Article
Biochemistry & Molecular Biology
Jiuchun Qiu, Daiqi Liu, Pengsha Li, Lingling Zhou, Lu Zhou, Xing Liu, Yue Zhang, Meng Yuan, Gary Tse, Guangping Li, Tong Liu
Summary: Oxidative stress and mitochondrial dysfunction play important roles in the development of diabetic cardiomyopathy in type 2 diabetes mellitus. This study established a type 2 diabetes model and found that inhibiting NADPH oxidase can improve ventricular remodeling and reduce the incidence of DCM.
Review
Biochemistry & Molecular Biology
Renu A. Kowluru
Summary: Diabetic retinopathy, a leading cause of vision loss in working-age adults, involves oxidative stress and the activation of Nox2 and Rac1, with inhibitors of these enzymes potentially serving as therapeutic interventions.
Article
Medicine, Research & Experimental
David W. Hammers
Summary: This study found that targeting NOX4 is an effective strategy to reduce fibrosis and promote muscle regeneration in disease-burdened muscle, specifically in a model of Duchenne muscular dystrophy (DMD).
Article
Biochemistry & Molecular Biology
Francesca Beretti, Francesca Farnetani, Luca Reggiani Bonetti, Luca Fabbiani, Manuela Zavatti, Antonino Maiorana, Giovanni Pellacani, Tullia Maraldi
Summary: This study reveals a correlation between high positivity for Nox4 and c-met in BRAF mutated patients with melanoma, and metastasis occurring at least one year later than diagnosis. In vitro experiments demonstrate that the HGF/c-met/Nox4/ROS axis triggers epithelial-mesenchymal transition. The findings suggest that Nox4 inhibitors could be a potential addition to current therapies for treating melanoma patients with BRAF mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Keshia S. Hendricks, Eunice E. To, Raymond Luong, Felicia Liong, Jonathan R. Erlich, Ajay M. Shah, Stella Liong, John J. O'Leary, Doug A. Brooks, Ross Vlahos, Stavros Selemidis
Summary: This study found that endothelial NOX4 oxidase is protective against influenza morbidity and reduces lung inflammation. This suggests that it may serve as a potential therapeutic target for limiting the inflammatory response caused by influenza virus.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Keum-Jin Yang, Won Jung Choi, Yoon-Kyung Chang, Cheol Whee Park, Suk Young Kim, Yu Ah Hong
Summary: Xanthine oxidase (XO) inhibition showed renoprotective effects in diabetic kidney disease (DKD) by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) and reducing oxidative stress. This study provides important insights into the therapeutic potential of XO inhibition in DKD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ajmal Ahmad, Mohd Imtiaz Nawaz, Mohammad Mairaj Siddiquei, Ahmed M. Abu El-Asrar
Summary: NADPH oxidase (NOX) is a major producer of reactive oxygen species (ROS) which may play a role in the early pathogenesis of diabetic retinopathy (DR). NOX4 could downregulate the expression of neuro-survival factors BDNF/SIRT1, while treatment with a plant-derived NOX inhibitor apocynin (APO) may alleviate the deleterious effects caused by hyperglycemia and/or diabetic mimic hypoxic condition in the early stages of DR.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Xiaowen Bao, Jiaqi Li, Chaoxing Ren, Jingxun Wei, Xuanzhao Lu, Xiaoxuan Wang, Wei Du, Xin Jin, Beiting Ma, Qi Zhang, Bo Ma
Summary: The study found that Aucubin (AU) can improve liver injury and fibrosis caused by type 2 diabetes (T2DM) by alleviating inflammatory responses and cell activation processes, and inhibiting oxidative stress. AU may be a potential drug for the treatment of diabetes-related liver diseases.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Medicine, Research & Experimental
Lingling Zhou, Yang Liu, Zhaojia Wang, Daiqi Liu, Bingxin Xie, Yue Zhang, Meng Yuan, Gary Tse, Guangping Li, Gang Xu, Tong Liu
Summary: The study found that NADPH oxidase activity is associated with the occurrence of atrial fibrillation in diabetic patients by promoting adverse atrial remodeling. The drug apocynin can inhibit NADPH oxidase activity, thus improving atrial oxidative stress and mitochondrial dysfunction. It may be a potential drug for atrial fibrillation treatment.
Article
Medicine, Research & Experimental
Piotr Szczepaniak, Mateusz Siedlinski, Diana Hodorowicz-Zaniewska, Ryszard Nosalski, Tomasz P. Mikolajczyk, Aneta M. Dobosz, Anna Dikalova, Sergey Dikalov, Joanna Streb, Katarzyna Gara, Pawel Basta, Jaroslaw Krolczyk, Joanna Sulicka-Grodzicka, Ewelina Jozefczuk, Anna Dziewulska, Blessy Saju, Iwona Laksa, Wei Chen, John Dormer, Maciej Tomaszewski, Pasquale Maffia, Marta Czesnikiewicz-Guzik, Filippo Crea, Agnieszka Dobrzyn, Javid Moslehi, Tomasz Grodzicki, David G. Harrison, Tomasz J. Guzik
Summary: Cardiovascular dysfunction in breast cancer survivors treated with neoadjuvant chemotherapy is caused by the inhibitory phosphorylation of eNOS and increased ROS production by NADPH oxidases, especially by docetaxel. These effects can be prevented by Nox4 or Rock inhibitors.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Seong Ji Woo, Youngmi Kim, Harry Jung, Jae Jun Lee, Ji Young Hong
Summary: In this study, we found that miR-148a may protect against tuberculous pleural fibrosis by inhibiting the expression of NOX4 and POLDIP2, and reducing fibrogenesis and epithelial mesenchymal transition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Leticia Guadalupe Fragoso-Morales, Jose Correa-Basurto, Martha Cecilia Rosales-Hernandez
Summary: Alzheimer's disease is a major human dementia characterized by memory loss associated with oxidative stress in brain cells. Overexpression of NADPH oxidase in AD leads to the production of large amounts of reactive oxygen species, damaging brain cells and vasculature, making it a potential therapeutic target for AD.
Article
Multidisciplinary Sciences
Guzal Khayrullina, Sara Bermudez, Deanna Hopkins, Young Yauger, Kimberly R. R. Byrnes
Summary: NOX2 knockout improves recovery after spinal cord injury, while acute inhibition of NOX4 fails to enhance long-term recovery. Both NOX2 and NOX4 reduce ROS production and oxidative stress markers, and NOX2 knockout shows a shift in microglial activation towards a more neuroprotective state.
Article
Biochemistry & Molecular Biology
Alexandra-Gela Lazar, Mihaela-Loredana Vlad, Adrian Manea, Maya Simionescu, Simona-Adriana Manea
Summary: Accumulating evidence supports the involvement of histone acetylation-based epigenetic mechanisms in the pathoetiology of diabetes-associated micro-/macrovascular complications, with a focus on diabetic kidney disease. Pharmacological inhibition of p300/CBP shows promise in down-regulating the expression of Nox subtypes, inflammation, and fibrosis in the diabetic kidney, potentially reducing the burden of DKD.
Article
Peripheral Vascular Disease
Xuesong Liu, Yansong Guo, Yuxue Yang, Chunlei Qi, Ting Xiong, Yue Chen, Gengze Wu, Chunyu Zeng, Daxin Wang
Summary: Oxidative stress plays a crucial role in the development of abdominal aortic aneurysm (AAA), with DRD4 having a potential protective effect through its antioxidative properties. Experimental evidence shows that activating DRD4 can reduce ROS production and alleviate pathological features of AAA. DRD4 may serve as a novel therapeutic target for AAA treatment by regulating the P38 MAPK/NOX4 axis to decrease ROS production.
Article
Cardiac & Cardiovascular Systems
Lin Wu, Guifang Huang, Xianguan Yu, Minzhong Ye, Lu Liu, Yesheng Ling, Xiangyu Liu, Dinghui Liu, Bin Zhou, Yong Liu, Jianrui Zheng, Suzhen Liang, Rui Pu, Xuemin He, Yanming Chen, Lanqing Han, Xiaoxian Qian
Summary: The study developed an ECG-based deep learning diagnosis system that can detect STEMI and predict culprit vessel occlusion, thereby improving the accuracy and effectiveness of STEMI diagnosis.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biology
Jin Wang, Jiayi Xie, Daosong Wang, Xue Han, Minqi Chen, Guojun Shi, Linjia Jiang, Meng Zhao
Summary: Using single-cell sequencing, researchers identified a specific subpopulation of megakaryocytes (MKs) that highly expressed CXCR4 and exhibited both immune characteristics and MK-specific features. These CXCR4(high) MKs interacted with myeloid cells to promote their migration and enhance bacterial phagocytosis, and they were also capable of antigen presentation to activate T cells. Furthermore, in response to bacterial infection, these CXCR4(high) MKs could exit circulation and infiltrate into the spleen, liver, and lung. The ablation of MKs suppressed the innate immune response and impaired the anti-bacterial effects of T cells in mice.
Article
Endocrinology & Metabolism
Rong Gao, Jin Wang, Xuemin He, Tongtong Wang, Li Zhou, Zhitao Ren, Jifeng Yang, Xiaoxin Xiang, Shiyi Wen, Zhuojun Yu, Heying Ai, Yuchan Wang, Hua Liang, Shasha Li, Yan Lu, Yanhua Zhu, Guojun Shi, Yanming Chen
Summary: This study comprehensively analyzed the RNA-seq profiles of NAFLD patients and controls, revealing the association of ER homeostasis and hepatokines with NAFLD progression. Genes in the brown module were significantly associated with fibrosis stage and NAS. Some genes showed good capacity in distinguishing fibrosis stage, NAS, and NAFLD. Furthermore, some genes were identified as secretome genes.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Xiaoli Zhao, Guifang Huang, Lin Wu, Min Wang, Xuemin He, Jyun-Rong Wang, Bin Zhou, Yong Liu, Yesheng Lin, Dinghui Liu, Xianguan Yu, Suzhen Liang, Borui Tian, Linxiao Liu, Yanming Chen, Shuhong Qiu, Xujing Xie, Lanqing Han, Xiaoxian Qian
Summary: A CNN-LSTM model was established to diagnose LVH using 12-lead ECG with higher sensitivity than current diagnostic criteria. The model performed better in male patients and may be a simple and effective screening tool for LVH.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jifeng Yang, Yaping Zhi, Shiyi Wen, Xuya Pan, Heting Wang, Xuemin He, Yan Lu, Yanhua Zhu, Yanming Chen, Guojun Shi
Summary: Dysregulated production of peptide hormones can lead to various endocrine diseases. Endoplasmic reticulum associated degradation (ERAD) plays a crucial role in maintaining ER proteostasis by degrading misfolded proteins. Targeting ERAD for regulating peptide hormone production is limited, and herbal products provide potential alternative therapeutics. In this study, a virtual screening was performed to identify compounds targeting SEL1L-HRD1 ERAD machinery, and Cryptochlorogenic acid (CCA) was found to enhance ERAD activity and promote the secretion of well-folded peptide hormone. These findings contribute to drug discovery strategies for targeting ER protein homeostasis and provide candidate compounds for hormone-related diseases.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Medicine, General & Internal
Lin Wu, Bin Zhou, Dinghui Liu, Linli Wang, Ximei Zhang, Li Xu, Lianxiong Yuan, Hui Zhang, Yesheng Ling, Guangyao Shi, Shiye Ke, Xuemin He, Borui Tian, Yanming Chen, Xiaoxian Qian
Summary: This study aimed to develop a machine learning model using the LASSO algorithm to automatically diagnose acute STEMI based on ECG features. The model achieved high accuracy in diagnosing STEMI and showed similar performance to experienced cardiologists and better performance than other doctors. For identifying LAD or non-LAD, the model also performed well.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Zheyao Wen, Xuemin He, Jin Wang, Heting Wanga, Ting Li, Siying Wen, Zhitao Ren, Nan Cai, Jifeng Yang, Mei Li, Heying Ai, Yan Lu, Yanhua Zhu, Guojun Shi, Yanming Chen
Summary: Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus. Chronic hyperglycemia and hyperlipidemia lead to endothelial inflammation, but the detailed mechanisms are not fully understood. This study analyzed single cell RNA sequencing data and found that the STING pathway is highly expressed in mouse retinal vessels. Further experiments showed that STING and p-TBK1 protein levels were increased in retinal endothelial cells of mice fed with a high fat diet. In vitro experiments demonstrated that STING pathway activation was induced by ER stress and potentiated by IRE1 alpha-XBP1 signaling. These findings suggest that targeting the STING pathway may provide a therapeutic approach for treating DR and other microvascular complications.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Rong Gao, Heting Wang, Ting Li, Jin Wang, Zhitao Ren, Nan Cai, Heying Ai, Shasha Li, Yan Lu, Yanhua Zhu, Xintao Shuai, Xuemin He, Guojun Shi, Yanming Chen
Summary: This study identifies major urinary proteins (MUPs), specifically MUP1, as novel proteins involved in regulating the endoplasmic reticulum (ER) stress response and potential therapeutic targets for non-alcoholic fatty liver disease (NAFLD). MUP1 is misfolded and trapped in the ER during ER stress, and recombinant MUP1 treatment alleviates ER stress response and improves insulin resistance in hepatocytes.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Gastroenterology & Hepatology
Nan Cai, Xuanrong Chen, Jia Liu, Zheyao Wen, Siyin Wen, Wen Zeng, Shuo Lin, Yanming Chen, Guojun Shi, Longyi Zeng
Summary: This study aimed to investigate the effect of glucokinase (GK) activation on glucose and lipid metabolism in diet-induced obese mice. The results showed that GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation. Further studies revealed that GK activation activated the hepatic PERK-UPR signaling pathway through increasing lipogenic gene expression, leading to hepatic lipid accumulation.
Article
Endocrinology & Metabolism
Xiaoxin Xiang, Yanhua Zhu, Xuya Pan, Wei Xin, Jianning Chen, Weijian Tang, Ruomi Guo, Wu Yuan, Xuemin He, Li Zhou, Zhitao Ren, Siying Wen, Heting Wang, Yan Lu, Shasha Li, Tufeng Chen, Yuqi Zhou, Zulin Dou, Mengyin Cai, Xiaoyue Zhang, Yanming Chen, Guojun Shi
Summary: This study investigates the role of endoplasmic reticulum stress in mediating obesity-induced diaphragmatic dysfunction. The results show that people with obesity exhibit weakened diaphragmatic strength and lipid accumulation, which is also observed in obese mice. Inhibition of PERK/JNK signaling reverses lipid-induced impairment and elastic damage in C2C12 myotubes.
Article
Cell Biology
Heting Wang, Xuya Pan, Xiaoxin Xiang, Yang Zhang, Jianning Chen, Shiyi Wen, Jin Wang, Rong Gao, Jifeng Yang, Yaping Zhi, Siying Wen, Yubao Zheng, Ting Li, Heying Ai, Xuemin He, Yan Lu, Yanhua Zhu, Chunliang Li, Yanming Chen, Guojun Shi
Summary: By conducting a CRISPR screen, we found that RBBP8, an endonuclease involved in DNA damage repair, is necessary for ATF4 activation during ER stress. Deletion of RBBP8 led to impaired cell cycle progression, reduced proliferation, attenuated ATF4 activation, and lowered protein synthesis. RBBP8 was highly expressed in the liver and responsive to ER stress. In liver cancer tissues, both RBBP8 and ATF4 were highly expressed, and their expression correlated positively. Overexpression of RBBP8 promoted ATF4 activation under ER stress in vitro. These findings provide insights into how cells adapt to ER stress and how tumor cells survive in anticancer treatments, suggesting potential therapeutic strategies against liver disease.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Yue Li, Yi Yang, Jin Wang, Peihong Cai, Mei Li, Xixiang Tang, Ying Tan, Yuchan Wang, Fan Zhang, Xiaofeng Wen, Qiaoxing Liang, Yuanpeng Nie, Tufeng Chen, Xiang Peng, Xuemin He, Yanhua Zhu, Guojun Shi, Wai W. Cheung, Lai Wei, Yanming Chen, Yan Lu
Summary: Type 2 diabetes (T2D) is closely associated with obesity, and the factors driving the transition from excessive weight gain to glucose metabolism disruption are still uncertain. This study found that CD27(-) MAIT cells in the blood of obese individuals with T2D were elevated and produced high levels of IL-17, which may be correlated with impaired glucose metabolism in obese people. Additionally, gut barrier dysfunction and the accumulation of Bacteroides ovatus bacteria in the peripheral blood were found to contribute to the abnormality of MAIT cells and may be associated with T2D risk in obese individuals.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)