PHF2 regulates sarcomeric gene transcription in myogenesis.

Myogenesis is regulated mainly by transcription factors known as Myogenic Regulatory Factors (MRFs), and the transcription is affected by epigenetic modifications. However, the epigenetic regulation of myogenesis is poorly understood. Here, we focused on the epigenomic modification enzyme, PHF2, which demethylates histone 3 lysine 9 dimethyl (H3K9me2) during myogenesis. Phf2 mRNA was expressed during myogenesis, and PHF2 was localized in the nuclei of myoblasts and myotubes. We generated Phf2 knockout C2C12 myoblasts using the CRISPR/Cas9 system and analyzed global transcriptional changes via RNA-sequencing. Phf2 knockout (KO) cells 2 d post differentiation were subjected to RNA sequencing. Gene ontology (GO) analysis revealed that Phf2 KO impaired the expression of the genes related to skeletal muscle fiber formation and muscle cell development. The expression levels of sarcomeric genes such as Myhs and Mybpc2 were severely reduced in Phf2 KO cells at 7 d post differentiation, and H3K9me2 modification of Mybpc2, Mef2c and Myh7 was increased in Phf2 KO cells at 4 d post differentiation. These findings suggest that PHF2 regulates sarcomeric gene expression via epigenetic modification.

Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan.

BACKGROUND: Subcutaneous immunoglobulin is one of the standard treatments for hypogammaglobulinemia in primary immunodeficiencies (PID) worldwide. In Japan, IgPro20 (Hizentra® ; l-proline-stabilized 20% human subcutaneous immunoglobulin) is approved for agammaglobulinemia or hypogammaglobulinemia due to PID or secondary immunodeficiency (SID); however, its safety and effectiveness has not previously been assessed in a real-world setting. METHODS: This multicenter, open label post-marketing surveillance study was conducted between January 2014 and March 2019. Patients who received IgPro20 due to PID or SID were included after informed consent. Physicians completed a case report form for each patient. Safety was determined from reported adverse events (AEs), adverse drug reactions, and serious AEs (SAEs); effectiveness was assessed by infection rates after the first IgPro20 dose. RESULTS: Of 85 patients receiving IgPro20 in the safety analysis, 39 developed AEs (45.9%; PID n = 28, SID n = 11). At least one adverse drug reaction was observed in 27 patients (31.8%; PID n = 21, SID n = 6), and the most common were injection site reactions (n = 17, 20.0%). Four patients (PID n = 3, SID n = 1) reported SAEs but two were unrelated to IgPro20 administration. The infection rate decreased from 0.54 per patient during the 6 months before IgPro20 to 0.39 per patient during IgPro20 treatment. Serious bacterial infections occurred in six patients before IgPro20 (7.9%; PID n = 2; SID n = 4) but in only one patient with SID during IgPro20 treatment (1.2%). CONCLUSIONS: In Japan, IgPro20 was considered safe and effective among patients with agammaglobulinemia or hypogammaglobulinemia due to PID or SID.

Effect of Periodontal Disease on Long-Term Outcomes After Percutaneous Coronary Intervention for De Novo Coronary Lesions in Non-Smokers.

BACKGROUND: This study aimed to investigate the effect of periodontal disease (PD) on the outcomes of patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI).Methods and Results: The study included 77 consecutive non-smoking patients with de novo coronary lesions treated with a drug-eluting stent (DES). Periodontal measurements, including the community periodontal index (CPI), were performed by independent periodontists. A CPI score of ≥3 was used to define PD. The occurrence of major adverse cardiac events (MACEs), which were defined as a composite of cardiovascular death, non-fatal myocardial infarction, target lesion revascularization, or non-target lesion revascularization, was compared between patients with and without PD. Of the 77 patients, 49 (63.6%) exhibited a CPI score of 3 or 4 and were assigned to the PD group. The remaining 28 patients (36.4%) were assigned to the non-PD group. Baseline clinical characteristics and angiographic findings were comparable between the 2 groups. MACEs occurred in 13 (26.5%) of the PD patients and 2 (7.1%) of the non-PD patients. Kaplan-Meier analysis showed a significantly lower MACE-free survival rate in the PD group than for the non-PD group (P=0.034). CONCLUSIONS: PD at baseline was associated with an increased risk of MACEs in CAD patients who were treated with a DES for de novo coronary lesions.

[Treatment Options for Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP): With a Focus on Immunoglobulin Treatment].

The disease state and clinical course of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are diverse, and the response to treatment varies from patient to patient. Therefore, it is necessary to select a treatment and determine the appropriate dose and dosage interval while monitoring the clinical course after treatment initiation. In this article, we will discuss points to be considered and the results of studies that can be used as references in order to make an appropriate choice at each stage of CIDP treatment.

Treatment of In-Stent Restenosis by Excimer Laser Coronary Atherectomy and Drug-Coated Balloon: Serial Assessment with Optical Coherence Tomography.

OBJECTIVES: We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR). BACKGROUND: Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown. METHODS: A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months. RESULTS: Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm2 vs. -0.09 ± 1.25 mm2, p = 0.05, -0.49 ± 1.48 mm2 vs. 0.28 ± 0.78 mm2, p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85). CONCLUSIONS: Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome.

Effect of drug-coated balloon on stent restenosis, neointimal proliferation, and coronary dissection: an optical coherence tomography analysis.

AIM: The aim of this study was to assess the acute and mid-term effects of drug-coated balloon (DCB) in terms of the healing process of non-flow-limiting dissections and changes in the neointimal area after DCB treatment using frequency domain optical coherence tomography (FD-OCT). PATIENTS AND METHODS: Thirty-six consecutive patients with in-stent restenosis pretreated with a scoring balloon were evaluated (19 and 17 patients with and without a DCB, respectively). FD-OCT was performed before and after each procedure during percutaneous coronary intervention and at 6 months of follow-up. RESULTS: Clinical characteristics and baseline FD-OCT findings were comparable between the two groups. No patient required stent implantation because of low-pressure DCB-related dissections. In the acute phase, the DCB distributed paclitaxel to the vessel wall without increasing dissections. The DCB did not reduce the neointimal area by itself. At 6 months, more dissections healed in the DCB group (-4.5±2.3 vs. -2.7±1.3, P=0.02). The DCB group showed less change in the neointimal area (-0.04±0.92 vs. 1.06±1.57 mm, P=0.03). CONCLUSION: The low-pressure DCB was not intended to expand the lumen, but instead to attach paclitaxel to the vessel wall by using FD-OCT examination. The DCB reduced the number of dissections and prevented neointimal proliferation during the mid-term follow-up.