Fogeredetű őssejtek izolálása és jellemzése = Isolation and characterisation of postnatal stem cells of dental origin

Kutatásainkhoz a K61543 kutatási pályázatmellé elnyertük a IN67250 nemzetközi kiegészítő támogatást is, így beszámolónk ezek összefoglaló zárójelentése. Vizsgálataink célja emberi fogbélből és parodontális ligamentumból származó őssejtek izolálása és jellemzése, in vitro modell-rendszerek és eljárások kidolgozása a fogeredetű, és így potenciálisan a fogak és a parodontális szövetek részleges vagy teljes regenerációjára felhasználható őssejtek azonosítására, izolálására és fejlődési, differenciálódási képességeik meghatározására, illetve ectodermális sejtekkel való kölcsönhatásaik jellemzésére. Munkánk során emberi fogak pulpájából (dental pulp stem cell=DPSC) és a parodontális ligamentumból (periodontal ligament stem cells=PDLSC) illetve emberi nyálmirigyekből (PTHSG) preparáltunk pluripotens őssejteket tartalmazó sejtkultúrákat. Ezen kultúrákat molekuláris és sejtbiológiai módszerekkel jellemeztük, a sejteket különböző irányú differenciálódásra / transdifferenciálódásra bírtuk. Az osteogén differenciálódás mellett ki kell emelnünk mind a DPSC, mind a PDLSC sejtek képességét a neuronális differenciálódásra az általunk kidolgozott három lépésből álló protokoll mellett. Fentieken túl egy új állatkísérletes tesztrendszert dolgoztunk ki az osseointegráció, illetve a parodontális ligamentum és a fogbél regenerációjának tanulmányozására. Mindezek megalapozzák további ilyen irányú kutatásainkat, az emberi fogeredetű sejtek in vivo regenerációs alkalmazásának kidolgozására. | The originally supported K61543 research grant received additional support by IN67250, which is a supplementary international extension of the same project. Therefore, this is a joint report of the twin grants. The purpose of our study was to isolate and characterize human stem cells from dental pulp and periodontal ligament, to develop in vitro model systems and processes, for identification of stem cells, which have the potential for full or partial regeneration dental and periodontal tissues. On the course of our work we prepared cultures containing pluripotent postnatal stem cells from the dental pulp (dental pulp stem cell=DPSC), from the periodontal ligament (periodontal ligament stem cells=PDLSC), and from the salivary glands (PTHSG). We characterized these cultures and developed methods for their differentiation / transdifferentiation in vitro. Besides the osteogenic differentiation we must highlight the potency of both DPSC and PDLSC cells for neuronal differentiation when our newly developed three step protocol is used. Moreover we also developed and in vivo animal test model for studying osseointegration, periodontal and pulp regeneration. These results will give the foundation of our future work towards the application of human stem cells of dental origin in biological regeneration of damaged tissues

SPIRE Point Source Catalog Explanatory Supplement

The Spectral and Photometric Imaging Receiver (SPIRE) was launched as one of the scientific instruments on board of the space observatory Herschel. The SPIRE photometer opened up an entirely new window in the Submillimeter domain for large scale mapping, that up to then was very difficult to observe. There are already several catalogs that were produced by individual Herschel science projects. Yet, we estimate that the objects of only a fraction of these maps will ever be systematically extracted and published by the science teams that originally proposed the observations. The SPIRE instrument performed its standard photometric observations in an optically very stable configuration, only moving the telescope across the sky, with variations in its configuration parameters limited to scan speed and sampling rate. This and the scarcity of features in the data that require special processing steps made this dataset very attractive for producing an expert reduced catalog of point sources that is being described in this document. The Catalog was extracted from a total of 6878 unmodified SPIRE scan map observations. The photometry was obtained by a systematic and homogeneous source extraction procedure, followed by a rigorous quality check that emphasized reliability over completeness. Having to exclude regions affected by strong Galactic emission, that pushed the limits of the four source extraction methods that were used, this catalog is aimed primarily at the extragalactic community. The result can serve as a pathfinder for ALMA and other Submillimeter and Far-Infrared facilities. 1,693,718 sources are included in the final catalog, splitting into 950688, 524734, 218296 objects for the 250\mu m, 350\mu m, and 500\mu m bands, respectively. The catalog comes with well characterized environments, reliability, completeness, and accuracies, that single programs typically cannot provide

Gender-specific outcomes in immune checkpoint inhibitor therapy for advanced or metastatic urothelial cancer: a systematic review and meta-analysis.

PURPOSE To analyze gender-specific differences in survival parameters in advanced or metastatic urothelial cancer patients undergoing immune checkpoint inhibition. METHODS The primary aim of this systematic review and meta-analysis was to evaluate gender-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), overall survival (OS) and objective response rate (ORR). The sources MEDLINE, Embase and Cochrane Library were systematically searched from January 2010 to June 2022. No restrictions were made concerning language, study region or publication type. A comparison of gender-specific differences in survival parameters was performed using a random-effects meta-analysis. A risk of bias assessment was done using the ROBINS-I tool. RESULTS Five studies were included. In a random-effect meta-analysis of the studies, PCD4989g and IMvigor 211 with both using atezolizumab, females were more likely to have better objective response rate (ORR) than men (OR 2.24; 95% CI 1.20-4.16; p = 0.0110). In addition, females had a comparable median OS to men (MD 1.16; 95% CI - 3.15-5.46; p = 0.598). In summary, comparing all results, a tendency was seen toward better response rates and survival parameters in female patients. The risk of bias assessment yielded an overall low risk of bias. CONCLUSIONS There is a tendency toward better outcomes in women for immunotherapy in advanced or metastatic urothelial cancer, but only for the antibody atezolizumab women have a significantly better ORR. Unfortunately, many studies fail to report gender-specific outcomes. Therefore, further research is essential when aiming for individualized medicine. This research should address immunological confounders

Solution Equilibrium Studies of Anticancer Ruthenium(II)-η6-p-cymene Complexes of Pyridinecarboxylic Acids

Stoichiometry and stability of antitumor ruthenium(II)-η6-p-cymene complexes of picolinic acid and its 6-methyl and 6-carboxylic acid derivatives were determined by pH-potentiometry, 1H NMR spectroscopy and UV–Vis spectrophotometry in aqueous solution in the presence or absence of coordinating chloride ions. The picolinates form exclusively mono-ligand complexes in which they can coordinate via the bidentate (O,N) mode and a chloride or a water molecule is found at the third binding site of the ruthenium(II)-η6-p-cymene moiety depending on the conditions. [Ru(η6-p-cymene)(L)(H2O/Cl)] species are predominant at physiological pH in all studied cases. Hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange results in the formation of the mixed-hydroxido species [Ru(η6-p-cymene)(L)(OH)] in the basic pH range. There is no indication for the decomposition of the mono-ligand complexes during 24 h in the ruthenium(II)-η6-p-cymene-picolinic acid system between pH 3 and 11; however, a slight dissociation with a low reaction rate was found in the other two systems leading to the appearance of the dinuclear trihydroxido-bridged species [Ru2(η6-p-cymene)2(OH)3]+ and free ligands at pH > 10. The replacement of the chlorido by an aqua ligand in [Ru(η6-p-cymene)(L)Cl] was also monitored and equilibrium constants for the exchange process were determined

Prediction of Biochemical Recurrence Based on Molecular Detection of Lymph Node Metastasis After Radical Prostatectomy.

Background Molecular detection of lymph node (LN) micrometastases by analyzing mRNA expression of epithelial markers in prostate cancer (PC) patients provides higher sensitivity than histopathological examination. Objective To investigate which type of marker to use and whether molecular detection of micrometastases in LNs was predictive of biochemical recurrence. Design setting and participants LN samples from PC patients undergoing radical prostatectomy with extended LN dissection between 2009 and 2011 were examined for the presence of micrometastases by both routine histopathology and molecular analyses. Outcome measurements and statistical analysis The mRNA expression of a panel of markers of prostate epithelial cells, prostate stem cell-like cells, epithelial-to-mesenchymal transition, and stromal activation, was performed by quantitative real-time polymerase chain reaction. The expression levels of these markers in LN metastases from three PC patients were compared with the expression levels in LN from five control patients without PC in order to identify the panel of markers best suited for the molecular detection of LN metastases. The predictive value of the molecular detection of micrometastases for biochemical recurrence was assessed after a follow-up of 10 yr. Results and limitations Prostate epithelial markers are better suited for the detection of occult LN metastases than molecular markers of stemness, epithelial-to-mesenchymal transition, or reactive stroma. An analysis of 1023 LNs from 60 PC patients for the expression of prostate epithelial cell markers has revealed different expression levels and patterns between patients and between LNs of the same patient. The positive predictive value of molecular detection of occult LN metastasis for biochemical recurrence is 66.7% and the negative predictive value is 62.5%. Limitations are sample size and the hypothesis-driven selection of markers. Conclusions Molecular detection of epithelial cell markers increases the number of positive LNs and predicts tumor recurrence already at surgery. Patient summary We show that a panel of epithelial prostate markers rather than single genes is preferred for the molecular detection of lymph node micrometastases not visible at histopathological examination

Mandatory communication skills training for oncologists: enforcement does not substantially impact satisfaction

Purpose: Even though there is evidence that both patients and oncology clinicians are affected by the quality of communication and that communication skills can be effectively trained, so-called Communication Skills Trainings (CSTs) remain heterogeneously implemented. Methods: A systematic evaluation of the level of satisfaction of oncologists with the Swiss CST before (2000-2005) and after (2006-2012) it became mandatory. Results: Levels of satisfaction with the CST were high, and satisfaction of physicians participating on a voluntary or mandatory basis did not significantly differ for the majority of the items. Conclusions: The evaluation of physicians' satisfaction over the years and after introduction of mandatory training supports recommendations for generalized implementation of CST and mandatory training for medical oncologists

RACE-OC Project: Rotation and variability in the epsilon Chamaeleontis, Octans, and Argus stellar associations

We aim at determining the rotational and magnetic-related activity properties of stars at different stages of evolution. We focus our attention primarily on members of young stellar associations of known ages. Specifically, we extend our previous analysis in Paper I (Messina et al. 2010, A&A 520, A15) to 3 additional young stellar associations beyond 100 pc and with ages in the range 6-40 Myr: epsilon Chamaeleontis (~6 Myr), Octans (~20 Myr), and Argus (~40 Myr). Additional rotational data of eta Chamaeleontis and IC2391 clusters are also considered. Rotational periods were determined from photometric time-series data obtained by the All Sky Automated Survey (ASAS) and the Wide Angle Search for Planets (SuperWASP) archives. With the present study we have completed the analysis of the rotational properties of the late-type members of all known young loose associations in the solar neighborhood. Considering also the results of Paper I, we have derived the rotation periods of 241 targets: 171 confirmed, 44 likely, 26 uncertain. The period of the remaining 50 stars known to be part of loose associations still remains unknown. This rotation period catalogue, and specifically the new information presented in this paper at ~6, 20, and 40 Myr, contributes significantly to a better observational description of the angular momentum evolution of young stars.Comment: Accepted by Astronomy & Astrophysics. Onlines figures will be available at CD