Review
Biochemistry & Molecular Biology
Ayleen Fernandez-Fierro, Samanta C. Funes, Mariana Rios, Camila Covian, Jorge Gonzalez, Alexis M. Kalergis
Summary: The heme oxygenase (HO) system involves three isoforms, with HO-1 being the most studied and overexpression of this enzyme promoting anti-inflammatory products. However, overexpression of HO leading to neonatal jaundice has prompted the development of inhibitors. Various types of inhibitors have been identified, including competitive and non-competitive ones, with potential medical implications in metabolic diseases and immune-mediated diseases such as cancer and Alzheimer's disease. Selective inhibition of HO isoforms may contribute to the treatment of these ailments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Shao-Wei Li, Terumi Takahara, Weitao Que, Masayuki Fujino, Wen-Zhi Guo, Shin-Ichi Hirano, Li-Ping Ye, Xiao-Kang Li
Summary: Hydrogen-rich water (HRW) protects mice with nonalcoholic fatty liver disease by increasing the expression of Sirt1 in hepatocytes, which leads to the suppression of abnormal fat metabolism. In a NASH mouse model, HRW reduces the expression of inflammatory cytokines, alleviates tissue damage, and reverses preexisting hepatic fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhen Liang, Zhaoshi Zheng, Qi Guo, Meng Tian, Jing Yang, Xiu Liu, Xiaojuan Zhu, Songyan Liu
Summary: This study investigates the role of hypoxia-inducible factor (HIF)-1 alpha/heme oxygenase (HO)-1 in hippocampal neuron ferroptosis during epilepsy. The results suggest that there are metabolic differences between epilepsy patients and healthy individuals, with increased oxidative stress, heightened bilirubin, and augmented iron metabolism in epileptic blood. The active HIF-1 pathway in epileptic pathogenesis and perturbations in HIF-1 alpha signaling are reinforced by the analysis. The study implicates that HIF-1 alpha/HO-1 potentially regulates hippocampal neuronal ferroptosis, iron metabolism, and oxidative stress, thereby promoting the propagation of epilepsy.
Review
Biochemistry & Molecular Biology
Maria G. Detsika, Elias A. Lianos
Summary: Heme oxygenase-1 has a new cytoprotective role by regulating the complement control protein, which helps prevent kidney injury. Targeting HO-1 induction in specific cells could be a novel approach to attenuate complement-dependent kidney diseases.
Article
Biochemistry & Molecular Biology
Qiushi Xu, Yunhui Fan, Juan J. Loor, Yusheng Liang, Hongming Lv, Xudong Sun, Hongdou Jia, Chuang Xu
Summary: Aloin exhibits anti-inflammatory, antioxidant, and anti-apoptotic effects in NASH, and its protective potential against liver injury is mediated through the activation of the Nrf2/HO-1 pathway.
Review
Biochemistry & Molecular Biology
Carlos Jimenez-Cortegana, Alba Garcia-Galey, Malika Tami, Pilar del Pino, Isabel Carmona, Soledad Lopez, Gonzalo Alba, Victor Sanchez-Margalet
Summary: NAFLD affects a quarter of the global population and poses a significant health and economic burden across all countries. The lack of approved pharmacotherapy and well-established diagnostic strategies for this disease highlights the urgency for further research and management efforts. Studies have shown a strong relationship between the hormone leptin and the development of NAFLD, suggesting potential advancements in disease management through further investigation of its role.
Article
Nutrition & Dietetics
Kiyoung Lim, Minkyu Kang, Junggil Park
Summary: The study investigated the association between spontaneous fasting ketonuria and liver fibrosis in NAFLD patients without prediabetes and diabetes mellitus. Results showed that patients with ketonuria were younger, had lower levels of glucose and insulin resistance, and had an inverse association with liver fibrosis compared to patients without ketonuria. The presence of ketonuria in these patients may have favorable metabolic effects.
Article
Multidisciplinary Sciences
Peng Li, Yuyi Zhang, Qiongxia Li, Yubo Zhang
Summary: This study aimed to investigate the immunosuppressive effects of haem oxygenase-1 (HO-1) on bone marrow mesenchymal stem cells (BMMSCs) in the rejection of transplanted liver allografts in rats. The results showed that HO-1 enhanced the immunosuppressive effects of BMMSCs and reduced acute rejection in orthotopic liver transplantation.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Hye-Eun Choi, Eun Jeong Jeon, Dong Young Kim, Mi Jin Choi, Hana Yu, Jea Il Kim, Hyae Gyeong Cheon
Summary: This study investigated the effects of sodium salicylate on adipocyte browning and found that it can induce browning by up-regulating HO-1 and promoting M2 polarization.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yang Ho, Tzen-Wen Chen, Tung-Po Huang, Ying-Hwa Chen, Der-Cherng Tarng
Summary: This study found that serum bilirubin levels and HO-1 and UGT1A1 gene polymorphisms were associated with cardiovascular disease among patients receiving chronic hemodialysis.
Article
Pharmacology & Pharmacy
Yen-Chang Chen, Jia-Hong Chen, Cheng-Fang Tsai, Chen-Teng Wu, Miao-Hsiang Wu, Pei-Chun Chang, Wei-Lan Yeh
Summary: The study found that nicardipine can inhibit the migration and colony formation of breast cancer cells, and increase the expression of Nrf2 and HO-1. The reduction of matrix metalloproteinase-9 by nicardipine is regulated by Nrf2/HO-1 axis and its catalytic end products.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cristina Fernandez-Mendivil, Enrique Luengo, Paula Trigo-Alonso, Nuria Garcia-Magro, Pilar Negredo, Manuela G. Lopez
Summary: The study revealed that overexpression of HO-1 in microglial cells in aged mice leads to neurotoxic iron accumulation, oxidative stress, and cognitive decline. Inhibiting HO-1 or using an iron chelator can prevent these issues, providing new insights for treating age-related neurodegenerative diseases.
Review
Cell Biology
Mohammad Sadeghi, Mehrdad Fathi, Jamshid Gholizadeh Navashenaq, Hamed Mohammadi, Mehdi Yousefi, Mohammad Hojjat-Farsangi, Afshin Namdar, Ali Akbar Movasaghpour Akbari, Farhad Jadidi-Niaragh
Summary: Heme oxygenase-1 (HO-1) is overexpressed in hematological malignancies and associated with disease severity. It induces tumor progression and prevents apoptosis through various pathways, making it a potential therapeutic target. However, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) remains unclear.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Xiangyun Li, Jianbo Yu, Lirong Gong, Yuan Zhang, Shuan Dong, Jia Shi, Cui Li, Yuting Li, Yanfang Zhang, Haibo Li
Summary: Sepsis-induced acute lung injury leads to oxidative stress, inflammation, apoptosis, and changes in Golgi morphology. Activating the HO-1 pathway can alleviate Golgi stress and oxidative stress, providing a therapeutic target for treating acute lung injury.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Maria G. Detsika, Ioanna Nikitopoulou, Dimitris Veroutis, Alice G. Vassiliou, Edison Jahaj, Stamatis Tsipilis, Nikolaos Athanassiou, Hariklia Gakiopoulou, Vassilis G. Gorgoulis, Ioanna Dimopoulou, Stylianos E. Orfanos, Anastasia Kotanidou
Summary: The increase in HO-1 expression observed in critically ill COVID-19 patients is associated with disease progression and poor outcome. The upregulation of HO-1 in blood and tissues of severe patients may serve as a protective mechanism against coagulation and thrombosis.
Article
Pharmacology & Pharmacy
Khaled Alganem, Abdul-Rizaq Hamoud, Justin F. Creeden, Nicholas D. Henkel, Ali S. Imami, Alex W. Joyce, William G. Ryan, Jacob B. Rethman, Rammohan Shukla, Sinead M. O'Donovan, Jarek Meller, Robert McCullumsmith
Summary: Biological regulatory networks are complex and challenging to study. Functional proteomics assessments are necessary to understand the active state of regulatory processes. Protein kinase activity profiling platforms, in combination with computational modeling techniques, provide valuable insights into the active state of regulatory systems and potential drug targets.
CURRENT OPINION IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
David Travis Thomas, Nicholas R. DelCimmuto, Kyle D. Flack, David E. Stec, Terry D. Hinds
Summary: Exercise is commonly prescribed for chronic metabolic diseases due to its insulin sensitizing, cardio-protective, and weight maintenance effects. Exercise increases the production of reactive oxygen species (ROS), which triggers the upregulation of endogenous antioxidants to protect against oxidative damage and inflammation. Plasma bilirubin, the most potent antioxidant, is elevated through the protective mechanisms of heme oxygenase-1 (HO-1) and biliverdin reductase A (BVRA) during exercise. Bilirubin protects against ROS and inflammation, and serves as a hormone that activates the nuclear receptor transcription factor PPAR alpha. Increasing plasma bilirubin can drive metabolic adaptations that improve outcomes of weight management, inflammation, type II diabetes, and cardiovascular diseases. This review aims to describe the function of bilirubin as an antioxidant and metabolic hormone, and how it interacts with exercise to improve outcomes of weight management.
Article
Gastroenterology & Hepatology
Justin F. Creeden, Zachary A. Kipp, Mei Xu, Robert M. Flight, Hunter N. B. Moseley, Genesee J. Martinez, Wang-Hsin Lee, Khaled Alganem, Ali S. Imami, Megan R. McMullen, Sanjoy Roychowdhury, Atta M. Nawabi, Jennifer A. Hipp, Samir Softic, Steven A. Weinman, Robert McCullumsmith, Laura E. Nagy, Terry D. Hinds
Summary: This study explores the similarities in fibrotic signaling networks in humans and rodents, identifying potential antifibrotic effects that may improve outcomes in liver diseases. The activation of certain protein kinases, such as the insulin receptor, is found to be hyperactive in fibrotic liver disease in both species. The findings establish a comprehensive kinase atlas for liver fibrosis, identifying analogous signaling events conserved among humans and rodents.
Review
Medicine, Research & Experimental
Olufunto O. Badmus, Sarah A. Hillhouse, Christopher D. Anderson, Terry D. Hinds Jr, David E. Stec
Summary: Metabolic-associated fatty liver disease (MAFLD) is a condition characterized by fat accumulation in the liver along with metabolic dysfunction, leading to an increased risk of cardiovascular diseases. The regulation of hepatic lipid metabolism involves various pathways, and imbalances in these pathways can result in hepatic lipid accumulation and the progression of inflammation and fibrosis. This review explores the molecular mechanisms involved in the regulation of hepatic lipids and discusses emerging therapies that target these pathways as potential future treatments for MAFLD.
Article
Medicine, Research & Experimental
Jacqueline R. Leachman, Cole Cincinelli, Nermin Ahmed, Carolina Dalmasso, Mei Xu, Eva Gatineau, Barbara S. Nikolajczyk, Frederique Yiannikouris, Terry D. Hinds, Analia S. Loria
Summary: This study investigates the effects of Maternal Separation and Early Weaning (MSEW) on adipose tissue function and its role in exacerbating obesity in female mice. The study reveals that the mineralocorticoid receptor (MR) plays a critical role in promoting adipocyte hypertrophy by preventing lipolysis and promoting triglyceride formation and storage.
Article
Biochemistry & Molecular Biology
Apurva Lad, Jonathan Hunyadi, Jacob Connolly, Joshua D. Breidenbach, Fatimah K. Khalaf, Prabhatchandra Dube, Shungang Zhang, Andrew L. Kleinhenz, David Baliu-Rodriguez, Dragan Isailovic, Terry D. Hinds, Cara Gatto-Weis, Lauren M. Stanoszek, Thomas M. Blomquist, Deepak Malhotra, Steven T. Haller, David J. Kennedy
Summary: In a murine NAFLD model, chronic exposure to MC-LR led to significant hepatotoxicity, impaired toxin metabolism, and dysregulation of key signaling pathways. Treatment with antioxidants such as NAC and pNaKtide showed improvement in hepatic inflammation and oxidative stress, suggesting the potential reversal of MC-LR metabolism impairments with targeted antioxidant therapy.
Editorial Material
Physiology
Terry D. Hinds Jr, David E. Stec, Claudio Tiribelli
Article
Biochemistry & Molecular Biology
Evelyn A. A. Bates, Zachary A. A. Kipp, Genesee J. J. Martinez, Olufunto O. O. Badmus, Mangala M. M. Soundarapandian, Donald Foster, Mei Xu, Justin F. F. Creeden, Jennifer R. R. Greer, Andrew J. J. Morris, David E. E. Stec, Terry D. D. Hinds
Summary: By using GNUR treatment in mice with NAFLD, the study found that it can increase plasma bilirubin levels, decrease plasma urobilin levels, reduce liver fat content and ceramide production, lower blood glucose and insulin levels, and decrease inflammatory mediators, thus improving overall liver health.
Article
Biochemistry & Molecular Biology
Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr
Summary: This study found that bilirubin levels are lower in obese individuals compared to lean individuals. Obesity leads to an increase in the UGT1A1 enzyme, which clears bilirubin from the blood. As a result, more conjugated bilirubin enters the intestine and is converted into urobilin, which is then absorbed through the hepatic portal vein. The study also revealed a negative correlation between bilirubin levels and BMI and adiposity in obese individuals, while urobilin levels were positively associated with BMI and adiposity. Obese women were found to have higher insulin resistance, and urobilin levels showed a stronger linear correlation with insulin resistance in women compared to men. These findings suggest that plasma urobilin levels are associated with obesity and its comorbidities such as insulin resistance.
Article
Biochemistry & Molecular Biology
Zachary A. Kipp, Genesee J. Martinez, Evelyn A. Bates, Agil B. Maharramov, Robert M. Flight, Hunter N. B. Moseley, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr
Summary: Studies show that increasing plasma bilirubin levels can help prevent and treat hepatic lipid accumulation in metabolic diseases like obesity and diabetes. Using mice on a high-fat diet, researchers found that bilirubin nanoparticles effectively reduce liver fat content by inhibiting the accumulation of ceramides and lowering the expression of enzymes responsible for ceramide production. These findings suggest that bilirubin nanoparticles have potential for improving metabolic health.
Review
Biochemistry & Molecular Biology
Shahnaz D. Vellani, Anthony Nigro, Shangari Varatharajan, Lance D. Dworkin, Justin Fortune Creeden
Summary: Evasion of innate immunity is commonly used by tumor cells to survive and thrive. Immunotherapeutic agents can overcome this evasion and have been clinically effective in various types of cancer. Recently, immunological strategies have been investigated as potential therapeutic and diagnostic modalities for managing carcinoid tumors. This article summarizes recent developments in immunotherapeutic and diagnostic modalities for carcinoid management.
Review
Biochemistry & Molecular Biology
Alexander J. J. Didier, Jennifer Stiene, Lauren Fang, Dean Watkins, Lance D. D. Dworkin, Justin F. F. Creeden
Summary: Oxidative stress, characterized by an imbalance between pro-oxidant molecules and antioxidant defense systems, is considered a major contributor to cancer development. Antioxidant supplementation, such as vitamins A, C, and E, has shown potential in reducing the risk of certain types of cancer, although there are conflicting findings. This review provides an overview of the role of oxidative stress in cancer formation and discusses the potential benefits and limitations of preventive antioxidant strategies.
Article
Multidisciplinary Sciences
Melissa A. Curtis, Rohan K. Dhamsania, Rachel C. Branco, Ji-Dong Guo, Justin Creeden, Kari L. Neifer, Carlie A. Black, Emily J. Winokur, Elissar Andari, Brian G. Dias, Robert C. Liu, Shannon L. Gourley, Gary W. Miller, James P. Burkett
Summary: Neurodevelopmental disorders (NDDs) pose a significant public health challenge, particularly in the United States where they affect up to 17% of children. Recent research has linked prenatal exposure to pyrethroid pesticides to an increased risk of NDDs. Using a mouse model, this study found that low-dose developmental exposure to the pyrethroid deltamethrin resulted in behavioral abnormalities and striatal dopamine dysfunction in the offspring.