The role of Qa-2, the functional homolog of HLA-G, in a Behcet's disease-like mouse model induced by the herpes virus simplex

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the HLA-G molecule is a genetic risk factor for Behcet's disease (BD). In this study, we evaluated the level of Qa-2, a murine nonclassical class I MHC molecule and possible functional homolog of HLA-G, to determine if it was associated with various symptoms of BD-like mice. In addition, we investigated siRNA (small interfering RNA) treatment to determine if it inhibited Qa-2 expression, thereby changing the symptoms of mice.</p> <p>Methods</p> <p>RNA interference (RNAi) and vector transfection were employed to manipulate gene expression <it>in vivo </it>in mice. siRNA (small interfering RNA) or Qa-2 expression vector was applied to inhibit or up-regulate Qa-2 expression, respectively.</p> <p>Results</p> <p>The Qa-2 levels in granulocytes were lower in BD-like mice than in normal controls. The silencing of Qa-2 by intravenous injection of siRNA (500 nmol/mouse, 4 times at 3-day intervals) specifically reduced the Qa-2 levels and worsened the BD-like symptoms.</p> <p>Conclusions</p> <p>Silencing Qa-2 by injecting siRNA into mice resulted in deterioration of symptoms in BD-like mice.</p

Explicitly determined sea ice emissivity and emission temperature over the Arctic for surface‐sensitive microwave channels

Data assimilation of satellite microwave measurements is one of the importantkeys to improving weather forecasting over the Arctic region. However, the useofsurface-sensitivemicrowave-soundingchannelmeasurementsfordataassim-ilation or retrieval has been limited, especially during winter, due to the poorlyconstrained sea ice emissivity. In this study, aiming at more use of those channelmeasurements in the data assimilation, we propose an explicit method for speci-fying the surface radiative boundary conditions (namely emissivity and emittinglayer temperature of snow and ice). These were explicitly determined with aradiativetransfermodelforsnowandiceandwithsnow/icephysicalparameters(i.e. snow/ice depths and vertical distributions of temperature, density, salinity,and grain size) simulated from the thermodynamically driven snow/ice growthmodel. We conducted 1D-Var experiments in order to examine whether thisapproach can help to use the surface-sensitive microwave temperature channelmeasurements over the Arctic sea ice region for data assimilation. Results showthat (1) the surface-sensitive microwave channels can be used in the 1D-Varretrieval, and (2) the specification of the radiative boundary condition at thesurface using the snow/sea ice emission model can significantly improve theatmospheric temperature retrieval, especially in the lower troposphere (500hPato surface). The successful retrieval suggests that useful information can beextracted from surface-sensitive microwave-sounding channel radiances oversea ice surfaces through the explicit determination of snow/ice emissivity andemitting layer temperature

A Carcinoembryonic Antigen-Secreting Adenocarcinoma Arising in Tailgut Cyst : Clinical Implications of Carcinoembryonic Antigen

Tailgut cysts (TGCs) are rare congenital cysts that occur in the retrorectal or presacral spaces. Although most tailgut cysts have been reported as benign, there have been at least 9 cases associated with malignant change. We report herein on an unusual case of a 40-year-old woman with a carcinoembryonic antigen (CEA)-producing adenocarcinoma arising within a TGC who underwent surgical resection and local radiation therapy. Despite the complete resection, metastatic adenocarcinoma developed five months after surgery. CEA-producing adenocarcinoma from a TGC is extremely rare and only two cases, including this case, have been reported in the English medical literature. Besides CEA, the serum levels of CA 19-9 became markedly elevated in this patient. Given that the serum CEA level decreased to the normal range after complete resection of tumor and that the tumor recurrence was associated with a rebound of the CEA serum level, our case shows that serial measurements of serum CEA can be used for treatment planning and for assessing the patient's treatment response for this rare disease

Expression of inflammatory biomarkers from cultured sebocytes was influenced by treatment with vitamin D

Background: Inflammatory cytokines are the key factor in the pathophysiology of acne. It is well known that keratinocytes synthesize many kinds of inflammatory cytokines. In addition, it is reported that inflammatory cytokines are also expressed from sebocytes, which originate from the same stem cells with keratinocytes. Aim: To clarify changes in the expression of inflammatory biomarkers from cultured sebocytes after treatment with vitamin D. Materials and Methods: Reverse transcription-polymerase chain reaction (RT-PCR) was done to measure changes in the expression of inflammatory biomarkers, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α), and several subtypes of matrix metalloproteinases (MMPs) after treatment of a group of cultured sebocytes with vitamin D. Vitamin D receptor (VDR) small interfering RNA (siRNA) was added in the other group of cultured sebocytes to assure the role of vitamin D on the expression of inflammatory biomarkers. Enzyme-linked immunosorbent assay (ELISA) was also performed in the vitamin D-treated sebocytes. Results: Cultured sebocytes showed non-significant changes in the gene expression of inflammatory biomarkers after treatment with vitamin D. In cultured sebocytes treated with a VDR siRNA, the expression of inflammatory biomarkers was not blocked after treatment with vitamin D. ELISA showed a significant decrease in the expression of IL-6, IL-8, and MMP-9, but a significant increase in the expression of MMP-1 and MMP-3, after treatment with vitamin D (10 -6 M). Conclusion: Expression of inflammatory biomarkers is influenced by treatment with vitamin D in cultured sebocytes, but not through VDR

Probiotics reduce repeated water avoidance stress-induced colonic microinflammation in Wistar rats in a sex-specific manner.

The colonic response to stress is greater in female rats than in male rats. The aim of this study was to evaluate the effect of probiotics in the repeated water avoidance stress (rWAS)-induced colonic microinflammation model of Wistar rats in a sex-specific manner. The three groups (no-stress, WAS, and WAS with probiotics) were exposed to r-WAS for 1 h daily for 10 days, and Lactobacillus farciminis was administered by oral gavage for 10 days to animals in the probiotics group. The visceromotor response (VMR) to colorectal distension (CRD) was assessed using a barostat and noninvasive manometry before and after WAS exposure. Immunohistochemistry for mast cells and real-time polymerase chain reaction (RT-PCR) for detection of mucosal cytokines were performed using distal colon tissue after the animals were sacrificed. Significant reduction of VMR to CRD (visceral analgesia) was observed at 60 mmHg in the female WAS group (P = 0.045), but not in males. In addition, the female WAS with probiotics group showed a significantly lower colonic mucosal mast cell count in comparison to the female WAS group (P = 0.013), but this phenomenon was not observed in the male group. The colonic mucosal mRNA levels of interferon-γ (IFNR), tumor necrosis factor-α (TNFA), interleukin (IL) 6, and IL17 were higher in the female WAS group than in the male WAS group. The mRNA levels of IFNR, TNFA, and IL6 were significantly decreased in WAS females who received probiotics (all P < 0.050). In conclusion, rWAS is induced in a sex-specific manner. A 10-day-long treatment with L. farciminis is an effective therapy for rWAS-induced colonic microinflammation in female rates, but not in male rats

Antiallergic effect of Gami-hyunggyeyeongyotang on ovalbumin-induced allergic rhinitis in mouse and human mast cells

Background: Gami-hyunggyeyeongyotang (GMHGYGT) is a polyherbal medicine derived from an oriental prescription traditionally used in the treatment of allergic diseases such as allergic rhinitis (AR). This study aimed to evaluate the effects of GMHGYGT on ovalbumin (OVA) sensitization/challenge-induced AR in BALB/C mice, through examination of allergic inflammatory response regulation, as well as examination of human mast cells (HMC-1). Methods: Nasal symptoms were evaluated in the OVA-induced allergic rhinitis mouse model, and total immunoglobulin (Ig)E and OVA-specific IgE levels in serum were investigated. Eosinophil infiltration and thickness of the nasal mucosa, and levels of interleukin (IL)-1β and caspase-1 were also measured by immunohistochemistry. Additionally, the effect of GMHGYGT on the phorbol-12-myristate-13-acetate plus calcium ionophore A23187-induced phosphorylation of extracellular signal-regulated kinase, C-Jun N-terminal kinase and p38 in HMC-1 cells was investigated. Results: GMHGYGT was demonstrated to have antiallergic effects on the nasal symptoms of the OVA-induced mouse model, decreasing serum levels of OVA-specific IgE and levels of the cytokines IL-5, IL-6, IL-1β, monocyte chemotactic protein-1, and macrophage inflammatory protein-2. GMHGYGT reduced the number of eosinophils in the nasal mucosa and thickness of the nasal septum, and inhibited the expression of IL-1β and caspase-1. Moreover, it inhibited the phosphorylation of extracellular signal-regulated kinase and C-Jun N-terminal kinase, as well as the activation of nuclear factor-κB on protein level in HMC-1 cells. Conclusion: These results suggest that GMHGYGT has therapeutic potential for the treatment of allergic rhinitis

Establishment of chemosensitivity tests in triple-negative and BRCA-mutated breast cancer patient-derived xenograft models.

PURPOSE:A patient-derived xenograft (PDX) model is an in vivo animal model which provides biological and genomic profiles similar to a primary tumor. The characterization of factors that influence the establishment of PDX is crucial. Furthermore, PDX models can provide a platform for chemosensitivity tests to evaluate the effectiveness of a target agent before applying it in clinical trials. METHODS:We implanted 83 cases of breast cancer into NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic mice, to develop PDX models. Clinicopathological factors of primary tumors were reviewed to identify the factors affecting engraftment success rates. After the establishment of PDX models, we performed olaparib and carboplatin chemosensitivity tests. We used PDX models from triple-negative breast cancer (TNBC) with neoadjuvant chemotherapy and/or germline BRCA1 mutations in chemosensitivity tests. RESULTS:The univariate analyses (p<0.05) showed factors which were significantly associated with successful engraftment of PDX models include poor histologic grade, presence of BRCA mutation, aggressive diseases, and death. Factors which were independently associated with successful engraftment of PDX models on multivariate analyses include poor histologic grade and aggressive diseases status. In chemosensitivity tests, a PDX model with the BRCA1 L1780P mutation showed partial response to olaparib and complete response to carboplatin. CONCLUSIONS:Successful engraftment of PDX models was significantly associated with aggressive diseases. Patients who have aggressive diseases status, large tumors, and poor histologic grade are ideal candidates for developing successful PDX models. Chemosensitivity tests using the PDX models provide additional information about alternative treatment strategies for residual TNBC after neoadjuvant chemotherapy

Improved corrosion resistance of extruded Mg-8Sn-1Zn-1Al alloy by microalloying with Mn

We report that microalloying with Mn substantially enhances the corrosion resistance of extruded Mg-8Sn-1Zn-1Al alloy. The corrosion rates, measured by immersion tests in 0.6 M NaCl solution at 25 degrees C, were 4.37 and 246.72 mm y(-1) for the quaternary alloys with and without 0.1 wt% Mn, respectively. The enhanced corrosion resistance due to Mn microalloying is attributed to reduced H-2 evolution rate, attained by a change in the type of Al-containing intermetallic particles, which led to a reduction of the particles&apos; electrcichemical nobility. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reservedclose00

Thyroid Hormone Disruption by Water-Accommodated Fractions of Crude Oil and Sediments Affected by the <i>Hebei Spirit</i> Oil Spill in Zebrafish and GH3 Cells

A crude oil and the coastal sediments that were affected by the <i>Hebei Spirit</i> Oil Spill (HSOS) of Taean, Korea were investigated for thyroid hormone disruption potentials. Water-accommodated fractions (WAFs) of Iranian Heavy crude oil, the major oil type of HSOS, and the porewater or leachate of sediment samples collected along the coast line of Taean were tested for thyroid disruption using developing zebrafish and/or rat pituitary GH3 cells. Major polycyclic aromatic hydrocarbons (PAHs) and their alkylated forms were also measured from the test samples. In zebrafish larvae, significant decreases in whole-body thyroxine (T₄) and triiodothyronine (T₃) levels, along with transcriptional changes of thyroid regulating genes, were observed following 5 day exposure to WAFs. In GH3 cells, transcriptions of thyroid regulating genes were influenced following the exposure to the sediment samples, but the pattern of the regulatory change was different from those observed from the WAFs. Composition of PAHs and their alkylated homologues in the WAFs could partly explain this difference. Our results clearly demonstrate that WAFs of crude oil can disrupt thyroid function of larval zebrafish. Sediment samples also showed thyroid disrupting potentials in the GH3 cell, even several years after the oil spill. Long-term ecosystem consequences of thyroid hormone disruption due to oil spill deserve further investigation