bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of acute liver allograft rejection by IL-10-engineered mesenchymal stem cells
Authors: Niu J , Yue W , Song Y , Zhang Y , Qi X , Wang Z , Liu B , Shen H , Hu X 
Published: February 2014

Summary
Hepatic allograft rejection remains a challenging problem, with acute rejection episode as the major barrier for long-term survival in liver transplant recipients. To explore a strategy to prevent allograft rejection, we hypothesized that mesenchymal stem cells (MSCs) genetically engineered with interleukin-10 (IL-10) could produce beneficial effects on orthotopic liver transplantation (OLT) in the experimental rat model. Syngeneic MSCs transduced with IL-10 were delivered via the right jugular vein 30 min post-orthotopic transplantation in the rat model. To evaluate liver morphology and measure cytokine concentration, the blood and liver samples from each animal group were collected at different time-points (3, 5 and 7 days) post-transplantation. The mean survival time of the rats treated with MSCs–IL-10 was shown to be much longer than those treated with saline. According to Banff scheme grading, the saline group scores increased significantly compared with those in the MSCs–IL-10 group. Retinoid acid receptor-related orphan receptor gamma t (RORγt) expression was more increased in the saline group compared to those in the MSCs–IL-10 group in a time-dependent manner; forkhead box protein 3 (FoxP3) expression also decreased significantly in the saline group compared with those in the MSCs–IL-10 group in a time-dependent manner. The expression of cytokines [IL-17, IL-23, IL-6, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] in the saline groups increased significantly compared with the time-point-matched MSCs–IL-10 group, whereas cytokine expression of (IL-10, TGF-β1) was deceased markedly compared to that in the MSCs–IL-10 group. These results suggest a potential role for IL-10-engineered MSC therapy to overcome clinical liver transplantation rejection.
Interleukin-37 ameliorates myocardial ischaemia/reperfusion injury in mice
Authors: Wu B , Meng K , Ji Q , Cheng M , Yu K , Zhao X , Tony H , Liu Y , Zhou Y , Chang C , Zhong Y , Zhu Z , Zhang W , Mao X , Zeng Q 
Published: February 2014

Summary
Innate immune and inflammatory responses are involved in myocardial ischaemia/reperfusion (I/R) injury. Interleukin (IL)-37 is a newly identified member of the IL-1 family, and functions as a fundamental inhibitor of innate immunity and inflammation. However, its role in myocardial I/R injury remains unknown. I/R or sham operations were performed on male C57BL/6J mice. I/R mice received an injection of recombinant human IL-37 or vehicle, immediately before reperfusion. Compared with vehicle treatment, mice treated with IL-37 showed an obvious amelioration of the I/R injury, as demonstrated by reduced infarct size, decreased cardiac troponin T level and improved cardiac function. This protective effect was associated with the ability of IL-37 to suppress production of proinflammatory cytokines, chemokines and neutrophil infiltration, which together contributed to a decrease in cardiomyocyte apoptosis and reactive oxygen species (ROS) generation. In addition, we found that IL-37 inhibited the up-regulation of Toll-like receptor (TLR)-4 expression and nuclear factor kappa B (NF-kB) activation after I/R, while increasing the anti-inflammatory IL-10 level. Moreover, the administration of anti-IL-10R antibody abolished the protective effects of IL-37 in I/R injury. In-vitro experiments further demonstrated that IL-37 protected cardiomyocytes from apoptosis under I/R condition, and suppressed the migration ability of neutrophils towards the chemokine LIX. In conclusion, IL-37 plays a protective role against mouse myocardial I/R injury, offering a promising therapeutic medium for myocardial I/R injury.
Expression of interleukin (IL)-19 and IL-24 in inflammatory bowel disease patients: a cross-sectional study
Authors: Fonseca-Camarillo G , Furuzawa-Carballeda J , Granados J , Yamamoto-Furusho J K 
Published: February 2014

Summary
Interleukin (IL)-19 and IL-24 belong to the IL-20 subfamily, and are involved in host defence against bacteria and fungi, tissue remodelling and wound healing. Nevertheless, no previous studies have explored their expression in Mexican mestizo patients with inflammatory bowel disease (IBD). The aim of the study was to characterize and to enumerate peripheral and tissue IL-19- and IL-24-producing cells, as well as gene expression in patients with IBD with regard to its clinical activity. We studied a total of 77 patients with ulcerative colitis (UC), 36 Crohn's disease (CD) and 33 patients as control group (without endoscopic evidence of intestinal inflammation). Gene expression was measured by real-time–polymerase chain reaction (RT–PCR). Protein expression was detected in biopsies by immunohistochemistry and in freshly isolated peripheral blood mononuclear cells by flow cytometry. IL-19 and IL-24 gene expression was elevated significantly in patients with active IBD versus the inactive disease and non-inflammatory control groups (P &lt; 0·05). However, IL-19- and IL-24-producing cells were only increased in active CD versus active UC and non-inflammatory tissues (P &lt; 0·05). IL-19 was produced conspicuously by circulating B cells and monocytes in patients with inactive disease (P &lt; 0·05). Conversely, IL-24 was noticeably synthesized by peripheral B cells, CD4+ T cells, CD8+ T cells and monocytes in patients with active disease. In conclusion, IL-19- and IL-24-producing cells in active CD patients were increased compared with active UC and non-inflammatory tissues. These cytokines could significantly shape and differentiate inflammatory process, severity and tolerance loss between UC and CD pathophysiology.
High salt intake does not exacerbate murine autoimmune thyroiditis
Authors: Kolypetri P , Randell E , Van Vliet B N , Carayanniotis G 
Published: February 2014

SummaryRecent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases.
Endogenous interleukin (IL)-17A promotes pristane-induced systemic autoimmunity and lupus nephritis induced by pristane
Authors: Summers S A , Odobasic D , Khouri M B , Steinmetz O M , Yang Y , Holdsworth S R , Kitching A R 
Published: February 2014

Summary
Interleukin (IL)-17A is increased both in serum and in kidney biopsies from patients with lupus nephritis, but direct evidence of pathogenicity is less well established. Administration of pristane to genetically intact mice results in the production of autoantibodies and proliferative glomerulonephritis, resembling human lupus nephritis. These studies sought to define the role of IL-17A in experimental lupus induced by pristane administration. Pristane was administered to wild-type (WT) and IL-17A−/− mice. Local and systemic immune responses were assessed after 6 days and 8 weeks, and autoimmunity, glomerular inflammation and renal injury were measured at 7 months. IL-17A production increased significantly 6 days after pristane injection, with innate immune cells, neutrophils (Ly6G+) and macrophages (F4/80+) being the predominant source of IL-17A. After 8 weeks, while systemic IL-17A was still readily detected in WT mice, the levels of proinflammatory cytokines, interferon (IFN)-γ and tumour necrosis factor (TNF) were diminished in the absence of endogenous IL-17A. Seven months after pristane treatment humoral autoimmunity was diminished in the absence of IL-17A, with decreased levels of immunoglobulin (Ig)G and anti-dsDNA antibodies. Renal inflammation and injury was less in the absence of IL-17A. Compared to WT mice, glomerular IgG, complement deposition, glomerular CD4+ T cells and intrarenal expression of T helper type 1 (Th1)-associated proinflammatory mediators were decreased in IL-17A−/− mice. WT mice developed progressive proteinuria, but functional and histological renal injury was attenuated in the absence of IL-17A. Therefore, IL-17A is required for the full development of autoimmunity and lupus nephritis in experimental SLE, and early in the development of autoimmunity, innate immune cells produce IL-17A.
Effects of cigarette smoke on Toll-like receptor (TLR) activation of chronic obstructive pulmonary disease (COPD) macrophages
Authors: Metcalfe H J , Lea S , Hughes D , Khalaf R , Abbott-Banner K , Singh D 
Published: February 2014

SummaryChronic obstructive pulmonary disease (COPD) is characterized by an abnormal innate immune response. We have investigated the changes in the innate immune response of COPD alveolar macrophages exposed to both cigarette smoke and Toll-like receptor (TLR) stimulation. COPD and control alveolar macrophages were exposed to cigarette smoke extract (CSE) followed by TLR-2, -4 and -5 ligands [Pam3CSK4, lipopolysaccharide (LPS) and phase I flagellin (FliC), respectively] or non-typeable Haemophilus influenzae (NTHi). CSE exposure suppressed TLR-induced tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and regulated on activation, normal T cell expressed and secreted (RANTES) production in both COPD and control alveolar macrophages, but had no effect on interleukin 8 (CXCL8) production. Similarly, CSE suppressed NTHi-induced TNF-α but not NTHi-induced CXCL8 production in COPD alveolar macrophages. Gene expression analysis showed that CSE suppressed LPS-induced TNF-α transcription but not CXCL8 transcription in COPD alveolar macrophages. The dampening effect of CSE on LPS-induced cytokine production was associated with a reduction in p38, extracellular signal regulated kinase (ERK) and p65 activation. In conclusion, CSE caused a reduced innate immune response in COPD alveolar macrophages, with the exception of persistent CXCL8 production. This could be a mechanism by which alveolar macrophages promote neutrophil chemotaxis under conditions of oxidative stress and bacterial exposure.
Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009–10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals
Authors: Milanetti F , Germano V , Nisini R , Donatelli I , Di Martino A , Facchini M , Ferlito C , Cappella A , Crialesi D , Caporuscio S , Biselli R , Rossi F , Salemi S , D'Amelio R 
Published: February 2014

Summary
Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009–10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals.
Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids – differences in vivo and in vitro
Authors: Heydenreich B , Bellinghausen I , Lund L , Henmar H , Lund G , Adler Würtzen P , Saloga J 
Published: February 2014

Summary
Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4+ T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo.
A case–control study of hyponatraemia as an independent risk factor for inpatient mortality
Authors: Tzoulis Ploutarchos , Bagkeris Emmanouil , Bouloux Pierre‐Marc 
Published: February 2014

SummaryObjectivesHyponatraemia is strongly associated with increased inpatient mortality, but it is unknown whether hyponatraemia per se contributes to excess mortality. Our hypothesis was that if hyponatraemic patients had significantly greater mortality compared with controls despite no difference with regard to gender, age, comorbidities and type of primary pathology, this would incriminate hyponatraemia as an independent predictor of mortality.DesignSingle‐centre, case–control study.PatientsCases (N = 139) were hospitalized patients with serum Na ≤ 128 mmol/l over 3 months. Controls were 254 age‐ and gender‐matched patients residing in the same hospital ward with serum Na > 128 mmol/l.MeasurementsData were collected about age, gender, comorbidities, drug history, serum creatinine, intensive care unit (ICU) admission and length of hospitalization. The main outcome measure was inpatient mortality.ResultsHyponatraemic patients had an inpatient mortality rate of 17·3% and were more than three times more likely to die during their hospital stay compared with controls (OR 3·33, 95% CI 1·68–6·58, P < 0·01) despite no statistically significant difference with respect to age, gender, comorbidities, use of common drugs, serum creatinine, ICU admission rate and length of hospitalization. Comparison of cases with the normonatraemic subgroup of controls demonstrated that cases were almost 12 times more likely to die during admission than normonatraemic controls (OR 11·89, 95% CI 2·75–51·51, P < 0·01).ConclusionsThis study showed that hyponatraemia is an independent predictor of mortality, and hyponatraemia per se is likely to contribute to excess mortality. Further studies are needed to examine whether correction of hyponatraemia can reduce mortality.
Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study
Authors: Pivonello Rosario , Petersenn Stephan , Newell‐Price John , Findling James W. , Gu Feng , Maldonado Mario , Trovato Andrew , Hughes Gareth , Salgado Luiz R. , Lacroix André , Schopohl Jochen , Biller Beverly M.K. ,   Pasireotide B2305 Study Group
Published: February 2014

SummaryObjectiveSigns and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with Cushing's disease.DesignPhase III study with double‐blind randomization of two pasireotide doses.MethodsPatients (n = 162) with persistent/recurrent or de novo Cushing's disease and urinary free cortisol (UFC) levels ≥1·5× upper limit of normal (ULN) were randomized to receive subcutaneous pasireotide (600/900 μg bid). At month 3, patients with UFC ≤2 × ULN and not exceeding the baseline value continued their randomized dose; all others received 300 μg bid uptitration. At month 6, patients could enter an open‐label phase until month 12 with a maximal dose of 1200 μg bid. Changes in signs and symptoms of hypercortisolism over 12 months' treatment in patients still enroled in the study and with evaluable measurements were assessed in relation to degree of UFC control.ResultsReductions in blood pressure were observed even without full UFC control and were greatest in patients who did not receive antihypertensive medications during the study. Significant reductions in total cholesterol and low‐density lipoprotein (LDL)‐cholesterol were observed in patients who achieved UFC control. Reductions in BMI, weight and waist circumference occurred during the study even without full UFC control. Adverse effects were typical of somatostatin analogues except for hyperglycaemia‐related events, which were experienced by 72·8% of patients.ConclusionsIn the largest Phase III study of medical therapy in Cushing's disease, significant improvements in signs and symptoms were seen during 12 months of pasireotide treatment, as UFC levels decreased.
Circulating microRNAs in autoimmune thyroid diseases
Authors: Yamada Hiroya , Itoh Mitsuyasu , Hiratsuka Izumi , Hashimoto Shuji 
Published: February 2014

SummaryContextAutoimmune thyroid diseases (AITDs), including Graves’ disease (GD) and Hashimoto's thyroiditis (HT), are the most common autoimmune diseases. MicroRNAs (miRNAs) are small noncoding RNAs, which can play pivotal roles in immune functions and development of autoimmunity. Recently, it has been recognized that identification of circulating miRNAs can provide important and novel information regarding disease pathogenesis and clinical condition. However, the role circulating miRNAs in AITD has not yet been described.ObjectiveThe aim of this study was to characterize the different circulating levels of miRNA in patients with AITD.Design and methodsSixty‐four participants who met the criteria for HT or GD and healthy subjects were recruited. Microarrays were used to analyse the expression patterns of miRNA in serum obtained from patients with HT and GD and healthy subjects. After analysing the microarray data, four interesting miRNAs (miR‐16, miR‐22, miR‐375 and miR‐451) were selected and validated by quantitative real‐time PCR.ResultsSeveral miRNAs were observed to be differently expressed in serum from patients with AITD compared with healthy subjects by microarray analysis. Further analysis consistently showed that serum levels of miR‐22, miR‐375 and miR‐451 were increased in patients with HT. On the other hand, the serum levels of miR‐16, miR‐22, miR‐375 and miR‐451 were increased in patients with GD compared with healthy subjects.ConclusionsWe revealed that different levels of serum miRNAs were associated with GD and HT, which may play a role in the pathogenesis of these diseases.
Why parents matter: exploring the impact of a hegemonic concern with the timetable for the child
Authors: Holt Kim , Kelly Nancy 
Published: February 2014

AbstractIn a climate of austerity, timescales and targets, this paper probes whether parents matter sufficiently within the current child protection system in England. Evidence suggests that achieving partnership working in the context of child protection has become increasingly illusive, particularly when parents are notified that the local authority is considering compulsory intervention to remove their children under the Children Act 1989. Recent changes to legislation, policy and practice ushered in with the aim of achieving earlier decisions within the time frame for the child are laudable, but there are consequences for both children and their parents. The aspirations of the Public Law Outline (2008) are well rehearsed, but the changes being introduced with the recent reform of the family justice system, alongside particular constructions of parenting, may be failing to recognize the potential of many parents, if offered appropriate support, to care safely for their children.
Open spaces, supple bodies? Considering the impact of agile working on social work office practices
Authors: Jeyasingham Dharman 
Published: February 2014

AbstractThere has been a shift towards social workers in many areas of the UK being based in large open plan offices and working more flexibly and remotely in space. This approach is commonly referred to as ‘agile working’. The paper explores the impact of agile working on social workers' practices and experiences in office spaces. It discusses data from an ethnographic study of children's safeguarding social work teams in two locations. One team was based in a large open plan office and was engaged in agile working, the other team was located in a much smaller office and was not using this approach. Data from observations of practice, analysis of material spaces, and interviews with social workers and those responsible for planning office space are examined. The paper concludes that there are qualitative differences between such spaces which are due to agile working arrangements and which are likely to impact significantly on social workers' experiences of practice, interactions with colleagues and development of practice knowledge. The data also suggest a lack of understanding in social work of the spatial requirements of practitioners and the significance that private and open space has for children's social work in the current UK context.