Interaction of Apoptotic Cells with Macrophages Upregulates COX-2/PGE 2

Recognition of apoptotic cells by macrophages is crucial for resolution of inflammation, immune tolerance, and tissue repair. Cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and hepatocyte growth factor (HGF) play important roles in the tissue repair process. We investigated the characteristics of macrophage COX-2 and PGE2 expression mediated by apoptotic cells and then determined how macrophages exposed to apoptotic cells in vitro and in vivo orchestrate the interaction between COX-2/PGE2 and HGF signaling pathways. Exposure of RAW 264.7 cells and primary peritoneal macrophages to apoptotic cells resulted in induction of COX-2 and PGE2. The COX-2 inhibitor NS-398 suppressed apoptotic cell-induced PGE2 production. Both NS-398 and COX-2-siRNA, as well as the PGE2 receptor EP2 antagonist, blocked HGF expression in response to apoptotic cells. In addition, the HGF receptor antagonist suppressed increases in COX-2 and PGE2 induction. The in vivo relevance of the interaction between the COX-2/PGE2 and HGF pathways through a positive feedback loop was shown in cultured alveolar macrophages following in vivo exposure of bleomycin-stimulated lungs to apoptotic cells. Our results demonstrate that upregulation of the COX-2/PGE2 and HGF in macrophages following exposure to apoptotic cells represents a mechanism for mediating the anti-inflammatory and antifibrotic consequences of apoptotic cell recognition

The First Successful Transapical Aortic Valve Implant in Korea

Transcatheter aortic valve implantation is an alternative to open heart surgery in high risk patients with severe aortic stenosis. High mortality and complications related to cardiopulmonary bypass for conventional open heart surgery can be avoided with this new less invasive technique. In case of concomitant severe arterial disease, the transapical approach is recommended rather than transfemoral access. An 80-yr-old man with symptomatic aortic stenosis and who had very high surgical risk factors such as diabetes mellitus, hypertension, a history of stroke, bronchial asthma including poor pulmonary function and hepatocellular carcinoma was treated with a transapical aortic valve replacement. The expected mortality in this patient was 25.4% by Euroscore if we performed the conventional aortic valve surgery. The patient was discharged and was well at the 45 follow-up days. We report the first case of successful transcatheter transapical aortic valve implantation which is available recently in Korea

Modeling Acute Myocardial Infarction and Cardiac Fibrosis Using Human Induced Pluripotent Stem Cell-Derived Multi-Cellular Heart Organoids

Heart disease involves irreversible myocardial injury that leads to high morbidity and mortality rates. Numerous cell-based cardiac in vitro models have been proposed as complementary approaches to non-clinical animal research. However, most of these approaches struggle to accurately replicate adult human heart conditions, such as myocardial infarction and ventricular remodeling pathology. The intricate interplay between various cell types within the adult heart, including cardiomyocytes, fibroblasts, and endothelial cells, contributes to the complexity of most heart diseases. Consequently, the mechanisms behind heart disease induction cannot be attributed to a single-cell type. Thus, the use of multi-cellular models becomes essential for creating clinically relevant in vitro cell models. This study focuses on generating self-organizing heart organoids (HOs) using human-induced pluripotent stem cells (hiPSCs). These organoids consist of cardiomyocytes, fibroblasts, and endothelial cells, mimicking the cellular composition of the human heart. The multi-cellular composition of HOs was confirmed through various techniques, including immunohistochemistry, flow cytometry, q-PCR, and single-cell RNA sequencing. Subsequently, HOs were subjected to hypoxia-induced ischemia and ischemia-reperfusion (IR) injuries within controlled culture conditions. The resulting phenotypes resembled those of acute myocardial infarction (AMI), characterized by cardiac cell death, biomarker secretion, functional deficits, alterations in calcium ion handling, and changes in beating properties. Additionally, the HOs subjected to IR efficiently exhibited cardiac fibrosis, displaying collagen deposition, disrupted calcium ion handling, and electrophysiological anomalies that emulate heart disease. These findings hold significant implications for the advancement of in vivo-like 3D heart and disease modeling. These disease models present a promising alternative to animal experimentation for studying cardiac diseases, and they also serve as a platform for drug screening to identify potential therapeutic targets

Sammelrezension

1.) Hanft, Anke / Simmel, Annika (Hrsg.): Vermarktung von Hochschulweiterbildung. Waxmann Verlag: Münster, 2007. 192 S. ISBN 978-3-8309-1785-4. 2.) Bremer, Helmut: Soziale Milieus, Habitus und Lernen: Zur sozialen Selektivität des Bildungswesens am Beispiel der Weiterbildung. Juventa Verlag: Weinheim, 2007. 308 S. ISBN 978-37799-1585-0. 3.) Dust, Martin: 'Unser Ja zum neuen Deutschland': Katholische Erwachsenenbildung von der Weimarer Republik zur Nazi-Diktatur. Studien zur Bildungsreform, Bd. 49. Peter Lang: Frankfurt, 2007. 631 S. ISBN 978-3-631-55693-1. 4.) Gieseke, Wiltrud: Lebenslanges Lernen und Emotionen: Wirkungen von Emotionen auf Bildungsprozesse aus beziehungstheoretischer Perspektive. W. Bertelsmann Verlag: Bielefeld, 2007. 280 S. ISBN 978-3-7639-3331-0. 5.) Heuer, Ulrike / Siebers, Ruth: Weiterbildung am Beginn des 21. Jahrhunderts: Festschrift für Wiltrud Gieseke. Erwachsenenpädagogisches Institut Berlin e.V. Waxmann Verlag: Münster, 2007. 496 S. ISBN 978-3-8309-1811-0. 6.) Janetzko, Dietmar: Eigenlogik: Zur Rolle subjektiver Theorien bei der Bildungsmotivation. Waxmann Verlag: Münster, 2007. 188 S. ISBN 978-3-8309-1693-2. 7.) Kaiser, Arnim / Kaiser, Ruth / Hohmann, Reinhard (Hrsg.): Lernertypen - Lernumgebung - Lernerfolg: Erwachsene im Lernfeld. W. Bertelsmann Verlag: Bielefeld, 2007. 284 S. ISBN 978-3-7639-3560-4. 8.) Koerrenz, Ralf / Meilhammer, Elisabeth / Schneider, Käthe (Hrsg.): Wegweisende Werke zur Erwachsenenbildung. Verlag IKS Garamond: Jena, 2007. 613 S. ISBN 978-3-938203-51-4. 9.) Schiersmann, Christiane: Berufliche Weiterbildung: Lehrbuch. VS Verlag für Sozialwissenschaften: Wiesbaden, 2007. 272 S. ISBN 3-8100-3891-1. 10.) West, Linden / Alheit, Peter / Andersen, Anders Siig / Merill, Barbara (Hrsg.): Using Biographical and Life History Approaches in the Study of Adult and Lifelong Learning. European Perspectives European Studies in Lifelong Learning and Adult Learning Research, Vol. 2. Peter Lang Verlag: Frankfurt a. M., 2007. 310 S. ISBN 978-3-631-56286-4

Towards a fitting procedure for deeply virtual Compton scattering at next-to-leading order and beyond

Combining dispersion and operator product expansion techniques, we derive the conformal partial wave decomposition of the virtual Compton scattering amplitude in terms of complex conformal spin to twist-two accuracy. The perturbation theory predictions for the deeply virtual Compton scattering (DVCS) amplitude are presented in next-to-leading order for both conformal and modified minimal subtraction scheme. Within a conformal subtraction scheme, where we exploit predictive power of conformal symmetry, the radiative corrections are presented up to next-to-next-to-leading order accuracy. Here, because of the trace anomaly, the mixing of conformal moments of generalized parton distributions (GPD) at the three-loop level remains unknown. Within a new proposed parameterization for GPDs, we then study the convergence of perturbation theory and demonstrate that our formalism is suitable for a fitting procedure of DVCS observables.Comment: LaTeX, 100 pages, 16 figures, 5 tables; Secs. 5.1 and 5.2 revised, minor corrections, version to be published in Nucl.Phys.

Risk Factors for Predicting Hypoxia in Adult Patients Undergoing Bronchoscopy under Sedation

Background: Flexible bronchoscopy is one of the essential procedures for the diagnosis and treatment of pulmonary diseases. The purpose of this study was to identify the risk factors associated with the occurrence of hypoxia in adults undergoing flexible bronchoscopy under sedation. Methods: We retrospectively analyzed 2,520 patients who underwent flexible bronchoscopy under sedation at our tertiary care university hospital in South Korea January 1, 2013-December 31, 2014. Hypoxia was defined as more than 5%-point reduction in the baseline percutaneous oxygen saturation (SpO(2)) or SpO(2) 1 minute during the procedure. Results: The mean age was 64.7 +/- 13.5, and 565 patients developed hypoxia during the procedure. The mean sedation duration and midazolam dose for sedation were 31.1 minutes and 3.9 mg, respectively. The bivariate analysis showed that older age, a low forced expiratory volume in one second (FEV1), use of endobronchial ultrasound, the duration of sedation, and the midazolam dose were associated with the occurrence of hypoxia during the procedure, while the multivariate analysis found that age >60 (odds ratio [OR], 1.32), a low FEV1 (OR, 0.99), and a longer duration of sedation (>40 minutes; OR, 1.33) were significant risk factors. Conclusion: The findings suggest that patients older than age 60 and those with a low FEV1 tend to develop hypoxia during the bronchoscopy under sedation. Also, longer duration of sedation (>40 minutes) was a significant risk factor for hypoxia.11Nscopuskc

Cadmium resistance in tobacco plants expressing the MuSI gene

MuSI, a gene that corresponds to a domain that contains the rubber elongation factor (REF), is highly homologous to many stress-related proteins in plants. Since MuSI is up-regulated in the roots of plants treated with cadmium or copper, the involvement of MuSI in cadmium tolerance was investigated in this study. Escherichia coli cells overexpressing MuSI were more resistant to Cd than wild-type cells transfected with vector alone. MuSI transgenic plants were also more resistant to Cd. MuSI transgenic tobacco plants absorbed less Cd than wild-type plants. Cd translocation from roots to shoots was reduced in the transgenic plants, thereby avoiding Cd toxicity. The number of short trichomes in the leaves of wild-type tobacco plants was increased by Cd treatment, while this was unchanged in MuSI transgenic tobacco. These results suggest that MuSI transgenic tobacco plants have enhanced tolerance to Cd via reduced Cd uptake and/or increased Cd immobilization in the roots, resulting in less Cd translocation to the shoots

PPARγ Agonist and Angiotensin II Receptor Antagonist Ameliorate Renal Tubulointerstitial Fibrosis

The peroxisome proliferator activated receptor (PPAR)γ agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARγ agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-β1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-β/Smad2 in the treated groups, PAI-1 and TGF-β are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARγ agonist might be used in the treatment of renal fibrotic disease