Neurotrophic Effect of Citrus 5-Hydroxy-3,6,7,8,3′,4′-Hexamethoxyflavone: Promotion of Neurite Outgrowth via cAMP/PKA/CREB Pathway in PC12 Cells

5-Hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5-OH-HxMF), a hydroxylated polymethoxyflavone, is found exclusively in the Citrus genus, particularly in the peels of sweet orange. In this research, we report the first investigation of the neurotrophic effects and mechanism of 5-OH-HxMF in PC12 pheochromocytoma cells. We found that 5-OH-HxMF can effectively induce PC12 neurite outgrowth accompanied with the expression of neuronal differentiation marker protein growth-associated protein-43(GAP-43). 5-OH-HxMF caused the enhancement of cyclic AMP response element binding protein (CREB) phosphorylation, c-fos gene expression and CRE-mediated transcription, which was inhibited by 2-naphthol AS-E phosphate (KG-501), a specific antagonist for the CREB-CBP complex formation. Moreover, 5-OH-HxMF-induced both CRE transcription activity and neurite outgrowth were inhibited by adenylate cyclase and protein kinase A (PKA) inhibitor, but not MEK1/2, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K) or calcium/calmodulin-dependent protein kinase (CaMK) inhibitor. Consistently, 5-OH-HxMF treatment increased the intracellular cAMP level and downstream component, PKA activity. We also found that addition of K252a, a TrKA antagonist, significantly inhibited NGF- but not 5-OH-HxMF-induced neurite outgrowth. These results reveal for the first time that 5-OH-HxMF is an effective neurotrophic agent and its effect is mainly through a cAMP/PKA-dependent, but TrKA-independent, signaling pathway coupling with CRE-mediated gene transcription. A PKC-dependent and CREB-independent pathway was also involved in its neurotrophic action

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Quantitative changes in various sugar concentrations during fermentation of doughs, sponges and brews

Call number: LD2668 .T4 1968 T32Master of Scienc

Resveratrol analog-3,5,4 '-trimethoxy-trans-stilbene inhibits invasion of human lung adenocarcinoma cells by suppressing the MAPK pathway and decreasing matrix metalloproteinase-2 expression

Resveratrol (3,5,4'-trihydroxystilbene) is a natural polyphenol that presents various physiological activities. It has been reported that the methylated derivatives of resveratrol show better potential antifungal and antiproliferative activities than resveratrol. In the present Study, we investigated the inhibitory effect of 3,5,4'-trimethoxy-trans-stilbene (MR-3), a methylated derivative of resveratrol, on the invasion of A549 cells (a human lung adenocarcinoma cell line). We found that treatment with MR-3 at the concentration of 5 mu M resulted in antiadhesive, antimigratory, and antiinvasive activities oil A549 cells through the suppression of matrix metalloproteinase (MMP)-2 protein expression and transcriptional levels in a time-dependent manner. The suppression of MMP-2 expression by MR-3 led to an inhibition of A549 cell invasion by inactivating phosphorylation of SAPK/c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways. A time-dependent inhibition of protein levels for p65, c-Jun, and c-Fos in the nucleus by MR-3 treatment was also observed. In conclusion, Our data demonstrate that the antiinvasive effects of MR-3 on A549 cells are likely mediated through the inhibition of phosphorylation of JNK and p38, as well as a reduction in the protein levels of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) in the nucleus, ultimately leading to downregulation of MMP-2 expression

Health-Associated Nutrition and Exercise Behaviors in Relation to Metabolic Risk Factors Stratified by Body Mass Index

This study aimed to investigate the relationships of nutrition and exercise behaviors on metabolic risk factors (MRF) when body mass index (BMI) was considered. Health-associated nutrition and exercise behaviors were assessed by a questionnaire, anthropometric values, blood pressure and biochemical determinations that were obtained from 4017 workers. The nutrition score was negatively associated with triglycerides in the overweight subgroup and with systolic blood pressure (SBP) in the obese subgroup. The exercise score was negatively associated with triglycerides and waist circumference (WC) and positively associated with SBP and high-density lipoprotein cholesterol (HDL-C) in the ideal weight subgroup as well as being negatively associated with WC and positively associated with HDL-C in the overweight subgroup. Similarly, the exercise score was negatively associated with WC and positively associated with SBP in the obese subgroup. However, no significant association was found between nutrition or exercise behavior and MRF in the underweight subgroup. In conclusion, the relationships of exercise and nutrition behaviors on MRF varied for different levels of BMI. Exercise showed a significant association with lower WC. Moreover, its effect showed a gradient trend in accordance with the levels of BMI. For ameliorating MRF, exercise seemed to have better effects than nutrition behavior, especially in the ideal weight subgroup

Comparison of the Efficacies of Direct-Acting Antiviral Treatment for HCV Infection in People Who Inject Drugs and Non-Drug Users

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users

Basal accretion, a major mechanism for mountain building in Taiwan revealed in rock thermal history

International audienceDeep tectonic processes are key integral components in the evolution of mountain belts, while observations of their temporal development are generally obscured by thermal resetting, retrograde alteration and structural overprinting. Here we recorded an integrated rock time-temperature history for the first time in the pro-wedge part of the active Taiwan arc-continent collision starting from sedimentation through cleavage-forming state to its final exhumation. The integrated thermal and age results from the Raman Spectroscopy of Carbonaceous Material (RSCM) method, zircon U-Pb laser ablation dating, and in-situ 40Ar/39Ar laser microprobe dating suggest that the basal accretion process was crucial to the development of the Taiwanese orogenic wedge. The basal accretion process commenced early in the mountain building history (∼6 Ma) and gradually migrated to greater depths, as constrained by persistent plate convergence and cleavage formation under nearly isothermal state at similar depths until ∼ 2.5 Ma recorded in the early-accreted units. Such development essentially contributed to mountain root growth by the increased depth of the wedge detachment and the downward wedge thickening during the incipient to full collision stages in the Taiwan mountain belt

Taiwan Perspective: Developing Smart Living Technology

<p>The pursuit of <em>Smart Living Technology</em> is a recent trend in which technology is applied to daily life to increase efficiency, affordability and sustainability. The principle behind <em>Smart Living Technology</em> is that technology should be used to advance the needs of human beings and to increase the quality of life by the power of human creativity while at the same time sustaining the environment for future generations. As such, intelligent networks should be adopted to provide humans with full information to control an individual’s personal environment. Wireless technology can play a key role in enabling smart energy monitoring by allowing consumers to make more informed choices and to connect products and devices to a coordinated management system. The development of <em>Smart Living Technology</em> is based on the concept of user driven innovations. Various Living Labs have been established around the world as development centers for extension of this <em>Smart Living Technology</em>.</p> In this paper, the background and current developments of <em>Smart Living Technology</em> are reviewed, followed by real examples taking place in Taiwan. Finally, the focus and future plan for Taiwan are discussed including a strategy for further development of <em>Smart Living Technology</em> in Taiwan

7-Ketocholesterol Induces Lipid Metabolic Reprogramming and Enhances Cholesterol Ester Accumulation in Cardiac Cells

7-Ketocholesterol (7KCh) is a major oxidized cholesterol product abundant in lipoprotein deposits and atherosclerotic plaques. Our previous study has shown that 7KCh accumulates in erythrocytes of heart failure patients, and further investigation centered on how 7KCh may affect metabolism in cardiomyocytes. We applied metabolomics to study the metabolic changes in cardiac cell line HL-1 after treatment with 7KCh. Mevalonic acid (MVA) pathway-derived metabolites, such as farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, phospholipids, and triacylglycerols levels significantly declined, while the levels of lysophospholipids, such as lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), considerably increased in 7KCh-treated cells. Furthermore, the cholesterol content showed no significant change, but the production of cholesteryl esters was enhanced in the treated cells. To explore the possible mechanisms, we applied mRNA-sequencing (mRNA-seq) to study genes differentially expressed in 7KCh-treated cells. The transcriptomic analysis revealed that genes involved in lipid metabolic processes, including MVA biosynthesis and cholesterol transport and esterification, were differentially expressed in treated cells. Integrated analysis of both metabolomic and transcriptomic data suggests that 7KCh induces cholesteryl ester accumulation and reprogramming of lipid metabolism through altered transcription of such genes as sterol O-acyltransferase- and phospholipase A2-encoding genes. The 7KCh-induced reprogramming of lipid metabolism in cardiac cells may be implicated in the pathogenesis of cardiovascular diseases