When studying polyethylenimine derivatives as nonviral vectors for gene delivery, among the important issues to be addressed are high toxicity, low transfection efficiency, and nucleic acid polyplex condensation. The molecular weight of polyethylenimine, PEGylation, biocompatibility and, also, supramolecular structure of potential carrier can all influence the nucleic acid condensation behavior, polyplex size, and transfection efficiency. The main challenge in building an efficient carrier is to find a correlation between the constituent components, as well as the synergy between them, to transport and to release, in a specific manner, different molecules of interest. In the present study, we investigated the synergy between components in dynamic combinatorial frameworks formed by connecting PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) and low molecular weight polyethylenimine components to 1,3,5-benzenetrialdehyde, via reversible imine bond, applying a dynamic combinatorial chemistry approach. We report comparative structural and morphological data, DNA binding affinity, toxicity and transfection efficiency concerning the ratio of polyethylenimine and presence or absence of poly-(ethyleneglycol)-bis(3-aminopropyl) in composition of dynamic combinatorial frameworks. In vitro biological assessments have revealed the fact that nonviral vectors containing poly-(ethyleneglycol)-bis(3-aminopropyl) and the lowest amount of polyethylenimine have significant transfection efficiency at N/P 50 ratio and display insignificant cytotoxicity on the HeLa cell line.
Polyethylene glycol (PEG) functionalization of non-viral vectors represents a powerful tool through the formation of an overall surface charge shielding ability, which is fundamental for efficient nucleic acid delivery systems. The degree of non-viral vector PEGylation and the molecular weight of utilized PEG is crucial since the excessive use of PEG units may lead to a considerable reduction of the DNA-binding capacity and, subsequently, in a reduction of in vitro transfection efficiency. Herein, we report a detailed study on a series of dynamic combinatorial frameworks (DCFs) containing PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) of different lengths, and branched low molecular weight polyethylenimine components, reversibly connected in hyperbranched structures, as efficient dynamic non-viral vectors. The obtained frameworks were capable of forming distinct supramolecular amphiphilic architectures, shown by transmission electron microscopy (TEM) and dynamic light scattering (DLS), with sizes and stability depending on the length of PEG units. The interaction of PEGylated DCFs with nucleic acids was investigated by agarose gel retardation assay and atomic force microscopy (AFM), while their transfection efficiency (using pCS2+MT-Luc DNA as a reporter gene) and cytotoxicity were evaluated in HeLa cells. In addition, the data on the influence of the poly-(ethyleneglycol)-bis(3-aminopropyl) length in composition of designed frameworks over transfection efficiency and tolerance in human cells were analyzed and compared.
The biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as antifouling in biomedical devices. Experimental studies have shown...
We report novel molecules incorporating the nontoxic squalene scaffold and different carbonic anhydrase inhibitors (CAIs). Potent inhibitory action, in the low‐nanomolar range, was detected against isoforms hCA II for sulfonamide derivatives, which proved to be selective against this isoform over the tumor‐associate hCA IX and XII isoforms. On the other hand, coumarin derivatives showed weak potency but high selectivity against the tumor‐associated isoform CA IX. These compounds are interesting candidates for preclinical evaluation in glaucoma or various tumors in which the two enzymes are involved. In addition, an in silico study of inhibitor‐bound hCA II revealed extensive interactions with the hydrophobic pocket of the active site and provided molecular insights into the binding properties of these new inhibitors.
The Historical Population Database of Transylvania (HPDT) is a research tool developed by the Centre for Population Studies at Babeș-Bolyai University Cluj-Napoca starting with 2014, whose goal is to host digitalized information from parish registersthe main sources for population history in Transylvania and Hungary until 1895. The database is covering roughly the period 1850-1914: from the first modern census in the Austrian Empire to the upper limit allowed by the Romanian Law 16/1996 (i.e. a tresshold of 100 years, in the present day the limit being the year 1919). Curerntly, there are more than 400.000 individuals recorded within the database, which requires constant cleaning, standardization and linkage. The main objective of this undergoing entreprise consists in providing a research tool equally useful to the scientific milieu through its rich and complex data, and to the general public by means of its genealogical interface. The present work has the purpose to document the transcription and data entry processes related to HPDT, by detailing the rules applied in transferring the information from the primary sources into the digital framework.
ResumenEl presente trabajo busca presentar y discutir algunos de los temas relacionados con la estabilidad de matrimonios mixtos (entre etnias y confesiones religiosas) durante el periodo de entreguerras en Cluj. Estos temas incluyen la influencia de la ideología y el contexto político sobre la vida doméstica y la vulnerabilidad de la relación de pareja frente a las presiones sociales. El periodo estudiado permite el análisis de las relaciones interétnicas de entreguerras, en una época en la que conceptos tales AbstractThis study aims to present and discuss some of the issues relating to the stability of (ethnically and confessionally) mixed marriages in interwar Cluj, including the impact of the ideological atmosphere and the political context on domestic life and the vulnerability of a couple's relationship to social pressures. The choice of period allows the examination of interethnic relations in an interwar period, where notions like nationalism, xenophobia, and eugenics made and unmade govern- como nacionalismo, xenofobia y eugenesia alzaban y derrumbaban gobiernos. El lugar estudiado, además, permite el examen de las relaciones interétni-cas en una ciudad habitada por cuatro grupos ét-nicos notablemente numerosos y siete confesiones religiosas. El análisis de una muestra de 2500 matrimonios contraídos en 1922, 1930 y 1938 intenta relacionar la duración de los matrimonios con el tipo (monógamo o mixto) y con otras variables tales como la edad al casarse y la situación profesional de los cónyuges.ments. The choice of location too allows the study of interethnic relations in a city inhabited by four considerably populous ethnic groups and seven confessions. By using a sample of 2,500 marriages contracted in 1922, 1930, and 1938, the analysis aims at assessing the duration of marriages in relation to their types (monogamous or mixed) and several independent variables, such as age at marriage and the spouses' professional status.Palabras clave divorcio, matrimonio mixto, Transilvania, Cluj, entreguerras.
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