Antidiabetic Effect of Fermented Mesembryanthemum crystallinum L. in db/db Mice Involves Regulation of PI3K-Akt Pathway.

Type 2 diabetes (T2D) is a serious health issue with increasing incidences worldwide. However, current medications have limitations due to side effects such as decreased appetite, stomach pain, diarrhea, and extreme tiredness. Here, we report the effect of fermented ice plant (FMC) in the T2M mouse model of db/db mice. FMC showed a greater inhibition of lipid accumulation compared to unfermented ice plant extract. Two-week oral administration with FMC inhibited body weight gain, lowered fasting blood glucose, and improved glucose tolerance. Serum parameters related to T2D including insulin, glycosylated hemoglobin, adiponectin, and cholesterols were improved as well. Histological analysis confirmed the protective effect of FMC on pancreas and liver destruction. FMC treatment significantly increased the expression and phosphorylation of IRS-1, PI3K, and AKT. Additionally, AMP-activated protein kinase phosphorylation and nuclear factor erythroid 2-related factor 2 were also increased in the liver tissues of db/db mice treated with FMC. Overall, our results indicate the anti-diabetic effect of FMC; therefore, we suggest that FMC may be useful as a therapeutic agent for T2D.

Structure and substrate specificity determinants of NfnB, a dinitroaniline herbicide-catabolizing nitroreductase from Sphingopyxis sp. strain HMH.

Nitroreductases are emerging as attractive bioremediation enzymes, with substrate promiscuity toward both natural and synthetic compounds. Recently, the nitroreductase NfnB from Sphingopyxis sp. strain HMH exhibited metabolic activity for dinitroaniline herbicides including butralin and pendimethalin, triggering the initial steps of their degradation and detoxification. However, the determinants of the specificity of NfnB for these herbicides are unknown. In this study, we performed structural and biochemical analyses of NfnB to decipher its substrate specificity. The homodimer NfnB is a member of the PnbA subgroup of the nitroreductase family. Each monomer displays a central α + ß fold for the core domain, with a protruding middle region and an extended C-terminal region. The protruding middle region of Val75-Tyr129 represents a structural extension that is a common feature to members of the PnbA subgroup and functions as an opening wall connecting the coenzyme FMN-binding site to the surface, therefore serving as a substrate binding site. We performed mutational, kinetic, and structural analyses of mutant enzymes and found that Tyr88 in the middle region plays a pivotal role in substrate specificity by determining the dimensions of the wall opening. The mutation of Tyr88 to phenylalanine or alanine caused significant changes in substrate selectivity toward bulkier dinitroaniline herbicides such as oryzalin and isopropalin without compromising its activity. These results provide a framework to modify the substrate specificity of nitroreductase in the PnbA subgroup, which has been a challenging issue for its biotechnological and bioremediation applications.

Inflammatory cytokines and retinal nonperfusion area in quiescent proliferative diabetic retinopathy.

PURPOSE: We sought to investigate the association between inflammatory cytokine levels and retinal capillary nonperfusion area in eyes with quiescent proliferative diabetic retinopathy (PDR). METHODS: Samples of aqueous humor were collected from 67 eyes (n = 42 patients) with treatment-naïve PDR. Levels of interleukin (IL)-10, IL-1ß, IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor-α (TNF-α) were obtained using multiplex bead assay. Areas of capillary nonperfusion at the posterior pole and peripheral retina were measured via ultra-widefield fluorescein angiography and correlated with cytokine levels. RESULTS: The levels of IL-10, IL-6, IL-8, MCP-1, and TNF-α were positively correlated with the nonperfusion area of the peripheral retina (r = 0.298, 0.401, 0.265, 0.435, and 0.393; all P ≤ 0.030). There were positive correlations between IL and 10, IL-6, IL-8, MCP-1, and TNF-α (all R ≥ 0.247; all P ≤ 0.043). IL-1ß did not show a significant correlation with the nonperfusion area (P = 0.972 for posterior pole and 0.392 for periphery) but was positively correlated with TNF-α (r = 0.334; P = 0.006). CONCLUSIONS: An increased level of inflammation was observed in PDR eyes with larger nonperfusion areas, which suggests inflammation as a possible target for suppressing PDR progression associated with nonperfusion.

Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α.

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1ß, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.

Estimation of Thermal Sensation Based on Wrist Skin Temperatures.

Thermal comfort is an essential environmental factor related to quality of life and work effectiveness. We assessed the feasibility of wrist skin temperature monitoring for estimating subjective thermal sensation. We invented a wrist band that simultaneously monitors skin temperatures from the wrist (i.e., the radial artery and ulnar artery regions, and upper wrist) and the fingertip. Skin temperatures from eight healthy subjects were acquired while thermal sensation varied. To develop a thermal sensation estimation model, the mean skin temperature, temperature gradient, time differential of the temperatures, and average power of frequency band were calculated. A thermal sensation estimation model using temperatures of the fingertip and wrist showed the highest accuracy (mean root mean square error [RMSE]: 1.26 ± 0.31). An estimation model based on the three wrist skin temperatures showed a slightly better result to the model that used a single fingertip skin temperature (mean RMSE: 1.39 ± 0.18). When a personalized thermal sensation estimation model based on three wrist skin temperatures was used, the mean RMSE was 1.06 ± 0.29, and the correlation coefficient was 0.89. Thermal sensation estimation technology based on wrist skin temperatures, and combined with wearable devices may facilitate intelligent control of one's thermal environment.

Electrochemical analysis based on nanoporous structures.

Analytical applications and the underlying principles of unique electrochemistry in nanoporous structures are reviewed and discussed. In addition to the conventional concept of enlarged surface area, the structural effects of nanoporous materials can play significant roles such as discriminative electrokinetics, the nano-confinement effect, electrical double layer overlapping, ion-selective impedance, etc. The applications described in this review article include solid-state pH sensors, miniaturized pseudo-reference electrodes, nonenzymatic glucose monitoring, ion diodes, transistors, extracellular neural probes, and a few more. Further intensive research is required to develop creative analytical tools based on nanoporous structures and to unravel the underlying physicochemical principles.

Effects of exercise training at lactate threshold and detraining for 12 weeks on body composition, aerobic performance, and stress related variables in obese women.

PURPOSE: The purpose of this study was to investigate the effect of diet plus exercise training and detraining for 12 weeks on body composition, aerobic performance, and stress-related variables in obese women. METHODS: Twenty-five women in their 20s-40s with 30% body fat and body mass indices above 25 kg/m2 were divided into HRLT (heart rate at lactate threshold) and HRLT + 5% groups. Dietary intervention of 70% recommended dietary allowance (RDA) and exercise treatment composed of aerobic exercises on a bicycle (30 min) and treadmill (30 min) were then performed. These interventions were performed three times a week for 12 weeks. RESULTS: Dietary intake was significantly decreased, while daily activity significantly increased within the 12-week intervention period, and this effect was sustained after 12 weeks of detraining. Exercise training based on dietary intake and daily activity presented a significantly decreased weight and % body fat, improvement of aerobic performance, and a significant increase in heart rate variability (HRV) (e.g., average of all RR intervals and the square root mean squared differences of successive RR intervals) as stress-related variables. It was also confirmed that the improvement of body composition and stress-related variables were maintained even after detraining. CONCLUSION: Our results suggest that 70% RDA of dietary intervention and exercise training corresponding to HRLT and HRLT + 5% for 12 weeks were effective in improving body composition and aerobic performance, and relieving stress. In particular, enhanced HRV persisted for up to 12 weeks after the end of exercise training in obese women.

Cuff-Less Blood Pressure Estimation Using Pulse Waveform Analysis and Pulse Arrival Time.

Using the massive MIMIC physiological database, we tried to validate pulse wave analysis (PWA) based on multiparameters model whether it can continuously estimate blood pressure (BP) values on single site of one hand. In addition, to consider the limitation of insufficient data acquirement for home user, we used pulse arrival time (PAT) driven BP information to determine the individual scale factors of the PWA-BP estimation model. Experimental results indicate that the accuracy of the average regression model has error standard deviations of  mmHg (PAT),  mmHg (PWA) for SBP and  mmHg (PAT),  mmHg (PWA) for DBP on 23 subjects over a 1 day period. We defined a local-model which is extracted regression model from sparsely selected small dataset, contrast to full dataset for 24h (average-model). The limit of BP estimation accuracy from the local-model of PWA is lower than that of PAT-BP average-model. Whereas the error of the BP estimation local-model was reduced using more data for scaling, it required more than four times the 1 min data extracted over the 12 h calibration period to predict BP for 1 day. This study shows that PWA has possibility to estimate BP value and PAT-driven BP information could be used to determine the individual scale factors of the PWA-BP estimation model for home users.

Nonenzymatic continuous glucose monitoring in human whole blood using electrified nanoporous Pt.

This paper describes the first devised method for the nonenzymatic and electrochemical glucose monitoring in 100% human whole blood and serum. The nanoporous Pt electrode allows for the selective amplification of glucose oxidation in the presence of electroactive interfering species without the need for enzymatic reaction. The outer membrane was particularly optimized to allow glucose molecules to be electrochemically detected against the numerous constituents of human blood. The proposed sensor provided reproducible amperometric responses to glucose in human serum and whole blood. Its sensitivity was maintained for at least 7h under constantly electrified conditions, and continued to work properly after 30 days of storage in human whole blood and serum. Unlike the enzyme-based glucose sensors, it was found to be minimally affected by thermal fluctuation, so as to remain successful even after steam sterilization at high temperature (134 °C) and pressure (0.22 Mpa). The unprecedented long-term stability and sterilization compatibility observed herein suggest a promising alternative to conventional enzymatic glucose sensors for many analytical and clinical applications, particularly for continuous glucose monitoring devices designed to potentially lead to a closed-loop artificial pancreas by combining them with an insulin pump.

Fermentation enhances the in vitro antioxidative effect of onion (Allium cepa) via an increase in quercetin content.

Yellow onion (Allium cepa) extract showed enhanced antioxidative effects in 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC) and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and acetyl ester (CM-H(2)DCFDA) assay after being treated with a crude enzyme extract from soybean paste fungi, Aspergillus kawachii. HPLC analysis showed two increased and two decreased peaks after enzyme treatment. The decreased peaks were identified as quercetin-3,4'-di-O-ß-d-glucoside (1) and quercetin-4'-O-ß-d-glucoside (2), and peaks that increased were quercetin-3-O-ß-d-glucoside (3) and quercetin (4), respectively. It was expected that 3 and 4 were originated from the glucosidic cleavage of their glucosides, 1 and 2. Among the increased compounds, only quercetin (4) showed strong antioxidative activity in the DPPH assay. In addition, the protective effect against glutamate-induced neurotoxicity in HT22 cells was increased when treated with 25 µg/ml of fermented onion. The enhanced neuroprotective effect was also originated from the increased quercetin content. As a consequence, fermentation raised the quercetin content in onion, and subsequently increased the antioxidative and neuroprotective activities.

Segmentation of solid nodules in ultrasonographic breast image based on wavelet transform.

An accurate segmentation of solid nodules in ultrasonographic (US) breast image is presented. 1-level 2-dimensional Discrete Wavelet Transform (DWT) is used to create features reflecting the texture information of the original image. Using these features, the texture classification is achieved. Finally, solid nodule region is segmented from the classified texture region. Proper threshold for texture classification is automatically decided. Empirically acquired information about the relationship between the texture characteristic of the original image and the optimal threshold is examined and used. Presented algorithm is applied to 284 malignant solid nodules and 300 benign solid nodules and the resulting images are presented.