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1.
J Microbiol ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995433

ABSTRACT

DNA double-strand break (DSB) repair is a fundamental cellular process crucial for maintaining genome stability, with homologous recombination and non-homologous end joining as the primary mechanisms, and various alternative pathways such as single-strand annealing (SSA) and microhomology-mediated end joining also playing significant roles under specific conditions. IRC genes were previously identified as part of a group of genes associated with increased levels of Rad52 foci in Saccharomyces cerevisiae. In this study, we investigated the effects of IRC gene mutations on DSB repair, focusing on uncharacterized IRC10, 19, 21, 22, 23, and 24. Gene conversion (GC) assay revealed that irc10Δ, 22Δ, 23Δ, and 24Δ mutants displayed modest increases in GC frequencies, while irc19Δ and irc21Δ mutants exhibited significant reductions. Further investigation revealed that deletion mutations in URA3 were not generated in irc19Δ mutant cells following HO-induced DSBs. Additionally, irc19Δ significantly reduced frequency of SSA, and a synergistic interaction between irc19Δ and rad52Δ was observed in DSB repair via SSA. Assays to determine the choice of DSB repair pathways indicated that Irc19 is necessary for generating both GC and deletion products. Overall, these results suggest a potential role of Irc19 in DSB repair pathways, particularly in end resection process.

2.
Toxics ; 12(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38251006

ABSTRACT

Polyhexamethylene guanidine phosphate (PHMG-p) is a common biocidal disinfectant that is widely used in industry and household products. However, PHMG-p was misused as a humidifier disinfectant (HD) in South Korea, which had fatal health effects. Various health problems including cardiovascular diseases were observed in HD-exposed groups. However, the potential underlying mechanism of HD-associated cardiovascular diseases is poorly understood. Here, we examined the procoagulant activity of platelets caused by PHMG-p and clarified the underlying mechanism. PHMG-p enhanced phosphatidylserine (PS) exposure through alteration of phospholipid transporters, scramblase, and flippase. Intracellular calcium elevation, intracellular ATP depletion, and caspase-3 activation appeared to underlie phospholipid transporter dysregulation caused by PHMG-p, which was mediated by oxidative stress and mitochondrial dysfunction. Notably, antioxidant enzyme catalase and calcium chelator EGTA reversed PHMG-p-induced PS exposure and thrombin generation, confirming the contributive role of oxidative stress and intracellular calcium in the procoagulant effects of PHMG-p. These series of events led to procoagulant activation of platelets, which was revealed as enhanced thrombin generation. Collectively, PHMG-p triggered procoagulant activation of platelets, which may promote prothrombotic risks and cardiovascular diseases. These findings improve our understanding of HD-associated cardiovascular diseases.

3.
Front Cardiovasc Med ; 9: 849474, 2022.
Article in English | MEDLINE | ID: mdl-35479283

ABSTRACT

Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.

4.
Acupunct Med ; 39(6): 603-611, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34044603

ABSTRACT

INTRODUCTION: Acute pain significantly delays early physiological recovery and results in chronic functional disability in patients with traumatic multiple rib fractures (MRFs). This prospective cohort study aimed to investigate the feasibility of acupuncture combined with multidisciplinary care during recovery in patients with traumatic MRFs. METHODS: Twenty patients with traumatic MRFs who were admitted to a regional trauma centre in South Korea were enrolled. A combination of acupuncture and multidisciplinary inpatient ward management was provided at the trauma ward. Patients were permitted to continue acupuncture treatments at outpatient clinics for 3 months after the traumatic events. Clinical outcomes, including pain, acute physiological recovery, quality of life, patient satisfaction with the care provided, respiratory function and use of opioids, were evaluated up to 6 months after trauma. RESULTS: Seventeen (85%) participants completed the 6-month follow-up. One patient withdrew consent during admission due to discomfort after three sessions of acupuncture. The proportion of patients with above-moderate level of pain decreased from 95% at baseline to 41% at 6 months. Quality of life appeared to deteriorate consistently throughout the study period. Around 80% of respondents expressed satisfaction with the acupuncture treatments and stated that they found acupuncture to be acceptable. Over 94% of respondents reported slight or considerable improvement. CONCLUSION: The provision of acupuncture combined with multidisciplinary care for recovery in patients with traumatic MRFs was feasible in a regional trauma centre in South Korea. Randomised trials are needed to investigate the role of acupuncture combined with multidisciplinary care in the future. TRIAL REGISTRATION NUMBER: KCT0002911 (Clinical Research Information Service).


Subject(s)
Acupuncture Therapy , Rib Fractures/therapy , Adult , Aged , Cohort Studies , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Satisfaction , Prospective Studies , Quality of Life , Republic of Korea , Rib Fractures/physiopathology , Rib Fractures/psychology , Rib Fractures/rehabilitation
5.
J Microbiol ; 59(4): 401-409, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33779953

ABSTRACT

Eukaryotic genomes contain many duplicated genes closely located with each other, such as the hexose transporter (HXT) genes in Saccharomyces cerevisiae. They can potentially recombine via single-strand annealing (SSA) pathway. SSA between highly divergent sequences generates heteroduplex DNA intermediates with many mismatches, which can be corrected by mismatch repair (MMR), resulting in recombinant sequences with a single junction point. In this report, we demonstrate that SSA between HXT1 and HXT4 genes in MMR-deficient yeast cells produces recombinant genes with multiple-junctions resulting from alternating HXT1 and HXT4 tracts. The mutations in MMR genes had differential effects on SSA frequencies; msh6Δ mutation significantly stimulated SSA events, whereas msh2Δ and msh3Δ slightly suppressed it. We set up an assay that can identify a pair of recombinant genes derived from a single heteroduplex DNA. As a result, the recombinant genes with multiple-junctions were found to accompany genes with single-junctions. Based on the results presented here, a model was proposed to generate multiple-junctions in SSA pathway involving an alternative short-patch repair system.


Subject(s)
DNA Mismatch Repair , Monosaccharide Transport Proteins/genetics , Nucleic Acid Heteroduplexes/genetics , Saccharomyces cerevisiae/genetics , Base Pair Mismatch , DNA, Fungal , DNA-Binding Proteins/genetics , Fungal Proteins/genetics , Genes, Fungal , Mutation , Recombination, Genetic
6.
J Microbiol ; 58(11): 957-966, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33125670

ABSTRACT

Eukaryotic genomes contain numerous homologous repeat sequences including redundant genes with divergent homology that can be potential recombination targets. Recombination between divergent sequences is rare but poses a substantial threat to genome stability. The hexose transporter (HXT) gene family shares high sequence similarities at both protein and DNA levels, and some members are placed close together in tandem arrays. In this study, we show that spontaneous interstitial deletions occur at significantly high rates in HXT gene clusters, resulting in chimeric HXT sequences that contain a single junction point. We also observed that DNA double-strand breaks created between HXT genes produce primarily interstitial deletions, whereas internal cleavage of the HXT gene resulted in gene conversions as well as deletion products. Interestingly, interstitial deletions were less constrained by sequence divergence than gene conversion. Moreover, recombination-defective mutations differentially affected the survival frequency. Mutations that impair single-strand annealing (SSA) pathway greatly reduced the survival frequency by 10-1,000-fold, whereas disruption of Rad51-dependent homologous recombination exhibited only modest reduction. Our results indicate that recombination in the tandemly repeated HXT genes occurs primarily via SSA pathway.


Subject(s)
DNA Repair , DNA, Fungal/genetics , Monosaccharide Transport Proteins/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , DNA Breaks, Double-Stranded , Homologous Recombination , Multigene Family
7.
Int J Endocrinol ; 2018: 1835486, 2018.
Article in English | MEDLINE | ID: mdl-29808087

ABSTRACT

BACKGROUND: Limited information exists about the impact of nonalcoholic fatty liver disease (NAFLD) on mild renal insufficiency. We compared the relative influence of NAFLD, metabolic syndrome (MetS), and subclinical inflammation, alone or in combination, on mild renal insufficiency. METHODS: This study included 1174 Korean adults. NAFLD was diagnosed using ultrasonography. Mild renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) ≥ 60 and <90 mL/min/1.73 m2. RESULTS: In partial correlation analysis, several components of MetS and liver aminotransferase levels, but not high-sensitivity C-reactive protein (hsCRP), were associated with eGFR. Multivariate logistic regression analysis demonstrated the independent association of NAFLD (P = 0.034) and MetS (P = 0.018) with mild renal insufficiency, but not elevated hsCRP (P = 0.885). Furthermore, NAFLD without the MetS group (odds ratio (95% confidence interval) = 1.56 (1.05-2.34)) or MetS without the NAFLD group (1.82 (1.11-3.00)) was associated with mild renal insufficiency after adjusting for confounding variables. However, individuals with high hsCRP showed no relationship with mild renal insufficiency, irrespective of the existence of NAFLD. CONCLUSIONS: This study demonstrated that NAFLD and MetS are independently associated with mild renal insufficiency, whereas subclinical inflammation did not affect the risk for mild renal insufficiency in Korean adults.

8.
Food Res Int ; 105: 982-988, 2018 03.
Article in English | MEDLINE | ID: mdl-29433297

ABSTRACT

The purpose of this study was to investigate the applicability of green tea seed (GTS) extract as a natural preservative in food. Food preservative ability and mutagenicity studies of GTS extract and identification of antimicrobial compounds from GTS extract were carried out. The GTS extract showed only anti-yeast activity against Candida albicans with MIC value of 938µg/mL and Zygosaccharomyces rouxii with a MIC of 469µg/mL. The active compounds were identified as theasaponin E1 (1), assamsaponin A (2), and assamsaponin B (3). And GTS extracts didn't show mutagenicity because there were no dose-dependent changes in colonies of Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA regardless of the metabolic activation system. And GTS extract also showed a potent food preservation affect which eliminated all yeast below the MIC value in application test at soy sauce. Overall, these results indicate that GTS extract could be a safe and effective food preservative with anti-yeast activity.


Subject(s)
Antifungal Agents/pharmacology , Camellia sinensis/chemistry , Food Microbiology/methods , Food Preservation/methods , Food Preservatives/pharmacology , Plant Extracts/pharmacology , Seeds/chemistry , Soy Foods/microbiology , Antifungal Agents/isolation & purification , Antifungal Agents/toxicity , Camellia sinensis/toxicity , Candida albicans/drug effects , Candida albicans/growth & development , Escherichia coli/drug effects , Escherichia coli/genetics , Escherichia coli/growth & development , Food Preservatives/isolation & purification , Food Preservatives/toxicity , Microbial Sensitivity Tests , Mutagenicity Tests , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/isolation & purification , Oleanolic Acid/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Salmonella typhimurium/growth & development , Saponins/isolation & purification , Saponins/pharmacology , Seeds/toxicity , Zygosaccharomyces/drug effects , Zygosaccharomyces/growth & development
9.
Diabetes Res Clin Pract ; 136: 100-107, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29199003

ABSTRACT

AIMS: Meteorin-like (Metrnl) was recently identified as a novel adipomyokine induced by exercise and cold exposure. Metrnl improves glucose tolerance, increases systemic energy expenditure, induces white adipose browning, and promotes anti-inflammatory gene programs in obese/diabetic mice. However, the relationship of Metrnl with diabetes and cardiometabolic risk variables in humans has not been explored. METHODS: In 800 subjects (400 patients with type 2 diabetes and 400 non-diabetes), Metrnl concentration was measured with an enzyme-linked immunosorbent assay, and the correlations of Metrnl level with anthropometric parameters, lifestyle factors, body composition values, and laboratory measurements were assessed. RESULTS: Metrnl concentration was significantly higher in patients with diabetes than in those without diabetes [median (inter-quartile range); diabetes: 1219.9 (1020.6, 1535.6), non-diabetes: 1131.2 (993.1, 1313.6) pg/ml, P < .001]. After adjustment for age and sex, Metrnl level was significantly associated with fasting plasma glucose, blood pressure, lipid profile, and eGFR, but not with BMI or percent body fat. Multiple stepwise regression analysis exhibited that Metrnl level was independently associated with diabetes status (P < .001), eGFR (P < .001), and total cholesterol (P = .026) (R2 = 0.127). In multiple logistic regression analysis, the odds ratio for the risk of diabetes was 3.53 (95% confidence interval: 2.04-6.10) in the highest tertile of Metrnl compared to the lowest after adjustment for confounding factors. CONCLUSIONS: This study is the first to demonstrate that Metrnl level is elevated in human subjects with type 2 diabetes and is inversely related to various cardiometabolic risk factors, including renal function.


Subject(s)
Diabetes Mellitus, Type 2/blood , Enzyme-Linked Immunosorbent Assay/methods , Exercise/physiology , Intercellular Signaling Peptides and Proteins/metabolism , Nerve Tissue Proteins/metabolism , Obesity/complications , Animals , Body Mass Index , Female , Humans , Male , Mice , Middle Aged , Risk Factors
10.
J Gerontol A Biol Sci Med Sci ; 73(3): 386-392, 2018 03 02.
Article in English | MEDLINE | ID: mdl-28407041

ABSTRACT

Background: Previous studies have shown that chronic kidney disease (CKD) is associated with accelerated loss of skeletal muscle in patients on dialysis. However, the relationships of sarcopenia with albuminuria and early-stage CKD in patients with type 2 diabetes have not been examined. Methods: We analyzed diabetic subgroup data from 409 patients with type 2 diabetes from the Korean Sarcopenic Obesity Study (KSOS). Sarcopenia was defined as a skeletal muscle mass index (SMI; SMI [%] = total skeletal muscle mass [kg]/weight [kg] × 100) less than 2 SD below the sex-specific mean for a younger reference group. The estimated glomerular filtration rates and urinary albumin-to-creatinine ratios were used to assess renal function and albuminuria. Results: The prevalence of sarcopenia was significantly increased in the albuminuria group compared with the normo-albuminuria group (26.7% vs 12.6%, p = .001), as well as in CKD 3 group compared with the CKD 1-2 group (46.7% vs 15.1%, p = .005). After adjusting for age, SMI was negatively correlated with urinary albumin-to-creatinine ratios and positively correlated with aspartate aminotransferase, alanine aminotransferase, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. Multiple logistic regression analysis revealed that the odds ratio for albuminuria association was 3.02 (95% CI 1.37-6.67) in the lowest tertile of SMI compared with the highest tertile after adjusting for various confounding factors. Conclusions: Sarcopenia is more prevalent in individuals with albuminuria than in those without albuminuria. Furthermore, increased albuminuria is independently associated with low muscle mass in patients with type 2 diabetes.


Subject(s)
Albuminuria/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Renal Insufficiency, Chronic/physiopathology , Sarcopenia/physiopathology , Aged , Albuminuria/epidemiology , Biomarkers/metabolism , Body Composition , Cross-Sectional Studies , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Kidney Function Tests , Male , Middle Aged , Muscle, Skeletal/physiopathology , Prevalence , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Republic of Korea/epidemiology , Sarcopenia/epidemiology
11.
Int J Endocrinol ; 2018: 7918714, 2018.
Article in English | MEDLINE | ID: mdl-30675162

ABSTRACT

BACKGROUND: Previous studies have suggested the existence of distinct body size subgroups according to metabolic health referred to as metabolically healthy obesity (MHO) and metabolically abnormal but normal weight (MANW) patients. Although nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and metabolic syndrome, the relationship between these phenotypes and fetuin-A, a representative hepatokine, has not been explored. METHODS: We examined the association between circulating fetuin-A levels, metabolic health phenotypes, cardiometabolic risk parameters, and subclinical atherosclerosis in 290 subjects who were randomly selected from an ongoing cohort study. RESULTS: Fetuin-A concentrations were significantly associated with detrimental anthropometric and laboratory measurements, including increased waist circumference, blood pressure, alanine aminotransferase, fasting plasma glucose, and triglyceride levels. Furthermore, fetuin-A levels were significantly increased in the metabolically abnormal (MA) group compared to the metabolically healthy (MH) group in subjects without obesity (717.1 [632.1, 769.7] vs. 599.5 [502.0, 709.3], P = 0.001) and subjects with obesity (704.1 [595.5-880.9] vs. 612.2 [547.9-802.1], P = 0.016). In addition, brachial-ankle pulse wave velocity (baPWV), which reflects arterial stiffness, was higher in MA individuals compared to MH individuals. Multiple logistic regression analysis revealed that both individuals without obesity (P for trend = 0.017) and with obesity (P for trend = 0.028) in the higher tertiles of fetuin-A had an increased risk of MA than those in the lowest tertile. CONCLUSIONS: This study demonstrates that fetuin-A levels are significantly associated with metabolic health phenotypes, such as MHO and MANW, in Korean adults.

12.
Diabetes Metab J ; 41(4): 284-295, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28868826

ABSTRACT

BACKGROUND: Long-term durable glycemic control is a difficult goal in the management of type 2 diabetes mellitus (T2DM). We evaluated the factors associated with durable glycemic control in a real clinical setting. METHODS: We retrospectively reviewed the medical records of 194 new-onset, drug-naïve patients with T2DM who were diagnosed between January 2011 and March 2013, and were followed up for >2 years. Glycemic durability was defined as the maintenance of optimal glycemic control (glycosylated hemoglobin [HbA1c] <7.0%) for 2 years without substitution or adding other glucose-lowering agents. Clinical factors and glycemic markers associated with glycemic durability were compared between two groups: a durability group and a non-durability group. RESULTS: Patients in the durability group had a higher baseline body mass index (26.1 kg/m² vs. 24.9 kg/m²) and lower HbA1c (8.6% vs. 9.7%) than the non-durability group. The initial choice of glucose-lowering agents was similar in both groups, except for insulin and sulfonylureas, which were more frequently prescribed in the non-durability group. In multiple logistic regression analyses, higher levels of education, physical activity, and homeostasis model assessment of ß-cell function (HOMA-ß) were associated with glycemic durability. Notably, lower HbA1c (<7.0%) at baseline and first follow-up were significantly associated with glycemic durability (adjusted odds ratio [OR], 7.48; 95% confidence interval [CI], 2.51 to 22.3) (adjusted OR, 9.27; 95% CI, 1.62 to 53.1, respectively), after adjusting for confounding variables including the types of glucose-lowering agents. CONCLUSION: Early achievement of HbA1c level within the glycemic target was a determinant of long-term glycemic durability in new-onset T2DM, as were higher levels of education, physical activity, and HOMA-ß.

13.
PLoS One ; 12(4): e0174717, 2017.
Article in English | MEDLINE | ID: mdl-28376109

ABSTRACT

OBJECTIVE: Previous studies have shown that leukocyte cell-derived chemotaxin 2 (LECT2), a recently discovered hepatokine, is associated with the inflammatory response and insulin resistance. We examined circulating plasma LECT2 levels in the subjects with non-alcoholic fatty liver disease (NAFLD) or metabolic syndrome. METHODS: We analyzed plasma LECT2 levels from the subjects of age- and sex-matched 320 adults with or without NAFLD who completed a health check-up at the Health Promotion Center of Korea University Guro Hospital. RESULTS: Individuals with NAFLD showed significantly higher LECT2 levels (31.2 [20.9, 41.5] vs. 24.5[16.3, 32.7] ng/ml, P <0.001) as well as components of MetS compared to those without NAFLD. Furthermore, circulating LECT2 concentrations were greater in subjects with MetS (32.6 [17.8, 45.0] vs. 27.0 [18.7, 33.7] ng/ml, P = 0.016) and were associated with anthropometric measures of obesity, lipid profiles, high sensitivity C-reactive protein (hsCRP) and liver aminotransferase levels. However, there was no significant relationship between LECT2 levels and indicators of subclinical atherosclerosis, such as carotid intima-media thickness (CIMT) and brachial ankle pulse wave velocity (baPWV). Multivariate analysis demonstrated a progressively increasing trend of odds ratios for NAFLD according to quartiles of LECT2 levels after adjusting for risk factors, although the relationship was attenuated after further adjustment for waist circumference and lipid levels. CONCLUSION: Circulating LECT2 concentrations were increased in individuals with NAFLD and those with MetS, but not in those with atherosclerosis. The relationship between LECT2 and both NAFLD and MetS might be mediated by its association with abdominal obesity and lipid metabolism. TRIAL REGISTRATION: Clinicaltrials.gov NCT01594710.


Subject(s)
Atherosclerosis/blood , Intercellular Signaling Peptides and Proteins/blood , Metabolic Syndrome/blood , Non-alcoholic Fatty Liver Disease/blood , Adult , Aged , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Dyslipidemias/blood , Female , Humans , Lipid Metabolism , Male , Middle Aged , Obesity, Abdominal/blood , Republic of Korea , Risk Factors
14.
Biochim Biophys Acta Mol Basis Dis ; 1863(6): 1436-1444, 2017 06.
Article in English | MEDLINE | ID: mdl-28215577

ABSTRACT

BACKGROUND & OBJECTIVE: Sestrin2 (sesn2) has recently gained attention as an important regulator for various metabolic disorders. Sesn2 is involved in AMP-activated protein kinase (AMPK) activation, which leads to anti-inflammatory and anti-oxidative responses. However, the role of sesn2 in the endothelium has not yet been clarified. METHODS: To evaluate sesn2-mediated anti-atherosclerotic effects, siRNA to silence sesn2 expression was introduced to human umbilical vein endothelial cells (HUVECs), THP-1 cells and C57BL/6 mice. Lipopolysaccharide (LPS) was administrated to sesn2-knockdown cells and mice to induce atherosclerotic signals. RESULTS: Knockdown of sesn2 was involved with atherosclerotic reactions caused by LPS treatment through decrease of AMPK phosphorylation. In sesn2-knockdown HUVECs and THP-1 cells, LPS-mediated nuclear factor kappa B (NF-κB) phosphorylation and secretion of pro-inflammatory cytokines were both significantly increased. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly increased after sesn2-knockdown. Furthermore, LPS-induced reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and cell toxicity were all significantly elevated after sesn2-knockdown in HUVECs. Interestingly, all these pro-atherosclerotic effects were fully abrogated by treatment with an AMPK activator. In aortic tissue samples from C57BL/6 mice, sesn2-knockdown using siRNA oligomers resulted in reduced AMPK phosphorylation and induction of LPS-mediated NF-κB phosphorylation, leading to up-regulation of adhesion molecules and ER stress-related signaling. CONCLUSION: Knockdown of sesn2 aggravates atherosclerotic processes by increasing pro-inflammatory reactions and ER stress in the endothelium via an AMPK-dependent mechanism, suggesting that sesn2 might be a novel therapeutic target for atherosclerosis.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Atherosclerosis , Endoplasmic Reticulum Stress , Nuclear Proteins/metabolism , Signal Transduction , AMP-Activated Protein Kinases/genetics , Animals , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/therapy , Gene Knockdown Techniques , Human Umbilical Vein Endothelial Cells , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/therapy , Mice , Nuclear Proteins/genetics , Peroxidases , THP-1 Cells
15.
Infect Chemother ; 49(4): 286-292, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29299896

ABSTRACT

Endogenous endophthalmitis secondary to group B Streptococcus (GBS) is extremely rare, particularly in healthy adults. However, the visual prognosis is poor. We report the first South Korean case of GBS infective endocarditis presenting as endogenous endophthalmitis and skin and soft tissue infection. Cultures of blood, vitreous humor, and pus from skin aspirates yielded a penicillin-susceptible serotype V strain of Streptococcus agalactiae. After 6 weeks, the patient completely recovered from GBS infective endocarditis. However, despite early antibiotic treatment and early surgical intervention, the patient's right eye developed phthisis bulbi and was a candidate for evisceration.

16.
Acta Clin Belg ; 71(4): 253-7, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27075785

ABSTRACT

OBJECTIVE AND IMPORTANCE: Infective endocarditis involving the tricuspid valve is an uncommon condition, and a consequent haemothorax associated with pulmonary embolism is extremely rare. Particularly, there are no guidelines for the management of this complication. We describe a rare case of pulmonary embolism and infarction followed by a haemothorax due to infective endocarditis of the tricuspid valve caused by Streptococcus sanguinis. CLINICAL PRESENTATION: A 25-year-old man with a ventricular septal defect (VSD) presented with fever. On physical examination, his body temperature was 38.8 °C, and a grade III holosystolic murmur was heard. A chest X-ray did not reveal any specific findings. A transoesophageal echocardiogram showed a perimembranous VSD and echogenic material attached to the tricuspid valve. All blood samples drawn from three different sites yielded growth of pan-susceptible S. sanguinis in culture bottles. On day 12 of hospitalization, the patient complained of pleuritic chest pain without fever. Physical examination revealed reduced breathing sounds and dullness in the lower left thorax. On his chest computed tomography scan, pleural effusion with focal infarction and pulmonary embolism were noted on the left lower lung. Thoracentesis indicated the presence of a haemothorax. INTERVENTION: Our case was successfully treated using antibiotic therapy alone with adjunctive chest tube insertion, rather than with anticoagulation therapy for pulmonary embolism or cardiac surgery. CONCLUSION: When treating infective endocarditis caused by S. sanguinis, clinicians should include haemothorax in the differential diagnosis of patients complaining of sudden chest pain.


Subject(s)
Endocarditis, Bacterial , Hemothorax/etiology , Streptococcal Infections , Adult , Anti-Bacterial Agents/therapeutic use , Chest Tubes , Hemothorax/microbiology , Humans , Male , Streptococcus
17.
Endocrinol Metab (Seoul) ; 30(4): 614-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26354493

ABSTRACT

A brown tumor is a benign fibrotic, erosive bony lesion caused by localized, rapid osteoclastic turnover, resulting from hyperparathyroidism. Although brown tumors are one of the most pathognomonic signs of primary hyperparathyroidism, they are rarely seen in clinical practice. In this report, we present a case of 20-year-old woman with recurrent fractures and bone pain. Plain digital radiographs of the affected bones revealed multiple erosive bone tumors, which were finally diagnosed as brown tumors associated with primary hyperparathyroidism due to a parathyroid adenoma. This case shows that multiple, and clinically severe form of brown tumors can even occur in young patients.

18.
Biomed Res Int ; 2013: 213109, 2013.
Article in English | MEDLINE | ID: mdl-23509691

ABSTRACT

BACKGROUND: Point-of-care testing (POCT) coagulometers are increasingly being used in the hospital setting. We investigated whether the prothrombin time international normalized ratio (INR) results by CoaguChek XS Plus (Roche Diagnostics GmbH, Mannheim, Germany) can be used reliably without being confirmed with the INR results by STA-R system (Diagnostica Stago S.A.S, Asnières sur Seine, France). METHODS: A total of 118 INR measurements by CoaguChek XS Plus and STA-R were compared using Passing/Bablok regression analysis and Bland-Altman plot. Agreement of the INR measurements was further assessed in relation to dosing decision. RESULTS: The correlation of INR measurements between CoaguChek XS Plus and STA-R was excellent (correlation coefficient = 0.964). The mean difference tended to increase as INR results increased and was 0.25 INR in the therapeutic range (2.0-3.0 INR). The overall agreement was fair to good (kappa = 0.679), and 21/118 (17.8%) INR measurements showed a difference in dosing decision. CONCLUSION: The positive bias of CoaguChek XS Plus may be obvious even in the therapeutic INR range, and dosing decision based on the CoaguChek XS Plus INR results would be different from that based on the STA-R results. The INR measurements by POCT coagulometers still need to be confirmed with the laboratory INR measurements.


Subject(s)
Blood Coagulation Tests/instrumentation , Blood Coagulation Tests/standards , International Normalized Ratio/methods , International Normalized Ratio/standards , Adolescent , Adult , Aged , Aged, 80 and over , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Child , Female , Humans , Male , Middle Aged , Prothrombin Time/methods , Regression Analysis , Reproducibility of Results , Young Adult
19.
Transfus Apher Sci ; 47(1): 21-5, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22490391

ABSTRACT

BACKGROUND: Leukocyte reduction filters are widely used for platelet transfusion therapy, and effective leukocyte removal is mandatory for transfusion safety. We evaluated both the performance of leukocyte reduction filters for platelets and the effect of filtration on platelet function. METHODS: A total of 100 pooled products (eight platelet concentrates were randomly pooled for each product) were used in this study: 50 were filtered by BioP-plus (Fresenius Kabi AG, Homburg, Germany) and 50 by PXL-8 (Pall Corporation, East Hills, NY, USA). Leukocyte reduction, platelet recovery, and filtration time were evaluated in each leukocyte reduction filter. Platelet aggregation responses to thrombin receptor activation peptide stimulation were compared in pre- and post-filtration products using impedance aggregometry (Multiplate Analyzer, Dynabyte Medical, Munich, Germany). RESULTS: Leukocyte counts were uniformly less than 8.3×10(5) in all the post-filtration products, except one filtered by the PXL-8. Leukocyte reduction was 99.1% for BioP-plus and 99.7% for PXL-8, and platelet recovery was 84.2% for the BioP-plus and 86.7% for PXL-8. Filtration time of the BioP-plus was significantly shorter than that of PXL-8. Post-filtration platelet aggregation tended to decrease in both filters, showing no difference between them. CONCLUSIONS: Both BioP-plus and PXL-8 leukocyte reduction filters for platelets performed well with effective leukocyte reduction and satisfactory platelet recovery. Although platelet function was decreased after filtration procedures, its clinical relevance is uncertain.


Subject(s)
Blood Platelets/cytology , Blood Platelets/metabolism , Leukapheresis/instrumentation , Platelet Aggregation , Female , Humans , Leukapheresis/methods , Leukocyte Count/methods , Male , Platelet Function Tests/methods
20.
J Agric Food Chem ; 56(10): 3772-6, 2008 May 28.
Article in English | MEDLINE | ID: mdl-18439016

ABSTRACT

The influence of salinity stress on the growth, appearance, and nutritional compounds, especially phenolic compounds and carotenoids, of romaine lettuce (Lactuca sativa L.), a low salt tolerant plant, was studied. The dry weight, height, and color of the lettuce plants were significantly changed by long-term irrigation (15 days) with higher NaCl concentration (i.e., >100 mM). However, no significant differences were observed in the growth and appearance among the control, all short-term treatments (2 days; 50, 100, 500, and 1000 mM), and long-term irrigation with low salt concentration. Moreover, in romaine lettuce treated with long-term irrigation with 5 mM NaCl, the total carotenoid content increased without color change, and the contents of major carotenoids in romaine lettuce, lutein and beta-carotene, increased 37 and 80%, respectively. No differences were observed in lutein and beta-carotene contents in short-term-treated lettuce. The phenolic content of the romaine lettuce declined with short-term salt irrigation, whereas there were no significant differences among treatments exposed to long-term irrigation. This research indicates that long-term irrigation with relatively low salt concentration, rather than short-term irrigation with high salt concentration, can increase carotenoid content in romaine lettuce without causing a tradeoff in yield or visual quality.


Subject(s)
Agriculture/methods , Lactuca/chemistry , Lactuca/growth & development , Salinity , Carotenoids/analysis , Lactuca/drug effects , Phenols/analysis , Sodium Chloride/administration & dosage , Sodium Chloride/analysis , Water/analysis
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