Alzheimer's Disease, Oestrogen and Mitochondria: an Ambiguous Relationship

Hormonal deficit in post-menopausal women has been proposed to be one risk factor in Alzheimer's disease (AD) since two thirds of AD patients are women. However, large treatment trials showed negative effects of long-term treatment with oestrogens in older women. Thus, oestrogen treatment after menopause is still under debate, and several hypotheses trying to explain the failure in outcome are under discussion. Concurrently, it was shown that amyloid-beta (Aβ) peptide, the main constituent of senile plaques, as well as abnormally hyperphosphorylated tau protein, the main component of neurofibrillary tangles, can modulate the level of neurosteroids which notably represent neuroactive steroids synthetized within the nervous system, independently of peripheral endocrine glands. In this review, we summarize the role of neurosteroids especially that of oestrogen in AD and discuss their potentially neuroprotective effects with specific regard to the role of oestrogens on the maintenance and function of mitochondria, important organelles which are highly vulnerable to Aβ- and tau-induced toxicity. We also discuss the role of Aβ-binding alcohol dehydrogenase (ABAD), a mitochondrial enzyme able to bind Aβ peptide thereby modifying mitochondrial function as well as oestradiol levels suggesting possible modes of interaction between the three, and the potential therapeutic implication of inhibiting Aβ-ABAD interactio

Anti-Inflammatory Effects of Inonotus obliquus in Colitis Induced by Dextran Sodium Sulfate

A total of 28 male BALB/c mice (average weight 20.7 ± 1.6 g) were divided into 4 treatment groups and fed a commercial diet (A), a commercial diet + induced colitis by dextran sodium sulfate (DSS) (B), Inonotus obliquus (IO) administration (C), and IO administration + induced colitis by DSS (D). IO treatment (C, D) decreased the expression of tumor necrosis factor (TNF)-α and signal transducers and activators of transcription (STAT)1 compared to those of the colitis induced group (B). The expressions of IL-4 and STAT6 were decreased in group D compared to the colitis induced group (B). The serum immunoglobulin (Ig)E level decreased in IO treatment groups (C, D) compared to no IO treatment groups (A and B) although there was no significant difference between the IO treatment groups. Extract from IO itself had a weak cytotoxic effect on murine macrophage cell line (RAW264.7 cells). Extract from IO inhibited lipopolysaccharide- (LPS-) induced, TNF-α, STAT1, pSTAT1, STAT6, and pSTAT6 production in RAW264.7 cells

Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A

Background/AimsThe early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA.MethodsSamples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA.ResultsThe concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an "equivocal" result was regarded as positive; and 79.1% and 100%, respectively, when an "equivocal" result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA.ConclusionsThe qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti-HAV and may be more sensitive during the window period

Chiral electroluminescence from thin-film perovskite metacavities

Chiral light sources realized in ultracompact device platforms are highly desirable for various applications. Among active media employed for thin-film emission devices, lead-halide perovskites have been extensively studied for photoluminescence due to their exceptional properties. However, up to date, there have been no demonstrations of chiral electroluminescence with a substantial degree of circular polarization (DCP), being critical for the development of practical devices. Here, we propose a new concept of chiral light sources based on a thin-film perovskite metacavity and experimentally demonstrate chiral electroluminescence with DCP approaching 0.38. We design a metacavity created by a metal and a dielectric metasurface supporting photonic eigenstates with close-to-maximum chiral response. Chiral cavity modes facilitate asymmetric electroluminescence of pairs of left and right circularly polarized waves propagating in the opposite oblique directions. The proposed ultracompact light sources are especially advantageous for many applications requiring chiral light beams of both helicities.Comment: 20 pages, 4 figure

No association between the IL28B SNP and response to peginterferon plus ribavirin combination treatment in Korean chronic hepatitis C patients

Background/AimsThere are few available data regarding the association between the single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) and a sustained virologic response (SVR) to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy in Korean chronic hepatitis C patients.MethodsThis was a retrospective cohort study of 156 patients with chronic hepatitis C virus (HCV) infection who received combination treatment of PEG-IFN plus RBV. Blood samples from these patients were analyzed to identify the IL28B SNPs at rs12979860, rs12980275, rs8099917, and rs8103142. Association analyses were performed to evaluate the relationships between each IL28B SNP and SVRs.ResultsSeventy six patients with HCV genotype 1 and 80 with genotype non-1 were enrolled. The frequencies of rs12979860 CC and CT genotypes were 90.4% and 9.6%, respectively; those of rs12980275 AA and AG genotypes were 87.2% and 12.8%, respectively; those of rs8099917 TT and TG genotypes were 92.3% and 7.7%, respectively; and those of rs8103142 TT and CT genotypes were 90.4% and 9.6%, respectively. Among the patients with HCV genotype 1, the SVR rates were 69.7% and 80.0% for rs12979860 CC and CT, respectively (P=0.71). Among the HCV genotype non-1 patients, SVR rates were 88.0% and 100% for rs12979860 CC and CT (P=1.00), respectively.ConclusionsGenotypes of the IL28B SNP that are known to be favorable were present in most of the Korean patients with chronic hepatitis C in this study. Moreover, the IL28B SNP did not influence the SVR rate in either the HCV genotype 1 or non-1 patients. Therefore, IL28B SNP analysis might be not useful for the initial assessment, prediction of treatment outcomes, or treatment decision-making of Korean chronic hepatitis C patients

第718回 千葉医学会例会・第二内科例会 14.

No correlation between pThr514 CRMP2 and pSer396 tau in LBD parietal cortex. a Bar graph of mean (± SEM) pSer396 tau to total tau ratios. Scatter plots of pThr514 CRMP2 with pSer396 tau : total tau in total homogenate fractions of b LBD (DLB + PDD), c DLB and d PDD parietal cortex, with insets indicating rho and p values. Available N for control = 19; PDD = 19 and DLB = 20. No significant differences (p > 0.05) were found for multiple pair-wise comparisons of pSer396 : total tau between groups (Kruskal-Wallis H tests), or for pThr514 CRMP2 correlations with pSer396 tau : total tau ratios (Spearman). (PDF 106 kb

PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1−/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1−/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.So-Young Lee received National Research Foundation Grant of Korea (NRF2019R1A2C4070492), funded by the Korean government (https://www.nrf.re.kr) for this work. Soonchul Lee received National Research Foundation Grant of Korea (NRF-2019R1C1C1004017), funded by the Korean government (https://www.nrf.re.kr) for this work

Stretchable and transparent electrodes based on in-plane structures

Stretchable electronics has attracted great interest with compelling potential applications that require reliable operation under mechanical deformation. Achieving stretchability in devices, however, requires a deeper understanding of nanoscale materials and mechanics beyond the success of flexible electronics. In this regard, tremendous research efforts have been dedicated toward developing stretchable electrodes, which are one of the most important building blocks for stretchable electronics. Stretchable transparent thin-film electrodes, which retain their electrical conductivity and optical transparency under mechanical deformation, are particularly important for the favourable application of stretchable devices. This minireview summarizes recent advances in stretchable transparent thin-film electrodes, especially employing strategies based on in-plane structures. Various approaches using metal nanomaterials, carbon nanomaterials, and their hybrids are described in terms of preparation processes and their optoelectronic/mechanical properties. Some challenges and perspectives for further advances in stretchable transparent electrodes are also discussed. © 2015 The Royal Society of Chemistry.open0

Pretransplant malnutrition, inflammation, and atherosclerosis affect cardiovascular outcomes after kidney transplantation

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Malnutrition, inflammation, and atherosclerosis (MIA) syndrome is associated with a high mortality rate in patients with end-stage renal disease. However, the clinical relevance of MIA syndrome in kidney transplantation (KT) recipients remains unknown. Methods We enrolled 1348 adult KT recipients. Recipients were assessed based on serum albumin, cholesterol, or body mass index for the malnutrition factor and C-reactive protein level for the inflammation factor. Any history of cardiovascular (CV), cerebrovascular, or peripheral vascular disease satisfied the atherosclerosis factor. Each MIA factors were assessed by univariate analysis and we calculated an overall risk score by summing up scores for each independent variable. The enrolled patients were divided into 4 groups depending on the MIA score (0, 2–4, 6, 8–10). Results The patients with higher MIA score showed worse outcome of fatal/non-fatal acute coronary syndrome (ACS) (p < 0.001) and composite outcomes of ACS and all-cause mortality (p < 0.001) than with the lower MIA score. In multivariate analysis, ACS showed significantly higher incidence in the MIA score 8-10 group than in the MIA score 0 group (Hazard ratio 6.12 95 % Confidence interval 1.84–20.32 p = 0.003). Conclusions The presence of MIA factors before KT is an independent predictor of post-transplant CV outcomes