E1A Activates Transcription of p73 and Noxa to Induce Apoptosis

p73, a member of the p53 family of proteins, transcriptionally activates a number of genes involved in the control of cell cycle and apoptosis. Overexpression of p73 was detected in a large number of primary head and neck cancers, and in the established cell lines examined, these all contained inactivating p53 mutations. The significance of p73 overexpression in the pathogenesis of head and neck cancer is currently unclear. We have shown that the expression of adenovirus 5 E1A in a panel of head and neck cancer cell lines induces apoptosis independently of their p53 status. In this study we examined the role of p73 and its transcriptional targets in E1A-mediated induction of apoptosis. E1A expression resulted in significant activation of the TAp73 promoter but had no effect on the alternative, DeltaNp73 promoter. E1A also increased expression of endogenous TAp73 mRNA and protein. E1A mutants lacking the p300- and/or pRB-binding sites showed reduced ability to activate the TAp73 promoter. Additionally, mutations in the E2F1-binding sites in the TAp73 promoter impaired activation by E1A. Importantly, expression of the 13S isoform of E1A substantially induced the p53 apoptotic target Noxa in several p53-deficient cancer cell lines. Our results indicate that E1A activation of p73 and the p53 apoptotic target Noxa can occur in the absence of a functional p53. This activation is likely to play a key role in the mechanism of p53-independent apoptosis induced by E1A in some cancers and may provide an avenue for future cancer therapies

In Vitro Assessment of the Anti-Proliferative and Anti-Viability Effects of Salivary Gland Extracts from Hyalomma ticks (Acari: Ixodidae) on Human Colorectal Cancer Cells

Background: The saliva and salivary glands of ticks possess a wide range of immuno-pharmacologically active mole­cules that effectively modulate the activity of enzymes, antibodies, and amines that have a role in different biological processes. Derived components from saliva and salivary glands of hard ticks Ixodidae have been characterized as poten­tial natural sources for discovering promising anti-cancer drug candidates. Methods: The anti-cancer activity of salivary gland extracts (SGEs) from Hyalomma anatolicum, Hyalomma drome­darii, Hyalomma marginatum, and Hyalomma schulzei was assessed. MTT assays and flow cytometry were done on the HT-29 colorectal cancer cell line to evaluate the anti-viability and proliferative inhibition. Results: Based on the MTT assay results, the SGEs from Hy. dromedarii had the highest and lowest substantial anti-viability effects on the HT-29 cancer cell and human foreskin fibroblast (HFF) normal cell, respectively. The cytometric assessment revealed a significant increase in the apoptosis and necrosis ratio of the HT-29 cancer cells after treatment with Hy. dromedarii SGEs. Conclusion: The results demonstrated that Hy. dromedarii SGEs have significant anti-proliferative, anti-viability, and apoptotic potential. The result of this study suggests that Hy. dromedarii SGEs is an appropriate candidate for further investigations to identify and purify the mechanisms and molecules involved in the anti-cancer activity of the SGEs

Relationship between serum anti-heat shock protein 27 antibody levels and obesity

Background Heat shock protein 27 (HSP27) is an intracellular molecular chaperone that is expressed at high levels following the exposure of cells to environmental stressors such as heat, toxins, and free radicals. High levels of HSP antigens and antibody titers have been reported in several conditions including cardiovascular disease and cancers. We measured serum anti-HSP27 antibody levels in 993 subjects and assessed the associations between serum anti-HSP27 antibody levels and demographic characteristics including coronary risk factors. Methods A total of 993 subjects were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Demographic, clinical, and biochemical parameters and serum anti-HSP27 antibody titers were determined in all the subjects. Results Serum anti-HSP27 antibody levels increased with increasing age in men. No significant differences in levels were detected between men and women. Serum anti-HSP27 antibody levels were significantly higher in obese subjects than in nonobese subjects (P = 0.046); however, no significant influence of smoking status was observed. Moreover, serum anti-HSP27 antibody titers were positively associated with age, body mass index, waist/hip ratio, the presence of diabetes mellitus, nonsmoking habit, serum triglycerides, cholesterol, and high-sensitivity c-reactive protein. Conclusion We have found that serum anti-HSP27 antibody titers are related to several cardiovascular risk factors, necessitating further studies on the value of this emerging marker for risk stratification

Uncovering the Role of Intention in Active and Passive Perception

According to the embodied approach to cognition, perception and action are tightly intertwined, as perception is for action and is guided by action. To better understand what this view implies behaviorally, we studied how active movement and intentionality during perceptual exploration affect perceptual accuracy. Participants explored two-dimensional objects using a sensory substitution device, then reported their object size estimates. We manipulated 1) their control over exploratory movements as being either Active (control present) or Passive (control absent) and 2) their knowledge of the task goals, being either Specific (task-focused) or Generic. We found no difference between the Active and Passive conditions but significantly higher perceptual accuracy in Specific Intention trials compared to Generic Intention ones. These results clarify the nature of active perception and contribute to the growing body of evidence that higher level cognitive goals shape how we dynamically sample even low level sensory information from the world

Determining the effectiveness of cognitive behavioral therapy interventions based on the transdiagnostic approach in the treatment of common mental health problems : Presenting an experience from the Islamic Republic of Iran

Introduction: There is growing support to develop transdiagnostic approaches that provide new insights into mental health problems and cut across the existing traditional diagnostic boundaries all over the world. The present study was conducted to test the transdiagnostic cognitive behavioral therapy (TCBT) approach in treating patients with common mental health problems and evaluate its effectiveness compared to the current treatment settings of the healthcare system. Methods: A randomized controlled trial was conducted in Semnan Province, north of Iran. The study took pace in urban health centers. A sample of 520 Iranian adults, tested as positive on the Kessler Psychological Distress Scale, were enrolled. Participants who received a score above the cut-off point in any of the three mental health disorders (depression, anxiety, or obsessive compulsive disorder [OCD]) based on the locally validated study instrument were randomly allocated to the study. The intervention group received TCBT during eight sessions provided by trained general health service providers without previous mental health training; the standby control group received Mental Health Services as Usual (MHSU). The post-test interviews were conducted using the study instrument after the completion of both group treatments. Results: A total of 459 individuals (87.8% female) ultimately entered the study. The withdrawal rate was 24% (53 participants in the TCBT and 56 in the MHSU). Reduction in depression, anxiety, and OCD symptoms was significant within each group and when comparing TCBT and MHSU (mean difference). Conclusion: This trial recommends that the transdiagnostic CBT approach can be effective in improving common mental health problems and functions among individuals by trained general healthcare providers in the primary healthcare system. The results can be more useful in decision making when defining the process of providing mental healthcare in the National Primary Healthcare System