Article
Chemistry, Analytical
Jie Zhang, Zengchen Liu, Fengshou Tian, Yahong Chen
Summary: A fluorescent compound derived from coumarin and hemicyanine was synthesized and characterized in this paper, showing higher ratiometric fluorescence response activity toward NAD(P)H compared to other commonly coexisting compounds in the cell microenvironment. The fluorescence identification mechanism was deduced to be a redox reaction between the sensor and NAD(P)H. This ratiometric fluorescent probe provides a theoretical basis for sensing NAD(P)H in vitro and in vivo, and was used to build a sensitive detection platform of NAD(P)H-dependent enzyme activity based on the fluorescence method.
ANALYTICAL METHODS
(2021)
Article
Endocrinology & Metabolism
Fan Yang, Xuan Deng, Ye Yu, Lei Luo, Xianda Chen, Jinping Zheng, Yugang Qiu, Feng Xiao, Xiaomei Xie, Yuzheng Zhao, Jun Guo, Feifei Hu, Xuguang Zhang, Zhenyu Ju, Yong Zhou
Summary: The association between whole blood NAD(+) contents and aging differed significantly between males and females, with a loss of blood NAD(+) observed only in males, especially in the male middle-aged population. Considering gender differences is crucial in future studies related to NAD(+).
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Cell Biology
Claudia Christiano Silva Chini, Heidi Soares Cordeiro, Ngan Le Kim Tran, Eduardo Nunes Chini
Summary: The geroscience hypothesis suggests that addressing the biology of aging can prevent or mitigate chronic diseases. The relationship between NAD metabolism and cellular senescence is complex, but understanding it is necessary for exploring NAD replacement therapies.
Article
Biochemistry & Molecular Biology
Chengting Luo, Changmei Yang, Xueying Wang, Yuling Chen, Xiaohui Liu, Haiteng Deng
Summary: Research showed that nicotinamide supplementation can reduce fat mass in obese mice, improve glucose tolerance, and enhance mitochondrial function in adipose tissue. Nicotinamide activates NAMPT and increases cellular NAD(+) levels to reprogram cellular metabolism for better adipose tissue function.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2022)
Article
Neurosciences
Chen Shen, Cong Chen, Tong Wang, Tong-Yao Gao, Min Zeng, Yun-Bi Lu, Wei-Ping Zhang
Summary: Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme in the salvaging synthesis pathway of nicotinamide adenine dinucleotide (NAD). Depletion of NAMPT can lead to cognitive deficiency in hippocampus neurons and increase the risk of neurodegeneration due to mitochondrial dysfunction.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Cell Biology
Lola E. Navas, Amancio Carnero
Summary: NAD+ plays a crucial role in cell homeostasis, participating in both redox and nonredox reactions. Tumor cells need to maintain high levels of NAD+ through the salvage pathway to meet their demands. NAMPT, the rate-limiting enzyme in this pathway, has been identified as a potential target for cancer therapy.
Review
Physiology
Julianna D. Zeidler, Sonu Kashyap, Kelly A. Hogan, Eduardo Nunes Chini
Summary: During the COVID-19 pandemic, it has been observed that the elderly and individuals with age-related syndromes are more susceptible to severe immune responses. CD38 has been implicated in the altered immunometabolism resulting from COVID-19 infection, suggesting it as a potential therapeutic target.
PHYSIOLOGICAL REVIEWS
(2022)
Review
Plant Sciences
Chen Guo, Qingxia Huang, Yisa Wang, Yao Yao, Jing Li, Jinjin Chen, Mingxia Wu, Zepeng Zhang, E. Mingyao, Hongyu Qi, Peng Ji, Qing Liu, Daqing Zhao, Hang Su, Wenxiu Qi, Xiangyan Li
Summary: This research provides a summary of the latest findings on the prevention and treatment of various diseases through the regulation of NAD(+) metabolism by natural products. The natural products mainly include phenols, flavonoids, glycosides, quinones, terpenoids, pyrazines, alkaloids, and phenylpropanoids, which have antioxidant, energy-producing, anti-inflammatory, anti-apoptotic, and anti-aging effects.
Review
Physiology
David Walzik, Wiebke Jonas, Niklas Joisten, Sergen Belen, Rob C. I. Wuest, Gilles Guillemin, Philipp Zimmer
Summary: Nicotinamide adenine dinucleotide (NAD(+)) is a coenzyme with various cell functions and has been found to be associated with diseases and aging. Exercise is suggested to restore NAD(+) homeostasis through metabolic adaption. This review discusses the impact of acute exercise and exercise training on NAD(+) metabolism and highlights their potential value as NAD(+)-boosting strategies.
Article
Nutrition & Dietetics
Nengzhi Pang, Qianrong Hu, Yujia Zhou, Ying Xiao, Wenli Li, Yijie Ding, Yunan Chen, Mingtong Ye, Lei Pei, Qiuyan Li, Yingying Gu, Yan Sun, Evandro Fei Fang, Mianrong Chen, Zhenfeng Zhang, Lili Yang
Summary: The study aimed to explore the health benefits of boosting NAD levels with NR on HCC. The results showed that NR supplementation alleviated HCC-induced weight loss and metastasis to the lung, and decreased HCC progression and metastasis in both in vivo and in vitro experiments. Therefore, supplementing NR may serve as an effective treatment for the suppression of HCC progression.
Article
Biochemistry & Molecular Biology
Shivansh Goyal, Akhilesh Paspureddi, Mu-Jie Lu, Hsin-Ru Chan, Scott N. Lyons, Crystal N. Wilson, Marc Niere, Mathias Ziegler, Xiaolu A. Cambronne
Summary: SLC25A51 is a mitochondrial carrier protein that transports NAD(+) across the inner mitochondrial membrane. In this study, Molecular Dynamics simulations are used to investigate the mechanism of NAD(+) transport by SLC25A51. The simulations reveal spontaneous binding of cardiolipin phospholipids to specific sites on the exterior of SLC25A51, and mutation of these sites impairs cardiolipin binding and transporter activity. Additionally, the study identifies binding sites for NAD(+) in SLC25A51 and shows that its selectivity for NAD(+) is guided by electrostatic interactions.
Review
Biochemistry & Molecular Biology
Renata Novak Kujundzic
Summary: Immune response and inflammation caused by SARS-CoV-2 infection challenge the host's NAD(+) metabolism. The depletion of NAD(+) and elevation of its metabolites contribute to the development of a systemic disease. The robustness of the host's NAD(+) salvage pathway before infection determines the severity of COVID-19 and persistence of symptoms after infection resolution.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Borut Poljsak, Vito Kovac, Irina Milisav
Summary: The use of NAD+ boosters as dietary supplements has gained popularity due to increasing interest in anti-ageing strategies and health-promoting lifestyles. However, there are uncertainties regarding dosage, timing, safety, and side effects. More clinical trials and research are needed to determine proper dosages, treatment durations, and long-term consequences of increased NAD+ levels.
Review
Biochemistry & Molecular Biology
Roberto Campagna, Arianna Vignini
Summary: This review discusses the pathways involved in NAD(+) biosynthesis, the relationship between NAD(+) levels and various diseases, and strategies to increase intracellular NAD(+) levels. It also focuses on the impact of NAD(+) imbalance and NAD(+)-dependent enzyme alterations on endothelial cell function and the development of vascular dysfunction in different pathological conditions.
Article
Hematology
Jessica Venugopal, Jintao Wang, Chiao Guo, Daniel T. Eitzman
Summary: Pharmacological IL-1R antagonism improves anaemia in a murine SCD model. IL-1 beta stimulation of platelets promotes erythrocyte sickling, possibly mediated by platelet-derived TGF-beta-induced reactive oxygen species generation through erythrocyte NADPH oxidase.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Respiratory System
Katja Hoenzke, Benedikt Obermayer, Christin Mache, Diana Fathykova, Mirjana Kessler, Simon Doekel, Emanuel Wyler, Morris Baumgardt, Anna Loewa, Karen Hoffmann, Patrick Graff, Jessica Schulze, Maren Mieth, Katharina Hellwig, Zeynep Demir, Barbara Biere, Linda Brunotte, Angeles Mecate-Zambrano, Judith Bushe, Melanie Dohmen, Christian Hinze, Sefer Elezkurtaj, Mario Toennies, Torsten T. Bauer, Stephan Eggeling, Hong-Linh Tran, Paul Schneider, Jens Neudecker, Jens C. Rueckert, Kai M. Schmidt-Ott, Jonas Busch, Frederick Klauschen, David Horst, Helena Radbruch, Josefine Radke, Frank Heppner, Victor M. Corman, Daniela Niemeyer, Marcel A. Mueller, Christine Goffinet, Ronja Mothes, Anna Pascual-Reguant, Anja Erika Hauser, Dieter Beule, Markus Landthaler, Stephan Ludwig, Norbert Suttorp, Martin Witzenrath, Achim D. Gruber, Christian Drosten, Leif-Erik Sander, Thorsten Wolff, Stefan Hippenstiel, Andreas C. Hocke
Summary: This study reveals that severe lung injury in COVID-19 may result from macrophage-triggered immune activation rather than direct viral damage to the alveolar compartment.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Multidisciplinary Sciences
Maik Pietzner, Robert Lorenz Chua, Eleanor Wheeler, Katharina Jechow, Julian D. S. Willett, Helena Radbruch, Saskia Trump, Bettina Heidecker, Hugo Zeberg, Frank L. Heppner, Roland Eils, Marcus A. Mall, J. Brent Richards, Leif-Erik Sander, Irina Lehmann, Soeren Lukassen, Nicholas J. Wareham, Christian Conrad, Claudia Langenberg
Summary: This study integrates genomic, proteomic, and single-cell data to identify ELF5 as a candidate risk gene for severe COVID-19. ELF5 shows consistent associations with different outcome definitions and is specifically expressed in respiratory epithelial cells, which are likely targets of SARS-CoV-2.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Stephanie Staudte, Konrad Klinghammer, Philipp Sebastian Jurmeister, Paul Jank, Jens-Uwe Blohmer, Sandra Liebs, Peter Rhein, Anja E. Hauser, Ingeborg Tinhofer
Summary: Detection of circulating tumor cells (CTCs) has been established as an independent prognostic marker in solid cancer. This study evaluated the suitability of the Arnnis brand ImageStream X MkII (ISX) imaging flow cytometer for protein expression analysis and treatment monitoring in CTCs. The results showed that the ISX-based protocol was sensitive and specific in detecting phospho-EGFR and gamma H2AX foci in CTCs, and allowed assessment of protein expression heterogeneity within the CTC population.
Article
Immunology
Valentina Strohmeier, Geoffroy Andrieux, Susanne Unger, Anna Pascual-Reguant, Adam Klocperk, Maximilian Seidl, Otavio Cabral Marques, Marleen Eckert, Katja Graewe, Michelle Shabani, Caroline von Spee-Mayer, David Friedmann, Ina Harder, Sylvia Gutenberger, Baerbel Keller, Michele Proietti, Alla Bulashevska, Bodo Grimbacher, Jan Provaznik, Vladimir Benes, Sigune Goldacker, Christoph Schell, Anja E. Hauser, Melanie Boerries, Peter Hasselblatt, Klaus Warnatz
Summary: This study found that about 15% of patients with common variable immunodeficiency (CVID) develop a small intestinal enteropathy, resembling celiac disease, which is associated with chronic norovirus infection. The study also revealed that the lack of immune cells, T cell imbalance, and increased inflammation markers are related to the development and severity of the disease. Additionally, chronic norovirus infection exacerbates the increase in inflammation markers. This study contributes to a better understanding of the pathogenesis of CVID enteropathy and provides a theoretical basis for finding relevant treatment strategies.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Rheumatology
Lennard Ostendorf, Marie Burns, Dimitrios Laurin Wagner, Philipp Enghard, Kerstin Amann, Henrik Mei, Kai-Uwe Eckardt, Evelyn Seelow, Adrian Schreiber
Summary: Daratumumab, an anti-CD38 antibody, was found to be safe and effective in treating treatment-refractory AAV. Two patients with severe renal and pulmonary manifestations showed significant clinical and immunological improvements after receiving daratumumab treatment.
Article
Immunology
Mikhail Lebedin, Clara Vazquez Garcia, Lisa Spatt, Christoph Ratswohl, Charlotte Thibeault, Lennard Ostendorf, Tobias Alexander, Friedemann Paul, Leif Erik Sander, Florian Kurth, Kathrin de la Rosa
Summary: Diverse autoantibodies in COVID-19 have unclear functional implications. ACE2 is one of the targets of autoantibodies. Elevated levels of sACE2 and anti-ACE2 IgG were observed in critically ill patients, but they were poorly correlated. IgGs recognizing ACE2, IFN alpha 2, and CD26 correlated strongly in severe COVID-19, with some showing polyreactivity. Promiscuous autoantibodies did not impair ACE2 and IFN alpha 2 activity, while specific anti-IFN alpha 2 IgG compromised cytokine function.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Neurosciences
Kamil Sebastian Rosiewicz, Bakhrom Muinjonov, Severine Kunz, Helena Radbruch, Jessy Chen, Rene Juettner, Janis Kerkering, Julia Ucar, Tadhg Crowley, Ben Wielockx, Friedemann Paul, Marlen Alisch, Volker Siffrin
Summary: Astrocytes play a crucial role in maintaining the blood-brain barrier and supporting neuronal functions. In this study, transgenic mice with astrocyte-specific activation of the hypoxia-response program were investigated. The deletion of oxygen sensors in these mice led to an exacerbation of autoimmune encephalomyelitis, accompanied by immune cell infiltration. The study also highlighted the loss of gap-junctional Connexin-43 in these astrocytes, which was induced by vascular endothelial growth factor-alpha expression.
Article
Immunology
Dirk Reinhold, Vadim Farztdinov, Yan Yan, Christian Meisel, Henrik Sadlowski, Joachim Kuehn, Frank H. Perschel, Matthias Endres, Emrah Duezel, Stefan Vielhaber, Karina Guttek, Alexander Goihl, Morten Veno, Bianca Teegen, Winfried Stoecker, Paula Stubbemann, Florian Kurth, Leif E. Sander, Markus Ralser, Carolin Otto, Simon Streit, Sven Jarius, Klemens Ruprecht, Helena Radbruch, Jorgen Kjems, Michael Muelleder, Frank Heppner, Peter Koertvelyessy
Summary: Patients with COVID-19 may experience various neurological symptoms, but the role of the central nervous system (CNS) in COVID-19 is still unclear. The inflammatory response in the cerebrospinal fluid (CSF) of COVID-19 patients was studied, and it was found that there were attenuated inflammatory changes compared to patients with herpes simplex virus encephalitis (HSVE). The inflammatory mediators in the CSF of COVID-19 patients were likely derived from the systemic circulation rather than produced within the CNS. Further investigation is needed to understand the relevance of blood-derived mediators of inflammation in the CSF for neurological COVID-19 and post-COVID-19 symptoms.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Multidisciplinary Sciences
Spyridon Lipka, Lennard Ostendorf, Udo Schneider, Falk Hiepe, Falko Apel, Tobias Alexander
Summary: This study aimed to investigate the contributions of neutrophils and NETs to the pathogenesis of GPA. The results showed that GPA patients had increased levels of activated and immature LDGs, and their sera degraded NETs less effectively, which weakly correlated with markers of disease activity.
Article
Multidisciplinary Sciences
Ronja Mothes, Anna Pascual-Reguant, Ralf Koehler, Juliane Liebeskind, Alina Liebheit, Sandy Bauherr, Lars Philipsen, Carsten Dittmayer, Michael Laue, Regina von Manitius, Sefer Elezkurtaj, Pawel Durek, Frederik Heinrich, Gitta A. Heinz, Gabriela M. Guerra, Benedikt Obermayer, Jenny Meinhardt, Jana Ihlow, Josefine Radke, Frank L. Heppner, Philipp Enghard, Helena Stockmann, Tom Aschman, Julia Schneider, Victor M. Corman, Leif E. Sander, Mir-Farzin Mashreghi, Thomas Conrad, Andreas C. Hocke, Raluca A. Niesner, Helena Radbruch, Anja E. Hauser
Summary: Inflammation, lung pathology, and development of COVID-19 are associated with SARS-CoV-2 infection. This study demonstrates the spatial association of CCL18 and CCL21 with lung pathology in severe COVID-19. The activation of adventitial niches plays a crucial role in the prolonged lung immunopathology observed in severe COVID-19.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Immunology
Carolin Ulbricht, Yu Cao, Raluca A. Niesner, Anja E. Hauser
FRONTIERS IN IMMUNOLOGY
(2023)
Letter
Rheumatology
Tobias Alexander, Lennard Ostendorf, Robert Biesen, Udo Schneider, Gerd R. Burmester, Falk Hiepe
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Letter
Rheumatology
Lennard Ostendorf, Frederic Muench, Lena Thormaehlen, Zaza Galbavy, Roland Korner, Jens Nee, Udo Schneider
Article
Clinical Neurology
Ana Luisa de Almeida Marcelino, Simon Streit, Marie Alice Homeyer, Hans-Christian Bauknecht, Helena Radbruch, Klemens Ruprecht, Harald Pruess
Summary: Hypertrophic pachymeningitis (HP) is a rare immune-mediated disease characterized by dura mater thickening and cranial neuropathy. Traditional systemic immunotherapies may not always be effective, so intraventricular chemotherapy with methotrexate, cytarabine, and dexamethasone was used in a 57-year-old patient with HP. The treatment showed positive effects by reducing inflammatory markers in the cerebrospinal fluid and preventing further progression of visual and hearing loss.
CASE REPORTS IN NEUROLOGY
(2023)
