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Aims: To evaluate the effects of initiating sodium‐glucose cotransporter‐2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase‐4 (DPP‐4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). Materials and Methods: We used an active‐comparator, new‐user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP‐4 inhibitor users for analysis using propensity‐score matching. Results: During 13 708.59 person‐years of follow‐up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP‐4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all‐cause death and end‐stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all‐cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36–0.915), all‐cause death (HR 0.731, 95% CI 0.567–0.942), and ESRD (HR 0.076, 95% CI 0.018–0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. Conclusions: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. Materials and Methods: In this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. Results: The multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. Conclusions: Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is an important lung disease characterized by complicated symptoms including emphysema. We aimed to explore the mechanisms underlying the protective effect of green tea extract (GTE) on cigarette smoke condensate (CSC)‐induced emphysema by demonstrating the reduction of macrophage‐induced protease expression through GTE treatment in vivo and in vitro. Mice were intranasally administered 50 mg/kg CSC once a week for 4 weeks, and doses of 100 or 300 mg/kg GTE were administered orally once daily for 4 weeks. GTE significantly reduced macrophage counts in bronchoalveolar lavage fluid and emphysematous lesions in lung tissues in CSC‐exposed mice. In addition, GTE suppressed CSC‐induced extracellular signal‐regulated kinase (ERK)/activator protein (AP)‐1 phosphorylation followed by matrix metalloproteinases (MMP)‐9 expression as revealed by western blotting, immunohistochemistry, and zymography in CSC‐instilled mice. These underlying mechanisms related to reduced protease expression were confirmed in NCI‐H292 cells stimulated by CSC. Taken together, GTE effectively inhibits macrophage‐driven emphysematous lesions induced by CSC treatment, and these protective effects of GTE are closely related to the ERK/AP‐1 signaling pathway, followed by a reduced protease/antiprotease imbalance. These results suggest that GTE can be used as a supplementary agent for the prevention of emphysema progression in COPD patients. [ABSTRACT FROM AUTHOR]

Background: The thyroid isthmus is located directly anterior to the trachea and is covered by the strap muscles. Several studies have suggested that papillary thyroid carcinoma (PTC) in the isthmus is more aggressive and is associated with a poor prognosis. The purpose of this meta-analysis was to assess the clinicopathological characteristics and recurrence rates of PTC in the isthmus compared to PTC at other sites. Methods: Relevant articles were obtained by searching the PubMed database. A meta-analysis was performed using 11 eligible studies. Results: The rate of extrathyroidal extension was 0.502 (95% confidence interval [CI]: 0.239–0.764) and 0.454 (95% CI: 0.331–0.582) for isthmus PTC and PTC at other site, respectively; however, the difference in the rates was not statistically significant. Lymphovascular invasion did not significantly differ between isthmus PTC (0.179 [95% CI: 0.102–0.297]) and PTC at other sites (0.114 [95% CI: 0.066–0.188]). The rate of central lymph node (LN) metastasis was significantly higher in isthmus PTC (0.527 [95% CI: 0.435–0.617]) than in PTC at other sites (0.352 [95% CI: 0.280–0.432]). No significant difference was observed between the two groups in terms of lateral cervical LN metastasis rate. Isthmus PTC was more likely to have a prominent recurrence rate (0.046 [95% CI: 0.022–0.094]) than PTC at other sites (0.010 [95% CI: 0.001–0.070]); however, the difference was not statistically significant (because of the small number of included studies). Conclusions: The results of this meta-analysis indicated that isthmus PTC was associated with an increased risk of central LN metastasis. Isthmus PTC seems to have a slightly higher recurrence rate than PTC at other sites. Therefore, considering the potential of the isthmus location as an unfavorable factor, more attention should be focused on isthmus PTC, and a more aggressive approach such as prophylactic central LN dissection might provide better outcomes in PTC management. [ABSTRACT FROM AUTHOR]

This study explored counselors' conceptualization and use of encouragement as a therapeutic tool. Responses to two questions from 100 South Korean youth counselors were analyzed using consensual qualitative research–modified. As a result, six categories emerged under each domain. Implications for counseling and future studies are discussed. Este estudio exploró la conceptualización y el uso del apoyo como herramienta terapéutica por parte los consejeros. Usando el método modificado de investigación cualitativa consensual, se analizaron las respuestas proporcionadas a dos preguntas por 100 consejeros surcoreanos que trabajan con jóvenes. Como resultado, surgieron seis categorías bajo cada dominio. Se discuten las implicaciones para la consejería e investigaciones futuras. [ABSTRACT FROM AUTHOR]

In this study, we determined whether p53 expression affected the sensitivity of non-small cell lung cancer (NSCLC) and colon cancer cells to bleomycin (BLM). Two human NSCLC cell lines (A549 expressing wild-type p53 and p53-null H1299) and two colon cancer cell lines (HCT116 p53+/+ and its p53 deficient subline HCT116 p53−/−) were subjected to treatment with BLM. Cells were treated with various concentrations of BLM, and cellular viability was assessed by formazan assay. To investigate the role of p53 in BLM sensitivity, we transduced cells with adenovirus with wild-type p53, dominant-negative p53, and GFP control, and analyzed the effect on cellular viability. Cells expressing wild-type p53 were more sensitive to BLM than p53-null cells in both NSCLC and colon cancer cells. Sensitivity to BLM of the cells with wild-type p53 was reduced by overexpression of dominant-negative p53, while BLM sensitivity of p53-null cells was increased by wild-type p53 in both NSCLC cells and colon cancer cells. In conclusion, our data show that p53 sensitizes all four cancer cells lines tested to BLM toxicity and overexpression of p53 confers sensitivity to the cytotoxic activity of the anticancer agent in p53-null cells. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:260-269, 2010; View this article online at . DOI 10.1002/jbt.20334 [ABSTRACT FROM AUTHOR]

The Wnt/β-catenin signaling pathway is involved in the melanocyte differentiation and melanoma development. However, the effect of β-catenin for dendrite formation has not been clearly elucidated yet in normal human epidermal melanocytes (NHEM). To investigate the effect of β-catenin, we transduced NHEM with recombinant adenovirus expressing β-catenin. Forced expression of β-catenin led to the dramatic morphological changes of NHEM, including the reduction of dendrite length and enlargement of cell body. Concomitantly with, the protein levels for dendrite formation-related molecules, such as Rac1 and Cdc42, were markedly decreased. In addition, phosphorylation of p38 MAPK was significantly reduced by β-catenin, potentiating its inhibitory role for dendrite formation. Interestingly, overexpression of β-catenin led to the increase of protein kinase C ζ (PKCζ) level, while protein kinase C δ (PKCδ) was decreased by β-catenin, suggesting that those PKCs were β-catenin-downstream modulators in NHMC. When PKCζ was overexpressed, dendrites were shortened, with the reduced protein levels for Rac1 and Cdc42. In contrast, PKCδ overexpression led to the elongation of dendrites, with the increased levels for Rac1 and Cdc42. These results suggest that β-catenin play an inhibitory role for dendrite formation through the modulation of PKCζ and PKCδ. [ABSTRACT FROM AUTHOR]

There are many techniques for evaluating melanosome transfer to keratinocytes but the spectrophotometric quantification of melanosomes incorporated by keratinocyte phagocytosis has not been previously reported. Here we describe a new method that allows the spectrophotometric visualization of melanosome uptake by normal human keratinocytes in culture. Fontana-Masson staining of keratinocytes incubated with isolated melanosomes showed the accumulation of incorporated melanosomes in the perinuclear areas of keratinocytes within 48 h. Electron microscopic observations of melanosomes ingested by keratinocytes revealed that many phagosomes containing clusters of melanosomes or their fragments were localized in the perinuclear area. A known inhibitor of keratinocyte phagocytosis which inhibits protease-activated receptor-2, i.e., soybean trypsin inhibitor, decreased melanosome uptake by keratinocytes in a dose-dependent manner. These data suggest that our method is a useful model to quantitate keratinocyte phagocytosis of melanosomes visually in vitro. [ABSTRACT FROM AUTHOR]