1,720,960 research outputs found
A potent ion channel blocker, hydroquinidine, exhibits strong anti-cancer activity on colon, pancreatic, and hepatocellular cancer cells
No full textBackground: Despite recent advances in drug discovery, cancer is still one of the most lethal health problems worldwide. In most cases, standard therapy methods and multi-modal treatments fail, and new therapeutic approaches are required. Ion channels are essential in multiple cellular processes regulating cell division, differentiation, and death. Recent studies on ion-channel modulators emphasize their potential to suppress tumor growth. In that regard, we reasoned that an underinvestigated potassium channel modulator, Hydroquinidine (HQ), may exhibit an anti-carcinogenic activity. Methods and results: HQ’s potential as an anti-neoplastic compound was examined using colony formation assay, wound healing assay, soft agar assay, and Annexin-V assay in the colon, pancreatic, and hepatocellular carcinomas. Our findings unveiled a remarkable anti-cancer activity of HQ by decreasing colony-forming ability, migration capacity, tumorigenicity, and proliferation and stimulating cellular death. HQ significantly reduced the formed colonies and tumorigenicity for all cells. It displayed a significant anti-migrative effect on hepatocellular carcinoma cells and promoted apoptosis in pancreatic and liver cancer cells. The altered gene expression profile upon HQ treatment was in accordance with observed cellular effects. Cells incubated with HQ downregulated the genes acting in cell division and survival, whereas the expression level of genes functioning in cell cycle arrest and apoptosis was elevated. Conclusion: Our data indicate HQ’s competency to limit cancer growth and suggest its utilization as a novel potent anti-carcinogenic agent. Future studies are necessary to provide new insights into the HQ action mechanism and to evaluate its capacity in in-vivo
m 6 A Pathway Regulators Are Frequently Mutated in Breast Invasive Carcinoma and May Play an Important Role in Disease Pathogenesis
No full textBreast invasive carcinoma (BIC) is one of the most commonly observed and the deadliest cancer among women. Studies examining the role of epigenetics and regulation of gene expression stand to make important strides in clinical management of BIC. In this context, messenger-RNA (mRNA) modification by regulatory proteins is noteworthy. Methylation of the adenosine base on the sixth nitrogen position is termed as N6-methyladenosine (m6A) modification, and this is the most abundant mRNA modification in mammals. Using several publicly available datasets, we report, in this study, comprehensive analyses and new findings on the impact of epitranscriptome regulatory factors and genetic alterations in m6A pathway genes on BIC. Accordingly, mutation frequency, type, and expression levels were determined. Importantly, we found that VIRMA, METTL14, RBM15B, EIF3B, YTHDF1, and YTHDF3 genes hold potential significance as prognostic biomarker candidates as evidenced in particular by the overall survival analysis. Enrichment of gene ontology (GO) terms and KEGG pathways for the tumor samples with genetic alterations in the epitranscriptome regulatory pathways were investigated. Dysregulation of regulatory factors in breast cancer was associated with cell division, and survival-related pathways such as "nuclear division," and "chromosome segregation." Hence, the gained overactivity of these pathways may account for BIC's poor prognosis. In conclusion, these data underscore that m6A pathway regulators are frequently mutated in BIC and likely play a significant role in disease pathogenesis. Epitranscriptome pathway genes warrant further research attention as regulators of cancer growth and biological targets in BIC, and with an eye to personalized medicine in clinical oncology
Cellular and Molecular Comparison of Glioblastoma Multiform Cell Lines
No full textGlioblastoma multiform (GBM) is one of the most severe tumor types. It is highly invasive and characterized as a grade IV neoplastic cancer. Its resistance to chemotherapy-temozolomide (TMZ treatment)-in combination with tumor treating fields (TTFields), limits the cure of GBM. Therefore researchers are searching for new treatment options to increase the length of recurrence time and improve overall survival for GBM patients. Several cell lines have been established and are in use to understand the molecular basis of GBM and to test the developed drugs. On one hand, it is highly advantageous to utilize multiple cell lines with different genetic backgrounds to gain more insight into the characterization and treatment of the disease. However, on the other hand, characteristics of these cell lines such as proliferation rate, invasion, and colony formation capacity differ greatly among these cells. Hence, a detailed comparison concerning molecular and cellular features of commonly used cell lines is essential. In this study, cell proliferation and apoptosis rate, cell migration capacity, and gene expression profile of U87, Ln229, and SvGp12 cells have been investigated and compared
Hydroquinidine Displays a Significant Anti-carcinogenic Activity in Breast and Ovarian Cancer Cells via Inhibiting Cell-cycle and Stimulating Apoptosis
No full textBreast and ovarian cancers are women’s most commonly diagnosed cancers. Seeking an efficient anticarcinogenic compound is still a top priority regarding the aggressiveness of these cancers and the limited benefit of current therapies. Hydroquinidine (HQ) is a natural alkaloid used in arrhythmia and Brugada syndrome. As an ion channel blocker, HQ exhibits its activity by altering ion gradient and membrane potential. Considering the growing evidence of ion channel blockers’ antineoplastic potential, we were prompted to test HQ’s effect on breast and ovarian cancers. MCF-7 and SKOV-3 cell lines were used to inspect how HQ acts on survival, clonogenicity, migration, tumorigenicity, proliferation, and apoptosis. The molecular basis for the remarkable antiproliferative and proapoptotic effect of HQ in these cells was dissected by proteomics. CDK1, PSMB5, PSMC2, MCM2, MCM7, YWHAH, YWHAQ, and YWHAB proteins in HQ-treated MCF-7 cells, and RRM2, PSMD2, PSME2, COX2, COX4l1, and CDK6 proteins in HQ-treated SKOV-3 cells were found as low-abundant, which was noteworthy. Based on the in-depth analysis, upon HQ treatment, several cell cycle-related processes were found as suppressed, whereas apoptosis and ferroptosis pathways were found to be activated. The observed proteome alteration in cancer cells may provide mechanistic explanations for the growth-limiting effects of HQ at the cellular level
Axolotl: A resourceful vertebrate model for regeneration and beyond
No full textThe regenerative capacity varies significantly among the animal kingdom. Successful regeneration program in some animals results in the functional restoration of tissues and lost structures. Among the highly regenerative animals, axolotl provides multiple experimental advantages with its many extraordinary characteristics. It has been positioned as a regeneration model organism due to its exceptional renewal capacity, including the internal organs, central nervous system, and appendages, in a scar-free manner. In addition to this unique regeneration ability, the observed low cancer incidence, its resistance to carcinogens, and the reversing effect of its cell extract on neoplasms strongly suggest its usability in cancer research. Axolotl's longevity and efficient utilization of several anti-aging mechanisms underline its potential to be employed in aging studies
Association between the anthropometric measurements and dietary habits on telomere shortening in healthy older adults: A‐cross‐sectional study
Full text linkAim: This study aimed to evaluate the effect of anthropometric measurements and dietary habits on telomere length in healthy older residents in rural and urban areas. Methods: This was a cross-sectional study. The study population included 81 healthy older individuals aged >= 80 years. A quantitative food frequency questionnaire was used to determine dietary habits. Anthropometric measurements were taken by researchers. The telomere length of individuals was determined from leukocytes using quantitative polymerase chain reaction. Results: Urban women had longer telomeres than rural women (P < 0.05). Rural men had significantly higher hip circumference, middle-upper arm circumference and fat-free mass than urban men (P < 0.05). It was shown that while fresh vegetable consumption was higher in rural areas, carbonated drink consumption was higher in urban areas (P < 0.05). In women, homemade bread and sugar consumption were higher in rural areas, and honey consumption was higher in urban (P < 0.05). Red meat, milk-based dessert and pastry consumption explain telomere shortening by 22.5%, 24.8% and 17.9%, respectively. In addition, the model based on anthropometric measurements also contributes to explaining telomere shortening by 42.9%. Conclusion: Red meat, milk-based dessert and pastry consumption, and waist circumference, hip circumference, waist-to-hip ratio and waist-to-height ratio are associated with telomere length. Longer telomeres are associated with a healthy, balanced, adequate diet and maintaining a healthy body weight/proportion, and they are crucial for achieving healthy aging
In vitro anti-carcinogenic effect of andarine as a selective androgen receptor modulator on MIA-PaCa-2 cells by decreased proliferation and cell-cycle arrest at G0/G1 phase
No full textÖZET Bu çalışmanın temel amaçları, 1) sapkın sürücü davranışlarını incelemek; 2) bu davranışlarla öfke ve kazalara ilişkin sorumluluk atfı arasındaki ilişkiyi araştırmak; 3) kazaya karışan ve karışmayan sürücüleri demografik değişkenler, sürücü davranışları, öfke ve kazalara ilişkin sorumluluk atfı açısından karşılaştırmak; 4) kazaya karışma ve riskli sürücüyü öngören değişkenleri saptamaktır. Bu amaçla İzmir ve çevresinde yaşayan 324 erkek 46 kadın olmak üzere toplam 370 sürücüye Sürücü Davranışı Envanteri (SDE), Sürekli Öfke ve Öfke Tarz Ölçeği (SÖÖTÖ), Sorumluluk Atfı Öyküleri ve sürücülerin demografik özelliklerini araştıran Bireysel Bilgi Formu (BBF) uygulanmıştır. SDE'ne uygulanan faktör analizi sonucunda bu envanterin 5 faktörden oluştuğu görülmüştür. Bunlar: trafik kuralı ihlalleri, kurallara uyma ve önemseme, sürücülük stresi ve hatalar, aşırı kendine güven ve saldırgan sürücülük olarak adlandırılmıştır. Sosyo-demografik değişkenler ile sürücü davranışı arasındaki ilişkinin varyans analizi ile incelenmesiyle, genç grubun (18-25 yaş) diğer gruplardan daha fazla trafik kuralı ihlali yaptığı, daha fazla sürücülük stresi yaşadığı ve hata yaptığı, trafikte kendine aşırı güvendiği, saldırgan sürücü davranışlarında bulunduğu ve SDE'nin toplamından daha yüksek puan aldığı bulunmuştur. Kadın sürücüler daha fazla sürücü stresi yaşadıklarını ve hatalar yaptıklarını bildirmişler, toplam SDE'nden erkeklerden daha yüksek puan almışlardır. Çalışmamızda, sürücü davranışı ile sürekli öfke ve öfke ifade tarzı arasındaki ilişki korelasyon analizi ile incelenmiş, trafik kuralı ihlalleri ve saldırgan sürücülük boyutları ve toplam SDE puanı, hem içe yöneltilen, hem de dışa yöneltilen öfke ile anlamlı ve pozitif ilişkili bulunmuştur. Kurallara uyma ve önemseme olarak adlandırılan boyut ise hem içe yöneltilen, hem de dışa yöneltilen öfke ile anlamlı ve negatif bir ilişki göstermiştir.Kazaya karışan ve karışmayan sürücülerin kullanılan ölçeklerden aldıkları puanlar açısından farklılaşıp farklılaşmadığı, tek yönlü varyans analizleriyle incelenmiştir. Analizler sonucunda, kazaya karışan sürücülerin trafik kurallarını daha fazla ihlal ettiklerini, kurallara daha az uyduklarını ve kuralları önemsediklerini, daha fazla sürücülük stresi yaşadıklarını ve hata yaptıklarını, sürücülük becerileri konusunda kendilerine aşırı güvendiklerini ve saldırgan sürücülük davranışları gösterdiklerini bildirdikleri bulunmuştur. Fakat kazaya karışan ve karışmayan deneklerin SÖÖTÖ ve Sorumluluk Atfı Öyküleri puanları birbirinden farklılaşmamıştır. Araştırmamızda, logistik regresyon analizi ile kazaya karışmayı en iyi öngören sürücü özellikleri alkollü araba kullanmak ve sürücü stresi yaşamak ve hata yapmak olmuştur. Hem tehlikeli sayılan kurallara uymama (alkollü araba kullanma, trafik ışık ve işaretlerine, hız sınırlamalarına uymama) nedeniyle ceza alan, hem de kazaya karışan grup riskli sürücü olarak kabul edilmiştir. Logistik regresyon analizi sonucu, alkollü araba kullanmanın, sürücülük deneyiminin az olmasının, kurallara daha az uyma ve kuralları daha az önemsemenin, sürücülük becerisi bakımından kendine aşın güvenin, araba kullanırken stres yaşamanın ve hatalar yapmanın ve toplam SDE'nden yüksek puan almanın trafikteki riskli ya da başka bir deyişle kaza yapmaya eğilimli sürücüleri belirlemede en iyi öngörücü değişkenler olduğu bulunmuşturABSTRACT The purposes of this study were 1) investigating the aberrant driving behaviours, 2) exploring the relationship between these behaviours and responsibility attribution to accidents, 3) comparing drivers involved and not involved accidents, according to the demographic variables, driving behaviour, trait anger and anger expression and responsibility attribution, 4) finding variables which predict accident involved drivers and risky driving. The study was conducted on a sample of 370 (324 men and 46 women) drivers who live in İzmir. Data were collected by the Driver Behaviour Inventory (DBI), Trait Anger and Anger Expression Questionnaire (TAAEQ), Responsibility Attribution Stories (RAS) and Information Form, which assess demographic characteristics of drivers. Factor analysis of Driver Behaviour Inventory items yielded five factors: violations, obedience and consideration of traffic rules, driving stress and errors, exaggerated self- confidence and aggressive driving. Younger drivers (18-25) were more likely to report violations, driving stress and errors, exaggerated self-confidence, and aggressive driving. In addition female drivers were more likely to report driving stress and errors. Violations, aggressive driving and total DBI score were significantly and positively correlated to anger. However 'obedience and consideration of traffic rules' dimension was significantly and negatively correlated to anger. Accident involved drivers expressed less obedience and consideration of traffic rules, while reported more violations, driving stress and errors, self-confidence and aggressive driving. However accident involved and not involved groups did not differ significantly in terms of anger and responsibility attribution measures. Finally the logistic reggression analysis suggested that drinking and driving, driving stress and errors were the best predictors of accident involvement. In addition, less driving experience, obedience and consideration of traffic rules, more self-confidence, driving stress and errors and total DBI scores were found to be predictors of risky driving.
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
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