Lack of Association between Apolipoprotein E Polymorphism with Age at Onset of Subcortical Vascular Dementia

Background and Purpose: The relationship between apolipoprotein E (ApoE) and onset of vascular dementia remains controversial. The aim of this study was to evaluate the relationship between ApoE polymorphism and the onset of subcortical vascular dementia (SVaD) compared to Alzheimer’s disease (AD) and normal controls. Methods: The study was comprised of 61 patients with SVaD (42 Binswanger type, 19 lacunar type) and 112 patients with AD (16 early-onset AD, 96 late-onset AD) as well as 284 age-, gender- and education-matched normal controls. The diagnosis of SVaD was based on modified NINDS-AIREN criteria, and the diagnosis of AD was based on NINCDS-ADRDA criteria. ApoE polymorphism was genotyped in all participants. Results: None of the three ApoE alleles was more prevalent in SVaD patients compared to normal controls, which was the case when both Binswanger and lacunar types were analyzed separately. ApoE Ε4 did not accelerate the onset of SVaD (OR 1.66, 95% CI: 0.8–3.4), in contrast to a significant relation with late-onset AD (OR 3.78, 95% CI: 2.2–6.5). Conclusion: Our results suggest that ApoE polymorphism is not associated with the onset of SVaD and that the two subtypes of SVaD may share similar pathophysiologies

IRT5 Probiotics Changes Immune Modulatory Protein Expression in the Extraorbital Lacrimal Glands of an Autoimmune Dry Eye Mouse Model

PURPOSE. While the association between the gut microbiome and the immune system has been studied in autoimmune disorders, little is known about ocular disease. Previously we reported that IRT5, a mixture of five probiotic strains, could suppress autoimmune dry eye. In this study, we investigated the mechanism by which IRT5 performs its immunomodulatory function in a mouse model of autoimmune dry eye. METHODS. NOD.B10.H2b mice were used as an autoimmune dry eye model. Either IRT5 or PBS was gavaged orally for 3 weeks, with or without 5 days of antibiotic pretreatment. The effects on clinical features, extraorbital lacrimal gland and spleen proteins, and fecal microbiota were analyzed. RESULTS. The ocular staining score was lower, and tear secretion was higher, in the IRT5-treated groups than in the PBS-treated groups. After IRT5 treatment, the downregulated lacrimal gland proteins were enriched in the biological processes of defense response and immune system process. The relative abundances of 33 operational taxonomic units were higher, and 53 were lower, in the feces of the IRT5-treated groups than in those of the PBS-treated groups. IRT5 administration without antibiotic pretreatment also showed immunomodulatory functions with increases in the Lactobacillus helveticus group and Lactobacillus hamsteri. Additional proteomic assays revealed a decrease of proteins related to antigen-presenting processes in the CD11b(+) and CD11c(+) cells of spleen in the IRT5-treated groups. CONCLUSIONS. Changes in the gut microbiome after IRT5 treatment improved clinical manifestations in the autoimmune dry eye model via the downregulation of antigen-presenting processes in immune networks.11Ysciescopu

Sequential activation of phosphatidylinositol 3-kinase, beta pix, rac1, and nox1 in growth factor-induced production of h2o2

The generation of reactive oxygen species (ROS) in cells stimulated with growth factors requires the activation of phosphatidylinositol 3-kinase (PI3K) and the Rac protein. We report here that the COOHterminal region of Nox1, a protein related to gp91 phox (Nox2) of phagocytic cells, is constitutively associated with ␤Pix, a guanine nucleotide exchange factor for Rac. Both growth factor-induced ROS production and Rac1 activation were completely blocked in cells depleted of ␤Pix by RNA interference. Rac1 was also shown to bind to the COOH-terminal region of Nox1 in a growth factor-dependent manner. Moreover, the depletion of Nox1 by RNA interference inhibited growth factor-induced ROS generation. These results suggest that ROS production in growth factor-stimulated cells is mediated by the sequential activation of PI3K, ␤Pix, and Rac1, which then binds to Nox1 to stimulate its NADPH oxidase activity. Reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide (H 2 O 2 ), are produced in mammalian cells in response to the activation of various cell surface receptors and contribute to intracellular signaling and to the regulation of various biological activities, including host defense and metabolic conversion Nonphagocytic cells also produce superoxide anions in response to a variety of extracellular stimuli, including plateletderived growth factor (PDGF) and epidermal growth factor (EGF) (3, 5, 35, 38) Several homologs (Nox1, Nox3, Nox4, Nox5, Duox1, and Duox2) of gp91 phox (Nox2) have been identified in various nonphagocytic cell

Predictive factors that influence the survival rates in liver cirrhosis patients with spontaneous bacterial peritonitis

Background/AimsSpontaneous bacterial peritonitis (SBP) has been known to greatly influence the survival rate of patients with liver cirrhosis. However, the factors that affect the survival rate in patients with SBP need to be clarified.MethodsThis study enrolled 95 liver cirrhosis patients diagnosed with SBP. The laboratory findings of their serum and ascitic fluid were examined and the characteristics of the isolated microorganisms in their peritoneal fluid were analyzed.ResultsThe proportion of patients with culture-positive SBP was 41.1%, and 47 microorganisms were isolated from the ascitic fluid. The proportions of cultured bacteria that were Gram negative and Gram positive were 57.4% and 40.4%, respectively. The proportions of Escherichia coli, Klebsiella species, and Streptococcus species were 25.5%, 19.1%, and 19.1%, respectively. Enterococcus species represented 12.8% of the microorganisms cultured. The overall survival rates at 6, 12, and 24 months were 44.5%, 37.4%, and 32.2%, respectively. There was no relationship between the bacterial factors and the survival rate in SBP. Multivariate analysis revealed that the presence of hepatocellular carcinoma (HCC; P=0.001), higher serum bilirubin levels (≥3 mg/dL, P=0.002), a prolonged serum prothrombin time (i.e., international normalized ratio >2.3, P1.3 mg/dL, P<0.001), and lower glucose levels in the ascitic fluid (<50 mg/dL, P<0.001) were independent predictive factors of overall survival rate.ConclusionsHCC, higher serum bilirubin levels, a prolonged serum prothrombin time, renal dysfunction, and lower ascitic glucose levels are associated with higher mortality rates in cirrhotic patients with SBP

Thoracic Splenosis: A Case Report and the Importance of Clinical History

We present a case of thoracic splenosis in a 42-yr-old man with a medical history of abdominal surgery for a penetration injury with an iron bar of the left abdomen and back. He had been in good condition, but a chest radiograph taken during a regular checkup showed a multinodular left pleura-based mass. Computed tomography (CT) showed that the mass was well-enhanced and homogeneous, indicating a sclerosing hemangioma. Following its removal by video-assisted thoracoscopic surgery, the mass appeared similar to a hemangioma, with marked adhesion to the left side diaphragmatic pleura and lung parenchyma. Frozen section showed that the lesion was a solid mass consisted with abundant lymphoid cells, suggesting a low grade lymphoma. On permanent section, however, the mass was found to be composed of white pulp, red pulp, a thick capsule and trabeculae and was diagnosed as ectopic splenic tissue, or thoracic splenosis. Review of the patient's history and chest CT at admission revealed that the patient had undergone a splenectomy for the penetration injury 20 yr previously

Lowest threshold lasing modes localized on marginally unstable periodic orbits in a semiconductor microcavity laser

The lowest threshold lasing mode in a rounded D-shape microcavity is theoretically analyzed and experimentally demonstrated. To identify the lowest threshold lasing mode, we investigate threshold conditions of different periodic orbits by considering the linear gain condition due to the effective pumping region and total loss consisting of internal and scattering losses in ray dynamics. We compare the ray dynamical result with resonance mode analysis, including gain and loss. We find that the resonance modes localized on the pentagonal marginally unstable periodic orbit have the lowest threshold in our fabrication configuration. Our findings are verified by obtaining the path lengths and far-field patterns of lasing modes. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.1

Anthocyanins from Vitis coignetiae

Recently we have demonstrated that anthocyanins from fruits of Vitis coignetiae Pulliat (AIMs) have anticancer effects. Here, we investigate the effects of AIMs on cell proliferation and invasion as well as epithelial-mesenchymal transition (EMT) which have been linked to cancer metastasis in human uterine cervical cancer HeLa cells. AIMs inhibited the invasion of HeLa cells in a dose-dependent manner. AIMs inhibited MMP-9 expression in a dose-dependent manner. AIMs inhibited the motility of HeLa cells in a wound healing test. AIMs still suppressed NF-κB activation induced by TNF. AIMs also inhibited EMT in HeLa cells. AIMs suppressed vimentin, N-cadherin, and β-catenin expression and induced E-cadherin. AIMs also suppressed expression of β-catenin and Snail, which was regulated by GSK-3. These effects of AIMs were also limited in the HeLa cells treated with TNF. In conclusion, this study indicates that AIMs have anticancer effects by suppressing NF-κB-regulated genes and EMT, which relates to suppression of IκBα phosphorylation and GSK-3 activity, respectively. However, the effects of AIMs were attenuated in the TNF-high condition