Adoption/adaptation of universal principles and mutual influences of organizational models among ethno-nationally biased cooperative networks inside inter-war Romania

This paper identifies those elements that were common in all cooperative networks around the world by presenting the process of adoption of universal cooperative principles inside the provinces that were reunited in interwar Romania, while observing the mutual adaptation of organizational models among different ethno-cultural entities defined as minorities and the actual ethnic national majority. We operate methodologically according to a methodic circle that helped us to distinguish the historical sources of nationalist/nation-building rhetoric and the pragmatically achieved goals (balances). In case of cooperatives, we observed that constructive/interactive community-building goals and routine overwhelmed negative, reactive or even destructive nationalist goals. The latter did not reach the cooperative sector effectively or only remained dead letter on political manifestos and propaganda (boycott or sabotage) both in the prewar constituent period and the interwar era. Nevertheless, there was a continuous mutual (incongruent) influence among the neighboring networks, both in strategies, technics, architecture and organizational forms. This study tries to contribute to the research of the economic institutionalization and mobilization phase of nation-building as theorized by Anthony D. Smith and Miroslav Hroch by identifying those modern institutions, including savings banks and cooperative networks that assembled ethno-national entities into modern economic and market economy framework, while verifying the legitimacy or anachronism of using national ‘bias’ in case of these modern financial-economic institutions and cooperative networks

Oxidized Resveratrol Metabolites as Potent Antioxidants and Xanthine Oxidase Inhibitors

Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an ethoxy-substituted compound (7), and two ethoxy-substitute,0d dimers (8 and 9). Compounds 4, 7, 8, and 9 are reported here for the first time. All compounds without ethoxy substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies, compounds 2 and 4 were identified as potent competitive inhibitors of the enzyme, while compound 2 and the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound

Backstabbing P-gp: Side-Chain Cleaved Ecdysteroid 2,3-Dioxolanes Hyper-Sensitize MDR Cancer Cells to Doxorubicin without Efflux Inhibition

P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E). In contrast with previously studied ecdysteroid dioxolanes, the majority of the new compounds did not inhibit the efflux function of P-gp. Nevertheless, a strong, dose dependent sensitization to doxorubicin was observed on a P-gp transfected cancer cell line and on its susceptible counterpart. We also observed that the MDR cell line was more sensitive to the compounds’ effect than the non-MDR. Our results showed for the first time that the chemo-sensitizing activity of ecdysteroids can be fully independent of functional efflux pump inhibition, and suggest these compounds as favorable leads against MDR cancer