Article
Chemistry, Medicinal
Renshuai Zhang, Wenjing Liu, Jun Zeng, Jingsen Meng, Hongfei Jiang, Jie Wang, Dongming Xing
Summary: Cholesterol is a critical component of cell membranes, but elevated serum cholesterol levels are a major risk factor for heart disease. Understanding and developing NPC1L1 inhibitors, which can decrease cholesterol absorption, is an important research direction that presents both challenges and exciting therapeutic opportunities.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Shiqian Han, Qijun Wang, Yongfeng Song, Mao Pang, Chunguang Ren, Jing Wang, Dongwei Guan, Wei Xu, Fangyong Li, Fengchao Wang, Xinyuan Zhou, Carlos Fernandez-Hernando, Huiwen Zhang, Dianqing Wu, Zhijia Ye
Summary: Niemann-Pick disease type C (NP-C) is a genetic lysosomal disorder with limited therapeutic options. This study demonstrates that lithium treatment improves phenotypes and extends survival in NP-C mouse models by suppressing STING activation, SREBP2 processing, and target gene expression. Lithium impedes STING/SREBP2 transport, providing a mechanistic explanation for its effects. This reveals a potential therapeutic option for NP-C patients and a strategy to reduce active STING/SREBP2 pathway.
Article
Biochemistry & Molecular Biology
Jun Zeng, Wenjing Liu, Bing Liang, Lingyu Shi, Shanbo Yang, Jingsen Meng, Jing Chang, Xiaokun Hu, Renshuai Zhang, Dongming Xing
Summary: This study found that isoliquiritigenin (ISL) can lower cholesterol levels by downregulating NPC1L1 expression and competitively inhibiting cellular cholesterol uptake. This provides a theoretical basis for further investigating the molecular mechanisms of its cholesterol-lowering effect and inspires new drug research for cholesterol-lowering purposes through NPC1L1 inhibition.
Review
Chemistry, Medicinal
Marcos Morales-Tenorio, Tiziana Ginex, Miguel Angel Cuesta-Geijo, Nuria E. Campillo, Cesar Munoz-Fontela, Covadonga Alonso, Rafael Delgado, Carmen Gil
Summary: The Niemann-Pick C1 (NPC1) receptor plays a crucial role in regulating intracellular cholesterol trafficking and facilitating the entry of Ebola virus into host cells. Disruption of the NPC1/EBOV-GP interaction could be a promising strategy for developing drugs to inhibit viral entry and infection, although further research is needed to understand the molecular and structural details of this interaction.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Nina H. Pipalia, Syed Z. Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S. J. Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S. Ory, Frederick R. Maxfield
Summary: Inhibition of HSP90 clears cholesterol from LE/Ly in NPC1(I1061T) fibroblasts and enhances delivery of mutant NPC1(I1061T) protein. Additionally, HSP90 inhibition increases HSP70 expression, and overexpression of HSP70 reduces cholesterol storage in NPC1(I1061T) fibroblasts. This suggests that HSP90 inhibitors may improve NPC1 protein folding and relieve cholesterol accumulation in NPC1 mutant fibroblasts by increasing other chaperones.
JOURNAL OF LIPID RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Christin Voelkner, Maik Liedtke, Andreas Hermann, Moritz J. Frech
Summary: Niemann-Pick disease Type C1 and C2 are rare disorders caused by mutations in the NPC1 or NPC2 gene, leading to cholesterol accumulation in late endosomes and lysosomes. Clinical manifestations include neurological and systemic symptoms. iPSCs are a valuable tool for disease modeling and drug discovery in NPC1 research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Maria Teresa Fiorenza, Piergiorgio La Rosa, Sonia Canterini, Robert P. Erickson
Summary: Selective neuronal vulnerability is a common feature in degenerative disorders. This article focuses on the vulnerability of the cerebellum in Niemann-Pick C (NPC), discussing the impact of altered intracellular cholesterol trafficking on the development and functional maturation of cerebellar cells. The article also addresses the progression of cerebellar defects and the persistence of these defects in mouse models despite genetic manipulations.
Article
Biochemistry & Molecular Biology
Anouk G. Groenen, Anouk M. La Rose, Mengying Li, Venetia Bazioti, Arthur F. Svendsen, Niels J. Kloosterhuis, Albertina Ausema, Alle Pranger, M. Rebecca Heiner-Fokkema, Klary E. Niezen-Koning, Tom Houben, Ronit Shiri-Sverdlov, Marit Westerterp
Summary: This study found that elevated G-CSF levels and HSC mobilization may contribute to splenomegaly in patients with NPC1 disease.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Medicine, Research & Experimental
Denzil Furtado, Christina Cortez-Jugo, Ya Hui Hung, Ashley I. Bush, Frank Caruso
Summary: Researchers successfully used NPC1-encoded mRNA to combat protein insufficiency and pathogenic phenotype caused by biallelic NPC1 mutations, achieving treatment for the rare disease NP-C1. The gene engineering strategies greatly improved the expression efficiency of the mRNA.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biology
Cristin D. Davidson, Alana L. Gibson, Tansy Gu, Laura L. Baxter, Benjamin E. Deverman, Keith Beadle, Arturo A. Incao, Jorge L. Rodriguez-Gil, Hideji Fujiwara, Xuntian Jiang, Randy J. Chandler, Daniel S. Ory, Viviana Gradinaru, Charles P. Venditti, William J. Pavan
Summary: Niemann-Pick C1 disease (NPC1) is a rare, fatal neurodegenerative disease caused by mutations in NPC1 gene, resulting in cholesterol accumulation in lysosomes and leading to neurological complications. AAV-PHP.B vector shows greater efficiency in transducing the central nervous system of Npc1 mutant mice compared to AAV9, indicating potential for improved gene therapy in NPC1.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Ting-Ting Chu, Xintao Tu, Kun Yang, Jianjun Wu, Joyce J. Repa, Nan Yan
Summary: This study identifies a cGAS- and cGAMP-independent mode of STING activation that affects neuropathology and provides a therapeutic target for the treatment of Niemann-Pick disease type C.
Article
Pharmacology & Pharmacy
Jiang Du, Xinlei Liu, Yan Zhang, Xiaojing Han, Chunya Ma, Yanli Liu, Lihong Guan, Liang Qiao, Juntang Lin
Summary: This study found that combination treatment with HP beta CD and metformin did not prolong survival time or increase body weight in Npc1(-/-) mice, but it reduced inflammatory response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biology
Anika Prabhu, Insung Kang, Raffaella De Pace, Christopher A. Wassif, Hideji Fujiwara, Pamela Kell, Xuntian Jiang, Daniel S. Ory, Juan S. Bonifacino, Michael E. Ward, Forbes D. Porter
Summary: Niemann-Pick disease type C is a childhood-onset neurodegenerative disorder caused by mutations in NPC1 or NPC2 genes. A novel human iPSC-derived neuronal model of NPC1 has been developed, recapitulating key pathological features and showing potential for high-throughput drug screening.
Article
Pharmacology & Pharmacy
Shiqian Han, Huiwen Zhang, Mengni Yi, Xiaoqing Liu, Gustavo H. B. Maegawa, Yunding Zou, Qijun Wang, Dianqing Wu, Zhijia Ye
Summary: This study evaluated the safety and feasibility of lithium carbonate in NP-C1 patients and found that lithium treatment significantly reduced plasma 7-ketocholesterol concentrations, improved NPC Neurological Severity Scores, and enhanced swallowing capacity. Patients tolerated lithium well with no serious adverse events recorded.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Kiersten Campbell, Niamh X. Cawley, Rachel Luke, Katelin E. J. Scott, Nicholas Johnson, Nicole Y. Farhat, Derek Alexander, Christopher A. Wassif, Wenping Li, Stephanie M. Cologna, Elizabeth Berry-Kravis, An Dang Do, Ryan K. Dale, Forbes D. Porter
Summary: This study compared cerebrospinal fluid samples from individuals with NPC1 and non-NPC1 samples, and identified multiple proteins with altered levels in CSF from individuals with NPC1. Correlations between these proteins and clinically relevant phenotypic parameters were also observed. These findings may provide useful data for therapeutic trials of NPC1.
BIOMARKER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Minchun Jiang, Huanyu Ding, Yu Huang, Li Wang
Summary: Shear stress and metabolic disorder play crucial roles in the pathogenesis of atherosclerosis, with complex interactions between them potentially amplifying the proatherogenic effects through increased oxidative stress and inflammation. A deeper understanding of the cross talk network holds promise for comprehensive clinical management of atherosclerosis and the development of novel therapeutic strategies.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Cardiac & Cardiovascular Systems
Huina Zhang, Jinghui Dong, Chi-Wai Lau, Yu Huang
Summary: This study demonstrated that berberine reverses NTG tolerance by inhibiting PKC alpha activity in VSMCs. These findings suggest that berberine could be a promising drug for prevention of NTG tolerance and targeting PKC alpha in VSMCs may be a potential therapeutic strategy for reversal of NTG tolerance in blood vessels.
CARDIOVASCULAR DRUGS AND THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
Mingyu Huo, Xiaoyun Cao, Hongsong Zhang, Chi Wai Lau, Huiling Hong, Francis M. Chen, Yu Huang, Ajay Chawla, Xiao Yu Tian
Summary: This study aims to investigate the contribution of BMAL1 to the pro-fibrotic macrophage phenotype in the vasculature during hypertension.
CARDIOVASCULAR RESEARCH
(2022)
Article
Nutrition & Dietetics
Erika Kwek, Hanyue Zhu, Huafang Ding, Zouyan He, Wangjun Hao, Jianhui Liu, Ka Ying Ma, Zhen-Yu Chen
Summary: Peony seed oil (PSO) is effective in reducing plasma cholesterol and hepatic lipids, and favorably modulating gut microbiota associated with cholesterol metabolism.
EUROPEAN JOURNAL OF NUTRITION
(2022)
Article
Food Science & Technology
Jianming Tao, Lijun Liu, Qian Ma, Ka Ying Ma, Zhen-Yu Chen, Fayin Ye, Lin Lei, Guohua Zhao
Summary: Gamma-oryzanol has been found to have potential as a functional antioxidant in foods, although its ability to combat lipid oxidation is not as effective as butylated hydroxytoluene (BHT). This study demonstrated that gamma-oryzanol can inhibit oxygen consumption and prevent the decrease of polyunsaturated fatty acids in heated canola oil, especially at lower cooking temperatures.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Li Wang, Chak Kwong Cheng, Min Yi, Kathy O. Lui, Yu Huang
Summary: Vascular endothelium plays a crucial role in maintaining vascular homeostasis and regulating vascular function through the release of vasoactive molecules. Imbalance between relaxing and contracting factors derived from the endothelium leads to endothelial dysfunction, which is a critical contributor in aging and chronic cardiometabolic disorders. Oxidative stress and inflammation are key players in endothelial dysfunction and are considered as potential targets for intervention in patients with cardiovascular and metabolic diseases.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lei He, Cheng-Lin Zhang, Qinghua Chen, Li Wang, Yu Huang
Summary: Atherosclerotic vascular disease and its complications are leading causes of mortality globally. Studies have shown that endothelial cells are influenced by low or disturbed shear stress at curvatures and bifurcations in the arterial tree, playing a role in the formation and development of atherosclerotic plaques. Understanding mechanosensitive signaling cascades may offer new translational strategies for therapeutic intervention of atherosclerotic vascular disease.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Chak-Kwong Cheng, Wenbin Shang, Jian Liu, Wai-San Cheang, Yu Wang, Li Xiang, Chi-Wai Lau, Jiang-Yun Luo, Chi-Fai Ng, Yu Huang, Li Wang
Summary: This study found that the level of miR-181b is decreased in renal arteries of diabetic patients and in advanced glycation end products (AGEs)-treated renal arteries of non-diabetic patients. Transfection of miR-181b mimics can improve endothelium-dependent vasodilation in arteries of diabetic mice. Activation of AMPK and chronic exercise can upregulate miR-181b expression. These findings suggest a critical role of the AMPK/miR-181b axis in counteracting diabetes-associated endothelial dysfunction.
Editorial Material
Cardiac & Cardiovascular Systems
Kathy O. Lui, Yu Huang
CIRCULATION RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Huanyu Ding, Minchun Jiang, Chi Wai Lau, Jianfang Luo, Andrew M. M. Chan, Li Wang, Yu Huang
Summary: YAP inhibition by CBL0137 is a promising therapeutic approach for atherosclerotic vascular disease.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Jianhui Liu, Huafang Ding, Chi Yan, Zouyan He, Hanyue Zhu, Ka Ying Ma
Summary: The aim of this study was to explore the underlying mechanisms linking the intestinal microbiota and anti-obesity benefits of green tea, oolong tea, and black tea catechins. The results showed that the three tea catechins significantly alleviated obesity and low-grade inflammation, prevented hepatic steatosis, and upregulated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha). Metagenomic analysis indicated that the three tea catechins similarly changed the microbiota in terms of overall structure, composition, and protein functions by regulating metabolites and repressing lipopolysaccharides. Therefore, the anti-obese properties of tea catechins were partially mediated by their effects on gut microbiota, hepatic steatosis alleviation, and anti-inflammatory activity.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Biochemistry & Molecular Biology
Chak Kwong Cheng, Huanyu Ding, Minchun Jiang, Huiyong Yin, Maik Gollasch, Yu Huang
Summary: Perivascular adipose tissue (PVAT) refers to the aggregate of adipose tissue surrounding the vasculature, exhibiting the phenotypes of white, beige and brown adipocytes. PVAT is actively involved in the regulation of reactive oxygen species (ROS) homeostasis and inflammation in the vascular system. The phenotype-genotype of PVAT varies in different regions of the vasculature and plays a role in cardiovascular pathogenesis. Treatments targeting PVAT may provide new therapeutic insights for cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Zouyan He, Hanyue Zhu, Jianhui Liu, Erika Kwek, Ka Ying Ma, Zhen-Yu Chen
Summary: This study found that mangiferin can alleviate TMAO-induced atherosclerosis through its anti-inflammatory, cholesterol-lowering, and gut microbial modulatory activities.
Article
Medicine, Research & Experimental
Huina Zhang, Lu Peng, Yifan Wang, Wen Zhao, Wayne Bond Lau, Yajing Wang, Yu Li, Yunhui Du, Linyi Li, Yu Huang, Shaoping Nie, Yanwen Qin, Xinliang Ma, Yongxiang Wei
Summary: This study reveals the role of circulating extracellular vesicles (EVs) in regulating endothelial function through the delivery of miR-144 to endothelial cells, reducing the expression of nuclear factor erythroid 2-related factor 2. Erythrocytes were identified as the primary cellular source of miR-144-enriched serum-derived EVs, which were largely responsible for endothelial dysfunction induced by chronic intermittent hypoxia. Silencing miR-144 confirmed its essential role in this dysfunction. The findings expand our understanding of blood-borne substances involved in vascular homeostasis and suggest that anti-miR-144-loaded EVs could be a promising therapeutic approach for conditions such as obstructive sleep apnea or chronic intermittent hypoxia-induced endothelial dysfunction.
Article
Hematology
Wenbin Zhong, Xiuye Cao, Guoping Pan, Qun Niu, Xiaoqin Feng, Mengyang Xu, Mingchuan Li, Yu Huang, Qing Yi, Daoguang Yan
Summary: This study reveals that ORP4L is expressed in ATL cells and plays an important role in the initiation of T-cell leukemogenesis induced by HTLV-1. Loss of miR-31 leads to increased ORP4L expression, which interacts with PI3Kd to promote PI(3,4,5)P3 generation, resulting in AKT hyperactivation, NF-kappa B-dependent p53 inactivation, and pro-oncogene expression.
