bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of JMJD2B induces cell apoptosis via mitochondria‐mediated and death receptor‐mediated pathway activation in colorectal cancer
Authors: Sun Bei Bei , Fu Lin Na , Wang Yun Qian , Gao Qin Yan , Xu Jie , Cao Zhi Jun , Chen Ying Xuan , Fang Jing Yuan 
Published: June 2014

ObjectiveTo investigate the molecular mechanism of colorectal cancer (CRC) cell apoptosis induced by the Jumonji domain containing 2B (JMJD2B) silencing.MethodsBoth HCT116 and LoVo CRC cell lines were used for analyses. Cell apoptosis after JMJD2B silencing was determined by flow cytometry. JC‐1 fluorescence probe was applied to measure the mitochondrial outer membrane permeabilization by flow cytometry and fluorescence microscopy. Immunofluorescence was used to detect cytochrome C translocation from mitochondria to cytosol after JMJD2B silencing. The efficacy of JMJD2B silencing on the protein levels of Bcl‐2 family, caspase proteins, CCAAT/enhancer binding protein homologous protein (CHOP) and glucose‐regulated protein 78 (GRP78) were detected by Western blot.ResultsJMJD2B silencing induced CRC cell apoptosis via a decrease of the anti‐apoptotic gene Bcl‐2 family expression, leading to the translocation of Bak and Bax proteins and the promotion of mitochondrial membrane disruption, resulting in the release of cytochrome C from mitochondria and subsequent caspase‐9 and caspase‐3 cleavage. It also increased the amount of cleaved caspase‐8 involved in the death receptor‐related apoptotic pathway. Bcl‐2 homology 3 interacting‐domain death agonist (Bid), a specific caspase‐8 substrate involved in the Fas signaling pathway, subsequently induced cleavage via caspase‐8 activation. However, levels of CHOP and GRP78 remained unchanged after JMJD2B silencing.ConclusionsJMJD2B silencing induced CRC cell apoptosis via both mitochondria‐related and death receptor‐related pathways. The cleavage of Bid activated by caspase‐8 might serve as a crosstalk mediator between these two pathways in CRC.
Randomized controlled trial comparing the efficacy of mosapride plus omeprazole combination therapy to omeprazole monotherapy in gastroesophageal reflux disease
Authors: Yamaji Yutaka , Isomura Yoshihiro , Yoshida Shuntaro , Yamada Atsuo , Hirata Yoshihiro , Koike Kazuhiko 
Published: June 2014

ObjectiveWe investigated whether the prokinetic activity of mosapride, a 5‐hydroxytryptamine 4 receptor agonist, in combination with proton pump inhibitor (PPI) would ameliorate symptoms of gastroesophageal reflux disease (GERD) in Japanese patients.MethodsPatients who experienced reflux symptoms more than twice weekly were eligible for this study. In all, 60 patients were randomized to receive mosapride 5 mg thrice daily combined with omeprazole 10 mg once daily (GO group), or omeprazole alone (O group) for 4 weeks. The patients completed the frequency scale for the symptoms of GERD (FSSG) at the beginning and the end of the study. The primary outcome compared changes in the FSSG reflux‐related symptom (RS) score between treatment groups during the study period.ResultsThe FSSG RS scores significantly decreased both in the GO group and the O group, with no differences in improvement between the groups (−5.86 for the GO group vs −4.89 for the O group, P = 0.49). In non‐erosive reflux disease (NERD) patients the improvement was significantly lower than that in erosive GERD patients (−4.00 vs −7.67, P = 0.02). However, the addition of mosapride was effective in subgroup analyses of specific symptoms, such as burping.ConclusionsCombining mosapride with PPI provided no additional amelioration of reflux symptoms compared to PPI alone. Both regimens provided less relief from reflux symptoms in NERD than in erosive GERD patients. The addition of mosapride ameliorated reflux in patients with symptoms like burping.
Heterotrophic bicarbonate assimilation is the main process of de novo organic carbon synthesis in hadal zone of the Hellenic Trench, the deepest part of Mediterranean Sea
Authors: Yakimov Michail M. , La Cono Violetta , Smedile Francesco , Crisafi Francesca , Arcadi Erika , Leonardi Marcella , Decembrini Franco , Catalfamo Maurizio , Bargiela Rafael , Ferrer Manuel , Golyshin Peter N. , Giuliano Laura 
Published: June 2014

SummaryAmmonium‐oxidizing chemoautotrophic members of Thaumarchaea are proposed to be the key players in the assimilation of bicarbonate in the dark (ABD). However, this process may also involve heterotrophic metabolic pathways, such as fixation of carbon dioxide (CO2) via various anaplerotic reactions. We collected samples from the depth of 4900 m at the Matapan‐Vavilov Deep (MVD) station (Hellenic Trench, Eastern Mediterranean) and used the multiphasic approach to study the ABD mediators in this deep‐sea ecosystem. At this depth, our analysis indicated the occurrence of actively CO2‐fixing heterotrophic microbial assemblages dominated by Gammaproteobacteria with virtually no Thaumarchaea present. [14C]‐bicarbonate incorporation experiments combined with shotgun [14C]‐proteomic analysis identified a series of proteins of gammaproteobacterial origin. More than quarter of them were closely related with Alteromonas macleodii ‘deep ecotype’ AltDE, the predominant organism in the microbial community of MVD. The present study demonstrated that in the aphotic/hadal zone of the Mediterranean Sea, the assimilation of bicarbonate is associated with both chemolithoauto‐ and heterotrophic ABD. In some deep‐sea areas, the latter may predominantly contribute to the de novo synthesis of organic carbon which points at the important and yet underestimated role heterotrophic bacterial populations can play the in global carbon cycle/sink in the ocean interior.
Altered brain functional networks in heavy smokers
Authors: Lin Fuchun , Wu Guangyao , Zhu Ling , Lei Hao 
Published: June 2014

AbstractRecent neuroimaging studies have demonstrated that cigarette smoking is associated with changed brain structure and function. However, little is known about alterations of the topological organization of brain functional networks in heavy smokers. Thirty‐one heavy smokers and 33 non‐smokers underwent a resting‐state functional magnetic resonance imaging scan. The whole‐brain functional networks were constructed by thresholding the correlation matrices of 90 brain regions and their topological properties were analyzed using graph network analysis. Non‐parametric permutation tests were performed to investigate group differences in network topological measures and multiple regression analysis was conducted to determine the relationships between the network metrics and smoking‐related variables. Both heavy smokers and non‐smokers exhibited small‐world architecture in their brain functional networks. Compared with non‐smokers, however, heavy smokers showed altered topological measurements characterized by lower global efficiency, higher local efficiency and clustering coefficients and greater path length. Furthermore, heavy smokers demonstrated decreased nodal global efficiency mainly in brain regions within the default mode network, whereas increased nodal local efficiency predominated in the visual‐related regions. In addition, heavy smokers exhibited an association between the altered network metrics and the duration of cigarette use or the severity of nicotine dependence. Our results suggest that heavy smokers may have less efficient network architecture in the brain, and chronic cigarette smoking is associated with disruptions in the topological organization of brain networks. Our findings may further the understanding of the effects of chronic cigarette smoking on the brain and the pathophysiological mechanisms underlying nicotine dependence.
Genetic variations in the SPP1 promoter affect gene expression and the level of osteopontin secretion into bovine milk
Authors: Dudemaine P. L. , Thibault C. , Alain K. , Bissonnette N. 
Published: June 2014

SummaryOsteopontin (OPN) is now recognized as an important cytokine and extracellular integrin‐binding protein at the crossroads of inflammation and homeostasis. In a previous study, we found that OPN gene (SPP1) polymorphisms are associated with milk performance traits and somatic cell score (SCS), a parameter used to estimate the genetic value of udder health in dairy cattle. In this study, we assessed whether the genetic variations had an impact on SPP1 promoter activity, immune response and the level of OPN secreted into milk. The influence of DNA polymorphisms on the promoter activity of SPP1 was confirmed in vitro. To measure the impact of the genetic variations on OPN secretion into milk, we measured OPN levels in both plasma and milk throughout lactation. Cows were grouped by the OPN haplotypes associated with a high (H2 × H3) or low (H1 × H4) SCS. For both H2 × H3 and H1 × H4, the OPN level in plasma remained low throughout lactation, although the concentration in the milk of H1 × H4 cows increased more in late lactation. Moreover, the macrophages of H1 × H4 cows expressed a lower SPP1 and proinflammatory IL6 in response to infection. Regarding the immune cell response, cows with the genetic potential to secrete higher OPN levels during late lactation had macrophages expressing fewer proinflammatory cytokines, a situation that might explain the genetic association with low somatic cells. Although OPN's favorable roles during late lactation remain to be elucidated, the tissue remodeling properties associated with OPN may be beneficial for reducing the incidence of infection during the transition period in lactating cows.
Thymic stromal lymphopoietin plays divergent roles in murine models of atopic and nonatopic airway inflammation
Authors: Yadava K. , Massacand J. , Mosconi I. , Nicod L. P. , Harris N. L. , Marsland B. J. 
Published: June 2014

AbstractBackgroundThymic stromal lymphopoietin (TSLP) is a cytokine primarily produced by epithelial cells, which has been shown to be a potent inducer of T‐helper 2 (Th2)‐type responses. However, TSLP has pleiotropic effects upon immune cells, and although extensively studied in the context of atopic asthma, its relevance as a therapeutic target and its role in the pathogenesis of nonatopic asthma remains unknown. We sought to investigate the role of TSLP in atopic, nonatopic and viral‐induced exacerbations of pulmonary inflammation.MethodsUsing stringently defined murine models of atopic, nonatopic and virally exacerbated forms of pulmonary inflammation, we compared inflammatory responses of C57BL/6 wild‐type (WT) and TSLP receptor‐deficient (TSLPR KO) mice.ResultsThymic stromal lymphopoietin receptor (TSLPR) signaling was crucial for the development of atopic asthma. Specifically, TSLPR signaling to lung recruited CD4+ T cells enhanced eosinophilia, goblet cell hyperplasia, and overall inflammation within the airways. In contrast, the absence of TSLPR signaling was associated with strikingly exaggerated pulmonary neutrophilic inflammation in a nonatopic model of airway inflammation. The inflammation was associated with excessive levels of interleukin (IL)‐17A in the lungs, indicating that TSLP negatively regulates IL‐17A. In addition, in a model of influenza‐induced exacerbation of atopic airway inflammation, the absence of TSLPR signaling also led to exaggerated neutrophilic inflammation.ConclusionThymic stromal lymphopoietin plays divergent roles in the pathogenesis of atopic and nonatopic asthma phenotypes by either enhancing Th2 responses or curtailing T‐helper 17 responses. These findings raise important caveats for the design of therapeutic interventions targeting TSLP in asthma.
Review article: why, when and how to de‐escalate therapy in inflammatory bowel diseases
Authors: Pariente B. , Laharie D. 
Published: June 2014

SummaryBackgroundTherapeutic objectives are currently evolving in inflammatory bowel diseases (IBD) from control of symptoms towards improvement of long‐term disease outcomes. In patients achieving remission, safety concerns – infections or neoplasia – and economic issues are prompting de‐escalation strategies.AimTo give a complete overview of studies on de‐escalating therapy in IBD.MethodsA structured search in Pubmed, the Cochrane Library and EMBASE was performed using defined key words (inflammatory bowel diseases, Crohn's disease, ulcerative colitis, immunosuppressants, azathioprine, methotrexate, anti‐TNF, infliximab, adalimumab, de‐escalation, dose reduction, cessation, stopping, withdrawal), including full text articles and abstracts in English language.ResultsEleven studies were identified, investigating cessation of immunosuppressants (IS) and/or anti‐TNF treatments. Patients exposed to a combination of IS and anti‐TNF have an increased risk for infections, especially due to opportunistic agent, without any clear signal for associated cancers when compared to those receiving single therapy. In patients receiving IS alone, relapse rate at 12 months following IS cessation is close to 20% and 30% in Crohn's disease (CD) and ulcerative colitis (UC) respectively. There is no study specifically evaluating anti‐TNF treatment withdrawal in case of scheduled anti‐TNF monotherapy in IBD. In patients receiving combination therapy with IS and infliximab (IFX) for at least 6 months, relapse rate of IFX failure following IS cessation is near to 20% at 24 months and seems to be similar in patients who maintained combination therapy. In case of anti‐TNF therapy, cessation in CD patients in combo‐therapy proportion of relapse is high, close to 40% and 50% over 1 year and 2 years respectively. Regarding higher risk of adverse events, some special situations – young males, pregnancy and elderly – should be managed specifically and de‐escalating treatment considered.ConclusionsDe‐escalating treatment strategy should be mainly considered in patients with high risk of severe adverse events and low relapse risk (patients in deep remission) after drug withdrawal. For these reasons, cessation of anti‐TNF treatment and/or immunosuppressants should be a case by case decision in highly selected patients.
Latent profiles of parental self‐efficacy and children's multisource‐evaluated social competence
Authors: Junttila Niina , Vauras Marja 
Published: June 2014

BackgroundThe interrelation between mothers' parental self‐efficacy (PSE) and their school‐aged children's well‐being has been repeatedly proved. The lack of research in this area situates mainly on the absence of fathers, non‐existent family‐level studies, the paucity of independent evaluators, and the use of global PSE estimates.AimsWe aimed to qualitatively identify different subgroups of mothers, fathers, and couples based on their PSE factors. Furthermore, we aimed to study the interrelations between these PSE subgroups and children's school‐related social competence evaluated by the children themselves as well as by their peers, teachers, and parents.SampleSample (n = 981; girls n = 467; boys n = 514) consisted of fourth‐grade (mean age, 10 years old) children, their teachers, peers, and parents (mothers n = 876; fathers n = 696).MethodsLatent profile analysis was used to identify parents with similar patterns of PSE. The data of mothers and fathers were modelled separately and as a family‐level combination. Interrelations between PSE subgroups and children's multisource‐evaluated social competence were analysed with group comparisons.ResultsSeparate subgroups of mothers, fathers, and couples were identified and labelled based on their PSE profiles. Subgroups were found to differ among mothers' age and education and children's academic skills. Most of the interrelations between PSE subgroups and children's social competence were statistically significant in a sense that children of parents with strong PSE were evaluated as more prosocial and less antisocial than others.ConclusionDespite new perspectives on parents' PSE estimates and use of behaviour evaluators outside the family system, the interrelation between positive PSE and children's social competence and learning remains strong.
WHO‐histological criteria for myeloproliferative neoplasms: reproducibility, diagnostic accuracy and correlation with gene mutations and clinical outcomes
Authors: Alvarez‐Larrán Alberto , Ancochea Agueda , García Mar , Climent Fina , García‐Pallarols Francesc , Angona Anna , Senín Alicia , Barranco Carlos , Martínez‐Avilés Luz , Serrano Sergio , Bellosillo Beatriz , Besses Carlos 
Published: June 2014

SummaryBone marrow histology is included in the diagnostic criteria of myeloproliferative neoplasms (MPNs). However, some concerns have emerged about its reproducibility. To evaluate the diagnostic accuracy of histology and to assess its correlation with presence of mutations and clinical outcomes, two pathologists reviewed the bone marrow biopsies corresponding to 211 patients with MPN. Despite the low agreement in the evaluation of individual histopathological characteristics, the concordance among pathologists when establishing the diagnosis was good (Kappa index 0·67). The specificity of histology was 100%, 98·5% and 98% in polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF), respectively, whereas the sensitivity of histological diagnosis was low in PV and ET (32·5% and 54% respectively) and acceptable in PMF (75%). Thirteen out of 146 (9%) patients with clinical ET were diagnosed as prefibrotic PMF. No histological agreement or MPN otherwise unspecified was more frequently observed in JAK2 V617F‐positive ET than in CALR‐mutated cases, whereas megakaryocytic abnormalities and prefibrotic PMF were more frequently observed in CALR‐mutated ET. In conclusion, histological criteria of MPN have a limited diagnostic accuracy due to low sensitivity. Patients with JAK2 V617F‐positive MPN have a heterogeneous histology while CALR‐positive ET is associated with megakaryocyte abnormalities and prefibrotic PMF.
Preservation of the saphenous vein during laparoendoscopic single‐site inguinal lymphadenectomy: comparison with the conventional laparoscopic technique
Authors: Yuan Jun‐Bin , Chen Min‐Feng , Qi Lin , Li Yuan , Li Yang‐Le , Chen Cheng , Chen Jin‐bo , Zu Xiong‐Bing , Liu Long‐Fei 
Published: June 2014

ObjectiveTo prospectively study the surgical strategies and clinical efficacy of laparoendoscopic single‐site (LESS) inguinal lymphadenectomy compared with conventional endoscopic inguinal lymphadenectomy for the management of inguinal nodes.Patients and MethodsA total of 12 patients with squamous cell carcinoma of the penis who underwent penectomy between February and July 2013 were enrolled in the study. All 12 patients underwent bilateral inguinal lymphadenectomy (LESS inguinal lymphadenectomy in one limb and conventional endoscopic inguinal lymphadenectomy in the other) with preservation of the saphenous vein. All lymphatic tissue in the boundaries of the adductor longus muscle (medially), the sartorius muscle (laterally), 2 cm above the inguinal ligament (superiorly), the Scarpa fascia (superficially) and femoral vessels (deeply) was removed in both surgical techniques. All 24 procedures were performed by one experienced surgeon.ResultsAll 24 procedures (12 LESS and 12 conventional endoscopic inguinal lymphadenectomies) were completed successfully without conversion to open surgery. For LESS inguinal lymphadenectomy and conventional endoscopic inguinal lymphadenectomy groups, the mean ± sd operating time was 94.6 ± 14.8 min and 90.8 ± 10.6 min, respectively (P = 0.145). No significant differences in the incidence of postoperative complications (skin‐related problems, hecatomb, lower extremity oedema, lymphatic complications and overall complications) were noted between the two groups (P > 0.05). No lower extremity oedema occurred in any limbs of the two groups. No significant differences were observed in either lymph node clearance rate or detection rate of histologically positive lymph nodes (P > 0.05). The patient satisfaction rate with scar appearance and cosmetic results was significantly better in the LESS inguinal lymphadenectomy group than in the conventional endoscopic inguinal lymphadenectomy group of (75 vs 25%; P = 0.039).ConclusionsThis preliminary study suggests that both LESS inguinal lymphadenectomy and conventional endoscopic inguinal lymphadenectomy are safe and feasible procedures for inguinal lymphadenectomy. Preservation of the saphenous vein during LESS inguinal lymphadenectomy/conventional endoscopic inguinal lymphadenectomy can effectively reduce the incidence of postoperative lower extremity oedema. LESS inguinal lymphadenectomy seems to provide better cosmetic results than conventional endoscopic inguinal lymphadenectomy.
Cardiovascular research is thriving in China
Authors: Gao F , Sun R J , Ji Y , Yang B F 
Published: June 2014

Cardiovascular disease has become the leading cause of death and constitutes a serious public health issue in China. Faced with the burgeoning epidemic of cardiovascular disease and the huge burden and economic losses it causes, the Chinese government has attached the utmost importance to cardiovascular research, increasing funding to support basic and clinical studies, integrating resources and recruiting outstanding talent from overseas. The continued and growing support from the government has yielded substantial changes in terms of new discoveries, scientific publications and drug research and development within the last decade. In spite of the advances in cardiovascular research, China still faces significant challenges ahead in encouraging innovation, developing the prevention‐oriented health policies and strengthening international collaboration.Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
S‐nitrosation and neuronal plasticity
Authors: Santos A I , Martínez‐Ruiz A , Araújo I M 
Published: June 2014

Nitric oxide (NO) has long been recognized as a multifaceted participant in brain physiology. Despite the knowledge that was gathered over many years regarding the contribution of NO to neuronal plasticity, for example the ability of the brain to change in response to new stimuli, only in recent years have we begun to understand how NO acts on the molecular and cellular level to orchestrate such important phenomena as synaptic plasticity (modification of the strength of existing synapses) or the formation of new synapses (synaptogenesis) and new neurons (neurogenesis). Post‐translational modification of proteins by NO derivatives or reactive nitrogen species is a non‐classical mechanism for signalling by NO. S‐nitrosation is a reversible post‐translational modification of thiol groups (mainly on cysteines) that may result in a change of function of the modified protein. S‐nitrosation of key target proteins has emerged as a main regulatory mechanism by which NO can influence several levels of brain plasticity, which are reviewed in this work. Understanding how S‐nitrosation contributes to neural plasticity can help us to better understand the physiology of these processes, and to better address pathological changes in plasticity that are involved in the pathophysiology of several neurological diseases.Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6