bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus
Authors: Li Xiao-Juan , Ma Qing-Yu , Jiang You-Ming , Bai Xiao-Hui , Yan Zhi-Yi , Liu Qun , Pan Qiu-Xia , Liu Yue-Yun , Chen Jia-Xu 
Published: March 2017

AbstractAlthough the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.
Novel and traditional lipid-related biomarkers and their combinations in predicting coronary severity
Authors: Li Sha , Guo Yuan-Lin , Zhao Xi , Zhang Yan , Zhu Cheng-Gang , Wu Na-Qiong , Xu Rui-Xia , Qing Ping , Gao Ying , Li Xiao-Lin , Sun Jing , Liu Geng , Dong Qian , Li Jian-Jun 
Published: March 2017

AbstractWe investigated simultaneously traditional and novel lipid indices, alone or in combination, in predicting coronary severity assessed by Gensini score (GS) in 1605 non-lipid-lowering-drug-treated patients undergoing coronary angiography. Firstly, levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), non high density lipoprotein cholesterol (non-HDL-C), apolipoprotein (apo) B, lipoprotein (a) [Lp(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, small dense LDL (sdLDL) and large HDL were increased, while HDL-C and apoA1 levels were decreased as GS status (all p for trend <0.05). However, gender stratification analyses showed similar associations between lipids and GS in men but not in women. Secondly, multiple logistic regression analyses indicated that the 12 indices were predictive for high GS (≥24) but not for low GS (1–23) compared with normal coronary (GS = 0) except for TG (neither) and apoB (both). Finally, we found that interactions between two indices with mutually exclusive composition were positively associated with GS status except for couples of TC + apoC3, apoB/PCSK9/apoC3 + sdLDL-C. Concordant elevations in the two showed the highest predictive values for high GS (all p for trend <0.05). Therefore, lipid biomarkers were associated with coronary severity and their adverse changes in combination emerged greater risks in men but not in women.
Locating the Human Cardiac Conduction System Using a 3D Model of Its Nutritious Arteries
Authors: Xu Yu , Peng Yukun , Qu Rongmei , Zheng Guorong , Feng Feiyan , Feng Yan , He Linying , He Shanli , Li Zeyu , Liu Chang , Xiao Zhaoming , Ouyang Jun , Dai Jingxing 
Published: March 2017

AbstractIt is difficult for anatomists to dissect the human cardiac conduction system (CCS) on specimens as well as for cardiovascular clinicians to locate the CCS during cardiac operations. Here, we demonstrate a new method for locating the CCS using a 3D model of its nutritious arteries. First, we perfused the coronary arteries with contrast material and then acquired a set of data of thin computer tomography (CT) scans. Then, we generated a 3D model of the coronary artery and distinguished the arteries that supply the CCS. We then located the CCS on the 3D model via its nutritious arteries and dissected the CCS. Finally, the structures that were dissected were removed for histological and immunofluorescent staining. The results of histological and immunofluorescence examination proved the structure to be the CCS. Thus, we successfully located the CCS using a 3D model of its nutritious arteries. We suggest that with this new method, cardiac surgeons can locate a patient’s CCS during cardiac surgeries such as transcatheter aortic valve implantation (TAVI) or radiofrequency catheter ablation (RFCA).
Crystal structure of a raw-starch-degrading bacterial α-amylase belonging to subfamily 37 of the glycoside hydrolase family GH13
Authors: Liu Yanhong , Yu Jigang , Li Fudong , Peng Hui , Zhang Xuecheng , Xiao Yazhong , He Chao 
Published: March 2017

AbstractSubfamily 37 of the glycoside hydrolase family GH13 was recently established on the basis of the discovery of a novel α-amylase, designated AmyP, from a marine metagenomic library. AmyP exhibits raw-starch-degrading activity and consists of an N-terminal catalytic domain and a C-terminal starch-binding domain. To understand this newest subfamily, we determined the crystal structure of the catalytic domain of AmyP, named AmyPΔSBD, complexed with maltose, and the crystal structure of the E221Q mutant AmyPΔSBD complexed with maltotriose. Glu221 is one of the three conserved catalytic residues, and AmyP is inactivated by the E221Q mutation. Domain B of AmyPΔSBD forms a loop that protrudes from domain A, stabilizes the conformation of the active site and increases the thermostability of the enzyme. A new calcium ion is situated adjacent to the -3 subsite binding loop and may be responsible for the increased thermostability of the enzyme after the addition of calcium. Moreover, Tyr36 participates in both stacking and hydrogen bonding interactions with the sugar motif at subsite -3. This work provides the first insights into the structure of α-amylases belonging to subfamily 37 of GH13 and may contribute to the rational design of α-amylase mutants with enhanced performance in biotechnological applications.
An excessive increase in glutamate contributes to glucose-toxicity in β-cells via activation of pancreatic NMDA receptors in rodent diabetes
Authors: Huang Xiao-Ting , Li Chen , Peng Xiang-Ping , Guo Jia , Yue Shao-Jie , Liu Wei , Zhao Fei-Yan , Han Jian-Zhong , Huang Yan-Hong , Yang-Li  , Cheng Qing-Mei , Zhou Zhi-Guang , Chen Chen , Feng Dan-Dan , Luo Zi-Qiang 
Published: March 2017

AbstractIn the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucoseviaactivation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated byGluN1knockout. The NMDAR antagonist MK-801 orGluN1knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia.
A novel toolbox to investigate tissue spatial organization applied to the study of the islets of Langerhans
Authors: Tran Thi Nhu Hoa , Arrojo E. Drigo Rafael , Berggren Per-Olof , Boudier Thomas 
Published: March 2017

AbstractThanks to the development of new 3D Imaging techniques, volumetric data of thick samples, especially tissues, are commonly available. Several algorithms were proposed to analyze cells or nuclei in tissues, however these tools are limited to two dimensions. Within any given tissue, cells are not likely to be organized randomly and as such have specific patterns of cell-cell interaction forming complex communication networks. In this paper, we propose a new set of tools as an approach to segment and analyze tissues in 3D with single cell resolution. This new tool box can identify and compute the geographical location of single cells and analyze the potential physical interactions between different cell types and in 3D. As a proof-of-principle, we applied our methodology to investigation of the cyto-architecture of the islets of Langerhans in mice and monkeys. The results obtained here are a significant improvement in current methodologies and provides new insight into the organization of alpha cells and their cellular interactions within the islet’s cellular framework.
Discrete call types referring to predation risk enhance the efficiency of the meerkat sentinel system
Authors: Rauber R. , Manser M. B. 
Published: March 2017

AbstractSentinel behaviour, a form of coordinated vigilance, occurs in a limited range of species, mostly in cooperative breeders. In some species sentinels confirm their presence vocally by giving a single sentinel call type, whereby the rate and subtle acoustic changes provide graded information on the variation of perceived predation risk. In contrast, meerkat (Suricata suricatta) sentinels produce six different sentinel call types. Here we show that manipulation of perception of danger has different effects on the likelihood of emitting these different call types, and that these call types affect foraging individuals differently. Increasing the perceived predation risk by playing back alarm calls decreased the production rate of the common short note calls and increased the production rate of the rare long calls. Playbacks of short note calls increased foraging behaviour and decreased vigilance in the rest of the group, whereas the opposite was observed when playing long calls. This suggests that the common call types act as all-clear signals, while the rare call types have a warning function. Therefore, meerkats increase the efficiency of their sentinel system by producing several discrete call types that represent changes in predation risk and lead to adjustments of the group’s vigilance behaviour.
Copper transporters are responsible for copper isotopic fractionation in eukaryotic cells
Authors: Cadiou Jean-Loup , Pichat Sylvain , Bondanese Victor P. , Soulard Alexandre , Fujii Toshiyuki , Albarède Francis , Oger Philippe 
Published: March 2017

AbstractCopper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae, whose Cu import is similar to human. Wild type cells are enriched in 63Cu relative to 65Cu. Likewise, 63Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu reductase activity, however, no isotope fractionation is observed and when Cu is provided solely in reduced form for this strain, copper is enriched in 63Cu like in the case of the wild type. Our results demonstrate that Cu isotope fractionation is generated by membrane importers and that its amplitude is modulated by Cu reduction. Based on ab initio calculations, we propose that the fractionation may be due to Cu binding with sulfur-rich amino acids: methionine and cysteine. In hepatocellular carcinoma (HCC), lower expression of the STEAP3 copper reductase and heavy Cu isotope enrichment have been reported for the tumor mass, relative to the surrounding tissue. Our study suggests that copper isotope fractionation observed in HCC could be due to lower reductase activity in the tumor.
Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases
Authors: Maschietto Mariana , Bastos Laura Caroline , Tahira Ana Carolina , Bastos Elen Pereira , Euclydes Veronica Luiza Vale , Brentani Alexandra , Fink Günther , de Baumont Angelica , Felipe-Silva Aloísio , Francisco Rossana Pulcineli Vieira , Gouveia Gisele , Grisi Sandra Josefina Ferraz Ellero , Escobar Ana Maria Ulhoa , Moreira-Filho Carlos Alberto , Polanczyk Guilherme Vanoni , Miguel Euripedes Constantino , Brentani Helena 
Published: March 2017

AbstractSex differences in the prevalence of psychiatric disorders are well documented, with exposure to stress during gestation differentially impacting females and males. We explored sex-specific DNA methylation in the cord blood of 39 females and 32 males born at term and with appropriate weight at birth regarding their potential connection to psychiatric outcomes. Mothers were interviewed to gather information about environmental factors (gestational exposure) that could interfere with the methylation profiles in the newborns. Bisulphite converted DNA was hybridized to Illumina HumanMethylation450 BeadChips. Excluding XYS probes, there were 2,332 differentially methylated CpG sites (DMSs) between sexes, which were enriched within brain modules of co-methylated CpGs during brain development and also differentially methylated in the brains of boys and girls. Genes associated with the DMSs were enriched for neurodevelopmental disorders, particularly for CpG sites found differentially methylated in brain tissue between patients with schizophrenia and controls. Moreover, the DMS had an overlap of 890 (38%) CpG sites with a cohort submitted to toxic exposition during gestation. This study supports the evidences that sex differences in DNA methylation of autosomes act as a primary driver of sex differences that are found in psychiatric outcomes.
Identification of novel chemotherapeutic strategies for metastatic uveal melanoma
Authors: Fagone Paolo , Caltabiano Rosario , Russo Andrea , Lupo Gabriella , Anfuso Carmelina Daniela , Basile Maria Sofia , Longo Antonio , Nicoletti Ferdinando , De Pasquale Rocco , Libra Massimo , Reibaldi Michele 
Published: March 2017

AbstractMelanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.
Eosinophils are key regulators of perivascular adipose tissue and vascular functionality
Authors: Withers Sarah B. , Forman Ruth , Meza-Perez Selene , Sorobetea Daniel , Sitnik Kasia , Hopwood Thomas , Lawrence Catherine B. , Agace William W. , Else Kathryn J. , Heagerty Anthony M. , Svensson-Frej Marcus , Cruickshank Sheena M. 
Published: March 2017

AbstractObesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function.
Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis
Authors: Matsuzaki Sachiko , Darcha Claude , Pouly Jean-Luc , Canis Michel 
Published: March 2017

AbstractEndometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation. Increasing matrix stiffness with TGF-β1 stimulation reduced the number of cell-cell contacts. Cells that retained cell-cell contacts showed decreased expression of E-cadherin and zonula occludens 1 (ZO-1) to cell-cell junctions. Few deep endometriotic epithelial cells (DEE) grown on 30-kPa PGS, which may mimic in vivo tissue compliance of DIE, retained localization of E-cadherin to cell-cell junctions with TGF-β1 treatment. Immunohistochemical analysis showed no phosphorylated Smad 2/3 nuclear localization in E-cadherin+ epithelial cells of DIE. We hypothesize that EEE may undergo an EMT-like process after attachment of endometrium to peritoneum in a TGF-β1–rich microenvironment. However, TGF-β1 signaling may be absent in DIE, resulting in a more epithelial cell-like phenotype in a rigid microenvironment.
Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs
Authors: Pan Yongchu , Liu Hongliang , Wang Yanru , Kang Xiaozheng , Liu Zhensheng , Owzar Kouros , Han Younghun , Su Li , Wei Yongyue , Hung Rayjean J. , Brhane Yonathan , McLaughlin John , Brennan Paul , Bickeböller Heike , Rosenberger Albert , Houlston Richard S. , Caporaso Neil , Teresa Landi Maria , Heinrich Joachim , Risch Angela , Wu Xifeng , Ye Yuanqing , Christiani David C. , Amos Christopher I. , Wei Qingyi 
Published: March 2017

AbstractmRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.
TNF-α stimulates endothelial palmitic acid transcytosis and promotes insulin resistance
Authors: Li Wenjing , Yang Xiaoyan , Zheng Tao , Xing Shasha , Wu Yaogong , Bian Fang , Wu Guangjie , Li Ye , Li Juyi , Bai Xiangli , Wu Dan , Jia Xiong , Wang Ling , Zhu Lin , Jin Si 
Published: March 2017

AbstractPersistent elevation of plasma TNF-α is a marker of low grade systemic inflammation. Palmitic acid (PA) is the most abundant type of saturated fatty acid in human body. PA is bound with albumin in plasma and could not pass through endothelial barrier freely. Albumin-bound PA has to be transported across monolayer endothelial cells through intracellular transcytosis, but not intercellular diffusion. In the present study, we discovered that TNF-α might stimulate PA transcytosis across cardiac microvascular endothelial cells, which further impaired the insulin-stimulated glucose uptake by cardiomyocytes and promoted insulin resistance. In this process, TNF-α-stimulated endothelial autophagy and NF-κB signaling crosstalk with each other and orchestrate the whole event, ultimately result in increased expression of fatty acid transporter protein 4 (FATP4) in endothelial cells and mediate the increased PA transcytosis across microvascular endothelial cells. Hopefully the present study discovered a novel missing link between low grade systemic inflammation and insulin resistance.
Inhibition of cathepsin K promotes osseointegration of titanium implants in ovariectomised rats
Authors: Yi Chun , Hao Ke-Yi , Ma Ting , Lin Ye , Ge Xi-Yuan , Zhang Yu 
Published: March 2017

AbstractThe bone mineral deficiency in osteoporosis poses a threat to the long-term outcomes of endosseous implants. The inhibitors of cathepsin K (CatK) significantly affect bone turnover, bone mineral density (BMD) and bone strength in the patients with osteoporosis. Therefore, we hypothesised that the application of a CatK inhibitor (CatKI) could increase the osseointegration of endosseous implants under osteoporotic conditions. Odanacatib (ODN), a highly selective CatKI, was chosen as the experimental drug. Sixteen rats were randomised into 4 groups: sham, ovariectomy (OVX) with vehicle, OVX with low-dose ODN (5 mg/kg) and OVX with high-dose ODN (30 mg/kg). Titanium implants were placed into the distal metaphysis of bilateral femurs of each OVX rat. After 8 weeks of gavaging, CatKI treatment increased the removal torque, BMD and bone-to-implant contact (BIC). Moreover, high-dose CatKI exerted a better influence than low-dose CatKI. Furthermore, CatKI treatment not only robustly suppressed CatK gene (CTSK) expression, but also moderately reduced expression of the osteoblast-related genes Runx2, Collagen-1, BSP, Osterix, OPN, SPP1 and ALP. Thus, CatKI could affect the osteoblast-related genes, although the balance of bone turnover was achieved mainly by CatK inhibition. In conclusion, CatKI prevented bone loss and aided endosseous implantation in osteoporotic conditions.