Article
Cell Biology
Lele Zhu, Xiaofei Zhou, Meidi Gu, Jiseong Kim, Yanchuan Li, Chun-Jung Ko, Xiaoping Xie, Tianxiao Gao, Xuhong Cheng, Shao-Cong Sun
Summary: This study identified Dapl1 as a crucial regulator of CD8(+) T cell immunity, showing that Dapl1 deficiency can lead to functional exhaustion of CD8(+) T cells in chronic infection and cancer.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ji-Seon Park, Hwon Heo, Min-Seok Kim, Seung-Eun Lee, Sukyoung Park, Ki-Hyun Kim, Young-Ho Kang, Je Seong Kim, Young Hoon Sung, Woo Hyun Shim, Dong-Hou Kim, Youngsup Song, Seung-Yong Yoon
Summary: Social hierarchy has significant effects on social behavior, reward processing, and mental health, and lower social rank can lead to chronic stress and more serious problems. This study reveals that astrocyte-secreted amphiregulin plays a critical role in determining hierarchical ranks, and its regulation is mediated by cAMP response element-binding (CREB)-regulated transcription coactivator 3 (CRTC3) and CREB.
MOLECULAR PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Ke Xue, Shuai Chen, Jiayin Chai, Wenjing Yan, Xinyu Zhu, Dengyu Ji, Ye Wu, Huirong Liu, Wen Wang
Summary: The study aims to verify the role of nitrated cAMP-response element binding protein (CREB) in myocardial fibrosis after myocardial infarction (MI) and identify its downstream genes. It was found that nitrated CREB promoted MI-induced myocardial fibrosis by enhancing its phosphorylation, nuclear translocation, and binding activity to TORCs. Additionally, CREB directly accelerated the transcription of Col1a2 and Cxcl12 after MI.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Review
Cell Biology
Joel Nieto-Felipe, Alvaro Macias-Diaz, Jose Sanchez-Collado, Alejandro Berna-Erro, Isaac Jardin, Gines M. Salido, Jose J. Lopez, Juan A. Rosado
Summary: Store operated Ca2+ entry (SOCE) is essential for maintaining intracellular Ca2+ homeostasis and regulating cellular functions. STIM and Orai proteins mediate SOCE, which is initiated by activation of inositol 1,4,5-trisphosphate receptors. STIM proteins sense the decrease in endoplasmic reticulum Ca2+ concentration and activate plasma membrane Ca2+ channels formed by Orai proteins. STIM1/Orai-mediated Ca2+ signals finely regulate the activity of various transcription factors and influence multiple signaling events and cellular functions.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Jose G. Miranda, Wolfgang E. Schleicher, Kristen L. Wells, David G. Ramirez, Samantha P. Landgrave, Richard K. P. Benninger
Summary: This study examines how patterns of electrical activity regulate NFAT activation, gene transcription, and islet function, and provides insights into how these factors are disrupted in diabetes.
MOLECULAR METABOLISM
(2022)
Article
Peripheral Vascular Disease
Akiko Hiramatsu, Yuichiro Izumi, Koji Eguchi, Naomi Matsuo, Qinyuan Deng, Hideki Inoue, Yushi Nakayama, Hiroshi Nonoguchi, Jose Aramburu, Cristina Lopez-Rodriguez, Yutaka Kakizoe, Masataka Adachi, Takashige Kuwabara, Shokei Kim-Mitsuyama, Masashi Mukoyama
Summary: The study showed that renal tubular NFAT5 plays an important role in regulating sodium reabsorption through the epithelial sodium channel under high-salt conditions, thereby preventing salt-dependent hypertension.
Article
Multidisciplinary Sciences
Ewa Bielczyk-Maczynska, Meng Zhao, Peter-James H. Zushin, Theresia M. Schnurr, Hyun-Jung Kim, Jiehan Li, Pratima Nallagatla, Panjamaporn Sangwung, Chong Y. Park, Cameron Cornn, Andreas Stahl, Katrin J. Svensson, Joshua W. Knowles
Summary: This study identifies a rare genetic mutation associated with lower risk of type 2 diabetes and uncovers the role of Gpr151 in regulating hepatic glucose production in the liver.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Emma L. Lewis, Rong Xu, Jean-Christophe Beltra, Shin Foong Ngiow, Jordana Cohen, Rahul Telange, Alexander Crane, Deirdre Sawinski, E. John Wherry, Paige M. Porrett
Summary: Studies demonstrate that pregnancy induces exhausted CD8 T cells in mothers, prolonging allograft survival. Maternal CD8 T cells during pregnancy share exhaustion features with CD8 T cells from chronic infection and cancer.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Cell Biology
Wen Huang, Wei Lin, Baoqiang Chen, Jianhan Zhang, Peifen Gao, Yingying Fan, Yihan Lin, Ping Wei
Summary: The study reveals that T cell responses to antigens are regulated by multiple signaling pathways, and the mechanisms cells use to modulate T cell responses during pathway integration are still unclear. The calcium/NFAT and PKC/NF-KB pathways in T cell signaling integrate through a dynamic and combinatorial strategy to fine-tune T cell response genes. NFAT and NF-KB co-bind to immune response genes at the regulatory level, and the temporal relationships between the nuclear localization dynamics of NFAT and NF-KB are modulated by TCR and CAR activation signals. This physical and temporal integration contributes to distinct modes of expression modulation for genes.
Article
Medicine, Research & Experimental
Ling Li, Jinxia Zheng, Megan Stevens, Sebastian Oltean
Summary: Research on hallmarks of cancer has potential for developing new therapies by modulating cancer properties. A screen was used to identify compounds that modulate epithelial-mesenchymal transitions (EMTs) in prostate cancer, and three hit compounds were discovered. These compounds affect various properties of cancer cells and decrease cell migration, indicating their potential to modulate EMTs.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Horticulture
Guangwu Zhu, Chongtian Ma, Shuimiao Yu, Xueying Zhang, Jing Jiang, Xin Liu
Summary: Multiple genes related to leaf shape were discovered in the process of leaf development in tomato plants. Transcriptome sequencing and gene silencing experiments revealed that bHLH079, IAA-amino acid hydrolase, Gibberellin2ox7, Gibberellin20ox, WRKY44, and WRKY76 are endogenous regulators influencing tomato compound leaf development. This study provides a promising direction for revealing the molecular regulation mechanism underlying compound leaf development in tomatoes.
Article
Neurosciences
Wioletta Kazana, Dominika Jakubczyk, Jakub Siednienko, Aleksandra Zambrowicz, Jozefa Macala, Agnieszka Zablocka
Summary: In this study, it was found that yolkin, a polypeptide complex derived from hen egg yolk, can promote the proliferation of rat hippocampal precursor cells and upregulate the expression of BDNF through a CREB-dependent pathway. The upregulation of CREB phosphorylation by yolkin is dependent on the activation of cAMP/PKA and PI3K/Akt signaling pathways. These findings suggest that yolkin may play a comprehensive role in regulating neuronal survival and activity.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Siyuan Yin, Ru Song, Jiaxu Ma, Chunyan Liu, Zhenjie Wu, Guoqi Cao, Jian Liu, Guang Zhang, Huayu Zhang, Rui Sun, Aoyu Chen, Yibing Wang
Summary: In this study, the researchers investigated the role of RAMP1, a component of the CGRP receptor, in promoting the proliferation of mouse skin fibroblasts. They found that RAMP1 overexpression increased MSF proliferation through the G alpha i3-PKA-CREB-YAP axis. This finding provides valuable insights into the function of RAMP1 and suggests that targeting this pathway could be an attractive and accurate approach for skin wound treatment.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Multidisciplinary Sciences
Meng Du, Cheng Wang, Liuye Yang, Bing Liu, Zhe Zheng, Liu Yang, Fengxiao Zhang, Jiangtong Peng, Dan Huang, Kai Huang
Summary: Atherosclerosis is characterized by the rupture or erosion of unstable plaques, leading to thrombotic events such as myocardial infarction or stroke. In this study, researchers identified a long noncoding RNA called Noncoding Repressor of NFAT (Nron) as a critical regulator of plaque stability in atherosclerosis. Overexpression of Nron led to the formation of more vulnerable plaques, while knockout of Nron inhibited atherosclerosis development and promoted plaque stability. Mechanistically, Nron bound to and negatively regulated NFATc3, which inhibited the proliferation and promoted the apoptosis of vascular smooth muscle cells. Additionally, Nron increased the production and secretion of VEGFA from these cells, enhancing intra-plaque angiogenesis. Inhibition of Nron may hold potential as a therapeutic strategy for atherosclerosis.
Review
Oncology
Mohammad Taheri, Soudeh Ghafouri-Fard, Sajad Najafi, Julia Kallenbach, Elmira Keramatfar, Golnaz Atri Roozbahani, Mehdi Heidari Horestani, Bashdar Mahmud Hussen, Aria Baniahmad
Summary: This review outlines the roles and functions of several steroid hormones and growth factors in telomerase regulation, particularly in hormone-regulated cancers such as prostate, breast, and endometrial cancer.
CANCER CELL INTERNATIONAL
(2022)
Review
Pharmacology & Pharmacy
Barbara Schreier, Alexander Zipprich, Henriette Uhlenhaut, Michael Gekle
Summary: This narrative review summarizes the role of mineralocorticoid receptor (MR) in liver diseases and suggests that inhibiting MR in vivo may be beneficial for liver function. However, the underlying molecular mechanisms of MR in liver diseases are still not completely understood.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Barbara Schreier, Virginie Dubourg, Stefanie Huebschmann, Sindy Rabe, Sigrid Mildenberger, Michael Gekle
Summary: The study reveals that EGFR and AT1R synergistically regulate gene expression, leading to qualitative, quantitative, and temporal changes, potentially impacting cell stress and vascular biology. Synergistic activation of SRF via distinct pathways and transcription factors AP1 and EGR plays a key role in this process.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Stefanie Ruhs, Bruno Griesler, Ralf Huebschmann, Katharina Stroedecke, Nicole Straetz, Christian Ihling, Andrea Sinz, Antonia Masch, Mike Schutkowski, Michael Gekle, Claudia Grossmann
Summary: This study found that casein kinase 1 (CK1) acts as a co-activator of mineralocorticoid receptor (MR) GRE activity through direct and indirect phosphorylation. It accelerates the cytosolic-nuclear trafficking of MR, facilitates its nuclear accumulation and DNA binding, and increases the expression of MR-target genes that are relevant to pathological conditions.
Article
Biochemistry & Molecular Biology
Heike Braun, Michael Hauke, Robert Eckenstaler, Markus Petermann, Anne Ripperger, Niklas Kuehn, Edzard Schwedhelm, Beatrice Ludwig-Kraus, Frank Bernhard Kraus, Virginie Dubourg, Alma Zernecke, Barbara Schreier, Michael Gekle, Ralf A. Benndorf
Summary: The study found that vascular smooth muscle cell (VSMC)-specific TP deletion attenuated atherogenesis in mice, without impacting blood pressure or lipid profiles. Additionally, 8-iso-PGF2 alpha appears to reduce atherogenesis in Ldlr-deficient mice, especially in those lacking EC-specific TP. This suggests that the TP expressed in VSMC is involved in atherosclerotic lesion formation and 8-iso-PGF2 alpha has an inhibitory effect on atherogenesis in this experimental model.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Immunology
Lisa Paschold, Bianca Klee, Cornelia Gottschick, Edith Willscher, Sophie Diexer, Christoph Schultheiss, Donjete Simnica, Daniel Sedding, Matthias Girndt, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Summary: The COVID-19 pandemic highlights the importance of optimizing vaccination strategies for potential viral variants. Researchers have developed a sequencing-based protocol to track B cells and determine the level of immunoglobulin somatic hypermutation during the immunization period. The findings suggest that increasing antibody affinity to the ancestral strain is a priority when using vaccines not targeted at individual variants, as it may provide flexibility to compensate for strain-specific mutations. The study also shows that the third vaccine dose induces a rapid increase in somatic hypermutation, indicating increased affinity and potential protection against immune-escape variants.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Marie-Christin Schulz, Linda Voss, Gerald Schwerdt, Michael Gekle
Summary: The pathogenesis of chronic kidney disease involves extracellular acidosis, inflammation, fibrosis, and epithelial-to-mesenchymal transition (EMT). This study examined the effects of acidosis on tubule epithelial cells and fibroblasts and explored the role of cell crosstalk in these effects. Acidosis led to increased inflammation, EMT, and fibrosis; however, in co-culture, these effects were reversed or inhibited. The intercellular crosstalk between epithelial cells and fibroblasts was found to have a protective function in acidosis-induced damage.
Article
Virology
Christoph Schultheiss, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Summary: Post-acute sequelae of COVID-19 (PASC) are long-term consequences of SARS-CoV-2 infection that significantly impact life quality. This study reveals pronounced dysregulation in immune factors and persistence of viral protein in individuals with PASC, highlighting its biological heterogeneity. Further correlation with clinically defined PASC subtypes is needed.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Psychiatry
Janka Massag, Sophie Diexer, Bianca Klee, Daniela Costa, Cornelia Gottschick, Anja Broda, Oliver Purschke, Nils Opel, Mascha Binder, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica Hoell, Irene Moor, Jonas Rosendahl, Michael Gekle, Rafael Mikolajczyk
Summary: The Russian invasion of Ukraine has had a negative impact on the mental health of the German population, with anxiety and distress levels remaining elevated even after 6 months. Low-income individuals, especially those experiencing fears related to their personal financial situation, were most affected. Those who initially reacted strongly with fear were more likely to experience persistent symptoms of depression and anxiety.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Marie-Christin Schulz, Virginie Dubourg, Alexander Nolze, Michael Kopf, Gerald Schwerdt, Michael Gekle
Summary: The crosstalk between renal epithelial cells and interstitial fibroblasts in the kidney plays an important role in kidney pathophysiology. Acidosis enhances the cytoprotective Nrf2 pathway in renal epithelial cells co-cultivated with renal fibroblasts, leading to increased expression of the cytoprotective TKT. This protective response is not observed in monoculture.
Article
Psychiatry
Cornelia Gottschick, Sophie Diexer, Janka Massag, Bianca Klee, Anja Broda, Oliver Purschke, Mascha Binder, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. I. Hoell, Patrick Michl, Michael Gekle, Rafael Mikolajczyk
Summary: During the Russo-Ukrainian war, the German population experienced significant distress and anxiety due to the exposure to media reports of violence. Fear of the impact of war was associated with worse mental health, surpassing the reactions during the strictest COVID-19 restrictions.
Article
Infectious Diseases
Sophie Diexer, Bianca Klee, Cornelia Gottschick, Chao Xu, Anja Broda, Oliver Purschke, Mascha Binder, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Irene Moor, Michael Gekle, Rafael Mikolajczyk
Summary: The Omicron variant of the SARS-CoV-2 virus has become the dominant strain since 2022 and is associated with milder acute infection compared to previous variants. However, little is known about the occurrence of long-term symptoms after Omicron infection and how it is influenced by previous infections and/or vaccinations.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Virginie Dubourg, Marie-Christin Schulz, Philipp Terpe, Stefanie Ruhs, Michael Kopf, Michael Gekle
Summary: Extracellular acidosis has a significant impact on the transcriptional activity of non-tumor cells, leading to quantitative transcriptional alterations in different cell types. The regulator NCOA5 is identified as the only general acidosis-responsive gene. Gene Ontology enrichment analysis and upstream regulator analysis suggest a general acidosis response pattern involving the integrated stress response, TGF-β signaling, NFE2L2, and TP53.
Article
Mycology
Gerald Schwerdt, Michael Kopf, Michael Gekle
Summary: Despite previous research, the exact mechanism of action of ochratoxin A (OTA) still remains unclear. In this study, we observed that cells exposed to OTA exhibited increased glucose consumption and lactate production, indicating a potential involvement of cellular metabolism and mitochondria. Our findings suggest that OTA exposure impairs mitochondrial function, leading to a shift in cellular metabolism towards anaerobic glycolysis, which is supported by increased glucose uptake and glycogen degradation. We propose considering the impact of OTA on metabolism and mitochondria, as well as analyzing OTA-induced changes in the metabolome, as additional factors contributing to OTA toxicity.
MYCOTOXIN RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Barbara Schreier, Christian Stern, Sindy Rabe, Sigrid Mildenberger, Michael Gekle
Summary: In this study, the role of EGFRs in VSMCs and ECs for blood pressure homeostasis and acute vascular reactivity was investigated. The findings suggest that VSMC-EGFR has a significant impact on blood pressure changes induced by volume load, while EC-EGFR has a minor role in blood pressure regulation. Moreover, there is no significant difference in the response to AII and catecholamine stimulation between lean and obese animals, indicating that obesity and high-fat diet do not significantly affect these mechanisms.
Article
Cell Biology
Christoph Schultheiss, Edith Willscher, Lisa Paschold, Cornelia Gottschick, Bianca Klee, Svenja-Sibylla Henkes, Lidia Bosurgi, Jochen Dutzmann, Daniel Sedding, Thomas Frese, Matthias Girndt, Jessica I. Hoell, Michael Gekle, Rafael Mikolajczyk, Mascha Binder
Summary: Post-acute sequelae of COVID-19 (PASC) is a global problem with unknown molecular drivers. A study found that 67.8% of participants, mostly with mild infections, reported PASC, with symptoms including fatigue, dyspnea, and concentration deficit. These symptoms persisted in 60% of participants over an average 8-month follow-up period. PASC was associated with elevated plasma levels of IL-18, IL-6, and TNF.
CELL REPORTS MEDICINE
(2022)
