Article
Biochemistry & Molecular Biology
Natalie Gasterich, Sophie Wetz, Stefan Tillmann, Lena Fein, Anke Seifert, Alexander Slowik, Ralf Weiskirchen, Adib Zendedel, Andreas Ludwig, Steffen Koschmieder, Cordian Beyer, Tim Clarner
Summary: Astrocytes play a crucial role in responding to neurologic injuries and regulating immune responses, with LCN2 being involved in innate immune responses and iron regulation. However, studies suggest that LCN2 is not essential for basic astrocytic functions in the context of inflammation, but may have a regulatory effect on other cells like endothelial cells of the blood-brain barrier.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Jae-Hong Kim, Ri Jin Kang, Seung Jae Hyeon, Hoon Ryu, Hyejin Joo, Youngmin Bu, Jong-Heon Kim, Kyoungho Suk
Summary: Reactive glial cells play a role in brain injury, but their contribution to secondary inflammatory pathology and neurological deficits is poorly understood. This study investigates the role of Lipocalin-2 (LCN2) in neuroinflammation following brain injury. LCN2 expression is high in the mouse brain after controlled cortical impact (CCI) and photothrombotic stroke (PTS) injury. It is also significantly higher in patients with chronic traumatic encephalopathy (CTE). Astrocytes are the major source of LCN2 in the injured brain. Deficiency of LCN2 or injection of an LCN2 neutralizing antibody reduces brain lesions, behavioral deficits, and neuroinflammation. In cultured glial cells, LCN2 enhances proinflammatory cytokine gene expression and inhibits neurotropic factors expression. Overall, LCN2 mediates secondary damage response to traumatic and ischemic brain injury by promoting neuroinflammation and suppressing the expression of neurotropic factors.
Article
Biochemistry & Molecular Biology
Yi-Chinn Weng, Yu-Ting Huang, I-Chen Chiang, Pei-Ju Tsai, Yu-Wen Su, Wen-Hai Chou
Summary: The study found that LCN2 has neurotoxic effects on engrafted neurons during neural transplantation and can also modulate neuroinflammatory responses. Inhibition of LCN2 may be useful in reducing rejection after neural transplantation.
Article
Immunology
Eun Ae Jeong, Jaewoong Lee, Hyun Joo Shin, Jong Youl Lee, Kyung Eun Kim, Hyeong Seok An, Deok Ryong Kim, Kyu Yeong Choi, Kun Ho Lee, Gu Seob Roh
Summary: The study found that circulating TonEBP and LCN2 levels were higher in experimental diabetic mice or type 2 diabetic patients with cognitive impairment. TonEBP haploinsufficiency ameliorated the diabetic phenotypes, including adipose tissue macrophage infiltrations, neuroinflammation, blood-brain barrier leakage, and memory deficits.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Jae-Hong Kim, Osung Kwon, Anup Bhusal, Jiyoun Lee, Eun Mi Hwang, Hoon Ryu, Jae-Yong Park, Kyoungho Suk
Summary: This study reports the generation and characterization of conditional transgenic mice for lipocalin-2 (LCN2) expression. By delivering Cre recombinase under the control of a GFAP promoter, targeted overexpression of LCN2 in astrocytes of the hippocampus was achieved. These mice showed neuroinflammation, enhanced glial activation, increased proinflammatory cytokines, and impaired cognitive functions, providing a new in vivo model for neuroinflammation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Immunology
Xuwu Xiang, Xiaodong Tang, Yang Yu, Shulan Xie, Lu Liu, ManLi Chen, Rong Zhang, Xianhui Kang, Yueying Zheng, Guang Yang, Shuyuan Gan, Shengmei Zhu
Summary: This study found that LCN2 levels were significantly increased in the hippocampus of mice after surgery, independent of microglia presence. The increase of LCN2 led to the formation of proinflammatory microglia and contributed to surgery-induced neuroinflammation and cognitive decline in mice.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Erica Staurenghi, Valentina Cerrato, Paola Gamba, Gabriella Testa, Serena Giannelli, Valerio Leoni, Claudio Caccia, Annalisa Buffo, Wendy Noble, Beatriz Gomez Perez-Nievas, Gabriella Leonarduzzi
Summary: Among the brain hallmarks of Alzheimer's disease, reactive astrocytes are correlated with neuronal loss and cognitive deficits, while alterations in brain cholesterol metabolism contribute to AD pathogenesis. Oxysterols in AD brains induce astrocyte reactivity and the release of mediators that impact neuronal health and synapses, with lipocalin-2 playing a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.
Article
Biochemistry & Molecular Biology
Ye-Jin Cho, So-Hyun Park, Kwon-Yul Ryu
Summary: Astrocytes and microglia play crucial roles in maintaining brain homeostasis and the progression of neurological disorders. This study reveals that mild oxidative stress can downregulate the production of lipocalin-2 (LCN2) in glial cells, independently of the NF-kappa B signaling pathway. Additionally, Nrf2, another pathway involved in oxidative stress response, is not responsible for the downregulation of LCN2 in glial cells. These findings suggest that mild oxidative stress may be important in regulating LCN2 homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hyun Joo Shin, Eun Ae Jeong, Jong Youl Lee, Hyeong Seok An, Hye Min Jang, Yu Jeong Ahn, Jaewoong Lee, Kyung Eun Kim, Gu Seob Roh
Summary: The deficiency of LCN2 reduces neuronal cell death, BBB leakage, iron overload, and oxidative stress in KA-induced hippocampal cell death, and inhibits related neuroinflammatory responses, indicating a significant role of LCN2 in this process.
Review
Neurosciences
Daejin Lim, Jae-ho Jeong, Juhyun Song
Summary: Dementia accompanied by memory loss is a common neurodegenerative disease with increasing prevalence worldwide. Recent evidence suggests that lipocalin 2 (LCN2) plays a regulatory role in dementia and may be a promising therapeutic target to address the neuropathology of dementia.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Neurosciences
Juntao Cui, Yu Yuan, Jun Wang, Ning Song, Junxia Xie
Summary: In this study, it was discovered that iron chelator deferoxamine (DFO) can inhibit the upregulation of Lipocalin-2 (LCN2) in astrocytes, independent of iron overload. This inhibitory effect is similar to that of autophagy inducers and does not rely on the proteasome system or the NF-kappa B pathway. DFO also promotes secretory autophagy, which improves the upregulation of LCN2 in astrocytes.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Byung-Kwon Jung, Yujin Park, Boran Yoon, Jin-Sil Bae, Seung-Woo Han, Ji-Eun Heo, Dong-Eun Kim, Kwon-Yul Ryu
Summary: LCN2 is a secretory protein produced by activated microglia and reactive astrocytes under neuroinflammatory stress conditions, leading to neuronal apoptosis. This study demonstrates that LCN2 secretion can be reduced by proteasome inhibition and autophagic flux activation in reactive astrocytes stimulated with lipopolysaccharide. The results suggest that modulating LCN2 production and secretion may offer a new therapeutic approach for neuroinflammatory diseases.
Article
Cell Biology
James R. Tribble, Elizabeth Kastanaki, A. Bersan Uslular, Carola Rutigliani, Tim J. Enz, Pete A. Williams
Summary: This study demonstrates the potential of valproic acid in reducing retinal neuroinflammation and protecting retinal neurons. Valproic acid effectively reduces microglia and astrocyte inflammatory responses, and prevents the expression of pro-inflammatory cytokines in injured retina.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Marianela Evelyn Traetta, Nonthue Alejandra Uccelli, Sandra Cristina Zarate, Dante Gomez Cuautle, Alberto Javier Ramos, Analia Reines
Summary: This study reveals the reactive changes in cortical microglia and astroglia, as well as synaptic alterations in a rat model prenatally exposed to valproic acid. Additionally, it highlights the importance of communication between microglia and astroglia in neuroinflammation associated with autism spectrum disorder, suggesting it as a potential target for interventions.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Ying-Xin Zhao, Yi-Xi Tang, Xiao-Han Sun, Shi-Yong Zhu, Xue-Yan Dai, Xue-Nan Li, Jin-Long Li
Summary: This study utilized an in vivo model of neurotoxicity in quail to investigate the effects of DEHP exposure on astrocytes. The results revealed that DEHP exposure resulted in phosphorylation and translocation of Cx43 in astrocytes. Additionally, the study showed that DEHP exposure induced pro-inflammatory status and autophagosome formation in astrocytes. These findings provide valuable insights into the mechanisms of neurodegeneration caused by DEHP exposure and suggest a potential therapeutic target for its treatment.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen
Article
Biochemistry & Molecular Biology
Louis C. Penning, Marina Berenguer, Anna Czlonkowska, Kay L. Double, Petr Dusek, Carmen Espinos, Svetlana Lutsenko, Valentina Medici, Wiebke Papenthin, Wolfgang Stremmel, Jose Willemse, Ralf Weiskirchen
Summary: Wilson disease is a rare inherited metabolic disorder with diverse clinical presentations affecting the liver, neurological system, psychiatric status, and vision, often in combination. Mutations in the ATP7B gene lead to copper accumulation in hepatocytes and/or neurons, making clinical diagnosis challenging. Diagnosis is complicated by mild and non-specific manifestations, mutations with unclear effects on protein function, and ambiguous laboratory tests, particularly concerning serum ceruloplasmin levels. Establishing a global collaboration of researchers, clinicians, and patient advocacy groups is crucial for identifying and addressing the outstanding challenges of Wilson disease.
Review
Nutrition & Dietetics
Bodo C. C. Melnik, Swen Malte John, Pedro Carrera-Bastos, Loren Cordain, Claus Leitzmann, Ralf Weiskirchen, Gerd Schmitz
Summary: This review evaluates the impact of cow milk on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer pathogenesis. Recent prospective cohort studies support the association between cow's milk consumption and the risk of estrogen receptor-alpha-positive breast cancer. Milk contains various components that can increase systemic insulin-like growth factor 1, insulin, and estrogen signaling, promoting breast cancer. Potential oncogenic components of commercial milk include exosomal microRNAs, bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with certain gene mutations and genetic polymorphisms may be at increased risk for milk-induced breast cancer.
CURRENT NUTRITION REPORTS
(2023)
Article
Cell Biology
Lilach Barer, Sarah K. Schroeder, Ralf Weiskirchen, Eran Bacharach, Marcelo Ehrlich
Summary: Lipocalin-2 (LCN2) has pleiotropic functions in different types of cancers. This study found that LCN2 can regulate prostate cancer cells by affecting cytoskeleton organization and expression of inflammation mediators. It also showed that LCN2 can modulate prostate cancer cell susceptibility to oncolytic viruses by attenuating PERK activity and increasing interferon and interferon-stimulated gene expression.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2023)
Article
Immunology
Mihael Vucur, Ahmed Ghallab, Anne T. Schneider, Arlind Adili, Mingbo Cheng, Mirco Castoldi, Michael T. Singer, Veronika Buettner, Leonie S. Keysberg, Lena Kuesgens, Marlene Kohlhepp, Boris Goerg, Suchira Gallage, Jose Efren Barragan Avila, Kristian Unger, Claus Kordes, Anne-Laure Leblond, Wiebke Albrecht, Sven H. Loosen, Carolin Lohr, Markus S. Joerdens, Anne Babler, Sikander Hayat, David Schumacher, Maria T. Koenen, Olivier Govaere, Mark Boekschoten, Simone Joers, Carlos Villacorta-Martin, Vincenzo Mazzaferro, Josep M. Llovet, Ralf Weiskirchen, Jakob N. Kather, Patrick Starlinger, Michael Trauner, Mark Luedde, Lara R. Heij, Ulf P. Neumann, Verena Keitel, Johannes G. Bode, Rebekka K. Shneider, Frank Tacke, Bodo Levkau, Twan Lammers, Georg Fluegen, Theodore Alexandrov, Amy L. Collins, Glyn Nelson, Fiona Oakley, Derek A. Mann, Christoph Roderburg, Thomas Longerich, Achim Weber, Augusto Villanueva, Andre L. Samson, James M. Murphy, Rafael Kramann, Fabian Geisler, Ivan G. Costa, Jan G. Hengstle, Mathias Heikenwalder, Tom Luedde
Summary: A molecular switch in hepatocytes can reprogram between two forms of necroptosis signaling, which fundamentally impacts immune responses and hepatocarcinogenesis.
Article
Cell Biology
Erawan Borkham-Kamphorst, Steffen K. Meurer, Ralf Weiskirchen
Summary: The CCN protein family plays important biological functions in cell adhesion, migration, cell cycle progression, and control of extracellular matrix production and degradation. In the liver, CCN proteins are particularly involved in hepatic injury, disease, and remodeling. This study focused on CCN5/WISP2 and found that it is highly expressed in hepatic stellate cells, myofibroblasts, and portal myofibroblasts, while it is absent in hepatocytes. CCN5 upregulation during hepatic fibrosis induces endoplasmic reticulum stress, unfolded protein response, and apoptosis in portal myofibroblasts, potentially acting as a control mechanism against excessive fibrotic responses.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Cell Biology
Kiara Gaeberlein, Sarah K. Schroeder, Indrajit Nanda, Claus Steinlein, Thomas Haaf, Eva M. Buhl, Patrick Sauvant, Vincent Sapin, Armand Abergel, Ralf Weiskirchen
Summary: The rat hepatic stellate cell line PAV-1, established two decades ago, is a cellular model for studying hepatic retinoic acid metabolism. Despite being able to store retinyl esters and synthesize retinoic acid, this cell line has been overlooked. Genetically characterized established cell lines, like PAV-1, are valuable for biomedical research as working with in vivo models becomes more complicated.
Review
Cell Biology
Sabine Weiskirchen, Sarah K. K. Schroeder, Eva Miriam Buhl, Ralf Weiskirchen
Summary: The cultivation of cells in a favorable artificial environment has become an essential tool in cellular and molecular biology research. However, cell lines are often affected by misidentification, contamination, and specific biological and chemical hazards. This review offers an introduction to common problems encountered in cell culture laboratories and provides guidelines for preventing and addressing these issues.
Article
Information Science & Library Science
Mahsa Keshavarz-Fathi, Niloufar Yazdanpanah, Sajad Kolahchi, Heliya Ziaei, Gary L. Darmstadt, Tommaso Dorigo, Filip Dochy, Lisa Levin, Visith Thongboonkerd, Shuji Ogino, Wei-Hsin Chen, Matjaz Perc, Mark S. Tremblay, Bolajoko O. Olusanya, Idupulapati M. Rao, Nikos Hatziargyriou, Maziar Moradi-Lakeh, Federico Bella, Laszlo Rosivall, Amir H. Gandomi, Armin Sorooshian, Manoj Gupta, Ciprian Gal, Andres M. Lozano, Connie Weaver, Michael Tanzer, Alessandro Poggi, Sadaf G. Sepanlou, Ralf Weiskirchen, Anet Rezek Jambrak, Pedro J. Torres, Esra Capanoglu, Francisco J. Barba, Chua Kian Jon Ernest, Mariano Sigman, Stefano Pluchino, Gevork B. Gharehpetian, Seyed-Mohammad Fereshtehnejad, Muh-Hwa Yang, Sabu Thomas, Wenju Cai, Elisabetta Comini, Neil J. Scolding, Paul S. Myles, Juan J. Nieto, George Perry, Constantine Sedikides, Nima Rezaeia
Summary: Scientometrics and bibliometrics are subfields of library and information science that study the quantity and quality of research outputs. The h-index is the most well-known scientometric index, but it relies on the count of highly cited publications. To address this limitation, we developed a new index called the Universal Research Index (UR-Index) that considers the impact of every single publication. We incorporated additional variables such as publication type, leading role, co-author count, and source metrics into the UR-Index. However, we recognize that unconscious biases in these variables may disadvantage research from specific groups, and encourage efforts to improve equitable scholarly impact in science and academia.
JOURNAL OF ACADEMIC LIBRARIANSHIP
(2023)
Article
Biochemistry & Molecular Biology
Jan C. Kessel, Ralf Weiskirchen, Sarah K. Schroeder
Summary: Estrogen receptor alpha (ERa) is expressed in reproductive and non-reproductive tissues, and its impact on lipocalin 2 (LCN2) expression varies among tissues. This study found an inverse correlation between ERa and LCN2 expression in reproductive tissues, particularly in Esr1-deficient ovaries. However, no significant differences in LCN2 expression were observed in non-reproductive tissues. These findings provide insight into LCN2 regulation in relation to hormones and health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Sarah K. Schroeder, Natalie Gasterich, Sabine Weiskirchen, Ralf Weiskirchen
Summary: Human 25-kDa Lipocalin 2 (LCN2) was initially thought to be a circulating protein that transports small lipophilic molecules. However, further studies have shown its bacteriostatic properties, involvement in innate immunity, and regulation of various biological processes. The understanding of LCN2 receptors and their mechanisms is still lacking.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ralf Weiskirchen, Sarah K. Schroeder, Sabine Weiskirchen, Eva Miriam Buhl, Bodo Melnik
Summary: Extracellular vesicles, such as exosomes, are small bilayered biovesicles released by cells, enriched with biologically active components. Milk exosomes play a key role in infant growth and development, while exosomes derived from different cell types have regenerative and immunomodulatory properties. Isolation protocols for milk exosomes allow the purification of highly enriched fractions, expressing typical exosomal protein markers.
Article
Biochemistry & Molecular Biology
Marinela Krizanac, Paola Berenice Mass Sanchez, Sarah K. Schroeder, Ralf Weiskirchen, Anastasia Asimakopoulos
Summary: Perilipin 5 (PLIN5) is a lipid droplet coat protein highly expressed in oxidative tissues. It is regulated by peroxisome proliferator-activated receptors (PPARs) and cellular lipid status. Previous research focused on its role in non-alcoholic fatty liver disease (NAFLD) and lipid metabolism regulation. Limited studies connected PLIN5 to hepatocellular carcinoma (HCC), where its expression is upregulated. This study explores the regulation of PLIN5 by cytokines involved in HCC and NAFLD progression, revealing IL-6-induced upregulation mediated by the JAK/STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Letter
Gastroenterology & Hepatology
Ralf Weiskirchen