bluuebunny/crossref_metadata_2025_split huggingface dataset:
METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide‐induced inflammatory response in human dental pulp cells
Authors: Feng Zhihui , Li Qimeng , Meng Runsha , Yi Baicheng , Xu Qiong 
Published: March 2018

AbstractDental pulp inflammation is a widespread public health problem caused by oral bacterial infections and can progress to pulp necrosis and periapical diseases. N6‐methyladenosine (m6A) is a prevalent epitranscriptomic modification in mRNA. Previous studies have demonstrated that m6A methylation plays important roles in cell differentiation, embryonic development and stress responses. However, whether m6A modification affects dental pulp inflammation remains unknown. To address this issue, we investigated the expression of m6A and N6‐adenosine methyltransferase (METTL3, METTL14) as well as demethylases (FTO, ALKBH5) and found that the levels of m6A and METTL3 were up‐regulated in human dental pulp cells (HDPCs) stimulated by lipopolysaccharide (LPS). Furthermore, we knocked down METTL3 and demonstrated that METTL3 depletion decreased the expression of inflammatory cytokines and the phosphorylation of IKKα/β, p65 and IκBα in the NF‐κB signalling pathway as well as p38, ERK and JNK in the MAPK signalling pathway in LPS‐induced HDPCs. The RNA sequencing analysis revealed that the vast number of genes affected by METTL3 depletion was associated with the inflammatory response. Previous research has shown that METTL3‐dependent N6‐adenosine methylation plays an important role in mRNA splicing. In this study, we found that METTL3 knockdown facilitated the expression of MyD88S, a splice variant of MyD88 that inhibits inflammatory cytokine production, suggesting that METTL3 might inhibit the LPS‐induced inflammatory response of HDPCs by regulating alternative splicing of MyD88. These data shed light on new findings in epitranscriptomic regulation of the inflammatory response and open new avenues for research into the molecular mechanisms of dental pulp inflammation.
LncRNA CCAT2 promoted osteosarcoma cell proliferation and invasion
Authors: Yan Lihua , Wu Xiangkun , Yin Xianzhe , Du Feng , Liu Yongxi , Ding Xunmeng 
Published: March 2018

AbstractLong non‐coding RNA (lncRNA) plays important roles in tumour progression. Accumulating studies demonstrated that lncRNA colon cancer‐associated transcript 2 (CCAT2) acted as an oncogene in many tumours. However, the role of CCAT2 in the development of osteosarcoma has not been elucidated. In our study, we indicated that CCAT2 expression was up‐regulated in osteosarcoma tissues and cell lines (SOSP‐9607, MG‐63, U2OS and SAOS‐2). In addition, osteosarcoma cases with higher CCAT2 expression had a poorer disease‐free survival and shorter the overall survival time compared to those with lower expression. Overexpression of CCAT2 promoted osteosarcoma cell proliferation, invasion and cell cycle. Furthermore, ectopic expression of CCAT2 increased the expression of mesenchymal markers N‐cadherin, vimentin and snail and reduced the expression of N‐cadherin marker E‐cadherin. CCAT2 overexpression promoted the LATS2 and c‐Myc expression in osteosarcoma cell. These data indicated that CCAT2 served as an oncogene in osteosarcoma and promoted osteosarcoma cell proliferation, cell cycle and invasion.
Caveolin‐1 down‐regulation is required for Wnt5a‐Frizzled 2 signalling in Ha‐RasV12‐induced cell transformation
Authors: Lin Hsiu‐Kuan , Lin Hsi‐Hui , Chiou Yu‐Wei , Wu Ching‐Lung , Chiu Wen‐Tai , Tang Ming‐Jer 
Published: March 2018

AbstractCaveolin‐1 (Cav1) is down‐regulated during MK4 (MDCK cells harbouring inducible Ha‐RasV12 gene) transformation by Ha‐RasV12. Cav1 overexpression abrogates the Ha‐RasV12‐driven transformation of MK4 cells; however, the targeted down‐regulation of Cav1 is not sufficient to mimic this transformation. Cav1‐silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction‐related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I‐CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha‐RasV12‐inducing MK4 cells increased exosome‐like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I‐CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I‐CM (MK4+I‐EXs). Wnt5a, a downstream product of Ha‐RasV12, was markedly secreted by MK4+I‐CM and MK4+I‐EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha‐RasV12‐ and MK4+I‐CM‐induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down‐regulation, either by Ha‐RasV12 or targeted shRNA, increased frizzled‐2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I‐EXs in MDCK cells. These data suggest that Cav1‐dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha‐RasV12‐Wnt5a‐Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha‐RasV12‐driven cell transformation.
Microtubule defects in mesenchymal stromal cells distinguish patients with Progressive Supranuclear Palsy
Authors: Calogero Alessandra Maria , Viganò Mariele , Budelli Silvia , Galimberti Daniela , Fenoglio Chiara , Cartelli Daniele , Lazzari Lorenza , Lehenkari Petri , Canesi Margherita , Giordano Rosaria , Cappelletti Graziella , Pezzoli Gianni 
Published: March 2018

AbstractProgressive Supranuclear Palsy (PSP) is a rare neurodegenerative disease whose etiopathogenesis remains elusive. The intraneuronal accumulation of hyperphosphorylated Tau, a pivotal protein in regulating microtubules (MT), leads to include PSP into tauopathies. Pathological hallmarks are well known in neural cells but no word yet if PSP‐linked dysfunctions occur also in other cell types. We focused on bone marrow mesenchymal stromal cells (MSCs) that have recently gained attention for therapeutic interventions due to their anti‐inflammatory, antiapoptotic and trophic properties. Here, we aimed to investigate MSCs biology and to disclose if any disease‐linked defect occurs in this non‐neuronal compartment. First, we found that cells obtained from patients showed altered morphology and growth. Next, Western blotting analysis unravelled the imbalance in α‐tubulin post‐translational modifications and in MT stability. Interestingly, MT mass is significantly decreased in patient cells at baseline and differently changes overtime compared to controls, suggesting their inability to efficiently remodel MT cytoskeleton during ageing in culture. Thus, our results provide the first evidence that defects in MT regulation and stability occur and are detectable in a non‐neuronal compartment in patients with PSP. We suggest that MSCs could be a novel model system for unravelling cellular processes implicated in this neurodegenerative disorder.
In vitro models of multiple system atrophy from primary cells to induced pluripotent stem cells
Authors: Abati Elena , Di Fonzo Alessio , Corti Stefania 
Published: March 2018

AbstractMultiple system atrophy (MSA) is a rare neurodegenerative disease with a fatal outcome. Nowadays, only symptomatic treatment is available for MSA patients. The hallmarks of the disease are glial cytoplasmic inclusions (GCIs), proteinaceous aggregates mainly composed of alpha‐synuclein, which accumulate in oligodendrocytes. However, despite the extensive research efforts, little is known about the pathogenesis of MSA. Early myelin dysfunction and alpha‐synuclein deposition are thought to play a major role, but the origin of the aggregates and the causes of misfolding are obscure. One of the reasons for this is the lack of a reliable model of the disease. Recently, the development of induced pluripotent stem cell (iPSC) technology opened up the possibility of elucidating disease mechanisms in neurodegenerative diseases including MSA. Patient specific iPSC can be differentiated in glia and neurons, the cells involved in MSA, providing a useful human disease model. Here, we firstly review the progress made in MSA modelling with primary cell cultures. Subsequently, we focus on the first iPSC‐based model of MSA, which showed that alpha‐synuclein is expressed in oligodendrocyte progenitors, whereas its production decreases in mature oligodendrocytes. We then highlight the opportunities offered by iPSC in studying disease mechanisms and providing innovative models for testing therapeutic strategies, and we discuss the challenges connected with this technique.
Qiliqiangxin attenuates hypoxia‐induced injury in primary rat cardiac microvascular endothelial cells via promoting HIF‐1α‐dependent glycolysis
Authors: Wang Yanyan , Han Xueting , Fu Mingqiang , Wang Jingfeng , Song Yu , Liu Yuan , Zhang Jingjing , Zhou Jingmin , Ge Junbo 
Published: March 2018

AbstractProtection of cardiac microvascular endothelial cells (CMECs) against hypoxia injury is an important therapeutic strategy for treating ischaemic cardiovascular disease. In this study, we investigated the effects of qiliqiangxin (QL) on primary rat CMECs exposed to hypoxia and the underlying mechanisms. Rat CMECs were successfully isolated and passaged to the second generation. CMECs that were pre‐treated with QL (0.5 mg/mL) and/or HIF‐1α siRNA were cultured in a three‐gas hypoxic incubator chamber (5% CO2, 1% O2, 94% N2) for 12 hours. Firstly, we demonstrated that compared with hypoxia group, QL effectively promoted the proliferation while attenuated the apoptosis, improved mitochondrial function and reduced ROS generation in hypoxic CMECs in a HIF‐1α‐dependent manner. Meanwhile, QL also promoted angiogenesis of CMECs via HIF‐1α/VEGF signalling pathway. Moreover, QL improved glucose utilization and metabolism and increased ATP production by up‐regulating HIF‐1α and a series of glycolysis‐relevant enzymes, including glucose transport 1 (GLUT1), hexokinase 2 (HK2), 6‐phosphofructokinase 1 (PFK1), pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Our findings indicate that QL can protect CMECs against hypoxia injury via promoting glycolysis in a HIF‐1α‐dependent manner. Lastly, the results suggested that QL‐dependent enhancement of HIF‐1α protein expression in hypoxic CMECs was associated with the regulation of AMPK/mTOR/HIF‐1α pathway, and we speculated that QL also improved HIF‐1α stabilization through down‐regulating prolyl hydroxylases 3 (PHD3) expression.
Postprandial glucose‐lowering effect of premeal consumption of protein‐enriched, dietary fiber‐fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance
Authors: Bae Jae Hyun , Kim Lee Kyung , Min Se Hee , Ahn Chang Ho , Cho Young Min 
Published: March 2018

AbstractAims/IntroductionProtein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose‐lowering effect of a premeal protein‐enriched, dietary fiber‐fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT).Materials and MethodsThe participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide were measured.ResultsDuring the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon‐like peptide‐1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose‐dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups.ConclusionsAcute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early‐phase insulin secretion, possibly through enhancing glucagon‐like peptide‐1 secretion.
Study design and baseline characteristics of inpatients with diabetes mellitus in a tertiary hospital in China: A database study based on electronic medical records
Authors: Li Sheyu , Yu Chuan , Li Yun , Li Qianrui , Zhang Rui , Hou Qingtao , Zheng Tao , Ma Yi , Wang Miye , Su Na , Wu Ting , Liu Zhiwen , Sheng Xia , Li Nan , Liu Guanjian , Huang Yong , Xu Ting , Sun Xin , Tian Haoming 
Published: March 2018

AbstractAimTo describe the characteristics of inpatients with diabetes in a tertiary hospital in China using an electronic medical record (EMR)‐based database.MethodsWe identified the medical records of all patients with diabetes from nonpediatric departments of West China Hospital, Sichuan University (from February 2009 to December 2013), and extracted information on demographic, diagnosis, discharge outcome, department of discharge, laboratory test, and prescription from the EMR system. The quality of the database was assessed by analyzing missing data and extreme data and by reviewing the International Classification of Diseases 10th Revision (ICD‐10) coding.ResultsAmong 683,267 discharged patients, 56,784 (8.3%) patients diagnosed with diabetes were identified from all departments. Among the patients with diabetes, the average age was 63.5 ± 13.1 years and the overall death in hospital was 2.2%. Laboratory test results were highly completed in our database with no extreme or discrepant value identified. Anthropometric parameters were of a relatively low quality as 62.2% body‐mass index data were missing. HbA1c levels at admission were available for 36.7% patients with diabetes. The ICD‐10 coding of the diagnosis of diabetes was accurate in 88.6% records reviewed. Dyslipidemia (76.5%), hypertension (51.3%), chronic kidney disease (22.1%), and hyperuricemia (16.2%) were the most commonly presented comorbidities among inpatients with diabetes.ConclusionsOur study indicated a wide distribution of diabetes throughout the inpatients in a tertiary hospital in southwest China. This EMR‐based database of diabetes could be potentially useful in further investigations.
BEHAVIORAL ECONOMICS AND BEHAVIORAL FINANCE: A BIBLIOMETRIC ANALYSIS OF THE SCIENTIFIC FIELDS
Authors: Costa Daniel Fonseca , Carvalho Francisval de Melo , Moreira Bruno César de Melo 
Published: March 2018

AbstractThe aim of the study is to conduct a bibliometric analysis of the scientific field of Behavioral Economics and Behavioral Finance. The research was conducted using the Web of Science database, which returned 2617 articles, revealing that the amount of research within these fields has grown over time. Furthermore, the results also prove the relevance of the works of Daniel Kahneman and Amos Tversky for the field of Behavioral Economics and Finance, and Steven Hursh to Behavioral Economics. It is still possible to note that the field of Behavioral Economics encompasses subjects that connect human behavior with demand, consumption and price, with investments and with managerial decisions, as well as with the role played by heuristics and cognitive biases in decision‐making processes. In turn, the field of Behavioral Finance is more focused on the study of errors of judgment and of decision‐making characteristics in financial investments. Additionally, it is inferred that the field of Behavioral Economics is more wide‐ranging than the field of Behavioral Finance, as the latter is a byproduct of Behavioral Economics. Finally, a conclusion is then reached, demonstrating that the fields of Behavioral Economics and Finance have turned into an important field of study.
Impact of stent deformity induced by the kissing balloon technique for bifurcating lesions on in‐stent restenosis after coronary intervention
Authors: Gamou Tadatsugu , Sakata Kenji , Terai Hidenobu , Horita Yuki , Ikeda Masatoshi , Namura Masanobu , Yamagishi Masakazu , Kawashiri Masa‐aki 
Published: March 2018

ObjectivesTo investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in‐stent restenosis (ISR).BackgroundIn experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes.MethodsWe examined 370 coronary lesions where intravascular ultrasound (IVUS)‐guided second‐generation drug‐eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel.ResultsThe stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P < 0.0001) and the stent overstretch index was significantly higher (1.04 ± 0.08 vs 1.01 ± 0.06, P = 0.0007) in lesions with KBT (n = 174) compared to those without KBT (n = 196). The number of two‐stent technique in lesions with KBT was 31 (18%). In multivariate analysis, the degree of stent deformity indices was not associated with ISR in lesions with KBT; however, two‐stent technique use was the only independent predictor of ISR at 8 months (hazard ratio: 3.96, 95% confidence interval: 1.25‐12.5, P = 0.01).ConclusionsSecond‐generation DES deformity induced by KBT was not associated with mid‐term ISR.
An impact of Deoxynivalenol produced by Fusarium graminearum on broiler chickens
Authors: Yu Y.‐H. , Hsiao F. S.‐H. , Proskura W. S. , Dybus A. , Siao Y.‐H. , Cheng Y.‐H. 
Published: March 2018

SummaryDeoxynivalenol (DON) is a major mycotoxin from the trichothecene family of mycotoxins produced by Fusarium fungi that cause disease in grains. Food and feed contaminated with DON cause a variety of adverse health effects in humans and farm animals. However, the fermentation conditions of DON for toxicological study remain to be optimised. Deoxynivalenol levels were increased in a constant temperature of 20°C after fermentation for 7 and 14 days compared with cycling temperatures between 10–20°C and 15–20°C. We have established that optimum conditions for DON production on rice‐based medium is constant temperature at 20°C. In feeding experiments, the villus height and the ratio of villus height and crypt depth were reduced in the duodenum of DON‐fed broiler chickens, whereas a mycotoxin degradation agent efficiently reversed the abnormal morphology of the small intestine in the DON‐fed broilers. The expression of pro‐inflammatory gene, COX‐2, was induced in the spleen and bursa of Fabricius of DON‐fed broilers. This effect was alleviated in the presence of mycotoxin degradation agent. DON produced in solid‐state fermentation is able to cause toxic effects in broilers and induce an abnormal morphology of the small intestine, particularly the duodenum.
Age‐dependent leaf physiology and consequences for crown‐scale carbon uptake during the dry season in an Amazon evergreen forest
Authors: Albert Loren P. , Wu Jin , Prohaska Neill , de Camargo Plinio Barbosa , Huxman Travis E. , Tribuzy Edgard S. , Ivanov Valeriy Y. , Oliveira Rafael S. , Garcia Sabrina , Smith Marielle N. , Oliveira Junior Raimundo Cosme , Restrepo‐Coupe Natalia , da Silva Rodrigo , Stark Scott C. , Martins Giordane A. , Penha Deliane V. , Saleska Scott R. 
Published: March 2018

Summary

Satellite and tower‐based metrics of forest‐scale photosynthesis generally increase with dry season progression across central Amazônia, but the underlying mechanisms lack consensus.

We conducted demographic surveys of leaf age composition, and measured the age dependence of leaf physiology in broadleaf canopy trees of abundant species at a central eastern Amazon site. Using a novel leaf‐to‐branch scaling approach, we used these data to independently test the much‐debated hypothesis – arising from satellite and tower‐based observations – that leaf phenology could explain the forest‐scale pattern of dry season photosynthesis.

Stomatal conductance and biochemical parameters of photosynthesis were higher for recently mature leaves than for old leaves. Most branches had multiple leaf age categories simultaneously present, and the number of recently mature leaves increased as the dry season progressed because old leaves were exchanged for new leaves.

These findings provide the first direct field evidence that branch‐scale photosynthetic capacity increases during the dry season, with a magnitude consistent with increases in ecosystem‐scale photosynthetic capacity derived from flux towers. Interactions between leaf age‐dependent physiology and shifting leaf age‐demographic composition are sufficient to explain the dry season photosynthetic capacity pattern at this site, and should be considered in vegetation models of tropical evergreen forests.
Dense infraspecific sampling reveals rapid and independent trajectories of plastome degradation in a heterotrophic orchid complex
Authors: Barrett Craig F. , Wicke Susann , Sass Chodon 
Published: March 2018

SummaryHeterotrophic plants provide excellent opportunities to study the effects of altered selective regimes on genome evolution. Plastid genome (plastome) studies in heterotrophic plants are often based on one or a few highly divergent species or sequences as representatives of an entire lineage, thus missing important evolutionary‐transitory events.Here, we present the first infraspecific analysis of plastome evolution in any heterotrophic plant. By combining genome skimming and targeted sequence capture, we address hypotheses on the degree and rate of plastome degradation in a complex of leafless orchids (Corallorhiza striata) across its geographic range.Plastomes provide strong support for relationships and evidence of reciprocal monophyly betweenC. involutaand the endangeredC. bentleyi. Plastome degradation is extensive, occurring rapidly over a few million years, with evidence of differing rates of genomic change among the two principal clades of the complex. Genome skimming and targeted sequence capture differ widely in coverage depth overall, with depth in targeted sequence capture datasets varying immensely across the plastome as a function of GC content.These findings will help to fill a knowledge gap in models of heterotrophic plastid genome evolution, and have implications for future studies in heterotrophs.