 (ATF3) to confirm the analgesic effects of milnacipran. (3) Results: For the milnacipran groups, the decreased paw withdrawal thresholds to mechanical stimuli were significantly reversed when compared to the preadministration values and the values in the saline-injected control group (p < 0.0001). Milnacipran administration to cisplatin-induced peripheral neuropathic mice resulted in a significant suppression of neuronal ATF3 activation (p < 0.01). (4) Conclusions: Milnacipran given via IP injection attenuates mechanical allodynia in mouse models of cisplatin-induced poly-neuropathic pain. These effects were confirmed by significant suppression of neuronal ATF3 activation in the DRG.

5.
Gait Posture ; 106: 28-33, 2023 09.
Article En | MEDLINE | ID: mdl-37639962

BACKGROUND: Individuals with Chronic Ankle Instability (CAI) demonstrate altered gait mechanics, impaired proprioception, and decreased postural control. In addition, individuals with CAI have been found to have complex neurophysiological changes, including during dual-task perturbations. However, the results of studies on whether cognitive tasks affect postural control are inconclusive. RESEARCH QUESTION: Do individuals with CAI have worse dual-task performance compared to healthy controls? METHODS: We searched 4 electronic databases (PubMed, MEDLINE, Cumulative Index of Nursing and Allied Health Literature, and SPORTDiscus) from inception to October 2022. Search terms consisted of: ("dual-task*" OR "dual task*" OR dual-task OR Multitask* OR Multi-task* OR attention OR cognit*) AND (balance OR "postural control" OR "postural sway" OR kinetics OR kinematics OR gait) NOT (concussion OR "traumatic brain injury") combined using the operator "AND" ("ankle sprain" OR "ankle instability" OR CAI). Studies were included if the physical task was postural control or gait, and if they compared control and CAI groups. RESULTS: A total of 9 studies were included in the systematic-review portion, 5 of which were included in the meta-analysis. Due to assessing multiple types of dual-tasks, 10 effects were assessed for meta-analysis across postural control studies. A random-effects model for the control group in the mediolateral direction indicated a significant overall Fisher's Z mean effect size (Δ = 0.732, p = 0.029) with high heterogeneity between studies (Q=76.61; I2 = 88.25% P < 0.001). There were no significant differences between dual-tasking in the CAI group individually or when comparing control to CAI groups. SIGNIFICANCE: The results of our study indicate that cognitive loading did not affect the postural control except for the control group in the mediolateral direction. Variations in dual-task results may be due to the difficulty of the task as well as the heterogeneity of CAI groups.


Ankle , Joint Instability , Humans , Ankle Joint , Postural Balance/physiology , Gait , Task Performance and Analysis , Chronic Disease
6.
Article En | MEDLINE | ID: mdl-37607248

Ochratoxin A (OTA) is a stable toxin produced by fungal strains of Aspergillus and Penicillium. It is commonly found in a variety of food products, including dried fruit, coffee, and spices, raising concerns about their safety. This study was aimed to quantify OTA levels in different food products using HPLC with fluorescence detection. The pre-treatment process was optimised by employing immunoaffinity columns with Tween 20 to effectively remove interfering substances. An analytical method was developed, validated, and applied for OTA analysis in dried fruit, spices, and coffee samples. The validation procedure included determining detection and quantification limits, linearity, precision, and accuracy, as per the criteria specified by AOAC International. The validated method was successfully applied for OTA analysis in the selected food samples. Furthermore, health risk assessment was conducted based on the average intake and body weight of the Korean population. From the results, concentrations of OTA in the samples were found to be very low and therefore concluded not to pose significant threats to consumer health.


Fruit , Spices , Coffee , Risk Assessment
7.
Environ Monit Assess ; 195(6): 744, 2023 May 27.
Article En | MEDLINE | ID: mdl-37237150

To systematically manage water quality based on watersheds, it is necessary to understand the characteristics of changes in river water quality. This study used observational data of the Tamjin River water system to analyze changes in water quality due to farming activities during the farming period. Water quality trends were analyzed through a long-term trend analysis. Furthermore, the loads and sources of substances regulated under the total maximum daily load system were evaluated. Biochemical oxygen demand and total phosphorous, water quality factors of the target basin, showed recent increasing trends. Loads increased from April, which corresponded to the non-farming period before farming activities began, and characteristics of pollutant discharged in the basin from farming activities were observed. Pollutant sources were different from those observed in water systems with a high proportion of farming activities, and water quality management measures considering the target basin's characteristics were proposed. The results of this study will serve as logical baseline data for establishing water quality management plans.


Environmental Pollutants , Water Pollutants, Chemical , Water Quality , Water Pollution/analysis , Environmental Monitoring/methods , Environmental Pollutants/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis
8.
Phys Ther Sport ; 59: 80-84, 2023 Jan.
Article En | MEDLINE | ID: mdl-36525740

OBJECTIVES: To validate a choice-reaction hop test (CRHT) by assessing differences in timing versus the side-hop test (SHT), and to determine the CRHT's test-retest reliability. DESIGN: Test-retest reliability. SETTING: Laboratory. PARTICIPANTS: Forty-nine healthy adults participated (16 female; age = 22.7 ± 3.4 years; height = 174.9 ± 9.1 cm; mass = 75.4 ± 14.8 kg). MAIN OUTCOME MEASURES: Participants completed three trials each of the SHT and the CRHT in a counterbalanced order. Participants returned one-week later to repeat the CRHT. The fastest and the mean of the three trials were compared. RESULTS: Participants took significantly longer to complete the CRHT (Mean across 3 trials = 21.4 ± 3.4s, Fastest trial = 19.7 ± 3.0s) compared to the traditional SHT (10.4 ± 2.0s, p < 0.001). The CRHT demonstrated good-excellent test-retest reliability across testing days for both the mean across 3 trials (r = 0.890, p < 0.001, SEM = 1.13) and the fastest trial (r = 0.828, p < 0.001, SEM = 1.24). CONCLUSION: Compared to the SHT, the CRHT took longer to complete indicating its ability to stress neurocognitive function during an FPT. The CRHT demonstrated good-excellent test-retest reliability, which may allow it to be a useful measure in serial evaluations such as during rehabilitation benchmarking. The CRHT may be an effective FPT to assess combined physical and neurocognitive function to assist clinicians in evidence-based decision-making.


Physical Examination , Physical Functional Performance , Adult , Humans , Female , Young Adult , Reproducibility of Results
9.
Food Sci Biotechnol ; 31(7): 787-796, 2022 Jul.
Article En | MEDLINE | ID: mdl-35720463

Chlorophyll-rich samples, such as kale, interfere with the analysis of residual pesticides and adversely affect the integrity of tandem mass spectrometers. Dispersed solid-phase (d-SPE) extraction using graphitized carbon black effectively removes pigments from kale extracts; however, it also reduces the recoveries of 30 pesticides. To overcome this, alternative sorbents, including ENVI-Carb, ChloroFiltr, and Z-Sep+, were evaluated in this study. A sorbent combination based on 50 mg of Z-Sep+ was most advantageous (21/30), good precision (< 15%), excellent pigment removal capacity, and low matrix effect. The limit of quantification (0.0001-0.0040 mg/kg) was lower than the Korean maximum residue limits levels. The proposed method was validated according to international guidelines and applied to real kale samples. The results demonstrated that d-SPE using Z-Sep+ provides an effective strategy for ensuring mass spectrometry system integrity and improving the analytical accuracy in chlorophyll-rich samples. Supplementary information: The online version contains supplementary material available at 10.1007/s10068-022-01101-3.

10.
Sci Rep ; 12(1): 8648, 2022 05 23.
Article En | MEDLINE | ID: mdl-35606401

This study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.


Lung Diseases , Mycobacterium Infections, Nontuberculous , Mycobacterium , Humans , Mycobacterium/genetics , Mycobacterium Infections, Nontuberculous/diagnosis , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria , RNA, Ribosomal, 16S/genetics
11.
Nutrients ; 14(6)2022 Mar 18.
Article En | MEDLINE | ID: mdl-35334943

This study determined the beverage hydration index (BHI) and postprandial cardiac autonomic activity after consuming an isotonic beverage (IB) compared to distilled water (DW). Twenty-two participants (50% female; mean ± SD; age, 27 ± 3 year; height, 169.1 ± 12.6 cm; weight, 73.3 ± 13.8 kg; BF%, 23 ± 10%) completed two experimental trials where they consumed 1 L DW or an IB; after which urine volume and cardiac autonomic activity was measured through 240 min. Cardiac autonomic activity was quantified using heart rate (HR), log transformed heart rate variability measures (root mean square of successive R-R intervals; RMSSD; low frequency, LF; and high frequency, HF) and systolic time intervals (pre-ejection period, PEP). BHI was significantly greater after IB consumption at min 0 (MD [95% CI]; 1.31 [0.35, 2.27]), 180 min (0.09 [0.022, 0.16]), and 240 min (0.1 [0.03, 0.17]) compared to DW (p = 0.031). Net fluid balance was significantly greater in IB than DW at 180 min (90 [-16.80, 196.81]) and 240 min (106 [-13.88, 225.88]) (p = 0.037). HR decreased over time in both beverage trials but was higher following IB ingestion at 0 min (3.9 [-2.42, 10.22]), 30 min (5.3 [-0.94, 11.54]), and 60 min (2.7 [-3.42, 8.82]) (p = 0.0002). lnHF was greater 30 min post DW ingestion compared to IB (0.45 [-0.23, 1.13]) (p = 0.039). IB promotes greater fluid retention capacity compared to DW within 4 hours of consumption. The variations in cardiac autonomic measures may warrant further investigation in clinical populations (i.e., patients with autonomic failure).


Autonomic Nervous System , Drinking Water , Adult , Autonomic Nervous System/physiology , Beverages , Female , Heart Rate/physiology , Humans , Male , Water-Electrolyte Balance , Young Adult
12.
Respir Res ; 22(1): 322, 2021 Dec 28.
Article En | MEDLINE | ID: mdl-34963470

BACKGROUND: Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer. METHODS: 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses. RESULTS: In total, 84 patients were prospectively analyzed, of which 59 showed low (< 10%), and 25 showed high (≥ 10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group. CONCLUSION: The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.


B7-H1 Antigen/biosynthesis , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic/physiology , Immunotherapy/methods , Lung Neoplasms/metabolism , Microbiota/physiology , Aged , Antineoplastic Agents, Immunological , B7-H1 Antigen/genetics , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Female , Humans , Lung/metabolism , Lung/microbiology , Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Male , Middle Aged , Prospective Studies
13.
Ther Adv Chronic Dis ; 12: 20406223211056712, 2021.
Article En | MEDLINE | ID: mdl-34820080

BACKGROUND: Tuberculosis (TB) causes undernutrition, and it has a long recovery time after treatment. It is accompanied by adverse health outcomes, such as sarcopenia. OBJECTIVE: We aimed to evaluate the prevalence of sarcopenia and its association with protein and total energy intakes among Korean TB survivors. METHODS: Data of the population-based Korea National Health and Nutrition Examination Survey (2008-2011) were analyzed, including 9,203 participants aged ⩾ 40 years. We used three definitions for sarcopenia-appendicular skeletal muscle mass (ASM, kg) divided by body mass index (BMI, kg/m2), weight (kg), or height squared (m2). Daily protein and total energy intakes were estimated with a 24-h recall method. Multiple logistic regression was used to evaluate the association between dietary protein/total energy intake and sarcopenia among TB survivors. RESULTS: The prevalence of sarcopenia was 11.2%, 10.7%, and 24.3% among TB survivors with sarcopenia defined by ASM divided by BMI, weight, and height squared, respectively. The prevalence of sarcopenia among TB survivors was higher than among those without TB. After adjusting for age, weight, sex, education level, employment status, smoking status, and drinking status, sufficient protein and total energy intakes were associated with a lower risk of sarcopenia in TB survivors. CONCLUSION: The prevalence of sarcopenia was higher in TB survivors than in those without TB. We suggest consuming sufficient protein intake along with increasing total energy intake in TB survivors.

14.
Biomolecules ; 11(11)2021 11 08.
Article En | MEDLINE | ID: mdl-34827654

Lentinula edodes (shiitake) is a popular nutritious edible mushroom with a desirable aroma and flavor. Traditional cultivation of L. edodes on beds of logs has been replaced by cultivation on sawdust, but the effects of cultivation changes on L. edodes mushrooms have not been well characterized. We determined the metabolic profile, bioactive compounds, and antioxidant capacity in L. edodes grown on log or sawdust substrates. Metabolic profiles of L. edodes extracts were determined by 1H nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry. Principal component analysis score plots from 1H NMR analysis showed clear differences between samples. Concentrations of primary metabolites, especially amino acids, generally decreased in L. edodes grown on logs compared to sawdust. Phenolic compounds showed variations in concentration depending on the cultivation method. Bioactive compounds and their antioxidant capacity were analyzed spectrophotometrically. L. edodes cultivated on logs had high concentrations of bioactive compounds with strong antioxidant capacity compared to L. edodes cultivated on sawdust. Thus, the concentration of primary metabolites was high in L. edodes grown on sawdust, which produces a high growth rate. In contrast, log-cultivated L. edodes, which were similar to wild mushrooms, had high levels of bioactive compounds and high antioxidant capacity. This information is useful for determining optimal cultivation conditions for nutritional and medicinal uses of L. edodes mushrooms.


Shiitake Mushrooms , Antioxidants , Phenols , Wood
15.
Int J Mol Sci ; 22(20)2021 Oct 10.
Article En | MEDLINE | ID: mdl-34681602

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.


Cytokines/metabolism , Enzyme Activation/drug effects , Malates/pharmacology , Matrix Metalloproteinase 1/metabolism , Cell Culture Techniques , Cell Line , Cilia/metabolism , Cilia/pathology , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Interleukin-6/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Matrix Metalloproteinase 1/genetics , Models, Biological , Oxidative Stress/drug effects , Particulate Matter/toxicity , RNA Interference , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism , Tumor Suppressor Proteins/antagonists & inhibitors , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Up-Regulation/drug effects
16.
PLoS One ; 16(9): e0257822, 2021.
Article En | MEDLINE | ID: mdl-34591887

OBJECTIVE: This study aimed to determine the gender factors that influence regular exercise in patients with non-insulin-dependent diabetes mellitus (NIDDM) in Korea. METHODS: A total of 1,432 patients with NIDDM were recruited using raw data from the Korea National Health and Nutrition Survey conducted between 2016 and 2018. SAS 9.4 was adopted for data analyses, and the distributional difference was measured with multinomial logistic regression and Rao-Scott x2 statistics to identify the factors that influence the regular physical activities of patients. that the analysis only provides associations. RESULTS: Based on general characteristics, health behaviors, and conditions, patients with NIDDM in Korea were less physically active. In addition, patients with higher educational attainment, higher income, and higher subjective health conditions had a higher odds ratio for regular exercise. Meanwhile, the ratio was lower for smokers and those stressed up. CONCLUSION: A professional guide for the initial phase of training and consistent management is required to increase the involvement of patients with NIDDM in regular exercise. Therefore, it is important to maintain their motivation to continue exercising. Rather than providing a universal guideline, it is more important to provide customized programs and management plans which reflect factors that influence their engagement in physical activities, such as individual physical strength, stress level, alcohol consumption, and arthritis.


Diabetes Mellitus, Type 2/psychology , Exercise , Motivation , Adult , Aged , Female , Health Behavior , Humans , Logistic Models , Male , Middle Aged , Nutrition Surveys , Republic of Korea , Sex Characteristics
17.
Molecules ; 26(17)2021 Sep 06.
Article En | MEDLINE | ID: mdl-34500843

Primary cilia mediate the interactions between cells and external stresses. Thus, dysregulation of primary cilia is implicated in various ciliopathies, e.g., degeneration of the retina caused by dysregulation of the photoreceptor primary cilium. Particulate matter (PM) can cause epithelium injury and endothelial dysfunction by increasing oxidative stress and inflammatory responses. Previously, we showed that PM disrupts the formation of primary cilia in retinal pigment epithelium (RPE) cells. In the present study, we identified 2-isopropylmalic acid (2-IPMA) as a novel inducer of primary ciliogenesis from a metabolite library screening. Both ciliated cells and primary cilium length were increased in 2-IPMA-treated RPE cells. Notably, 2-IPMA strongly promoted primary ciliogenesis and restored PM2.5-induced dysgenesis of primary cilia in RPE cells. Both excessive reactive oxygen species (ROS) generation and activation of a stress kinase, JNK, by PM2.5 were reduced by 2-IPMA. Moreover, 2-IPMA inhibited proinflammatory cytokine production, i.e., IL-6 and TNF-α, induced by PM2.5 in RPE cells. Taken together, our data suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in RPE cells.


Inflammation/metabolism , Particulate Matter/metabolism , Retinal Pigment Epithelium/metabolism , Cilia/metabolism , Cilia/ultrastructure , Cytokines/metabolism , Enzyme Activation , Gene Knockdown Techniques , Humans , MAP Kinase Kinase 4/metabolism , Malates/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Retina
18.
Circulation ; 144(18): 1459-1472, 2021 11 02.
Article En | MEDLINE | ID: mdl-34474597

BACKGROUND: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. METHODS: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. RESULTS: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04-1.34], P=0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6-65.7], P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P<0.001; net reclassification index 1.05, P<0.001; integrated discrimination index 0.20, P<0.001). CONCLUSIONS: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02798731.


Heart Diseases/physiopathology , Heart Transplantation/adverse effects , Heart Transplantation/methods , Microcirculation/physiology , Female , Humans , Male , Middle Aged , Prospective Studies
19.
Arch Pharm Res ; 44(6): 621-631, 2021 Jun.
Article En | MEDLINE | ID: mdl-34100261

The maintenance of lysosomal integrity is essential for lysosome function and cell fate. Damaged lysosomes are degraded by lysosomal autophagy, lysophagy. The mechanism underlying lysophagy remains largely unknown; this study aimed to contribute to the understanding of this topic. A cell-based screening system was used to identify novel lysophagy modulators. Triamterene (6-phenylpteridine-2,4,7-triamine) was identified as one of the most potent lysophagy inducers from the screening process. We found that triamterene causes lysosomal rupture without affecting other cellular organelles and increases autophagy flux in HepG2 cells. Damaged lysosomes in triamterene-treated cells were removed by autophagy-mediated pathway, which was inhibited by depletion of the autophagy regulator, ATG5 or SQSTM1. In addition, treatment of triamterene decreased the integrity of lysosome and cell viability, which were rescued by removing the triamterene treatment in HepG2 cells. Hence, our data suggest that triamterene is a novel lysophagy inducer through the disruption of lysosomal integrity.


Autophagy/drug effects , Epithelial Sodium Channel Blockers/pharmacology , Lysosomes/drug effects , Triamterene/pharmacology , Autophagy/physiology , Cell Survival/drug effects , Cell Survival/physiology , HeLa Cells , Hep G2 Cells , Humans , Lysosomes/metabolism
20.
Endocrinol Metab (Seoul) ; 36(3): 607-618, 2021 06.
Article En | MEDLINE | ID: mdl-34154044

BACKGROUND: Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients. METHODS: Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed. RESULTS: The median daily iodine intake by 24-hour recall was 341.7 µg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine. CONCLUSION: Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.


Iodine , Thyroid Neoplasms , Adult , Diet , Humans , Nutrition Surveys , Thyroid Cancer, Papillary/epidemiology , Thyroid Neoplasms/epidemiology
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