Search

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5' upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars.

miR-23∼27∼24 was recently implicated in restricting Th2 immunity, as well as the differentiation and function of other effector T cell lineages. Interestingly, miR-24, unlike other family members, actually promotes Th1 and Th17 responses. In this article, we show that miR-24 drives the production of IFN-γ and IL-17 in T cells at least in part through targeting TCF1, a transcription factor known for its role in limiting Th1 and Th17 immunity. Surprisingly, whereas TCF1 was previously shown to promote Th2 responses through inducing GATA3, enforced TCF1 expression in miR-24-overexpressing T cells led to further downregulation of IL-4 and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity cannot be attributed to TCF1 repression by miR-24. Together, our data demonstrate a novel miR-24-TCF1 pathway in controlling effector cytokine production by T cells and further suggest miR-24 could function as a key upstream molecule regulating TCF1-mediated immune responses., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Total flavonoids of Humulus lupulus (TFHL) were prepared using ethanol extraction, liquid-liquid partition and purification with polyamide resin. Different dose of TFHL were orally administered to normal and hyperuricemic mice for 7 days. The xanthine oxidase (XOD) inhibitory activity and hypouricemic effects of TFHL on potassium oxonate-induced hyperuricemic mice were examined. The TFHL showed very potent XOD inhibitory activity with IC 50 =66.8 μg/mL. At a single oral dose of 100mg/kg TFHL, the serum uric acid levels of hyperuricemic mice significantly decreased (P<0.01) compared with a hyperuricemic control group, and the XOD activity was inhibited by 22%. Moreover, TFHL has a protective role against potassium oxonate-induced renal damage in mice. The results suggested that TFHL could be used as a promising drug or ingredient for treatment of hyperuricemia and gout.

Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP + cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs. Furthermore, preservation of Treg cells during systemic infection prevents PC loss, while Treg cell depletion in uninfected mice reduced PC populations. These studies suggest a role for Treg cells in PC biology and provide a potential target for the modulation of PCs during vaccine-induced humoral responses or autoimmunity., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner. Rather, dysregulation of Th1 responses and autoimmunity resulted from a perturbed Treg compartment. Excessive miR-27 expression in murine T cells severely impaired Treg differentiation. Moreover, Tregs with exaggerated miR-27-mediated gene regulation exhibited diminished homeostasis and suppressor function in vivo. Mechanistically, we determined that miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg biology. Collectively, our data show that miR-27 functions as a key regulator in Treg development and function and suggest that proper regulation of miR-27 is pivotal to safeguarding Treg-mediated immunological tolerance., Competing Interests: The authors have declared that no conflict of interest exists.

The aquatic spring viremia of carp virus (SVCV) causes significant mortality in common carp (Cyprinus carpio), and TBK1 plays a crucial role in the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) system by phosphorylating its substrates to induce type I interferons (IFNs) and cellular antiviral responses. In this study, we report that zebrafish STAT6 is induced during SVCV infection and reduces IFNφ1 expression by suppressing TBK1 phosphorylation. A typical IFN stimulatory response element (ISRE) motif was found in the promoter region of zebrafish STAT6, and zebrafish STAT6 transcription was significantly upregulated in the early stages of virus infection. Overexpression of STAT6 interfered with IFNφ1 promoter activity in response to SVCV infection. Additionally, TBK1-, but not MITA-mediated activation of the IFNφ1 promoter was impaired by STAT6. Co-immunoprecipitation and Western blot experiments indicated that MITA and IRF3 were significantly phosphorylated by TBK1, and that the N-terminal kinase domain of TBK1 was critical in this process. In the final step, STAT6 interacted with the N-terminal kinase domain of TBK1 causing dephosphorylation, which resulted in reductions in the phosphorylation of IRF3 and the production of IFNφ1. These results indicate that fish STAT6 can attenuate the kinase activity of TBK1, leading to suppression of IFNφ1 expression which may in turn facilitate virus replication., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Adipocytokines play an important role in adipose tissue homeostasis, especially in obesity-associated disorders such as non-alcoholic fatty liver and their complications including hepatocellular carcinoma (HCC). Although visfatin is an adipocytokine highly expressed in visceral fat that has been demonstrated to play a critical role in the progression of human malignancies, little is known about the role of visfatin in HCC associated with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection. In this study, we investigated whether plasma visfatin levels were altered in patients with HCC and the association between plasma visfatin levels and pretreatment hematologic profiles. Plasma visfatin levels were measured by enzyme-linked immunosorbent assays in 193 patients with different stages of HBV or HCV infection, and 92 healthy control subjects. The patients with HCC and chronic HCV or HBV infection had higher levels of visfatin than patients with HBV, HCV, and cirrhosis. In multivariate logistic regression analysis, levels of alpha-fetoprotein (AFP) (OR: 1.13, p=0.003), and plasma visfatin (OR: 1.17, p=0.046) were independently associated with HCC. Multiple stepwise regression analysis showed that plasma visfatin level was positively associated with age, aspartate aminotransferase to platelet ratio index (APRI), and AFP. Trend analyses confirmed that plasma visfatin concentration was associated with AFP>8ng/mL, cirrhosis, HCC, tumor size>5cm, and Barcelona Clinic Liver Cancer-C stage. These results suggested that the plasma visfatin level is associated with the presence of HCC, and that a higher plasma visfatin level may be important in the pathogenesis of HCC. Visfatin may act as both a protective and pro-inflammatory factor. Plasma visfatin concentration may serve as an additional tool to identify patients with more advanced necroinflammation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Patients with a history of cardiovascular disease are at high risk of developing secondary major adverse cardiac events (MACE). This study aimed to identify independent predictors of MACE after hospital admission which could be used to identify of high-risk patients who may benefit from preventive strategies., Methods: This study included 1,520 consecutive patients with coronary artery disease (CAD) (654 with acute coronary syndrome (ACS) and 866 with elective percutaneous coronary intervention (PCI) patients) who received PCI and/or stenting. MACE was defined as all-cause mortality or rehospitalization for a cardiovascular- related illness. Cardiovascular-related illnesses included heart failure, reinfarction (nonfatal), recurrence of angina pectoris and repeat PCI or coronary artery bypass graft., Results: During a mean follow-up period of 32 months, 558 of the 1,520 patients developed at least one MACE. Cox regression analysis showed that the baseline clinical and biochemical variables which associated with MACE were age, being illiterate, a widow or widower, and/or economically dependent, having triple vessel disease, stent implantation, anemia, and/or diabetes mellitus, waist to hip ratio (WHR), diastolic blood pressure, fasting glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), creatinine, estimated glomerular filtration rate (eGFR), red blood cell count, hemoglobin, hematocrit, and mean corpuscular-hemoglobin concentration (MCHC) in ACS patients, and age, malnourished, and/or economically dependent, taking hypoglycemic medication, having triple vessel disease, stent implantation, anemia, diabetes mellitus, and/or hypertension, WHR, fasting glucose, HDL-C, uric acid, creatinine, eGFR, high-sensitivity C-reactive protein, mean corpuscular volume, and MCHC in elective PCI patients. Using multivariate Cox regression analysis, we found the MACE's independent factors are triple vessel disease, stent implantation, hypertension, and eGFR in ACS patients, and having triple vessel disease, stent implantation, hypertension, and uric acid in elective PCI patients., Conclusions: Having triple vessel disease, stent implantation, hypertension, and eGFR or uric acid independently predicted MACE in patients with CAD after long-term follow-up. Fortunately, these factors are modifiable and should be identified and monitored early.

The immune system protects us from enormously diverse microbial pathogens but needs to be tightly regulated to avoid deleterious immune-mediated inflammation and tissue damage. A wide range of molecular determinants and cellular components work in concert to control the magnitude and duration of a given immune response. In the past decade, microRNAs (miRNAs), a major class of small non-coding RNA species, have been extensively studied as key molecular players in immune regulation. In this chapter, we will discuss how miRNAs function as negative regulators to restrict innate and adaptive immune responses. Moreover, we will review the current reports regarding miRNAs in human immunological diseases. Finally, we will also address the emerging roles of other non-coding RNAs, long non-coding RNAs (lncRNAs) in particular, in the regulation of the immune system.

Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication., Importance: TBK1 is a pivotal phosphokinase that activates host IFN production to defend against viral infection; thus, it is a potential target for viruses to negatively regulate IFN response and facilitate viral evasion. We report that the SVCV P protein functions as a decoy substrate for cellular TBK1, leading to the reduction of IRF3 phosphorylation and suppression of IFN expression. These findings reveal a novel immune evasion mechanism of SVCV., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Interferon (IFN) regulatory factors (IRF) are the crucial transcription factors for IFN expression, leading host cell response to viral infection. In mammals, only IRF6 is unaffected by IFN expression in the IRF family; however, in fish, a lower vertebrate, whether IRF6 is related to IFN regulation is unclear. In this study, we identified that zebrafish IRF6 was a positive regulator of IFN transcription and could be phosphorylated by both MyD88 and TBK1. First, the transcript level of cellular irf6 was upregulated by treatment with poly I:C (a mimic of viral RNAs), indicating IRF6 might be involved in the process of host cell response to viruses. Overexpression of IRF6 could upregulate IFN promoter activity significantly, meaning IRF6 is a positive regulator of IFN transcription. Subsequently, at the protein regulation level and in the interaction relationship, IRF6 was phosphorylated by and associated with both MyD88 and TBK1. In addition, overexpression of IRF6 activated the transcription of isg15, rig-i and mavs of host cells; meanwhile, the transcripts of p, m and n genes of SVCV were significantly declined in IRF6-overexpressing cells. Taken together, our data demonstrate that fish IRF6 is distinguished from the homolog of mammals by being a positive regulator of IFN transcription and phosphorylated by MyD88 and TBK1, suggesting that differences in the IRF6 regulation pattern exist between lower and higher vertebrates., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Cysteine (Cys) and histidine (His) both play indispensable roles in many important biological activities. An enhanced Cys level can result in Alzheimer's and cardiovascular diseases. Likewise, His plays a significant role in the growth and repair of tissues as well as in controlling the transmission of metal elements in biological bases. Therefore, it is meaningful to detect Cys and His simultaneously. In this work, a novel terbium (III) coordination polymer-Cu (II) ensemble (Tb(3+)/GMP-Cu(2+)) was proposed. Guanosine monophosphate (GMP) can self-assemble with Tb(3+) to form a supramolecular Tb(3+) coordination polymer (Tb(3+)/GMP), which can be suited as a time-resolved probe. The fluorescence of Tb(3+)/GMP would be quenched upon the addition of Cu(2+), and then the fluorescence of the as-prepared Tb(3+)/GMP-Cu(2+) ensemble would be restored again in the presence of Cys or His. By incorporating N-Ethylmaleimide and Ni(2+) as masking agents, Tb(3+)/GMP-Cu(2+) was further exploited as an integrated logic system and a specific time-resolved fluorescent "turn-on" assay for simultaneously sensing His and Cys was designed. Meanwhile it can also be used in plasma samples, showing great potential to meet the need of practical application., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Clostridium difficile toxin A causes acute gut inflammation in animals and humans. It is known to downregulate the tight junctions between colonic epithelial cells, allowing luminal contents to access body tissues and trigger acute immune responses. However, it is not yet known whether this loss of the barrier function is a critical factor in the progression of toxin A-induced pseudomembranous colitis. We previously showed that NADH:quinone oxidoreductase 1 (NQO1) KO (knockout) mice spontaneously display weak gut inflammation and a marked loss of colonic epithelial tight junctions. Moreover, NQO1 KO mice exhibited highly increased inflammatory responses compared with NQO1 WT (wild-type) control mice when subjected to DSS-induced experimental colitis. Here, we tested whether toxin A could also trigger more severe inflammatory responses in NQO1 KO mice compared with NQO1 WT mice. Indeed, our results show that C. difficile toxin A-mediated enteritis is significantly enhanced in NQO1 KO mice compared with NQO1 WT mice. The levels of fluid secretion, villus disruption, and epithelial cell apoptosis were also higher in toxin A-treated NQO1 KO mice compared with WT mice. The previous and present results collectively show that NQO1 is involved in the formation of tight junctions in the small intestine, and that defects in NQO1 enhance C. difficile toxin A-induced acute inflammatory responses, presumably via the loss of epithelial cell tight junctions.

MicroRNA (miRNA) deficiency impairs the generation of T follicular helper (Tfh) cells, but the contribution of individual miRNAs to this phenotype remains poorly understood. In this study, we performed deep sequencing analysis of miRNAs expressed in Tfh cells and identified a five-miRNA signature. Analyses of mutant mice deficient of these miRNAs revealed that miR-22 and miR-183/96/182 are dispensable, but miR-155 is essential for the generation and function of Tfh cells. miR-155 deficiency led to decreased proliferation specifically at the late stage of Tfh cell differentiation and reduced CD40 ligand (CD40L) expression on antigen-specific CD4(+) T cells. Mechanistically, miR-155 repressed the expression of Peli1, a ubiquitin ligase that promotes the degradation of the NF-κB family transcription factor c-Rel, which controls cellular proliferation and CD40L expression. Therefore, our study identifies a novel miR-155-Peli1-c-Rel pathway that specifically regulates Tfh cell generation and function., (© 2016 Liu et al.)

The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but their role in the differentiation of the TH1 and TFH subsets of helper T cells is not well understood. Here, TH1 cells showed more robust Id2 expression than that of TFH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of TFH cells. Furthermore, TH1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of TH1 cells following infection with Toxoplasma gondii. The TFH cell-defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of TH1 cells and TFH cells.

Background: A significant number of patients with chronic kidney disease (CKD) have cardiac abnormalities, and left ventricular systolic dysfunction (LVSD) is a common manifestation. p-Cresylsulfate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, the associations among serum total PCS, major adverse cardiovascular events, all-cause mortality, and QTc prolongation have also been found in previous studies. We thus investigated the association of total PCS and CKD with LVSD in the clinical setting., Methods: We included 403 consecutive patients with stable angina. To evaluate LV function, all patients underwent echocardiography. To measure the serum total PCS concentrations and estimated glomerular filtration rate (eGFR), blood samples were obtained., Results: Multiple regression analysis showed that left atrium diameter, left ventricular mass index, end diastolic interventricular septal thickness, left ventricular end-systolic diameter, left ventricular end-systolic volume, stroke volume, left ventricular end-systolic volume index, left ventricular ejection fraction (LVEF), and the interventricular septum/posterior wall of the left ventricle were independently associated with total PCS (all p<0.05). In addition, a significantly decreased LVEF was present in patients with lower and higher serum total PCS and with CKD, and with higher serum total PCS and without CKD than from those with lower serum total PCS concentrations and without CKD (p=0.004). In the multivariate logistic regression analysis, when patients without CKD and lower PCS were used as reference group, patients with the higher total PCS concentration and without CKD had an odds ratio of 3.59 for the risk of LVSD, the lower total PCS concentration and with CKD had an odds ratio of 3.89 for the risk of LVSD, and the higher total PCS concentration and with CKD had an odds ratio of 4.04 for the risk of LVSD (p=0.039, p=0.038, and p=0.020, respectively)., Conclusions: High serum concentrations of total PCS or CKD, or both, represent an increased risk of impaired LV systolic function in stable angina patients., (Copyright © 2016 Elsevier B.V. All rights reserved.)

For a virus to replicate efficiently, it must try and inhibit host IFN expression because IFN is an important host defense at early stages after viral infection. For aquatic viruses, the mechanisms used to escape the hosts IFN system are still unclear. In this study, we show that the N protein of spring viremia of carp virus (SVCV) inhibits zebrafish IFNφ1 production by degrading the mitochondrial antiviral signaling protein (MAVS). First, the upregulation of IFNφ1 promoter activity stimulated by polyinosinic:polycytidylic acid, retinoic acid-inducible gene I (RIG-I) or MAVS was suppressed by the SVCV infection. However, the upregulation by the downstream factor of the RIG-I-like receptor signaling pathway, TANK-binding kinase 1, was not affected. Notably, at the protein level, MAVS decreased remarkably when cells were infected with SVCV. Second, consistent with the result of the SVCV infection, overexpression of the N protein of SVCV blocked the IFNφ1 transcription activated by MAVS and downregulated MAVS expression at the protein level but not at the mRNA level. Further analysis demonstrated that the N protein targeted MAVS for K48-linked ubiquitination, which promoted the degradation of MAVS. These data indicated that fish MAVS could be degraded by the N protein of SVCV through the ubiquitin-proteasome pathway. To our knowledge, this is the first article of a fish RIG-I-like receptor pathway interfered by an aquatic virus in an ubiquitin-proteasome manner, suggesting that immune evasion of a virus also exists in lower vertebrates., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Clostridium difficile toxin A is known to cause deacetylation of tubulin proteins, which blocks microtubule formation and triggers barrier dysfunction in the gut. Based on our previous finding that the Clostridium difficile toxin A-dependent activation of histone deacetylase 6 (HDAC-6) is responsible for tubulin deacetylation and subsequent microtubule disassembly, we herein examined the possible effect of potassium acetate (PA; whose acetyl group prevents the binding of tubulin to HDAC-6) as a competitive/false substrate. Our results revealed that PA inhibited toxin A-induced deacetylation of tubulin and recovered toxin A-induced microtubule disassembly. In addition, PA treatment significantly decreased the production of IL-6 (a marker of inflamed tissue) in the toxin A-induced mouse enteritis model. An in vitro HDAC assay revealed that PA directly inhibited HDAC-6-mediated tubulin deacetylation, indicating that PA acted as a false substrate for HDAC-6. These results collectively indicate that PA treatment inhibits HDAC-6, thereby reducing the cytotoxicity and inflammatory responses caused by C. difficile toxin A.

In this work, we presented a simple, label-free and rapid-responsive fluorescence assay for iodide (I(-)) detection based on "molecular beacon (MB)"-hosted thioflavin T (ThT), achieving a limit of detection as low as 158 nM. The proposed method exhibited very good selectivity to I(-) ions over other anions interference due to the strong binding force between I(-) ions with Hg(2+). Upon the addition of I(-) ions, it would capture Hg(2+) from a T-Hg(2+)-T complex belonging to the MB-like DNA hairpin structure, which eventually quenched the initial fluorescence as output. In addition, it was successfully applied for operation of an integrated DNA logic gate system and to the determination of I(-) in real samples such as human urine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The"Association of Han medicine of State of Manchuria"was a puppet TCM academic society founded by the Puppet Manchukuo government, with well-organization system and widespread scope. During its period, though some efforts were made to promoting the TCM academic progress, improving the quality of TCM doctors, developing TCM clinic, education, academic research and administration, its essence was still a tool for the puppet government to controlling, transforming and utilizing TCM.

The epithelial cells of the gut form a physical barrier against the luminal contents. The collapse of this barrier causes inflammation, and its therapeutic restoration can protect the gut against inflammation. EGF enhances mucosal barrier function and increases colonocyte proliferation, thereby ameliorating inflammatory responses in the gut. Based on our previous finding that the insect peptide CopA3 promotes neuronal growth, we herein tested whether CopA3 could increase the cell proliferation of colonocytes, enhance mucosal barrier function, and ameliorate gut inflammation. Our results revealed that CopA3 significantly increased epithelial cell proliferation in mouse colonic crypts and also enhanced colonic epithelial barrier function. Moreover, CopA3 treatment ameliorated Clostridium difficile toxin As-induced inflammation responses in the mouse small intestine (acute enteritis) and completely blocked inflammatory responses and subsequent lethality in the dextran sulfate sodium-induced mouse model of chronic colitis. The marked CopA3-induced increase of colonocyte proliferation was found to require rapid protein degradation of p21(Cip1/Waf1), and an in vitro ubiquitination assay revealed that CopA3 directly facilitated ubiquitin ligase activity against p21(Cip1/Waf1). Taken together, our findings indicate that the insect peptide CopA3 prevents gut inflammation by increasing epithelial cell proliferation and mucosal barrier function., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, we show that the miR-23∼27∼24 clusters regulate multiple aspects of T cell biology, particularly helper T (Th) 2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23∼27∼24 clusters revealed that miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, although overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17, and induced regulatory T cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest that tight regulation of miR-23∼27∼24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses., (© 2016 Cho et al.)

Background: American ginseng (Panax quinquefolius L.) and Chinese jujube (Zizyphus jujuba Mill.) are commonly used in traditional Chinese medicine to enhance immune function., Objective: The present study aimed to develop one Chinese prescription, Shenzao Cha (SZC), consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice., Methods: Normal ICR mice received intragastric administration of SZC (1.3, 2.6, and 5.2 g raw material/kg body weight) once daily for four weeks, while a control group received the same amount of sterile water., Results: SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4-fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased., Conclusions: SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement.

Objectives: Even though shift work has been suspected to be a risk factor for cardiovascular disease, little research has been done to determine the logical underlying inflammation mechanisms. This study investigated the association between shift work and circulating total and differential leukocyte counts among Chinese steel workers., Methods: The subjects were 1,654 line workers in a steel plant, who responded to a cross-sectional survey with a questionnaire on basic attributes, life style, and sleep. All workers in the plant received a periodic health checkup. Total and differential leukocytes counts were also examined in the checkup., Results: Shift workers had higher rates of alcohol use, smoking, poor sleep, poor physical exercise, and obesity than daytime workers. In further analysis, we found that the peripheral total WBC, monocyte, neutrophil, and lymphocyte counts were also greater in shift workers than in daytime workers. When subjects were divided into quartiles according to total WBC, neutrophil, monocyte, and lymphocyte counts, increased leukocyte count was associated with shift work. Using stepwise linear regression analysis, smoking, obesity, and shift work were independently associated with total WBC, monocyte, neutrophil, and lymphocyte counts., Conclusions: This study indicates that peripheral total and differential leukocyte counts are significantly higher in shift workers, which suggests that shift work may be a risk factor of cardiovascular disease. Applicable intervention strategies are needed for prevention of cardiovascular disease for shift workers.

Background: Prostate cancer remains the most common cancer in men. Qualitative or semi-quantitative immunochromatographic measurements of prostate specific antigen (PSA) have been shown to be simple, noninvasive and feasible. The aim of this study was to evaluate an optimized gold immunochromatographic strip device for the detection of PSA, in which the results can be analysed using a Chromogenic Rapid Test Reader to quantitatively assess the test results., Methods: This reader measures the reflectance of the signal line via a charge-coupled device camera. For quantitative analysis, PSA concentration was computed via a calibration equation. Capillary blood samples from 305 men were evaluated, and two independent observers interpreted the test results after 12 min. Blood samples were also collected and tested with a conventional quantitative assay., Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of the PSA rapid quantitative test system were 100, 96.6, 89.5, 100, and 97.4 %, respectively. Reproducibility of the test was 99.2, and interobserver variation was 8 % with a false positive rate of 3.4 %. The correlation coefficient between the ordinary quantitative assay and the rapid quantitative test was 0.960., Conclusions: The PSA rapid quantitative test system provided results quickly and was easy to use, so that tests using this system can be easily performed at outpatient clinics or elsewhere. This system may also be useful for initial cancer screening and for point-of-care testing, because results can be obtained within 12 min and at a cost lower than that of conventional quantitative assays.

We recently reported that the antimicrobial peptide Lumbricusin (NH2-RNRRWCIDQQA), isolated from the earthworm, increases cell proliferation in neuroblastoma SH-SY5Y cells. Here, we investigated whether Lumbricusin has neurotropic activity in mouse neural stem cells (MNSCs) and a protective effect in a mouse model of Parkinson's disease (PD). In MNSCs isolated from mouse brains, Lumbricusin treatment significantly increased cell proliferation (up to 12%) and reduced the protein expression of p27(Kip1) through proteasomal protein degradation but not transcriptional regulation. Lumbricusin inhibited the 6-OHDA-induced apoptosis of MNSCs, and also showed neuroprotective effects in a mouse PD model, ameliorating the motor impairments seen in the pole, elevated body swing, and rotation tests. These results suggest that the Lumbricusin-induced promotion of neural cell proliferation via p27(Kip1) degradation has a protective effect in an experimental PD model. Thus, the antimicrobial peptide Lumbricusin could possibly be developed as a potential therapeutic agent for the treatment of PD.

In this work, we present a new type of functional organic/inorganic hybrid supraparticle that spontaneously assembles from silver ions (Ag(+)), iodide ions (I(-)) and thioflavin T (ThT) under aqueous solution conditions. ThT alone in aqueous solution was weakly fluorescent with an emission band at 494 nm, which was related to the monomer. However, in the above-mentioned hybrid supraparticle (i.e., ThT@AgI SP) structure, the ThT monomer can form a dimer with a new emission band. The new band shifted to 546 nm and the emission intensity increased. We further present a facile strategy of reversible fluorescence switching of ThT by a simple cation (Ag(+)) and anions (I(-) and S(2-)), which can be employed for the ratiometric fluorescence detection of Ag(+) with high sensitivity and selectivity. The linear range of detecting Ag(+) was from 100 nM to 10 μM, with a limit of detection as low as approximately 50 nM. Moreover, it can be successfully applied for the operation of a logic gate system and to the sensing of Ag(+) in real water samples.

IFNs create the first line of host cells to defense viral infection, however, unrestricted expression of IFN can be hazardous to the host. IRF7 is the master regulator of type I IFN expression. To our knowledge, non research about the inhibition of IFN expression by targeting IRF7 has been reported in fish. In this study, we reported that the splicing variant of wildtype MAVS (MAVS&#95;tv1), MAVS&#95;tv2, negatively regulated IRF7-mediated IFN production. Firstly, in vivo, the transcriptional levels of MAVS&#95;tv2 in trunk kidney and spleen from the zebrafish infected with SVCV were monitored. Then, in vitro, the protein expression pattern of MAVS&#95;tv2 in zebrafish cell lines was detected using anti-MAVS&#95;tv2 antibody. Furthermore, overexpression of MAVS&#95;tv2 decreased the activation of IFN1 promoter that induced by IRF7 in a dose-dependent manner, whereas it had little effect on IRF3, a close relative of IRF7. In addition, such inhibition was also observed in IRF7-mediated epcIFN promoter and ISRE activities, but not in the activation of the promoters of type II IFNs and NF-ĸB, due to IRF7 not regulating their expression. Lastly, overexpression of MAVS&#95;tv2 decreased the transcriptional levels of several IFN-stimulated genes activated by IRF7. These findings suggest that MAVS&#95;tv2 is a negative regulator of IFN1 by targeting IRF7., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

MicroRNA (miRNA)-dependent regulation of gene expression confers robustness to cellular phenotypes and controls responses to extracellular stimuli. Although a single miRNA can regulate expression of hundreds of target genes, it is unclear whether any of its distinct biological functions can be due to the regulation of a single target. To explore in vivo the function of a single miRNA-mRNA interaction, we mutated the 3' UTR of a major miR-155 target (SOCS1) to specifically disrupt its regulation by miR-155. We found that under physiologic conditions and during autoimmune inflammation or viral infection, some immunological functions of miR-155 were fully or largely attributable to the regulation of SOCS1, whereas others could be accounted only partially or not at all by this interaction. Our data suggest that the role of a single miRNA-mRNA interaction is dependent on cell type and biological context., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Interferon regulatory factor 4 (IRF4) plays pivotal roles in both innate and adaptive immune responses in mammals. In fish, there are two homologues of irf4, irf4a and irf4b. In this study, we examined the regulatory patterns of zebrafish irf4a and irf4b by STAT6 and c-Rel. Firstly, expression of irf4a and irf4b was monitored in several tissues at mRNA level. By infection with SVCV, irf4a and irf4b were upregulated in both kidney and spleen, and were immediately induced by treatment with poly I:C in ZF4 cells. Moreover, the activation of irf4a promoter was regulated by overexpression of stat6 and c-rel in a cooperation manner, which could be inhibited by mutation of the putative binding sites of STAT6 and c-Rel in irf4a promoter region. However, irf4b promoter was activated slightly only by STAT6 but not c-Rel. Furthermore, overexpression of irf4a inhibited the activation of its own promoter under induction of STAT6 and c-Rel, which was the result of that IRF4a bound to STAT6 and c-Rel directly. In addition, cellular location analysis showed that IRF4a was located only in nuclear region. These data indicate that fish irf4a can also be upregulated by STAT6 and c-Rel., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Circulating levels of visfatin, a ubiquitous adipokine, may reflect both the severity of plaque as well as degree of plaque stabilization in acute myocardial injury. The purpose of this study was to test whether the level of visfatin is associated with the occurrence of major adverse cardiovascular events (MACEs) in patients with acute ST-elevation myocardial infarction (STEMI)., Methods: Consecutive patients (n=185) with acute STEMI were prospectively enrolled in the study. ELISA was used to measure plasma visfatin concentrations. Composite MACEs included death, recurrent myocardial infarction, target lesion revascularization or re-advanced heart failure., Results: Plasma visfatin levels were significantly higher in composite MACE patients than in non-MACE patients. A multivariate Cox hazard regression model revealed that the predictive independent risk factors for the occurrence of composite MACEs were visfatin level (relative risk = 1.04) and age (relative risk = 6.05). When patients were grouped according to their plasma visfatin levels, composite MACEs occurred more frequently in patients presenting with high visfatin levels. Moreover, Kaplan-Meier analysis revealed that high visfatin levels were significantly associated with the occurrence of composite MACEs., Conclusions: The level of plasma visfatin may be associated with risk of composite MACEs in STEMI patients, and may be useful for risk stratification.

In this work, a label-free molecular beacon (MB)-like biosensor is designed for the determination of H2O2 and glucose based on the fluorescence regulation of Hoechst dyes hosted by the designed AT-rich single-stranded DNA (ssDNA), in which Hg(2+) and cysteine (Cys) act as activators. The designed AT-rich ssDNA (ATprobe) can be directed to form a hairpin with an Hg(2+)-induced T-Hg(2+)-T complex, which provides a medium for enhancing the fluorescence of Hoechst dyes significantly. On the other hand, Cys can effectively grab Hg(2+) from the T-Hg(2+)-T complex by thiol-Hg(2+) interactions, destructing the hairpin and then switching the Hoechst dyes to the fluorescence "off" state. Combined with these properties, we have demonstrated its application for label-free fluorescence "turn on" detection of H2O2. The sensing mechanism is based on the specific reaction between H2O2 and Cys catalyzed by I(-), the resulting disulfide reverses the Cys-mediated fluorescence decrease of the MB-hosted Hoechst dyes. The approach achieves a low detection limit of 0.1 μM for H2O2. Moreover, this method is further applied to the noninvasive detection of glucose in artificial saliva and urine samples, combining with glucose oxidase (GOx) for the oxidation of glucose and formation of H2O2. Compared to traditional methods, the proposed design is cost-effective, simple to prepare and manipulate without fluorescence labeling or chemical modification.

Cathelicidin antimicrobial peptides (CAMPs) represent a crucial component of the innate immune system in vertebrates. Although widely studied in mammals, little is known about the structure and function of fish CAMPs. Further to the previous findings, two more cathelicidin genes and multiple transcripts from rainbow trout were identified in the present study. Interestingly, we found that trout have evolved energy-saving forms of cathelicidins with the total deletion of the characteristic cathelin-like domain. Sequence analysis revealed that salmonid CAMPs have formed a special class of antimicrobial peptides in vertebrates with three distinctive hallmarks: the N terminus is intensified by positive charges, the central region consists of repetitive motifs based on RPGGGS, and the C terminus is lowly charged. Immunofluorescence localization of trout CAMPs demonstrated that these peptides expressed mainly at the mucosal layer of gut. Meanwhile, signals around sinusoids were also detected in head kidney. Moreover, the biological activities of trout CAMPs were proved to be mediated by the N terminus. Additionally, the repetitive motifs characteristically existing in Salmonidae increased the structural flexibilities of peptides and further increased the antibacterial and IL-8-stimulating activities. Unlike most α helical and cytotoxic mammalian CAMPs, trout CAMPs, mainly consisting of β-sheet and random coil, exhibited no cytotoxic activities. The distinctive structural features of trout CAMPs provide new insights into the understanding of the evolution of CAMPs in vertebrates. Moreover, the high bacterial membrane selectivity of trout CAMPs will help to design excellent peptide antibiotics., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

Purpose: Epicardial fat is visceral adipose tissue that possesses inflammatory properties. Inflammation and obesity are associated with cardiovascular disease and arrhythmogenesis, but little is known about the relationship between epicardial fat and PR-Interval prolongation. The purpose of this study was to investigate the association between epicardial adipose tissue (EAT) volume and PR-interval prolongation as assessed by computed tomography (CT) and Twelve-lead ECGs., Methods: Patients (n=287) were referred for 64-slice CT for exclusion of coronary artery disease and EAT volumes were determined. Twelve-lead ECGs were obtained from each subject and were evaluated by two independent readers., Results: Patients with significant PR interval prolongation had higher median EAT volume than patients with normal PR interval. Statistically significant correlations were observed between the EAT volume and the PR interval (p = 0.183, p = 0.003), and QRS duration (p = 0.144, p = 0.018). Multivariate and trend analyses confirmed that EAT volume was independently associated with the presence of PR interval prolongation. The receiver operator characteristics curve of EAT volume showed that an EAT volume &gt;144.4 cm&sup3; was associated with PR interval prolongation., Conclusion: This study indicates that EAT volume is highly associated with PR interval prolongation. Whether epicardial fat plays a role in the pathogenesis of PR interval prolongation requires future investigation.

IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.

It is relatively difficult to diagnose bacterial sepsis in nephrolithiasis patients. The aim of the study is to evaluate the diagnostic ability of presepsin in the differential diagnosis including SIRS, infection, or sepsis and to compare its diagnostic value with other markers, mainly as CRP, procalcitonin (PCT), and white blood cell (WBC) in patients of nephrolithiasis presenting with SIRS. 39 patients of nephrolithiasis who were diagnosed as SIRS were prospectively investigated. Plasma presepsin was detected by Pathfast presepsin assay system; CRP and PCT were measured as well. Additionally, 25 nephrolithiasis patients without SIRS were included. At all timing samples, patients were classified as SIRS or non-SIRS group. Median plasma presepsin levels were significantly increased in the SIRS group compared with non-SIRS group (452 pg/mL versus 178 ng/mL, P < 0.001), and presepsin was markedly elevated even in the early stage of SIRS (584 pg/mL 6 h, 660 pg/mL 24 h versus 452 pg/mL, P < 0.001). According to the receiver-operating characteristic (ROC) analysis, presepsin demonstrated a high diagnostic value compared with either PCT or CRP. In the early stage of SIRS, presepsin remained a highly sensitive (74.7%) and specific (88.4%) diagnostic marker compared with either PCT, CRP, or WBC. Moreover, the areas under the curve (AUCs) of presepsin (84.6%) were also superior to those seen in either PCT (79.6%) or CRP (71.8%). Thus plasma presepsin levels have comparable performance in SIRS for patients with nephrolithiasis.

A novel lanthanide coordination polymer nanoparticle (LCPN)-based ternary complex was synthesized via the self-assembly of a terbium ion (Tb(3+)) with a nucleotide (GMP) and a mercury ion (Hg(2+)) in aqueous solution. The as-prepared LCPN-based ternary complex (Tb-GMP-Hg) can be applied to the development of time-resolved luminescence assays and oxidase-based biosensors.

Background: p-Cresylsulfate (PCS), a protein-bound uraemic retention solute, is known to cause endothelial dysfunction and possibly plays a role in coronary atherosclerosis. Furthermore, the association among serum total PCS, major adverse cardiovascular events, and all-cause mortality were also found in previous studies. However, little is known about the relationship between total PCS level and prolonged QT interval. We assessed whether serum total PCS level is related with prolonged QT interval by measuring 12-lead electrocardiogram (ECG) recording in stable angina patients with early stage of renal failure., Methods: Serum total PCS concentrations were measured by using the Ultra Performance LC System in 154 consecutive stable angina patients. A 12-lead ECG recording was obtained from each subject., Results: Patients with abnormal corrected QT (QTc) interval have higher median serum total PCS levels than patients with normal QTc interval. Statistically significant associations were observed between the serum total PCS levels and the QTc interval (r=0.217, P=0.007). Using multivariate and trend analyses, serum total PCS level was independently associated with QTc prolongation., Conclusions: This study indicates that serum total PCS levels are significantly higher in the presence of abnormal QTc interval and are associated with the QTc prolongation. Whether total PCS plays a role in the pathogenesis of QTc prolongation requires future investigation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Previous studies have shown that diallyl disulfide (DADS), a naturally occurring anticancer agent in garlic, arrested human gastric cancer cells (MGC803) in the G2/M phase of the cell cycle. Due to the importance of cell cycle redistribution in DADS-mediated anticarcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. In the present study, the northern blot analysis showed that mRNA expression of for Chkl and Chk2 was unchanged. Notably, DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, activated phospho-ATR (ATM-RAD3-related gene), and dowregulated CDC25C and cyclin B1 expression. Furthermore, CDC25C was immunoprecipitated by anti-Chk1 but not anti-Chk2. Results of the overexpression and knockdown studies, showed that Chk1 but not Chk2 regulated the DADS-induced G2/M arrest of MGC803 cells. The overexpression of Chk1 resulted in significantly increased DADS-induced G2/M arrest, increased DADS-induced Chk1 phosphorylation and inhibited CDC25C expression. Knockdown of Chk1 reduced DADS‑induced G2/M arrest and blocked the DADS-induced inhibition of CDC25C and cyclin B1 expression. These results suggested that Chk1 is important in DADS‑induced cell cycle G2/M arrest in the human MGC803 gastric cancer cell line. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/CDC25C/cyclin B1.

Objective: To investigate the inhibition of sanguinarine on S180 sarcoma in mice and the effect of angiogenesis., Methods: S180 subcutaneous implanted tumor model mice were randomly divided into six groups: control group, cyclophosphamide (CTX) group, sanguinarine (10, 20 and 40 mg/kg) groups and combination group. The mice were sacrificed on the 10th day to measure the tumor weight and volumes, and caculate the tumor growth inhibition. Histopathology was performed, while immunohistochemistry was applied for assessment of MVD (microvascular density) and the expression of VEGF (vascular endothelial growth factor)., Results: The growth of tumors were significantly inhibited in the treatment groups (CTX group, sanguinarine 20 and 40 mg/kg groups, and combination group). HE staining showed tumor cell atypia and pathologic micosis were lower than that of the control group. Scattered and fusion of the slice necrosis foci were observed in the treatment groups. CTX, sanguinarine (20 and 40 mg/kg) and combination significantly reduced the expression of MVD and VEGF compared with the control group (P < 0.01, P < 0.05)., Conclusion: Sanguinarine can effectively inhibit the growth of S180 implanted tumors via reducing MVD and the expression of VEGF, which is associated with its anti-angiogenesis.

IFN regulatory factor (IRF) 10 belongs to the IRF family and exists exclusively in birds and fish. Most IRFs have been identified as critical regulators in the IFN responses in both fish and mammals; however, the role of IRF10 is unclear. In this study, we identified IRF10 in zebrafish (Danio rerio) and found that it serves as a negative regulator to balance the innate antiviral immune responses. Zebrafish IRF10 (DrIRF10) was induced by intracellular polyinosinic:polycytidylic acid in ZF4 (zebrafish embryo fibroblast-like) cells. DrIRF10 inhibited the activation of zebrafish IFN1 (DrIFN1) and DrIFN3 promoters in epithelioma papulosum cyprinid cells in the presence or absence of polyinosinic:polycytidylic acid stimulation through direct interaction with the IFN promoters, and this inhibition was also shown to block IFN signaling. Overexpression of DrIRF10 was able to abolish the induction of DrIFN1 and DrIFN3 mediated by the retinoic acid-inducible gene I-like receptors. In addition, functional domain analysis of DrIRF10 showed that either the DNA binding domain or the IRF association domain is sufficient for its inhibitory activity for IFN signaling. Lastly, overexpression of DrIRF10 decreased the transcription level of several IFN-stimulated genes, resulting in the susceptibility of host cells to spring viremia of carp virus infection. Collectively, these data suggest that DrIRF10 inhibits the expression of DrIFN1 and DrIFN3 to avoid an excessive immune response, a unique regulation mechanism of the IFN responses in lower vertebrates., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Background: The purpose of this study was to investigate whether the pretreatment total and differential leukocyte counts can predict the prognosis of patients with oral cavity cancer., Methods: In a retrospective analysis of patients treated between 2004 and 2011, medical records of 202 patients with oral cavity cancer were evaluated., Results: Patients with oral cavity cancer, the peripheral total white blood cell (WBC) count, monocyte, and neutrophil counts and neutrophil lymphocyte ratio increased with the advancement of clinical stage. In contrast, the lymphocyte count decreased. Further, total WBC, monocyte, and neutrophil counts were increased in those with pathologic stage T4 and poor tumor differentiation, and the monocyte count was also increased in those with lymph node metastasis. Moreover, the pretreatment circulating monocyte count was an independent prognostic factor for cancer-specific survival., Conclusion: A higher pretreatment circulating monocyte count can be considered as a useful prognostic marker in patients with oral cavity cancer., (Copyright © 2014 Wiley Periodicals, Inc.)

MicroRNAs (miRNAs) are 19-24 nucleotide long non-coding RNA species that regulate the expression of multiple target genes at the post-transcriptional level. They are required for normal immune system development and function, and their expression is dynamically regulated in different immune cell subsets during lineage differentiation and immune response. Aberrant expression of miRNAs results in dysregulated innate and adaptive immunity. This in turn can lead to failure to fight against invading pathogens and the development of autoimmune diseases and hematopoietic malignancies. In this article, we review current progress in miRNA research in immunity in both physiological and pathological settings. We also discuss research limitations and challenges that researchers are just beginning to solve.

There are no antivirals or vaccines available to treat Enterovirus 71 (EV71) infections. Although the type I interferon response, elicited upon virus infection, is critical to establishing host antiviral innate immunity, EV71 fails to induce this response efficiently. Here we provide new insights into potential anti-EV71 therapy by showing that neutralization of EV71-induced miR-146a prevents death in mice by restarting the production of type I interferon. EV71 infection upregulates miR-146a, which targets IRAK1 and TRAF6 involved in TLR signalling and type I interferon production. We further identify AP1 as being responsible for the EV71-induced expression of miR-146a. Surprisingly, knocking out miR-146a or neutralizing virus-induced miR-146a by specific antagomiR restores expressions of IRAK1 and TRAF6, augments IFNβ production, inhibits viral propagation and improves survival in the mouse model. Our results suggest that enterovirus-induced miR-146a facilitates viral pathogenesis by suppressing IFN production and provide a clue to developing preventive and therapeutic strategies for enterovirus infections.

Introduction: Visfatin (also known as pre-B cell colony-enhancing factor) is increased in patients with chronic kidney disease and has been linked with coronary atherosclerosis. Given that it has been reported that visfatin plays a role in endothelial dysfunction in chronic kidney disease patients, we examined associations between visfatin levels and several markers related to atherosclerosis., Materials and Methods: The association between visfatin and atherosclerotic risk factors was studied in 173 chronic kidney disease patients (130 men and 43 women). Serum levels of visfatin were measured by the enzyme-linked immunosorbent assay., Results: With increasing visfatin tertiles, patients proved to have a larger number of vessels with stenosis and a higher likelihood of coronary artery disease, as well as having incrementally lower estimated glomerular filtration rate and serum albumin and higher total leukocyte, neutrophil, and monocyte counts; high-sensitivity C-reactive protein; and brain natriuretic peptide levels. Visfatin showed significant positive correlations with low-density lipoprotein cholesterol, uric acid, blood urea nitrogen, creatinine, brain natriuretic peptide, E-selectin, total leukocyte count, neutrophil count, and high-sensitivity C-reactive protein, and a significant negative correlation with estimated glomerular filtration rate and albumin. Only E-selectin was independently associated with visfatin in multiple linear regression analysis., Conclusions: This study indicates that plasma visfatin levels are significantly higher in the presence of coronary artery disease and are correlated with E-selectin levels, which suggest that increased plasma visfatin may be involved in the pathogenesis of coronary atherosclerosis in CKD patients.

Background: Secreted frizzled-related protein 5 (Sfrp5), an endogenous inhibitor of wingless-type MMTV integration site family (Wnt) signalling, is an anti-inflammatory adipokine whose expression is perturbed in models of obesity and type 2 diabetes mellitus (T2DM). Wnt member 5a (Wnt5a) is a representative ligand, and recent reports suggest that Wnt5a is involved in inflammatory diseases and metabolic disorders. The aim of this study was to investigate whether plasma Wnt5a and Sfrp5 levels are altered in patients with T2DM., Methods: Plasma Sfrp5 and Wnt5a concentrations were measured through enzyme-linked immunosorbent assay in type 2 diabetic and nondiabetic subjects., Results: A total of 82 patients with T2DM and 42 nondiabetic subjects were studied. Plasma Sfrp5 levels were found to be elevated in patients with T2DM (9.4 ± 9.0 vs 7.4 ± 10.9 ng/mL, p = 0.006). In contrast, Wnt5a levels were decreased (6.8 ± 12.6 vs 9.1 ± 4.0 ng/dL, p < 0.001). Increasing concentrations of Sfrp5 were independently and significantly associated with T2DM. Multiple logistic regression analysis revealed Sfrp5 as an independent association factor for T2DM, even after full adjustment of known biomarkers. In a multiple linear regression analysis, only the fasting glucose level was positively associated with the plasma Sfrp5 level., Conclusions: Our results indicate that Sfrp5 may play a role in the pathogenesis of T2DM., (Copyright © 2013 John Wiley & Sons, Ltd.)

Foxp3⁺ regulatory T (Treg) cells are a crucial immunosuppressive population of CD4⁺ T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood. Here we report that peripheral Treg cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2-dependent and costimulation-dependent process. By contrast, excess Treg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-xL and Bcl-2 were dispensable for survival of Treg cells, whereas Mcl-1 was critical for survival of Treg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways.

Objective: To explore how to improve follow-up rate and follow-up quality in studies related to quality of life., Methods: A retrospective cross-sectional study was performed in patients with rectal cancer who underwent primary surgery at the Gastrointestinal Surgery Department, The First Affiliated Hospital, Sun Yat-sen University from August 2002 to February 2011 using the European Organization for Research and Treatment of Cancer QLQ-C30 and CR-38 questionnaires. The influence factors of follow-up rate and reasons for missing sex-related items were analyzed., Results: A total of 438 questionnaires were issued. Two hundred and eighty-five responses were received and the follow-up rate was 65.1%. Two hundred and sixty-two patients returned the questionnaires by mail. Responders and non-responders did not differ by sociodemographic and clinical characteristics including sex, age, postoperative time, complication, clinical stage and stoma. Significant differences were found when comparing the missing sex-related items grouped by sex, age, education and working status., Conclusions: Follow-up mode of mail supplemented by interview is suitable for current reality in China in studies on quality of life. Targeted methods should be adopted when investigating the different patient groups to improve follow-up rate of studies on quality of life and sexual function survey.

By using solution culture method, this paper studied the effects of exogenous nitric oxide (NO) on the antioxidants and antioxidases in the ascorbate-glutathione (AsA-GSH) cycle in tomato (Lycopersicon esculentum Mill. ) seedling roots under copper stress.Exogenous NO could affect the metabolic cycle of AsA-GSH in tomato roots under copper stress. Applying appropriate amount of exogenous NO increased the AsA and GSH contents, AsA/DHA and GSH/GSSG ratios, and decreased the DHA and GSSG contents in tomato roots under copper stress. With the addition of 100 micro mol L-1 of BSO, exogenous NO increased the AsA content, AsA/DHA ratio, and the AAO, MDHAR, and DHAR activities, and decreased the DHA, GSH, and GSSG contents and the APX and GR activities. When 250 micro mol L-1 of BSO was added, exogenous NO increased the contents of AsA, GSH, and GSSG, AsA/DHA ratio, and the activities of APX and GR, and decreased the DHA content and the AAO, DHAR and MDHAR activities. It was suggested that exogenous NO could affect the metabolic cycle of AsA-GSH in tomato roots under copper stress, and mitigate the damage of copper stress to tomato roots via regulating the AsA/DHA and GSH/GSSG ratios to alleviate oxidative stress.