Cardiac Reprogramming and Gata4 Overexpression Reduce Fibrosis and Improve Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a major health concern. Pathological stimuli and interactions between cardiac fibroblasts (CFs) and other cell types may lead to cardiac fibrosis and diastolic dysfunction, which are hallmarks of HFpEF. Interstitial and perivascular cardiac fibrosis correlates with poor prognosis in HFpEF; however, mechanisms of fibrosis remain poorly elucidated, and targeted therapies are lacking.

Diagnostic Value of Combined Light and Electron Microscopic Examination in Endomyocardial Biopsy in Patients With Cardiac Amyloidosis.

Background: Despite advances in imaging techniques, endomyocardial biopsy remains the gold standard for confirming cardiac amyloidosis (CA) and defining the amyloid type. Electron microscopy may detect amyloid deposits with greater sensitivity than light microscopy; however, its capabilities have not been thoroughly investigated.

Methods: Patients with pathologically diagnosed CA were prospectively enrolled.

Development of adeno-associated viral vectors targeting cardiac fibroblasts for efficient in vivo cardiac reprogramming.

Overexpression of cardiac reprogramming factors, including GATA4, HAND2, TBX5, and MEF2C (GHT/M), can directly reprogram cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs). Adeno-associated virus (AAV) vectors are widely used clinically, and vectors targeting cardiomyocytes (CMs) have been extensively studied. However, safe and efficient AAV vectors targeting CFs for in vivo cardiac reprogramming remain elusive.

Association Between Right Bundle Branch Block and Ventricular Arrhythmia in Patients With Cardiac Sarcoidosis.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown.

Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.

Cardiac reprogramming reduces inflammatory macrophages and improves cardiac function in chronic myocardial infarction.

Cardiomyocytes (CMs) have little regenerative capacity. After myocardial infarction (MI), scar formation and myocardial remodeling proceed in the infarct and non-infarct areas, respectively, leading to heart failure (HF). Prolonged activation of cardiac fibroblasts (CFs) and inflammatory cells may contribute to this process; however, therapies targeting these cell types remain lacking.

Flk1 Deficiency and Hypoxia Synergistically Promote Endothelial Dysfunction, Vascular Remodeling, and Pulmonary Hypertension.

Background: The mechanisms underlying pulmonary hypertension (PH) remain largely unknown; further, why advanced vascular remodeling preferentially occurs in arterioles is yet to be answered. VEGF (vascular endothelial growth factor) regulates angiogenesis through Flk1 (fetal liver kinase 1) and Flt1 (fms-like tyrosine kinase 1) on endothelial cells (ECs), which may be related to PH pathogenesis. However, spatiotemporal expression patterns of Flk1 and Flt1 in the pulmonary vascular system and the role of endothelial Flk1 in PH development remain poorly understood.

MEF2C/p300-mediated epigenetic remodeling promotes the maturation of induced cardiomyocytes.

Cardiac transcription factors (TFs) directly reprogram fibroblasts into induced cardiomyocytes (iCMs), where MEF2C acts as a pioneer factor with GATA4 and TBX5 (GT). However, the generation of functional and mature iCMs is inefficient, and the molecular mechanisms underlying this process remain largely unknown. Here, we found that the overexpression of transcriptionally activated MEF2C via fusion of the powerful MYOD transactivation domain combined with GT increased the generation of beating iCMs by 30-fold.

Development of direct cardiac reprogramming for clinical applications.

The incidence of cardiovascular diseases is increasing worldwide, and cardiac regenerative therapy has great potential as a new treatment strategy, especially for ischemic heart disease. Direct cardiac reprogramming is a promising new cardiac regenerative therapy that uses defined factors to induce transdifferentiation of endogenous cardiac fibroblasts (CFs) into induced cardiomyocyte-like cells (iCMs). In vivo reprogramming is expected to restore lost cardiac function without necessitating cardiac transplantation by converting endogenous CFs that exist abundantly in cardiac tissues directly into iCMs.

Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial.

Background: Wasabi (Eutrema japonicum) is a common pungent spice used in Japan. 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) found in the rhizome of wasabi has been shown to have anti-inflammatory and antioxidant effects, as well as improve neuroinflammation and memory. Therefore, we hypothesized that these effects would be beneficial for treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Direct Reprogramming Improves Cardiac Function and Reverses Fibrosis in Chronic Myocardial Infarction.

Background: Because adult cardiomyocytes have little regenerative capacity, resident cardiac fibroblasts (CFs) synthesize extracellular matrix after myocardial infarction (MI) to form fibrosis, leading to cardiac dysfunction and heart failure. Therapies that can regenerate the myocardium and reverse fibrosis in chronic MI are lacking. The overexpression of cardiac transcription factors, including (MGTH), can directly reprogram CFs into induced cardiomyocytes (iCMs) and improve cardiac function under acute MI.

Additional diagnostic value of electron microscopic examination in endomyocardial biopsy in patients with suspected non-ischemic cardiomyopathy.

Background: Electron microscopy enables a finely detailed analysis of ultra-structural features, and hence, it generally has an added diagnostic value to light microscopy alone. However, no studies have verified the additional diagnostic value of electron microscopic examination in patients with suspected non-ischemic cardiomyopathy.

Methods: A total of 294 consecutive patients with non-ischemic cardiomyopathy who underwent endomyocardial biopsy were prospectively enrolled.

Long-term survival after surgical or transcatheter aortic valve replacement for low or intermediate surgical risk aortic stenosis: Comparison with general population.

Background: Long-term survival after surgery for severe aortic stenosis (AS) provides important information regarding the choice between surgical (SAVR) and transcatheter (TAVR) aortic valve replacement. This study investigated the long-term survival of AS patients with low or intermediate surgical risk who underwent SAVR or TAVR in our institution versus that of the Japanese general population.

Methods: From 2009 to 2019, 1276 consecutive patients underwent SAVR or TAVR for severe AS.

Chronic kidney disease and clinical outcomes in patients with COVID-19 in Japan.

Background: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear.

Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage.

Adult hearts have limited regenerative capacity. Hence, after acute myocardial infarction (MI), dead myocardial tissues are digested by immune cells and replaced by fibrosis, leading to ventricular remodeling and heart failure at the chronic stage. Direct reprogramming of the cardiac fibroblasts (CFs) into induced cardiomyocytes (iCMs) with cardiac transcription factors, including Gata4, Mef2c, and Tbx5 (GMT), may have significant potential for cardiac repair.

Gene expression profiling of α-gustducin-expressing taste cells in mouse fungiform and circumvallate papillae.

Taste buds are complex sensory organs embedded in the epithelium of fungiform papillae (FP) and circumvallate papillae (CV). The sweet, bitter, and umami tastes are sensed by type II taste cells that express taste receptors (Tas1rs and Tas2rs) coupled with the taste G-protein α-gustducin. Recent studies revealed that the taste response profiles of α-gustducin-expressing cells are different between FP and CV, but which genes could generate such distinctive cell characteristics are still largely unknown.

Simultaneous Aortic Valve-in-Valve and Ascending Stent Grafting for Prosthetic Valve Stenosis and Ascending Flap.

Report on total endovascular repair for a diseased aortic valve and the ascending aorta is few. Therefore, we report a case of prosthetic aortic valve stenosis and internal bovine pericardial flap after ascending aortic replacement complicated by congestive heart failure and hemolysis. Because the patient had high surgical risk and was anatomically suitable to undergo ascending endovascular repair, simultaneous transcatheter aortic valve-in-valve implantation and ascending endografting were performed.

Drinking Ice-Cold Water Reduces the Severity of Anticancer Drug-Induced Taste Dysfunction in Mice.

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders.

Transcatheter aortic valve replacement as a bridge to surgical aortic valve replacement in a younger patient with extremely high surgical risk.

A 50-year-old man with decompensated aortic stenosis displayed significantly reduced ejection fraction, an ascending aortic aneurysm (55 mm in diameter), and bilateral giant bullae, and was evaluated as having extremely high surgical risk. Therefore, as a bridge to definitive treatment, he simultaneously underwent transcatheter aortic valve replacement (TAVR) and upper left lung lobectomy. His heart function recovered 6 months later and he underwent surgical aortic valve replacement (SAVR) and graft replacement of the ascending aorta.

Renin-angiotensin system inhibitors and the severity of coronavirus disease 2019 in Kanagawa, Japan: a retrospective cohort study.

Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak initiated on the Diamond Princess Cruise Ship at Yokohama harbor in February 2020, we have been doing our best to treat COVID-19 patients. In animal experiments, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are reported to suppress the downregulation of angiotensin converting enzyme 2 (ACE2), and they may inhibit the worsening of pathological conditions. We aimed to examine whether preceding use of ACEIs and ARBs affected the clinical manifestations and prognosis of COVID-19 patients.

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure.

Background: It remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression.

Methods And Results: Patients with HF with repetitive IRVF evaluations were enrolled.