bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation
Authors: Kang Lin-Lin , Zhang Dong-Mei , Ma Chun-Hua , Zhang Jian-Hua , Jia Ke-Ke , Liu Jia-Hui , Wang Rong , Kong Ling-Dong 
Published: June 2016

AbstractFructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis.
Biological Nitrogen Removal through Nitritation Coupled with Thiosulfate-Driven Denitritation
Authors: Qian Jin , Zhou Junmei , Zhang Zhen , Liu Rulong , Wang Qilin 
Published: June 2016

AbstractA novel biological nitrogen removal system based on nitritation coupled with thiosulfate-driven denitritation (Nitritation-TDD) was developed to achieve a high nitrogen removal rate and low sludge production. A nitritation sequential batch reactor (nitritation SBR) and an anoxic up-flow sludge bed (AnUSB) reactor were applied for effective nitritation and denitritation, respectively. Above 75% nitrite was accumulated in the nitritation SBR with an influent ammonia loading rate of 0.43 kg N/d/m3. During Nitritation-TDD operation, particle sizes (d50) of the sludge decreased from 406 to 225 um in nitritation SBR and from 327–183 um in AnUSB reactor. Pyrosequencing tests revealed that ammonium-oxidizing bacteria (AOB) population was stabilized at approximately 7.0% (calculated as population of AOB-related genus divided by the total microbial population) in the nitritation SBR. In contrast, nitrite-oxidizing bacteria (NOB) population decreased from 6.5–0.6% over the same time, indicating the effective nitrite accumulation in the nitritation SBR. Thiobacillus, accounting for 34.2% in the AnUSB reactor, was mainly responsible for nitrogen removal via autotrophic denitritation, using an external source of thiosulfate as electron donor. Also, it was found that free nitrous acid could directly affect the denitritation activity.
Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity
Authors: Jia Haobo , Ma Jianxiong , Lv Jianwei , Ma Xinlong , Xu Weiguo , Yang Yang , Tian Aixian , Wang Ying , Sun Lei , Xu Liyan , Fu Lin , Zhao Jie 
Published: June 2016

AbstractTo investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus.
Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: metabolic basis for dementia
Authors: Xu Jingshu , Begley Paul , Church Stephanie J. , Patassini Stefano , McHarg Selina , Kureishy Nina , Hollywood Katherine A. , Waldvogel Henry J. , Liu Hong , Zhang Shaoping , Lin Wanchang , Herholz Karl , Turner Clinton , Synek Beth J. , Curtis Maurice A. , Rivers-Auty Jack , Lawrence Catherine B. , Kellett Katherine A. B. , Hooper Nigel M. , Vardy Emma R. L. C. , Wu Donghai , Unwin Richard D. , Faull Richard L. M. , Dowsey Andrew W. , Cooper Garth J. S. 
Published: June 2016

AbstractImpairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer’s disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma-copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case-control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD.
Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with γ-glutamyl hydroxymethyl rhodamine green
Authors: Shinden Yoshiaki , Ueo Hiroki , Tobo Taro , Gamachi Ayako , Utou Mitsuaki , Komatsu Hisateru , Nambara Sho , Saito Tomoko , Ueda Masami , Hirata Hidenari , Sakimura Shotaro , Takano Yuki , Uchi Ryutaro , Kurashige Junji , Akiyoshi Sayuri , Iguchi Tomohiro , Eguchi Hidetoshi , Sugimachi Keishi , Kubota Yoko , Kai Yuichiro , Shibuta Kenji , Kijima Yuko , Yoshinaka Heiji , Natsugoe Shoji , Mori Masaki , Maehara Yoshihiko , Sakabe Masayo , Kamiya Mako , Kakareka John W. , Pohida Thomas J. , Choyke Peter L. , Kobayashi Hisataka , Ueo Hiroaki , Urano Yasuteru , Mimori Koshi 
Published: June 2016

AbstractSentinel lymph node biopsy is performed as a standard procedure in breast cancer surgery, and the development of quick and simple methods to detect metastatic lesions is in high demand. Here, we validated a new fluorescent method using γ-glutamyl hydroxymethyl rhodamine green to diagnose metastatic lymph nodes in breast cancer. One hundred and forty-nine lymph nodes from 38 breast cancer patients were evaluated in this study. Comparison of fluorescent and pathological images showed that this fluorescent method was successful for visualizing breast cancer cells in lymph nodes. This method had a sufficiently high sensitivity (97%), specificity (79%) and negative predictive value (99%) to render it useful for an intraoperative diagnosis of cancer. These preliminary findings suggest that this novel method is useful for distinguishing non-cancerous specimens from those in need of careful examination and could help save time and cost for surgeons and pathologists.
Fast 180° magnetization switching in a strain-mediated multiferroic heterostructure driven by a voltage
Authors: Peng Ren-Ci , Hu Jia-Mian , Momeni Kasra , Wang Jian-Jun , Chen Long-Qing , Nan Ce-Wen 
Published: June 2016

AbstractVoltage-driven 180° magnetization switching provides a low-power alternative to current-driven magnetization switching widely used in spintronic devices. Here we computationally demonstrate a promising route to achieve voltage-driven in-plane 180° magnetization switching in a strain-mediated multiferroic heterostructure (e.g., a heterostructure consisting of an amorphous, slightly elliptical Co40Fe40B20 nanomagnet on top of a Pb(Zr,Ti)O3 film as an example). This 180° switching follows a unique precessional path all in the film plane and is enabled by manipulating magnetization dynamics with fast, local piezostrains (rise/release time <0.1 ns) on the Pb(Zr,Ti)O3 film surface. Our analyses predict ultralow area energy consumption per switching (~0.03 J/m2), approximately three orders of magnitude smaller than that dissipated by current-driven magnetization switching. A fast overall switching time of about 2.3 ns is also demonstrated. Further reduction of energy consumption and switching time can be achieved by optimizing the structure and material selection. The present design provides an additional viable route to realizing low-power and high-speed spintronics.
Prognostic risk model development and prospective validation among patients with cervical cancer stage IB2 to IIB submitted to neoadjuvant chemotherapy
Authors: Huang Kecheng , Sun Haiying , Li Xiong , Hu Ting , Yang Ru , Wang ShaoShuai , Jia Yao , Chen Zhilan , Tang Fangxu , Shen Jian , Qin Xiaomin , Zhou Hang , Yang Runfeng , Gui Juan , Wang Lin , Zhao Xiaolin , Zhang Jincheng , Liu Jiong , Guo Lili , Li Shuang , Wang Shixuan 
Published: June 2016

AbstractThis study was designed to develop a risk model for disease recurrence among cervical cancer patients who underwent neoadjuvant chemotherapy and radical surgery. Data for 853 patients were obtained from a retrospective study and used to train the model and then data for 447 patients from a prospective cohort study were employed to validate the model. The Cox regression model was used for calculating the coefficients of the risk factors. According to risk scores, patients were classified into high-, intermediate- and low-risk groups. There were 49 (49/144, 34%) recurrences observed in the high-risk group (with a risk score ≥ 2.65), compared with 3 (3/142, 2%) recurrences in the low-risk group (with a risk score < 0.90). Disease-free survival (DFS) was significantly different (log-rank p < 0.001) among the three risk groups; the risk model also revealed a significant increase in the accuracy of predicting 5-year DFS with the area under the ROC curve (AUC = 0.754 for risk model vs 0.679 for FIGO stage system); the risk model was also validated with data from the prospective study (log-rank p < 0.001, AUC = 0.766). Both high-risk and intermediate-risk patients can be more effectively identified by this risk model.
Forced rather than voluntary exercise entrains peripheral clocks via a corticosterone/noradrenaline increase in PER2::LUC mice
Authors: Sasaki Hiroyuki , Hattori Yuta , Ikeda Yuko , Kamagata Mayo , Iwami Shiho , Yasuda Shinnosuke , Tahara Yu , Shibata Shigenobu 
Published: June 2016

AbstractExercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; however, mechanisms underlying this entrainment are yet to be elucidated. Here, we showed that the bioluminescence rhythm of peripheral clocks in PER2::LUC mice was strongly entrained by forced treadmill and forced wheel-running exercise rather than by voluntary wheel-running exercise at middle time during the inactivity period. Exercise-induced entrainment was accompanied by increased levels of serum corticosterone and norepinephrine in peripheral tissues, similar to the physical stress-induced response. Adrenalectomy with norepinephrine receptor blockers completely blocked the treadmill exercise-induced entrainment. The entrainment of the peripheral clock by exercise is independent of the suprachiasmatic nucleus clock, the main oscillator in mammals. The present results suggest that the response of forced exercise, but not voluntary exercise, may be similar to that of stress and possesses the entrainment ability of peripheral clocks through the activation of the adrenal gland and the sympathetic nervous system.
Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway
Authors: Zhang Wei , Xue Deting , Yin Houfa , Wang Shengdong , Li Chao , Chen Erman , Hu Dongcai , Tao Yiqing , Yu Jiawei , Zheng Qiang , Gao Xiang , Pan Zhijun 
Published: June 2016

AbstractHSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin.
Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels
Authors: Hu Xiang , Ma Xiaojing , Pan Xiaoping , Luo Yuqi , Xu Yiting , Xiong Qin , Bao Yuqian , Jia Weiping 
Published: June 2016

AbstractClinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and ≥25.0 kg/m2; all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A-FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels.
LTP-1, a novel antimitotic agent and Stat3 inhibitor, inhibits human pancreatic carcinomas in vitro and in vivo
Authors: Huang Han-Li , Chao Min-Wu , Chen Chung-Chun , Cheng Chun-Chun , Chen Mei-Chuan , Lin Chao-Feng , Liou Jing-Ping , Teng Che-Ming , Pan Shiow-Lin 
Published: June 2016

AbstractPancreatic cancer is the leading cause of cancer death worldwide with a poor survival rate. The objective of this study was to determine the mechanism of action of a novel antimitotic and Stat3 inhibitor, LTP-1, on human pancreatic cancer in vitro and in vivo. We found that LTP-1 inhibited pancreatic cancer cell growth and viability with significant G2/M arrest and disruption of microtubule dynamics. LTP-1 also caused G2/M arrest-independent Stat3 dephosphorylation along with ERK activation, which indicated the possible dual function of LTP-1. Long-term treatment of LTP-1 also induced polyploidy, activated caspases, induced subG1 cell population and therefore, triggered pancreatic cancer cell apoptosis. Finally, we used an in vivo xenograft model to demonstrate that LTP-1 suppressed the growth of pancreatic adenocarcinoma. In summary, our data suggest that LTP-1 may alter microtubule dynamics, which ultimately causes polyploidy and apoptosis, thereby inhibiting pancreatic cancer growth in vitro and in vivo. This study provides evidence that LTP-1 could be a potential therapeutic agent for further development of pancreatic cancer treatment.
Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases
Authors: Lee Wen-Chung 
Published: June 2016

AbstractThe Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use.
Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease
Authors: Kim Sokho , Park Surim , Kim Bumseok , Kwon Jungkee 
Published: June 2016

AbstractRecently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway’s IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD.
‘Nothing of chemistry disappears in biology’: the Top 30 damage-prone endogenous metabolites
Authors: Lerma-Ortiz Claudia , Jeffryes James G. , Cooper Arthur J.L. , Niehaus Thomas D. , Thamm Antje M.K. , Frelin Océane , Aunins Thomas , Fiehn Oliver , de Crécy-Lagard Valérie , Henry Christopher S. , Hanson Andrew D. 
Published: June 2016

Many common metabolites are intrinsically unstable and reactive, and hence prone to chemical (i.e. non-enzymatic) damage in vivo. Although this fact is widely recognized, the purely chemical side-reactions of metabolic intermediates can be surprisingly hard to track down in the literature and are often treated in an unprioritized case-by-case way. Moreover, spontaneous chemical side-reactions tend to be overshadowed today by side-reactions mediated by promiscuous (‘sloppy’) enzymes even though chemical damage to metabolites may be even more prevalent than damage from enzyme sloppiness, has similar outcomes, and is held in check by similar biochemical repair or pre-emption mechanisms. To address these limitations and imbalances, here we draw together and systematically integrate information from the (bio)chemical literature, from cheminformatics, and from genome-scale metabolic models to objectively define a ‘Top 30’ list of damage-prone metabolites. A foundational part of this process was to derive general reaction rules for the damage chemistries involved. The criteria for a ‘Top 30’ metabolite included predicted chemical reactivity, essentiality, and occurrence in diverse organisms. We also explain how the damage chemistry reaction rules (‘operators’) are implemented in the Chemical-Damage-MINE (CD-MINE) database (minedatabase.mcs.anl.gov/#/top30) to provide a predictive tool for many additional potential metabolite damage products. Lastly, we illustrate how defining a ‘Top 30’ list can drive genomics-enabled discovery of the enzymes of previously unrecognized damage-control systems, and how applying chemical damage reaction rules can help identify previously unknown peaks in metabolomics profiles.
Story Goodness in Adolescents With Autism Spectrum Disorder (ASD) and in Optimal Outcomes From ASD
Authors: Canfield Allison R. , Eigsti Inge-Marie , de Marchena Ashley , Fein Deborah 
Published: June 2016

Purpose
This study examined narrative quality of adolescents with autism spectrum disorder (ASD) using a well-studied “story goodness” coding system.

Method

Narrative samples were analyzed for distinct aspects of story goodness and rated by naïve readers on dimensions of story goodness, accuracy, cohesiveness, and oddness. Adolescents with high-functioning ASD were compared with adolescents with typical development (TD;
n
= 15 per group). A second study compared narratives from adolescents across three groups: ASD, TD, and youths with “optimal outcomes,” who were diagnosed with ASD early in development but no longer meet criteria for ASD and have typical behavioral functioning.

Results
In both studies, the ASD group's narratives had lower composite quality scores compared with peers with typical development. In Study 2, narratives from the optimal outcomes group were intermediate in scores and did not differ significantly from those of either other group. However, naïve raters were able to detect qualitative narrative differences across groups.

Conclusions
Findings indicate that pragmatic deficits in ASD are salient and could have clinical relevance. Furthermore, results indicate subtle differences in pragmatic language skills for individuals with optimal outcomes despite otherwise typical language skills in other domains. These results highlight the need for clinical interventions tailored to the specific deficits of these populations.