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Quercetin and its glycosides possess various health beneficial functions, but comparative study of them on energy metabolism in different tissues are not well studied. In this study, we investigated AMP-activated protein kinase regulated glucose metabolism in the skeletal muscle and lipid metabolism in the white adipose tissue and liver to compare the effectiveness of quercetin and its glycosides, namely isoquercitrin, rutin, and enzymatically modified isoquercitrin, in male ICR mice. The mice were fed a standard or high-fat diet supplemented with 0.1% quercetin and its glycosides for 13 weeks. Quercetin glycosides, but not quercetin, decreased body weight gain and fat accumulation in the mesenteric adipose tissue in high-fat groups. All compounds decreased high-fat diet-increased plasma glucose and insulin levels. Moreover, all compounds significantly increased AMP-activated protein kinase phosphorylation in either standard or high-fat diet-fed mice in all tissues tested. As its downstream events, all compounds induced glucose transporter 4 translocation in the muscle. In the white adipose tissue and liver, all compounds increased lipogenesis while decreased lipolysis. Moreover, all compounds increased browning markers and decreased differentiation markers in adipose tissue. Therefore, quercetin and its glycosides are promising food components for prevention of adiposity and hyperglycemia through modulating AMP-activated protein kinase-driven pathways.

Quercetin possesses various health beneficial functions, but its poor bioavailability limits these functions. Enzymatically modified isoquercitrin (EMIQ) is a quercetin glycoside with a greater bioavailability than quercetin. In this study, we investigated whether EMIQ regulates energy metabolism in mice and its underlying molecular mechanism. Male C57BL/6 mice were fed a normal diet with different doses of EMIQ or quercetin (0.02%, 0.1% and 0.5%) for two weeks. Supplementation with 0.1% EMIQ significantly decreased white adipose tissue (WAT) weight. Supplementation with 0.02% and 0.1% EMIQ promoted phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in the WAT, liver, and muscle. In the WAT, 0.1% EMIQ downregulated peroxisome proliferator-activated receptor (PPAR)γ, CCAAT-enhancer-binding protein (C/EBP)α, C/EBPβ, and sterol regulatory element-binding protein 1 expression, as well as upregulated mitochondrial uncoupling protein (UCP) 2 and carnitine palmitoyltransferase-1 expression. Supplementation with 0.1% EMIQ also promoted the expression of thermogenesis-associated factors including PPARγ coactivator α (PGC-1α), UCP1, PR-domain containing protein 16, and sirtuin 1 in the WAT. In the liver, EMIQ promoted the phosphorylation of acetyl-CoA carboxylase, and increased the expression of PPARα, constitutive androstane-receptor, and farnesoid X receptor. Furthermore, supplementation with 0.02% or 0.1% EMIQ suppressed the plasma glucose level accompanied by the translocation of glucose transporter 4 to the plasma membrane of the muscle. Our results suggest that EMIQ is a potential food additive for the regulation of energy metabolism through AMPK phosphorylation.

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Papillary thyroid carcinoma arising from ovarian mature cystic teratoma is clinically rare. We herein present a case of live birth following two laparoscopic surgeries for papillary thyroid carcinoma arising in a mature ovarian cystic teratoma. A 30-year-old female patient, gravida 1 para 1, was treated by laparoscopic bilateral ovarian cystectomy for suspicion of bilateral mature cystic teratoma. The diagnosis of papillary thyroid carcinoma arising from right ovarian mature cystic teratoma was established based on postoperative pathological examination of the tumor. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. The patient underwent laparoscopic fertility-preserving unilateral (right) salpingo-oophorectomy. Following an extensive discussion with the patient and her family, appropriate informed consent was obtained for the treatment option and the patient and her family chose to preserve her fertility. She could have a baby following the treatment and no evidence of disease for 6 years. Gynecologists should be aware of the possibility of such rare cases, and the available surgical interventions should be fully discussed with patients who wish to preserve their fertility. Laparoscopic fertility-sparing surgery may be a feasible option when encountering such a rare condition.

Non-neural granular cell tumors (GCTs) are clinically rare, whereas cases arising in the uterine corpus are exceedingly rare. Only three uterine cervical cases of GCTs have been reported to date and, to the best of our knowledge, there are no reports of GCT of the uterine corpus in the literature. We herein describe the first case of non-neural GCT arising from the uterine corpus reported to date. A 55-year-old premenopausal woman was referred to the Department of Obstetrics and Gynecology of Hashimoto Municipal Hospital (Wakayama, Japan) with a suspected uterine tumor. The tumor presented as a uterine leiomyoma-like mass on radiological examinations, but the diagnosis of non-neural GCT was established based on pathological and immunohistochemical examinations. Microscopically, histological examination of the entire surgical specimen revealed large polygonal cells with abundant eosinophilic granular cytoplasm and round to oval nuclei. Immunohistochemistry revealed positive periodic acid-Schiff staining of the cytoplasmic granules, which was resistant to diastase. In addition, the tumor cells stained positive for CD68, but negative for S-100, neuron-specific enolase, cytokeratin, CD34, α-smooth muscle actin, desmin, estrogen receptor and progesterone receptor. It is important for gynecologists to be aware of the possibility of non-neural GCT of the uterine corpus, for which accurate diagnosis, complete resection and long-term follow-up are crucial, as it may be easily misdiagnosed as uterine leiomyoma.

BackgroundDietary management is highly important for the maintenance of renal function in patients with chronic kidney disease (CKD). Cerebral oxygen saturation (rSO2) was reportedly associated with the estimated glomerular filtration rate (eGFR) and cognitive function. However, data concerning the association between cerebral rSO2 and dietary intake of CKD patients is limited.MethodsThis was a single-center observational study. We recruited 67 CKD patients not undergoing dialysis. Cerebral rSO2 was monitored using the INVOS 5100c oxygen saturation monitor. Energy intake was evaluated by dietitians based on 3-day meal records. Daily protein and salt intakes were calculated from 24-h urine collection.ResultsMultivariable regression analysis showed that cerebral rSO2 was independently associated with energy intake (standardized coefficient: 0.370) and serum albumin concentration (standardized coefficient: 0.236) in Model 1 using parameters with p < 0.10 in simple linear regression analysis (body mass index, Hb level, serum albumin concentration, salt and energy intake) and confounding factors (eGFR, serum sodium concentration, protein intake), and the energy/salt index (standardized coefficient: 0.343) and Hb level (standardized coefficient: 0.284) in Model 2 using energy/protein index as indicated by energy intake/protein intake and energy/salt index by energy intake/salt intake in place of salt, protein and energy intake.ConclusionsCerebral rSO2 is affected by energy intake, energy/salt index, serum albumin concentration and Hb level. Sufficient energy intake and adequate salt restriction is important to prevent deterioration of cerebral oxygenation, which might contribute to the maintenance of cognitive function in addition to the prevention of renal dysfunction in CKD patients.

Synovial sarcoma is clinically rare, and cases of synovial sarcoma arising in the omentum are particularly rare. Only 3 cases have been reported in the literature to dtae, and they were associated with a poor prognosis. We herein report a rare case of aggressive primary omental synovial sarcoma presenting as an ovarian malignancy. A 53-year-old multigravida woman was referred to our hospital due to progressive abdominal distension. Magnetic resonance imaging revealed a large heterogeneous mass with an irregular component occupying the lower abdominal cavity, with an intact uterus. Intraoperative examination revealed a solid mass arising from the lower omentum. The diagnosis of omental synovial sarcoma was established based on postoperative pathological and immunohistochemical examination of the tumor. The patient underwent multiple surgical resection procedures due to the development of metastases in the liver, lungs and abdominal cavity and received adjuvant chemotherapy including doxorubicin-ifosfamide, pazopanib and trabectedin. Such rare neoplasms may be difficult to diagnose preoperatively based on radiological examinations alone. Thus, gynecologists should be aware of the possibility of omental synovial sarcoma, and combined surgical and chemotherapeutic interventions are required to control such aggressive tumors.

Although toxic shock syndrome (TSS) is rare, multiorgan failure can occur without early identification and appropriate therapy. In particular, a few cases of postpartum TSS due to methicillin-resistant Staphylococcus aureus (MRSA) have been reported. Here, we describe a rare case in which a 32-year-old Japanese woman had TSS due to MRSA that was caused by a perineal infection after a normal vaginal delivery. Twelve days after giving birth to a healthy child, she was readmitted to our hospital due to a 2-day fever and perineal pain without uterine tenderness. She developed emesis and watery diarrhea on the night of admission. On the second day, a diffuse cutaneous macular rash appeared over her trunk. Laboratory data revealed deteriorated renal function and thrombocytopenia. Her history and clinical results were compatible with a typical course of TSS. Administration of ceftriaxone and clindamycin was started immediately after admission and was effective. The patient recuperated steadily over the next week with desquamation of the skin. MRSA was isolated from her vaginal discharge and was found to produce TSS toxin 1 (TSST-1). Furthermore, since MRSA was not detected in the nasal and vaginal cavity during pregnancy, it suggests that vaginal colonization can also occur postpartum and be the disease source in mothers. Therefore, MRSA infections should be considered when treating for postpartum TSS.

Correlations between mammalian target of rapamycin (mTOR) expression, and clinicopathological features, outcome and Akt expression in endometrial endometrioid adenocarcinoma (EEC) were investigated. Tumour samples were obtained from 82 patients with EEC who had undergone hysterectomy, and phosphorylated mTOR (p-mTOR) and Akt (p-Akt) expression in the cytoplasm and nucleus was analysed by immunohistochemical staining. Nuclear p-mTOR was significantly elevated in poorly differentiated tumours and positively correlated with lymph node involvement (P = 0.05). Nuclear p-mTOR expression was associated with significantly shorter relapse-free survival (RFS) (P < 0.01) and slightly shorter overall survival (OS) (P = 0.08). Cytoplasmic expression of p-mTOR was not correlated with any clinicopathological factors. Although not significant, cytoplasmic p-mTOR expression was associated with shorter PFS and OS (P = 0.09, P = 0.283, respectively). Neither cytoplasmic nor nuclear p-Akt expression was associated with clinicopathological factors or with survival. Localisation of p-mTOR may be critical for tumour progression and outcomes in patients with EEC.

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.

[1] The Japan Meteorological Agency (JMA) has started the practical service of Earthquake Early Warning (EEW) and a very dense deployment of receiving units is expected in the near future. The receiving/alarm unit of an EEW system is equipped with a CPU and memory and is on-line via the internet. By adding an inexpensive seismometer and A/D converter, this unit is transformed into a real-time seismic observatory, which we are calling a home seismometer. If the home seismometer is incorporated in the standard receiving unit of EEW, then the number of seismic observatories will be drastically increased. Since the background noise inside a house caused by human activity may be very large, we have developed specialized software for on-site warning using the home seismometer. We tested our software and found that our algorithm can correctly distinguish between noise and earthquakes for nearly all the events.

The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant condition that confers a predisposition to multiple tumors of the skin appendages. CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis. Expression of CYLD has been detected in various organs, but its expression in salivary gland tumor (SGT) is still unknown. Adenoid cystic carcinoma (ACC) is a well known and typical malignant SGT ACC was previously known as cylindroma in view of its marked histological resemblance to dermal cylindroma. In this study, the expressions of CYLD and NF-kappaB mRNA in HSG, a human SGT cell line, were found to be increased by TNF-alpha stimulation. Immunohistochemistry clearly demonstrated the expression of CYLD and NF-kappaB-related factors in ACC tissue.

Etude du mecanisme par lequel le lycoricidinol isole des bulbes de lycoris radiata supprime l'induction de la production d'ethylene par l'auxine chez Vigna radiata