Article
Immunology
Zi-Chen Li, Fang-Fang Xu, Jiang-Tao Fu, Shen-Xi Ouyang, Qi Cao, Yu-Ying Yan, Dong-Jie Li, Fu-Ming Shen, Min Ni
Summary: This study reveals the crucial role of STING in acetaminophen-induced acute liver injury and suggests that inhibiting the STING-NLRP3 pathway could be a potential therapeutic strategy for acute liver injury. The activation of STING and enhanced inflammation were observed in the liver of APAP-overdosed mice, and Sting mutation resulted in less liver damage and changes in immune cell infiltration. Moreover, Sting mutation limited NLRP3 activation and the expression of inflammatory cytokines. The NLRP3 inhibitor MCC950 also showed promising results in ameliorating APAP-induced liver injury and inflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Alexandre Louvet, Line Carolle Ntandja Wandji, Elise Lemaitre, Marion Khaldi, Claire Lafforgue, Florent Artru, Benoit Quesnel, Guillaume Lassailly, Sebastien Dharancy, Philippe Mathurin
Summary: ALI caused by therapeutic doses of APAP is associated with more severe liver injury than overdose, and only occurs in patients with excess drinking and/or fasting.
Article
Biotechnology & Applied Microbiology
Hui Yang, Qilong Cao, Zhixin Yuan, Xianggen Wu, Mengshuang Li
Summary: The study evaluated the feasibility of using DG as a nanocarrier for loading FIT to strengthen treatment against liver injury induced by acetaminophen overdose. Results showed successful fabrication of DG-FIT with excellent physicochemical properties and significant in vivo efficacy.
Article
Chemistry, Multidisciplinary
Madi Sun, Peiyu Chen, Kai Xiao, Xiang Zhu, Zhibin Zhao, Chenyang Guo, Xuan He, Tongfei Shi, Qingguo Zhong, Yong Jia, Yu Tao, Mingqiang Li, Kam W. Leong, Dan Shao
Summary: This study finds that the temporal pattern of circulating cell-free DNA (cfDNA) is strongly associated with damage and inflammation parameters in APAP-induced liver injury (AILI). CfDNA is comparable to ALT in predicting mortality and outperforms ALT when combined with ALT in AILI. Depleting cfDNA or neutrophils alleviates liver damage, while adding cfDNA or adoptive transfer of neutrophils exacerbates the damage. The combination of DNase I and N-acetylcysteine significantly attenuates AILI. This study establishes that cfDNA is a mechanistic biomarker to predict mortality in AILI mice. The combination of scavenging cfDNA and reducing oxidative damage provides a promising treatment for AILI.
Review
Biochemistry & Molecular Biology
Xiaopeng Cai, Huiqiang Cai, Jing Wang, Qin Yang, Jun Guan, Jingwen Deng, Zhi Chen
Summary: This review summarizes three main mechanisms involved in the pathogenesis of acetaminophen-induced liver injury (AILI): hepatocyte necrosis, sterile inflammation, and hepatocyte regeneration. Relevant factors are discussed, and potential treatment options for AILI patients and promising novel strategies are described.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2022)
Review
Cell Biology
En Huang, Shuxin Li
Summary: LKB1, a master kinase of AMPKs and AMPK-related kinases, plays a crucial role in regulating neuronal polarization and neural development. By interacting with downstream signals, LKB1 regulates the polarization and axon branching of neurons. Modulating LKB1 activity is important for repairing an injured nervous system.
Article
Microbiology
Xuewei Sun, Qian Cui, Juan Ni, Xiaoguang Liu, Jin Zhu, Tingting Zhou, HuaYing Huang, Ke OuYang, Yulong Wu, Zhan Yang
Summary: In this study, we found that a monoclonal anti-Toll-like receptor 4 antibody can alleviate APAP-induced acute liver injury through changes in the gut microbiota, metabolic pathways, and gut barrier function. This work suggested that the gut microbiota can be a therapeutic target of APAP-induced acute liver injury, and we performed foundation for further research.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Liam A. McMorrow, Adrian Kosalko, Daniel Robinson, Alberto Saiani, Adam J. Reid
Summary: Patients with major peripheral nerve injury have poor recovery outcomes due to slow axonal regeneration and deterioration in the ability of the distal stump to support axonal growth. Schwann cells play a crucial role in nerve regeneration, but chronic denervation leads to instability in their repair phenotype and hinders regeneration support. Recent research on the cellular machinery, particularly the role of c-Jun, has opened opportunities for therapeutic intervention to support prolonged neural regeneration.
Article
Biochemistry & Molecular Biology
Yasaman Etemadi, Jephte Y. Akakpo, Anup Ramachandran, Hartmut Jaeschke
Summary: Acetaminophen (APAP) overdose can lead to severe liver injury and acute liver failure. The clinically approved antidote, N-acetylcysteine (NAC), has a limited therapeutic window. In this study, the researchers investigated the potential of activating the transcription factor Nrf2 as a treatment for APAP-induced liver injury. They found that short-term treatment with the Nrf2 activator sulforaphane did not effectively activate Nrf2 or protect against liver injury. They also compared the effectiveness of sulforaphane with NAC and found that NAC provided superior protection. These findings suggest that Nrf2 activators may not be suitable for treating APAP overdose compared to NAC.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Qianhui Li, Feng Chen, Fei Wang
Summary: Acute liver failure caused by drug overdose is a significant clinical problem. In addition to the direct toxicity of the drug, inflammation plays a crucial role in the development and severity of the disease. Understanding the involvement of immune cells and their effector molecules is essential for identifying new therapeutic targets.
CELL AND BIOSCIENCE
(2022)
Review
Biotechnology & Applied Microbiology
Benjamin R. Slavin, Karim A. Sarhane, Nicholas von Guionneau, Phillip J. Hanwright, Chenhu Qiu, Hai-Quan Mao, Ahmet Hoke, Sami H. Tuffaha
Summary: IGF-1 shows promise as a therapeutic target for peripheral nerve injuries, with various administration approaches being investigated in the literature. However, further research is needed to determine the optimal dosage ranges for clinical application.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biology
Jinrui Dong, Sivakumar Viswanathan, Eleonora Adami, Sebastian Schafer, Fathima F. Kuthubudeen, Anissa A. Widjaja, Stuart A. Cook
Summary: The study reveals that the synthetic IL6ST binding protein HyperIL6 inhibits IL11-related signaling and toxicities, promoting liver regeneration and suggesting IL11, not IL6, as crucial for this process.
Review
Oncology
Xiaolong Tang, Zaihua Yan, Yandong Miao, Wuhua Ha, Zheng Li, Lixia Yang, Denghai Mi
Summary: Copper, as an essential nutrient, can have both beneficial and toxic effects on cells. Utilizing copper-dependent diseases or copper toxicity may provide new strategies for specific disease treatments. Especially in cancer cells, high copper concentration makes it a critical nutrient for tumor growth, and intervening in cancer cell copper metabolism could be a potential tumor treatment strategy. This review discusses copper metabolism in the body, its role in tumor cell growth and programmed cell death, and the potential of copper-related drugs in cancer treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xiyue Shen, Saddam Muhammad Ishaq, Qiao'e Wang, Juntao Yuan, Junling Gao, Zhongbing Lu
Summary: DDAH1 plays a protective role in APAP-induced liver injury by attenuating oxidative stress, inflammation, and damage to the liver through influencing xenobiotic metabolism and glutathione metabolism pathways. Increasing hepatic DDAH1 expression and activity may be a novel approach for treating drug-induced acute liver injury.
Article
Cell Biology
Anne Vonada, Amita Tiyaboonchai, Sean Nygaard, Jeffrey Posey, Alexander Mack Peters, Shelley R. Winn, Alessio Cantore, Luigi Naldini, Cary O. Harding, Markus Grompe
Summary: The study demonstrates that therapeutic modified hepatocytes can be efficiently selected in preclinical models by using mildly hepatotoxic acetaminophen, leading to significant expansion of transgene-bearing hepatocytes and reaching therapeutic thresholds in genetic liver diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Urology & Nephrology
Anissa A. Widjaja, Shamini G. Shekeran, Eleonora Adami, Joyce G. Wei Ting, Jessie Tan, Sivakumar Viswanathan, Sze Yun Lim, Puay Hoon Tan, Norbert Huebner, Thomas Coffman, Stuart A. Cook
Summary: This study demonstrates that neutralizing IL-11 antibody can reduce fibrosis, inflammation, and epithelial-to-mesenchymal transition while improving renal function in an Alport syndrome mouse model. Combined with ACE inhibition, anti-IL-11 therapy can synergistically extend lifespan. These findings suggest that targeting IL-11 holds promise for treating progressive kidney disease in Alport syndrome.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Benjamin Ng, Sivakumar Viswanathan, Anissa A. Widjaja, Wei-Wen Lim, Shamini G. Shekeran, Joyce Wei Ting Goh, Jessie Tan, Fathima Kuthubudeen, Sze Yun Lim, Chen Xie, Sebastian Schafer, Eleonora Adami, Stuart A. Cook
Summary: IL11 plays an important role in the activation of pancreatic stellate cells (PSCs) in pancreatitis, and targeting IL11 may be a potential therapeutic approach for fibrosis in pancreatitis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sonia P. Chothani, Eleonora Adami, Anissa A. Widjaja, Sarah R. Langley, Sivakumar Viswanathan, Chee Jian Pua, Nevin Tham Zhihao, Nathan Harmston, Giuseppe D'Agostino, Nicola Whiffin, Wang Mao, John F. Ouyang, Wei Wen Lim, Shiqi Lim, Cheryl Q. E. Lee, Alexandra Grubman, Joseph Chen, J. P. Kovalik, Karl Tryggvason, Jose M. Polo, Lena Ho, Stuart A. Cook, Owen J. L. Rackham, Sebastian Schafer
Summary: This study identified 7,767 smORFs with translational profiles matching those of known proteins, and discovered highly cell-type- and tissue-specific smORFs and a subset encoding highly conserved amino acid sequences in the human genome. Integration with mass-spectrometry data confirmed the presence of 603 small peptides at the protein level and provided insights into their subcellular localization.
Review
Cell Biology
Jason Hongting Leung, Benjamin Ng, Wei-Wen Lim
Summary: This article reviews the role of interleukin-11 (IL11) as a potential biomarker in non-small cell lung cancer (NSCLC). It identifies the need for biomarkers in NSCLC and summarizes the available information. Accumulating evidence suggests IL11 to be a potential biomarker in NSCLC patients, but further research is needed.
Letter
Gastroenterology & Hepatology
Madhulika Tripathi, Brijesh Kumar Singh, Paul Michael Yen
JOURNAL OF HEPATOLOGY
(2023)
Article
Multidisciplinary Sciences
Jin Zhou, Jeremy Pang, Madhulika Tripathi, Jia Pei Ho, Anissa Anindya Widjaja, Shamini Guna Shekeran, Stuart Alexander Cook, Ayako Suzuki, Anna Mae Diehl, Enrico Petretto, Brijesh Kumar Singh, Paul Michael Yen
Summary: The study found that spermidine can restore liver cell function impaired by non-alcoholic steatohepatitis (NASH) and prevent the progression of NASH in mice.
NATURE COMMUNICATIONS
(2022)
Article
Hematology
Benjamin Ng, Chen Xie, Liping Su, Fathima F. Kuthubudeen, Xiu-Yi Kwek, Daryl Yeong, Chee Jian Pua, Stuart A. Cook, Wei-Wen Lim
Summary: Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in the FBN1 gene. IL11 plays a role in causing lung disease in a mouse model of MFS. Inhibition of IL11 signaling can reduce lung emphysema, fibrosis, and inflammation in MFS mice, suggesting that targeting IL11 signaling could be a potential holistic approach for treating multiorgan morbidity in MFS.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sangam Rajak, Archana Tewari, Sana Raza, Pratima Gupta, Bandana Chakravarti, Baby Anjum, Madhulika Tripathi, Brijesh K. Singh, Paul M. Yen, Amit Goel, Sujoy Ghosh, Rohit A. Sinha
Summary: Nonalcoholic steatohepatitis (NASH) is a pivotal stage in the progression of nonalcoholic fatty liver disease (NAFLD) and increases the risk of serious liver diseases. Identifying reliable molecular players in the etiology of NASH has been difficult. Furthermore, there are currently no approved drugs for NASH treatment. This study highlights the involvement of CFTR in the pathogenesis of NASH and suggests the possibility of its pharmacological inhibition in human NASH.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Editorial Material
Biochemistry & Molecular Biology
Madhulika Tripathi, Brijesh Kumar Singh
Summary: Orphan nuclear receptor estrogen-related receptor alpha (ERR alpha) plays a crucial role in regulating energy metabolism, but its hyperactivation in breast cancer leads to cell migration, proliferation, and tumour development. The study by Brindisi et al. reveals that cholesterol can activate ERR alpha endogenously, promoting breast cancer aggressiveness, highlighting the potential anti-tumour effects of cholesterol-lowering drugs like statins.
Article
Biochemistry & Molecular Biology
Yi Ning Yong, Jiangwen Dong, Leroy Sivappiragasam Pakkiri, Christiani Jeyakumar Henry, Sumanto Haldar, Chester Lee Drum
Summary: Using targeted metabolomics, we compared the postprandial metabolic responses between breakfast and dinner timing, and high and low glycemic index meals in a group of healthy older Chinese adults. The findings suggest that eating dinner late may lead to worse metabolic state while the glycemic index of the meal has minimal impact on metabolic responses.
Review
Biochemistry & Molecular Biology
Mei Li Ng, Xu Ang, Kwan Yi Yap, Jun Jie Ng, Eugene Chen Howe Goh, Benjamin Bing Jie Khoo, Arthur Mark Richards, Chester Lee Drum
Summary: Oxidative stress (OS) damages various components of cells and tissues through reactive oxygen species (ROS), leading to inflammation and heart failure (HF). Circulating biomarkers generated by OS, such as NADPH oxidases, advanced glycation end-products, and myeloperoxidase, can reflect pathobiological changes in HF and hold potential for diagnosis, risk stratification, and therapeutic targeting. This review evaluates current OS-related biomarkers and their associations with clinical outcomes, with a focus on identifying promising biomarkers for HF management.
Editorial Material
Pathology
Anissa A. Widjaja, Stuart A. Cook
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Mark Sweeney, Katie O'Fee, Chelsie Villanueva-Hayes, Ekhlas Rahman, Michael Lee, Konstantinos Vanezis, Ivan Andrew, Wei-Wen Lim, Anissa Widjaja, Paul J. R. Barton, Stuart A. Cook
Summary: This study demonstrates that IL11 expression in cardiomyocytes can lead to severe cardiac fibrosis and inflammation, as well as endothelial-to-mesenchymal transition and left ventricular dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
