Targeted Proteomics of Isolated Glomeruli from the Kidneys of Diabetic Rats: Sorbin and SH3 Domain Containing 2 Is a Novel Protein Associated with Diabetic Nephropathy

To evaluate proteins associated with the development of diabetic nephropathy, a major cause of the end-stage renal disease, we analyzed protein expression in isolated glomeruli from spontaneous type 2 diabetic (OLETF) rats and their age-matched control littermates (LETO) in the early and proteinuric stages of diabetic nephropathy using QSTAR Elite LC-MS/MS. Among the 191 and 218 proteins that were altered significantly in the OLETF rats, twenty-four were actin cytoskeleton-associated proteins implicated in the formation of stress fibers, and the impairment of actin polymerization, intermediate filaments and microtubules. Importantly, sorbin and SH3 domain containing 2 (SORBS2), which is involved in the formation of stress fibers, was significantly upregulated in both stages of diabetic nephropathy (1.49- and 1.97-fold, resp.). Immunohistochemical and quantitative-PCR analyses revealed upregulation of SORBS2 in podocytes of glomeruli of OLETF rats. Our findings suggested that SORBS2 may be associated with the development of diabetic nephropathy possibility by reorganization of actin filaments

High-performance Ge/Si electro-absorption optical modulator up to 85°C and its highly efficient photodetector operation

We studied a high-speed Ge/Si electro-absorption optical modulator (EAM) evanescently coupled with a Si waveguide of a lateral p–n junction for a high-bandwidth optical interconnect over a wide range of temperatures from 25 °C to 85 °C. We demonstrated 56 Gbps high-speed operation at temperatures up to 85 °C. From the photoluminescence spectra, we confirmed that the bandgap energy dependence on temperature is relatively small, which is consistent with the shift in the operation wavelengths with increasing temperature for a Ge/Si EAM. We also demonstrated that the same device operates as a high-speed and high-efficiency Ge photodetector with the Franz-Keldysh (F-K) and avalanche-multiplication effects. These results demonstrate that the Ge/Si stacked structure is promising for both high-performance optical modulators and photodetectors integrated on Si platforms

Enhanced Urinary Bladder, Liver and Colon Carcinogenesis in Zucker Diabetic Fatty Rats in a Multiorgan Carcinogenesis Bioassay: Evidence for Mechanisms Involving Activation of PI3K Signaling and Impairment of p53 on Urinary Bladder Carcinogenesis

In the present study, modifying effects of diabetes on carcinogenesis induced in type 2 diabetes mellitus model Zucker diabetic fatty (ZDF) rats were investigated using a multiorgan carcinogenesis bioassay. Our re sults demonstrated enhancement of urinary bladder, colon and liver carcinogenesis in ZDF rats treated with five types of carcinogens (DMBDD). Elevated insulin and leptin and decreased adiponectin levels in the serum may be responsible for the high susceptibility of type 2 diabetes mellitus model rats to carcinogenesis in these organs. Possible mechanisms of increased susceptibility of diabetic rats to bladder carcinogenesis could be activation of the PI3K pathway and suppression of p53 in the urothelium in consequence of the above serum protein alterations

Direct measurement of radial strain in the inner-half layer of the left ventricular wall in hypertensive patients

SummaryBackgroundTwo-dimensional speckle tracking echocardiography (2D-STE) is a novel technology that directly measures regional left ventricular (LV) wall contraction. This study aimed to directly measure inner-layer thickening (radial strain) of the LV using 2D-STE, and to examine the relationship between radial strain and the degree of hypertrophy.MethodsThe study enrolled 63 untreated hypertensive patients with normal geometry (N group, n=32) or concentric hypertrophy (CH group, n=31), classified according to LV mass index (LVMI) and relative wall thickness (RWT). Thirty normotensive subjects (C group, n=30) served as controls. Radial strain (ɛ) in the inner half (ɛi) and all layers of the LV wall (ɛa) were calculated from the LV short-axis view by 2D-STE.ResultsLV ejection fraction did not differ significantly among the groups. However, ɛi and ɛa were significantly lower in the CH group compared with the C and N groups (p<0.01). A ratio of ɛi to ɛa was significantly lower in the CH group compared with the C and N groups (p<0.01). A multivariate regression model that included midwall fractional shortening, E/e′, LVMI, RWT, and LV ejection fraction showed that LVMI (p=0.002) and RWT (p=0.014) were independent predictors (R2=0.59) of ɛi.ConclusionRadial strain in the inner half layer of the LV wall decreases in parallel with the degrees of LV concentricity and hypertrophy in hypertensive patients. Radial strain in the inner half layer may identify subtle systolic dysfunction even in hypertensive patients with preserved LV chamber function

Involvement of resistin-like molecule β in the development of methionine-choline deficient diet-induced non-alcoholic steatohepatitis in mice

Resistin-like molecule β (RELMβ) reportedly has multiple functions including local immune responses in the gut. In this study, we investigated the possible contribution of RELMβ to non-alcoholic steatohepatitis (NASH) development. First, RELMβ knock-out (KO) mice were shown to be resistant to methionine-choline deficient (MCD) diet-induced NASH development. Since it was newly revealed that Kupffer cells in the liver express RELMβ and that RELMβ expression levels in the colon and the numbers of RELMβ-positive Kupffer cells were both increased in this model, we carried out further experiments using radiation chimeras between wild-type and RELMβ-KO mice to distinguish between the contributions of RELMβ in these two organs. These experiments revealed the requirement of RELMβ in both organs for full manifestation of NASH, while deletion of each one alone attenuated the development of NASH with reduced serum lipopolysaccharide (LPS) levels. The higher proportion of lactic acid bacteria in the gut microbiota of RELMβ-KO than in that of wild-type mice may be one of the mechanisms underlying the lower serum LPS level the former. These data suggest the contribution of increases in RELMβ in the gut and Kupffer cells to NASH development, raising the possibility of RELMβ being a novel therapeutic target for NASH

Impact of frailty on long-term mortality in older patients receiving intensive care via the emergency department

The aim of this study was to evaluate whether frailty was associated with 6-month mortality in older adults who were admitted to the intensive care unit (ICU) with an illness requiring emergency care. The investigation was a prospective, multi-center, observational study conducted among the ICUs of 17 participating hospitals. Patients >= 65 years of age who were admitted to the ICU directly from an emergency department visit were assessed to determine their baseline Clinical Frailty Scale (CFS) scores before the illness and were surveyed 6 months after admission. Among 650 patients included in the study, the median age was 79 years old, and overall mortality at 6 months was as low as 21%, ranging from 6.2% in patients with CFS 1 to 42.9% in patients with CFS >= 7. When adjusted for potential confounders, CFS score was an independent prognostic factor for mortality (one-point increase in CFS, adjusted risk ratio with 95% confidence interval 1.19 [1.09-1.30]). Quality of life 6 months after admission worsened as baseline CFS score increased. However, there was no association between total hospitalization cost and baseline CFS. CFS is an important predictor of long-term outcomes among critically ill older patients requiring emergent admission

Membrane vesicle-mediated bacterial communication

The classical quorum-sensing (QS) model is based on the assumption that diffusible signaling molecules accumulate in the culture medium until they reach a critical concentration upon which expression of target genes is triggered. Here we demonstrate that the hydrophobic signal N-hexadecanoyl-L-homoserine lactone, which is produced by Paracoccus sp., is released from cells by the aid of membrane vesicles (MVs). Packed into MVs, the signal is not only solubilized in an aqueous environment but is also delivered with varying propensities to different bacteria. We propose a novel MV-based mechanism for binary trafficking of hydrophobic signal molecules, which may be particularly relevant for bacteria that live in open aqueous environments

Plasma Xanthine Oxidoreductase Activity Associated with Glycemic Control in Patients with Pre-Dialysis Chronic Kidney Disease

Introduction: Xanthine oxidoreductase (XOR) activity plays an important role as a pivotal source of reactive oxygen species, which is associated with cardiovascular disease (CVD) events. Patients with CKD have increased risk of CVD events. In the present study, factors associated with plasma XOR activity in pre-dialysis CKD patients were investigated. Methods: In this cross-sectional study, plasma XOR activity in 118 pre-dialysis CKD patients (age 68 [57–75] years; 64 males, 26 with diabetes mellitus [DM]) was determined using a newly established highly sensitive assay based on (13C2,15N2) xanthine and liquid chromatography/triple quadrupole mass spectrometry. Results: Plasma glucose, hemoglobin A1c, and estimated glomerular filtration (eGFR) were significantly and positively correlated with plasma logarithmically transformed XOR (ln-XOR) activity. In multiple regression analyses, eGFR and hemoglobin A1c or plasma glucose were significantly, independently, and positively associated with plasma ln-XOR activity after adjusting for several confounders. Plasma XOR activity was significantly higher in CKD patients with (n = 26) than in those without (n = 92) DM (62.7 [32.3–122] vs. 25.7 [13.4–45.8] pmol/h/mL, p &#x3c; 0.001). A total of 38 patients were taking uric acid-lowering drugs. Multiple regression analysis of CKD patients not administered uric acid-lowering drugs (n = 80) showed no significant association between eGFR and plasma ln-XOR activity. In contrast, association between glycemic control and plasma ln-XOR activity was significant even in CKD patients without uric acid-lowering drug treatment. Conclusions: These results indicate the importance of glycemic control in CKD patients in regard to decreased XOR, possibly leading to a decrease in CVD events