Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: Possibly involvement of metallothionein expression in astrocytes

Astrocytes exert neuroprotective effects through production of antioxidant molecules and neurotrophic factors. A recent study showed that stimulation of astrocyte serotonin 1A (5-HT1A) receptors promotes astrocyte proliferation and upregulation of the antioxidant molecules metallothionein (MT)-1,2, which protect dopaminergic neurons against oxidative stress. Rotigotine, an anti-parkinsonian drug, can bind to dopamine and 5-HT1A receptors. In this study, we examined neuroprotective effects of rotigotine in models of Parkinson's disease and involvement of astrocyte 5-HT1A receptors in neuroprotective effects of rotigotine against dopaminergic neurodegeneration. Rotigotine increased the number of astrocytes and MT-1,2 expression in cultured astrocytes. Pretreatment with conditioned media from rotigotine-treated astrocytes significantly inhibited 6-hydroxydopamine (6-OHDA)-induced dopaminergic neurotoxicity. These effects were completely blocked by a 5-HT1A antagonist or MT-1,2 specific antibody. Subcutaneous administration of rotigotine increased MT-1,2 expression in striatal astrocytes and prevented reduction of dopaminergic neurons in the substantia nigra of a 6-OHDA-lesioned mouse model of Parkinson's disease. These effects were blocked by co-administration with a 5-HT1A antagonist. These results suggest that rotigotine exerts neuroprotective effects through upregulation of MT expression in astrocytes by targeting 5-HT1A receptors. Our findings provide a possible therapeutic application of rotigotine to prevent dopaminergic neurodegeneration in Parkinson's disease

Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer

Backgrounds: The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host–tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). Methods: Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. Results: The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). Conclusions: Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer

Infrared Absorption and Its Sources of CdZnTe at Cryogenic Temperature

To reveal the causes of infrared absorption in the wavelength region between electronic and lattice absorptions, we measured the temperature dependence of the absorption coefficient of p-type low-resistivity (∼102 Ωcm) CdZnTe crystals. We measured the absorption coefficients of CdZnTe crystals in four wavelength bands (λ=6.45, 10.6, 11.6, 15.1 μm) over the temperature range of T=8.6-300 K with an originally developed system. The CdZnTe absorption coefficient was measured to be α=0.3-0.5 cm−1 at T=300 K and α=0.4-0.9 cm−1 at T=8.6 K in the investigated wavelength range. With an absorption model based on transitions of free holes and holes trapped at an acceptor level, we conclude that the absorption due to free holes at T=150-300 K and that due to trapped-holes at T<50 K are dominant absorption causes in CdZnTe. We also discuss a method to predict the CdZnTe absorption coefficient at cryogenic temperature based on the room-temperature resistivity

Results of Hepatic Resection for Liver Metastasis of Gastric Cancer : A Single Center Experience

Background : Surgical indication for hepatic resection is controversial in gastric cancer liver metastasis (GLM). The aim of this study is to clarify the effect of hepatic resection for GLM. Methodology : Ten patients who underwent hepatic resection for GLM between 2001 and 2013 were enrolled in this study. Six patients underwent synchronous hepatic resection and gastrectomy, and the remaining four patients underwent metachronous hepatic resection. Six patients had solitary liver metastasis, and 4 patients had multiple liver metastasis. The median follow-up period was 12.4 months (the range being 0.5months to 50 months). Result : The actual 1- year and 3-year overall survival rates for the patients who underwent hepatic resection are 88.9% and 17.8%, respectively. The median survival time was 21.5 months. And the 1-year recurrence free survival time was 20.0%. The median recurrence free survival rate was 4.7 months. Regarding post-operative recurrence, synchronous hepatic resection tended to be a recurrence factor (p=0.08). Conclusion : Hepatic resection for GLM has an acceptable outcome. Metachronous hepatic resection tends to have a better outcome than synchronous hepatic resection for the treatment of GLM

Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury

Background: The sympathetic nervous system regulates immune cell dynamics. However, the detailed role of sympathetic signaling in inflammatory diseases is still unclear because it varies according to the disease situation and responsible cell types. This study focused on identifying the functions of sympathetic signaling in macrophages in LPS-induced sepsis and renal ischemia-reperfusion injury (IRI).Methods: We performed RNA sequencing of mouse macrophage cell lines to identify the critical gene that mediates the anti-inflammatory effect of β2-adrenergic receptor (Adrb2) signaling. We also examined the effects of salbutamol (a selective Adrb2 agonist) in LPS-induced systemic inflammation and renal IRI. Macrophage-specific Adrb2 conditional knockout (cKO) mice and the adoptive transfer of salbutamol-treated macrophages were used to assess the involvement of macrophage Adrb2 signaling.Results: In vitro, activation of Adrb2 signaling in macrophages induced the expression of T cell Ig and mucin domain 3 (Tim3), which contributes to anti-inflammatory phenotypic alterations. In vivo, salbutamol administration blocked LPS-induced systemic inflammation and protected against renal IRI; this protection was mitigated in macrophage-specific Adrb2 cKO mice. The adoptive transfer of salbutamol-treated macrophages also protected against renal IRI. Single-cell RNA sequencing revealed that this protection was associated with the accumulation of Tim3-expressing macrophages in the renal tissue.Conclusions: The activation of Adrb2 signaling in macrophages induces anti-inflammatory phenotypic alterations partially via the induction of Tim3 expression, which blocks LPS-induced systemic inflammation and protects against renal IRI

Bone marrow stromal cell antigen-1 (CD157) regulated by sphingosine kinase 2 mediates kidney fibrosis

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2−/−) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1- phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1−/− mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis

Wing Load and Angle of Attack Identification by Integrating Optical Fiber Sensing and Neural Network Approach in Wind Tunnel Test

The load and angle of attack (AoA) for wing structures are critical parameters to be monitored for efficient operation of an aircraft. This study presents wing load and AoA identification techniques by integrating an optical fiber sensing technique and a neural network approach. We developed a 3.6-m semi-spanned wing model with eight flaps and bonded two optical fibers with 30 fiber Bragg gratings (FBGs) each along the main and aft spars. Using this model in a wind tunnel test, we demonstrate load and AoA identification through a neural network approach. We input the FBG data and the eight flap angles to a neural network and output estimated load distributions on the eight wing segments. Thereafter, we identify the AoA by using the estimated load distributions and the flap angles through another neural network. This multi-neural-network process requires only the FBG and flap angle data to be measured. We successfully identified the load distributions with an error range of &#8722;1.5&#8211;1.4 N and a standard deviation of 0.57 N. The AoA was also successfully identified with error ranges of &#8722;1.03&#8211;0.46&#176; and a standard deviation of 0.38&#176;