@article{JanzWalzCirnuetal.2024, author = {Janz, Anna and Walz, Katharina and Cirnu, Alexandra and Surjanto, Jessica and Urlaub, Daniela and Leskien, Miriam and Kohlhaas, Michael and Nickel, Alexander and Brand, Theresa and Nose, Naoko and W{\"o}rsd{\"o}rfer, Philipp and Wagner, Nicole and Higuchi, Takahiro and Maack, Christoph and Dudek, Jan and Lorenz, Kristina and Klopocki, Eva and Erg{\"u}n, S{\"u}leyman and Duff, Henry J. and Gerull, Brenda}, title = {Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes}, series = {Molecular Metabolism}, volume = {79}, journal = {Molecular Metabolism}, issn = {2212-8778}, doi = {10.1016/j.molmet.2023.101859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350393}, year = {2024}, abstract = {Highlights • Loss of DNAJC19's DnaJ domain disrupts cardiac mitochondrial structure, leading to abnormal cristae formation in iPSC-CMs. • Impaired mitochondrial structures lead to an increased mitochondrial respiration, ROS and an elevated membrane potential. • Mutant iPSC-CMs show sarcomere dysfunction and a trend to more arrhythmias, resembling DCMA-associated cardiomyopathy. Background Dilated cardiomyopathy with ataxia (DCMA) is an autosomal recessive disorder arising from truncating mutations in DNAJC19, which encodes an inner mitochondrial membrane protein. Clinical features include an early onset, often life-threatening, cardiomyopathy associated with other metabolic features. Here, we aim to understand the metabolic and pathophysiological mechanisms of mutant DNAJC19 for the development of cardiomyopathy. Methods We generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) of two affected siblings with DCMA and a gene-edited truncation variant (tv) of DNAJC19 which all lack the conserved DnaJ interaction domain. The mutant iPSC-CMs and their respective control cells were subjected to various analyses, including assessments of morphology, metabolic function, and physiological consequences such as Ca\(^{2+}\) kinetics, contractility, and arrhythmic potential. Validation of respiration analysis was done in a gene-edited HeLa cell line (DNAJC19tv\(_{HeLa}\)). Results Structural analyses revealed mitochondrial fragmentation and abnormal cristae formation associated with an overall reduced mitochondrial protein expression in mutant iPSC-CMs. Morphological alterations were associated with higher oxygen consumption rates (OCRs) in all three mutant iPSC-CMs, indicating higher electron transport chain activity to meet cellular ATP demands. Additionally, increased extracellular acidification rates suggested an increase in overall metabolic flux, while radioactive tracer uptake studies revealed decreased fatty acid uptake and utilization of glucose. Mutant iPSC-CMs also showed increased reactive oxygen species (ROS) and an elevated mitochondrial membrane potential. Increased mitochondrial respiration with pyruvate and malate as substrates was observed in mutant DNAJC19tv HeLa cells in addition to an upregulation of respiratory chain complexes, while cellular ATP-levels remain the same. Moreover, mitochondrial alterations were associated with increased beating frequencies, elevated diastolic Ca\(^{2+}\) concentrations, reduced sarcomere shortening and an increased beat-to-beat rate variability in mutant cell lines in response to β-adrenergic stimulation. Conclusions Loss of the DnaJ domain disturbs cardiac mitochondrial structure with abnormal cristae formation and leads to mitochondrial dysfunction, suggesting that DNAJC19 plays an essential role in mitochondrial morphogenesis and biogenesis. Moreover, increased mitochondrial respiration, altered substrate utilization, increased ROS production and abnormal Ca\(^{2+}\) kinetics provide insights into the pathogenesis of DCMA-related cardiomyopathy.}, language = {en} } @article{RockelWagnerSpengeretal.2023, author = {Rockel, Anna F. and Wagner, Nicole and Spenger, Peter and Erg{\"u}n, S{\"u}leyman and W{\"o}rsd{\"o}rfer, Philipp}, title = {Neuro-mesodermal assembloids recapitulate aspects of peripheral nervous system development \(in\) \(vitro\)}, series = {Stem Cell Reports}, volume = {18}, journal = {Stem Cell Reports}, number = {5}, issn = {2213-6711}, doi = {10.1016/j.stemcr.2023.03.012}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349925}, pages = {1155-1165}, year = {2023}, abstract = {Summary Here we describe a novel neuro-mesodermal assembloid model that recapitulates aspects of peripheral nervous system (PNS) development such as neural crest cell (NCC) induction, migration, and sensory as well as sympathetic ganglion formation. The ganglia send projections to the mesodermal as well as neural compartment. Axons in the mesodermal part are associated with Schwann cells. In addition, peripheral ganglia and nerve fibers interact with a co-developing vascular plexus, forming a neurovascular niche. Finally, developing sensory ganglia show response to capsaicin indicating their functionality. The presented assembloid model could help to uncover mechanisms of human NCC induction, delamination, migration, and PNS development. Moreover, the model could be used for toxicity screenings or drug testing. The co-development of mesodermal and neuroectodermal tissues and a vascular plexus along with a PNS allows us to investigate the crosstalk between neuroectoderm and mesoderm and between peripheral neurons/neuroblasts and endothelial cells. Highlights •Novel neuro-mesodermal assembloid model of peripheral nervous system development •Model covers neural crest cell induction, migration, and ganglion formation •Ganglia send projections to the mesodermal as well as neural compartment •Peripheral ganglia and nerve fibers interact with a co-developing vascular plexus}, language = {en} } @article{AktasUpcinHenkeetal.2019, author = {Aktas, Bertal H. and Upcin, Berin and Henke, Erik and Padmasekar, Manju and Qin, Xuebin and Erg{\"u}n, S{\"u}leyman}, title = {The Best for the Most Important: Maintaining a Pristine Proteome in Stem and Progenitor Cells}, series = {Stem Cells International}, journal = {Stem Cells International}, doi = {10.1155/2019/1608787}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227769}, pages = {1-20}, year = {2019}, abstract = {Pluripotent stem cells give rise to reproductively enabled offsprings by generating progressively lineage-restricted multipotent stem cells that would differentiate into lineage-committed stem and progenitor cells. These lineage-committed stem and progenitor cells give rise to all adult tissues and organs. Adult stem and progenitor cells are generated as part of the developmental program and play critical roles in tissue and organ maintenance and/or regeneration. The ability of pluripotent stem cells to self-renew, maintain pluripotency, and differentiate into a multicellular organism is highly dependent on sensing and integrating extracellular and extraorganismal cues. Proteins perform and integrate almost all cellular functions including signal transduction, regulation of gene expression, metabolism, and cell division and death. Therefore, maintenance of an appropriate mix of correctly folded proteins, a pristine proteome, is essential for proper stem cell function. The stem cells' proteome must be pristine because unfolded, misfolded, or otherwise damaged proteins would interfere with unlimited self-renewal, maintenance of pluripotency, differentiation into downstream lineages, and consequently with the development of properly functioning tissue and organs. Understanding how various stem cells generate and maintain a pristine proteome is therefore essential for exploiting their potential in regenerative medicine and possibly for the discovery of novel approaches for maintaining, propagating, and differentiating pluripotent, multipotent, and adult stem cells as well as induced pluripotent stem cells. In this review, we will summarize cellular networks used by various stem cells for generation and maintenance of a pristine proteome. We will also explore the coordination of these networks with one another and their integration with the gene regulatory and signaling networks.}, language = {en} } @article{WoersdoerferErguen2023, author = {W{\"o}rsd{\"o}rfer, Philipp and Erg{\"u}n, S{\"u}leyman}, title = {"Organoids": insights from the first issues}, series = {Organoids}, volume = {2}, journal = {Organoids}, number = {2}, issn = {2674-1172}, doi = {10.3390/organoids2020006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313694}, pages = {79 -- 81}, year = {2023}, abstract = {No abstract available}, language = {en} } @article{PatzerKunzHuflageetal.2023, author = {Patzer, Theresa Sophie and Kunz, Andreas Steven and Huflage, Henner and Conrads, Nora and Luetkens, Karsten Sebastian and Pannenbecker, Pauline and Paul, Mila Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Grunz, Jan-Peter}, title = {Ultrahigh-resolution photon-counting CT in cadaveric fracture models: spatial frequency is not everything}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {10}, issn = {2075-4418}, doi = {10.3390/diagnostics13101677}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319281}, year = {2023}, abstract = {In this study, the impact of reconstruction sharpness on the visualization of the appendicular skeleton in ultrahigh-resolution (UHR) photon-counting detector (PCD) CT was investigated. Sixteen cadaveric extremities (eight fractured) were examined with a standardized 120 kVp scan protocol (CTDI\(_{vol}\) 10 mGy). Images were reconstructed with the sharpest non-UHR kernel (Br76) and all available UHR kernels (Br80 to Br96). Seven radiologists evaluated image quality and fracture assessability. Interrater agreement was assessed with the intraclass correlation coefficient. For quantitative comparisons, signal-to-noise-ratios (SNRs) were calculated. Subjective image quality was best for Br84 (median 1, interquartile range 1-3; p ≤ 0.003). Regarding fracture assessability, no significant difference was ascertained between Br76, Br80 and Br84 (p > 0.999), with inferior ratings for all sharper kernels (p < 0.001). Interrater agreement for image quality (0.795, 0.732-0.848; p < 0.001) and fracture assessability (0.880; 0.842-0.911; p < 0.001) was good. SNR was highest for Br76 (3.4, 3.0-3.9) with no significant difference to Br80 and Br84 (p > 0.999). Br76 and Br80 produced higher SNRs than all kernels sharper than Br84 (p ≤ 0.026). In conclusion, PCD-CT reconstructions with a moderate UHR kernel offer superior image quality for visualizing the appendicular skeleton. Fracture assessability benefits from sharp non-UHR and moderate UHR kernels, while ultra-sharp reconstructions incur augmented image noise.}, language = {en} } @article{HuflageGrunzPatzeretal.2023, author = {Huflage, Henner and Grunz, Jan-Peter and Patzer, Theresa Sophie and Pannenbecker, Pauline and Feldle, Philipp and Sauer, Stephanie Tina and Petritsch, Bernhard and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Kunz, Andreas Steven}, title = {Potential of unenhanced ultra-low-dose abdominal photon-counting CT with tin filtration: a cadaveric study}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {4}, issn = {2075-4418}, doi = {10.3390/diagnostics13040603}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304122}, year = {2023}, abstract = {Objectives: This study investigated the feasibility and image quality of ultra-low-dose unenhanced abdominal CT using photon-counting detector technology and tin prefiltration. Materials and Methods: Employing a first-generation photon-counting CT scanner, eight cadaveric specimens were examined both with tin prefiltration (Sn 100 kVp) and polychromatic (120 kVp) scan protocols matched for radiation dose at three different levels: standard-dose (3 mGy), low-dose (1 mGy) and ultra-low-dose (0.5 mGy). Image quality was evaluated quantitatively by means of contrast-to-noise-ratios (CNR) with regions of interest placed in the renal cortex and subcutaneous fat. Additionally, three independent radiologists performed subjective evaluation of image quality. The intraclass correlation coefficient was calculated as a measure of interrater reliability. Results: Irrespective of scan mode, CNR in the renal cortex decreased with lower radiation dose. Despite similar mean energy of the applied x-ray spectrum, CNR was superior for Sn 100 kVp over 120 kVp at standard-dose (17.75 ± 3.51 vs. 14.13 ± 4.02), low-dose (13.99 ± 2.6 vs. 10.68 ± 2.17) and ultra-low-dose levels (8.88 ± 2.01 vs. 11.06 ± 1.74) (all p ≤ 0.05). Subjective image quality was highest for both standard-dose protocols (score 5; interquartile range 5-5). While no difference was ascertained between Sn 100 kVp and 120 kVp examinations at standard and low-dose levels, the subjective image quality of tin-filtered scans was superior to 120 kVp with ultra-low radiation dose (p < 0.05). An intraclass correlation coefficient of 0.844 (95\% confidence interval 0.763-0.906; p < 0.001) indicated good interrater reliability. Conclusions: Photon-counting detector CT permits excellent image quality in unenhanced abdominal CT with very low radiation dose. Employment of tin prefiltration at 100 kVp instead of polychromatic imaging at 120 kVp increases the image quality even further in the ultra-low-dose range of 0.5 mGy.}, language = {en} } @article{GredicKarnatiRuppertetal.2023, author = {Gredic, Marija and Karnati, Srikanth and Ruppert, Clemens and Guenther, Andreas and Avdeev, Sergey N. and Kosanovic, Djuro}, title = {Combined pulmonary fibrosis and emphysema: when Scylla and Charybdis ally}, series = {Cells}, volume = {12}, journal = {Cells}, number = {9}, issn = {2073-4409}, doi = {10.3390/cells12091278}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313571}, year = {2023}, abstract = {Combined pulmonary fibrosis and emphysema (CPFE) is a recently recognized syndrome that, as its name indicates, involves the existence of both interstitial lung fibrosis and emphysema in one individual, and is often accompanied by pulmonary hypertension. This debilitating, progressive condition is most often encountered in males with an extensive smoking history, and is presented by dyspnea, preserved lung volumes, and contrastingly impaired gas exchange capacity. The diagnosis of the disease is based on computed tomography imaging, demonstrating the coexistence of emphysema and interstitial fibrosis in the lungs, which might be of various types and extents, in different areas of the lung and several relative positions to each other. CPFE bears high mortality and to date, specific and efficient treatment options do not exist. In this review, we will summarize current knowledge about the clinical attributes and manifestations of CPFE. Moreover, we will focus on pathophysiological and pathohistological lung phenomena and suspected etiological factors of this disease. Finally, since there is a paucity of preclinical research performed for this particular lung pathology, we will review existing animal studies and provide suggestions for the development of additional in vivo models of CPFE syndrome.}, language = {en} } @article{KirchmeierMeierottJung2023, author = {Kirchmeier, Peter and Meierott, Lenz and Jung, Klaus}, title = {Taraxacum sect. Borealia Hand.-Mazz. in den Alpen}, series = {Forum Geobotanicum}, volume = {11}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2023.1230}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-347512}, pages = {35-56}, year = {2023}, abstract = {The presence of Taraxacum microspecies of the section Borealia in the European Alps has been known from France, Suisse, Austria, Italy and Slowenia. The five known species are Taraxacum gallicum, T. handelii, T. kraettlii, T. mazzettii and T. melzerianum. From 2004 up to 2014 these localities have been visited. Detailed examinations of many collections make it possible to add characteristics and precise the descriptions and correct mistakes, eliminate ambiguities and fill gaps in the original descriptions. Numerous photos, drawings and a new determination key will make the access to the section Borealia easier. A new species of section Borealia, T. cimae-gallinae, from the mountain H{\"u}hnerspiel near Sterzing (Italy, South Tyrol) is described. The habitats of the Borealia in the alpine level are mostly gravel floors on wind-swept ridges or on summit levelings. The environment of Borealia-species is threatened by ski tourism or by the changes from global warming.}, subject = {Pflanzen}, language = {de} } @article{WatermannMeyerWagneretal.2023, author = {Watermann, Christoph and Meyer, Malin Tordis and Wagner, Steffen and Wittekindt, Claus and Klussmann, Jens Peter and Erguen, Sueleyman and Baumgart-Vogt, Eveline and Karnati, Srikanth}, title = {Peroxisomes are highly abundant and heterogeneous in human parotid glands}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms24054783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311079}, year = {2023}, abstract = {The parotid gland is one of the major salivary glands producing a serous secretion, and it plays an essential role in the digestive and immune systems. Knowledge of peroxisomes in the human parotid gland is minimal; furthermore, the peroxisomal compartment and its enzyme composition in the different cell types of the human parotid gland have never been subjected to a detailed investigation. Therefore, we performed a comprehensive analysis of peroxisomes in the human parotid gland's striated duct and acinar cells. We combined biochemical techniques with various light and electron microscopy techniques to determine the localization of parotid secretory proteins and different peroxisomal marker proteins in parotid gland tissue. Moreover, we analyzed the mRNA of numerous gene encoding proteins localized in peroxisomes using real-time quantitative PCR. The results confirm the presence of peroxisomes in all striated duct and acinar cells of the human parotid gland. Immunofluorescence analyses for various peroxisomal proteins showed a higher abundance and more intense staining in striated duct cells compared to acinar cells. Moreover, human parotid glands comprise high quantities of catalase and other antioxidative enzymes in discrete subcellular regions, suggesting their role in protection against oxidative stress. This study provides the first thorough description of parotid peroxisomes in different parotid cell types of healthy human tissue.}, language = {en} } @article{DrenckhahnGottschlichZonneveld2023, author = {Drenckhahn, Detlev and Gottschlich, G{\"u}nter and Zonneveld, Ben}, title = {Neubeschreibungen und 2C-Werte von Pilosella macranthela subsp. silvae-pici (Spessart-Mausohrhabichtskraut) und Pilosella ottonis (Otto-Mausohrhabichtskraut) mit einer {\"U}bersicht {\"u}ber das Vorkommen von P. macranthela-Taxa in Bayern.}, series = {Forum Geobotanicum}, volume = {11}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2023.1114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-344797}, pages = {21-34}, year = {2023}, abstract = {A pentaploid taxon from the Pilosella macranthela group was discovered in Lower Franconia/Bavaria which is newly described here as P. macranthela subsp. sylvae-pici. It grows mainly in the Bavarian Bunter Spessart and occurs with three small, isolated stands also in the limestone area of the Main valley and Tauber area. Its habit of growth is intermediate between the furcata and laxicephala types of Pilosellae with epigeal and partly hypogeal stolons and a tendency to form clusters. The upper and lower surfaces of the rosette leaves have stellate hairs. The peduncles and the phyllaries are densely covered with dark glandular hairs with yellowish glandular heads. The lateral teeth of the ligules often are separated by incisions. A tetra- und pentaploid transitional taxon between P. macranthela subsp. sylvae-pici and P. officinarum is described as P. ottonis. P. ottonis is tetra- and pentaploid with up to 7 capitula. It is densely covered with dark stalk glands on phyllaries and resembles forms of P. acutifolia in habit. The phyllaries of P. ottonis are covered with numerous epidermal papillae with a diameter of about 10-20 μm and in this aspect resemble P. macranthela subsp. sylvae-pici and P. glomerata. However, in P. officinarum epidermal papillae are absent. Plants of genetically heterogeneous tetra- and heptaploid P. macranthela have been found outside the Spessart as spontaneous hybrids between P. glomerata and P. officinarum and also occur sporadically without P. glomerata in the vicinity.}, subject = {Habichtskraut}, language = {de} } @article{RajendranRajendranGuptaetal.2022, author = {Rajendran, Ranjithkumar and Rajendran, Vinothkumar and Gupta, Liza and Shirvanchi, Kian and Schunin, Darja and Karnati, Srikanth and Giraldo-Vel{\´a}squez, Mario and Berghoff, Martin}, title = {Interferon beta-1a versus combined interferon beta-1a and oligodendrocyte-specific FGFR1 deletion in experimental autoimmune encephalomyelitis}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {20}, issn = {1422-0067}, doi = {10.3390/ijms232012183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290401}, year = {2022}, abstract = {Recombinant beta interferons-1 (IFNβ-1) are used as first line therapies in patients with relapsing multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the CNS. IFNβ-1a/b has moderate effects on the prevention of relapses and slowing of disease progression. Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known to play a key role in the pathology of MS and its model EAE. To investigate the effects of short-term treatment with s.c. IFNβ-1a versus the combined application of s.c. IFNβ-1a and oligodendrocyte-specific deletion of FGFR1 (Fgfr1\(^{ind-/-}\) mice) in MOG\(_{35-55}\)-induced EAE. IFNβ-1a (30 mg/kg) was applied s.c. from days 0-7 p.i. of EAE in controls and Fgfr1\(^{ind-/-}\) mice. FGFR signaling proteins associated with inflammation/degeneration in MS/EAE were analyzed by western blot in the spinal cord. Further, FGFR1 in Oli-neu oligodendrocytes were inhibited by PD166866 and treated with IFNβ-1a (400 ng/mL). Application of IFNβ-1a over 8 days resulted in less symptoms only at the peak of disease (days 9-11) compared to controls. Application of IFNβ-1a in Fgfr1\(^{ind-/-}\) mice resulted in less symptoms primarily in the chronic phase of EAE. Fgfr1\(^{ind-/-}\) mice treated with IFNβ-1a showed increased expression of pERK and BDNF. In Oli-neu oligodendrocytes, treatment with PD166866 and IFNβ-1a also showed an increased expression of pERK and BDNF/TrkB. These data suggest that the beneficial effects in the chronic phase of EAE and on signaling molecules associated with ERK and BDNF expression are caused by the modulation of FGFR1 and not by interferon beta-1a. FGFR may be a potential target for therapy in MS.}, language = {en} } @article{GottschlichDrenckhahnMeierottetal.2023, author = {Gottschlich, G{\"u}nter and Drenckhahn, Detlev and Meierott, Lenz and Zonneveld, Ben}, title = {Hieracium maculatum subsp. pseudogougetianum, eine neue Unterart aus dem Mainfr{\"a}nkischen Muschelkalkgebiet}, series = {Forum Geobotanicum}, volume = {11}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2023.0923}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327601}, pages = {15-20}, year = {2023}, abstract = {In Lower Franconia/Northern Bavaria, a well-defined subspecies of the Hieracium maculatum group was detected. This subspecies is restricted to the slopes of the Main valley between W{\"u}rzburg and Hasloch with a hot spot (>90\% of total population) between the villages Th{\"u}ngersheim and Retzbach. Due to some similarities with H. glaucinum subsp. prasiophaeum (synonym: subsp. gougetianum) the subspecies is named H. maculatum subsp. pseudogougetianum. This subspecies grows preferentially on shell-bearing limestone gravels and begins flowering as early as mid-April. Head involucra are whitish hairy mixed with dark stalked glands. The basal leaf rosette consists of ovate to elliptic, toothed to serrate, dark spotted leaves, glabrous, glaucous above. Stems bear 1-3(4) stalked stem leaves and usually form long lateral flowering branches from the leaf axils. Like some other H. maculatum subspecies, H. maculatum subsp. pseudogougetianum is tetraploid with a mean genome weight (2C value) of 14.5 pg, distinguishing it from the H. glaucinum group, whose studied taxa are invariably triploid (mean 10.1 pg).}, subject = {Korbbl{\"u}tler}, language = {de} } @article{KustiatiErguenKarnatietal.2022, author = {Kustiati, Ulayatul and Erg{\"u}n, Suleyman and Karnati, Srikanth and Nugrahaningsih, Dwi Aris Agung and Kusindarta, Dwi Liliek and Wihadmadyatami, Hevi}, title = {Ethanolic extract of Ocimum sanctum Linn. Inhibits cell migration of human lung adenocarcinoma cells (A549) by downregulation of integrin αvβ3, α5β1, and VEGF}, series = {Scientia Pharmaceutica}, volume = {90}, journal = {Scientia Pharmaceutica}, number = {4}, issn = {2218-0532}, doi = {10.3390/scipharm90040069}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290540}, year = {2022}, abstract = {Adenocarcinoma lung cancer is a type of non-small cell lung carcinoma (NSCLC), which accounts for 85\% of lung cancer incidence globally. The therapies that are being applied, both conventional therapies and antibody-based treatments, are still found to have side effects. Several previous studies have demonstrated the ability of the ethanolic extract of Ocimum sanctum Linn. (EEOS) as an ethnomedicine with anti-tumor properties. The aim of this study was to determine the effect of Ocimum sanctum Linn. ethanolic extract in inhibiting the proliferation, angiogenesis, and migration of A549 cells (NSCLC). The adhesion as well as the migration assay was performed. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression of αvβ3 integrins, α5β1 integrins, and VEGF. The cells were divided into the following treatment groups: control (non-treated/NT), positive control (AP3/inhibitor β3 80 µg/mL), cisplatin (9 µg/mL), and EEOS at concentrations of 50, 70, 100, and 200 µg/mL. The results showed that EEOS inhibits the adhesion ability and migration of A549 cells, with an optimal concentration of 200 µg/mL. ELISA testing showed that the group of A549 cells given EEOS 200 µg/mL presented a decrease in the optimal expression of integrin α5β1, integrin αvβ3, and VEGF.}, language = {en} } @article{Gottschlich2023, author = {Gottschlich, G{\"u}nter}, title = {Hieracium rotundatum subsp. silvae-bavaricae, eine neue Hieracium-Sippe aus dem Bayerischen Wald (Deutschland)}, series = {Forum Geobotanicum}, volume = {11}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2023.0912}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-327145}, pages = {8-14}, year = {2023}, abstract = {Hieracium rotundatum subsp. silvae-bavaricae is described as new for science and illustrated. The new subspecies belongs to a group of species (H. rotundatum, H. transylvanicum) whose main distribution is in the Balkans. The changeful nomenclatural history of the species name is described. Diagnostic features to distinguish the growth habit-similar species H. murorum, H. rotundatum and H. transylvanicum are discussed. Particular attention is drawn to the importance of the development of the basic leaf cycle. Contrary to previous knowledge, the northwestern distribution limit of H.rotundatum extends now to southeastern Bavaria. During the search for H. rotundatum a morphologically conspicuous subspecies of H. rotundatum could be detected, which is described here as new.}, subject = {Habichtskraut}, language = {de} } @article{Haveman2023, author = {Haveman, Rense}, title = {Phytosociological notes on hedges in South Ayrshire, Scotland}, series = {Forum Geobotanicum}, volume = {11}, journal = {Forum Geobotanicum}, issn = {1867-9315}, doi = {10.3264/FG.2023.0420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312634}, pages = {1-7}, year = {2023}, abstract = {On the basis of four relev{\´e}es of hedges around Straiton en Dailly in South Ayrshire, Scotland, some features of hedges are discussed. On the basis of the brambles, the vegetation of these hedges can be assigned to the Pruno-Rubion sprengelii, which comprises the bramble scrubs of circumneutral and nutrient rich soils in West Europe (Haveman et al. 2017, Haveman \& de Ronde 2019). Until now, this alliance was thought to be restricted to the northwestern edge of the European continent, but based on these relev{\´e}es and the known distribution area of Rubus nemoralis and Rubus polyanthemus, both characteristic for the Pruno-Rubion sprengelii, large parts of North England and Scotland have to be included in the distribution area of the alliance. The Pruno-Rubion sprengelii is optimally developed in rather narrow structures, like hedges, which are pruned every year. Here, brambles and herbs alike can grow with and under the shrubs, facilitated by the light that reaches large parts of the ground. Where the economic base of hedges perishes, they are not longer maintained, and the shrubs can grow out to their natural proportions. This changes the amount of light reaching the surface in the inner parts of the thicket, changing the competition between the species. The brambles as well as the herbs are displaced to the outer edges of the scrub, and the vegetation "dissociates" in a high-growing scrub, a fore-mantle ("cuff") with brambles, and a fringe with perennial herbs. These elements can hardly ever be assigned to the Pruno-Rubion anymore. The Pruno-Rubion sprengelii in optima forma is a scrub in which the three elements (shrubs, brambles, and herbs) grow closely intertwined. This is rarely found in natural landscapes, and thus the alliance is a typical element of the old farmer landscape. What is more: the typical species of the alliance, like Rubus nemoralis and R. polyanthemus, could only evolve after the landscape was opened by farmers in the last six millennia (Matzke-Hajek 1997), giving way to Rubus ulmifolius to expand its distribution area. This caused an explosion of hybrids which stabilised through apomixis into the wealth of Rubus species inhibiting the West European landscape nowadays (Sochor et al. 2015). Many of these species have their original home in a man-made landscape. Therefore, the Pruno-Rubion sprengelii can be characterised as a "farmers alliance" pur sang.}, subject = {Brombeere}, language = {en} } @article{ReschkeSalvadorSchlegeletal.2022, author = {Reschke, Moritz and Salvador, Ellaine and Schlegel, Nicolas and Burek, Malgorzata and Karnati, Srikanth and Wunder, Christian and F{\"o}rster, Carola Y.}, title = {Isosteviol sodium (STVNA) reduces pro-inflammatory cytokine IL-6 and GM-CSF in an in vitro murine stroke model of the blood-brain barrier (BBB)}, series = {Pharmaceutics}, volume = {14}, journal = {Pharmaceutics}, number = {9}, issn = {1999-4923}, doi = {10.3390/pharmaceutics14091753}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286275}, year = {2022}, abstract = {Early treatment with glucocorticoids could help reduce both cytotoxic and vasogenic edema, leading to improved clinical outcome after stroke. In our previous study, isosteviol sodium (STVNA) demonstrated neuroprotective effects in an in vitro stroke model, which utilizes oxygen-glucose deprivation (OGD). Herein, we tested the hypothesis that STVNA can activate glucocorticoid receptor (GR) transcriptional activity in brain microvascular endothelial cells (BMECs) as previously published for T cells. STVNA exhibited no effects on transcriptional activation of the glucocorticoid receptor, contrary to previous reports in Jurkat cells. However, similar to dexamethasone, STVNA inhibited inflammatory marker IL-6 as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion. Based on these results, STVNA proves to be beneficial as a possible prevention and treatment modality for brain ischemia-reperfusion injury-induced blood-brain barrier (BBB) dysfunction.}, language = {en} } @article{ShityakovNagaiErguenetal.2022, author = {Shityakov, Sergey and Nagai, Michiaki and Erg{\"u}n, S{\"u}leyman and Braunger, Barbara M. and F{\"o}rster, Carola Y.}, title = {The protective effects of neurotrophins and microRNA in diabetic retinopathy, nephropathy and heart failure via regulating endothelial function}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {8}, issn = {2218-273X}, doi = {10.3390/biom12081113}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285966}, year = {2022}, abstract = {Diabetes mellitus is a common disease affecting more than 537 million adults worldwide. The microvascular complications that occur during the course of the disease are widespread and affect a variety of organ systems in the body. Diabetic retinopathy is one of the most common long-term complications, which include, amongst others, endothelial dysfunction, and thus, alterations in the blood-retinal barrier (BRB). This particularly restrictive physiological barrier is important for maintaining the neuroretina as a privileged site in the body by controlling the inflow and outflow of fluid, nutrients, metabolic end products, ions, and proteins. In addition, people with diabetic retinopathy (DR) have been shown to be at increased risk for systemic vascular complications, including subclinical and clinical stroke, coronary heart disease, heart failure, and nephropathy. DR is, therefore, considered an independent predictor of heart failure. In the present review, the effects of diabetes on the retina, heart, and kidneys are described. In addition, a putative common microRNA signature in diabetic retinopathy, nephropathy, and heart failure is discussed, which may be used in the future as a biomarker to better monitor disease progression. Finally, the use of miRNA, targeted neurotrophin delivery, and nanoparticles as novel therapeutic strategies is highlighted.}, language = {en} } @article{ErguenWoersdoerfer2022, author = {Erg{\"u}n, S{\"u}leyman and W{\"o}rsd{\"o}rfer, Philipp}, title = {Organoids, assembloids and embryoids: New avenues for developmental biology, disease modeling, drug testing and toxicity assessment without animal experimentation}, series = {Organoids}, volume = {1}, journal = {Organoids}, number = {1}, issn = {2674-1172}, doi = {10.3390/organoids1010004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284101}, pages = {37 -- 40}, year = {2022}, abstract = {No abstract available}, language = {en} } @article{SchmidtAltDeoghareetal.2022, author = {Schmidt, Sven and Alt, Yvonne and Deoghare, Nikita and Kr{\"u}ger, Sarah and Kern, Anna and Rockel, Anna Frederike and Wagner, Nicole and Erg{\"u}n, S{\"u}leyman and W{\"o}rsd{\"o}rfer, Philipp}, title = {A blood vessel organoid model recapitulating aspects of vasculogenesis, angiogenesis and vessel wall maturation}, series = {Organoids}, volume = {1}, journal = {Organoids}, number = {1}, issn = {2674-1172}, doi = {10.3390/organoids1010005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284043}, pages = {41 -- 53}, year = {2022}, abstract = {Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. Here we present a novel, cost-effective, and easy to manufacture vascular organoid model. To engineer the organoids, a defined number of human induced pluripotent stem cells are seeded in non-adhesive agarose coated wells of a 96-well plate and directed towards a lateral plate mesoderm fate by activation of Wnt and BMP4 signaling. We observe the formation of a circular layer of angioblasts around days 5-6. Induced by VEGF application, CD31\(^+\) vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. These cells arrange to form a primitive vascular plexus from which angiogenic sprouting is observed after 10 days of culture. The differentiation outcome is highly reproducible, and the size of organoids is scalable depending on the number of starting cells. We observe that the initial vascular ring forms at the interface between two cell populations. The inner cellular compartment can be distinguished from the outer by the expression of GATA6, a marker of lateral plate mesoderm. Finally, 14-days-old organoids were transplanted on the chorioallantois membrane of chicken embryos resulting in a functional connection of the human vascular network to the chicken circulation. Perfusion of the vessels leads to vessel wall maturation and remodeling as indicated by the formation of a continuous layer of smooth muscle actin expressing cells enwrapping the endothelium. In summary, our organoid model recapitulates human vasculogenesis, angiogenesis as well as vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.}, language = {en} } @article{GergsJahnSchulzetal.2022, author = {Gergs, Ulrich and Jahn, Tina and Schulz, Nico and Großmann, Claudia and Rueckschloss, Uwe and Demus, Uta and Buchwalow, Igor B. and Neumann, Joachim}, title = {Protein phosphatase 2A improves cardiac functional response to ischemia and sepsis}, series = {International Journal of Molecular Sciences}, volume = {23}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms23094688}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284035}, year = {2022}, abstract = {Reversible protein phosphorylation is a posttranslational modification of regulatory proteins involved in cardiac signaling pathways. Here, we focus on the role of protein phosphatase 2A (PP2A) for cardiac gene expression and stress response using a transgenic mouse model with cardiac myocyte-specific overexpression of the catalytic subunit of PP2A (PP2A-TG). Gene and protein expression were assessed under basal conditions by gene chip analysis and Western blotting. Some cardiac genes related to the cell metabolism and to protein phosphorylation such as kinases and phosphatases were altered in PP2A-TG compared to wild type mice (WT). As cardiac stressors, a lipopolysaccharide (LPS)-induced sepsis in vivo and a global cardiac ischemia in vitro (stop-flow isolated perfused heart model) were examined. Whereas the basal cardiac function was reduced in PP2A-TG as studied by echocardiography or as studied in the isolated work-performing heart, the acute LPS- or ischemia-induced cardiac dysfunction deteriorated less in PP2A-TG compared to WT. From the data, we conclude that increased PP2A activity may influence the acute stress tolerance of cardiac myocytes.}, language = {en} }