Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer

The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs

Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival.

In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival via the senescence-associated secretory phenotype. Understanding the properties of tumor cells that allow survival after chemotherapy treatment is paramount. Using time-lapse and confocal microscopy to observe interactions of cells in treated tumors, we show here that chemotherapy-induced senescent cells frequently engulf both neighboring senescent or nonsenescent tumor cells at a remarkable frequency. Engulfed cells are processed through the lysosome and broken down, and cells that have engulfed others obtain a survival advantage. Gene expression analysis showed a marked up-regulation of conserved macrophage-like program of engulfment in chemotherapy-induced senescent cell lines and tumors. Our data suggest compelling explanations for how senescent cells persist in dormancy, how they manage the metabolically expensive process of cytokine production that drives relapse in those tumors that respond the worst, and a function for their expanded lysosomal compartment

Aktywność fizyczna studentów kierunku fizjoterapia Warszawskiego Uniwersytetu Medycznego

Background. Regular physical activity allows maintenance of physical fitness at an optimal level and also contributes to greater care for other elements of a healthy lifestyle. The promotion of physical activity should be one of the tasks of health professionals, including physiotherapists. The aim of this study was to assess physical activity levels of physiotherapy students. Material and methods. This study involved 853 students (634 women and 219 men) of the Faculty of Physiotherapy of the Medical University of Warsaw (444 first-year students and 409 second-year students). The research tools were the International Physical Activity Questionnaire – short version (IPAQ-SF) and the author’s own survey to obtain information on the type of physical activity and reasons for taking it up or not. Results. Men had significantly higher levels of physical activity than women (p<0.001). The physical activity levels of second-year female students were higher than those of first-year female students (p=0.026). Among men, there was no significant difference between first and second-year students. Conclusions. More than half of those surveyed do not engage in any physical activity outside of curriculum activities. The results obtained in this study may form the basis for continuing research with the participation of various groups of subjects and using more advanced technologies and research tools.Wprowadzenie. Regularna aktywność fizyczna pozwala na utrzymanie wydolności fizycznej na optymalnym poziomie, a ponadto przyczynia się do większej dbałości o inne elementy zdrowego stylu życia. Propagowanie aktywności fizycznej powinno być jednym z zadań pracowników służby zdrowia, w tym fizjoterapeutów. Celem badania była ocena poziomu aktywności fizycznej studentów fizjoterapii. Materiał i metody. W badaniu wzięło udział 853 studentów (634 kobiet i 219 mężczyzn) kierunku fizjoterapia Warszawskiego Uniwersytetu Medycznego (444 studentów pierwszego roku oraz 409 studentów drugiego roku). Narzędziami badawczymi były Międzynarodowy Kwestionariusz Aktywności Fizycznej – wersja krótka (IPAQ-SF) oraz autorska ankieta służąca uzyskaniu informacji dotyczącej rodzaju aktywności fizycznej oraz motywów jej podejmowania lub niepodejmowania. Wyniki. Mężczyźni charakteryzowali się istotnie wyższym poziomem aktywności fizycznej niż kobiety (p<0,001). Poziom aktywności fizycznej studentek drugiego roku był wyższy niż u studentek pierwszego roku (p=0,026). Wśród mężczyzn nie stwierdzono istotnych różnic między studentami pierwszego i drugiego roku. Wnioski. Ponad połowa badanych nie podejmuje żadnej aktywności fizycznej poza zajęciami programowymi. Uzyskane w niniejszej pracy wyniki mogą stanowić podstawę kontynuowania badań z udziałem różnych grup badanych oraz z wykorzystaniem bardziej zaawansowanych technologii i narzędzi badawczych

Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.

Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe