Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.

Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.

Reductive Transformation of Hexavalent Chromium in Ice Decreases Chromium Toxicity in Aquatic Animals.

In this study, the toxicity of hexavalent chromium [Cr(VI)] reduced by citric acid in ice was measured using representative aquatic model invertebrates (i.e., rotifer, water flea, amphipod, and polychaete) and a vertebrate (zebrafish) by analyzing short- and/or long-term endpoints that are frequently applied to each animal. Cr(VI) reduction in the presence of citric acid was markedly enhanced in the ice phase compared to that in an aqueous solution through the freeze concentration effect. The highly concentrated Cr(VI) and citric acid in ice grain boundaries were also confirmed using in situ cryogenic confocal Raman spectroscopy. Overall, exposure to Cr(VI) resulted in higher acute and/or chronic effects on aquatic animals, such as drastic mortality, growth inhibition, and decrease in offspring number, whereas the animals were increasingly tolerant to Cr(VI) that was reduced in the ice phase. Sublethal concentrations of Cr(VI) significantly decreased the antioxidant capacity in the aquatic animals. However, when the same concentrations of Cr(VI) were reduced in ice, these treatments showed no modulation or increase in the antioxidant defense system. Taken together, our results suggest that Cr(VI) reduction into Cr(III) was successfully achieved in ice and that this methodology can decrease the actual toxicity of Cr(VI) in aquatic animals.

Freezing-enhanced oxidation of iodide by hydrogen peroxide in the presence of antifreeze proteins from the Arctic yeast Leucosporidium sp.AY30.

Ice-binding proteins (IBPs), originating from Arctic or Antarctic microorganisms, have freeze-inhibiting characteristics, allowing these organisms to survive in polar regions. Despite their significance in polar environments, the mechanism through which IBPs affect the chemical reactions in ice by controlling ice crystal formation has not yet been reported. In this study, a new mechanism for iodide (I-) activation into triiodide (I3-), which is the abundant iodine species in seawater, by using hydrogen peroxide (H2O2) in a frozen solution with IBPs was developed. A significant enhancement of I- activation into I3- was observed in the presence of Arctic-yeast-originating extracellular ice-binding glycoprotein (LeIBP) isolated from Leucosporidium sp. AY30, and a further increase in the I3- concentration was observed with the introduction of H2O2 to the frozen solution (25 times higher than in the aqueous solution after 24 h of reaction). The reaction in the ice increased with an increase in LeIBP concentration. The in-situ pH measurement in ice using cresol red (CR) revealed protons accumulated in the ice grain boundaries by LeIBP. However, the presence of LeIBP did not influence the acidity of the ice. The enhanced freeze concentration effect of H2O2 by LeIBP indicated that larger ice granules were formed in the presence of LeIBP. The results suggest that LeIBP affects the formation and morphology of ice granules, which reduces the total volume of ice boundaries throughout the ice. This leads to an increased local concentration of I- and H2O2 within the ice grain boundaries. IBP-assisted production of gaseous iodine in a frozen environment provides a previously unrecognized formation mechanism of active iodine species in the polar regions.

Physiological and molecular responses of the Antarctic harpacticoid copepod Tigriopus kingsejongensis to salinity fluctuations - A multigenerational study.

Since Antarctica and the surrounding Southern Ocean are facing global climate change, biota inhabiting those coastal regions is now challenged by environmental fluctuations including coastal freshening. In this study, the effects of salinity range of 0-75 (practical salinity unit, PSU) on the Antarctic harpacticoid copepod Tigriopus kingsejongensis was investigated by measurement of 96 h survival rate, lifespan, and sex ratio with further analysis of multigenerational growth parameters and mRNA expressions under salinity of 15-45. Different stages of the copepods (i.e., nauplius, male, and female) generally showed tolerance to hypo- and hypersalinity, wherein female copepods were more tolerant than males when exposed to salinity fluctuations. Lifespan was significantly shortened by hypo- and hypersalinity compared to control salinity (34), but there was no significant difference in the sex ratio between salinity treatments. Multigenerational experiments across five generations revealed that exposure to salinities of 15 and 45 reduced body length compared to that in control salinity and the first generation of each salinity group. Our results provide evidence regarding T. kingsejongensis on their preferred salinity ranges, physiological limit to salinity fluctuations, and population dynamics in future salinity.

Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis.

BACKGROUND: Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD). OBJECTIVE: We aimed to investigate the role of NKT cells in AD development, especially in skin. METHODS: Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy-controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4-conditionally deficient or CXCL12 transgenic mice. RESULTS: CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD. CONCLUSIONS: CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.

BAFF Inhibition Effectively Suppresses the Development of Anti-HLA.A2 Antibody in the Highly Sensitized Mouse Model.

B cell activating factor (BAFF) is a cytokine that plays a role in the survival, proliferation and differentiation of B cells. We proposed to observe the effects of BAFF inhibition on the humoral immune responses of an allosensitized mouse model using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and were treated with anti-BAFF monoclonal antibody (mAb) (named Sandy-2) or control IgG1 antibody. HLA.A2-specific IgG was reduced in BAFF-inhibited mice compared to the control group (Δ-13.62 vs. Δ27.07, p < 0.05). BAFF inhibition also resulted in increased pre-pro and immature B cell proportions and decreased mature B cells in the bone marrow (p < 0.05 vs. control). In the spleen, an increase in transitional B cells was observed with a significant decrease in marginal and follicular B cells (p < 0.05 vs. control). There was no significant difference in the proportions of long-lived plasma and memory B cells. Microarray analysis showed that 19 gene probes were significantly up- (>2-fold, p < 0.05) or down-regulated (≤2-fold, p < 0.05) in the BAFF-inhibited group. BAFF inhibition successfully reduced alloimmune responses through the reduction in alloantibody production and suppression of B cell differentiation and maturation. Our data suggest that BAFF suppression may serve as a useful target in desensitization therapy.

Broussochalcone A Is a Novel Inhibitor of the Orphan Nuclear Receptor NR4A1 and Induces Apoptosis in Pancreatic Cancer Cells.

The orphan nuclear receptor 4A1 (NR4A1) is overexpressed in pancreatic cancer and exhibits pro-oncogenic activity, and NR4A1 silencing and treatment with its inactivators has been shown to inhibit pancreatic cancer cells and tumor growth. In this study, we identified broussochalcone A (BCA) as a new NR4A1 inhibitor and demonstrated that BCA inhibits cell growth partly by inducing NR4A1-mediated apoptotic pathways in human pancreatic cancer cells. BCA downregulated specificity protein 1 (Sp1)-mediated expression of an anti-apoptotic protein, survivin, and activated the endoplasmic reticulum (ER) stress-mediated apoptotic pathway. These results suggest that NR4A1 inactivation contributes to the anticancer effects of BCA, and that BCA represents a potential anticancer agent targeting NR4A1 that is overexpressed in many types of human cancers.

Acridine Based Small Molecular Hole Transport Type Materials for Phosphorescent OLED Application.

Two small molecular hole-transporting type materials, namely 4-(9,9-dimethylacridin-10(9H)-yl)-N-(4-(9,9-dimethylacridin-10(9H)-yl)phenyl)-N-phenylaniline (TPA-2ACR) and 10,10'-(9-phenyl-9H-carbazole-3,6-diyl)bis(9,9-dimethyl-9,10-dihydroacridine) (PhCAR-2ACR), were designed and synthesized using a single-step Buchwald-Hartwig amination between the dimethyl acridine and triphenylamine or carbazole moieties. Both materials showed high thermal decomposition temperatures of 402 and 422 °C at 5% weight reduction for PhCAR-2ACR and TPA-2ACR, respectively. TPA-2ACR as hole-transporting material exhibited excellent current, power, and external quantum efficiencies of 55.74 cd/A, 29.28 lm/W and 21.59%, respectively. The achieved device efficiencies are much better than that of the referenced similar, 1,1-Bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC)-based device (32.53 cd/A, 18.58 lm/W and 10.6%). Moreover, phenyl carbazole-based PhCAR-2ACR showed good device characteristics when applied for host material in phosphorescent OLEDs.

Inorganic nitrogen compounds reduce immunity and induce oxidative stress in red seabream.

In this study, the effect of ammonia derived from different stocking densities on immunological, hematological, and oxidative stress parameters was analyzed in the blood or liver of red seabream. Density- and time-dependent increases in inorganic nitrogen compounds were measured for 20 days by analyzing the three major inorganic nitrogen compounds, total ammonia nitrogen, nitrite nitrogen, and nitrate nitrogen. Three immunity parameters, alternative complement activity, lysozyme activity, and total immunoglobulin content were significantly decreased in the blood at the highest stocking density (10 kg m-3). The concentrations of hemoglobin and white blood cells were significantly decreased at 10 kg m-3, while there was no significant change in red blood cells. The significant increases in cortisol level and the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase at 10 kg m-3 clearly supported inorganic nitrogen compounds-triggered stress. A significant elevation of lipid peroxidation value and depletion of intracellular glutathione were observed at 5 and/or 10 kg m-3 in the liver tissue. The hepatic enzymatic activities of antioxidant defense enzymes, catalase and superoxide dismutase were also significantly increased. When a protein skimmer removes the inorganic nitrogen compounds at the highest density, most parameters showed no significant change. Taken together, these results suggest that accumulated inorganic nitrogen compounds at the highest stocking density inhibit innate immunity and induce oxidative stress in red seabream. This information will be helpful to maintain homeostasis of red seabream by controlling immunity and oxidative status through inorganic nitrogen compounds removal in intensive culture condition.

Development and Evaluation of Olive Flounder cyp1a1-Luciferase Assay for Effective Detection of CYP1A-Inducing Contaminants in Coastal Sediments.

Flounders have been widely used as indicator species for monitoring the benthic environment of marine coastal regions owing to their habitat and feeding preferences in or on sandy sediments. Here, a single-step, sensitive, specific, and simple luciferase assay was developed, using the olive flounder cyp1a1 gene, for effective detection of CYP1A-inducing contaminants in coastal sediments. The developed cyp1a1-luciferase assay was highly sensitive to the widely used CYP1A inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo[a]pyrene (B[a]P), and 3,3',4,4',5-pentachlorobiphenyl (PCB 126). In the case of TCDD, significant dose-dependent increases in luciferase activity (0.3-300 ng/L) were detected. The assay was more sensitive to PCB 126 than to B[a]P. The assay also involved the highly sensitive expression of luciferase to extracted mixtures of PCBs and polycyclic aromatic hydrocarbons (PAHs) collected from coastal sediments. PCBs were more capable of cyp1a1 induction in the assay system at small doses than PAHs in environmental samples. Using the cyp1a1-luciferase assay along with water or sediment chemistry will certainly aid in diagnosing CYP1A-inducing contaminants in coastal environments.

Maladaptive neurovisceral interactions in patients with Internet gaming disorder: A study of heart rate variability and functional neural connectivity using the graph theory approach.

Heart rate variability (HRV) can be used to represent the regulatory adaptive system and is a proxy for neurovisceral integration. Consistent with the view that, like other addictions, Internet gaming disorder (IGD) involves disrupted regulatory function, the present study hypothesized that IGD patients would show (a) decreased HRV, (b) ineffective functional neural connectivity, and (c) differential patterns of association between HRV and functional neural connectivity relative to healthy controls (HCs). The present study included 111 young adults (53 IGD patients and 58 age- and sex-matched HCs) who underwent simultaneous recordings with an electrocardiogram and electroencephalogram during a resting state. Heart rate (HR), HRV, and functional neural connectivity were calculated using the graph theory approach. Compared with the HCs, the IGD patients exhibited elevated HR and decreased HRV based on the high frequency (HF), which reflects suppression of parasympathetic and/or vagal tone. The IGD patients also exhibited a heightened theta band characteristic path length (CPL) compared with HCs, indicating decreased efficacy of the functional network. Furthermore, IGD patients exhibited negative correlations between the standard deviation of the normal-to-normal interval index (SDNNi) and theta and delta CPL values, which were not observed in HCs. In conclusion, the present findings suggest that IGD patients might have maladaptive brain-body integration features involving disruptions of the autonomic nervous system and brain function.

TMARg, a Novel Anthraquinone Isolated from Rubia cordifolia Nakai, Increases Osteogenesis and Mineralization through BMP2 and ß-Catenin Signaling.

BACKGROUND: Plant extracts have long been regarded as useful medicines in the treatment of human diseases. Rubia cordifolia Nakai has been used as a traditional medicine, as it has pharmacological properties such as antioxidant and anti-inflammatory activity. However, the biological functions of TMARg, isolated from the roots of R. cordifolia, in osteoblast differentiation remain unknown. This study was performed to investigate the pharmacological effects and intracellular signaling of TMARg in the osteoblast differentiation of pre-osteoblast MC3T3-E1 cells and mesenchymal precursor C2C12 cells. METHODS: Cell viability was evaluated using an MTT assay. Early and late osteoblast differentiation was examined by analyzing the activity of alkaline phosphatase (ALP), and by staining it with Alizarin red S (ARS). Cell migration was determined by using migration assays. Western blot analysis and immunocytochemical analysis were used to examine the intracellular signaling pathways and differentiation proteins. RESULTS: In the present study, TMARg showed no cytotoxicity and increased the osteoblast differentiation in pre-osteoblasts, as assessed from the alkaline phosphate (ALP) staining and activity and ARS staining. TMARg also induced BMP2 expression and increased the p-smad1/5/8-RUNX2 and ß-catenin pathways in both MC3T3-E1 and C2C12 cells. Furthermore, TMARg activated mitogen-activated protein kinases (MAPKs) and increased the cell migration rate. In addition, the TMARg-mediated osteoblast differentiation was suppressed by BMP and Wnt inhibitors with the downregulation of BMP2 expression. CONCLUSION: These findings demonstrate that TMARg exerts pharmacological and biological effects on osteoblast differentiation through the activation of BMP2 and ß-catenin signaling pathways, and suggest that TMARg might be a potential phytomedicine for the treatment of bone diseases.

Expression of B subunit of E. coli heat-labile enterotoxin in the progenies of transgenic tobacco bred by crossing nuclear- and chloroplast-transgenic lines.

The B subunit of Escherichia coli heat-labile toxin (LTB) is a model antigen that induces a strong immune response upon oral administration and enhances immune responses to conjugated and co-administered antigens. We previously examined high expression levels of LTB in plants by chloroplast and synthetic LTB gene expression and found substantially higher expression levels of LTB, compared to nuclear LTB expression in wild-type plants. The 2.5% LTB protein of total soluble protein that was observed by chloroplast transformation was approximately 250-fold greater expression than that of LTB via nuclear genome integration. In addition, the amount of LTB protein found in transgenic tobacco leaves using a synthetic LTB gene was 2.2% of the total soluble plant protein, which was approximately 200-fold higher than that in plants with native LTB gene expression. The purpose of our experiment was to increase LTB levels in plants by crossing chloroplast-transformed and synthetic LTB transgenic lines produced previously to express higher LTB levels. LTB protein levels in the F1 transgenic tobacco plants was significantly higher (3.3%), compared to the 2.2% of chloroplast-transformed line or 2.8% of synthetic LTB gene line. Our results suggest that LTB expression was successfully enhanced in the F1 hybrid generation of transgenic tobacco plants.

Reciprocal interaction between macrophage migration inhibitory factor and interleukin-8 in gout.

OBJECTIVES: Macrophage migration inhibitory factor (MIF) is a proinflammatory, chemotactic, and tissue destructive cytokine. This study determined monosodium urate crystal-induced MIF production and its interaction with interleukin (IL)-8 in gout. METHODS: Peripheral blood (PB), synovial fluid (SF), and clinical data were obtained from 98 patients with gout. SF and serum concentrations of MIF and IL-8 were measured using ELISA. SF monocytes and neutrophils were cultured with monosodium urate (MSU) crystals and the cytokine production was determined. The signalling pathways involved were determined using signal inhibitors. The interaction between MIF and IL-8 was investigated. RESULTS: SF MIF was higher in acute gout and that in serum was higher in patients with intercritical gout compared with controls. SF MIF was positively correlated with SF leukocyte and neutrophil counts and IL-8. The expression of MIF was similar in SF neutrophils and monocytes, while IL-8 was higher in monocytes. MSU crystals induced MIF production in monocytes and IL-8 production in neutrophils. This effect was decreased by inhibiting Fc-gamma receptor 1 and toll-like receptor 4. IL-8 increased MIF production in monocytes while MIF increased interleukin-8 production in neutrophils. CONCLUSIONS: MIF and IL-8 are highly produced in acute gout. MSU crystals induced MIF production in monocytes and IL-8 production in neutrophils with a reciprocal interaction between the two cytokines.

Effects of resveratrol on Th17 cell-related immune responses under tacrolimus-based immunosuppression.

BACKGROUND: We previously reported that tacrolimus (Tac) does not decrease T helper 17 cells (Th17) response in kidney transplantation. In this study, we evaluated whether Resveratrol (Resv) has immunosuppressive effects by decreasing Th17 responses in Tac-based immunosuppression. METHODS: We investigated the effects of Resv under Tac-treatment conditions, on CD4+ T cell differentiation to Th17 cells in peripheral blood mononuclear cells (PBMCs), and proliferation of CD4+ T cells co-cultured with human renal proximal tubular epithelial cells (HRPTEpiCs). The effects of Resv on Th17 cells were tested in the murine skin transplant model. RESULTS: In PBMCs, Tac did not but combination of Tac and Resv further suppressed Th17 immune response. In the co-culture study, combination of Resv to Tac significantly decreased HRPTEpiC-induced T cell proliferation compared to Tac alone. Resv treatment in the Jurkat cell induced the expression of AMP-activated protein kinase and suppressed the expression of mammalian target of rapamycin (mTOR), suggesting blocking Th17 pathway by Resv. In the murine skin transplant model, combination of Resv to Tac significantly prolonged skin graft survival accompanied by the suppression of Th17 cells, compared to either the Tac-alone or control groups. CONCLUSION: The results of our study suggest that Resv provides additional immunosuppressive effects to Tac by suppressing effector CD4+ T cells, especially Th17 cells, in the transplantation setting.

Clinical and diagnostic significance of serum immunoglobulin A rheumatoid factor in primary Sjogren's syndrome.

OBJECTIVES: The aim of this study was to investigate the diagnostic accuracy of rheumatoid factor (RF) isotype for the detection of primary Sjogren's syndrome (pSS) and evaluate the clinical and serological associations of immunoglobulin (Ig) A RF in patients with pSS. MATERIALS AND METHODS: RF levels were measured in 77 and 37 patients with pSS and idiopathic sicca symptoms, respectively, using ELISA and analysed with respect to clinical and laboratory disease characteristics. Receiver operating characteristic curves were used to determine and compare the diagnostic accuracy of IgA RF with other diagnostic tests. RESULTS: Serum levels of IgA RF were significantly higher in patients with pSS than in those with idiopathic sicca symptoms. IgA RF showed sensitivity, specificity, positive, and negative predictive values of 83.1, 78.4, 88.9, and 69.0%, respectively, for pSS diagnosis. IgA RF was associated with xerostomia, severe sialoscintigraphic grade, low unstimulated salivary flow rate (USFR), antinuclear antibody, high IgG and IgM/G RF levels, and low C3 levels in patients with pSS. IgA RF titres had positive correlations with sialoscintigraphic grade and IgG and IgG/M RF levels and had negative correlations with USFR and C3 levels. CONCLUSION: Our findings confirmed the potential of IgA RF to distinguish pSS from idiopathic sicca symptoms. The presence of IgA RF in patients with pSS was associated with significantly worse exocrine function and active serologic profile. No association between IgA RF and extra-glandular manifestations was noted. CLINICAL RELEVANCE: IgA RF should be the predictive and diagnostic marker in patients with pSS.

Identification of 74 cytochrome P450 genes and co-localized cytochrome P450 genes of the CYP2K, CYP5A, and CYP46A subfamilies in the mangrove killifish Kryptolebias marmoratus.

BACKGROUND: The mangrove killifish Kryptolebias marmoratus is the only vertebrate that reproduces by self-fertilizing and is an important model species in genetics and marine ecotoxicology. Using whole-genome and transcriptome sequences, we identified all members of the cytochrome P450 (CYP) family in this model teleost and compared them with those of other teleosts. RESULTS: A total of 74 cytochrome P450 genes and one pseudogene were identified in K. marmoratus. Phylogenetic analysis indicated that the CYP genes in clan 2 were most expanded, while synteny analysis with other species showed orthologous relationships of CYP subfamilies among teleosts. In addition to the CYP2K expansions, five tandem duplicated gene copies of CYP5A were observed. These features were unique to K. marmoratus. CONCLUSIONS: These results shed a light on CYP gene evolution, particularly the co-localized CYP2K, CYP5A, and CYP46A subfamilies in fish. Future studies of CYP expression could identify specific endogenous and exogenous environmental factors that triggered the evolution of tandem CYP duplication in K. marmoratus.

Forced expression of CD200 improves the differentiation capability and immunoregulatory functions of mesenchymal stromal cells.

OBJECTIVE: In order to identify specific mesenchymal stromal cell (MSC) populations with enhanced therapeutic efficacy, we evaluated the functional changes associated with the stable expression of CD200, which is associated with immune regulatory function and osteogenic differentiation, in human bone marrow-derived MSCs (CD200/MSCs). RESULTS: We detected significantly greater osteogenesis and chondrogenesis in CD200/MSCs than in mock-transfected MSCs. In addition, the immune regulatory function of MSCs in mixed lymphocyte reactions was enhanced by CD200 gene transfection. In CD200/MSCs, the secretion of inflammatory cytokines, i.e., IL-6 and IL-8, was reduced, and levels of the anti-inflammatory factors IL-10, FOXP3, and indoleamine 2,3-dioxygenase 1 were elevated. Finally, CD200 transfection increased the stemness of MSCs, as evidenced by greater colony numbers in colony-forming unit fibroblast assays and analyses of NANOG and OCT-4 expression. CONCLUSIONS: These results suggest that CD200/MSCs have therapeutic applications, and further in-depth research should focus on the development of a clinically applicable cell-based therapeutic strategy.

De novo transcriptome assembly of brackish water flea Diaphanosoma celebensis based on short-term cadmium and benzo[a]pyrene exposure experiments.

To develop a brackish water flea as a promising model for marine monitoring, Diaphanosoma celebensis were exposed to two pollutants, cadmium (Cd) and benzo[a]pyrene (BaP), which have different chemical characteristics and distinct modes of metabolic action on aquatic animals. Twenty-four hours after exposure to Cd (2 mg/L) or BaP (25 µg/L), whole body transcriptomes were analyzed. In total, 99.6 Mbp were assembled from nine libraries, resulting in 98,458 transcripts with an N50 of 1883 bp and an average contig length of 968 bp. Functional gene annotations were performed using Gene Ontology, Eukaryotic Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Cd significantly modulated endocrine and digestive enzyme system. Following BaP treatment, DNA repair and circadian rhythm related metabolisms were significantly modulated. Both the chemicals induced stress response and detoxification metabolism. This brackish water flea genomic information will be useful to monitor estuaries and coastal regions, as water fleas have been confirmed as promising sentinel models in freshwater ecosystems.

Superoxide dismutase 3 attenuates experimental Th2-driven allergic conjunctivitis.

Allergic conjunctivitis is an inflammatory eye disease mediated by Th2 type immune response. The role of extracellular superoxide dismutase 3 (SOD3) in immune response and allergic conjunctival inflammation was examined in a murine model for experimental allergic conjunctivitis (EAC). Allergic conjunctivitis was induced in mice by allergen challenge with ovalbumin in alum via the conjunctival sac. SOD3 was topically applied and allergy indicators were compared. Clinical signs associated with conjunctivitis, such as OVA-specific IgE production, IgG1/G2a ratio and eosinophil infiltration, were drastically reduced in mice treated with SOD3. They also had less dendritic cells and CD4+ T cells in conjunctiva than controls. Attenuated allergic inflammation was accredited to reduced Th2 type cytokine responses and increased Treg cytokine in draining lymph node. The characteristics of EAC were attributed to the absence of SOD3. Our findings suggest that SOD3 might be considered as a potential target for Th2-driven allergic conjunctival inflammation.