Designing a novel photoinduced electron transfer-based small-molecule fluorescent probe specific for CYP3A isozymes.

Cytochrome P450 (CYPs) are oxidoreductases distributed in various tissues in plants and animals. Among the CYP families, CYP3A is the most abundant in vivo, particularly in humans, and it is involved in the metabolism of many drugs. It is crucial to measure CYP3A activity for both pharmaceuticals and agrochemicals because inhibition or induction of this enzyme can seriously affect the occurrence of toxicity or efficacy.

Below-the-elbow intervention for Buerger's disease.

An increasing attention has been paid to endovascular therapy for lower limb ischemia in patients with Buerger's disease. However, critical hand ischemia in Buerger's disease patients has been underappreciated despite a tremendous advancement of endovascular therapy for peripheral arterial disease. Herein, we describe endovascular "hand" salvage with a below-the-elbow intervention.

Effect of single tibial artery revascularization on microcirculation in the setting of critical limb ischemia.

Background: Benefits of 2-dimensional (2D) angiosome-oriented infrapopliteal revascularization remain controversial. The aim of this retrospective study was to clarify the effect of single tibial artery revascularization on the dorsal and plantar microcirculation of critically ischemic limbs based on skin perfusion pressure (SPP).

Methods And Results: Fifty-seven interventions that only involved either anterior tibial artery (ATA) or posterior tibial artery (PTA) revascularization were included in this study.

Vasospastic limb ischemia presenting acute and chronic limb ischemia.

Vasospastic limb ischemia might have been underappreciated compared to vasospasm in other territories such as heart and brain. However, an increasing awareness of this vascular disorder can be translated to an improved patients' care. Herein, we report a case of vasospasm presenting acute and chronic limb ischemia in four extremities.

Contemporary crossing techniques for infrapopliteal chronic total occlusions.

The synergism of technical refinement and advanced technology has significantly increased the popularity of infrapopliteal intervention. Since chronic total occlusion (CTO) is a common disorder among patients with symptomatic infrapopliteal artery disease, infrapopliteal CTO intervention is now evolving rapidly in the field of endovascular intervention. Guidewire crossing through the CTO is essential for a successful procedure.

Impact of aortorenal morphology on renal artery stent procedures: significance of aortic tortuosity and renal artery derivation.

Purpose: To clarify the impact of aortorenal morphology on renal artery stenting procedures.

Methods: A retrospective study evaluated 142 consecutive renal artery stenting procedures performed for de novo atherosclerotic renal artery stenosis in 119 patients (62 men; mean age 72±9 years, range 41-93). All procedures were done via a transfemoral approach without distal protection.

Endovascular recanalization of failed distal bypass in Buerger's disease.

In the treatment of Buerger's disease, bypass surgery with the use of an autologous vein has served as a treatment option in cases in which distal target vessel has been available. However, failed bypass occlusion can result in a devastating clinical scenario. Herein, we report a successful endovascular revascularization of failed distal bypass graft as a last resort for a patient with Burger's disease with ischemic rest pain and extensive tissue loss.

A novel selective androgen receptor modulator, NEP28, is efficacious in muscle and brain without serious side effects on prostate.

Age-related androgen depletion is known to be a risk factor for various diseases, such as osteoporosis and sarcopenia. Furthermore, recent studies have demonstrated that age-related androgen depletion results in accumulation of β-amyloid protein and thereby acts as a risk factor for the development of Alzheimer's disease. Supplemental androgen therapy has been shown to be efficacious in treating osteoporosis and sarcopenia.

Subintimal angioplasty of lengthy femorotibial total occlusion in Buerger's disease.

Purpose: To report successful subintimal angioplasty of a lengthy femorotibial occlusion in a patient with Buerger's disease, with wound healing and limb salvage.

Case Report: A 38-year-old female heavy smoker was referred to our hospital for treatment of extensive infectious tissue loss, with severe foot pain 1 month after early failure of a distal bypass graft. Angiography revealed total occlusion in the femoropopliteal and infrapopliteal arteries.

Discovery of potent and orally bioavailable 17β-hydroxysteroid dehydrogenase type 3 inhibitors.

We have previously reported the discovery of a new class of potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) derived from benzylidene oxazolidinedione and thiazolidinedione scaffolds. In this study, these analogs were designed, synthesized, and evaluated in a human cell-based assay. The detailed structure-activity relationship (SAR) surrounding this pharmacophore were developed, and consequently a number of compounds from this series demonstrated single-digit nanomolar 17β-HDS3 inhibitory activity in vitro.

Identification of oxazolidinediones and thiazolidinediones as potent 17β-hydroxysteroid dehydrogenase type 3 inhibitors.

Novel and potent inhibitors of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) were identified based on oxazolidinedione and thiazolidinedione derivatives, starting from a high-throughput screening hit, 5-(3-bromo-4-hydroxybenzyl)-3-(4-methoxyphenyl)-1,3-thiazol-2-one. 5-(3-Bromo-4-hydroxybenzylidene)-3-(4-methoxyphenyl)-2-thioxo-1,3-thiazolidin-4-one exhibited a promising activity profile and demonstrated significant selectivity over the related 17β-HSD isoenzymes and nuclear receptors.

Coumarins as novel 17beta-hydroxysteroid dehydrogenase type 3 inhibitors for potential treatment of prostate cancer.

The synthesis and SAR studies of 3- and 4-substituted 7-hydroxycoumarins as novel 17beta-HSD3 inhibitors are discussed. The most potent compounds from this series exhibited low nanomolar inhibitory activity with acceptable selectivity versus other 17beta-HSD isoenzymes and nuclear receptors.

Crossveinless-2 controls bone morphogenetic protein signaling during early cardiomyocyte differentiation in P19 cells.

Increasing evidence indicates that bone morphogenetic proteins (BMPs) are crucial for cardiac induction, specification, and development. Although signaling of BMPs is tightly regulated through soluble BMP-binding proteins, how they regulate BMP signaling during cardiac differentiation remains unknown. To identify molecules responsible for BMP signaling during early cardiomyocyte differentiation of P19 cells, cDNA subtraction was performed.

Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling.

Cardiac chamber formation involves dynamic changes in myocardial organization, including trabeculation and expansion of the compact layer. The positional cues that regulate myocardial patterning, however, remain unclear. Through ligation of the Plexin-A1 receptor, the transmembrane-type semaphorin Sema6D regulates endocardial cell migration.

Atrial natriuretic peptide inhibits cardiomyocyte hypertrophy through mitogen-activated protein kinase phosphatase-1.

Cardiac hypertrophy is formed in response to hemodynamic overload. Although a variety of factors such as catecholamines, angiotensin II (AngII), and endothelin-1 (ET-1) have been reported to induce cardiac hypertrophy, little is known regarding the factors that inhibit the development of cardiac hypertrophy. Production of atrial natriuretic peptide (ANP) is increased in the hypertrophied heart and ANP has recently been reported to inhibit the growth of various cell types.