01780nas a2200217   4500008004100000020001400041245010500055210006900160260001600229300001000245490000700255520110000262100002101362700001801383700001801401700002101419700002201440700002101462700002401483856005501507       2024                        eng d  a2045-232200aGliflozins, sucrose and flavonoids are allosteric activators of lecithin-cholesterol acyltransferase0 aGliflozins sucrose and flavonoids are allosteric activators of l  c2024/10/30/  a260850 v143 aAbstract            Lecithin-cholesterol acyltransferase (LCAT) serves as a pivotal enzyme in preserving cholesterol homeostasis via reverse cholesterol transport, a process closely associated with the onset of atherosclerosis. Impaired LCAT function can lead to severe LCAT deficiency disorders for which no pharmacological treatment exists. LCAT-based therapies, such as small molecule positive allosteric modulators (PAMs), against LCAT deficiencies and atherosclerosis hold promise, although their efficacy against atherosclerosis remains challenging. Herein we utilized a quantitative in silico metric to predict the activity of novel PAMs and tested their potencies with in vitro enzymatic assays. As predicted, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), sucrose and flavonoids activate LCAT. This has intriguing implications for the mechanism of action of gliflozins, which are commonly used in the treatment of type 2 diabetes, and for the endogenous activation of LCAT. Our results underscore the potential of molecular dynamics simulations in rational drug design.1 aNiemelä, Akseli1 aGiorgi, Laura1 aNouri, Sirine1 aYurttaş, Betül1 aRauniyar, Khushbu1 aJeltsch, Michael1 aKoivuniemi, Artturi  uhttps://www.nature.com/articles/s41598-024-77104-302239nas a2200193   4500008004100000020002200041245004600063210004100109250000600150260002900156300001200185520168900197100002001886700001901906700002101925700002201946700002701968856005001995       2015                        eng d  a978-3-934371-53-800aThe genetic causes of primary lymphedema.0 agenetic causes of primary lymphedema  a6  aColognebViavital Verlag  a210-2293 aEnglish:
Primary lymphedema can be treated, but not cured. In addition, their diagnosis is due to heterogeneous phenotypes often ambiguous. However, these problems can be tackled by identifying the edema-causing genetic lesions to yield unambiguous diagnoses and by developing specific treatments that address the underlying, molecular cause. New developments in molecular biology are providing the necessary tools for these tasks and in the recent years the genetic causes of many forms of primary lymphedema have been identified, notably by exome sequencing. For a significant proportion of lymphatic disorders multifactorial genetic causes are suspected.
This chapter provides an overview of the current knowledge on the genetic origin, the categorization as well as the molecular and biochemical causes of primary lymphedema.

German:
Primäre Lymphödeme sind behandelbar, aber nicht heilbar. Zudem ist die Diagnostik aufgrund heterogener Phänotypen oft nicht eindeutig. Um diese Probleme anzugehen, müssen die das Ödem verursachenden genetischen Ursachen gefunden, diagnostiziert und gezielt behandelt werden. Die hierzu notwendigen Techniken liefern die neuen Entwicklungen in der Molekularbiologie. Insbesondere durch die Technik der Exom-Sequenzierung wurden in den letzten Jahren die genetischen Ursachen vieler primärer Lymphödeme identifiziert. Für einen weiteren großen Anteil dieser Erkrankungen werden multifaktorielle genetische Dispositionen vermutet.
Dieses Kapitel gibt einen Überblick über den derzeitigen Kenntnisstand der genetischen Ursachen, der Kategorisierung sowie der molekularbiologischen und biochemischen Grundlagen primärer Lymphödeme.1 aMattonet, Kenny1 aWilting, Jörg1 aJeltsch, Michael1 aWeissleder, Horst1 aSchuchhardt, Christian  uhttps://jeltsch.org/Mattonet2015a?language=en01736nas a2200169   4500008004100000245005000041210005000091260001400141300001200155490000800167520126400175100002101439700002001460700001801480700001901498856004901517       2003                        eng d00aGenesis and pathogenesis of lymphatic vessels0 aGenesis and pathogenesis of lymphatic vessels  c2003/Oct/  a69 - 840 v3143 aThe lymphatic system is generally regarded as supplementary to the blood vascular system, in that it transports interstitial fluid, macromolecules, and immune cells back into the blood. However, in insects, the open hemolymphatic (or lymphohematic) system ensures the circulation of immune cells and interstitial fluid through the body. The Drosophila homolog of the mammalian vascular endothelial growth factor receptor (VEGFR) gene family is expressed in hemocytes, suggesting a close relationship to the endothelium that develops later in phylogeny. Lymph hearts are typical organs for the propulsion of lymph in lower vertebrates and are still transiently present in birds. The lymphatic endothelial marker VEGFR-3 is transiently expressed in embryonic blood vessels and is crucial for their development. We therefore regard the question of whether the blood vascular system or the lymphatic system is primary or secondary as open. Future molecular comparisons should be performed without any bias based on the current prevalence of the blood vascular system over the lymphatic system. Here, we give an overview of the structure, function, and development of the lymphatics, with special emphasis on the recently discovered lymphangiogenic growth factors.1 aJeltsch, Michael1 aTammela, Tuomas1 aAlitalo, Kari1 aWilting, Jörg  uhttp://view.ncbi.nlm.nih.gov/pubmed/1294236201905nas a2200217   4500008004100000245009100041210006900132260001400201300001500215490000800230520128700238100001401525700001201539700001301551700001501564700001601579700001501595700001401610700001501624856004801639       1997                        eng d00aGenomic organization of human and mouse genes for vascular endothelial growth factor C0 aGenomic organization of human and mouse genes for vascular endot  c1997/Oct/  a25176 - 830 v2723 aWe report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C6C10CRC, and exon 6 encodes additional C10CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-kappaB transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.1 aChilov, D1 aKukk, E1 aTaira, S1 aJeltsch, M1 aKaukonen, J1 aPalotie, A1 aJoukov, V1 aAlitalo, K  uhttp://view.ncbi.nlm.nih.gov/pubmed/9312130