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Background: It is unclear whether increased left ventricular (LV) thickness is associated with worse clinical outcomes in severe aortic stenosis (AS). The aim of this study was to determine the effect of increased LV wall thickness (LVWT) on major clinical outcomes in patients with severe AS., Methods and Results: This study included 290 severe AS patients (mean age 69.4 ± 11.0 years; 136 females) between January 2008 and December 2018. For outcome assessment, the endpoint was defined as death from all causes, cardiovascular death, and the aortic valve replacement (AVR) surgery rate. During follow-up (48.7 ± 39.0 months), 157 patients had AVR, 43 patients died, and 28 patients died from cardiovascular causes. Patients with increased LVWT underwent AVR surgery much more than those without LVWT (60.0% vs. 39.0%, p < 0.001). Furthermore, in patients with increased LVWT, the all-cause and cardiovascular death rates were significantly lower in the AVR group than in the non-AVR group (8.8% vs. 27.3%, p < 0.001, 4.8%, vs. 21.0%, p < 0.001). Multivariate analysis revealed that increased LVWT, age, dyspnea, and AVR surgery were significantly correlated with cardiovascular death., Conclusions: In patients with severe AS, increased LVWT was associated with a higher AVR surgery rate and an increased rate of cardiovascular death independent of other well-known prognostic variates. Thus, these findings suggest that increased LVWT might be used as a potential prognostic factor in severe AS patients.

Abstract: Optimal medical therapy (OMT) plays a crucial role in the secondary prevention of established coronary artery disease. The renin-angiotensin system (RAS) is an important target of OMT. However, there is limited evidence on whether there is any difference in the combined effect of OMT according to the classes of RAS blockade [angiotensin-converting enzyme inhibitor (ACEI) vs. angiotensin receptor blocker (ARB)]. Based on the nationwide National Health Insurance database in South Korea, 39,096 patients who received OMT after percutaneous coronary intervention between July 2013 and June 2017 were enrolled. Patients were stratified into either acute myocardial infarction (AMI) or angina cohort and analyzed according to the class of RAS blockade included in OMT at discharge (ACEI vs. ARB). The primary end point was all-cause mortality. The study population had a median follow-up of 2.3 years (interquartile range, 1.3-3.3 years). In the propensity score-matched AMI cohort (8219 pairs), the risk for all-cause mortality was significantly lower in patients with ACEI-based OMT than in those with ARB-based OMT (hazard ratio 0.83 of ACEI, 95% confidence interval 0.73-0.94, P = 0.003). However, in the propensity score-matched angina cohort (6693 pairs), the mortality risk was comparable, regardless of the class of RAS blockade (hazard ratio 1.13, 95 confidence interval 0.99-1.29, P = 0.08). In conclusion, in this nationwide cohort study involving patients receiving OMT after percutaneous coronary intervention, ACEI-based OMT was associated with a significantly lower risk of all-cause mortality in patients with AMI in comparison with ARB, but not in those with angina., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In the course of screening for cosmetic ingredients by measuring antioxidant and antiwrinkle and whitening and anti-inflammatory activities, skin-related activity was tested using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, elastase inhibition, tyrosinase inhibition, and nitric oxide assay. Several Polygonaseae extracts were found to show potent activity. The results showed that the Persicaria senticosa methanolic extract has the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ABTS radical scavenging activities (IC 50 61.0 and 17.5  μ g/mL). In the elastase inhibition assay and nitric oxide assay, the IC 50 of methanolic extract of Persicaria senticosa was 739.7  μ g/mL and 71.8  μ g/mL. The Persicaria senticosa 70% ethanolic extract partitioned with n-hexane, CH 2 Cl 2 , EtOAc, n-BuOH, and aqueous fractions. The purification of EtOAc soluble layer was by column chromatography separation and MPLC analysis of Compounds 1-7 . It was identified as loliolide ( 1 ), quercetin-3-O-glucoside ( 2 ), quercetin-3-O-glucuronide ( 3 ), 4-methoxy caftraric acid ( 4 ), kaempferol-3-(6-methylglucuronide) ( 5 ), quercetin-3-(6-methylglucuronide) ( 6 ), and quercetin ( 7 ). Structure was elucidated by a combination of 1D and 2D NMR and MS spectrometry as well as comparison with reported literatures. Radical scavenging effect on DPPH, tyrosinase inhibition, and nitric oxide assay on several compounds from Persicaria senticosa was found to show potent activity. The results showed that Compound 7 has the NO assay (IC 50 29.7  μ M). For DPPH, the IC 50 of Compounds 2 , 3 , 5 , and 7 was 39.6, 31.2, 37.0, and 22.7  μ M. In tyrosinase inhibitory activity, the IC 50 of Compound 7 was 14.3  μ M., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Yun-Hyeok Choi et al.)

Angiogenesis plays important roles in pathological conditions such as cancer and inflammation as well as normal tissue development and homeostasis. Here, we investigated the effects and molecular mechanisms of α-viniferin, an oligostilbene isolated from Caragana sinica, on human umbilical vein endothelial cell responses in vitro and angiogenic sprouting in aortic rings ex vivo. α-viniferin treatment inhibited mitogen-induced HUVEC proliferation by retinoblastoma protein hypophosphorylation. In addition, α-viniferin suppressed mitogen-induced HUVEC adhesion, migration, invasion, and microvessel outgrowth. These anti-angiogenic activities of α-viniferin might be mediated through downregulation of cell cycle-related proteins, vascular endothelial growth factor receptor-2 (VEGFR-2), and matrix metalloproteinase-2. Furthermore, inactivation of VEGFR-2/p70 ribosomal S6 kinase signaling pathway was found to be involved in α-viniferin-mediated modulation of endothelial cell responses. Our results demonstrate the pharmacological functions and molecular mechanisms of α-viniferin in regulating angiogenesis, suggesting the therapeutic potential of α-viniferin to treat and prevent various angiogenesis-related diseases., (© 2020 John Wiley & Sons, Ltd.)

Background/aims: Although statins are widely used to reduce the risk of cardiovascular disease (CVD) including stroke and myocardial infarction (MI), it is reported that statin use increases the incidence of herpes zoster (HZ) that is associated with increased risk of CVD. So, we evaluated the mediation effect of HZ caused by statin use on CVD., Methods: We analyzed a prospective cohort from the National Health Insurance Service-database of South Korea. All individuals received a medical check-up and were followed-up from 2002 to 2013., Results: A total of 275,382 individuals > 40 years old were followed up for 11 years from 2003. Of these, 11,415 people (4%) were classified as statin users and 263,967 (96%) as non-statin users. Those who used statins had significantly lower risks of cardiovascular events, stroke, and MI compared with non-statin users; the adjusted hazard ratios in the multivariate analysis were 0.90 (95% confidence interval [CI], 0.82 to 0.98), 0.88 (95% CI, 0.80 to 0.98), and 0.91 (95% CI, 0.79 to 1.07), respectively. When we calculated the mediating effect of cardiovascular events by statin use through HZ, 11.6% of the total beneficial effect of cardiovascular events by statin use was mitigated through the occurrence of HZ caused by statin use. This mediating effect was higher in the younger age group (< 60 years)., Conclusion: This study showed that statin use reduced CVD by 10%, but the protective effect of statin use against CVD was mitigated by approximately 10% through the development of HZ caused by statin use.

Background The CHA 2 DS 2 -VASc score has been validated for stroke risk prediction in patients with atrial fibrillation (AF). Antithrombotic therapy is not recommended for low-risk patients with AF (CHA 2 DS 2 -VASc 0 [male] or 1 [female]). We studied a cohort of initially low-risk patients with AF in relation to their development of incident comorbidities and their treatment on oral anticoagulation therapy. Methods and Results We assessed data from 14 441 low-risk patients with AF (CHA 2 DS 2 -VASc score of 0 [male] or 1 [female]) using the Korean National Health Insurance Service database, in relation to their development of incident stroke risk factors and adverse outcomes. The clinical end point was the occurrence of ischemic stroke, major bleeding, all-cause death, or the composite outcome (ischemic stroke + major bleeding + all-cause death). In our cohort, 2615 (29.1%) male and 1650 (30.3%) female patients acquired at least 1 new stroke risk factor during a mean follow-up of 2.0 years. Among the patients with an increasing CHA 2 DS 2 -VASc score ≥1, male and female patients treated with oral anticoagulants had a significantly lower risk of ischemic stroke (male: hazard ratio [HR], 0.62 [95% CI, 0.44-0.82; P =0.003]; female: HR, 0.65 [95% CI, 0.47-0.84; P =0.007]), all-cause death (male: HR, 0.67 [95% CI, 0.49-0.88; P =0.009]; female: HR, 0.82 [95% CI, 0.63-1.02; P =0.185]), and composite outcomes (male: HR, 0.78 [95% CI, 0.61-0.95; P =0.042]; female: HR, 0.79 [95% CI, 0.62-0.96; P =0.045]) than patients not treated with oral anticoagulants. Conclusions Approximately 30% of patients acquired ≥1 stroke risk factor over a 2-year follow-up period. Low-risk patients with AF should be regularly reassessed to adequately identify those with incident stroke risk factors that would merit thromboprophylaxis for the prevention of stroke and the composite outcome.

Background and Objectives: In acute ST-segment elevation myocardial infarction (STEMI), on-site transmission of electrocardiogram (ECG) has been shown to reduce systemic time delay to reperfusion and improve outcomes. However, it has not been adopted in community-based emergency transport system in Korea., Methods: Busan Regional Cardio-cerebrovascular Center and Busan Metropolitan City Fire and Safety Headquarters (BMFSH) jointly developed and conducted a pre-hospital ECG transmission program. Seven tertiary hospitals and 22 safety stations of BMFSH participated. Systemic time delay to reperfusion of STEMI patients in the program was compared with that of 95 patients transported by 119 emergency medical system (EMS) before the program was implemented., Results: During the study period, 289 ECG transmissions were made by 119 EMS personnel, executed within 5 minutes in 88.1% of cases. Of these, 42 ECGs were interpreted as ST-segment elevation. Final diagnosis of STEMI was made in 20 patients who underwent primary percutaneous coronary intervention. With the program, systemic time delay to reperfusion was significantly reduced (median [interquartile range; IQR], 76.0 [62.2-98.7] vs. 90.0 [75.0-112.0], p<0.01). Significant reduction of door-to-balloon time was also observed (median [IQR], 45.0 [34.0-69.5] vs. 58.0 [51.0-68.0], p=0.03). The proportion of patients with systemic time delay shorter than 90 minutes rose (51.6% vs. 75.0%, p=0.08) with pre-hospital ECG transmission., Conclusions: We developed and implemented a community-based pre-hospital ECG transmission program for expeditious triage of STEMI patients. Significant reductions of systemic time delay and door-to-balloon time were observed. The expanded use of pre-hospital ECG transmission should be encouraged to realize the full potential of this program., Competing Interests: The author has no financial conflicts of interest., (Copyright © 2020. The Korean Society of Cardiology.)

Background: It is important to differentiate between primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and ALK-negative systemic ALCL with skin involvement, as the prognoses and treatments for these two diseases are considerably different., Objective: This study aimed to compare the expressions of multiple myeloma oncogene 1 (MUM-1) and B-cell lymphoma 6 (Bcl-6) in PC-ALCL and ALK-negative systemic ALCL., Methods: This retrospective qualitative study investigated the clinical features of 7 patients with ALK-negative PC-ALCL, 5 patients with ALK-negative systemic ALCL with skin involvement, and 6 patients with ALK-positive systemic ALCL with skin involvement. The MUM-1 and Bcl-6 expressions were evaluated using immunohistochemistry., Results: The MUM-1 expression rates were 85.7% in the PC-ALCL cases and 100% in the ALK-negative systemic ALCL with skin involvement cases. The Bcl-6 expression rates were 28.5% in the PC-ALCL cases and 20% in the ALK-negative systemic ALCL cases with skin involvement., Conclusion: Although the cutaneous manifestations of ALK-negative systemic ALCL and PC-ALCL are similar, the prognoses and treatment approaches are considerably different. Our results indicate that MUM-1 expression is commonly expressed in both types of ALCL, but Bcl-6 is less commonly expressed in PC-ALCL cases and systemic ALCL with skin involvement cases., Competing Interests: None., (IJCEP Copyright © 2020.)

We performed this study to characterize the difference between the inflammatory and non-inflammatory status in diseased dogs by measuring salivary C-reactive protein (CRP) levels. In addition, we assessed whether a correlation exists between CRP levels in saliva and those in serum. CRP levels were measured in 32 client-owned dogs, which were then divided into inflammation and non-inflammation groups based on the serum CRP level. The salivary CRP level was higher in the inflammation group than in the non-inflammation group ( p < 0.05). Furthermore, there was a positive correlation between the salivary and serum CRP levels ( R = 0.866, p < 0.001). These data suggest that canine salivary CRP measurements can effectively and non-invasively detect an inflammatory state in dogs.

Background: The inhibitors for renin-angiotensin-aldosterone system (RAAS) have different mechanisms of action in coronary artery disease (CAD). This study sought to compare the clinical outcomes between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) therapy in patients with CAD undergoing contemporary percutaneous coronary intervention (PCI)., Methods: Based on the National Health Insurance claims data in South Korea, patients aged 18 years or older who had undergone PCI between July 2011 and June 2015 were enrolled. The study participants were classified either as patients with acute myocardial infarction (AMI, n = 21,747) or angina (n = 28,708). And according to the post PCI discharge medications, patients were categorized into ACEI and ARB therapy groups. The primary endpoint was all-cause death, and the two groups were compared using a propensity-score matching analysis., Results: The study population had a median follow-up of 2.2 years (interquartile range, 1.2-3.2). In the propensity-score matched AMI group (8341 pairs), the occurrence of all-cause death was significantly lower in the ACEI group than in the ARB group (hazard ratio [HR] of ACEI, 0.823; 95% confidence interval [CI]: 0.715-0.947; p = 0.006). In the propensity-score matched angina group (10,878 pairs), there was no difference in the incidence of the primary endpoint between the ACEI and ARB groups (HR of ACEI, 1.113; 95% CI: 0.986-1.257; p = 0.084)., Conclusions: In this nationwide Korean cohort study, ACEI therapy in patients with AMI and concomitant PCI showed a significant reduction in all-cause mortality rates when compared to that with ARB therapy., Competing Interests: Declaration of competing interest Dr. Martin Strauss has received speaking honorarium from Servier., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: The relationship between high-density lipoprotein cholesterol and the severity of coronary artery disease beyond low-density lipoprotein cholesterol, the primary target of cholesterol-lowering therapy, remains uncertain. We evaluated the association between high-density lipoprotein cholesterol and obstructive coronary artery disease using parameters of any obstructive plaque, obstructive plaque in the left main coronary artery or proximal left anterior descending artery, and obstructive plaque in multi-vessels, according to low-density lipoprotein cholesterol levels., Methods and Results: We analyzed 5130 asymptomatic non-diabetics who underwent coronary computed tomography angiography for general health examination. Obstructive plaque was defined as a plaque with ≥50% luminal diameter stenosis. The participants were divided into three groups based on low-density lipoprotein cholesterol levels of ≤129, 130-159, and ≥160 mg/dl. The prevalence of any obstructive plaque (5.9% vs 6.4% vs 10.6%) and obstructive plaque in the left main coronary artery or proximal left anterior descending artery (2.1% vs 2.1% vs 4.3%) significantly increased with low-density lipoprotein cholesterol category (all p  < 0.05). Compared with subjects with high-density lipoprotein cholesterol level ≥40 mg/dl, those with high-density lipoprotein cholesterol level <40 mg/dl had a significantly higher prevalence of any obstructive plaque (10.4% vs 5.1%), obstructive plaque in the left main coronary artery or proximal left anterior descending artery (3.6% vs 1.8%), and obstructive plaque in multi-vessels (4.3% vs 1.1%), only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p  < 0.05). Multiple regression analysis showed that increased high-density lipoprotein cholesterol levels were associated with a reduced risk of all obstructive coronary artery disease parameters only in the group with low-density lipoprotein cholesterol level ≤129 mg/dl (all p  < 0.05)., Conclusion: Increased high-density lipoprotein cholesterol levels were independently associated with a lower risk of obstructive coronary artery disease in asymptomatic non-diabetics with low low-density lipoprotein cholesterol levels.

Atopic dermatitis (AD) is a chronic inflammatory disease. Combretum quadrangulare ( C. quadrangulare ) is used as a traditional medicine to improve various pathologies in Southeast Asia. In this study, we investigated the effects of C. quadrangulare ethanol extract (CQ) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD like skin lesions in BALB/c mice. After administration with CQ (100, 200, and 400 mg/kg) for 6 weeks, AD symptoms, protein expression, immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and ceramidase level were measured in skin lesions of DNCB-induced BALB/c mice. CQ group improved the dermatitis score, skin pH, transepidermal water loss (TEWL), and skin hydration. Furthermore, histological analysis revealed that CQ attenuated the increased epidermal thickness and infiltration of mast cells caused by DNCB. CQ also increased the expression of filaggrin, and reduced the expression of ceramidase, serum IgE level, and the number of eosinophils. CQ effectively inhibited cytokines and chemokines such as interleukin (IL)-6, IL-13, TARC, and thymic stromal lymphopoietin (TSLP) at the mRNA levels, as well as the activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in the skin lesions. Taken together, these findings demonstrate that CQ may be an effective treatment of AD-like skin lesions by inhibiting the expression of inflammatory mediators via the MAPK signaling pathways.

Background: The CYP2C19*2 or *3 loss-of-function (LOF) allele is associated with high platelet reactivity (HPR) on clopidogrel treatment. East Asians may benefit from a lower dose of prasugrel due to their more potent platelet inhibitory response. The impact of LOF alleles on the pharmacodynamic response to half-dose prasugrel in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) is unknown., Methods: Seventy patients with the LOF alleles were assigned to half-dose prasugrel (n = 35, 30-mg load followed by 5 mg daily) or clopidogrel (n = 35, 600-mg load followed by 75 mg daily). The primary endpoint was the rate of HPR, defined as VerifyNow-P2Y12 reaction unit (PRU) >235, at 24 h post loading., Results: Prasugrel achieved a lower PRU compared to clopidogrel after loading (119 [56-175] vs. 245 [189-299]), at 24 h (34 [8-58] vs. 196 [122-244]), and at 30 days (134 [98-189] vs. 203 [144-248]). Prasugrel had a lower rate of HPR after loading (5.7% vs. 57.1%, p <0.001), at 24 h (2.9% vs. 28.6%, p=0.006), and at 30 days (11.4% vs. 34.3%, p=0.004). Prasugrel had a similar rate of optimal platelet reactivity at 30 days (71.4% vs. 60.0%, p=0.450). There was no significant difference in the occurrence of periprocedural myonecrosis within 48 h after PCI with clopidogrel and prasugrel (22.9% vs. 17.1%, p>0.960)., Conclusions: Half-dose prasugrel provided potent platelet inhibition in NSTE-ACS patients that were carriers of the CYP2C19*2 or *3 allele, with a lower rate of HPR. Periprocedural myonecrosis was not significantly different in the 2 groups., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Homocysteine has been known as a risk factor for cardiovascular disease. This study sought to evaluate the influence of homocysteine on the risk of subclinical coronary atherosclerosis in asymptomatic individuals., Methods: We reviewed 3,186 asymptomatic individuals (mean age 53.8 ± 8.0 years, 2,202 men [69.1%]) with no prior history of coronary artery disease who voluntarily underwent coronary computed tomographic angiography (CCTA) and laboratory tests as part of a general health examination. The subjects were stratified into tertiles according to their homocysteine levels. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA. Logistic regression analysis was used to determine the association between homocysteine levels and subclinical coronary atherosclerosis., Results: The prevalence of significant coronary artery stenosis, any atherosclerotic, calcified, mixed, and non-calcified plaques increased with homocysteine tertiles (all p < 0.05). However, after adjustment for cardiovascular risk factors, there were no statistically significant differences in the adjusted odds ratios (ORs) for any atherosclerotic plaque (OR 1.06; 95% CI [confidence interval] 0.85-1.32; p = 0.610), calcified plaques (OR 1.17; 95% CI 0.92-1.48; p = 0.199), non-calcified plaques (OR 0.80; 95% CI 0.61-1.04; p = 0.089), and mixed plaques (OR 1.42; 95% CI 0.96-2.11; p = 0.077) between the third and first homocysteine tertiles. In addition, the adjusted OR for significant coronary artery stenosis (OR 0.92; 95% CI 0.63-1.36; p = 0.687) did not differ between the first and third tertiles., Conclusions: In asymptomatic individuals, homocysteine is not associated with an increased risk of subclinical coronary atherosclerosis., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The present study is a descriptive survey conducted to identify factors influencing supportive care needs of patients with multiple myeloma treated with chemotherapy., Methods: A structured questionnaire was provided to 141 patients with multiple myeloma who were treated as inpatients or outpatients at Seoul St. Mary's Hospital of the Catholic University of Korea. Data were analyzed with t test, ANOVA, Scheffe's test, correlational analysis, and linear regression analysis using SPSS version 21.0., Results: The mean score of supportive care needs of patients with multiple myeloma was 1.51 out of 4 points. Of supportive care needs, information on future disease outcome scored the highest, with a mean score of 2.12, followed by easy and candid explanation by health care staff (2.11), and information on foods that are healthy for cancer patients (2.02). The mean score of disease-related knowledge was 0.52 of 1 point, and diagnostic test results scored the lowest among the subdomains of disease-related knowledge. The mean score of emotional state was 1.13 out of 3 points, mean anxiety score was 1.01 out of 3 points, and mean depression score was 1.26 out of 3 points. Anxiety and depression were identified as factors influencing supportive care needs of patients with multiple myeloma., Conclusions: The present study demonstrated that the supportive care needs of patients with multiple myeloma are associated with their emotional state. The supportive care needs of patients with multiple myeloma should be identified at an individual level, and should be addressed to reduce anxiety and depression.

Objective: We compared the long-term outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease in a real-world population., Background: CABG is the standard of care for ULMCA disease. Contemporary randomized trials have reported conflicting results with the two revascularization strategies for the treatment of ULMCA disease at intermediate-term follow-up., Methods: We evaluated 422 consecutive patients with ULMCA disease who underwent CABG (n = 273) or PCI (n = 149) from 1998-2008. The primary outcome measure was major adverse cardiac and cerebrovascular event (MACCE) rate, defined as the composite of all-cause death, myocardial infarction (MI), stroke, or target-vessel revascularization (TVR) at 10 years. Propensity-score matched (PSM) analysis was used to assess long-term MACCE., Results: The cumulative 10-year incidence of risk for MACCE was not significantly different between the PCI and CABG groups (24.8% vs 20.5%, respectively; log rank P=.22; log rank PSM P=.45). The risk for all-cause death was not significantly different between the two groups (log rank P=.09; PSM log rank P=.51). The risk for stroke was significantly lower with PCI (log rank P=.02), but was not significant after matching (PSM log rank P=.27). The risk for TVR was significantly higher with PCI vs CABG prior to and after matching (log rank P<.001; log rank PSM P=.01). There were no significant differences in MACCE between the two groups when stratified by SYNTAX scores ≤22% (log rank P=.61) and >23% (log rank P=.06)., Conclusion: In patients with ULMCA disease, PCI was comparable with CABG for long-term MACCE and death rates. The TVR rate was higher in the PCI group.

Background: The term triple-negative breast cancer (TNBC) is used to describe breast cancers without expression of estrogen receptor, progesterone receptor or HER2 amplification. To advance targeted treatment options for TNBC, it is critical that the subtypes within this classification be described in regard to their characteristic biology and gene expression. The Cancer Genome Atlas (TCGA) dataset provides not only clinical and mRNA expression data but also expression data for microRNAs., Results: In this study, we applied the Lehmann classifier to TCGA-derived TNBC cases which also contained microRNA expression data and derived subtype-specific microRNA expression patterns. Subsequent analyses integrated known and predicted microRNA-mRNA regulatory nodes as well as patient survival data to identify key networks. Notably, basal-like 1 (BL1) TNBCs were distinguished from basal-like 2 TNBCs through up-regulation of members of the miR-17-92 cluster of microRNAs and suppression of several known miR-17-92 targets including inositol polyphosphate 4-phosphatase type II, INPP4B., Conclusions: These data demonstrate TNBC subtype-specific microRNA and target mRNA expression which may be applied to future biomarker and therapeutic development studies.

In this study, we investigated the effects and molecular mechanisms of 2-phenylbenzimidazole-5-sulphonic acid (PBSA), an ultraviolet B protecting agent used in sunscreen lotions and moisturizers, on ovarian cancer cell responses and tumour angiogenesis. PBSA treatment markedly blocked mitogen-induced invasion through down-regulation of matrix metalloproteinase (MMP) expression and activity in ovarian cancer SKOV-3 cells. In addition, PBSA inhibited mitogen-induced cell proliferation by suppression of cyclin-dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G 1 phase cell cycle arrest. These anti-cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen-activated protein kinase kinase 3/6-p38 mitogen-activated protein kinase (MKK3/6-p38 MAPK ) activity and subsequent down-regulation of MMP-2, MMP-9, Cdk4, Cdk2 and integrin β1, as evidenced by treatment with p38 MAPK inhibitor SB203580. Furthermore, PBSA suppressed the expression and secretion of vascular endothelial growth factor in SKOV-3 cells, leading to inhibition of capillary-like tubular structures in vitro and angiogenic sprouting ex vivo. Taken together, our results demonstrate the pharmacological effects and molecular targets of PBSA on modulating ovarian cancer cell responses and tumour angiogenesis, and suggest further evaluation and development of PBSA as a promising chemotherapeutic agent for the treatment of ovarian cancer., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Introduction: Uwhangchungsimwon (UCW) is one of the most representative standardized herbal drugs for the treatment of central nervous system diseases, including mood disorders, and has been used for over 600 years in Korea and China. In spite of the long clinical application of UCW, no experimental evidence for its use against depressive disorders exists. Here, we performed an animal study to investigate the anti-depressive effect of UCW and the underlying mechanisms., Methods: A social isolation-induced depressive-like model was produced using C57BL/6J male mice by housing the mice individually for 31 days, and the mice underwent daily oral administration of distilled water, UCW (100, 200, 400 mg/kg) or fluoxetine (20 mg/kg) during the final 17 days. A tail suspension test (TST), forced swimming test (FST), and open field test (OFT) were used to explore the effects of UCW on depressive-like behaviors. 5-Hydroxytryptamine (5-HT) was measured in the dorsal raphe nuclei (DRN) using immunofluorescence. The serum corticosterone level was measured with its receptor and catecholamine, along with cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus., Results: Social isolation stress effectively induced depressive-like behaviors, and UCW treatment significantly improved the symptoms of depressive-like behavior in the FST, TST, and OFT. The isolation stress-induced depletion of 5-HT was significantly ameliorated by UCW treatment. UCW also attenuated the activation of the glucocorticoid receptor (GR) and the elevated serum corticosterone level, as well as the hippocampal levels of dopamine and norepinephrine. Dexametasone-derived translocation of GR was inhibited by UCW treatment in PC12 cells and HT22 cells. In addition, alterations of tryptophan hydroxylase 2 (TPH2), BDNF, and CREB in the protein analyses were notably regulated by UCW treatment., Conclusions: These results provide animal-based evidence for the anti-depressive effect of UCW, and its underlying mechanisms may involve regulating the serotonergic system, the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophin., (Copyright © 2020 Oh, Lee, Kim, Oh, Kim, Lee, Cho, Jeon, Cho and Son.)

Correction for 'One-step synthesis and electrochemical performance of a PbMoO4/CdMoO4 composite as an electrode material for high-performance supercapacitor applications' by Tarugu Anitha et al., Dalton Trans., 2019, 48, 10652-10660.

Background: Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs)., Methods: This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m 2 ; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles., Results: The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex., Conclusions: TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

Background: Cross-species analysis of protein-protein interaction (PPI) networks provides an effective means of detecting conserved interaction patterns. Identifying such conserved substructures between PPI networks of different species increases our understanding of the principles deriving evolution of cellular organizations and their functions in a system level. In recent years, network alignment techniques have been applied to genome-scale PPI networks to predict evolutionary conserved modules. Although a wide variety of network alignment algorithms have been introduced, developing a scalable local network alignment algorithm with high accuracy is still challenging., Results: We present a novel pairwise local network alignment algorithm, called LePrimAlign, to predict conserved modules between PPI networks of three different species. The proposed algorithm exploits the results of a pairwise global alignment algorithm with many-to-many node mapping. It also applies the concept of graph entropy to detect initial cluster pairs from two networks. Finally, the initial clusters are expanded to increase the local alignment score that is formulated by a combination of intra-network and inter-network scores. The performance comparison with state-of-the-art approaches demonstrates that the proposed algorithm outperforms in terms of accuracy of identified protein complexes and quality of alignments., Conclusion: The proposed method produces local network alignment of higher accuracy in predicting conserved modules even with large biological networks at a reduced computational cost.

Branched-chain amino acid (BCAA) catabolism and high levels of enzymes in the BCAA metabolic pathway have recently been shown to be associated with cancer growth and survival. However, the precise roles of BCAA metabolism in cancer growth and survival remain largely unclear. Here, we found that BCAA metabolism has an important role in human pancreatic ductal adenocarcinoma (PDAC) growth by regulating lipogenesis. Compared with nontransformed human pancreatic ductal (HPDE) cells, PDAC cells exhibited significantly elevated BCAA uptake through solute carrier transporters, which were highly upregulated in pancreatic tumor tissues compared with normal tissues. Branched-chain amino-acid transaminase 2 (BCAT2) knockdown markedly impaired PDAC cell proliferation, but not HPDE cell proliferation, without significant alterations in glutamate or reactive oxygen species levels. Furthermore, PDAC cell proliferation, but not HPDE cell proliferation, was substantially inhibited upon knockdown of branched-chain α-keto acid dehydrogenase a (BCKDHA). Interestingly, BCKDHA knockdown had no significant effect on mitochondrial metabolism; that is, neither the level of tricarboxylic acid cycle intermediates nor the oxygen consumption rate was affected. However, BCKDHA knockdown significantly inhibited fatty-acid synthesis, indicating that PDAC cells may utilize BCAAs as a carbon source for fatty-acid biosynthesis. Overall, our findings show that the BCAA metabolic pathway may provide a novel therapeutic target for pancreatic cancer.

The templated self-assembly of block copolymers (BCPs) with a high Flory-Huggins interaction parameter (χ) can effectively create ultrafine, well-ordered nanostructures in the range of 5-30 nm. However, the self-assembled BCP patterns remain limited to possible morphological geometries and materials. Here, we introduce a novel and useful self-assembly method of di-BCP blends capable of generating diverse hybrid nanostructures consisting of oxide and metal materials through the rapid microphase separation of A-B/B-C BCP blends. We successfully obtained various hybridized BCP morphologies which cannot be acquired from a single di-BCP, such as hexagonally arranged hybrid dot and dot-in-hole patterns by controlling the mixing ratios of the solvents with a binary solvent annealing process. Furthermore, we demonstrate how the binary solvent vapor annealing process can provide a wide range of pattern geometries to di-BCP blends, showing a well-defined spontaneous one-to-one accommodation in dot-in-hole nanostructures. Specifically, we show clearly how the self-assembled BCPs can be functionalized via selective reduction and/or an oxidation process, resulting in the excellent positioning of confined silica nanodots into each nanospace of a Pt mesh. These results suggest a new method to achieve the pattern formation of more diverse and complex hybrid nanostructures using various blended BCPs.

Background: Ticagrelor reduced the rate of myocardial infarction and death compared with clopidogrel in patients with acute coronary syndrome. However, little is understood about chronic treatment of ticagrelor on microvascular dysfunction. The objective of this study was to assess the impact of ticagrelor maintenance treatment on microvascular system and coronary flow in comparison with clopidogrel., Methods: This study was a nonblinded, open-label, parallel-group, prospective, randomized controlled trial that enrolled 120 patients with acute coronary syndrome requiring stent implantation. Patients were randomized into the ticagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 to 600 mg loading dose, 75 mg daily thereafter) group. The primary end point was coronary microvascular dysfunction as measured by an index of microcirculatory resistance (IMR) at 6 months after treatment., Results: The baseline clinical characteristics and physiological parameters, such as fractional flow reserve, coronary flow reserve, and IMR, did not differ between the ticagrelor and clopidogrel groups. Six-month follow-up physiological data showed that the IMR value was significantly lower in the ticagrelor group than the clopidogrel group (15.57±5.65 versus 21.15±8.39, P <0.01), and coronary flow reserve was higher in the ticagrelor group than in the clopidogrel group (3.85±0.72 versus 3.37±0.76, P <0.01). However, there was no difference in fractional flow reserve (0.87±0.08 versus 0.87±0.09, P =0.94) between the 2 groups. The improvement in IMR after 6 months of treatment was higher in the ticagrelor group ( P <0.01). Analyses of 223 nonculprit vessels of registered patients based on physiological results showed no differences in baseline fractional flow reserve (0.93±0.13 versus 0.92±0.09, P =0.58), coronary flow reserve (3.62±1.27 versus 3.51±1.24, P =0.16), or IMR (21.37±12.37 versus 24.19±21.08, P =0.22) or in follow-up fractional flow reserve (0.91±0.09 versus 0.91±0.08, P =0.67), coronary flow reserve (3.91±1.22 versus 3.75±1.16, P =0.36), or IMR (19.43±10.32 versus 21.52±18.90, P =0.34) between the 2 groups., Conclusions: Compared with clopidogrel, 6 months of ticagrelor therapy significantly improved microvascular dysfunction in acute coronary syndrome patients with stent implantation., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02618733.

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients.

Homogeneously ultrathin nanocubes of PbMoO4/CdMoO4 nanocomposites, which are useful for energy storage applications, were prepared on nickel foam using a one-step chemical bath deposition method. The capacitive performance of the synthesized PbMoO4/CdMoO4 electrode material was examined by cyclic voltammetry, galvanostatic charge/discharge, and electrochemical impedance spectroscopy in a three-electrode configuration. This unique structure can provide more electroactive sites and a larger surface area, which can enhance the electrochemical performance. The PbMoO4/CdMoO4 redox-active material achieved a high specific capacitance of 1840.32 F g-1 at a current density of 1 A g-1 in a 3 M KOH solution. This electrode exhibited excellent long cycle life stability with ∼81.4% specific capacitance retention after 5000 cycles at a current density of 4 A g-1, which is superior to that of individual PbMoO4 and CdMoO4 nanosheets. The prepared PbMoO4/CdMoO4 composite electrode displayed excellent electrocapacitive properties, which can be attributed to the synergetic effects of PbMoO4 and CdMoO4. These results suggest that the PbMoO4/CdMoO4 nanocube arrays have the potential to meet the requirements of practical electrochemical energy storage applications.

Ethnopharmacological Relevance: Banha-sasim-tang (BST; Hange-shashin-to in Kampo medicine; Banxia xiexin tang in traditional Chinese medicine) is a traditional Chinese harbal medicine that has been commonly used for gastrointestinal disorders., Aim of the Study: To investigate the pharmacological effects of BST, a standardized herbal drug, on main symptoms of functional dyspepsia including delayed gastric emptying, and underlying mechanisms of action in mouse model., Methods and Materials: Balb/C mice were pretreated with BST (25, 50, 100 mg/kg, po) or mosapride (3 mg/kg, po) for 3 days, and then treated with loperamide (10 mg/kg, ip) after 19 h fasting. A solution of 0.05% phenol red (500 μL) or 5% charcoal diet (200 μL) was orally administered, followed by scarifying and assessment of gastric emptying or gastro-intestinal motility. C-kit (immunofluorescence), nNOS (western blot) and gastric contraction-related gene expression were examined in stomach tissue., Results: The loperamide injection substantially delayed gastric emptying, while the BST pretreatment significantly attenuated this peristaltic dysfunction, as evidenced by the quantity of stomach-retained phenol red (p < 0.05 or 0.01) and stomach weight (p < 0.05 or 0.01). The BST pretreatment significantly tempered the loperamide-induced inactivation of c-kit and nNOS (p < 0.05 or 0.01) as well as the contraction-related gene expression, such as the 5HT 4 receptor (5HT 4 R), anoctamin-1 (ANO1), ryanodine receptor 3 (RYR3) and smooth muscle myosin light chain kinase (smMLCK). The BST pretreatment also significantly attenuated the alterations in gastro-intestinal motility (p < 0.01)., Conclusion: Our results are the first evidence of the prokinetic agent effects of Banha-sasim-tang in a loperamide-induced FD animal model. The underlying mechanisms of action may involve the modulation of peristalsis via activation of the interstitial cells of Cajal and the smooth muscle cells in the stomach., (Copyright © 2019. Published by Elsevier B.V.)

Background: It is unclear whether asymmetry itself plays a role in developing eccentric aortic regurgitation (AR) in patients with tricuspid aortic valve (TAV). The aim of this study was to determine whether an asymmetric aortic valve structure may have association with the development of eccentric AR in patients with TAV., Methods: Of the 164 410 patients who underwent echocardiography between January 2006 and January 2018 at Dong-A University Hospital, 306 (mean age 69.9 ± 12.6 years; 62% men) eccentric AR were identified. After excluding patients with bicuspid and prolapsed AV, 104 patients who had eccentric AR with TAV were enrolled for the study. Comprehensive echocardiographic AV cusp measurements were compared to those of 104 age- and gender-matched control patients with central AR., Results: In the eccentric and central AR groups, 66 (63.5%) and 48 patients (46.2%) had asymmetric AV, respectively. Mean cusp height was significantly larger in the eccentric AR group than in the central AR group (1.8 ± 0.3 cm vs 1.7 ± 0.2 cm, P = 0002). Furthermore, the mean cusp area and average asymmetry index of the cusp area were also significantly larger in the eccentric AR group than in the central AR group (2.6 ± 0.8 cm 2 vs 2.3 ± 0.6 cm 2 , P = 0.001, and 7.1 ± 4.5% vs 4.9 ± 2.5%, P < 0.001, respectively)., Conclusion: AV asymmetry indices of eccentric AR were significantly larger than those of patients with central AR. These data suggest that the presence of asymmetric AV might have association with the development of eccentric AR in patients with TAV., (© 2019 Wiley Periodicals, Inc.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

The American College of Cardiology/American Heart Association (ACC/AHA) recently published a Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. However, the data in other ethnic groups are not well known. We evaluated the prevalence and associated cardiovascular prognosis of Korean subjects with newly reclassified hypertension based on the 2017ACC/AHA guideline. We analyzed data from the Korean Health and Genome Study (n = 10,038). Supine blood pressure (BP) was measured thrice following a standardized protocol and averaged. There was a significant linear relation between BP profiles and cardiovascular disease (CVD)/mortality. Hazard ratio for CVD increased above a systolic BP of 120mm Hg. Systolic BP ≥130mm Hg was significantly associated with increased risk of CVD, coronary heart disease, stroke, CVD death, and total deaths. There was a similar significant linear relation with diastolic BP categories between CVD risk and death. BP is associated with an increased risk of CVD or all-cause mortalities. Moreover, the new BP categories of the 2017ACC/AHA guideline could be applicable for predicting CVD and death in Korean population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Perovskite solar cells (PSCs) fabricated on transparent polymer substrates are considered a promising candidate as flexible solar cells that can emulate the advantages of organic solar cells, which exhibit considerable freedom in their device design thanks to their light weight and mechanically flexibility while achieving high photocurrent conversion efficiency, comparable to that of their conventional counterparts fabricated on rigid glasses. However, the full realization of highly efficient, flexible PSCs is largely prevented by technical difficulties in simultaneously attaining a transparent electrode with efficient charge transport to meet the specifications of PSCs. In this study, an effective strategy for resolving this technical issue has been devised by proposing a simple but highly effective technique to fabricate an efficient, multilayer TiO 2 /Ag (O) /ZnO (TAOZ) configuration. This configuration displays low losses in optical transmittance and electrical conductivity owing to its completely continuous, ultrathin metallic Ag (O) transparent electrode, and any notable current leakage is suppressed by its pinhole-free TiO 2 electron transport layer. These features are a direct consequence of the rapid evolution of Ag (O) and TiO 2 into ultrathin, completely continuous, pinhole-free layers owing to the dramatically improved wetting of metallic Ag (O) with a minimal dose of oxygen ( ca. 3 at%) during sputtering. The TAOZ configuration exhibits an average transmittance of 88.5% in the spectral range of 400-800 nm and a sheet resistance of 8.4 Ω sq -1 while demonstrating superior mechanical flexibility to that of the conventional TiO 2 on ITO configuration. The photocurrent conversion efficiency of flexible PSCs is significantly improved by up to 11.2% thanks to an optimum combination of optoelectrical performance and pinhole-free morphologies in the TAOZ configuration., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Aortic dilatation is a major risk factor for aortic dissection. The aim of the present study was to assess the relationship between left ventricular (LV) geometry and maximal ascending aorta (MAA)., Methods: We reviewed data from patients who were diagnosed with acute type A aortic dissection and who underwent surgical management from December 2002 to March 2016 at Dong-A University Hospital. Among 151 patients with non-Marfan aortic dissection in the study, 50 who had echocardiography preoperatively were investigated and MAA diameter was analyzed by LV geometric patterns., Results: Patients' mean age was 59.6 ± 13.5 years and 38.0% were male. The mean MAA diameter was 52.9 ± 8.5 mm. MAA diameter was significantly correlated with LV mass index (r = 0.62, P < 0.001). On analysis by LV geometry, MAA diameter showed a significant difference between the 4 groups (P = 0.02), and the eccentric and concentric hypertrophy groups showed significantly larger MAA diameter than the other two groups., Conclusion: MAA diameter was associated with LV mass index and was significantly different between LV geometry types. In this study, not only concentric hypertrophy but also eccentric LV hypertrophy was related to larger MAA in type A aortic dissection patients.

Objectives: It is unclear whether high-intensity statin therapy provides incremental clinical benefits over moderate-intensity statin therapy in Asian patients with angina. This study sought to compare the clinical outcomes of moderate- and high-intensity statin therapies in patients undergoing percutaneous coronary intervention (PCI) for angina in Korean patients., Methods: Based on the national health insurance claims data in South Korea, patients aged 18 years or older without a known history of coronary artery disease, who underwent PCI with drug-eluting stents due to angina between 2011 and 2015, were enrolled. According to the intensity of statin therapy, patients were categorized into moderate-intensity statin therapy (n = 23,863) and high-intensity statin therapy (n = 9,073) groups. The primary endpoint, defined as a composite of all-cause death and myocardial infarction, was compared between the two groups using a propensity-score matching analysis., Results: During the follow-up period (median, 2.0 years; interquartile range, 1.1-3.1), 1,572 patients had 1,367 deaths and 242 myocardial infarctions. After propensity-score matching, there were 8,939 matched pairs. There was no significant difference in the incidence of the primary endpoint between the two groups (adjusted hazard ratio of high-intensity statin therapy, 1.093; 95% confidence interval: 0.950-1.259; p = 0.212)., Conclusions: In Korean patients undergoing PCI with drug-eluting stents for angina, the high-intensity statin therapy did not provide additional clinical benefits over the moderate-intensity statin therapy., Competing Interests: The authors have declared that no competing interests exist.

Background: Dual antiplatelet therapy (DAPT) helps prevent ischemic events after coronary stenting but comes with an increased risk of bleeding. Several risk scores have been proposed for the management of patients receiving DAPT, but no standardized tool exists for the purpose. We sought to compare the performance of the new PRECISE-DAPT (Predicting Bleeding Complication in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines), and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) scores for the prediction of bleeding in Korean patients receiving DAPT., Methods and Results: Nine hundred and four consecutive patients who underwent stent implantation received DAPT. One-year bleedings were assessed using TIMI (Thrombolysis in Myocardial Infarction), GUSTO (Global Use of Strategies to Open Occluded Arteries), and BARC (Bleeding Academic Research Consortium). Bleeding events occurred in 154 patients (17.0%) by BARC type ≥3a criteria, 119 patients (13.2%) by the TIMI minor or major criteria, and 80 patients (8.8%) by the GUSTO moderate or severe criteria. In the C statistic analysis, CRUSADE, ACUITY, and PRECISE-DAPT scores showed high area under the curve values for 1-year bleeding (area under the curve 0.73, 0.75, and 0.75 for TIMI minor or major bleeding; area under the curve 0.81, 0.79, and 0.82 for GUSTO moderate to severe; and area under the curve 0.79, 0.81, and 0.81 for BARC type ≥3a, respectively). The discriminate ability of PRECISE-DAPT was similar to CRUSADE and ACUITY in bleeding complications. However, the PRECISE-DAPT score was better at reclassifying the risk of 1-year bleeding compared with ACUITY for the 3 bleeding criteria., Conclusions: The PRECISE-DAPT score is a simple 5-item risk score that represents a standardized tool for the prediction of 1-year bleeding in Korean patients receiving DAPT, regardless of bleeding definition.

Kummerowia striata ( K. striata ) is used as a traditional medicine for inflammation-related therapy. To determine whether it has beneficial anti-melanogenic and anti-oxidant activities, we investigated the biological activities of the ethanol extract of Kummerowia striata (EKS) using a variety of in vitro and cell culture model systems. The anti-melanogenic activity was assessed in B16F10 melanoma cells in terms of melanin synthesis and in vitro tyrosinase inhibitory activity. The anti-oxidant assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS). EKS showed strong anti-oxidant activities in DPPH and ABTS assays. The mRNA transcription levels and protein expression levels of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor decreased in a dose-dependent manner with EKS treatment. Additionally, EKS did not affect cell viability at different concentrations used in this study, indicating that the mechanism of action of EKS-mediated inhibition of melanin synthesis does not involve cytotoxicity. Also, we confirmed that p-coumaric acid and quercetin are important compounds for anti-melanogenesis and antioxidant properties of EKS. Collectively, our findings demonstrate for the first time that EKS possesses anti-melanogenic and anti-oxidant activities. Further evaluation and development of EKS as a functional supplement or cosmetic may be useful for skin whitening and reducing wrinkles.

Aims: The early diastolic mitral annular velocity (e') and mitral E/e' criteria for clinically evaluating diastolic dysfunction in patients with atrial fibrillation (AF) are almost the same as in patients with sinus rhythm. In this study, we aimed to investigate whether e' is useful to assess diastolic function in AF patients., Methods: Thirty patients who underwent successful electric cardioversion (EC) due to persistent AF and who maintained sinus rhythm for 1 month after EC were enrolled in this study. Transthoracic echocardiography was performed on all patients before and 1 month after EC. Standard diastolic parameters, the global longitudinal strain (GLS), and left ventricular (LV) twist were measured., Results: Conventional Doppler parameters measured before EC were not significantly different from 1 month after EC. However, the lateral and septal e' were significantly decreased 1 month after EC (from 12.8 ± 2.5 to 9.8 ± 2.3 cm/s and from 9.5 ± 1.9 to 7.1 ± 1.5 cm/s, respectively, P < 0.001). Likewise, the lateral and septal E/e' were also significantly increased 1 month after EC (P < 0.001). The GLS was significantly improved from -15.9 ± 2.2% to -19.4 ± 2.4% after EC (P < 0.001), as was the LV twist (from 5.8 ± 1.7° to 9.1 ± 2.4°, P < 0.001)., Conclusion: We demonstrated that e' was significantly higher in AF compared with during sinus rhythm in the same patients. Thus, in AF patients, diastolic dysfunction should be suspected even when e' values are normal., (© 2018 Wiley Periodicals, Inc.)

Motivation: Cross-species analysis of large-scale protein-protein interaction (PPI) networks has played a significant role in understanding the principles deriving evolution of cellular organizations and functions. Recently, network alignment algorithms have been proposed to predict conserved interactions and functions of proteins. These approaches are based on the notion that orthologous proteins across species are sequentially similar and that topology of PPIs between orthologs is often conserved. However, high accuracy and scalability of network alignment are still a challenge., Results: We propose a novel pairwise global network alignment algorithm, called PrimAlign, which is modeled as a Markov chain and iteratively transited until convergence. The proposed algorithm also incorporates the principles of PageRank. This approach is evaluated on tasks with human, yeast and fruit fly PPI networks. The experimental results demonstrate that PrimAlign outperforms several prevalent methods with statistically significant differences in multiple evaluation measures. PrimAlign, which is multi-platform, achieves superior performance in runtime with its linear asymptotic time complexity. Further evaluation is done with synthetic networks and results suggest that popular topological measures do not reflect real precision of alignments., Availability and Implementation: The source code is available at http://web.ecs.baylor.edu/faculty/cho/PrimAlign., Supplementary Information: Supplementary data are available at Bioinformatics online.

Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level. We also found that either pyruvate or α-ketoglutarate supplementation markedly rescues pancreatic cancer cell growth following matrine treatment. Inhibition of mitochondrial energy production results from matrine-mediated autophagy inhibition by impairing the function of lysosomal protease. Matrine-mediated autophagy inhibition requires stat3 downregulation. Furthermore, we found that the antitumor effect of matrine on pancreatic cancer growth depends on the mutation of the KRAS oncogene. Together, our data suggest that matrine can suppress the growth of KRAS-mutant pancreatic cancer by inhibiting autophagy-mediated energy metabolism., (© 2018 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: Mood disorders, depression, and loneliness are established risk factors for thrombotic occlusions. Social relationships in general, and marital status in particular may play a role in predicting cardiovascular outcomes and survival after ST-segment elevation myocardial infarction (STEMI), but the evidence is inconclusive especially in Asians., Methods: The Korean patients presented with STEMI (n=980) constituted married (n=780); or widowed, divorced, or single (WDS, n=200) groups. After the matching for age, and gender, the groups were matched 1:1, with each group containing 172 patients. Clinical characteristics and STEMI prognosis such as major adverse cardiovascular events (MACE) and death at 1year, in married versus WDS patients were collected, and retrospectively analyzed., Results: Overall, the total of 70 non-fatal MACE and 51 deaths occurred. At 1-year, the WDS patients exhibited significantly more MACE (44 vs.26; p=0.016), deaths (32 vs. 19; p=0.049) and shorter time to MACE occurrence (p=0.018), compared to the married patients. There were no differences in revascularization, cerebral infarction, cerebral bleeding, major bleeding, coronary artery bypass graft, early mortality and the overall survival between groups., Conclusion: Marital status may be linked to 1-year MACE including survival following STEMI, while being married may improve vascular outcomes compared to WDS in Korean patients. Further larger cohort or/and uniformed national registry studies are required to validate these data, and expand the evidence beyond East Asians., (Copyright © 2017 Elsevier Inc. All rights reserved.)

[This corrects the article on p. 612 in vol. 60, PMID: 29184873.].

Clausena excavata (C. excavata) has been used as a traditional medicine for the treatment of abdominal pain, enteritis, dysentery, and malaria. The present study was designed to evaluate the effect of a 50% ethanol extract of C. excavata (ECE) on weight loss, adipocyte size, and obesity-related biochemical parameters in high-fat diet (HFD)-induced obese mice. After 6 weeks of HFD + ECE administration, HFD-induced total fat, subcutaneous fat, and visceral fat were evaluated by micro-computed tomography. The serum levels of triglyceride (TG), total cholesterol (TCH), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were evaluated with a biochemical analyzer, and leptin and adiponectin levels in the serum were assessed via enzyme-linked immunoassay (ELISA). Moreover, adipocyte size and lipid formation in the liver were examined. We found that weight gain, epididymal fat pad weight, adipocyte size, and lipid formation were markedly attenuated in the livers of HFD-induced obese mice treated with ECE. Furthermore, TG, TCH, and leptin decreased in the serum, whereas adiponectin increased. In conclusion, our data show that ECE has potent anti-obesity activity in vivo and support the development of ECE as a potential therapeutic agent for the treatment of obesity., (Copyright © 2018. Published by Elsevier Masson SAS.)

We tested the hypothesis that higher levels of bilirubin, a bile pigment with antioxidant properties, are associated with a decreased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the association between serum total bilirubin (TB) on CVD and CVD death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648 females) and evaluated for the development of new onset CVD from 2001 to 2012 (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile categories. In addition to MetS itself, individual components of MetS significantly decreased with increased bilirubin tertiles. Moreover, the incidence of CVD decreased across bilirubin tertile categories. The hazard ratios (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655-1.000) and CVD death (HR 0.513, 95% CI 0.267-0.985) was significantly lower in the highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (< 0.44 mg/dL) after adjusting for all confounding variables. In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident CHD and CVD death.

It has been previously demonstrated that ticagrelor can reduce mortality compared to clopidogrel in acute coronary syndrome (ACS) patients. However, the mechanism for this mortality reduction remains uncertain. The objective of the present study is to assess the impact of chronic ticagrelor treatment on microvascular circulation. A total of 120 participants aged 20-85 years with clinical diagnosis of ACS will be randomized in a 1:1 fashion to the following two groups: ticagrelor 90 mg twice daily; clopidogrel 75 mg once daily. To evaluate the status of microcirculation, the primary end point is coronary microvascular dysfunction measured using an index of microcirculatory resistance (IMR) at 6 months after receiving the study agent. The purpose of this trial is to investigate whether ticagrelor, beyond its antiplatelet efficacy, could improve coronary microcirculation more effectively than clopidogrel for patients with ACS.

Background: Advanced age, poor left ventricular function, and congestive heart failure are known predictors of atrial fibrillation (AF) in acute myocardial infarction (AMI) patients. Recent advances in AMI treatment may have changed the occurrence of new-onset AF. Thus, we investigated the factors associated with the development of new-onset AF in ST elevation myocardial infarction (STEMI) patients., Methods: This study included 527 STEMI patients [mean age, 60.6±12.8 years; 102 (19.4%) women] who underwent primary percutaneous coronary intervention (PCI) in the previous 7 years. New-onset AF was evaluated following STEMI treated by primary PCI. Patients who developed AF during this follow-up period were compared with those who did not develop AF to identify factors that were associated with the development of AF., Results: New-onset AF was documented in 81 patients (15.4%) at 1 year after STEMI. Patients with new-onset AF (n=81) tended to be older (p<0.001); were more often female (p=0.009); had more congestive heart failure (p=0.015); had less use of beta-blockers (p=0.001); had more often used antiarrhythmic drugs (p<0.001); experienced cardiogenic shock more frequently (p=0.038); had lower left ventricular ejection fraction (p=0.024); and had higher E velocity (p<0.001), E/e' (p=0.011), and left atrial volume index (LAVI; p=0.029) than the 446 patients with no AF. Multivariate regression analysis revealed that cardiogenic shock, LAVI, and age were predictors of new-onset AF in STEMI patients (OR 2.823, 1.254, and 1.124; p=0.005, <0.001, and 0.028, respectively)., Conclusion: Cardiogenic shock was a new predictor of new-onset AF in STEMI patients., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Whether genetic polymorphisms (GP) impact residual platelet aggregation (RPA) following prasugrel is unclear, especially during maintenance phase. We assessed the influence of CYP2C19 GP carriers on RPA in the prospective observational cohort study., Methods and Results: All post-stent patients (n = 206) received prasugrel 60 mg loading and either 5 or 10 mg daily maintenance with aspirin100 mg. RPA levels by light transmission aggregometry (LTA), multiplate electrode aggregometry (MEA), and VerifyNow (P2Y12 reaction units, PRU) with CYP2C19 GP were measured simultaneously. Demographics and clinical characteristics were not useful for predicting response after prasugrel. GP carriers exhibited higher RPA (PRU: p = 0.001, LTA: p = 0.001, MEA: p = 0.023) than noncarriers. CYP2C19 carriers had higher RPA for 5 mg (n = 35; LTA: p = 0.043, MEA: p = 0.023) and reached significance for 10 mg (n = 27; LTA: p = 0.001, PRU: p = 0.001) prasugrel. When divided into extensive, intermediate, and poor metabolizers, all exhibited statistical differences among the 3 groups (LTA: 14.9 ± 12.3%, 22.6 ± 14.9%, 22.9 ± 15.6%, p = 0.002; PRU: 104.1 ± 70.8%, 141.8 ± 78.0%, 151.0 ± 84.8%, p = 0.003; MEA: 19.7 ± 8.9%, 24.4 ± 12.2%, 28.1 ± 14.7%, p = 0.002)., Conclusion: CYP2C19 GP impacts RPA during maintenance phase prasugrel in Korean outpatients. This effect is consistent for both of the approved prasugrel doses potentially affecting long-term outcomes including bleeding risks. However, the clinical utility of these findings is still uncertain, and requires more evidence from larger randomized trials beyond East Asians., (© 2018 S. Karger AG, Basel.)

Background: Diminished vascular tone is an established biomarker of heart damage. Little is known about the extent of coronary vessel tone (CVT) with spasm as assessed by dual-acquisition multidetector computed tomography angiography (MCTA) in patients with vasospastic angina (VSA)., Objective: We evaluated the CVT modulated by intravenous nitrate injection (INI) using MCTA imaging in VSA patients., Methods: Twenty-one VSA patients (60 ± 9 years; 76% males) who underwent initial MCTA (without morning vasodilation), followed by an intracoronary ergonovine provocation test were included. Within 3 days after the initial MCTA patients received INI followed by 28-vessel segment spasm analyzed by MCTA 3D software, applying the following formula as the definition of CVT index (CVTI): (CSAIV nitrate - CSAinitial/CSAIV nitrate) ×100 %, where CSA is the cross-sectional area., Results: Compared to the initial MCTA measures, the INI provocation resulted in the significant increase of average diameter and CSA at the spasm site (2.60 mm [2.11-3.16] vs. 1.42 mm [1.13-2.13]; 5.37 mm2 [3.67-7.54] vs. 1.62 mm2 [1.02-3.02]; p < 0.001). The CVTI at the spastic segments was higher than at the proximal reference segments (41.0% [21.8-52.3] vs. 18.8% [5.9-26.6] for CVTI diameter; 65.1% [38.6-77.0] vs. 33.9% [5.2-48.1] for CVTI CSA, respectively). To predict VSA, the cut-off value for CVTI diameter was 38.6% (AUC 0.777; 95% CI 0.653-0.901) and 62.5% (AUC 0.779; 95% CI 0.657-0.902) for CVTI CSA in a receiver-operating characteristic curve analysis, with 57.1% sensitivity and 92.9% specificity., Conclusions: This novel imaging technique for assessing CVT by dual-acquisition MCTA after applying INI provocation is suitable for the detection of coronary artery spasm in patients with VSA., (© 2017 S. Karger AG, Basel.)

Transparent, conductive, and superhydrophobic nanocomposite coatings were fabricated on the polyethylene terephthalate substrate by a spray method. Different concentrations of multi-walled carbon nanotubes (MWCNTs) entwined with SiO 2 nanoparticles, which originated from the hydrolysis and condensation of tetraethyl orthosilicate, were sprayed to form MWCNTs/SiO 2 nanocomposite coatings. The coatings were characterized by scanning electron microscopy, contact angle measurements, and other analytical techniques. The surface morphology, hydrophobicity, transparency, and conductivity of the nanocomposite coating were found to be strongly dependent on the MWCNT concentration. With increasing MWCNT concentration, the hydrophobicity increased first and then decreased, and the optical transmittance and sheet resistance decreased. The enhanced hydrophobicity was associated with the surface microstructure and chemical composition of the coating. The decreased hydrophobicity resulted mainly from the decrease in the trapped air between the water droplet and the nanocomposite coating. Owing to the hierarchically porous 3-dimensional microstructure and opportune fluorinated MWCNT content, the nanocomposite coating with 0.2wt% MWCNTs exhibited the best hydrophobicity with a contact angle of 156.7°, good transparency with 95.7% transmittance and relatively high conductivity with a sheet resistance of 3.2×10 4 Ωsq -1 ., (Copyright © 2017 Elsevier Inc. All rights reserved.)