Article
Cell Biology
Elise P. Gomez-Sanchez, Celso E. Gomez-Sanchez
Summary: This review provides a brief overview of the discovery and elucidation of three cloned 11 beta-hydroxysteroid dehydrogenase enzymes in humans, as well as their role in regulating metabolism and immune cell differentiation. Additionally, it discusses pathological examples associated with disruptions in the functions of these enzymes.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Review
Medicine, General & Internal
Jonathan Seckl
Summary: 11 beta-HSDs are enzymes that convert active 11-hydroxy glucocorticoids to their inert 11-keto forms. 11 beta-HSD2 inactivates glucocorticoids and has important roles in the kidney and developing foetal brain. In contrast, 11 beta-HSD1 amplifies active glucocorticoid levels in the brain and is associated with age-related cognitive decline.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Elizabeta Georgieva, Stefan L. Leber, Cora Wex, Christoph Garbers
Summary: The study reveals that perturbation of the actin cytoskeleton is not sufficient to induce NF-kappa B activation and IL-6 secretion, but it reduces IL-6-induced activation of STAT3 in Hep3B cells. Additionally, IL-6 receptor proteolysis by ADAM10 is not dependent on the integrity of the actin cytoskeleton.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Rodrigo Zuloaga, Daniela Aravena-Canales, Jorge Eduardo Aedo, Cesar Osorio-Fuentealba, Alfredo Molina, Juan Antonio Valdes
Summary: In aquaculture, cortisol is believed to perform glucocorticoid and mineralocorticoid functions in teleosts. However, recent data suggest that 11-deoxycorticosterone (DOC) released during stress events may also modulate the compensatory response. A transcriptomic analysis on rainbow trout revealed that DOC induced differentially expressed transcripts (DETs) mainly associated with muscle contraction, sarcomere organization, and cell adhesion. Further analysis showed that DOC's function in skeletal muscle stress response is differentially modulated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and is complementary to cortisol.
Article
Biochemistry & Molecular Biology
Hanwen Li, Sihan Hu, Runze Wu, Hongyou Zhou, Kai Zhang, Ke Li, Wenzheng Lin, Qin Shi, Hao Chen, Shan Lv
Summary: This study demonstrated that 11 beta-HSD1 plays a significant role in facilitating osteoclasts formation and maturation through the Hippo signaling pathway. Knock-in mice with high expression of 11 beta-HSD1 showed a significant decrease in bone volume, while specific knock-out in osteoclasts provided protection to the skeleton. In vitro experiments confirmed that high expression of 11 beta-HSD1 promoted osteoclast formation and maturation.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Endocrinology & Metabolism
Rachel M. B. Bell, Elisa Villalobos, Mark Nixon, Allende Miguelez-Crespo, Lee Murphy, Angie Fawkes, Audrey Coutts, Matthew G. F. Sharp, Martha Koerner, Emma Allan, Onno C. Meijer, Rene Houtman, Alex Odermatt, Katharina R. Beck, Scott G. Denham, Patricia Lee, Natalie Z. M. Homer, Brian R. Walker, Ruth A. Morgan
Summary: Carbonyl reductase 1 regulates glucocorticoid and mineralocorticoid receptor activation in adipose tissue, influencing glucose homeostasis in lean mice.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Juliane Lokau, Christoph Garbers
Summary: IL-6 and IL-11 are important pleiotropic cytokines that signal through specific receptors, with unique structures. Research has shown that chimeric receptors containing the stalk region of IL-11R can be blocked by a protease inhibitor other than ADAM10 during cleavage.
Article
Plant Sciences
Mengsha Wei, Liping Huang, Qin Li, Xinyi Qiao, Ziming Zhao, Jie Yin, Aimin Fu, Jieru Guo, Xincai Hao, Lianghu Gu, Jianping Wang, Chunmei Chen, Hucheng Zhu, Yonghui Zhang
Summary: Five aromatic ergosterols with unique ring systems, named spectasterols A-E (1-5), were isolated from Aspergillus spectabilis. Compound 3 demonstrated cytotoxic activity and anti-inflammatory effects, inducing cell cycle arrest and apoptosis in HL60 cells, and inhibiting COX-2 levels and NF-kappa B p65 nuclear translocation.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Paula Aldaz, Amaya Fernandez-Celis, Natalia Lopez-Andres, Imanol Arozarena
Summary: Dexamethasone (DEXA) is commonly used in glioblastoma (GBM) patients to reduce brain inflammation, activating the glucocorticoid receptor (GR) which can influence the mineralocorticoid receptor (MR) signaling. MR signaling in GBM has been shown to have anti-proliferative effects and inhibit the self-renewal of GSCs, while spironolactone (SPI) may not have significant anti-neoplastic potential in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Alberto Dinarello, Annachiara Tesoriere, Paolo Martini, Camilla Maria Fontana, Davide Volpato, Lorenzo Badenetti, Francesca Terrin, Nicola Facchinello, Chiara Romualdi, Oliana Carnevali, Luisa Dalla Valle, Francesco Argenton
Summary: In this study, zebrafish mutant lines and transgenic models were used to analyze the mechanism of action of glucocorticoids. The differences in gene expression patterns between different mutant lines revealed a complex network of GC-dependent transcription. The study also showed that the glucocorticoid receptor GR plays a crucial role in the transcriptional activity of Stat3, and both glucocorticoids and the mineralocorticoid receptor MR are necessary for the correct transcription of certain target genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Israel Hernandez-Bustamante, Yanina Santander-Plantamura, Dulce Mata-Espinosa, Andres Reyes-Chaparro, Estela I. Bini, Ivan Torre-Villalvazo, Armando R. Tovar, Jorge Barrios-Payan, Brenda Marquina-Castillo, Rogelio Hernandez-Pando, Andrea Carranza
Summary: Metabolic syndrome is the precursor of type 2 diabetes mellitus, and tuberculosis is a global threat and a major cause of morbi-mortality in developing countries. People with type 2 diabetes mellitus are more susceptible to Mycobacterium tuberculosis infection. Our study found that DHEA can directly inhibit the growth of Mycobacterium tuberculosis, and in silico docking analysis and molecular dynamic simulation studies supported this conclusion.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Medicinal
Yeo Dae Yoon, Myeong Youl Lee, Byeong Jo Choi, Chang Woo Lee, Hyunju Lee, Joo-Hee Kwon, Jeong-Wook Yang, Jong Soon Kang
Summary: This study found that Terrein has a protective effect against LPS-induced endotoxemia by reducing the production of inflammatory cytokines. The anti-inflammatory effect of Terrein might be mediated, at least in part, by blocking the activation of NF-kappa B, JNK, and p38 MAPK signaling pathways.
Article
Nutrition & Dietetics
Yuki Nouchi, Eiji Munetsuna, Hiroya Yamada, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Miyuki Ikeya, Itsuki Kageyama, Takuya Wakasugi, Atsushi Teshigawara, Yuji Hattori, Yoshiki Tsuboi, Hiroaki Ishikawa, Koji Suzuki, Koji Ohashi
Summary: This study aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring. By giving female Sprague Dawley rats HFCS solution, it was found that HFCS led to a decrease in activity of GC-metabolizing enzyme 11 beta-Hsd2 and an increase in renal miR-27a expression. These findings suggest that the elevation of circulating GC levels in offspring induced by maternal HFCS consumption may be explained by a decrease in 11 beta-Hsd2 activity via renal miR-27a expression.
Article
Environmental Sciences
Shaowei Wang, Jingyi Zheng, Yang Zhu, Yiyan Wang, Huitao Li, Ren-shan Ge
Summary: The study found that most BPA analogues are more potent inhibitors of human and rat 11 beta-HSD1 enzymes, with structure-dependent and species-dependent inhibition.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Pharmacology & Pharmacy
Michael Weingartner, Simon Stucheli, Denise Kratschmar, Julia Birk, Petra Klusonova, Karen E. Chapman, Gareth G. Lavery, Alex Odermatt
Summary: The study found that the plasma ratio of UDC-Tau to 7oxoLC-Tau can serve as a biomarker for decreased 11 beta-HSD1 oxoreduction activity in different mouse models. Enzyme product to substrate ratios were more reliable markers of 11 beta-HSD1 activity than absolute levels due to large inter-individual variations in bile acid concentrations. The persistence of oxoreduction activity in the face of cofactor loss indicates the existence of an alternative NADPH source in the endoplasmic reticulum.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Infectious Diseases
Michael Weingartner, Simon Stucheli, Fadi Jebbawi, Bruno Gottstein, Guido Beldi, Britta Lundstrom-Stadelmann, Junhua Wang, Alex Odermatt
Summary: Infection with Echinococcus multilocularis induces UPR and ERS in mice, which can be ameliorated by treatment with albendazole or alpha PD-L1. These treatments reverse the changes in protein expression levels and inflammatory cytokines induced by the infection, offering potential for improved therapies for patients with AE.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Oncology
Gabrielle Leclercq, Llucia Alberti Servera, Sabrina Danilin, John Challier, Nathalie Steinhoff, Claudia Bossen, Alex Odermatt, Valeria Nicolini, Pablo Umana, Christian Klein, Marina Bacac, Anna-Maria Giusti, Anneliese Schneider, Helene Haegel
Summary: This study investigated the biological mechanisms of cytokine release after treatment with T cell bispecific antibodies (TCBs) and identified T cells as the triggers and monocytes and neutrophils as the amplifiers of the cytokine cascade. Moreover, it demonstrated the contribution of neutrophils to TCB-mediated cytokine release using single-cell RNA sequencing.
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Lariviere, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Summary: This study aimed to identify small molecules that can reduce cytokine release while maintaining T cell-mediated tumor killing. By screening a library of FDA-approved kinase inhibitors, mTOR, JAK, and Src kinase inhibitors were found to modulate cytokine release. Further in vitro and in vivo experiments confirmed these findings and supported the evaluation of these inhibitors as a treatment to prevent cytokine release syndrome (CRS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Food Science & Technology
Birgit Geueke, Ksenia J. Groh, Maricel V. Maffini, Olwenn V. Martin, Justin M. Boucher, Yu-Ting Chiang, Frank Gwosdz, Phoenix Jieh, Christopher D. Kassotis, Paulina Lanska, John Peterson Myers, Alex Odermatt, Lindsey V. Parkinson, Verena N. Schreier, Vanessa Srebny, Lisa Zimmermann, Martin Scheringer, Jane Muncke
Summary: Food packaging plays a crucial role in today's globalized food system, but it can also contribute to the migration of hazardous chemicals into food. In order to assess the impact of food contact materials (FCMs) on human health, it is necessary to identify the chemicals they contain, known as food contact chemicals (FCCs). This study compiled a comprehensive database of migrating and extractable FCCs (FCCmigex) based on information from 1210 studies. The findings reveal that 2881 FCCs have been detected in six FCM groups, with 65% of these being previously unknown. Plastic, with 1975 detected FCCs, is the most extensively studied FCM. This knowledge expands our understanding of FCCs to 14,153 chemicals and can contribute to the development of non-hazardous FCMs, promoting safer food production and supporting a circular economy.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2023)
Article
Endocrinology & Metabolism
Laura L. Gathercole, Nikolaos Nikolaou, Shelley E. Harris, Anastasia Arvaniti, Toryn M. Poolman, Jonathan M. Hazlehurst, Denise Kratschmar, Marijana Todorcevic, Ahmad Moolla, Niall Dempster, Ryan C. Pink, Michael F. Saikali, Liz Bentley, Trevor M. Penning, Claes Ohlsson, Carolyn L. Cummins, Matti Poutanen, Alex Odermatt, Roger D. Cox, Jeremy W. Tomlinson
Summary: AKR1D1 controls bile acid homeostasis in vivo, and altering its activity can affect insulin tolerance and lipid homeostasis in a sex-dependent manner.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Pharmacology & Pharmacy
Silvia G. Inderbinen, Manuel Kley, Michael Zogg, Manuel Sellner, Andre Fischer, Jacek Kedzierski, Stephanie Boudon, Anton M. Jetten, Martin Smiesko, Alex Odermatt
Summary: ROR gamma t is a key protein that regulates immune responses, and impaired function may contribute to inflammatory and autoimmune diseases and promote skin cancer. Certain chemicals commonly used in cosmetics and body care products have been found to activate ROR gamma t and potentially worsen skin diseases. Further research is needed to assess the concentrations of these compounds in tissues and target cells, and their significance in activating ROR gamma t.
Article
Multidisciplinary Sciences
Daniel T. Meier, Leila Rachid, Sophia J. Wiedemann, Shuyang Traub, Kelly Trimigliozzi, Marc Stawiski, Loic Sauteur, Denise Winter, Christelle Le Foll, Catherine Bregere, Raphael Guzman, Alex Odermatt, Marianne Boeni-Schnetzler, Marc Y. Donath
Summary: Defective insulin processing due to deficiency of insulin prohormone convertase 1/3 (PC1/3) leads to hyperglycemia and hyperphagic obesity. Impaired insulin maturation, rather than impaired pro-islet amyloid polypeptide processing, is the cause of obesity. Insulin therapy can prevent hyperphagia. Furthermore, decreased PC1/3 expression levels in pancreatic islets are negatively correlated with body mass index in humans.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Anna Keppner, Miguel Correia, Sara Santambrogio, Teng Wei Koay, Darko Maric, Carina Osterhof, Denise Winter, Angele Clerc, Michael Stumpe, Frederic Chalmel, Sylvia Dewilde, Alex Odermatt, Dieter Kressler, Thomas Hankeln, Roland H. Wenger, David Hoogewijs
Summary: Spermatogenesis relies on the gene expression program driven by Adgb, where the absence of Adgb leads to male infertility and abnormal sperm shape. Adgb interacts with Sept10, and the absence of Adgb mislocalizes Sept10 in sperm, revealing the importance of Adgb in proper sperm head shaping and flagellum formation.
Article
Biochemistry & Molecular Biology
Verena N. Schreier, Alex Odermatt, Frank Welle
Summary: Polyethylene terephthalate (PET) is widely used as a food contact material due to its good mechanical properties and recyclability. This study utilized migration modeling to evaluate the migration potential of 52 PET oligomers in various application scenarios. Results were compared with safety thresholds to identify potential risks associated with certain oligomers or applications.
Article
Medicine, Research & Experimental
Mesut Berber, Sining Leng, Agnieszka Wengi, Denise V. Winter, Alex Odermatt, Felix Beuschlein, Johannes Loffing, David T. Breault, David Penton
Summary: The Cn/NFATC4 pathway plays an important regulatory role in the signal transduction pathway of aldosterone synthesis.
Article
Biochemistry & Molecular Biology
Leonora Szabo, Nadia Cummins, Paolo Paganetti, Alex Odermatt, Andreas Papassotiropoulos, Celeste Karch, Jurgen Gotz, Anne Eckert, Amandine Grimm
Summary: Abnormal tau protein disrupts the interaction between the endoplasmic reticulum (ER) and mitochondria, leading to impaired mitochondrial function and cholesterol metabolism. This study shows that abnormal tau loosens the association between ER and mitochondria, particularly through the VAPB-PTPIP51 pathway. Disruption of the ER-mitochondria interaction results in altered levels of mitochondrial cholesterol and pregnenolone, which can be restored by inhibiting GSK3 beta.
Article
Toxicology
Marie-Christin Jager, Friedrich L. Joos, Denise V. Winter, Alex Odermatt
Summary: Azole antifungal drugs have the potential to inhibit human CYP enzymes, leading to adverse effects on adrenal cortex steroidogenesis. This study used the H295R cell model to predict the inhibitory effects of posaconazole and itraconazole on adrenal steroid synthesis. The results provide valuable information for further investigations on the mechanism of action.
CURRENT RESEARCH IN TOXICOLOGY
(2023)
Article
Physiology
Laurent Bourqui, Denise V. Winter, Alex Odermatt, Dominique Loffing-Cueni, Johannes Loffing
Summary: This study introduces a novel transgenic mouse model (Slc12a1-creERT2) that allows for inducible and highly efficient gene targeting in the renal thick ascending limb (TAL), which can facilitate physiological studies on the regulation of TAL function.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)