Article
Chemistry, Organic
Sarah Al Muthafer, Christoph Schissler, Vanessa Koch, Hannes Kuhner, Martin Nieger, Stefan Brase
Summary: In this study, the concise semisynthesis of natural cardenolide uzarigenin and its diastereoisomer allo-uzarigenin was achieved in nine and seven steps, respectively, starting from epi-androsterone. The stereoselective introduction of the beta-hydroxy group at C-14 via Mukaiyama oxidation and the installation of the butenolide ring at C-17 using a Stille-cross-coupling reaction were discussed. By directing the hydrogenation via a protecting group strategy, both the C-17 beta isomer and allo-uzarigenin were obtained stereoselectively.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Lei Yu, Yu-Cai Zheng, Zhi-Xiong Li, Ai-Lin Wang, Wei-Dong Feng, Kai-Qing Rao
Summary: This study compared the expression of corticosterone metabolic enzyme genes in Tibetan and broiler chicken embryos and found differences in gene expression levels. It provides essential information for further research on the internal mechanism of maternal glucocorticoid programming on offspring.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
(2023)
Article
Cell Biology
Fei-Er Feng, Gao-Chao Zhang, Feng-Qi Liu, Yun He, Xiao-Lu Zhu, Xiao Liu, Yu Wang, Jing-Zhi Wang, Hai-Xia Fu, Yu-Hong Chen, Wei Han, Ying-Jun Chang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Summary: Thrombocytopenia caused by HCMV infection may be influenced by the virus through specific pathways during megakaryocyte maturation, apoptosis, and platelet generation; Inhibitors targeting PDGFRα and αvβ3 significantly reduce HCMV infection in megakaryocytes, suggesting potential therapeutic alternatives for viral infections.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Stefanie Hahner, Philipp E. Hartrampf, Patrick W. Mihatsch, Marc Nauerz, Britta Heinze, Heribert Haenscheid, Carmina Teresa Fuss, Rudolf A. Werner, Christina Pamporaki, Matthias Kroiss, Martin Fassnacht, Andreas K. Buck, Andreas Schirbel
Summary: This study reports a new theranostic approach for the diagnosis and treatment of adrenocortical carcinoma using adrenal specific radiotracers. The results show that this treatment leads to disease stabilization and partial tumor size reduction, with limited toxicities.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Chemistry, Multidisciplinary
Thomas P. Corner, Ryan Z. R. Teo, Yue Wu, Eidarus Salah, Yu Nakashima, Giorgia Fiorini, Anthony Tumber, Amelia Brasnett, James P. Holt-Martyn, William D. Figg Jr, Xiaojin Zhang, Lennart Brewitz, Christopher J. Schofield
Summary: The study identified N-hydroxythiazole derivatives that selectively inhibit factor inhibiting hypoxia-inducible factor-alpha (FIH) without affecting other 2OG oxygenases. These inhibitors modulate the expression of FIH-dependent HIF target genes and suppress lipid accumulation in adipocytes. This research is of significant importance for the development of more selective 2OG oxygenase inhibitors.
Article
Chemistry, Organic
Arka Das, Christine Jonathan, Rana Saha, Md Imran Ahmed, Subhendu Bhowmik
Summary: A regioselective decarboxylative alkynylation of tetrahydro-beta-carboline-1-carboxylic acid under peroxide-free condition is reported, which exhibits high selectivity for the 1-position of tetrahydro-beta-carboline. Depending on the reagent, the reaction can produce alkynylated or enaminone products. The reaction proceeds through sequential decarboxylative iminium ion formation followed by an alkynylation and oxidative rearrangement cascade.
Article
Endocrinology & Metabolism
Hanna F. Nowotny, Leah Braun, Frederick Vogel, Martin Bidlingmaier, Martin Reincke, Lea Tschaidse, Matthias K. Auer, Christian Lottspeich, Stefan A. Wudy, Michaela F. Hartmann, James Hawley, Joanne E. Adaway, Brian Keevil, Katharina Schilbach, Nicole Reisch
Summary: This study analyzed the contribution of 11-oxygenated C19 steroids to hyperandrogenemia in female patients with Cushing's disease. The results showed that untreated patients with Cushing's disease had significantly elevated levels of 11oxC19 steroids, while these levels dropped significantly after surgery and medication treatment.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Kazuhiro Watanabe, Atsumi Tsuji-Hosokawa, Atsuko Hashimoto, Kaoru Konishi, Nobuyuki Ishige, Harumi Yajima, Akito Sutani, Hisae Nakatani, Maki Gau, Kei Takasawa, Toshihiro Tajima, Tomonobu Hasegawa, Tomohiro Morio, Kenichi Kashimada
Summary: This study utilized LC-MS/MS to screen for 21-hydroxylase deficiency (21OHD) and developed a new screening algorithm. The results demonstrated that 21DOF, (4AD + 17 alpha OHP)/F, and 11DOF/17 alpha OHP were more relevant markers for 21OHD screening compared to 17 alpha OHP.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Endocrinology & Metabolism
Yusuf Ali, Maniselvan Kuppusamy, Carolina Velarde-Miranda, Clara M. Gomez-Sanchez, Maria Plonczynski, Celso E. Gomez-Sanchez, Elise P. Gomez-Sanchez
Summary: The mineralocorticoid receptor (MR) has similar affinity for aldosterone and glucocorticoids, but 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) plays a crucial role in providing prereceptor specificity for aldosterone. Increasing expression of 11 beta HSD2 decreases the concentration of glucocorticoids and reduces MR transactivation by glucocorticoids in a dose-dependent manner, demonstrating the efficacy of this enzyme.
JOURNAL OF THE ENDOCRINE SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Schuyler D. Vickers, Stephanie A. Shumar, Dominique C. Saporito, Amina Kunovac, Quincy A. Hathaway, Breeanna Mintmier, Judy A. King, Rachel D. King, Vazhaikkurichi M. Rajendran, Aniello M. Infante, John M. Hollander, Roberta Leonardi
Summary: NUDT7 is an enzyme highly expressed in the liver and located in peroxisomes. It hydrolyzes CoA species, affecting peroxisomal lipid metabolism and the synthesis of bile acids. Deletion of Nudt7 gene alters the composition of the hepatic acyl-CoA pool and promotes the production of certain bile acid derivatives.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Lin, Meng-Ying Ye, Qian-Yun Fu, Chao-Lin Pan, Ya-Jie Liu, Li-Ming Zheng, Qiang Hong, Yuan-Hua Chen
Summary: Elevated serum cholic acid (CA) due to gestational cholestasis is associated with fetal growth restriction (FGR). CA induces FGR by causing placental glucocorticoid barrier dysfunction and activating the GCN2/eIF2 alpha pathway via excessive production of reactive oxygen species (ROS). NAC, an inhibitor, can rescue CA-induced FGR by inhibiting the activation of the GCN2/eIF2 alpha pathway and restoring the protein level of 11 beta-Hydroxysteroid dehydrogenase-2 (11 beta-HSD2) in placental trophoblasts.
Article
Chemistry, Medicinal
Lennart Brewitz, Yu Nakashima, Sonia K. Piasecka, Eidarus Salah, Sally C. Fletcher, Anthony Tumber, Thomas P. Corner, Tristan J. Kennedy, Giorgia Fiorini, Armin Thalhammer, Kirsten E. Christensen, Mathew L. Coleman, Christopher J. Schofield
Summary: Jumonji-C domain-containing protein 5 (JMJD5) is an important 2-oxoglutarate-dependent oxygenase that has various functions in development, circadian rhythm, and cancer. This study discovered potent JMJD5 inhibitors, which are 5-aminoalkyl-substituted derivatives of the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylic acid (2,4-PDCA). Crystallographic analyses showed that these inhibitors bind to JMJD5 in an induced fit manner, with the C5 substituent of 2,4-PDCA binding to the substrate-binding pocket of JMJD5. Cellular studies revealed that these lead compounds displayed similar phenotypes as clinically observed JMJD5 variants with reduced catalytic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jose Luis Viveros-Ceballos, Lizeth A. Matias-Valdez, Francisco J. Sayago, Carlos Cativiela, Mario Ordonez
Summary: Two new strategies have been developed for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (Tic(p)) (+/-)-2. These strategies involve the formation of a key intermediate, the highly electrophilic N-acyliminium ion, and provide the target compound in good yield using mild reaction conditions and readily available starting materials. These strategies complement existing methodologies and contribute to the easy accessibility of (+/-)-2 for further research.
Article
Pharmacology & Pharmacy
Bin Shi, Fang-Fang Xu, Cai-Ping Xiang, Chuan-Yan Li, Ping Fan, Hao Wang
Summary: This study reveals the involvement of HIF1α/VEGF feedback loop in 5-Fu resistance, suggesting potential therapeutic targets for colorectal cancer treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Prajakatta Mulay, Cindy Chen, Vijay Krishna
Summary: This study discovered that pyridoxal-5'-phosphate (PLP) has catalytic activity and can breakdown cysteine to produce hydrogen sulfide (H2S) in the absence of enzymes and multivalent metal ions. The reaction of PLP with cysteine forms a thiazolidine product, which can slowly decompose to produce H2S. This research provides important insights into the role of PLP in metabolic pathways.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Olexander M. Semenenko, Victoria V. Lipson, Alina O. Sadchenko, Olga V. Vashchenko, Natalia A. Kasian, Liliia Sviechnikova, Longin M. Lisetski, Mykola L. Babak, Volodymyr M. Vakula, Oleksandr Borysov, Yuliia Holota, Sergey O. Zozulya, Petro O. Borysko, Olexander Mazepa
Summary: An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids has been developed and their structures and properties have been fully established. The hybrids showed inferior interactions with artificial lipid membranes, possibly due to their increasing lipophilicity.
Article
Biochemistry & Molecular Biology
Mohadese Yaghoobi Anzabi, Piotr Cmoch, Roman Luboradzki, Zbigniew Pakulski
Summary: Friedelin and 3-acetoxyfriedel-3-en-2-one, known as friedelane triterpenoids, have been isolated from cork smoker wash solids and used as starting materials for the synthesis of new friedelane derivatives. Reduction reactions result in the formation of friedelinol and epi-cerin derivatives.
Article
Biochemistry & Molecular Biology
Detlef Thieme, Aniko Krumbholz, Martin Bidlingmaier, Christoph Geffert, Annika Hameder, Andreas Stoever, Matthias Graw, Annekathrin M. Keiler
Summary: Ethanol can affect testosterone metabolism and potentially influence steroid biosynthesis and blood steroid profiles. The study emphasizes the importance of sufficient time interval from food and ethanol intake during blood sampling, particularly for diagnostics in doping control.
Article
Biochemistry & Molecular Biology
Masanobu Murao, Tetsuo Imano, Yoshinobu Sato, Masaaki Nakajima
Article
Biochemistry & Molecular Biology
Jingyuan Wang, Ye Feng, Brian Liu, Wen Xie
Summary: Sulfation and desulfation of steroids are opposing processes that regulate steroid homeostasis and are involved in steroid-related diseases. Cytosolic sulfotransferase and steroid sulfatase modify and regulate steroids to affect hormonal dysregulation, metabolic diseases, and cancer.
Article
Biochemistry & Molecular Biology
Noah K. Babel, Brian J. Feldman
Summary: Our research identified a previously unrecognized ADAMTS1-PTN-Wnt pathway in regulating adipose precursor cell behavior. The non-muscle myosin protein MYH9 was found to be a key target of this pathway for modulating adipogenesis. These findings offer potential for developing novel therapeutics for obesity and related metabolic disorders.
Article
Biochemistry & Molecular Biology
Martiniano Bello
Summary: This study explores the structural and thermodynamic basis of molecular recognition between ERβ and DPN and its derivatives using molecular dynamics simulations and end-point methods. The results show that the MMGBSA approach is able to reproduce experimental trends and identify eight residues that strongly interact with the ligands.