Article
Biochemistry & Molecular Biology
Mariia Emelianova, Anastasiia Gainullina, Nikolay Poperechnyi, Alexander Loboda, Maxim Artyomov, Alexey Sergushichev
Summary: This article introduces an updated pipeline GATOM and the corresponding web-service Shiny GATOM, which uses transcriptional and/or metabolomic data to find the most regulated metabolic subnetwork between two conditions. The method features a new metabolic network topology based on atom transition, which improves interpretability of the analysis results, and provides a corresponding exact solver and database analysis capabilities.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
DuoYao Cao, Zakir Khan, Xiaomo Li, Suguru Saito, Ellen A. Bernstein, Aaron R. Victor, Faizan Ahmed, Aoi O. Hoshi, Luciana C. Veiras, Tomohiro Shibata, Mingtian Che, Lei Cai, Ryan E. Temel, Jorge F. Giani, Daniel J. Luthringer, Ajit S. Divakaruni, Derick Okwan-Duodu, Kenneth E. Bernstein
Summary: This study found that increased macrophage ACE expression can enhance macrophage lipid metabolism, cholesterol efflux, and phagocytic function, thereby reducing the incidence of atherosclerosis. This finding has important implications for the treatment of cardiovascular disease.
CARDIOVASCULAR RESEARCH
(2023)
Review
Immunology
Min-Sub Lee, Steven J. Bensinger
Summary: Cholesterol plays a critical role in maintaining the integrity, fluidity, and biochemical function of mammalian cells. Macrophages can rapidly reprogram their cholesterol metabolism in response to immune activation signals. This review discusses current knowledge of cellular cholesterol homeostasis and highlights the reprogramming of cholesterol metabolism in macrophages during immune responses. It also explores the effects of these changes on sensitivity to microbial toxins and the potential therapeutic applications in diseases associated with tissue damage caused by cholesterol-dependent toxins.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Review
Hematology
Helin Tercan, Niels P. Riksen, Leo A. B. Joosten, Mihai G. Netea, Siroon Bekkering
Summary: Trained immunity is a persistent hyperresponsive phenotype developed by innate immune cells after stimulation, causing cells to remember pathogens and endogenous molecules. While providing cross-protection in infectious diseases, trained immunity may lead to excessive immune responses in diseases driven by chronic systemic inflammation.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Review
Hematology
Robin P. Choudhury, Laurienne Edgar, Mikael Ryden, Edward A. Fisher
Summary: Physiological functions are intricately intertwined, with evidence from immunometabolism field showing that cells can be programmed by changes in metabolic environment through epigenetic modifications, causing persistent changes. Understanding these processes can have significant implications for the diagnosis and treatment of diabetes and related metabolic states.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Yifei Chen, Fangpu Yu, Yu Zhang, Mengmeng Li, Mingxue Di, Weijia Chen, Xiaolin Liu, Yun Zhang, Mei Zhang
Summary: Tongxinluo (TXL) is a traditional Chinese medication that plays a key role in the formation and progression of atherosclerotic plaques by inhibiting lipid deposition through enhancing autophagy in macrophages. It also reverses the inhibitory effect of class I histone deacetylases on the expression of Beclin-1.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Chunhua Liu, Wei Zhang, Guozheng Xu, Daolai Zhang, Cheng Zhang, Sen Qiao, Zhimei Wang, Hongmei Wang
Summary: The risk of high-grade gliomas in women increases after menopause, potentially due to hormone fluctuations. Aging of the brain after menopause is associated with glioma risk, as confirmed by proteomics and the MALDI-MSI experiment.
Article
Multidisciplinary Sciences
Chenglong Sun, Anqiang Wang, Yanhe Zhou, Panpan Chen, Xiangyi Wang, Jianpeng Huang, Jiamin Gao, Xiao Wang, Liebo Shu, Jiawei Lu, Wentao Dai, Zhaode Bu, Jiafu Ji, Jiuming He
Summary: This study explores the spatial signature of metabolic remodeling in gastric cancer by integrating mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics, allowing for the visualization of metabolic heterogeneity. Mapping tumor metabolic remodeling and its interaction with non-tumor cells improves our understanding of tumor biology and helps in designing advanced therapeutic strategies.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Katherine A. Robinson, Naveed Akbar, Kajus Baidzajevas, Robin P. Choudhury
Summary: Metabolic diseases are associated with inflammation, which negatively affects cardiovascular health. Evidence shows that long-term hyperactivation of innate immune cells and their bone marrow progenitors, known as trained immunity, accelerates atherosclerosis in cardiometabolic diseases. Understanding the mechanisms of trained immunity can lead to the development of novel therapies for reducing cardiovascular risk in metabolic diseases.
Article
Immunology
Yan Li, Qingshan Ma, Xiaoyuan Shi, Guiqin Liu, Changfa Wang
Summary: This study explored the differences in gut microbiome and differentially expressed genes related to lipid metabolism and the immune system in the donkey hindgut. The study found significant differences in dominant bacteria among different sections of the hindgut, particularly between the cecum and dorsal colon sites. It also identified interesting DEGs related to lipid metabolism and the immune system, with the PPAR pathway being mainly enriched in the cecum. Furthermore, the study revealed a complex relationship between the gut microbiome and gene expression, especially in relation to the immune system.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Environmental Sciences
Junchao Duan, Qinglin Sun, Shiqian Liu, Lisen Lin, Xiaoke Ren, Tianyu Li, Qing Xu, Zhiwei Sun
Summary: This study investigated the impact of PM2.5 and a high-fat diet on atherosclerosis and cardiovascular disease. The results showed that co-exposure to PM2.5 and a high-fat diet led to lipid deposition and vascular dysfunction, along with endoplasmic reticulum stress and immune system activation. Furthermore, the lipid and atherosclerosis signaling pathways played a critical role in PM2.5-induced vascular injury.
ENVIRONMENTAL POLLUTION
(2022)
Article
Veterinary Sciences
Zhiwei Kong, Bin Li, Chuanshe Zhou, Qinghua He, Yuzhong Zheng, Zhiliang Tan
Summary: This experiment revealed the mechanism of hypoxia adaptation, showing that hypoxia exposure is associated with elevated glycerophospholipid metabolism mediated by AGPAT2, leading to lipid disorders and apoptosis. These findings update the understanding of increased adaptability of dairy cows exposed to hypoxia at the metabolic level.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Engineering, Biomedical
Lili Cheng, Peng Zhang, Yadong Liu, Zhuoyin Liu, Junjie Tang, Langtao Xu, Jie Liu
Summary: Due to the immunosuppressive tumor microenvironment (ITM), immune checkpoint blockade and vaccine therapies often lead to an inadequate immune response. However, the activation of the STING pathway through the use of multifunctional hybrid exosomes has shown promising results in enhancing cancer immunotherapy. These hybrid exosomes can induce polarization of tumor-associated macrophages (TAMs) to the M1 phenotype, release DNA-targeting agents to induce DNA damage, and stimulate cGAS/STING activation, resulting in significant anti-tumor and antimetastatic efficacy.
Article
Cell Biology
Yun Zhao, Zhongshun Liu, Guoqiang Liu, Yuting Zhang, Sheng Liu, Dailin Gan, Wennan Chang, Xiaoxia Peng, Eun Suh Sung, Keegan Gilbert, Yini Zhu, Xuechun Wang, Ziyu Zeng, Hope Baldwin, Guanzhu Ren, Jessica Weaver, Anna Huron, Toni Mayberry, Qingfei Wang, Yujue Wang, Maria Elena Diaz-Rubio, Xiaoyang Su, M. Sharon Stack, Siyuan Zhang, Xuemin Lu, Ryan D. Sheldon, Jun Li, Chi Zhang, Jun Wan, Xin Lu
Summary: Tumor-infiltrating neutrophils (TINs) escape ferroptosis through the Acod1-dependent immunometabolism switch and promote metastasis. Inhibition of Acod1 reduces TIN infiltration, enhances antitumor T cell immunity, and improves the efficacy of immune checkpoint blockade.
Article
Gastroenterology & Hepatology
Yanru Ma, Xinyu Zhang, Baoqin Xuan, Danjie Li, Nan Yin, Lijun Ning, Yi-Lu Zhou, Yuqing Yan, Tianying Tong, Xiaoqiang Zhu, Xiaowen Huang, Muni Hu, Zhenhua Wang, Zhe Cui, Huabin Li, Jiqiu Wang, Jing-Yuan Fang, Ruixin Liu, Haoyan Chen, Jie Hong
Summary: FTO downregulation promotes UC by decreasing CerS6 expression, resulting in increased S1P accumulation in IECs and exacerbating colitis via m6A-dependent mechanisms. UC patients with lower FTO expression may have a better response to vedolizumab treatment.
Review
Hematology
Isidoro Cobo, Tiffany Tanaka, Christopher K. Glass, Calvin Yeang
Summary: Recent studies have characterized abnormal inflammatory signaling as a result of DNMT3A and TET2 deficiency in monocytes and macrophages, immune cells with prominent roles in atherosclerosis. While specific DNA methylation signatures associated with these known epigenetic regulators have been identified, diverse modulatory functions of DNMT3A and TET2 have also been characterized, urging further cell and context-specific experimental studies to define how DNMT3A and TET2 may nonenzymatically activate inflammatory pathways with clinically meaningful consequences.CHIP, common in elderly individuals, provides an opportunity to understand and potentially modify age-related chronic inflammatory ASCVD risk.
CURRENT OPINION IN HEMATOLOGY
(2022)
Article
Immunology
Isidoro Cobo, Tiffany N. Tanaka, Kailash Chandra Mangalhara, Addison Lana, Calvin Yeang, Claudia Han, Johannes Schlachetzki, Jean Challcombe, Bethany R. Fixsen, Mashito Sakai, Rick Z. Li, Hannah Fields, Michal Mokry, Randy G. Tsai, Rafael Bejar, Koen Prange, Menno de Winther, Gerald S. Shadel, Christopher K. Glass
Summary: Loss of function mutations in DNMT3A and TET2 result in a type I interferon response, leading to increased risk of cardiovascular disease. These mutations impair mitochondrial DNA integrity and activate the cGAS signaling pathway. DNMT3A and TET2 regulate the expression of transcription factor A mitochondria by interacting with RBPJ and ZNF143, thereby maintaining mitochondrial DNA integrity.
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
Cell Biology
Larissa Traxler, Joseph R. Herdy, Davide Stefanoni, Sophie Eichhorner, Silvia Pelucchi, Attila Szucs, Alice Santagostino, Yongsung Kim, Ravi K. Agarwal, Johannes C. M. Schlachetzki, Christopher K. Glass, Jessica Lagerwall, Douglas Galasko, Fred H. Gage, Angelo D'Alessandro, Jerome Mertens
Summary: This study investigated the metabolic changes and transcriptional alterations in sporadic Alzheimer's disease (AD) utilizing induced neurons (iNs) from AD patients. The pathological isoform switching of PKM2 was found to contribute to neuronal vulnerability and loss in AD. Chemical modulation of PKM2 could reverse these changes and enhance neuronal resilience against cell death.
Article
Immunology
Zsolt Czimmerer, Laszlo Halasz, Bence Daniel, Zsofia Varga, Krisztian Bene, Apolka Domokos, Marten Hoeksema, Zeyang Shen, Wilhelm K. Berger, Timea Cseh, Karoly Jambrovics, Zsuzsanna Kolostyak, Ferenc Fenyvesi, Judit Varadi, Szilard Poliska, Gyorgy Hajas, Istvan Szatmari, Christopher K. Glass, Attila Bacsi, Laszlo Nagy
Summary: Prior exposure to microenvironmental signals can alter the response of macrophages. IL-4-polarized macrophages were found to exhibit hyperinflammatory gene expression upon LPS exposure, contrary to previous beliefs. This extended synergy was supported by epigenomic remodeling, NF-kappa B-p65 cistrome expansion, and increased enhancer activity.
Article
Neurosciences
Kristina Battis, Jazmin B. Florio, Michael Mante, Addison Lana, Isabel Naumann, Carina Gauer, Vera Lambrecht, Simon Julian Mueller, Isidoro Cobo, Bethany Fixsen, Ha Yeon Kim, Eliezer Masliah, Christopher K. Glass, Johannes C. M. Schlachetzki, Robert A. Rissman, Juergen Winkler, Alana Hoffmann
Summary: This study reveals the complex role of myeloid cells in multiple system atrophy and emphasizes the importance of balancing their beneficial and adverse effects before clinical translation.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Clinical Neurology
Fatemeh Seifar, Ashok R. Dinasarapu, H. A. Jinnah
Summary: Numerous studies have found an association between low levels of uric acid (UA) and Parkinson's disease (PD), suggesting that low UA may contribute to oxidative stress and the degeneration of dopamine neurons, leading to the onset and progression of PD symptoms. However, recent research has raised questions about this explanation, proposing that low UA may be a biomarker rather than a causative factor for PD.
MOVEMENT DISORDERS
(2022)
Review
Gastroenterology & Hepatology
Daniel Q. Huang, Michael Downes, Ronald M. Evans, Joseph L. Witztum, Christopher K. Glass, Rohit Loomba
Summary: The global burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with individuals with NAFLD at higher risk for cardiovascular disease, sharing multiple disease mechanisms.
SEMINARS IN LIVER DISEASE
(2022)
Article
Cell & Tissue Engineering
Joseph R. Herdy, Larissa Traxler, Ravi K. Agarwal, Lukas Karbacher, Johannes C. M. Schlachetzki, Lena Boehnke, Dina Zangwill, Doug Galasko, Christopher K. Glass, Jerome Mertens, Fred H. Gage
Summary: The concept of senescence extends beyond proliferating cells, as senescence-like features have been observed in neurons, including those affected by Alzheimer's disease. Targeting senescent neurons could be a strategy for preventing or treating AD.
Article
Neurosciences
Johannes C. M. Schlachetzki, Yi Zhou, Christopher K. Glass
Summary: Cognitive impairment is prevalent in individuals with HIV despite antiretroviral therapy, with evidence suggesting that the brain may serve as a sanctuary for HIV persistence. Recent advances in understanding the diversity of microglia in HIV, including their epigenome, transcriptome, and function, highlight their potential role in driving HIV-associated neurocognitive disorders.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kei-ichiro Arimoto, Sayuri Miyauchi, Ty D. Troutman, Yue Zhang, Mengdan Liu, Samuel A. Stoner, Amanda G. Davis, Jun-Bao Fan, Yi-Jou Huang, Ming Yan, Christopher K. Glass, Dong-Er Zhang
Summary: Immunotherapy is an effective cancer treatment, but not for all patients, prompting the need for alternative strategies. Inducing cancer immunogenic cell death (ICD) shows promise in promoting robust immune responses against tumor-associated antigens. Depletion of USP18, a negative regulator of interferon signaling, selectively induces ICD in cancer cells, suggesting targeting USP18 as a potential cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Reem Abdel-Haq, Johannes C. M. Schlachetzki, Joseph C. Boktor, Thaisa M. Cantu-Jungles, Taren Thron, Mengying Zhang, John W. Bostick, Tahmineh Khazaei, Sujatha Chilakala, Livia H. Morais, Greg Humphrey, Ali Keshavarzian, Jonathan E. Katz, Matthew Thomson, Rob Knight, Viviana Gradinaru, Bruce R. Hamaker, Christopher K. Glass, Sarkis K. Mazmanian
Summary: Parkinson's disease is a movement disorder characterized by neuroinflammation, alpha-synuclein pathology, and neurodegeneration. The gut microbiome, which is altered in PD, may impact motor and GI symptoms. Feeding a prebiotic high-fiber diet can improve motor deficits and reduce alpha-synuclein aggregation in PD-like mice, potentially through its effects on the gut microbiome and microglial activation.
Article
Cell Biology
Kaitlyn M. Roman, Ashok R. Dinasarapu, Alison Vanschoiack, P. Martin Ross, David Kroeppler, H. A. Jinnah, Ellen J. Hess
Summary: The dorsal striatum is organized into functional territories based on corticostriatal inputs onto SPNs. The molecular identity of SPNs is mediated by differentially expressed genes across striatal territories, revealing heterogeneity in gene expression related to synaptic function in both direct and indirect SPNs. Understanding the complex spatiomolecular organization of the striatum is crucial for studying normal function and region-specific dysfunction in striatal disorders.
Review
Neurosciences
Rosa C. Paolicelli, Amanda Sierra, Beth Stevens, Marie-Eve Tremblay, Adriano Aguzzi, Bahareh Ajami, Ido Amit, Etienne Audinat, Ingo Bechmann, Mariko Bennett, Frederick Bennett, Alain Bessis, Knut Biber, Staci Bilbo, Mathew Blurton-Jones, Erik Boddeke, Dora Brites, Bert Brone, Guy C. Brown, Oleg Butovsky, Monica J. Carson, Bernardo Castellano, Marco Colonna, Sally A. Cowley, Colm Cunningham, Dimitrios Davalos, Philip L. De Jager, Bart de Strooper, Adam Denes, Bart J. L. Eggen, Ukpong Eyo, Elena Galea, Sonia Garel, Florent Ginhoux, Christopher K. Glass, Ozgun Gokce, Diego Gomez-Nicola, Berta Gonzalez, Siamon Gordon, Manuel B. Graeber, Andrew D. Greenhalgh, Pierre Gressens, Melanie Greter, David H. Gutmann, Christian Haass, Michael T. Heneka, Frank L. Heppner, Soyon Hong, David A. Hume, Steffen Jung, Helmut Kettenmann, Jonathan Kipnis, Ryuta Koyama, Greg Lemke, Marina Lynch, Ania Majewska, Marzia Malcangio, Tarja Malm, Renzo Mancuso, Takahiro Masuda, Michela Matteoli, Barry W. McColl, Veronique E. Miron, Anna Victoria Molofsky, Michelle Monje, Eva Mracsko, Agnes Nadjar, Jonas J. Neher, Urte Neniskyte, Harald Neumann, Mami Noda, Bo Peng, Francesca Peri, V. Hugh Perry, Phillip G. Popovich, Clare Pridans, Josef Priller, Marco Prinz, Davide Ragozzino, Richard M. Ransohoff, Michael W. Salter, Anne Schaefer, Dorothy P. Schafer, Michal Schwartz, Mikael Simons, Cody J. Smith, Wolfgang J. Streit, Tuan Leng Tay, Li-Huei Tsai, Alexei Verkhratsky, Rommy von Bernhardi, Hiroaki Wake, Valerie Wittamer, Susanne A. Wolf, Long-Jun Wu, Tony Wyss-Coray
Summary: Microglial research has made significant progress, but the current classification system fails to accurately describe their diversity, leading to misconceptions about their functions. To address this issue, a group of multidisciplinary experts has proposed a naming framework and recommendations to help researchers better understand and describe the different states and functions of microglia.
Meeting Abstract
Clinical Neurology
Emily Hansen, Anna S. Warden, Cristina Mora, Gabriela Ramirez, Samantha Mak, Sanjana Narayan, Samantha Trescott, Shreya Shriram, Zahara Keulen, Christopher K. Glass, Nicole G. Coufal
ANNALS OF NEUROLOGY
(2022)