1,720,971 research outputs found
The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2
Get PDFMultiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells. These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM
Role of Capsaicin in Oxidative Stress and Cancer
No full textCapsaicin has been shown to induces apoptosis in various trasformed cell types in vitro and in vivo
Caloric restriction increases the sensitivity to the hyperphagic effect of nociceptin/orphanin FQ limiting its ability to reduce binge eating in female rats
No full textRationale: Nociceptin/Orphanin FQ (N/OFQ) is a functional antagonist of
corticotropin releasing factor, the main mediator of the stress response. Stress
represents a key determinant of binge eating (BE) for highly palatable food
(HPF).
Objectives: In relation to the anti-stress properties of N/OFQ, we
evaluated its effect on BE. After the observation that episodes of food restriction
increase the sensitivity to its hyperphagic effects, the function of NOP receptor
and N/OFQ was investigated after cycles of food restrictions.
Materials and methods: In BE experiments, four groups were used: rats
fed normally and not stressed or stressed, rats exposed to cycles of
restriction/re-feeding and then stressed, or not stressed. In the other
experiments, two groups were used: rats exposed or not to food restriction.
Results: Only restricted and stressed rats exhibited BE for HPF
(containing chocolate cream). Intracerebroventricular injections of N/OFQ 0.5
nmol/rat significantly reduced BE. N/OFQ 1 nmol/rat did not reduce BE but
significantly increased HPF intake following food restrictions. Cycles of food
restriction increased animals’ sensitivity to the hyperphagic effect of N/OFQ for
HPF. In situ hybridization studies following food restrictions showed decreased
ppN/OFQ mRNA expression in the bed nucleus of the stria terminalis and
increased expression of ppN/OFQ and NOP receptor mRNA in the ventral
tegmental area and in the ventromedial hypothalamus, respectively.
Conclusions: These findings indicate that, N/OFQ slightly reduces BE at
low doses, while higher doses increase HPF intake, due to increased sensitivity
to its hyperphagic effect following a history of caloric restrictions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Epigenetic, Genetic, and Acquired Regulation of Cav3 T-Type Calcium Channel Expression and Function in Tumor Growth and Progression
Get PDFT-type Ca2+ channels are a specific channel family controlling proliferation, differentiation, angiogenesis,
and invasion of tumor cells. Molecular biology has identified three main subfamilies of α1 subunits, called
Cav1, Cav2, and Cav3. The third subfamily contains three members, called T-types: Cav3.1 (α1G), Cav3.2
(α1H), and Cav3.3 (α1I). The Cav3 channels are expressed in normal tissues throughout the body as well as
in different types of tumors such as breast, glioma/neuroblastomas, colorectal, gastric, hepatic and prostate
tumors, T cell leukemia, retinoblastoma (RB), and phaeochromocytoma. It has been shown that increased
functional expression of Cav3 channels plays a role in abnormal proliferation of tumor cells. In addition, a
crosstalk between the Rho-ROCK pathway and Cav3 channels in tumor cell migration and invasion has
been demonstrated. Cav3 expression is strictly regulated during cell differentiation and tumor formation.
Inactivation of Cav3 genes by aberrant methylation plays a major role in tumor development and
progression. In this regard, since hypermethylation of CpG islands is thought to be the major epigenetic
modification repressing gene transcription, Cav3.1 has been regarded as a candidate tumor suppressor gene.
In contrast, CpG sites in the Cav3.2 gene were hypomethylated, and thus this gene is considered to be a
candidate oncogene, regulated by methylation. Finally, Cav3 functional diversity may also result from the
generation of splice variants. Alterations in the expression of different splice variants, and their expression
during tumor development and progression, may trigger variety in Ca2+ signaling, which may contribute to
the generation of more aggressive tumor clones
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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