A Potent Autophagy Inhibitor (Lys05) Enhances the Impact of Ionizing Radiation on Human Lung Cancer Cells H1299

Autophagy inhibition through small-molecule inhibitors is one of the approaches to increase the efficiency of radiotherapy in oncological patients. A new inhibitor—Lys05—with the potential to accumulate within lysosomes and to block autophagy was discovered a few years ago. Several studies have addressed its chemosensitizing effects but nothing is known about its impact in the context of ionizing radiation (IR). To describe its role in radiosensitization, we employed radioresistant human non-small cell lung carcinoma cells (H1299, p53-negative). Combined treatment of H1299 cells by Lys05 together with IR decreased cell survival in the clonogenic assay and real-time monitoring of cell growth more than either Lys05 or IR alone. Immunodetection of LC3 and p62/SQSTM1 indicated that autophagy was inhibited, which correlated with increased SQSTM1 and decreased BNIP3 gene expression determined by qRT-PCR. Fluorescence microscopy and flow cytometry uncovered an accumulation of lysosomes. Similarly, transmission electron microscopy demonstrated the accumulation of autophagosomes confirming the ability of Lys05 to potentiate autophagy inhibition in H1299 cells. We report here for the first time that Lys05 could be utilized in combination with IR as a promising future strategy in the eradication of lung cancer cells

Thermomechanical properties of nickel-titanium closed-coil springs and their implications for clinical practice

The aim was to study nickel-titanium closed-coil springs in a clinically relevant test setting with respect to the accuracy of the "preactivation" for nickel-titanium closed-coil springs application and whether it is possible to keep activation forces constant during the whole time of treatment

Vylepšené optické vlastnosti nanočástic ZnSexS1-x a Mn-dopovaných ZnSexS1-x připravených netoxickou syntézní cestou

A tunable approach for the non-phosphine synthesis of monodisperse, highly photoluminescent ZnSexS1-x and Mn-doped ZnSe0.1S0.9 quantum dots (QDs) using (Z)-1-(octadec-9-enyl)-3-phenylselenourea and (Z)-1-(octadec9-enyl)-3-phenylthiourea as novel sources of selenium and sulphur is provided. QDs syntheses were performed in an organic disperse medium at 280 degrees C using environmentally friendly and at the same time highly reactive N,N'disubstituted thio- and selenoureas. By varying the molar ratios of sulphur and selenium sources, ZnSexS1-x QDs, where x = 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, and 0.75, were obtained. Mn-doped ZnSe0.1S0.9 QDs (0.5-15 molar %) have been synthesized by the low cost hot-injection method. The presence of manganese in ZnSe0.1S0.9 QDs resulted in the appearance of the expected second emission band (579 nm), the maximum intensity of which was determined for Mn(5%):ZnSe0.1S0.9 QDs. According to the analytical data, ZnSexS1-x and Mn-doped ZnSe0.1S0.9 QDs are consistent with the desired elemental composition and uniform in size. The chemical composition, morphology and crystal structure of prepared undoped ZnSexS1-x and Mn-doped ZnSe0.1S0.9 QDs were studied by X-Ray diffraction (XRD), energy dispersive X-Ray spectroscopy (EDS), X-Ray photoelectron spectroscopy (XPS), scanning transmission electron microscopy (STEM) and transmission electron microscopy (TEM) analyses. The optical properties of nanocomposite materials based on synthesized ZnSexS1-x and Mn-doped ZnSe0.1S0.9 QDs in a polymer matrix of polyvinyl toluene (PVT) were also studied. It should be noted that transparent monoliths have the same photoluminescent characteristics as QDs. These results give proof of the chemical stability of the resulting nanomaterials and can contribute to their possible transfer in the photodetectors and LEDs production.Článek popisuje laditelný bezfosfinový postup syntézy monodisperzních, vysoce luminiscenčních ZnSexS1-x a Mn-dopovaných ZnSexS1-x nanočástic s využitím nových zdrojů S a Se na bázi (Z)-1-(octadec-9-enyl)-3-fenylselenomočoviny and (Z)-1-(octadec9-enyl)-3-fenylthiomočoviny. Syntézy nanočástic byly provedeny v organickém disperzním mediu při 250°C s využitím environmentálně přátelských a současně vysoce reaktivních N,N'disubstituovaných thio- a selenomočovin. Změnou molárních poměrů reagujících zdrojů síry a selenu byly připraveny částice o složení ZnSexS1-x, kde x = 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, 0.5, a 0.75. Mn-dopované částice ZnSe0.1S0.9 (0.5-15 molárních %) byly syntetizované levnou hot-injection metodou. Přítomnost Mn v nanočásticích ZnSe0.1S0.9 způsobila vznik očekávaného sekundárního emisního pásu (579 nm), jehož maximální intenzita byla potvrzena u částic složení Mn(5%):ZnSe0.1S0.9. Dle analytických dat, složení a uniformita připravených nanočástic odpovídá zamýšleným cílovým hodnotám. Chemické složení, morfologie a krystalová struktura ZnSexS1-x a Mn-dopovaných ZnSexS1-x nanočástic byla taktéž studována metodami Rentgenové difrakce (XRD), energiově-disperzní rentgenové spektroskopie (EDS), rentgenové foto-elektronové spektroskopie (XPS) skenovací transmisní elektronové mikroskopie (STEM) a transmisní elektronové mikroskopie (TEM). Optické vlastnosti nanokompozitních materiálů založených na syntetizovaných ZnSexS1-x a Mn-dopovaných ZnSexS1-x nanočásticích fixovaných v polymerní matrici polyvinyl toluenu (PVT) byly taktéž studovány v tomto článku. Připravené transparentní monolity měly stejné fotoluminiscenční charakteristiky jako připravené nanočástice. Výsledky potvrdily, že chemická stabilita připravených nanomateriálů přispívá k jejich možnému transferu pro fotodetektorové a LED aplikace

Directed reprogramming of comprehensively characterized dental pulp stem cells extracted from natal tooth

Abstract The aim of this study was to extensively characterise natal dental pulp stem cells (nDPSC) and assess their efficiency to generate human induced pluripotent stem cells (hiPSC). A number of distinguishing features prompted us to choose nDPSC over normal adult DPSC, in that they differed in cell surface marker expression and initial doubling time. In addition, nDPSC expressed 17 out of 52 pluripotency genes we analysed, and the level of expression was comparable to human embryonic stem cells (hESC). Ours is the first group to report comprehensive characterization of nDPSC followed by directed reprogramming to a pluripotent stem cell state. nDPSC yielded hiPSC colonies upon transduction with Sendai virus expressing the pluripotency transcription factors POU5F1, SOX2, c-MYC and KLF4. nDPSC had higher reprogramming efficiency compared to human fibroblasts. nDPSC derived hiPSCs closely resembled hESC in terms of their morphology, expression of pluripotency markers and gene expression profiles. Furthermore, nDPSC derived hiPSCs differentiated into the three germ layers when cultured as embryoid bodies (EB) and by directed differentiation. Based on our findings, nDPSC present a unique marker expression profile compared with adult DPSC and possess higher reprogramming efficiency as compared with dermal fibroblasts thus proving to be more amenable for reprogramming