1,720,993 research outputs found
The investigation of molecular mechanisms underlying anti-tumour and anti-neuroinflammation induced by Elephantopus scaber in in vitro and in vivo models / Chan Chim Kei
Elephantopus scaber L. is a perennial herb which is traditionally used for the treatment of various diseases including hepatitis, cancer, inflammation and eczema. Enormous attention has been drawn among the researchers to ascertain its multifarious pharmacological benefits especially anticancer. Considerable evidence has revealed that E. scaber exerts anticancer effect against several cancer cells. In this study, the anti-tumour and anti-neuroinflammatory effects of E. scaber leaves and the plausible underlying molecular mechanisms were elucidated using in vitro and in vivo models. The ethanol extract, hexane, ethyl acetate and aqueous fractions of E. scaber exhibited prominent cytotoxicity towards HCT116 and HT-29 colorectal cancer cells. E. scaber ethyl acetate fraction (ESEAF) revealed the most potent effect against HCT116 cells (IC50= 1.42 μg/mL). Induction of apoptosis by ESEAF resulted in the anti-proliferative effect as evidenced by the morphological and biochemical characteristics: nuclear shrinkage, chromatin condensation, DNA fragmentation and phosphatidylserine externalization. ESEAF potentiated the ROS generation and p53 activation leading to mitochondrial membrane potential depolarization. This consequently resulted in caspases cascade (caspase-3/7 and -9) and cleavage of poly (ADP-ribose) polymerase eventually apoptosis. Besides, N-acetyl-L-cysteine (NAC) abrogated the production of ROS and reversed the ESEAF-induced apoptosis implying that ESEAF mediated ROS-dependent intrinsic apoptosis in HCT116 cells. Bioassay-guided approach has led to the isolation of deoxyelephantopin (DET) from ESEAF which remarkably inhibited the growth of HCT116 cells. DET was discovered to induce cell cycle arrest at S phase which was modulated by a concerted action of cell cycle related-proteins including p21, p53, CDK2, CDK4, cyclin D1, A2, E2 and B1. Similar to ESEAF, a ROS inducing agent, DET dysregulated the Bcl-2 family members accompanied by the attenuation of the XIAP and survivin release and the activation of caspase cascades (caspase-8, -10, -9 and -3) implying the involvement of intrinsic and extrinsic pathways. Moreover, mitigation of PI3K/Akt pathway and activation of MAPK pathway were conferred by DET. Furthermore, the event of autophagy occurred upon ESEAF treatment as corroborated by the accumulation of LC3B-II and p62 degradation. In the presence of NAC, HCT116 cells were rescued from apoptosis and autophagy. Importantly, DET prominently suppressed HCT116 tumour growth on the mouse xenograft model which corresponded with the in vitro findings. In addition, the anti-neuroinflammatory effect of E. scaber leaves were investigated in lipopolysaccharide (LPS)-induced microglia cells (BV-2). In acute toxicity assay, oral administration of 2000mg/kg ESEAF did not result in any mortalities and adverse effects which were substantiated by the normal histopathological evidences. ESEAF also attenuated NF-κB translocation leading to the mitigation of the LPS-induced nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2 and prostaglandin E2 production. The production of pro-inflammatory mediators was suppressed via the inhibition of p38. Upon ESEAF treatment, the formation of ROS in LPS-stimulated BV-2 cells was found to decline following the activation of Nrf2 and HO-1 in which it promotes the scavenging activity of antioxidant enzymes and thus ameliorates neuroinflammation. Conclusively, cumulative findings provided the insight for the potential of E. scaber to be developed as nutraceutical for the intervention of cancer and neuroinflammatory disorders
Induction of mitochondrial-mediated apoptosis in HT-29 human colorectal adenocarcinoma cells by aqueous fraction of Nephelium ramboutan-ake rind. / Chan Chim Kei
The objective of this study was to evaluate the cytotoxic effect and elucidate the possible underlying apoptotic mechanisms of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake reduced the cell viability of HT-29, HCT-116, MDA-MB-231, Ca Ski cells by MTT assay. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the most potent cytotoxic effect against HT-29 cells in a dose-dependent manner. Further investigation for its plausible mechanisms was conducted by using flow cytometry and fluorescence microscopy. This study confirmed the induction of apoptosis by a series of archetypal apoptotic features such as chromatin condensation, DNA fragmentation, cell shrinkage and apoptotic body formation by Hoechst 33342/PI dual staining. The apoptotic mechanisms were further substantiated with the detection of DNA fragmentation by TUNEL assay and phosphatidylserine (PS) externalization on the outer leaflet of plasma membrane which detected by annexin V-FITC/PI binding confirming the early stage of apoptosis. In addition, mitochondrial permeability transition is a vital step in the induction of cellular apoptosis, and data clearly revealed that NRAF resulted in disruption of mitochondrial transmembrane potential (Δψm) in HT-29 cells. Dissipation of Δψm was indicated through a series of evidences such as increased generation of ROS and depletion of GSH, upregulation of Bax protein expression, as well as activation of caspase-3/7 and caspase-9. Collectively, these results suggested that NRAF induced mitochondrial-mediated apoptosis
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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