Die Kosten der Lipödem-Behandlung übersteigen den DRG-Erlös – Evaluation der operativen Behandlungskosten des Lipödems (Stadium III) an einer deutschen Universitätsklinik

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Author: Jiang, Jun ; Gawlik, Edith ; Eisenreich, Stefan ; Schoeffski, Oliver ; Moog, Philipp ; Machens, Hans-Günther ; Kükrek, Haydar

01 Nov 2024·Archives of Physiology and Biochemistry

A molecular and computational study of galbanic acid as a regulator of Sirtuin1 pathway in inhibiting lipid accumulation in HepG2 cells

Article

Author: Shokri Afra, Hajar ; Sadeghkhani, Farideh ; Khonakdar-Tarsi, Abbas ; Mahjoub, Soleiman ; Ghalehnoei, Hossein ; Musavi, Hadis

INTRODUCTIONSirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro.METHODSHepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns.RESULTSThe semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar.CONCLUSIONComputational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells.

01 Sep 2024·Bioorganic Chemistry

α-Glucosidase inhibition assay of galbanic acid and it amide derivatives: New excellent semi-synthetic α-glucosidase inhibitors

Article

Author: Mahdavi, Mohammad ; Larijani, Bagher ; Mirzazadeh, Roghieh ; Dastyafteh, Navid ; Mohammadi-Khanaposhtani, Maryam ; Mojtabavi, Somayeh ; Iraji, Aida ; Yazzaf, Rozita ; Palimi, Mahdie ; Halimi, Mohammad ; Faramarzi, Mohammad Ali ; Dadgar, Armin ; Sayahi, Mohammad Hosein ; Delnavazi, Mohammad-Reza

α-Glucosidase inhibitory activity of galbanic acid and its new amide derivatives 3a-n were investigated. Galbanic acid and compounds 3a-n showed excellent anti-α-glucosidase activity with IC₅₀ values ranging from 0.3 ± 0.3 μM to 416.0 ± 0.2 μM in comparison to positive control acarbose with IC₅₀ value of = 750.0 ± 5.6. In the kinetic study, the most potent compound 3h demonstrated a competitive mode of inhibition with K_i = 0.57 µM. The interaction of the most potent compound 3h with the α-glucosidase was further elaborated by in vitro Circular dichroism assessment and in silico molecular docking and Molecular dynamics studies. Compound 3h was also non-cytotoxic on human normal cells. In silico study on pharmacokinetics and toxicity profile of the most potent galbanic acid derivatives demonstrated that these compounds are valuable lead compounds for further study in order to achieve new anti-diabetic agents.

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Indication	Highest Phase	Country/Location	Organization	Date
Melanoma	Preclinical	Iran	Mashhad University of Medical Sciences	07 Feb 2024

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