Agave negatively regulates YAP and TAZ transcriptionally and post-translationally in osteosarcoma cell lines

Osteosarcoma (OS) is the most aggressive type of primary solid tumor that develops in bone. Whilst conventional chemotherapy can improve survival rates, the outcome for patients with metastatic or recurrent OS remains poor, so novel treatment agents and strategies are required. Research into new anticancer therapies has paved the way for the utilisation of natural compounds as they are typically less expensive and less toxic compared to conventional chemotherapeutics. Previously published works indicate that Agave exhibits anticancer properties, however potential molecular mechanisms remain poorly understood. In the present study, we investigate the anticancer effects of Agave leaf extract in OS cells suggesting that Agave inhibits cell viability, colony formation, and cell migration, and can induce apoptosis in OS cell lines. Moreover, Agave sensitizes OS cells to cisplatin (CDDP) and radiation, to overcome chemo- and radio-resistance. We demonstrate that Agave extract induces a marked decrease of Yes Associated Protein (YAP) and Tafazzin (TAZ) mRNA and protein expression upon treatment. We propose an initial mechanism of action in which Agave induces YAP/TAZ protein degradation, followed by a secondary event whereby Agave inhibits YAP/TAZ transcription, effectively deregulating the Nuclear Factor kappa B (NF-\u3baB) p65:p50 heterodimers responsible for transcriptional induction of YAP and TAZ

Prophylaxis of Acute Enteric Infections and Viral Hepatitis A under Emergency Situation in the Territory of the Amur Region

Hydrological natural disasters and post-flooding epidemiological situation are often attended by epidemic emergencies creating a threat to life-comforts sustaining and sanitary-epidemiologic welfare of a significant number of citizens. To evaluate the efficiency of preventive and anti-epidemic measures the analysis of acute enteric infection incidence rate in the Amur Region for the past decade, during the high water and in the post-flooding period in 2013 has been carried out. Displayed are the data concerning the prophylaxis of acute enteric infections and viral hepatitis A under the conditions of the emergency situation caused by natural calamities notably by flood in the Amur Region. Adequate planning and operative implementation of organizational, preventive and anti-epidemic measures have made it possible to control acute enteric and viral hepatitis A infection at the sporadic level

RANGING THE KHABAROVSK KRAY TERRITORIES BY THE LEVELS OF DYSENTERY EPIDEMIC MANIFESTATIONS

Aim: to reveal the Khabarovsk region territories that are under high risk of spread of dysentery in the period of large-scale flood fallout liquidation. Materials and methods. There was the analysis conducted of dysentery incidence during the period of 2003-2012 including distribution of annual and long-term annual average indicators per 100 000 inhabitants throughout administrative entities of Khabarovsk territory. We used methods that reveal tendencies and evaluated dynamic rates of dysentery epidemic process in time. Results and discussion. Khabarovsk region shows uneven levels of manifestations of epidemic process of dysentery not only during evaluation of annual incidence but also among certain administrative territories. During ten years preceding the flood in the Amur River region, long-term annual average level of incidence equaled to 42.7 ± 1.740/0000 The epidemic process was most intense in the Nanayi region, in other six administrative regions long-term annual average levels of incidence were exceeding similar averaged levels in Khabarovsk region. An intense epidemiologic situation on dysentery in several territories of the region was associated with registration of foci of clustered incidence caused by dysentery Sonne of alimentary and water-borne origin including atypical variants of Shigella Sonne. Conclusion. A year before the flood the elevation of dysentery incidence was registered in most of the territories of Khabarovsk Kray, and there was the evidence of outlined tendency of activation of epidemic process. This served as a basis for required adequate emergency measures for prophylaxis of dysentery

Retrospective Analysis of Enterovirus Infection Morbidity Rate in the Territory of the Amur Region and Peculiarities of Epidemic Process in the Period of Large-Scale Flood

There has been observed a tendency to increment of enterovirus morbidity rate over the past seven years. Foci of this infection have been formed in the area from time to time, with minor forms of the disease being predominant in clinical findings. Genetically enteroviruses circulating in the Amur Region have been characterized as homogenous; however there is a genetic relation among them with and, consequently, epidemiologic connection to enteroviruses originated from China. However, since May, 2013 there has been detected a boost activation of epidemic process as regards enteroviral infection, followed by the formation of two major foci with clustered infection, due to importation from Thailand as well. Emergency situation under conditions of flood (August-September, 2013) has contributed to aggravation of epidemiological situation on enteroviral infection. It has led to the increase in numbers of the exposed up to the maximum level for the past few years. In the territory of the temporal accommodation sites, where affected by high water and exposed to the infection population was placed, registered have been the cases of clustered enterovirus infection

Epidemiological Features of Enterovirus Infection during Flood on the Territory of Jewish Autonomous Region

Long-term manifestations of epidemiological process of enterovirus infection in the Jewish Autonomous Region were similar to those in the Khabarovsk Territory, though with a lower intensity. After establishment of emergency situation regime, in view of the rainfall flooding in 2013, enterovirus morbidity rate had been increasing within three weeks duration, then started to fall rapidly. Clustered cases of enterovirus infection were not registered. Viral serous meningitis ratio was insignificant as minor forms of the disease prevailed; coxsackie virus A-9 and echovirus-6 dominated. During the flood period isolated from samples of patients with minor forms of enteroviral disease were three enterovirus strains, type 71, sub-genotype C4a, possessing a high degree of genetic similarity to the Chinese ones, 2010-2011. All in all impact of the natural disaster on the epidemiological situation on enteroviral infection in the Jewish Autonomous Region turned to be insignificant

Multiannual Analysis of Epidemiological Process Manifestations as Regards Enteroviral Infection in the Khabarovsk Territory, and the Key Factors that Predetermine Aggravation of Epidemiological Situation under the Terms of Flood

Carried out has been retrospective analysis of epidemiological process manifestations as regards enteroviral infection in the Khabarovsk Region over the period of 7 years, prior to rainfall floods in 2013. Revealed is the possibility of aggravation of epidemiological situation during hydrological emergency situation. The premises are as follows: persistent due to specific climate conditions prevalent in the Khabarovsk Territory (high air and surface water temperatures, and high humidity rates) unfavorable epidemiological situation on enteroviral infections, virus-carriage in “healthy” people and extensive dissemination of enteroviruses in the water bodies of ambient environment. Moreover, widespread circulation of different enterovirus genotypes, including the isolates with high genetic similarity to the strains identified earlier in the adjoining People’s Republic of China, takes place

Epidemiological Characteristics of Enterovirus Infection in the Khabarovsk Territory under Hydrologic Emergency Situation

The paper contains the data on the role of high waters (2013) in changing epidemiological situation on enterovirus infections in the Khabarovsk Territory. The incidence rate in the region was characterized by the significant increase even before the flood, 2013. Thus, two peaks of enterovirus morbidity curve were identified for the period of a week: one - more intensive, another - coincident with flood outbreak. Enterovirus epidemiological process was notified by the changes in clinical picture among the infected population and cohort age-related structure. The percentage of the patients with enterovirus infections in the foci clusters and the index of people infected due to possible exposure to shattering impact of the flood, turned out to be low. However, revealed was high rate of heterogeneity of the circulating enterovirus strains, non-specific for the Khabarovsk territory and mostly originating from countries of Asia-Pacific region - coxsackie A viruses, which might stand for a possible cause of unfavorable epidemiological situation in 2013

A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer