In articular chondrocytes, nitric oxide (NO) production triggers dedifferentiation and apoptotic cell death that is regulated by the converse functions of two mitogen-activated protein kinase subtypes, extracellular signal-regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces signals that influence differentiation, survival, and apoptosis of various cell types, we investigated the roles and underlying molecular mechanisms of action of PKC isoforms in NO-induced dedifferentiation and apoptosis of articular chondrocytes. We report here that among the expressed isoforms, activities of PKC␣ and -were reduced during NO-induced dedifferentiation and apoptosis. Inhibition of PKC␣ activity was independent of NO-induced activation of ERK or p38 kinase and occurred due to blockage of expression. On the other hand, PKC activity was inhibited as a result of NO-induced p38 kinase activation and was observed prior to proteolytic cleavage by a caspase-mediated process to generate enzymatically inactive fragments. Inhibition of PKC␣ or -activities potentiated NO-induced apoptosis, whereas ectopic expression of these isoforms significantly reduced the number of apoptotic cells and blocked dedifferentiation. Ectopic expression of PKC␣ or -did not affect p38 kinase or ERK but inhibited the p53 accumulation and caspase-3 activation that are required for NO-induced apoptosis of chondrocytes. Therefore, our results collectively indicate that p38 kinase-independent and -dependent inhibition of PKC␣ and -, respectively, regulates NO-induced apoptosis and dedifferentiation of articular chondrocytes.

To assess the effectiveness of conservation‐based transplantation of the endangered orchid (Cypripedium japonicum), we compared the morphology, physiology, stem‐count change, and population viability of natural versus transplanted populations undergoing habitat management (repeated removal of competing understory vegetation) between 2009 and 2015 in South Korea. The restored site had lower transmitted light and soil humidity than the natural site. The natural and transplanted populations differed in leaf morphology and total chlorophyll content (natural: 1.00 ± 0.04, restored: 0.53 ± 0.06). No recruitment occurred during the monitoring period. Population viability tended to decrease in the restored population (λG = 0.97, μ = −0.05, σ2 = 0.036) and increase in the natural population (λG = 1.07, μ = 0.03, σ2 = 0.075). The repeated removal of competing understory vegetation had different effects on leaf traits, abundance, and reproductive properties of the endangered orchids in both populations. Notably, habitat management increased the stem count and flowering rate in natural C. japonicum but did not increase the fruit‐setting rate. Thus, despite repeated habitat management efforts (removal of competing understory vegetation), we conclude that the population viability of transplanted populations of the endangered orchid C. japonicum had poor long‐term viability compared with naturally occurring populations, a difference that is mainly attributed to inappropriate transplant‐site selection.

BACKGROUND The prognostic utility of follow-up transthoracic echocardiography (FU-TTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e’), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e’ values were associated with poor outcomes. However, no delta values predicted HCM-related cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events.

Background/Aims: Bleeding events after percutaneous coronary intervention (PCI) have important prognostic implications. Data on the influence of an abnormal ankle-brachial index (ABI) on both ischemic and bleeding events in patients undergoing PCI are limited.Methods: We included patients who underwent PCI with available ABI data (abnormal ABI, ≤ 0.9 or > 1.4). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, and major bleeding.Results: Among 4,747 patients, an abnormal ABI was observed in 610 patients (12.9%). During follow-up (median, 31 months), the 5-year cumulative incidence of adverse clinical events was higher in the abnormal ABI group than in the normal ABI group: primary endpoint (36.0% vs. 14.5%, log-rank test, <i>p</i> < 0.001); all-cause death (19.4% vs. 5.1%, log-rank test, <i>p</i> < 0.001); MI (6.3% vs. 4.1%, log-rank test, <i>p</i> = 0.013); stroke (6.2% vs. 2.7%, log-rank test, <i>p</i> = 0.001); and major bleeding (8.9% vs. 3.7%, log-rank test, <i>p</i> < 0.001). An abnormal ABI was an independent risk factor for all-cause death (hazard ratio [HR], 3.05; <i>p</i> < 0.001), stroke (HR, 1.79; <i>p</i> = 0.042), and major bleeding (HR, 1.61; <i>p</i> = 0.034).Conclusions: An abnormal ABI is a risk factor for both ischemic and bleeding events after PCI. Our study findings may be helpful in determining the optimal method for secondary prevention after PCI.

BACKGROUND Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder that results from a deficiency of α-galactosidase A enzyme activity in which glycosphingolipids gradually accumulate in multi-organ systems. Cardiac manifestations are the leading cause of mortality in patients with AFD. Among them, arrhythmias comprise a large portion of the heart disease cases in AFD, most of which are characterized by conduction disorders. However, atrial fibrillation as a presenting sign at the young age group diagnosed with AFD is uncommon. CASE SUMMARY We report a case of a 26-year-old man who was admitted with chest discomfort. Left ventricular hypertrophy was fulfilled in the criteria by the Sokolow-Lyon index and atrial fibrillation on the 12 Leads-electrocardiography (ECG) that was documented in the emergency room. After spontaneously restored to normal sinus rhythm, relationships between P and R waves, including a shorter PR interval on the ECG, were revealed. The echocardiographic findings showed thickened interventricular septal and left posterior ventricular walls. Based on the clues mentioned earlier, we realized the possibility of AFD. Additionally, we noticed the associated symptoms and signs, including bilateral mild hearing loss, neuropathic pain, anhidrosis, and angiokeratoma on the trunk and hands. He was finally diagnosed with classical AFD, which was confirmed by the gene mutation and abnormal enzyme activity of α-galactosidase A. CONCLUSION This case is a rare case of AFD as a presentation with atrial fibrillation at a young age. Confirming the relationship between P and Q waves on the ECG through sinus rhythm conversion may help in differential diagnosis of the cause of atrial fibrillation and hypertrophic myocardium.