摘要：
Aldehyde dehydrogenase 1 (ALDH1), a crucial aldehyde metabolizing enzyme, has six family members. The ALDH1 family is expressed in various tissues, with a significant presence in the liver. It plays a momentous role in several pathophysiological processes, including aldehyde detoxification, oxidative stress, and lipid peroxidation. Acetaldehyde detoxification is the fundamental function of the ALDH1 family in participating in vital pathological mechanisms. The ALDH1 family can catalyze retinal to retinoic acid (RA) that is a hormone-signaling molecule and plays a vital role in the development and adult tissues. Furthermore, there is a need for further and broader research on the role of the ALDH1 family as a signaling molecule. The ALDH1 family is widely recognized as a cancer stem cell (CSC) marker and plays a significant role in the proliferation, invasion, metastasis, prognosis, and drug resistance of cancer. The ALDH1 family also participates in other human diseases, such as neurodegenerative diseases, osteoarthritis, diabetes, and atherosclerosis. It can inhibit disease progression by inhibiting/promoting the expression/activity of the ALDH1 family. In this review, we comprehensively analyze the tissue distribution, and functions of the ALDH1 family. Additionally, we review the involvement of the ALDH1 family in diseases, focusing on the underlying pathological mechanisms and briefly talk about the current status and development of ALDH1 family inhibitors. The ALDH1 family presents new possibilities for treating diseases, with both its upstream and downstream pathways serving as promising targets for therapeutic intervention. This offers fresh perspectives for drug development in the field of disease research.
期刊：
Journal of Advanced Research,2024年 ISSN：2090-1232
通讯作者：
Hu, Haoliang;Chen, Linxi
作者机构：
[Wang, Jin; Hu, Haoliang] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China;[Jiang, Jinyong] Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou 416000, China;[Hu, Haoliang] College of Medicine, Hunan University of Arts and Science, Changde 415000, China. Electronic address: huhl@huas.edu.cn;[Chen, Linxi] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China. Electronic address: 1995001765@usc.edu.cn
通讯机构：
[Haoliang Hu; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China<&wdkj&>College of Medicine, Hunan University of Arts and Science, Changde 415000, China<&wdkj&>Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2023年238(3):485-497 ISSN：0021-9541
通讯作者：
Linxi Chen<&wdkj&>Meiqing Liu<&wdkj&>Linxi Chen Linxi Chen Linxi Chen<&wdkj&>Meiqing Liu Meiqing Liu Meiqing Liu
作者机构：
[Luo, Jingshun; Liu, Meiqing] Kunming Med Univ, Key Lab Cardiovasc Dis Yunnan Prov, Key Lab Tumor Immunol Prevent & Treatment Yunnan P, Cent Lab Yanan Hosp, Kunming, Yunnan, Peoples R China.;[Luo, Jingshun; Zhao, Hong; Chen, Linxi] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Inst Pharm & Pharmacol, Hengyang, Hunan, Peoples R China.;[Zhao, Hong] Univ South China, Nursing Coll, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Liu, Meiqing] Kunming Med Univ, Key Lab Cardiovasc Dis Yunnan Prov, Key Lab Tumor Immunol Prevent & Treatment Yunnan P, Cent Lab Yanan Hosp, Kunming 650000, Yunnan, Peoples R China.
通讯机构：
[Linxi Chen; Linxi Chen Linxi Chen Linxi Chen] I;[Meiqing Liu; Meiqing Liu Meiqing Liu Meiqing Liu] K;Key Laboratory of Cardiovascular Diseases of Yunnan Province, Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Central laboratory of Yan'an Hospital Affiliated to Kunming Medical University, Kunming, Yunnan, China<&wdkj&>Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, Hunan, China
期刊：
Frontiers in Pharmacology,2023年14:1146426 ISSN：1663-9812
通讯作者：
Tong, X.;Wang, G.
作者机构：
[Tong, Xiaoyong] School of Pharmaceutical Sciences, Chongqing University, Chongqing, China;[Tan, Yi] University of Louisville School of Medicine, Louisville, KY, United States;[Chen, Linxi] Institute of Pharmacy and Pharmacology, University of South China, Hunan, Hengyang, China;[Wang, Guixue] Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Modern Life Science Experiment Teaching Center at Bioengineering College of Chongqing University, Chongqing, China
通讯机构：
[Tong, X.] S;[Wang, G.] K;School of Pharmaceutical Sciences, China;Key Laboratory of Biorheological and Technology of Ministry of Education, China
关键词：
Cardio-cerebrovascular diseases;bio-nanotechnology;Bioactive substance;Traditional Chinese Medicine;Targeted Drug Delivery
摘要：
The endoplasmic reticulum (ER) is one of the most important organelles in cells, involved in protein synthesis, folding, and modification, as well as Ca2+ storage and release. ER homeostasis imbalances may contribute to various diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and cancer. Current research efforts primarily focus on ER-related disease mechanisms and drug candidate screening. Because disease processes involve multiple molecular events and signaling, an innovative tool is necessary to precisely detect key signaling molecules in the ER to accelerate the discovery of targeted therapeutics. In recent years, because of their real-time visualization, precise targeting, high sensitivity and specificity, low cytotoxicity, and synthetic tunability, fluorescent probes have been widely used to investigate biological processes and disease events. This review first introduces ER and its related biological processes, and the design rules of ER-targeted probes. Subsequently, based on the latest literature, it systematically summarizes the research progress of fluorescent probes for imaging physiological or pathological events in the ER. Lastly, it discusses the challenges of ER-targeted probes as well as the future development of probe engineering. We anticipate that this review will not only encourage the development of fluorescence probe engineering but will also enhance interdisciplinary research between chemistry, biology, pharmacology, and medicine, promoting for its widespread application.
摘要：
Ferrous ion (Fe2+) is a crucial metal ion in the body and participates in the diseases related to oxidation and reduction. Golgi apparatus is the main subcellular organelle of Fe2+ transport in cells, and the stability of its structure is related to the Fe2+ at an appropriate concentration. In this work, a turn-on type Golgi-targeting fluorescent chemosensor Gol-Cou-Fe2+ was rationally designed for sensitive and selective detection of Fe2+. Gol-Cou-Fe2+ showed excellent capacity of detecting exogenous and endogenous Fe2+ in HUVEC and HepG2 cells. It was used to capture the up-regulated Fe2+ level during the hypoxia. Moreover, the fluorescence of sensor was enhanced over time under Golgi stress combining with the reduce of Golgi matrix protein GM130. However, elimination of Fe2+ or addition of nitric oxide (NO) would restore the fluorescence intensity of Gol-Cou-Fe2+ and the expression of GM130 in HUVEC. Thus, development of chemosensor Gol-Cou-Fe2+ provides a new window for tracking Golgi Fe2+ and elucidating Golgi stress-related diseases.
作者机构：
[Xiong G.; Yang Z.] Department of Vascular Surgery, The Second Affiliated Hospital of University of South China, Hengyang, 421001, China;[Chen Z.; Chen L.] Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, College of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang, 421001, China
通讯机构：
[Chen, L.] I;[Xiong, G.] D;Institute of Pharmacy and Pharmacology, China;Department of Vascular Surgery, China
摘要：
G protein-coupled receptor 35 (GPR35), originally an orphan receptor, was discovered in 1998. At that time, the lack of pharmacological tools and convincingly defined endogenous ligands of GPR35 hindered the understanding of its functions and therapy. De Giovanni et al. recently discovered that 5- hydroxyindoleacetic acid (5-HIAA) is a new ligand of GPR35. Notably, 5-HIAA can promote neutrophil recruitment to inflammatory sites to clear pathogenic bacteria by activating GPR35. Interestingly, this new ligand is derived from platelets and mast cells. Based on this, we briefly commented that platelet and mast cell-derived 5-HIAA activates GPR35 on neutrophils to promote the inflammatory process.
摘要：
As an integral organelle in the eukaryote, the lysosome is the degradation center and metabolic signal center in living cells, and partakes in significant physiological processes such as autophagy, cell death and cellular senescence. Fluorescent probe has become a favorite tool for studying organelles and their chemical microenvironments because of its high specificity and non-destructive merits. Over recent years, it has been reported that increasingly new lysosome-targeted probes play a major role in the diagnosis and monitor of diseases, in particular cancer and neurodegenerative diseases. In order to deepen the relevant research on lysosome, it is challenging and inevitability to design novel lysosomal targeting probes. This review first introduces the concepts of lysosome and its closely related biological activities, and then introduces the fluorescent probes for lysosome in detail according to different detection targets, including targeting mechanism, biological imaging, and application in diseases. Finally, we summarize the specific challenges and discuss the future development direction facing the current lysosome-targeted fluorescent probes. We hope that this review can help biologists grasp the application of fluorescent probes and broaden the research ideas of researchers targeting fluorescent probes so as to design more accurate and functional probes for application in diseases.
作者机构：
[Li, Ao; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhao, Qun] Cent South Univ, Xiangya Hosp 3, Hlth Management Ctr, Changsha, Hunan, Peoples R China.;[Li, Zhiyue] Cent South Univ, Dept Orthoped, Xiangya Hosp 3, Changsha, Hunan, Peoples R China.
通讯机构：
[Linxi Chen] I;[Zhiyue Li] D;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Orthopedics, Third Xiangya Hospital of Central South University, Changsha, China
作者机构：
[Chen E.; Hu X.] Department of anesthesiology, the First Affiliated Hospital of University of South China, Hengyang, 421001, China;[Chen Z.; Chen L.] Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, College of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang, 421001, China
通讯机构：
[Chen, L.] I;[Hu, X.] D;Department of anesthesiology, China;Institute of Pharmacy and Pharmacology, China
作者机构：
Changde Research Centre for Artificial Intelligence and Biomedicine, College of Life and Environmental Sciences, Hunan University of Arts and Science,,Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical School, Unive;Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical School, University of South China;Department of Pharmacology, Yongzhou Vocational Technical College;Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical School, University of South China,,The First Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China;[Chen L.; Chen Z.] Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang, 421200, China
通讯机构：
[Fu, C.; Chen, L.] I;Institute of Pharmacy and Pharmacology, China
摘要：
The phospholipid molecules forming the phospholipid bilayer membrane have difficulties to complete spontaneous trans-bilayer shuttling due to the physicochemical properties and biological functions of the membrane bilayer. However, this transbilayer phospholipid transport is essential in biology. Phospholipid synthesis is concentrated on the membrane of the endoplasmic reticulum (ER) of cells, which occurs only in the monolipid layer on the cytoplasmic side. Therefore, the formation of a complete bilayer membrane requires the phospholipids to be flipped to the other side. Transmembrane translocation of lipids controls transbilayer lipid asymmetry in membranes. ATP-independent scramblases and energy-driven flippases are key factors in maintaining asymmetric phospholipid distribution by promoting transbilayer movement of specific lipids across the cytoplasmic leaflet. ER scramblases promote rapid turnover of lipids and allow them to equilibrate between two membrane leaflets in an ATP-independent manner. Intriguingly, ER transmembrane protein 41B (TMEM41B) was recently identified as a lipid scramblase which mediates transbilayer phospholipid movement and plays a prominent role in maintaining lipoprotein biogenesis and lipid metabolism. The ER is considered to initiate protein and lipid synthesis/transport in eukaryotic cells. Many neutral lipids, including phospholipids and cholesterol utilized for lipoprotein assembly, are synthesized in the ER lumen lipoproteins, indicating that there are tissue-specific phospholipid biosynthetic pathways that vigorously produce phospholipids on the rough ER membrane of liver or intestinal cells. One recent study revealed that the transmembrane cargo receptor SURF4 selectively transports hepatic lipid-carrying lipoproteins from the ER to the Golgi through coat protein complex II (COPII)-coated transport vesicles. Synergistic pairing between SURF4 and the molecular switch SAR1B operates a sensitive transport program for hepatic lipoprotein secretion and maintains circulating lipid homeostasis (Figure 1). Furthermore, TMEM41B is detected in a hepatic protein complex of SURF4 and lipoproteins, which is present in the SURF4-mediated ER transport of lipid cargos and implicated in lipid equilibration between the membrane leaflets.
期刊：
Journal of Drug Targeting,2022年30(3):244-258 ISSN：1061-186X
通讯作者：
Nian Fu<&wdkj&>Linxi Chen
作者机构：
[Jiang, Jinyong; Chen, Zhe; Chen, Linxi] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Inst Pharm & Pharmacol,Coll Basic Med Sci, Hengyang 421001, Peoples R China.;[Fu, Nian] Univ South China, Affiliated Nanhua Hosp, Dept Gastroenterol, Hengyang, Peoples R China.
通讯机构：
[Nian Fu] D;[Linxi Chen] I;Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, University of South China, Hengyang, China
作者机构：
[Hu, Xiaoling; Chen, Enlin] Department of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China;[Chen, Zhe; Chen, Linxi] Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, College of Basic Medical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, China
通讯机构：
[Xiaoling Hu] D;Department of Anesthesiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China
关键词：
Mitochondria;stem cells;wound healing
摘要：
Mitochondria regulate intracellular metabolism and are also involved in intercellular transfer in vitro and in vivo, thereby affecting the function of adjacent cells. Mitochondria can also be transferred to various differentiated cells to improve their respiratory function, ATP production, as well as protect damaged cells from apoptosis. Both in vivo and in vitro, mitochondria can be transferred from one cell to another to regulate cellular metabolism under physiological or pathophysiological conditions, referred to as "mitochondrial translocation". Mitochondrial translocation is associated in various situations such as repairing damaged cells, promoting cancer progression and enhancing chemoresistance. Platelets contain mitochondria that promote energy metabolism and various growth factors, thus playing an important role in pathophysiological processes such as thrombosis, hemostasis, inflammation and wound healing. Current studies suggest that mesenchymal stem cells (MSCs) can communicate with their microenvironment through bidirectional alternation of mitochondria to improve their wound healing capacity. Platelets or platelet-containing preparations such as platelet-rich plasma (PRP) can stimulate the proliferation and pro-angiogenic properties of MSCs under oxidative stress to enhance their survival. Recent studies by Levoux et al. have shown that activated platelet-derived mitochondria have the respiratory capacity to translocate to MSCs and stimulate the pro-angiogenic properties of MSCs through metabolic reprogramming, thereby promoting angiogenesis and wound healing. The mechanism of mitochondrial internalization of cells and energy metabolism is a new example of mitochondrial translocation altering somatic cell behavior and viability. Therefore, we aim to comment the mechanisms of platelet mitochondrial translocation and metabolic reprogramming of MSCs, suggesting that platelets or platelet-containing preparations such as platelet-rich plasma (PRP) may provide a practical guide for tissue injury treatment.
摘要：
Thyroid hormone/thyroid hormone receptor (TH/TR) axis is characterized by TH with the assistance of plasma membrane transporters to combine with TR and mediate biological activities. Growing evidence suggests that TH/TR participates in plenty of hepatic metabolism. Thus, this review focuses on the role of the TH/TR axis in the liver diseases. To be specific, the TH/TR axis may improve metabolic-associated fatty liver disease, hepatitis, liver fibrosis, and liver injury while exacerbating the progression of acute liver failure and alcoholic liver disease. Also, the TH/TR axis has paradoxical roles in hepatocellular carcinoma. The TH/TR axis may be a prospecting target to cure hepatic diseases.
摘要：
Xu et al. recently demonstrated that cryptochrome 4 (CRY4) protein, as a light-dependent magnetic receptor, can sense geomagnetic fields to guide night-migratory songbirds' navigation and evolution by the formation of composite radical pairs and electron transport. We aim to comment on CRY4 through radical pairs and electron transport for magnetic sensitive in night-migratory songbirds' migration and evolution. Additionally, we find that the role of magnetic fields is deeply concerning to the scientific community and very enlightening for the diagnosis and treatment of cancer and vascular disease. We believe that this commentary makes a significant contribution to the literature because it elaborates on the importance of the geomagnetic field to night-migratory songbirds and extends the diagnostic and therapeutic value to cancer and vascular disease.
作者机构：
[Gao, Jiayin; Gao, Anbo; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.;[Zhou, Hong] Univ South China, Affiliated Hosp 1, Dept Radiol, Hengyang 421001, Peoples R China.
通讯机构：
[Hong Zhou] D;[Linxi Chen] I;Department of Radiology of the First Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
关键词：
Ca2+;Cu;Golgi apparatus;metal ions;Zn2+
摘要：
The Golgi apparatus is a membrane-bound organelle that functions as a central role in the secretory pathway. Since the discovery of the Golgi apparatus, its structure and function have attracted ever-increasing attention from researchers. Recently, it has been demonstrated that metal ions are necessary for the Golgi apparatus to maintain its proper structure and functions. Given that metal ions play an important role in various biological processes, their abnormal homeostasis is related to many diseases. Therefore, in this paper, we reviewed the uptake and release mechanisms of the Golgi apparatus Ca2+, Cu, and Zn2+. Furthermore, we describe the diseases associated with Golgi apparatus Ca2+, Cu, and Zn2+ imbalance.
摘要：
<jats:title>Abstract</jats:title><jats:p>N<jats:sup>6</jats:sup>‐methyladenosine (m<jats:sup>6</jats:sup>A) is one of the most common internal modifications in messenger RNA, which is necessary for cell physiological activities. A recent study shows that during mammalian hematopoietic development, loss of m<jats:sup>6</jats:sup>A modification leads to the aberrant production of double‐stranded RNA, which results in the abnormal activation of innate immune response, and ultimately leads to hematopoietic failure. Accordingly, m<jats:sup>6</jats:sup>A modification provide us an attractive direction for us to understand mammalian hematopoietic development and innate immune response.</jats:p>
