Article
Pharmacology & Pharmacy
Soshi Narasaki, Soma Noguchi, Tomoaki Urabe, Kana Harada, Izumi Hide, Shigeru Tanaka, Yuhki Yanase, Taketoshi Kajimoto, Kazue Uchida, Yasuo M. Tsutsumi, Norio Sakai
Summary: The aim of this study was to identify the PKC domains involved in propofol-induced PKC translocation. The results showed that the C1 and C2 domains of PKCα and the C1B domain of PKC8 are involved in propofol-induced PKC translocation. In addition, the C1 domain inhibitor calphostin C inhibited propofol-induced PKC8 translocation and phosphorylation of endothelial nitric oxide synthase.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jaqueline Pereira Moura Soares, Diego Assis Goncalves, Ricardo Xisto de Sousa, Margareth Gori Mouro, Elisa M. S. Higa, Leticia Paulino Sperandio, Carolina Moraes Vitoriano, Elisa Bachir Santa Rosa, Fernanda Oliveira dos Santos, Gustavo Nery de Queiroz, Roberta Sessa Stilhano Yamaguchi, Gustavo Pereira, Marcelo Yudi Icimoto, Fabiana Henriques Machado de Melo
Summary: Cutaneous melanoma is the most aggressive type of skin cancer, and it progresses through different stages. Reactive oxygen species modulate oncogenic signaling pathways in all stages of melanoma development. The altered concentration of tetrahydrobiopterin disrupts cellular redox homeostasis and contributes to melanoma progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Amir Asgari, Paul Jurasz
Summary: Megakaryocytes are important members of the hematopoietic system, responsible for regulating vascular homeostasis through platelets. The process of megakaryopoiesis generates mature megakaryocytes which release proplatelets into blood vessels. Nitric oxide (NO) plays a modulatory role in hematopoiesis and hemostasis. This review summarizes the effect of NO and its signaling on megakaryopoiesis and thrombopoiesis under physiological and pathophysiological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Paul Guerby, Oriane Tasta, Audrey Swiader, Frederic Pont, Emmanuel Bujold, Olivier Parant, Christophe Vayssiere, Robert Salvayre, Anne Negre-Salvayre
Summary: Preeclampsia is a pregnancy disease exclusive to humans, characterized by gestational hypertension, proteinuria, oxidative stress, and imbalance between NO and ROS production, possibly due to placental abnormalities and oxidative stress.
Article
Hematology
Arvind K. Pandey, Markus Waldeck-Weiermair, Quinn S. Wells, Wusheng Xiao, Shambhu Yadav, Emrah Eroglu, Thomas Michel, Joseph Loscalzo
Summary: This study reveals that CD70 plays a regulatory role in endothelial NO and reactive oxygen species homeostasis and is associated with vascular phenotypes. CD70 knockdown leads to reduced NO levels and increased reactive oxygen species, which may be related to endothelial dysfunction and cardiovascular diseases, highlighting its significance in human vascular diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Agnieszka Zablocka, Dominika Jakubczyk, Katarzyna Leszczynska, Katarzyna Pacyga-Prus, Jozefa Macala, Sabina Gorska
Summary: This study investigated the ability of Bifidobacterium species to induce iNOS-dependent NO synthesis in macrophages. The results showed that Bifidobacterium can regulate the expression of iNOS and produce NO by activating MAPK kinases. TLR2 and TLR4 receptors are involved in Bifidobacterium-induced macrophage activation and NO production. The study suggests that Bifidobacterium has a protective mechanism in the intestine, and its efficacy is strain-dependent.
PROBIOTICS AND ANTIMICROBIAL PROTEINS
(2023)
Article
Biochemistry & Molecular Biology
Thuan Thai, Fei Zhong, Lei Dang, Enoch Chan, Jacqueline Ku, Ernst Malle, Carolyn L. Geczy, John F. Keaney, Shane R. Thomas
Summary: The study demonstrates that transcytosed MPO in endothelial cells activates eNOS by promoting phospholipase C-dependent calcium signaling and altering eNOS phosphorylation status. This activation occurs despite reduced cellular uptake of the eNOS substrate L-arginine. These findings suggest a compensatory signaling response in endothelial cells to maintain eNOS activity and NO production in the presence of MPO-induced oxidative stress.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Environmental Sciences
Hui Chen, Yongxiang Qin, Jiawei Pu, Jinxing Hu, Yuezhong Wen
Summary: This study investigated the toxicity of the chiral synthetic auxin herbicide DCPP to Arabidopsis, as well as the mutual regulation of NO, H2O2, O-2, and phytohormones at the enantiomeric level. The results revealed the important role of ROS in the enantioselective effect of DCPP and the potential redistribution of phytohormones between leaves and roots.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Pharmacology & Pharmacy
Tatsiana Suvorava, Sara Metry, Stephanie Pick, Georg Kojda
Summary: Vascular tone regulation by nitric oxide is a crucial physiological function, with endothelial dysfunction potentially being an underlying cause of hypertension. Increasing eNOS activity reduces blood pressure, while decreasing activity has the opposite effect. These findings have important implications for pre-hypertensive treatment.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Shupeng Hu, Qiangzhong Pi, Xiudan Xu, Jianghong Yan, Yongzheng Guo, Wanying Tan, An He, Zhe Cheng, Suxin Luo, Yong Xia
Summary: This study investigates the role of eNOS in vascular dysfunction induced by sepsis. Increased phosphorylation of eNOS in early sepsis leads to decreased vasodilation, while decreased levels of eNOS in late sepsis result in diminished nitric oxide-dependent relaxation responses.
Article
Food Science & Technology
Yang Liu, Kevin D. Croft, Jonathan M. Hodgson, Trevor Mori, Natalie C. Ward
Summary: Endothelial dysfunction may lead to atherosclerosis, while dietary nitrate/nitrite shows significant benefits on cardiovascular homeostasis. Research suggests that nitrate/nitrite may enhance eNOS activation by stimulating AMPK signaling pathway, potentially contributing to vascular protective effects.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biochemistry & Molecular Biology
Ming-Jie Hou, Pan Wang, Bao Ting Zhu
Summary: In this study, it was found that protein disulfide isomerase (PDI)-mediated neuronal nitric oxide synthase (nNOS) activation plays a critical role in chemically-induced ferroptosis, which is characterized by the accumulation of nitric oxide (NO), reactive oxygen species (ROS), and lipid-ROS. Inhibition or knockdown of PDI can effectively prevent ferroptotic cell death.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Article
Medicine, Research & Experimental
George J. Dugbartey
Summary: Kidney transplantation is the preferred treatment for patients with kidney failure. However, ischemia-reperfusion injury (IRI) poses a significant challenge to the long-term success of this intervention. Nitric oxide (NO) has emerged as a potential candidate for mitigating IRI and preventing graft rejection in kidney transplantation. This review provides an overview of the sources and protective effects of endogenous and exogenous NO in kidney transplantation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Jun -Ha Hwang, Woong Heo, Jung Il Park, Kyung Min Kim, Ho Taek Oh, Gi Don Yoo, Jeekeon Park, Somin Shin, Youjin Do, Mi Gyeong Jeong, Eun Sook Hwang, Jeong-Ho Hong
Summary: Endothelial TAZ is involved in the production of nitric oxide (NO) and inhibits damage-induced liver fibrosis. It regulates NO production by transcriptional regulation of Nos3. Loss of TAZ leads to capillarization of liver sinusoidal endothelial cells and a decrease in NO concentration, accelerating liver fibrosis.
Article
Cardiac & Cardiovascular Systems
Johan van Nispen, Marcus Voigt, Eric Song, Austin Armstrong, Margarita Fedorova, Vidul Murali, Joseph Krebs, Ashish Samaddar, Chandrashekhara Manithody, Ajay Jain
Summary: Parenteral nutrition is a life-saving nutritional therapy, but it can cause various side effects, especially liver disease. The adverse effects of PN on organ systems such as the brain and cardiovascular system are poorly studied.
CARDIOVASCULAR TOXICOLOGY
(2021)
Article
Cell Biology
Hongchao Guo, Xuan Yu, Yu Liu, David T. Paik, Johanne Marie Justesen, Mark Chandy, James W. S. Jahng, Tiejun Zhang, Weijun Wu, Freeborn Rwere, Shane Rui Zhao, Suman Pokhrel, Rabindra V. Shivnaraine, Souhrid Mukherjee, Daniel J. Simon, Amit Manhas, Angela Zhang, Che-Hong Chen, Manuel A. Rivas, Eric R. Gross, Daria Mochly-Rosen, Joseph C. Wu
Summary: The common ALDH2*2 variant affects around 8% of the global population and is associated with a severe loss of ALDH2 enzymatic activity and an increased risk of CAD. Empagliflozin, an SGLT2 inhibitor, has been shown to improve EC dysfunction caused by ALDH2*2, suggesting a potential preventive measure against CAD.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Clinical Neurology
Ming-Chyi Huang, Hsueh-Yuan Tu, Ren-Hua Chung, Hsiang-Wei Kuo, Tung-Hsia Liu, Che-Hong Chen, Daria Mochly-Rosen, Yu-Li Liu
Summary: Blood NFL levels are increased in patients with alcohol dependence and decrease after early abstinence. The ALDH2 rs671 polymorphism is associated with NFL levels. Reduction in NFL levels correlates with improvement of clinical symptoms.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Cardiac & Cardiovascular Systems
Riddhita Mukherjee, Laura H. Tetri, Sin-Jin Li, Giovanni Fajardo, Nicolai P. Ostberg, Kaleb B. Tsegay, Kanika Gera, Timothy T. Cornell, Daniel Bernstein, Daria Mochly-Rosen, Bereketeab Haileselassie
Summary: This study investigates the role of Drp1/p53 interaction in sepsis-induced myocardial dysfunction (SIMD). The results show that there is an increase in Drp1/p53 interaction following LPS treatment, leading to p53 localization to the mitochondria and mitochondrial dysfunction. Inhibiting the Drp1/p53 interaction can improve mitochondrial damage in SIMD.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Review
Chemistry, Medicinal
Valerio Ciccone, Marina Ziche, Andrea Spini, Sandra Donnini
Summary: Global repositories of postmarketing safety reports provide important insights into real-life drug toxicities beyond clinical trials. This scoping review focuses on spontaneous reporting systems studies (SRSs) of antiangiogenic drugs (AADs) in cancer patients and examines whether adverse events (AEs) identified in these studies were validated and mentioned in the respective Summary of Product Characteristics (SmPCs). The findings reveal a knowledge gap on the safety of AADs, particularly in relation to cardiovascular adverse events, which were not mentioned in the SmPCs despite established concerns. Additionally, a disproportionality signal for pericardial disease was found for axitinib, but not mentioned in the drug's SmPC. Despite the exclusion of pharmacoepidemiological studies, this scoping review presents a novel approach to identify potential safety concerns of drugs and guide postmarketing surveillance of AADs.
Article
Biology
An-Sheng Lee, Yen-Ling Sung, Szu-Hua Pan, Kuo-Tzu Sung, Cheng-Huang Su, Shiao-Li Ding, Ying-Jui Lu, Chin-Ling Hsieh, Yun-Fang Chen, Chuan-Chuan Liu, Wei-Yu Chen, Xuan-Ren Chen, Fa-Po Chung, Shih-Wei Wang, Che-Hong Chen, Daria Mochly-Rosen, Chung-Lieh Hung, Hung- Yeh, Shien-Fong Lin
Summary: This study reveals that the East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) is associated with the risk of ventricular arrhythmia caused by low-level alcohol consumption. Both human and mouse models demonstrate prolonged QT interval and increased ventricular arrhythmia episodes in individuals carrying ALDH2 variants. This research is important for formulating safe drinking guidelines and developing protective agents for ALDH2 deficient individuals.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Scott Burkholz, Michael Rubsamen, Luke Blankenberg, Richard T. Carback III, Daria Mochly-Rosen, Paul E. Harris
Summary: Analysis of next-generation sequencing data linked with clinical metadata reveals that Omicron reinfections occur at a higher frequency and within a shorter time interval compared to pre-Omicron variants. This suggests that a single infection may not generate the protective immunity required to defend against Omicron reinfections. Continued next-generation sequencing and inclusion of clinical metadata is necessary for effective surveillance, treatment, vaccine development, and public health recommendations.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yi-Cheng Chang, Hsiao-Lin Lee, Wenjin Yang, Meng-Lun Hsieh, Cai-Cin Liu, Tung-Yuan Lee, Jing-Yong Huang, Jiun-Yi Nong, Fu-An Li, Hsiao-Li Chuang, Zhi-Zhong Ding, Wei-Lun Su, Li-Yun Chueh, Yi-Ting Tsai, Che-Hong Chen, Daria Mochly-Rosen, Lee-Ming Chuang
Summary: Obesity and type 2 diabetes are global pandemics. Mutations in the ALDH2 gene result in reduced enzymatic activity, leading to metabolic disorders. Activating ALDH2 can improve diet-induced obesity, fatty liver, and glucose homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Luis Rios, Suman Pokhrel, Sin-Jin Li, Gwangbeom Heo, Bereketeab Haileselassie, Daria Mochly-Rosen
Summary: The researchers have identified a small molecule that can mimic the effects of a peptide inhibitor and reduce the burden of protein-related diseases. This study is important for understanding and potentially treating various pathologies associated with protein dysregulation.
NATURE COMMUNICATIONS
(2023)
Review
Geriatrics & Gerontology
Tetsumori Yamashima, Takuya Seike, Daria Mochly-Rosen, Che-Hong Chen, Mitsuru Kikuchi, Eishiro Mizukoshi
Summary: This review discusses the mechanism of neuronal death in Alzheimer's disease by focusing on Hsp70.1, which has a dual function as a chaperone protein and lysosomal stabilizer. It suggests that A beta is not the root cause of Alzheimer's disease, but rather a byproduct of autophagy/lysosomal failure resulting from hydroxynonenal-induced Hsp70.1 disorder. Enhancing ALDH2 activity to detoxify hydroxynonenal emerges as a promising strategy for preventing and treating Alzheimer's disease.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Review
Geriatrics & Gerontology
Takuya Seike, Che-Hong Chen, Daria Mochly-Rosen
Summary: Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that is crucial for alcohol and aldehyde metabolism. A common ALDH2 polymorphism found in East Asians, known as ALDH2*2 or E504K missense variant (SNP ID: rs671), has been associated with various diseases, including Alzheimer's disease (AD). Studies on mice have shown that ALDH2 deficiency and the presence of ALDH2*2 exacerbate the pathology of AD, indicating their involvement in the development of AD. Additionally, the relationship between heavy alcohol consumption and AD has also been explored, with chronic alcohol administration in ALDH2*2/*2 mice worsening the onset of AD-like symptoms. Therefore, ALDH2 polymorphism and alcohol consumption are likely to play important roles in the pathogenesis of AD.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Meeting Abstract
Critical Care Medicine
Vijith Vijayan, Hao Yan, Juliane Lohmeyer, Kolten Peterson, James Harden, Rachana Patil, Giulia Barbarito, Alice Bertaina, Robert Negrin, Daria Mochly-Rosen, Kenneth Weinberg, Bereketeab Haileselassie
CRITICAL CARE MEDICINE
(2023)
Meeting Abstract
Critical Care Medicine
Sin Jin Li, Ching-Yi Chen, Nicolai Ostberg, Laura Tetri, Timothy Cornell, Daria Mochly-Rosen, Bereketeab Haileselassie
CRITICAL CARE MEDICINE
(2023)
Article
Oncology
Samuel Flashner, Masataka Shimonosono, Yasuto Tomita, Norihiro Matsuura, Shinya Ohashi, Manabu Muto, Andres J. Klein-Szanto, J. Alan Diehl, Che-Hong Chen, Daria Mochly-Rosen, Kenneth Weinberg, Hiroshi Nakagawa
Summary: The carcinogenic alcohol metabolite acetaldehyde drives ESCC. Acetaldehyde is detoxified by ALDH2 which is suppressed by its common polymorphism. Here, we demonstrate that ALDH2 dysfunction and alcohol exposure cooperate in ESCC progression through cancer stem cell enrichment.
Article
Cardiac & Cardiovascular Systems
Ligia A. Kiyuna, Darlan S. Candido, Luiz R. G. Bechara, Itamar C. G. Jesus, Lisley S. Ramalho, Barbara Krum, Ruda P. Albuquerque, Juliane C. Campos, Luiz H. M. Bozi, Vanessa O. Zambelli, Ariane N. Alves, Nicolas Campolo, Mauricio Mastrogiovanni, Silvina Bartesaghi, Alejandro Leyva, Rosario Duran, Rafael Radi, Guilherme M. Arantes, Edecio Cunha-Neto, Marcelo A. Mori, Che-Hong Chen, Wenjin Yang, Daria Mochly-Rosen, Ian J. MacRae, Ludmila R. P. Ferreira, Julio C. B. Ferreira
Summary: This study investigates the mechanisms and potential treatment for the deleterious effects of 4-hydroxynonenal (4-HNE) in heart failure. The results show that 4-HNE inhibits Dicer, which impairs miRNA processing. Boosting 4-HNE clearance through pharmacological activation of aldehyde dehydrogenase 2 (ALDH2) restores Dicer activity and miRNA biogenesis, offering a potential treatment for heart failure patients.
EUROPEAN HEART JOURNAL
(2023)
Meeting Abstract
Oncology
Che-Hong Chen, Daria Mochly-Rosen, Su-I Hou
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)