Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.

Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

Objective: Data pertaining to the prognostic value of the combination of high neutrophilto-lymphocyte ratio (NLR) and anemia on admission in patients with ST-segment elevation myocardial infarction (STEMI) are limited. The objective of this study was to investigate the clinical value of baseline NLR in combination with anemia in predicting clinical outcomes after STEMI. Methods: A total of 5,194 consecutive patients with STEMI within 12 hours of symptom onset from the Korea Acute Myocardial Infarction Registry-National Institute of Health database between 2011 and 2015 were categorized into 4 groups according to their NLR and hemoglobin levels: low NLR (<4) without anemia (n=2,722; reference group); high NLR (≥4) without anemia (n=1,527); low NLR with anemia (n=508); and high NLR with anemia (n=437). The co-primary outcomes were 180-day and 3-year all-cause mortality. Results: Mortality rates significantly increased at the 3-year follow-up across the groups (3.3% vs. 5.4% vs. 16.5% vs. 21.7% for 180-day mortality and 5.3% vs. 9.0% vs. 23.8% vs. 33.4% for 3-year mortality; all p-trends <0.001). After adjusting for baseline covariates, the combination of high NLR and anemia was a significant predictor of 180-day mortality after STEMI with low NLR and no anemia as the reference (adjusted hazard ratio, 2.16; 95% confidence interval, 1.58–2.95; p<0.001). Similar findings were observed for the 3-year mortality. Conclusions This nationwide prospective cohort study showed that the combination of high NLR (≥4) and anemia is a strong predictor of all-cause mortality after STEMI.

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI).METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months.RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924).CONCLUSIONS: Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.
Aspirin ; Drug-Eluting Stents ; Hemorrhage ; Humans ; Incidence ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; Stents ; Stroke ; Thrombosis

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI). METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months. RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924). CONCLUSIONS Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.

OBJECTIVE: Data on the intensity of statin therapy for patients with acute myocardial infarction (MI) and very low baseline low-density lipoprotein (LDL) cholesterol level are lacking. We sought to assess the impact of statin intensity in patients with acute MI and LDL cholesterol <70 mg/dL. METHODS: A total of 1,086 patients with acute MI and baseline LDL cholesterol <70 mg/dL from the Korea Acute Myocardial Infarction Registry-National Institute of Health database were divided into less intensive statin (expected LDL reduction <40%, n=302) and more intensive statin (expected LDL reduction ≥40%, n=784) groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, MI, revascularization occurring at least 30 days after admission, and stroke, at 12 months. RESULTS: After 1:2 propensity matching, differences were not observed between less intensive (n=302) and more intensive statin (n=604) groups in incidence of cardiac death (0.3% vs. 0.3%) and hemorrhagic stroke (0.3% vs. 0.5%, p=0.727) at 12 months. Compared with the less intensive statin group, the more intensive statin group showed lower target-vessel revascularization (4.6% vs. 1.8%, p=0.027) and MACCE (11.6% vs. 7.0%, p=0.021). Major bleeding was not different between less intensive and more intensive statin groups (1.0% vs. 2.6%, p=0.118). CONCLUSION: More intensive statin therapy was associated with significantly lower major adverse cardiovascular events in patients with acute MI and very low LDL cholesterol compared with less intensive statin therapy.
Cholesterol ; Cholesterol, LDL ; Death ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Korea ; Lipoproteins ; Myocardial Infarction ; Stroke

OBJECTIVE: The complete blood count is the most widely available laboratory data in the early in-hospital period after acute myocardial infarction. We assessed the clinical utility of the combined use of hemoglobin (Hb) level and neutrophil to lymphocyte ratio (N/L) for early risk stratification in patients with non-ST-elevation myocardial infarction (STEMI). METHODS: We analyzed 6,157 consecutive patients with non-STEMI (65±12.4 years, male 69%) were included in the final analysis. Patients were categorized into 3 groups by using the median value of N/L (4.42) and the presence of anemia (Hb <13 mg/dL in men and <12 mg/dL in women): group I, low N/L & no anemia (n=3,170); group II, no group I or III (n=2,168); group III, high N/L & anemia (n=819). RESULTS: There were significant differences on clinical outcomes during 180-day follow-up among 3 groups. The prognostic discriminatory capacity of the combined use of Hb level and N/L was also significant in high-risk subgroups, such as patients with a renal dysfunction, multivessel coronary disease, low ejection fraction, and even in those having higher mortality risk based on the thrombolysis in myocardial infarction risk score. In a multi-variate logistic regression, after adjusting for multiple covariates, group III had higher incidence of major adverse cardiac events at 180-day (hazard ratio, 2.4; 95% confidence interval, 1.5–4.0;p≤0.001) compared with group I. CONCLUSIONS: The combined use of Hb level and N/L provides valuable timely information for early risk stratification in patients with non-STEMI.
Anemia ; Blood Cell Count ; Coronary Disease ; Follow-Up Studies ; Humans ; Incidence ; Logistic Models ; Lymphocytes* ; Male ; Mortality ; Myocardial Infarction* ; Neutrophils* ; Prognosis

BACKGROUND AND OBJECTIVES: The prognostic impact of left axis deviation (LAD) on clinical outcomes in acute heart failure syndrome (AHFS) with left bundle branch block (LBBB) is unknown. The aim of this study was to determine the prognostic significance of axis deviation in acute heart failure patients with LBBB. METHODS: Between March 2011 and February 2014, 292 consecutive AHFS patients with LBBB were recruited from 10 tertiary university hospitals. They were divided into groups with no LAD (n=189) or with LAD (n=103) groups according to QRS axis < −30 degree. The primary outcome was all-cause mortality. RESULTS: The median follow-up duration was 24 months. On multivariate analysis, the rate of all-cause death did not significantly differ between the normal axis and LAD groups (39.7% vs. 46.6%, adjusted hazard ratio, 1.01; 95% confidence interval, 0.66, 1.53; p=0.97). However, on the multiple linear regression analysis to evaluate the predictors of the left ventricular ejection fraction (LVEF), presence of LAD significantly predicted a worse LVEF (adjusted beta, −3.25; 95% confidence interval, −5.82, −0.67; p=0.01). Right ventricle (RV) dilatation was defined as at least 2 of 3 electrocardiographic criteria (late R in lead aVR, low voltages in limb leads, and R/S ratio < 1 in lead V5) and was more frequent in the LAD group than in the normal axis group (p < 0.001). CONCLUSIONS: Among the AHFS with LBBB patients, LAD did not predict mortality, but it could be used as a significant predictor of worse LVEF and RV dilatation (Trial registry at KorAHF registry, ClinicalTrial.gov, NCT01389843).
Bundle-Branch Block ; Dilatation ; Electrocardiography ; Extremities ; Follow-Up Studies ; Heart Failure ; Heart Ventricles ; Heart ; Hospitals, University ; Humans ; Linear Models ; Mortality ; Multivariate Analysis ; Stroke Volume