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2.
Pharmacol Rep ; 76(2): 368-378, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38498259

ABSTRACT

BACKGROUND: Excessive stress, a major problem in modern societies, affects people of all ages worldwide. Corticosterone is one of the most abundant hormones secreted during stressful conditions and is associated with various dysfunctions in the body. In particular, we aimed to investigate the protective effects of hygrolansamycin C (HYGC) against corticosterone-induced cellular stress, a manifestation of excessive stress prevalent in contemporary societies. METHODS: We isolated HYGC from Streptomyces sp. KCB17JA11 and subjected PC12 cells to corticosterone-induced stress. The effects of HYGC were assessed by measuring autophagy and the expression of mitogen-activated protein kinase (MAPK) phosphorylation-related genes. We used established cellular and molecular techniques to analyze protein levels and pathways. RESULTS: HYGC effectively protected cells against corticosterone-induced injury. Specifically, it significantly reduced corticosterone-induced oxidative stress and inhibited the expression of autophagy-related proteins induced by corticosterone, which provided mechanistic insight into the protective effects of HYGC. At the signaling level, HYGC suppressed c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation and p38 activation. CONCLUSIONS: HYGC is a promising candidate to counteract corticosterone-induced apoptosis and oxidative stress. Autophagy and MAPK pathway inhibition contribute to the protective effects of HYGC. Our findings highlight the potential of HYGC as a therapeutic agent for stress-related disorders and serve as a stepping stone for further exploration and development of stress management strategies.


Subject(s)
Corticosterone , p38 Mitogen-Activated Protein Kinases , Rats , Animals , Humans , Corticosterone/toxicity , p38 Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System , Oxidative Stress , Signal Transduction , Extracellular Signal-Regulated MAP Kinases/metabolism , Apoptosis , Autophagy
3.
Article in English | MEDLINE | ID: mdl-38212871

ABSTRACT

Background: In patients with type 2 diabetes mellitus (T2DM), diabetic kidney disease (DKD) is diagnosed based on clinical features. A kidney biopsy is used only in selected cases. This study aimed to reconsider the role of a biopsy in predicting renal outcomes. Methods: Clinical and laboratory parameters and renal biopsy results were obtained from 237 patients with T2DM who underwent renal biopsies at Soonchunhyang University Cheonan Hospital between January 2000 and March 2020 and were analyzed. Results: Of 237 diabetic patients, 29.1% had DKD only, 61.6% had non-DKD (NDKD), and 9.3% had DKD with coexisting NDKD (DKD/NDKD). Of the patients with DKD alone, 43.5% progressed to end-stage kidney disease (ESKD), while 15.8% of NDKD patients and 36.4% of DKD/NDKD patients progressed to ESKD (p < 0.001). In the DKD-alone group, pathologic features like ≥50% global sclerosis (p < 0.001), tubular atrophy (p < 0.001), interstitial fibrosis (p < 0.001), interstitial inflammation (p < 0.001), and the presence of hyalinosis (p = 0.03) were related to worse renal outcomes. The Cox regression model showed a higher risk of progression to ESKD in the DKD/NDKD group compared to the DKD-alone group (hazard ratio [HR], 2.73; p = 0.032), ≥50% global sclerosis (HR, 3.88; p < 0.001), and the degree of mesangial expansion (moderate: HR, 2.45; p = 0.045 and severe: HR, 6.22; p < 0.001). Conclusion: In patients with T2DM, a kidney biopsy can help in identifying patients with NDKD for appropriate treatment, and it has predictive value.

4.
ACS Omega ; 8(41): 38263-38271, 2023 Oct 17.
Article in English | MEDLINE | ID: mdl-37867696

ABSTRACT

Liquid chromatography-mass spectrometry (LC-MS/MS)-based molecular networking analysis was applied to Streptomyces sp. MC16. The automatic classification of the MolNetEnhancer module revealed that its major constituent was an angucycline derivative. By targeted isolation of unique clusters in the molecular network, which showed different patterns from typical angucycline compounds, two new N-acetylcysteine-attached angucycline derivatives (1 and 2) were isolated. The structures were elucidated based on intensive NMR analysis and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). All isolated compounds (1-4) were tested for their inhibitory effects on the proliferation of A431, A549, and HeLa cell lines. Antibiotics 100-1 (3) and vineomycinone B2 (4) showed moderate inhibitory effects on these three cell lines with IC50 values ranging from 18.5 to 59.0 µM, while compounds 1 and 2 with an additional N-acetylcysteine residue showed weak inhibitory effects only on the HeLa cell line with IC50 values of 54.7 and 65.2 µM, respectively.

5.
PLoS One ; 17(11): e0277412, 2022.
Article in English | MEDLINE | ID: mdl-36417387

ABSTRACT

Since the prohibition of antibiotics as animal growth promoters, demand for effective probiotic strains has steadily increased. The goal is to maintain productivity and mitigate environmental concerns in the livestock industry. There are many probiotic animal-diet supplements available, over 2,000 products in the Republic of Korea alone, with little explanation about the desirable properties of each probiotic strain. The purpose of this study was to describe the underlying logic and methods used to select two novel strains of probiotic candidates. To economically screen these candidates, the abundance of surfactin secreted was used as an in vitro marker. We used a modified oil-misting method to screen ~2,000 spore-forming bacteria for novel strains of Bacillus subtilis. Of these, 18 strains were initially selected based on the semiquantitative criterion that they secreted more surfactin than B. subtilis ATCC21322 on Luria-Berani (LB) agar plates. The whole genome sequence was determined for two of the 18 strains to verify their identity. A phylogeny of 1,162 orthologous genes, genome contents, and genome organization confirmed them as novel strains. The surfactin profiles produced by these two strains consisted of at least four isoforms similar to standard surfactin and enhanced cellulase activities up to 50%. Four fractionated individual isoforms of surfactin suppressed inflammation induced by lipopolysaccharides. The half-maximal inhibitory concentration (IC50) was about 20 µM for each isoform. Both selected strains were susceptible to seven important antibiotics. Our results implied that an abundant secretion of surfactin was a useful biomarker in vitro and could be utilized for mining probiotic candidates through high-throughput screening of environmental samples.


Subject(s)
Bacillus subtilis , Probiotics , Animals , Bacillus subtilis/genetics , Biological Transport , Research , Anti-Bacterial Agents
6.
J Infect Chemother ; 28(8): 1159-1164, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35513970

ABSTRACT

INTRODUCTION: After COVID-19 vaccination was initiated, the number of patients visiting the emergency department (ED) with vaccine-related adverse reactions increased. We investigated the clinical features of older adults (aged 65 years and older) visiting the ED with self-reported COVID-19 postvaccination fever. METHODS: We conducted a retrospective observational study at three EDs between March 2021 and September 2021. Patients who reported adverse reactions, fever (≥37.5 °C) and/or febrile sensation or rigors following COVID-19 vaccination were included. The demographic and clinical data of these patients were collected by reviewing their medical records. RESULTS: A total of 562 patients were selected, and 396 (70.5%) were female. The older adult group included 155 (27.6%) patients, and the median age was 75 (69-79 years). The older adults less frequently had a fever (≥37.5 °C) upon ED presentation (75.5% vs. 85.7%, respectively), used more emergency medical services (43.9% vs. 18.7%, respectively), and visited an ED more frequently during early hours (00:00-06:00) (31% vs. 20.1%, respectively) compared to the younger adults (p = 0.004, p < 0.001 and p = 0.036). Fewer older adults visited an ED within 2 days of fever onset (73.5% vs. 84%) (p = 0.012), and more older adults were admitted for medical conditions other than vaccine-related adverse reactions (32.9% vs. 4.2%) (p < 0.001). Older adults received more thorough testing (laboratory and imaging tests). Among the older adults, the admission rate was associated with age (p = 0.003). CONCLUSION: Older adults presenting with fever as an adverse reaction following COVID-19 vaccination less frequently had a fever upon visiting the ED, required more ED testing, and had higher admission rates for non-vaccination-related medical conditions.


Subject(s)
COVID-19 Vaccines , COVID-19 , Fever , Aged , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Emergency Service, Hospital , Female , Fever/chemically induced , Fever/diagnosis , Fever/epidemiology , Humans , Male , Retrospective Studies
7.
Eur J Pharmacol ; 923: 174938, 2022 May 15.
Article in English | MEDLINE | ID: mdl-35381263

ABSTRACT

Kurarinone (KR), a naturally occurring flavonoid in Sophora flavescens Aiton and a traditional herbal medicine, reportedly has anti-cancer activity against various cancer types both in vitro and in vivo. However, the cellular mechanism of KR remains unknown. Therefore, we aimed to elucidate the mechanism of cell cycle arrest induced by KR in human colorectal cancer cells. KR not only reduced cell proliferation but also induced G0/G1 arrest of colorectal cancer cell lines. The results of western blotting analysis showed that KR reduced the protein levels of cyclin D1/D3 and CDK4/6 by downregulating signaling proteins such as K-RAS, c-MYC, and p-extracellular signal-regulated kinase. Additionally, KR arrested the cell cycle in the G0/G1 phase in a p53-independent manner, and decreased the protein level of K-RAS by proteasomal degradation dependent on WDR76, an E3 ubiquitin ligase. From these results, we propose that KR could be a potent anti-cancer agent, acting through the degradation of K-RAS dependent on WDR76, regardless of the p53 status.


Subject(s)
Cell Cycle Proteins , Colorectal Neoplasms , DNA-Binding Proteins , Flavonoids , Apoptosis , Cell Cycle , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/drug therapy , DNA-Binding Proteins/metabolism , Flavonoids/pharmacology , G1 Phase Cell Cycle Checkpoints , Humans , Proto-Oncogene Proteins p21(ras) , Tumor Suppressor Protein p53/metabolism
8.
Arch Pharm Res ; 45(2): 105-113, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35201589

ABSTRACT

Phenalenone derivatives sourced from fungi are polyketides that have attracted significant interest because of their diverse chemical structures and potential bioactivities. As part of our ongoing quest to discover novel natural products with biological properties from diverse natural resources, three unreported phenalenone derivatives (1-3), named ent-12-methoxyisoherqueinone (1), (-)-scleroamide (2), and (+)-scleroamide (3), together with four known phenalenone derivatives, ent-atrovenetinone (4), isoherqueinone (5), herqueinone (6), and ent-peniciherquinone (7) were isolated from the Hawaiian soil fungus Penicillium herquei FT729, collected on the Big Island, Hawaii. Compounds 2 and 3 were enantiomers, which were separated using a chiral-phase HPLC column, which provided optically pure compounds 2 and 3. The structures of the novel compounds were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution ESIMS. Their absolute configurations were determined using quantum chemical electronic circular dichroism (ECD) calculations. The inhibitory activity of the isolated compounds (1-7) against indoleamine 2,3-dioxygenase 1 (IDO1) was assessed. Compounds 1, 5-7 inhibited IDO1, with IC50 values of 32.59, 36.86, 19.05, and 24.18 µM, respectively. These findings demonstrated that the phenalenone derivatives 1 and 5-7, as IDO1 inhibitors, are promising anticancer immunotherapeutic agents.


Subject(s)
Antineoplastic Agents/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Penicillium , Phenalenes/pharmacology , Soil Microbiology , Antineoplastic Agents/chemistry , Hawaii , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/drug effects , Inhibitory Concentration 50 , Phenalenes/chemistry , Structure-Activity Relationship
9.
J Korean Med Sci ; 37(6): e39, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35166076

ABSTRACT

Subacute thyroiditis (SAT) is a painful thyroiditis that often requires steroid therapy. Here, we report the first case of severe SAT in a patient who received the first dose of mRNA coronavirus disease 2019 (COVID-19) vaccination. A 34-year-old man without a viral prodrome felt a lump when swallowing 5 days after his first dose of mRNA-1273 (Moderna) vaccination. Ten days after vaccination, the patient visited the hospital and was advised to rest and take nonsteroidal anti-inflammatory drugs. He revisited the hospital 10 days later as symptoms aggravated with anterior neck pain, headache, fatigue, muscle weakness, and weight loss. Thyroid hormone levels and inflammatory markers were consistent with thyrotoxicosis. A thyroid ultrasound scan revealed typical SAT findings. His symptoms rapidly improved after receiving prednisone. A week later, the patient successfully completed his second dose of the vaccine. The thyroid function test results were nearly normal 1 month after the completion of the vaccination. We report this case to raise awareness of the occurrence of SAT after COVID-19 vaccination. As the risk of COVID-19 outweighs the minor risks of the vaccine, managing the side effects of the first vaccine dose is crucial to complete COVID-19 vaccination.


Subject(s)
2019-nCoV Vaccine mRNA-1273/adverse effects , Thyroiditis, Subacute/etiology , Vaccination/adverse effects , Adult , Humans , Male
10.
J Glob Antimicrob Resist ; 28: 43-48, 2022 03.
Article in English | MEDLINE | ID: mdl-34920175

ABSTRACT

OBJECTIVES: We conducted an in vitro investigation of the activity of rifamycins against planktonic and biofilm states of Staphylococcus aureus and Staphylococcus epidermidis isolates from patients with prosthetic joint infections (PJIs), characterised their rpoB gene mutations, and analysed the clinical outcomes of rifampicin-resistant isolates. METHODS: A total of 110 staphylococcal isolates were collected from patients with PJI. Antimicrobials tested using the broth microdilution method included rifampicin, rifabutin, rifapentine and rifaximin. We evaluated rpoB gene mutations to identify rifampicin resistance mechanisms. Clinical outcomes were assessed in rifampicin-resistant isolates. RESULTS: The 110 staphylococcal isolates included 85 S. aureus (55% methicillin-resistant) and 25 S. epidermidis (100% methicillin-resistant). Seven S. aureus isolates and two S. epidermidis isolates were resistant to rifampicin [minimum inhibitory concentration (MIC) ≥2 µg/mL] and these isolates exhibited rpoB gene mutations. Among the 78 rifampicin-susceptible S. aureus isolates and 23 S. epidermidis isolates, 76 S. aureus isolates (97.4%) and all S. epidermidis isolates (100%) were highly susceptible (MIC ≤ 0.06 µg/mL) to other rifamycins. The minimum biofilm bactericidal concentrations for ≥50% of isolates (MBBC50) to rifampicin, rifabutin, rifapentine and rifaximin were 4, 1, 2 and 4 µg/mL for S. aureus and 1, 0.125, 0.25 and 0.5 µg/mL for S. epidermidis, respectively, among rifampicin-susceptible isolates. Among nine patients bearing rifampicin-resistant isolates, only three (33%) had successful outcomes. CONCLUSION: Rifamycins other than rifampicin show promising antistaphylococcal activity, including antibiofilm activity. Rifamycin-resistant staphylococci exhibit rpoB gene mutations.


Subject(s)
Rifamycins , Staphylococcus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Humans , Mutation , Rifabutin/pharmacology , Rifampin/pharmacology , Rifamycins/pharmacology , Rifaximin , Staphylococcus/genetics , Staphylococcus aureus/genetics , Staphylococcus epidermidis/genetics
11.
J Clin Med ; 10(22)2021 Nov 16.
Article in English | MEDLINE | ID: mdl-34830605

ABSTRACT

Cudrania tricuspidata is a folk remedy used to treat inflammation in patients with tumors or liver damage. This study investigated the efficacy of Cudrania tricuspidata extract (CTE) for relieving the symptoms of functional dyspepsia. In an 8-week, randomized, double-blind, placebo-controlled study, 100 adults with any condition featured in the Rome IV criteria and a Gastrointestinal Symptoms Scale (GIS) score ≥4 were randomly allocated to take either a placebo (maltodextrin) or a 50 mg CTE tablet, which equally included celluloses, magnesium stearate, and silicon dioxide, twice daily, 20 January 2020, and 3 August 2020. Among the 83 participants finally analyzed, the CTE group was associated with a significant reduction in the gastrointestinal symptom rating scale (day 0: 8.0 ± 5.2, day 28: 4.7 ± 3.9, and day 56: 2.3 ± 2.4, p < 0.001, respectively) in comparison with the control group (day 0: 8.1 ± 4.7, day 28: 7.8 ± 5.7, and day 56: 7.5 ± 6.6, p > 0.05) after adjusting for smoking, drinking, eating habits, stress levels, and caffeine intake. The CTE group resulted in significant improvements of GIS, Nepean Dyspepsia Index (Korean version), and functional dyspepsia-related quality of life over time. There were no different adverse events (p = 0.523). These findings suggest that CTE is safe and efficacious for alleviating gastrointestinal symptoms in patients with functional dyspepsia.

12.
Micromachines (Basel) ; 12(4)2021 Apr 16.
Article in English | MEDLINE | ID: mdl-33923516

ABSTRACT

To use implantable biomedical devices such as electrocardiograms and neurostimulators in the human body, it is necessary to package them with biocompatible materials that protect the internal electronic circuits from the body's internal electrolytes and moisture without causing foreign body reactions. Herein, we describe a hydrogel surface-modified polyurethane copolymer film with concurrent water permeation resistance and biocompatibility properties for application to an implantable biomedical device. To achieve this, hydrophobic polyurethane copolymers comprising hydrogenated poly(ethylene-co-butylene) (HPEB) and aliphatic poly(carbonate) (PC) were synthesized and their hydrophobicity degree and mechanical properties were adjusted by controlling the copolymer composition ratio. When 10 wt% PC was introduced, the polyurethane copolymer exhibited hydrophobicity and water permeation resistance similar to those of HPEB; however, with improved mechanical properties. Subsequently, a hydrophilic poly(vinyl pyrrolidone) (PVP) hydrogel layer was formed on the surface of the polyurethane copolymer film by Fenton reaction using an initiator and crosslinking agent and the effect of the initiator and crosslinking agent immobilization time, PVP concentration and crosslinking agent concentration on the hydrogel properties were investigated. Finally, MTT assay showed that the hydrogel surface-modified polyurethane copolymer film displays excellent biocompatibility.

13.
Diagn Microbiol Infect Dis ; 99(1): 115173, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32992142
14.
Pharmaceutics ; 12(12)2020 Dec 18.
Article in English | MEDLINE | ID: mdl-33352912

ABSTRACT

Studies on ethanol-induced stress and acetaldehyde toxicity are actively being conducted, owing to an increase in alcohol consumption in modern society. In this study, ent-peniciherqueinone (EPQ) isolated from a Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 was found to reduce the acetaldehyde-induced cytotoxicity and oxidative stress in PC12 cells. EPQ increased cell viability in the presence of acetaldehyde-induced cytotoxicity in PC12 cells. In addition, EPQ reduced cellular reactive oxygen species (ROS) levels and restored acetaldehyde-mediated disruption of mitochondrial membrane potential. Western blot analyses revealed that EPQ treatment increased protein levels of ROS-scavenging heme oxygenase-1 and superoxide dismutase, as well as the levels of aldehyde dehydrogenase (ALDH) 1, ALDH2, and ALDH3, under acetaldehyde-induced cellular stress. Finally, EPQ reduced acetaldehyde-induced phosphorylation of p38 and c-Jun N-terminal kinase, which are associated with ROS-induced oxidative stress. Therefore, our results demonstrated that EPQ prevents cellular oxidative stress caused by acetaldehyde and functions as a potent agent to suppress hangover symptoms and alcohol-related stress.

15.
Bioorg Chem ; 105: 104397, 2020 12.
Article in English | MEDLINE | ID: mdl-33130348

ABSTRACT

The study of a Hawaiian volcanic soil-associated fungal strain Penicillium herquei FT729 led to the isolation of one unprecedented benzoquinone-chromanone, herqueilenone A (1) and two phenalenone derivatives (2 and 3). Their structures were determined through extensive analysis of NMR spectroscopic data and gauge-including atomic orbital (GIAO) NMR chemical shifts and ECD calculations. Herqueilenone A (1) contains a chroman-4-one core flanked by a tetrahydrofuran and a benzoquinone with an acetophenone moiety. Plausible pathways for the biosynthesis of 1-3 are proposed. Compounds 2 and 3 inhibited IDO1 activity with IC50 values of 14.38 and 13.69 µM, respectively. Compounds 2 and 3 also demonstrated a protective effect against acetaldehyde-induced damage in PC-12 cells.


Subject(s)
Enzyme Inhibitors/pharmacology , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Penicillium/chemistry , Phenalenes/pharmacology , Acetaldehyde/antagonists & inhibitors , Acetaldehyde/pharmacology , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Microbial Sensitivity Tests , Molecular Structure , PC12 Cells , Phenalenes/chemistry , Phenalenes/isolation & purification , Rats , Structure-Activity Relationship
16.
Chembiochem ; 21(16): 2253-2258, 2020 08 17.
Article in English | MEDLINE | ID: mdl-32212411

ABSTRACT

Xylaria species are prolific natural product producers. Here, we report the characterization of a new glycosylated incisterol derivative, called xyloneside A (1) and two known lignans (2 and 3) from the ascomycetous Xylaria sp. FB. The structure of xyloneside A (1) was determined by 1D and 2D NMR spectroscopy, high-resolution electrospray ionization mass spectrometry and electronic circular dichroism measurements. Xyloneside A is composed of a 1,2,3,4,5,10,19-heptanorergosterane skeleton and a ß-D-mannopyranose moiety. This is the first report of an incisterol derivative from an Ascomycete. The biological effects of the isolated metabolites on cytotoxicity, autophagy, cell-migration, and angiogenesis were evaluated.


Subject(s)
Antineoplastic Agents/chemistry , Xylariales/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Glycosylation , Humans
17.
Biochem Pharmacol ; 175: 113861, 2020 05.
Article in English | MEDLINE | ID: mdl-32081789

ABSTRACT

Autophagy plays a major role in cell survival and has therefore been exploited as an important strategy in cancer therapy. In this study, we evaluated the autophagy-regulatory effects of kushenol E (KE), a bi-prenylated flavonoid isolated from Sophora flavescens and found that KE increased LC3B-II levels while inducing the formation of autophagic vacuoles and immature autophagosomes in HeLa and HCT116 cells. Transmission electron microscopy images revealed that KE treatment generates immature autophagosomes. Furthermore, KE inhibited autophagosome maturation as demonstrated by blocking the degradation of EGFP puncta in HeLa cells stably expressing EGFP-mRFP-LC3B. It also reduced lysosomal activity and cathepsin maturation by disrupting lysosomal positioning, subsequently inducing apoptosis. Further, a combinatorial approach employing cellular thermal shift assays, revealed valosin-containing protein (VCP)/p97 as a potential target protein of KE; the knockdown and overexpression of VCP/p97 confirmed its involvement in regulating lysosomal positioning for autophagy maturation via direct interactions with KE. Thus, KE may possess autophagy-regulating properties mediated by binding to VCP/p97.


Subject(s)
Autophagy/drug effects , Flavonoids/pharmacology , Lysosomes/drug effects , Valosin Containing Protein/metabolism , Apoptosis/drug effects , Autophagosomes/drug effects , Autophagosomes/ultrastructure , Cell Culture Techniques , Cell Survival/drug effects , Gene Knockdown Techniques , HCT116 Cells , HeLa Cells , Humans , Lysosomes/metabolism , Lysosomes/ultrastructure , RNA, Small Interfering/genetics , Up-Regulation , Valosin Containing Protein/genetics
18.
J Infect Dis ; 218(11): 1813-1821, 2018 10 20.
Article in English | MEDLINE | ID: mdl-29982731

ABSTRACT

Background: Human natural killer T (NKT) cells are known to serve as regulatory and/or effector cells in infectious diseases. However, little is known about the role of NKT cells in Orientia tsutsugamushi infection. Accordingly, the objective of this study was to examine the level and function of NKT cells in patients with scrub typhus. Methods: This study included 62 scrub typhus patients and 62 healthy controls (HCs). NKT cell level and function in peripheral blood samples were measured by flow cytometry. Results: Proliferation of NKT cells and their ability to produce interferon-γ and interleukin-4 (IL-4) were significantly lower in scrub typhus patients compared to those in HCs. However, circulating NKT cell levels were comparable between patients and HCs. Expression levels of CD69, programmed death-1 (PD-1), lymphocyte activation gene-3 (LAG-3), and T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM-3) were significantly increased in scrub typhus patients. Elevated expression of CD69, PD-1, LAG-3, and TIM-3, impaired proliferation, and decreased IL-4 production by NKT cells were recovered in the remission phase. Conclusions: This study demonstrates that circulating NKT cells are numerically preserved but functionally impaired in scrub typhus patients. In addition, NKT cell dysfunction is recovered in the remission phase.


Subject(s)
Natural Killer T-Cells , Scrub Typhus , Aged , Aged, 80 and over , Case-Control Studies , Cell Proliferation , Cytokines/blood , Cytokines/metabolism , Female , Humans , Male , Middle Aged , Natural Killer T-Cells/immunology , Natural Killer T-Cells/metabolism , Orientia tsutsugamushi/immunology , Scrub Typhus/immunology , Scrub Typhus/metabolism , Scrub Typhus/physiopathology
19.
PLoS One ; 13(6): e0199454, 2018.
Article in English | MEDLINE | ID: mdl-29928059

ABSTRACT

This study aimed to identify clinical or microbiological factors affecting the clinical relevance of Corynebacterium striatum isolated from blood cultures. A total of 64 isolates from 51 patients identified as C. striatum by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequencing were assessed. More than two blood cultures were positive in 25 (48.1%) patients. Diabetes, solid tumor, and a history of previous exposure to antibiotics were more common in patients with multiple positive blood cultures. Charlson comorbidity scores were also higher, and more isolates were recovered after 48 hours of hospital stay in patients with multiple positive blood cultures. Strains recovered from patients with multiple positive blood cultures produced significantly more biofilm. Based on multilocus sequence typing (MLST), sequence type (ST) 20 (31.3%) was the most dominant, followed by ST2 (20.3%) and ST23 (10.9%). There was no relationship between the number of positive blood culture sets and sequence typing. In multivariate analyses, Carlson comorbidity score (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.09-3.36; P = 0.03) and biofilm formation were associated with multiple positive blood cultures (OR, 17.43; 95% CI, 3.71-81.91; P = 0.03). This study provides evidence that the biofilm phenotype could contribute to determining the clinical significance of C. striatum in patients with severe underlying conditions. The predominance of certain STs suggests the relatedness of C. striatum infection and the nosocomial environment.


Subject(s)
Blood Culture/methods , Corynebacterium Infections/blood , Corynebacterium/isolation & purification , Aged , Biofilms/growth & development , Corynebacterium/physiology , Female , Humans , Logistic Models , Male , Middle Aged
20.
J Neurogastroenterol Motil ; 23(3): 385-391, 2017 Jul 30.
Article in English | MEDLINE | ID: mdl-28478662

ABSTRACT

BACKGROUND/AIMS: Patient education has been shown to be beneficial in several diseases. To properly educate patients with gastroesophageal reflux disease (GERD), it is necessary to understand how much they already know about their disease. However, no study has examined the degree of disease knowledge in Korean patients with GERD. Therefore, we conducted this study to assess the degree of knowledge in such patients. METHODS: This multicenter prospective study was conducted from January 2014 to January 2015. A total of 746 patients (mean age, 52 years; 57.6% female) were enrolled from 7 hospitals in Korea. Inclusion criteria were diagnosis of GERD and ability to properly complete a survey. Degree of disease knowledge was assessed using the translated, validated Korean Urnes questionnaire, which consists of 22 items related to GERD. RESULTS: Mean percentage of correct answers was 46.3% and mean GERD knowledge score was 9.6. Degree of knowledge (mean percentage of correct answers) regarding etiology, prognosis, and treatment of GERD were 49.5%, 36.7%, and 37.5%, respectively. Degree of disease knowledge differed significantly according to age (P < 0.001), education (P < 0.001), income (P = 0.028), and occupation (P < 0.001). In multivariate analysis, using multiple logistic regression, the higher knowledge score group tended to have higher education and professional occupation. CONCLUSIONS: The surveyed Korean patients had relatively low disease knowledge, suggesting that a GERD educational program may be beneficial in Korea. Formulation of a program is underway.

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