bims-stacyt Biomed News
on Metabolism and the paracrine crosstalk between cancer and the organism
Issue of 2024‒09‒08
thirteen papers selected by
Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models.
  2. Immunological roles for resistin and related adipokines in obesity-associated tumors.
  3. Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes.
  4. Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.
  5. FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation.
  6. Protocol for establishing and evaluating a cancer cachexia mouse model.
  7. MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development.
  8. TREM2 Impairs Glycolysis to Interrupt Microglial M1 Polarization and Inflammation via JAK2/STAT3 Axis.
  9. Bioactive sphingolipids as emerging targets for signal transduction in cancer development.
  10. Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment.
  11. Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.
  12. A comprehensive review of animal models for cancer cachexia: Implications for translational research.
  13. CTGF regulated by ATF6 inhibits vascular endothelial inflammation and reduces hepatic ischemia-reperfusion injury.
  1. J Clin Invest. 2024 Sep 03. pii: e177606. [Epub ahead of print]134(17):
    Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models.
    Svena Verma, Sadna Budhu, Inna Serganova, Lauren Dong, Levi M Mangarin, Jonathan F Khan, Mamadou A Bah, Anais Assouvie, Yacine Marouf, Isabell Schulze, Roberta Zappasodi, Jedd D Wolchok, Taha Merghoub.
      Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy is more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor lactate efflux and enhanced glucose availability within the tumor microenvironment (TME). LDH inhibitors (LDHi) reduce glucose uptake and tumor growth in preclinical models, but their impact on tumor-infiltrating T cells is not fully elucidated. Tumor cells have higher basal LDH expression and glycolysis levels compared with infiltrating T cells, creating a therapeutic opportunity for tumor-specific targeting of glycolysis. We demonstrate that LDHi treatment (a) decreases tumor cell glucose uptake, expression of the glucose transporter GLUT1, and tumor cell proliferation while (b) increasing glucose uptake, GLUT1 expression, and proliferation of tumor-infiltrating T cells. Accordingly, increasing glucose availability in the microenvironment via LDH inhibition leads to improved tumor-killing T cell function and impaired Treg immunosuppressive activity in vitro. Moreover, combining LDH inhibition with immune checkpoint blockade therapy effectively controls murine melanoma and colon cancer progression by promoting effector T cell infiltration and activation while destabilizing Tregs. Our results establish LDH inhibition as an effective strategy for rebalancing glucose availability for T cells within the TME, which can enhance T cell function and antitumor immunity.
    Keywords:  Cancer immunotherapy; Glucose metabolism; Immunology; Metabolism; Pharmacology
    DOI:  https://doi.org/10.1172/JCI177606
  2. Int Immunopharmacol. 2024 Sep 03. pii: S1567-5769(24)01432-2. [Epub ahead of print]142(Pt A): 112911
    Immunological roles for resistin and related adipokines in obesity-associated tumors.
    Jingxin Zhang, Enting Lu, Lei Deng, Yaoxuan Zhu, Xiaoqing Lu, Xinyuan Li, Fangmei Li, Yan Yan, Jing-Yan Han, Yin Li, Yi Zhang.
      Rationale Obesity is an independent risk factor for the occurrence and development of tumors. Obesity is influenced by signaling of adipokines, which are secreted factors from adipocytes and resident immune cells within adipose tissues that mediate lipid metabolism. More recently, adipokines have been implicated in chronic inflammation as well as in tumor formation and growth. Among them, resistin has received increasing attention in research related to the growth and expansion of solid tumors and hematological cancers through various signaling pathways. Objective and findings We reviewed the physiological, biochemical, and immune functions of adipose tissue, with a focus on the structure and expression of resistin and adipokines within multiple adipose cell types, their signaling pathways and putative effects on tumor cells, as well as their in vivo regulation. Current evidence indicates that adipokines such as resistin act as pro-inflammatory factors to stimulate immune cells which, in turn, promotes tumor angiogenesis, connective tissue proliferation, and matrix fibrosis. Concurrently, in states of metabolic dysfunction and lipotoxicity in obese individuals, the numbers and functions of immune cells are compromised, leading to an immunosuppressive environment that fosters tumor cell survival and weak cancer immune monitoring. Conclusion Adipokines such as resistin are important to the development of obesity-related tumors. Clarifying the roles for obesity-related factors in immune regulation and tumor progression may lead to the discovery of novel anti-tumor strategies for targeting obesity factors such as resistin to limit tumor growth and manage obesity, or both.
    Keywords:  Adipokine; Adipose tissue; Immunological function; Obesity; Obesity-associated tumors; Resistin
    DOI:  https://doi.org/10.1016/j.intimp.2024.112911
  3. iScience. 2024 Aug 16. 27(8): 110544
    Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes.
    Atsushi Tanaka, Makiko Ogawa, Yihua Zhou, Yusuke Otani, Ronald C Hendrickson, Matthew M Miele, Zhuoning Li, David S Klimstra, Julia Y Wang, Michael H Roehrl.
      Pancreatic neuroendocrine tumors (PanNETs) represent well-differentiated endocrine neoplasms with variable clinical outcomes. Predicting patient outcomes using the current tumor grading system is challenging. In addition, traditional systemic treatment options for PanNETs, such as somatostatin analogs or cytotoxic chemotherapies, are very limited. To address these issues, we characterized PanNETs using integrated proteogenomics and identified four subtypes. Two proteomic subtypes showed high recurrence rates, suggesting clinical aggressiveness that was missed by current classification. Hypoxia and inflammatory pathways were significantly enriched in the clinically aggressive subtypes. Detailed analyses revealed metabolic adaptation via glycolysis upregulation and oxidative phosphorylation downregulation under hypoxic conditions. Inflammatory signature analysis revealed that immunosuppressive molecules were enriched in immune hot tumors and might be immunotherapy targets. In this study, we characterized clinically aggressive proteomic subtypes of well-differentiated PanNETs and identified candidate therapeutic targets.
    Keywords:  Cancer; Cancer systems biology; Genomics; Proteomics
    DOI:  https://doi.org/10.1016/j.isci.2024.110544
  4. Biomark Res. 2024 Sep 03. 12(1): 96
    Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment.
    Haixia Zhang, Shizhen Li, Dan Wang, Siyang Liu, Tengfei Xiao, Wangning Gu, Hongmin Yang, Hui Wang, Minghua Yang, Pan Chen.
      Tumor cells possess complex immune evasion mechanisms to evade immune system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) to modulate immune cell functions. When a tumor is sufficiently immunogenic, it can activate cytotoxic T-cells to target and destroy it. However, tumors adapt by manipulating their metabolic pathways, particularly glucose, amino acid, and lipid metabolism, to create an immunosuppressive TME that promotes immune escape. These metabolic alterations impact the function and differentiation of non-tumor cells within the TME, such as inhibiting effector T-cell activity while expanding regulatory T-cells and myeloid-derived suppressor cells. Additionally, these changes lead to an imbalance in cytokine and chemokine secretion, further enhancing the immunosuppressive landscape. Emerging research is increasingly focusing on the regulatory roles of non-tumor cells within the TME, evaluating how their reprogrammed glucose, amino acid, and lipid metabolism influence their functional changes and ultimately aid in tumor immune evasion. Despite our incomplete understanding of the intricate metabolic interactions between tumor and non-tumor cells, the connection between these elements presents significant challenges for cancer immunotherapy. This review highlights the impact of altered glucose, amino acid, and lipid metabolism in the TME on the metabolism and function of non-tumor cells, providing new insights that could facilitate the development of novel cancer immunotherapies.
    Keywords:  Immune evasion; Immunotherapy; Metabolic reprogramming; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s40364-024-00646-1
  5. Front Microbiol. 2024 ;15 1456108
    FGF21 upregulation by hepatitis C virus via the eIF2α-ATF4 pathway: implications for interferon signaling suppression and TRIM31-mediated TSC degradation.
    Liang Liu, Masahiko Ito, Satoshi Sakai, Jie Liu, Kazuyoshi Ohta, Kenji Saito, Kenji Nakashima, Shinya Satoh, Alu Konno, Tetsuro Suzuki.
      Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases and is known to induce endoplasmic reticulum (ER) stress, which alters cellular homeostasis and metabolic processes. While ER stress is implicated in HCV-related diseases, its precise role remains unclear. This study identifies fibroblast growth factor 21 (FGF21) as a key host factor significantly upregulated by HCV infection. Mechanistic analyses reveal that the activation of the FGF21 promoter by HCV is primarily mediated by the transcription factor ATF4, which is upregulated through the phosphorylation of eIF2α induced by ER stress. Additionally, CREBH activation further enhances ATF4 expression, contributing to increased FGF21 levels. TRIB3, upregulated by ATF4, acts as a negative regulator of FGF21 expression. The study also identifies FGF21-dependent upregulation of SOCS2 and TRIM31 in HCV-infected cells. SOCS2 contributes to the suppression of type 1 interferon signaling, aiding viral persistence, while TRIM31 promotes the degradation of the tumor suppressor protein TSC, activating the mTORC1 pathway and potentially promoting liver cell proliferation. These findings suggest that FGF21 upregulation in HCV-infected cells may play a role in both immune response regulation and cell proliferation, contributing to sustained viral infection and disease progression.
    Keywords:  ATF4; CREBH; ER stress; FGF21; SOCS2; TRIM31; hepatitis C virus
    DOI:  https://doi.org/10.3389/fmicb.2024.1456108
  6. STAR Protoc. 2024 Aug 31. pii: S2666-1667(24)00446-5. [Epub ahead of print]5(3): 103281
    Protocol for establishing and evaluating a cancer cachexia mouse model.
    Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yu Ren, Xiuhui Shi, Yang Cai, Alex X Arreola, Yi-Ping Li, Yuqing Zhang, Min Li.
      Cancer cachexia mouse models are needed to recapitulate the clinical features of patients with cachexia. Here, we present a protocol for the establishment and evaluation of cancer cachexia mouse models. We delineate the steps in preparing tumor cells for inoculation and surgical procedures. After the establishment of these mouse models, we describe essential techniques to assess cancer cachexia, including grip strength evaluation, tissue collection, and the calculation of cross-sectional areas of muscle tissue. For complete details on the use and execution of this protocol, please refer to Liu et al.,1 Yang et al.,2 Shi et al.,3 and Zhou et al.4.
    Keywords:  Cancer; Cell Biology; Cell culture; Health Sciences; Metabolism; Model Organisms; Systems biology
    DOI:  https://doi.org/10.1016/j.xpro.2024.103281
  7. Cancer Res. 2024 Sep 06.
    MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development.
    Jane Ding, Mohit Bansal, Yuxia Cao, Bingwei Ye, Rui Mao, Anamika Gupta, Sunil Sudarshan, Han-Fei Ding.
      Pseudouridylation is a common RNA modification that is catalyzed by the family of pseudouridine synthases (PUS). Pseudouridylation can increase RNA stability and rigidity, thereby impacting RNA splicing, processing, and translation. Given that RNA metabolism is frequently altered in cancer, pseudouridylation may be a functionally important process in tumor biology. Here, we showed that the MYC family of oncoproteins transcriptionally upregulates PUS7 expression during cancer development. PUS7 was essential for the growth and survival of MYC-driven cancer cells and xenografts by promoting adaptive stress responses and amino acid biosynthesis and import. ATF4, a master regulator of stress responses and cellular metabolism, was identified as a key downstream mediator of PUS7 functional activity. Induction of ATF4 by MYC oncoproteins and cellular stress required PUS7, and ATF4 overexpression overcame the growth inhibition caused by PUS7 deficiency. Mechanistically, PUS7 induced pseudouridylation of MCTS1 mRNA, which enhanced its translation. MCTS1, a noncanonical translation initiation factor, drove stress-induced ATF4 protein expression. A PUS7 consensus pseudouridylation site in the 3' untranslated region of ATF4 mRNA was crucial for the induction of ATF4 by cellular stress. These findings unveil a MYC-activated mRNA pseudouridylation program that mitigates cellular stress induced by MYC stimulation of proliferation and biomass production, suggesting that targeting PUS7 could be therapeutic strategy selectively against MYC-driven cancers.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-24-1102
  8. Cell Biochem Biophys. 2024 Sep 06.
    TREM2 Impairs Glycolysis to Interrupt Microglial M1 Polarization and Inflammation via JAK2/STAT3 Axis.
    Chanyuan Liu, Xueying Zhou.
      Cerebral ischemia/reperfusion injury (IRI) is a primary pathophysiological basis of ischemic stroke, a dreadful cerebrovascular event carrying substantial disability and lethality. Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane glycoprotein that has been notified as a protective factor for cerebral ischemic stroke. On this basis, the paper is thereby goaled to interpret the probable activity and downstream mechanism of TREM2 against cerebral IRI. Cerebral IRI was simulated in murine microglial BV2 cells under oxygen-glucose deprivation and reperfusion (OGD/R) conditions. Western blotting ascertained the expressions of TREM2 and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis-associated proteins. ELISA and RT-qPCR assayed the secretion of inflammatory cytokines. Immunofluorescence and western blotting estimated macrophage polarization. Glycolysis activation was measured through evaluating lactic acid and extracellular acidification rate (ECAR). RT-qPCR and western blotting examined the expressions of glycolytic genes. TREM2 was abnormally expressed and JAK2/STAT3 axis was aberrantly activated in BV2 cells in response to OGD/R. Elevation of TREM2 repressed the inflammatory reaction and glycolysis, inhibited the JAK2/STAT3 axis, whereas promoted M1-to-M2 polarization in OGD/R-injured BV2 cells. Upregulated TREM2 inactivated the glycolytic pathway to relieve OGD/R-induced inflammatory injury and M1 macrophage polarization. Besides, STAT3 activator, colivelin, aggravated the glycolysis, inflammatory injury and drove M1-like macrophage polarization in TREM2-overexpressing BV2 cells exposed to OGD/R. Collectively, TREM2 might produce anti-inflammatory potential in cerebral IRI, which might dependent on the inactivation of glycolytic pathway via intermediating the JAK2/STAT3 axis.
    Keywords:  Glycolysis; JAK2/STAT3 axis; M1/M2 polarization; Microglia; OGD/R; TREM2
    DOI:  https://doi.org/10.1007/s12013-024-01520-5
  9. Biochim Biophys Acta Rev Cancer. 2024 Sep 02. pii: S0304-419X(24)00107-0. [Epub ahead of print]1879(5): 189176
    Bioactive sphingolipids as emerging targets for signal transduction in cancer development.
    Wentao Jia, Jiaying Yuan, Jinbo Zhang, Shu Li, Wanfu Lin, Binbin Cheng.
      Sphingolipids, crucial components of cellular membranes, play a vital role in maintaining cellular structure and signaling integrity. Disruptions in sphingolipid metabolism are increasingly implicated in cancer development. Key bioactive sphingolipids, such as ceramides, sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glycosphingolipids, profoundly impact tumor biology. They influence the behavior of tumor cells, stromal cells, and immune cells, affecting tumor aggressiveness, angiogenesis, immune modulation, and extracellular matrix remodeling. Furthermore, abnormal expression of sphingolipids and their metabolizing enzymes modulates the secretion of tumor-derived extracellular vesicles (TDEs), which are key players in creating an immunosuppressive tumor microenvironment, remodeling the extracellular matrix, and facilitating oncogenic signaling within in situ tumors and distant pre-metastatic niches (PMNs). Understanding the role of sphingolipids in the biogenesis of tumor-derived extracellular vesicles (TDEs) and their bioactive contents can pave the way for new biomarkers in cancer diagnosis and prognosis, ultimately enhancing comprehensive tumor treatment strategies.
    Keywords:  Ceramides; Gangliosides; Sphingolipids; Tumor-derived extracellular vesicles
    DOI:  https://doi.org/10.1016/j.bbcan.2024.189176
  10. Cell Rep. 2024 Aug 31. pii: S2211-1247(24)01048-9. [Epub ahead of print]43(9): 114697
    Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment.
    Zhiwen Luo, Jie Mei, Xianwen Wang, Ruixin Wang, Zhao He, Yifat Geffen, Xiaomeng Sun, Xingyu Zhang, Junying Xu, Renwen Wan, Xinting Feng, Chunmeng Jiao, Xiaoping Su, Junming Sun, Shiyi Chen, Jiwu Chen, Wenjun Mao, Yunlong Yang, Yaying Sun.
      Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.
    Keywords:  CP: Cancer; CP: Immunology; extracellular matrix; immunotherapy; microRNA; tumor immune microenvironment; voluntary exercise
    DOI:  https://doi.org/10.1016/j.celrep.2024.114697
  11. Nat Genet. 2024 Sep 03.
    Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.
    Carina Shiau, Jingyi Cao, Dennis Gong, Mark T Gregory, Nicholas J Caldwell, Xunqin Yin, Jae-Won Cho, Peter L Wang, Jennifer Su, Steven Wang, Jason W Reeves, Tae Kyung Kim, Youngmi Kim, Jimmy A Guo, Nicole A Lester, Jung Woo Bae, Ryan Zhao, Nathan Schurman, Jamie L Barth, Maria L Ganci, Ralph Weissleder, Tyler Jacks, Motaz Qadan, Theodore S Hong, Jennifer Y Wo, Hannah Roberts, Joseph M Beechem, Carlos Fernandez-Del Castillo, Mari Mino-Kenudson, David T Ting, Martin Hemberg, William L Hwang.
      In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identified enrichment in interleukin-6 family signaling that functionally confers resistance to chemotherapy. Overall, this study demonstrates that characterization of the tumor microenvironment using single-cell spatial transcriptomics allows for the identification of molecular interactions that may play a role in the emergence of therapeutic resistance and offers a spatially based analysis framework that can be broadly applied to other contexts.
    DOI:  https://doi.org/10.1038/s41588-024-01890-9
  12. Genes Dis. 2024 Nov;11(6): 101080
    A comprehensive review of animal models for cancer cachexia: Implications for translational research.
    Li Li, Junaid Wazir, Zhiqiang Huang, Yong Wang, Hongwei Wang.
      Cancer cachexia is a multifactorial syndrome characterized by progressive weight loss and a disease process that nutritional support cannot reverse. Although progress has been made in preclinical research, there is still a long way to go in translating research findings into clinical practice. One of the main reasons for this is that existing preclinical models do not fully replicate the conditions seen in clinical patients. Therefore, it is important to understand the characteristics of existing preclinical models of cancer cachexia and pay close attention to the latest developments in preclinical models. The main models of cancer cachexia used in current research are allogeneic and xenograft models, genetically engineered mouse models, chemotherapy drug-induced models, Chinese medicine spleen deficiency models, zebrafish and Drosophila models, and cellular models. This review aims to revisit and summarize the commonly used animal models of cancer cachexia by evaluating existing preclinical models, to provide tools and support for translational medicine research.
    Keywords:  Animal model; Cancer cachexia; Muscle atrophy; Preclinical model; Weight loss
    DOI:  https://doi.org/10.1016/j.gendis.2023.101080
  13. Biochim Biophys Acta Mol Basis Dis. 2024 Sep 03. pii: S0925-4439(24)00484-8. [Epub ahead of print]1870(8): 167490
    CTGF regulated by ATF6 inhibits vascular endothelial inflammation and reduces hepatic ischemia-reperfusion injury.
    Dong-Jing Yang, Yang Bai, Min Wu, Yin-Ming Liang, Bin-Hui Zhou, Wenzhi Guo, Shui-Jun Zhang, Ji-Hua Shi.
      Vascular endothelial inflammation is crucial in hepatic ischemia-reperfusion injury (IRI). Our previous research has shown that connective tissue growth factor (CTGF), secreted by endothelial cells, protects against acute liver injury, but its upstream mechanism is unclear. We aimed to clarify the protective role of CTGF in endothelial cell inflammation during IRI and reveal the regulation between endoplasmic reticulum stress-induced activating transcription factor 6 (ATF6) and CTGF. Hypoxia/reoxygenation in endothelial cells, hepatic IRI in mice and clinical specimens were used to examine the relationships between CTGF and inflammatory factors and determine how ATF6 regulates CTGF and reduces damage. We found that activating ATF6 promoted CTGF expression and reduced liver damage in hepatic IRI. In vitro, activated ATF6 upregulated CTGF and downregulated inflammation, while ATF6 inhibition had the opposite effect. Dual-luciferase assays and chromatin immunoprecipitation confirmed that activated ATF6 binds to the CTGF promoter, enhancing its expression. Activated ATF6 increases CTGF and reduces extracellular regulated protein kinase 1/2 (ERK1/2) phosphorylation, decreasing inflammatory factors. Conversely, inhibiting ATF6 decreases CTGF and increases the phosphorylation of ERK1/2, increasing inflammatory factor levels. ERK1/2 inhibition reverses this effect. Clinical samples have shown that CTGF increases after IRI, inversely correlating with inflammatory cytokines. Therefore, ATF6 activation during liver IRI enhances CTGF expression and reduces endothelial inflammation via ERK1/2 inhibition, providing a novel target for diagnosing and treating liver IRI.
    Keywords:  Activating transcription factor 6; Connective tissue growth factor; Hepatic ischemia–reperfusion injury; Vascular endothelial inflammation
    DOI:  https://doi.org/10.1016/j.bbadis.2024.167490
This page is being maintained by Thomas Krichel. It was last updated on 2024‒10‒20 at 13:37.