Effects of Positive Airway Pressure on Cardiorespiratory Fitness in Patients with Concomitant Obstructive Sleep Apnea and Cardiovascular Disease.

Obstructive sleep apnea (OSA) is common in cardiovascular disease (CVD), although positive airway pressure (PAP) treatment has not been demonstrated to improve the cardiovascular outcome. The objective of this study is to investigate the impact of adherence to PAP therapy on cardiopulmonary exercise testing (CPET) performance in patients with concomitant OSA and CVD. This preliminary study involved symptomatic OSA patients requiring PAP treatment who had CVD.

Comparative Effectiveness of Long-Term Maintenance Beta-Blocker Therapy After Acute Myocardial Infarction in Stable, Optimally Treated Patients Undergoing Percutaneous Coronary Intervention.

Background The benefits of long-term maintenance beta-blocker (BB) therapy in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have not been well established. Methods and Results Using the Korean nationwide registry, a total of 7159 patients with AMI treated with PCI who received BBs at discharge and were free from death or cardiovascular events for 3 months after PCI were included in the analysis. Patients were divided into 4 groups according to BB maintenance duration: <12 months, 12 to <24 months, 24 to <36 months, and ≥36 months.

Evidence-Based Optimal Medical Therapy and Mortality in Patients With Acute Myocardial Infarction After Percutaneous Coronary Intervention.

Background The secondary prevention with pharmacologic therapy is essential for preventing recurrent cardiovascular events in patients experiencing acute myocardial infarction. Guideline-based optimal medical therapy (OMT) for patients with acute myocardial infarction consists of antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, β-blockers, and statins. We aimed to determine the prescription rate of OMT use at discharge and to evaluate the impact of OMT on long-term clinical outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention in the drug-eluting stent era using nationwide cohort data.

BAP1 as a guardian of genome stability: implications in human cancer.

BAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma.

Targeting BAP1 with small compound inhibitor for colon cancer treatment.

BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase. The gene encoding BAP1 is mutated in various human cancers, including mesothelioma, uveal melanoma and renal cell carcinoma. BAP1 plays roles in many cancer-related cellular functions, including cell proliferation, cell death, and nuclear processes crucial for genome stability, such as DNA repair and replication.

Clinical impact of statin intensity according to age in patients with acute myocardial infarction.

Background: The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI).

Methods: Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger (<75 years old) and elderly (≥75 years old) patients. Of 10,719 patients, we included 8,096 patients treated with drug-eluting stents.

BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability.

BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with tumor suppressor activity. The gene encoding BAP1 is mutated in various human cancers, with particularly high frequency in kidney and skin cancers, and BAP1 is involved in many cancer-related cellular functions, such as DNA repair and genome stability. Although BAP1 stimulates DNA double-strand break repair, whether it functions in nucleotide excision repair (NER) is unknown.

Relationship of Serial High-Sensitivity C-Reactive Protein Changes to Long-term Clinical Outcomes in Stabilised Patients After Myocardial Infarction.

Background: Little is known about the association between serial high-sensitivity C-reactive protein (hsCRP) measurements and long-term outcomes in post-myocardial infarction (MI) patients. We aimed to investigate the usefulness of serial hsCRP measurements for risk stratification in stabilised post-MI patients after percutaneous coronary intervention (PCI).

Methods: A total of 1018 patients who had hsCRP values at both baseline and 1 year after MI were included.

CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication.

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression.

The Bromodomain Inhibitor PFI-3 Sensitizes Cancer Cells to DNA Damage by Targeting SWI/SNF.

Many chemotherapeutic drugs produce double-strand breaks (DSB) on cancer cell DNA, thereby inducing cell death. However, the DNA damage response (DDR) enables cancer cells to overcome DNA damage and escape cell death, often leading to therapeutic resistance and unsuccessful outcomes. It is therefore important to develop inhibitors that target DDR proteins to render cancer cells hypersensitive to DNA damage.

Cytotoxic activity of bromodomain inhibitor NVS-CECR2-1 on human cancer cells.

Bromodomain (BRD), a protein module that recognizes acetylated lysine residues on histones and other proteins, has recently emerged as a promising therapeutic target for human diseases such as cancer. While most of the studies have been focused on inhibitors against BRDs of the bromo- and extra-terminal domain (BET) family proteins, non-BET family BRD inhibitors remain largely unexplored. Here, we investigated a potential anticancer activity of the recently developed non-BET family BRD inhibitor NVS-CECR2-1 that targets the cat eye syndrome chromosome region, candidate 2 (CECR2).

BAP1 promotes stalled fork restart and cell survival via INO80 in response to replication stress.

The recovery from replication stress by restarting stalled forks to continue DNA synthesis is crucial for maintaining genome stability and thereby preventing diseases such as cancer. We previously showed that BRCA1-associated protein 1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, promotes replication fork progression by stabilizing the INO80 chromatin remodeler via deubiquitination and recruiting it to replication forks during normal DNA synthesis. However, whether BAP1 functions in DNA replication under stress conditions is unknown.

Absence of Cytosolic 2-Cys Prx Subtypes I and II Exacerbates TNF-α-Induced Apoptosis via Different Routes.

There are abundant peroxiredoxin (Prx) enzymes, but an increase of cellular HO level always happens in apoptotic cells. Here, we show that cellular HO switches different apoptosis pathways depending on which type of Prx enzyme is absent. TNF-α-induced HO burst preferentially activates the DNA damage-dependent apoptosis pathway in the absence of PrxI.

INO80 haploinsufficiency inhibits colon cancer tumorigenesis via replication stress-induced apoptosis.

The INO80 chromatin-remodeling complex performs functions in many chromosomal processes that are crucial for genome stability, such as DNA replication and stalled replication fork recovery. Although these functions suggest that INO80 acts as a tumor suppressor, its specific role in tumorigenesis has remained obscure. Here, we show that a haploinsufficient mutation of Ino80, the catalytic ATPase of the INO80 complex, decreased intestinal adenomatous polyps and increased survival in an Apc mouse model of colon cancer.

Targeting BRG1 chromatin remodeler via its bromodomain for enhanced tumor cell radiosensitivity in vitro and in vivo.

Radiotherapy treats cancer by inducing DNA double-strand breaks (DSB) in tumor cells using ionizing radiation. However, DNA repair in tumor cells often leads to radioresistance and unsuccessful outcome. Inhibition of DNA repair by targeting repair proteins can increase radiosensitivity of tumor cells.

Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis.

The INO80 chromatin-remodelling complex has been implicated in DNA replication during stress in yeast. However, its role in normal DNA replication and its underlying mechanisms remain unclear. Here, we show that INO80 binds to replication forks and promotes fork progression in human cells under unperturbed, normal conditions.

A case of three consecutive events of acute myocardial infarctions in three different vessels.

A 51-year-old man was being admitted to the emergency department with chest pains. He had a history of acute myocardial infarction (MI) on two prior occasions and was successfully treated with drug eluting stents. He was diagnosed with 3 consecutive events of acute MI in 3 different vessels.

Genome-wide reorganization of histone H2AX toward particular fragile sites on cell activation.

γH2AX formation by phosphorylation of the histone variant H2AX is the key process in the repair of DNA lesions including those arising at fragile sites under replication stress. Here we demonstrate that H2AX is dynamically reorganized to preoccupy γH2AX hotspots on increased replication stress by activated cell proliferation and that H2AX is enriched in aphidicolin-induced replisome stalling sites in cycling cells. Interestingly, H2AX enrichment was particularly found in genomic regions that replicate in early S phase.

A case of patent ductus arteriosus with congestive heart failure in a 80-year-old man.

Patent ductus arteriosus (PDA) is a rare clinical finding in adult patients. Considering the increase in cases of PDA discovered incidentally on echocardiograms at young ages, and the life-shortening effect of PDA, it is rare to diagnose PDA in old patients. We report a case of an 80-year-old patient who experienced symptoms of congestive heart failure showed findings suggestive of PDA in echocardiogram and confirmed the diagnosis through a cardiac catheterization and a coronary angiography.

Genome-wide screen of human bromodomain-containing proteins identifies Cecr2 as a novel DNA damage response protein.

The formation of γ-H2AX foci after DNA double strand breaks (DSBs) is crucial for the cellular response to this lethal DNA damage. We previously have shown that BRG1, a chromatin remodeling enzyme, facilitates DSB repair by stimulating γ-H2AX formation, and this function of BRG1 requires the binding of BRGI to acetylated histone H3 on γ-H2AX-containing nucleosomes using its bromodomain (BRD), a protein module that specifically recognizes acetyl-Lys moieties. We also have shown that the BRD of BRG1, when ectopically expressed in cells, functions as a dominant negative inhibitor of the BRG1 activity to stimulate γ-H2AX and DSB repair.

Identification of genomic aberrations by array comparative genomic hybridization in patients with aortic dissections.

Background: The aim of the present study was to identify chromosomal loci that contribute to the pathogenesis of aortic dissection (AD) in a Korean population using array comparative genomic hybridization (CGH) and to confirm the results using real-time polymerase chain reaction (PCR).

Materials And Methods: Eighteen patients with ADs were enrolled in this study. Genomic DNA was extracted from individual blood samples, and array CGH analyses were performed.

The human Ino80 binds to microtubule via the E-hook of tubulin: implications for the role in spindle assembly.

The human INO80 chromatin remodeling complex, comprising the Ino80 ATPase (hIno80) and the associated proteins such as Tip49a, has been implicated in a variety of nuclear processes other than transcription. We previously have found that hIno80 interacts with tubulin and co-localizes with the mitotic spindle and is required for spindle formation. To better understand the role of hIno80 in spindle formation, we further investigated the interaction between hIno80 and microtubule.

Peroxiredoxin II restrains DNA damage-induced death in cancer cells by positively regulating JNK-dependent DNA repair.

The 2-Cys peroxiredoxins (Prx) belong to a family of antioxidant enzymes that detoxify reactive oxygen and nitrogen species and are distributed throughout the intracellular and extracellular compartments. However, the presence and role of 2-Cys Prxs in the nucleus have not been studied. This study demonstrates that the PrxII located in the nucleus protects cancer cells from DNA damage-induced cell death.

Human INO80 chromatin-remodelling complex contributes to DNA double-strand break repair via the expression of Rad54B and XRCC3 genes.

Recent studies have shown that the SWI/SNF family of ATP-dependent chromatin-remodelling complexes play important roles in DNA repair as well as in transcription. The INO80 complex, the most recently described member of this family, has been shown in yeast to play direct role in DNA DSB (double-strand break) repair without affecting the expression of the genes involved in this process. However, whether this function of the INO80 complex is conserved in higher eukaryotes has not been investigated.