Enhanced cancer therapy with cold-controlled drug release and photothermal warming enabled by one nanoplatform

Stimuli-responsive nanoparticles hold great promise for drug delivery to improve the safety and efficacy of cancer therapy. One of the most investigated stimuli-responsive strategies is to induce drug release by heating with laser, ultrasound, or electromagnetic field. More recently, cryosurgery (also called cryotherapy and cryoablation), destruction of diseased tissues by first cooling/freezing and then warming back, has been used to treat various diseases including cancer in the clinic. Here we developed a cold-responsive nanoparticle for controlled drug release as a result of the irreversible disassembly of the nanoparticle when cooled to below ∼10 °C. Furthermore, this nanoparticle can be used to generate localized heating under near infrared (NIR) laser irradiation, which can facilitate the warming process after cooling/freezing during cryosurgery. Indeed, the combination of this cold-responsive nanoparticle with ice cooling and NIR laser irradiation can greatly augment cancer destruction both in vitro and in vivo with no evident systemic toxicity

Akcja Oszczędnościowa i jej wpływ na reorganizację ustroju i zmianę kompetencji Prokuratorii Generalnej Rzeczypospolitej Polskiej w 1924 r.

"Z uruchomieniem w dniu 1 października 1920 r. poznańskiego oddziału, powołana w 1919 r. Prokuratoria Generalna objęła swoją kompetencją większość terytorium państwa polskiego. Prace organizacyjne trwały jednak nadal, gdyż wraz z zajmowaniem przez Rzeczypospolitą nowych obszarów, rozszerzała się właściwość terytorialna Prokuratorii Generalnej"(...

Rola zagranicznego wsparcia finansowego dla organizacji pozarządowych w Polsce

The importance of international funding among potential sources of financing third sector in Poland is rapidly growing. Particularly, EU funds have an important role to play. After the initial period ofomissions, more and more NGOs are applying for this kind of support. For some of them, especially for those whose statutory objectives are consistent with the priorities of the European Union, EU fundinghas become the main source of income.Brak abstraktu w języku polski

Świat przedmiotów w międzywojennej poezji Marii Pawlikowskiej-Jasnorzewskiej

Maria Pawlikowska-Jasnorzewska has paid much attention to ordinary objects in her interwar poetry. She often referred to various items in the titles of her poems and many times devoted the whole poems to them. The objects that interested the poet are easy to group. Thus we have the objects connected with correspondence (letters, telegrams, manuscripts), works of art and artifacts of art (paintings, carpets, painted plates), lady’s attributes (masks, items of clothing, accessories), as well as various mementos. All the items presented by the author are echoes of her interests, her life in the high culture circle and the travels she took. Pawlikowska-Jasnorzewska’s work shows the material dimension of the world, emphasizing its diversity. The poet noticed the details, ennobled them, found something extraordinary in ordinary things. Her goal was not only to praise the beauty of the object as it always encourages a deeper reflection, often put into an existential perspective. What is more, the author’s work shows the praise of the everyday life, which is characteristic of the Skamandrites, for whom she worked. However, when Pawlikowska-Jasnorzewska became interested in the avant-garde, she also expressed interest in technology and modernity, which also gave us a pretext for thinkin

Biosimilars in Oncology: From Development to Clinical Practice

Biologics play an integral role in the treatment of cancer not only for their therapeutic effects and ability to improve outcomes, but also as supportive care agents. Biologics are more complex to manufacture and take longer to bring to market. Because biologics are considerably more costly than small-molecule drugs, their use has placed an increasing economic demand on healthcare systems worldwide. Biosimilars are designed to be highly similar to existing branded biologics, but because biologics cannot be exactly copied, biosimilars should not be referred to as generic, exact versions of the innovator biologic. Biosimilars have the potential to increase access and provide lower cost options for cancer care as patent protection for some of the most widely used biologics begins to expire. Regulatory requirements for biosimilars are evolving, as are global harmonization and/or standardization strategies that can facilitate their robust clinical development. This review highlights critical factors involved with the integration of biosimilars into oncology treatment paradigms and practices. Clinicians will likely seek out practice guidelines and position statements from established scientific societies to help evaluate key information regarding biosimilars, such as efficacy, safety, comparability, and interchangeability with the reference biologic. Automatic substitution, nomenclature, extrapolation of clinical data from one indication to another, as well as parameters for ongoing pharmacovigilance are evolving considerations. Education of physicians and other healthcare providers, payers, and patients about biosimilars may facilitate informed decision making, promote acceptance of biosimilars into clinical practice, increase accessibility, and expedite associated health and economic benefits

Molecular phylogenetics and comparative modeling of HEN1, a methyltransferase involved in plant microRNA biogenesis

BACKGROUND: Recently, HEN1 protein from Arabidopsis thaliana was discovered as an essential enzyme in plant microRNA (miRNA) biogenesis. HEN1 transfers a methyl group from S-adenosylmethionine to the 2'-OH or 3'-OH group of the last nucleotide of miRNA/miRNA* duplexes produced by the nuclease Dicer. Previously it was found that HEN1 possesses a Rossmann-fold methyltransferase (RFM) domain and a long N-terminal extension including a putative double-stranded RNA-binding motif (DSRM). However, little is known about the details of the structure and the mechanism of action of this enzyme, and about its phylogenetic origin. RESULTS: Extensive database searches were carried out to identify orthologs and close paralogs of HEN1. Based on the multiple sequence alignment a phylogenetic tree of the HEN1 family was constructed. The fold-recognition approach was used to identify related methyltransferases with experimentally solved structures and to guide the homology modeling of the HEN1 catalytic domain. Additionally, we identified a La-like predicted RNA binding domain located C-terminally to the DSRM domain and a domain with a peptide prolyl cis/trans isomerase (PPIase) fold, but without the conserved PPIase active site, located N-terminally to the catalytic domain. CONCLUSION: The bioinformatics analysis revealed that the catalytic domain of HEN1 is not closely related to any known RNA:2'-OH methyltransferases (e.g. to the RrmJ/fibrillarin superfamily), but rather to small-molecule methyltransferases. The structural model was used as a platform to identify the putative active site and substrate-binding residues of HEN and to propose its mechanism of action

Kordian jako romantyczny homo viator

The story presented in Kordian is based on the symbolically rich theme of adventure that is strongly fixed in culture. The theme is being recalled and used here for the crea-tion of the character of the romantic hero who is believed to exist in the state of permanent travel. Kordian’s pilgrimage fulfils various functions and its ambiguity reveals itself at the different levels of the book, what can be analyzed from both internal and external sides of the text. The first frame is the echo of the author’s travel as well as the travel of his contemporaries; therefore, this road has become the attempt of reflection on the problem of the post-uprising condition of an individual and the entire nation. The wandering hero is looking for the goal, is trying to learn about himself and analyze the world around him. Thus, he works not only at the strictly personal levelbut alsoat the social one. His phased way has an educational and developmental character; it is a coherent study of mastering one’s deeper self-awareness. It is also a travel from mediocrity and anonymity to the individual who bears the status of a combatant in the service of his nation; and so from the lowlands to the heights, both literally (the road to the peak of Mount Blanc), as well as metaphorically – the climbing to the ideological and spiritual heights. Various interpretations of Kordian’s theme of travel not only accumulate but also penetrate and complement one another opening the way to further attempts of explanation of the mentioned topos. Different interpretations of the whole work enable to take a completely different perspective when trying to explain the role and symbolism of the road covered by the main character