Recent studies have shown that sodium–glucose cotransporter 2 inhibitors decrease the risk of heart failure in patients with type 2 diabetes. However, the precise mechanisms of action of these drugs ...are not well understood. In the present study, we evaluated the effect of treatment with tofogliflozin for 6 months on cardiac and vascular endothelial function in 26 patients with type 2 diabetes and heart diseases. Tofogliflozin treatment significantly decreased left ventricular end‐diastolic dimensions and significantly increased flow‐mediated vasodilation. Although E/e′ did not significantly change after treatment, the decrease observed in the E/e′ ratio was significantly correlated with the increase in acetoacetic acid and 3‐hydroxybutyrate levels. These results suggest that sodium–glucose cotransporter 2 inhibitor might improve left ventricular dilatation and vascular endothelial function in patients with type 2 diabetes. Furthermore, it is suggested that the elevation of ketone bodies induced by sodium–glucose cotransporter 2 inhibitors might contribute to a protective effect in left ventricular diastolic dysfunction.
In this study, we evaluated the effect of treatment with tofogliflozin for 6 months on cardiac and vascular endothelial function in 26 patients with type 2 diabetes and heart diseases. The results suggest that sodium–glucose cotransporter 2 inhibitor might improve left ventricular dilatation and vascular endothelial function in patients with type 2 diabetes. Furthermore, it is suggested that the elevation of ketone bodies induced by sodium–glucose cotransporter 2 inhibitors might contribute to a protective effect in left ventricular diastolic dysfunction.
To determine the comprehensive G protein-coupled receptor (GPCR) expression profile in ghrelin-producing cells and to elucidate the role of GPCR-mediated signaling in the regulation of ghrelin ...secretion, we determined GPCR expression profiles by RNA sequencing in the ghrelin-producing cell line MGN3-1 and analyzed the effects of ligands for highly expressed receptors on intracellular signaling and ghrelin secretion. Expression of selected GPCRs was confirmed in fluorescence-activated cell-sorted fluorescently tagged ghrelin-producing cells from ghrelin-promoter CreERT2/Rosa-CAG-LSL-ZsGreen1 mice. Expression levels of GPCRs previously suggested to regulate ghrelin secretion including adrenergic-β1 receptor, GPR81, oxytocin receptor, GPR120, and somatostatin receptor 2 were high in MGN3-1 cells. Consistent with previous reports, isoproterenol and oxytocin stimulated the Gs and Gq pathways, respectively, whereas lactate, palmitate, and somatostatin stimulated the Gi pathway, confirming the reliability of current assays. Among other highly expressed GPCRs, prostaglandin E receptor 4 agonist prostaglandin E2 significantly stimulated the Gs pathway and ghrelin secretion. Muscarine, the canonical agonist of cholinergic receptor muscarinic 4, stimulated both the Gq and Gi pathways. Although muscarine treatment alone did not affect ghrelin secretion, it did suppress forskolin-induced ghrelin secretion, suggesting that the cholinergic pathway may play a role in counterbalancing the stimulation of ghrelin by Gs (eg, by adrenaline). In addition, GPR142 ligand tryptophan stimulated ghrelin secretion. In conclusion, we determined the comprehensive expression profile of GPCRs in ghrelin-producing cells and identified two novel ghrelin regulators, prostaglandin E2 and tryptophan. These results will lead to a greater understanding of the physiology of ghrelin and facilitate the development of ghrelin-modulating drugs.
We developed and analyzed two types of transgenic mice: rat insulin II promoter-ghrelin transgenic (RIP-G Tg) and rat glucagon promoter-ghrelin transgenic mice (RGP-G Tg). The pancreatic tissue ...ghrelin concentration measured by C-terminal radioimmunoassay (RIA) and plasma desacyl ghrelin concentration of RIP-G Tg were about 1000 and 3.4 times higher than those of nontransgenic littermates, respectively. The pancreatic tissue n-octanoylated ghrelin concentration measured by N-terminal RIA and plasma n-octanoylated ghrelin concentration of RIP-G Tg were not distinguishable from those of nontransgenic littermates. RIP-G Tg showed suppression of glucose-stimulated insulin secretion. Arginine-stimulated insulin secretion, pancreatic insulin mRNA and peptide levels, β cell mass, islet architecture, and GLUT2 and PDX-1 immunoreactivity in RIP-G Tg pancreas were not significantly different from those of nontransgenic littermates. Islet batch incubation study did not show suppression of insulin secretion of RIP-G Tg in vitro. The insulin tolerance test showed lower tendency of blood glucose levels in RIP-G Tg. Taking lower tendency of triglyceride level of RIP-G Tg into consideration, these results may indicate that the suppression of insulin secretion is likely due to the effect of desacyl ghrelin on insulin sensitivity. RGP-G Tg, in which the pancreatic tissue ghrelin concentration measured by C-RIA was about 50 times higher than that of nontransgenic littermates, showed no significant changes in insulin secretion, glucose metabolism, islet mass, and islet architecture. The present study raises the possibility that desacyl ghrelin may have influence on glucose metabolism.
With its long operating range and ability to be used in a turbid environment, sonar sensor is mainly used to explore underwater environment. As a result, many algorithms based on the sonar have been ...developed. However, in the case of a multi-beam sonar, its mechanism causes crosstalk noise around the underwater object, which degrades the accuracy of these algorithms. In this paper, we propose a method to remove crosstalk noise from a sonar image by detecting the region where the crosstalk noise occurred using a convolutional neural network and filling the detected region with adjacent pixel values. The proposed method could accurately and effectively detect and remove crosstalk noise in a given sonar image. Therefore, the accuracy of the sonar-based algorithms such as a 3-D reconstruction of underwater terrain can be improved.
Ghrelin is a 28-amino acid peptide that regulates GH release together with GHRH and somatostatin. The expression of ghrelin has been detected in the stomach, small intestine, hypothalamus, pituitary ...gland, kidney, placenta, and testis. Recently it was reported that ghrelin is present in pancreatic α-cells and that it stimulates insulin secretion. In this study, we examined the ghrelin expression in two cases of glucagonoma and two cases of insulinoma by Northern blot analysis and immunohistochemistry. Ghrelin expression was identified in a case of glucagonoma associated with multiple endocrine neoplasm type I both by Northern blot analysis using total RNA and by immunohistochemistry, although the plasma ghrelin level was not elevated. This is the first case of tumor in which ghrelin gene expression was detected by Northern blot analysis using total RNA.
Background
Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non‐small cell lung cancer (NSCLC). This study ...aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement.
Methods
This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software.
Results
A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI‐OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression‐free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p‐value <0.001). ICI‐OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD‐L1 expression lower than 50%, more than three metastatic sites, neutrophil‐to‐lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv.
Conclusions
There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.
Our study evaluated hyperprogression in non‐small cell lung cancer patients treated with immune‐checkpoint inhibitor using a semiautomatic volume measurement. Patients experiencing hyperprogression by volumetric measurement had significantly worse progression‐free survival and overall survival after the initiation of immune‐checkpoint inhibitor than patients without it.
To distinguish true red tide water (particularly
Cochlodinium polykrikoides
blooms) from non-red tide water (false satellite high chlorophyll water) in the South Sea of Korea, we developed a ...systematic classification method using spectral information from MODIS level products and applied it to five different harmful algal bloom events. Red tide and nonred tide waters were classified based on four different criteria. The first step revealed that the radiance peaks of potential red tide water occurred at 555 and 678 nm. The second step separated optically different waters that were influenced by relatively low and high contributions of colored dissolved organic matter (CDOM) (including detritus) to chlorophyll. The third and fourth steps discriminated red tide water from non-red tide water based on the blue-to-green ratio in areas with lower and higher contributions of CDOM to chlorophyll, respectively. After applying the red tide classification (using the four criteria), the spectral response of the red tide water, which is influenced by pigment concentration, showed different slopes for the blue and green bands (lower slope at blue bands and higher slope at green bands). The opposite result was found for non-red tide water, due to decreasing phytoplankton absorption and increasing detritus/CDOM absorption at blue bands. The results were well matched with the discoloration of water (blue to dark red/brown) and delineated the areal coverage of
C. polykrikoides
blooms, revealing the nature of spatial and temporal variations in red tides. This simple spectral classification method led to increase user accuracy for
C. polykrikoides
and non-red tide blooms (>46% and >97%) and provided a more reliable and robust identification of red tides over a wide range of oceanic environments than was possible using chlorophyll
a
concentration, chlorophyll anomaly, fluorescence analysis, or proposed red tide detection algorithms.
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