Article
Medicine, Research & Experimental
Tae Seok Oh, Manal Zabalawi, Shalini Jain, David Long, Peter W. Stacpoole, Charles E. McCall, Matthew A. Quinn
Summary: This study reveals the relationship between sepsis and systemic metabolic abnormalities, as well as the interaction between liver and systemic metabolic reprogramming. It was found that sepsis leads to an increase in circulating free fatty acids and acylcarnitines, but a decrease in levels of amino acids and carbohydrates, resulting in a drastic shift in systemic fuel preference. Furthermore, glycine deficiency was identified as a common abnormality in the plasma and liver during sepsis, and the septic liver may contribute to systemic glycine deficiency by downregulating genes involved in glycine synthesis. Moreover, the study found that the intraperitoneal injection of the PDK inhibitor dichloroacetate reversed various metabolic abnormalities induced by sepsis, partly through the restoration of hepatic fuel metabolism.
Article
Toxicology
Danielle T. Phillippi, Sarah Daniel, Vaidehi Pusadkar, Victoria L. Youngblood, Kayla N. Nguyen, Rajeev K. Azad, Brian K. McFarlin, Amie K. Lund
Summary: Inhaled diesel exhaust particles (DEP) exposure alters gut microbial profiles and promotes systemic inflammation and cardiovascular disease (CVD) biomarkers. Probiotic treatment can mitigate these effects.
PARTICLE AND FIBRE TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Jintao Feng, Wei Jiang, Xiaofang Cheng, Benkun Zou, Alan W. Varley, Ting Liu, Guojun Qian, Wenjiao Zeng, Jianguo Tang, Qiang Zhao, Yiwei Chu, Yuanyuan Wei, Xiaobo Li, Robert S. Munford, Mingfang Lu
Summary: Research showed that acyloxyacyl hydrolase (AOAH) can prevent foam cell formation in mice, reduce cholesterol accumulation, and inflammation. Aoah(-/-) mice developed more arterial foam cells after being fed a high fat, high cholesterol diet and receiving small doses of LPSs.
Article
Multidisciplinary Sciences
Nathan L. Price, Xinbo Zhang, Pablo Fernandez-Tussy, Abhishek K. Singh, Sean A. Burnap, Noemi Rotllan, Leigh Goedeke, Jonathan Sun, Alberto Canfran-Duque, Binod Aryal, Manuel Mayr, Yajaira Suarez, Carlos Fernandez-Hernando
Summary: miR-33 is an intronic microRNA that regulates lipid metabolism by targeting ABCA1 to promote cholesterol efflux and improve HDL biogenesis. Liver-specific deficiency of miR-33 enhances glucose homeostasis, reduces fibrosis and inflammation, and increases circulating HDL-C levels. However, these changes are not sufficient to reduce atherosclerotic plaque size under hyperlipidemic conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Wenting Cheng, Wanjun Zhang, Xiaowen Xia, Jianzhong Zhang, Mingyue Wang, Yanting Li, Xin Li, Yuxin Zheng, Jing Liu, Rong Zhang, Jinglong Tang
Summary: Inhaled carbon black nanoparticles (CBNPs) are internalized by alveolar macrophages, leading to pulmonary inflammation and subsequent circulatory inflammation and damage to cerebrovascular tight junctions. The Wnt/beta-catenin signaling pathway is closely associated with cerebrovascular endothelial cell impairment. Inflammation in the lungs and circulatory system plays a significant role in the domino effect of inhaled CBNPs.
Article
Obstetrics & Gynecology
Oksana Shynlova, Lubna Nadeem, Anna Dorogin, Sam Mesiano, Stephen J. Lye
Summary: This study demonstrates that the selective progesterone receptor modulator, promegestone, can effectively prevent term labor and bacterial endotoxin-induced preterm birth in mice.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Article
Immunology
Zhiqiang Wang, Zhou Lu, Shengli Lin, Jie Xia, Ziwen Zhong, Zhangjuan Xie, Yun Xing, Jingbo Qie, Mengxia Jiao, Yifan Li, Haoyu Wen, Pengyuan Zhao, Dan Zhang, Pinghong Zhou, Jiawen Qian, Feifei Luo, Luman Wang, Hongxiu Yu, Jie Liu, Jie Gu, Ronghua Liu, Yiwei Chu
Summary: A subset of B cells expressing leucine-tRNA-synthase-2 (LARS2) with a transforming growth factor-beta 1 (TGF-beta 1) regulatory feature has been identified in both mouse and human colorectal cancer (CRC). These cells exhibit a leucine nutrient preference and are located outside the tertiary lymphoid structure. They are associated with colorectal hyperplasia and shortened survival in CRC patients. A leucine diet can induce the generation of LARS B cells, while deletion of Lars2 gene or leucine blockage can repress CRC immunoevasion. Mechanistically, LARS2 regulates mitochondrial nicotinamide adenine dinucleotide (NAD(+)) regeneration and oxidative metabolism, involving the NAD-dependent protein deacetylase sirtuin-1 (SIRT1).
Review
Biochemistry & Molecular Biology
Alex Cornwell, Alireza Badiei
Summary: Hydrogen sulfide (H2S) acts as a crucial mediator in immune cells, particularly macrophages, influencing cellular signaling, redox homeostasis, and energy metabolism. The regulation of endogenous H2S production and metabolism involves transsulfuration pathway (TSP) enzymes and sulfide oxidizing enzymes. H2S oxidation and persulfidation play important roles in cellular concentration and signaling. These sulfides have potential therapeutic implications in alleviating proinflammatory macrophage phenotypes and influencing energy metabolism processes. This review summarizes recent discoveries on the involvement of H2S in macrophage energy metabolism and redox regulation and their implications in inflammatory diseases.
Article
Immunology
Lele Fu, Haokun Liu, Wen Chen, Jamie Marie Hooft, Margareth Overland, Wanjie Cai, Dong Han, Xiaoming Zhu, Yunxia Yang, Junyan Jin, Shouqi Xie
Summary: In this study, an intestinal inflammation model was developed in gibel carp to investigate the correlation between enteritis and liver metabolism. The results showed that intestinal inflammation affected glycolysis, the TCA cycle, and pyrimidine metabolism in the liver, and the gut microbiota played a critical role in this process.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Jason Sadek, Derek T. Hall, Bianca Colalillo, Amr Omer, Anne-Marie K. Tremblay, Virginie Sanguin-Gendreau, William Muller, Sergio Di Marco, Marco Emilio Bianchi, Imed-Eddine Gallouzi
Summary: The study reveals that iNOS induces muscle wasting in cachexia by disrupting mitochondrial function and energy production processes. Clinically tested iNOS inhibitor GW274150 shows protective effects against muscle wasting in septic and cancer cachexia models.
EMBO MOLECULAR MEDICINE
(2021)
Article
Engineering, Environmental
Fatemeh Amin, Ali Roohbakhsh, Arghavan Memarzia, Hamid Reza Kazerani, Mohammad Hossein Boskabady
Summary: The study found that inhaled Paraquat has significant effects on systemic and lung inflammation and oxidative stress, with more pronounced effects in the immediate exposure condition compared to the late condition. The long-term impact of Paraquat toxicity suggests the need for more effective treatment strategies in Paraquat poisoning cases in the future.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Huanling Yao, Guojie Cao, Zheng Liu, Yue Zhao, Zhanchao Yan, Senzhen Wang, Yuehua Wang, Zhengwei Guo, Yanming Wang
Summary: Inhibition of NET formation can alleviate inflammatory damage and prolong the survival time of mice under endotoxic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Physiology
Victoria R. Kwiat, Gisienne Reis, Isela C. Valera, Kislay Parvatiyar, Michelle S. Parvatiyar
Summary: Obesity is closely associated with autoimmune diseases, with leptin playing a crucial role. Obesity not only enhances immune system activation but also leads to chronic inflammation and development of autoimmune diseases. In addition, other factors such as sustained platelet activation, gut dysbiosis, and aging are also linked to obesity and autoimmune diseases.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Peng Zhao, Xiaoli Sun, Zhongji Liao, Hong Yu, Dan Li, Zeyang Shen, Christopher K. Glass, Joseph L. Witztum, Alan R. Saltiel
Summary: Amlexanox has the potential to improve diet-induced hypertriglyceridemia atherogenesis through synergistic actions involving upregulation of bile acid synthesis, reduction of inflammation, and improvement of vascular dysfunction.
Article
Biochemistry & Molecular Biology
Jin Yu, Hong Zhu, Saeid Taheri, William Mondy, Stephen Perry, Mark S. Kindy
Summary: Plant-based nutritional supplementation can attenuate the progression of acute and chronic disorders by improving inflammatory responses and maintaining stable neurotransmitter levels. Experimentally induced inflammation by LPS affects glucose, insulin tolerance, and neurotransmitter levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Anupam Patgiri, Owen S. Skinner, Yusuke Miyazaki, Grigorij Schleifer, Eizo Marutani, Hardik Shah, Rohit Sharma, Russell P. Goodman, Tsz-Leung To, Xiaoyan Robert Bao, Fumito Ichinose, Warren M. Zapol, Vamsi K. Mootha
NATURE BIOTECHNOLOGY
(2020)
Review
Pharmacology & Pharmacy
Hideo Kimura
BRITISH JOURNAL OF PHARMACOLOGY
(2020)
Article
Multidisciplinary Sciences
Manjunatha Shivaraju, Udbhav K. Chitta, Robert M. H. Grange, Isha H. Jain, Diane Capen, Lan Liao, Jianming Xu, Fumito Ichinose, Warren M. Zapol, Vamsi K. Mootha, Jayaraj Rajagopal
Summary: Recent research has shown that airway basal stem cells have the ability to sense hypoxia and differentiate into solitary NE cells, which secrete a protective peptide called CGRP to mitigate hypoxic injury. This mechanism helps to explain the role of NE cells in the respiratory system and their response to environmental stimuli.
Editorial Material
Pharmacology & Pharmacy
Hideo Kimura
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Robert M. H. Grange, Rohit Sharma, Hardik Shah, Bryn Reinstadler, Olga Goldberger, Marissa K. Cooper, Akito Nakagawa, Yusuke Miyazaki, Allyson G. Hindle, Annabelle J. Batten, Gregory R. Wojtkiewicz, Grigorij Schleifer, Aranya Bagchi, Eizo Marutani, Rajeev Malhotra, Donald B. Bloch, Fumito Ichinose, Vamsi K. Mootha, Warren M. Zapol
Summary: Leigh syndrome, a severe mitochondrial neurodegenerative disease, has no effective treatment yet. However, in a mouse model of Leigh syndrome, hypoxia treatment has shown promise in preventing neurodegeneration and significantly extending lifespan. Mild hypoxia alone may not be effective, but when combined with nicotinic acid supplementation, it can provide modest improvement in neurodegeneration and lifespan. Therapies targeting both brain hyperoxia and NAD(+) deficiency may hold promise for treating Leigh syndrome.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Cell Biology
Takeo Uba, Yoshiyuki Matsuo, Chisato Sumi, Tomohiro Shoji, Kenichiro Nishi, Munenori Kusunoki, Hiroshi Harada, Hideo Kimura, Hidemasa Bono, Kiichi Hirota
Summary: Polysulfides play a crucial role in modulating intracellular oxygen homeostasis, regulating HIF activation, and influencing hypoxia-induced gene expression in a VHL- and mitochondria-dependent manner.
Article
Toxicology
Yusuke Miyazaki, Eizo Marutani, Takamitsu Ikeda, Xiang Ni, Kenjiro Hanaoka, Ming Xian, Fumito Ichinose
Summary: The study showed that the sulfonyl azide-based sulfide-specific scavenger SS20 has a rescue effect on H2S intoxication, improving survival rates and neurological outcomes. SS20 demonstrated efficacy not only in the ongoing exposure model but also when administered after cardiopulmonary arrest.
TOXICOLOGICAL SCIENCES
(2021)
Article
Multidisciplinary Sciences
Eizo Marutani, Masanobu Morita, Shuichi Hirai, Shinichi Kai, Robert M. H. Grange, Yusuke Miyazaki, Fumiaki Nagashima, Lisa Traeger, Aurora Magliocca, Tomoaki Ida, Tetsuro Matsunaga, Daniel R. Flicker, Benjamin Corman, Naohiro Mori, Yumiko Yamazaki, Annabelle Batten, Rebecca Li, Tomohiro Tanaka, Takamitsu Ikeda, Akito Nakagawa, Dmitriy N. Atochin, Hideshi Ihara, Benjamin A. Olenchock, Xinggui Shen, Motohiro Nishida, Kenjiro Hanaoka, Christopher G. Kevil, Ming Xian, Donald B. Bloch, Takaaki Akaike, Allyson G. Hindle, Hozumi Motohashi, Fumito Ichinose
Summary: The sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and its capacity to catabolize sulfide in mice, rats, and naturally hypoxia-tolerant ground squirrels. Silencing SQOR increased brain sensitivity to hypoxia, while neuron-specific SQOR expression prevented hypoxia-induced sulfide accumulation and ischemic brain injury. Pharmacological scavenging of sulfide maintained mitochondrial respiration in hypoxic neurons and made mice resistant to hypoxia, indicating a potential therapeutic target for ischemic brain injury.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Hideo Kimura
Summary: Initially considered a toxic gas, further research has shown that H2S has physiological roles and can act as a signaling molecule, working in synergy with NO to relax vascular smooth muscle. H2Sn, produced by 3MST, regulate the activity of ion channels and enzymes, and even affect tumor growth.
Article
Hematology
Rajeev Malhotra, Christopher J. Nicholson, Dongyu Wang, Vijeta Bhambhani, Samantha Paniagua, Charles Slocum, Haakon H. Sigurslid, Christian L. Lino Cardenas, Rebecca Li, Sophie L. Boerboom, Yin-Ching Chen, Shih-Jen Hwang, Chen Yao, Fumito Ichinose, Donald B. Bloch, Mark E. Lindsay, Gregory D. Lewis, Jayashri R. Aragam, Udo Hoffmann, Gary F. Mitchell, Naomi M. Hamburg, Ramchandran S. Vasan, Emelia J. Benjamin, Martin G. Larson, Warren M. Zapol, Susan Cheng, Jason D. Roh, Christopher J. O'Donnell, Christopher Nguyen, Daniel Levy, Jennifer E. Ho
Summary: This study finds an association between ucMGP levels and arterial stiffness, as well as future HFpEF. Experimental studies using mice also support the link between Mgp heterozygosity and arterial stiffness. These findings suggest a potential role of therapeutic targeting MGP in HFpEF.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Anesthesiology
Takamitsu Ikeda, Edilberto Amorim, Yusuke Miyazaki, Risako Kato, Eizo Marutani, Michael G. G. Silverman, Rajeev Malhotra, Ken Solt, Fumito Ichinose
Summary: The study found that early administration of sedation with propofol or dexmedetomidine can improve survival and neurological outcomes in mice resuscitated from cardiac arrest. The beneficial effects of sedation may be achieved through attenuation of cerebral hyperemia and enhancement of electroencephalographic slow-wave activity.
Article
Oncology
Eric M. Bressler, Ngoc-Quynh Chu, Robert C. Sabatelle, David A. Mahvi, Jenny T. Korunes-Miller, Fumiaki Nagashima, Fumito Ichinose, Rong Liu, Mark W. Grinstaff, Yolonda L. Colson, Chandrajit P. Raut
Summary: This study reports a novel local drug delivery approach that can prevent tumor recurrence and minimize drug-related adverse events following surgical resection of soft-tissue sarcomas.
Article
Biochemistry & Molecular Biology
Mariko Ezaka, Eizo Marutani, Yusuke Miyazaki, Eiki Kanemaru, Martin K. Selig, Sophie L. Boerboom, Katrina F. Ostrom, Anat Stemmer-Rachamimov, Donald B. Bloch, Gary J. Brenner, Etsuo Ohshima, Fumito Ichinose
Summary: This study found that glutathione trisulfide (GSSSG) can mitigate paclitaxel-induced peripheral neuropathy by preventing axonal degeneration and mitochondrial damage in peripheral sensory nerves, providing a new approach for the treatment or prevention of paclitaxel-induced peripheral neuropathy.
Article
Biochemistry & Molecular Biology
Eiki Kanemaru, Yusuke Miyazaki, Eizo Marutani, Mariko Ezaka, Shunsaku Goto, Etsuo Ohshima, Donald B. Bloch, Fumito Ichinose
Summary: The study investigates the effects of polysulfides on delayed paraplegia after spinal cord ischemia. The results show that administration of GSSSG can prevent paraplegia in mice and increase levels of polysulfides in the lumbar spinal cord, leading to decreased neurodegeneration and cell death. These findings suggest that targeted delivery of sulfane sulfur by polysulfides may have potential as a novel treatment approach for neurodegenerative diseases.
Review
Critical Care Medicine
Eizo Marutani, Fumito Ichinose
INTENSIVE CARE MEDICINE EXPERIMENTAL
(2020)