Pulse-Driven Magnetoimpedance Sensor Detection of Cardiac Magnetic Activity

This study sought to establish a convenient method for detecting biomagnetic activity in the heart. Electrical activity of the heart simultaneously induces a magnetic field. Detection of this magnetic activity will enable non-contact, noninvasive evaluation to be made. We improved the sensitivity of a pulse-driven magnetoimpedance (PMI) sensor, which is used as an electric compass in mobile phones and as a motion sensor of the operation handle in computer games, toward a pico-Tesla (pT) level, and measured magnetic fields on the surface of the thoracic wall in humans. The changes in magnetic field detected by this sensor synchronized with the electric activity of the electrocardiogram (ECG). The shape of the magnetic wave was largely altered by shifting the sensor position within 20 mm in parallel and/or perpendicular to the thoracic wall. The magnetic activity was maximal in the 4th intercostals near the center of the sterna. Furthermore, averaging the magnetic activity at 15 mm in the distance between the thoracic wall and the sensor demonstrated magnetic waves mimicking the P wave and QRS complex. The present study shows the application of PMI sensor in detecting cardiac magnetic activity in several healthy subjects, and suggests future applications of this technology in medicine and biology

Metabolomics reveals inosine 5′-monophosphate is increased during mice adipocyte browning

Adipocyte browning is one of the potential strategies for the prevention of obesity-related metabolic syndromes, but it is a complex process. Although previous studies make it increasingly clear that several transcription factors and enzymes are essential to induce browning, it is unclear what dynamic and metabolic changes occur in induction of browning. Here, we analyzed the effect of a beta-adrenergic receptor agonist (CL316243, accelerator of browning) on metabolic change in mice adipose tissue and plasma using metabolome analysis and speculated that browning is regulated partly by inosine 5'-monophosphate (IMP) metabolism. To test this hypothesis, we investigated whether Ucp-1, a functional marker of browning, mRNA expression is influenced by IMP metabolism using immortalized adipocytes. Our study showed that mycophenolic acid (MPA), an IMP dehydrogenase inhibitor, increases the mRNA expression of Ucp-1 in immortalized adipocytes. Furthermore, we performed a single administration of mycophenolate mofetil (MMF), a prodrug of MPA, to mice and demonstrated that MMF induces adipocyte browning and miniaturization of adipocyte size, leading to adipose tissue weight loss. These findings showed that IMP metabolism has a significant effect on adipocyte browning, suggesting that the regulator of IMP metabolism has the potential to prevent obesity

A case of an advanced renal collecting duct carcinoma in which initial therapeutic effect was achieved with pembrolizumab plus axitinib

Introduction Renal collecting duct carcinoma is often found in advanced cancers and has a poor prognosis. Here, we present the case of symptomatic metastatic collecting duct carcinoma in which we observed an initial therapeutic effect of immune checkpoint inhibitors plus tyrosine kinase inhibitors. Case presentation The patient was a 69‐year‐old male who was referred to our hospital for examination of a right chest tumor and related pain. Contrast‐enhanced computed tomography and tumor biopsy were performed, leading to a diagnosis of collecting duct carcinoma. A combination of pembrolizumab plus axitinib was initiated as first‐line therapy; right chest pain decreased, and tumor shrinkage was observed. Seven months after treatment initiation, tumor progression was noted. Cabozantinib was initiated as second‐line therapy; however, was discontinued due to patient fatigue. The patient died 15 months after the initiation of treatment. Conclusion For symptomatic metastatic collecting duct carcinoma, pembrolizumab plus axitinib may have initial therapeutic effects

Integration of bioassay and non-target metabolite analysis of tomato reveals that β-carotene and lycopene activate the adiponectin signaling pathway, including AMPK phosphorylation.

Adiponectin, an adipokine, regulates glucose metabolism and insulin sensitivity through the adiponectin receptor (AdipoR). In this study, we searched for metabolites that activate the adiponectin signaling pathway from tomato (Solanum lycopersicu). Metabolites of mature tomato were separated into 55 fractions by liquid chromatography, and then each fraction was examined using the phosphorylation assay of AMP-protein kinase (AMPK) in C2C12 myotubes and in AdipoR-knockdown cells by small interfering RNA (siRNA). Several fractions showed AMPK phosphorylation in C2C12 myotubes and siRNA-mediated abrogation of the effect. Non-targeted metabolite analysis revealed the presence of 721 diverse metabolites in tomato. By integrating the activity of fractions on AMPK phosphorylation and the 721 metabolites based on their retention times of liquid chromatography, we performed a comprehensive screen for metabolites that possess adiponectin-like activity. As the screening suggested that the active fractions contained four carotenoids, we further analyzed β-carotene and lycopene, the major carotenoids of food. They induced AMPK phosphorylation via the AdipoR, Ca2+/calmodulin-dependent protein kinase kinase and Ca2+ influx, in addition to activating glucose uptake via AdipoR in C2C12 myotubes. All these events were characteristic adiponectin actions. These results indicated that the food-derived carotenoids, β-carotene and lycopene, activate the adiponectin signaling pathway, including AMPK phosphorylation

The Mevalonate Pathway Is Indispensable for Adipocyte Survival

Summary: The mevalonate pathway is essential for the synthesis of isoprenoids and cholesterol. Adipose tissue is known as a major site for cholesterol storage; however, the role of the local mevalonate pathway and its synthesized isoprenoids remains unclear. In this study, adipose-specific mevalonate pathway-disrupted (aKO) mice were generated through knockout of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR). aKO mice showed serious lipodystrophy accompanied with glucose and lipid metabolic disorders and hepatomegaly. These metabolic variations in aKO mice were dramatically reversed after fat transplantation. In addition, HMGCR-disrupted adipocytes exhibited loss of lipid accumulation and an increase of cell death, which were ameliorated by the supplementation of mevalonate and geranylgeranyl pyrophosphate but not farnesyl pyrophosphate and squalene. Finally, we found that apoptosis may be involved in adipocyte death induced by HMGCR down-regulation. Our findings indicate that the mevalonate pathway is essential for adipocytes and further suggest that this pathway is an important regulator of adipocyte turnover. : Pathophysiology; Molecular Mechanism of Behavior; Diabetology; Specialized Functions of Cells Subject Areas: Pathophysiology, Molecular Mechanism of Behavior, Diabetology, Specialized Functions of Cell

LC-MS analysis data of Hexane III—HPLC fraction.

<p>LC-MS analysis data of Hexane III—HPLC fraction.</p

LC-MS analysis data of 90%MeOH IV—HPLC fraction.

<p>LC-MS analysis data of 90%MeOH IV—HPLC fraction.</p