摘要：
APJ, an orphan G protein-coupled receptor, is first identified through homology cloning in 1993. Apelin is endogenous ligand of APJ extracted from bovine stomach tissue in 1998. Apelin/APJ system is widely expressed in many kinds of cells such as endothelial cells, cardiomyocytes, especially vascular smooth muscle cell. Vascular smooth muscle cell (VSMC), an integral part of the vascular wall, takes part in many normal physiological processes. Our experiment firstly finds that apelin/APJ system enhances VSMC proliferation by ERK1/2-cyclin D1 signal pathway. Accumulating studies also show that apelin/APJ system plays a pivotal role in mediating the function of VSMC. In this paper, we review the exact role of apelin/APJ system in VSMC, including induction of proliferation and migration, enhance of contraction and relaxation, inhibition of calcification. Furthermore, we discuss the role of apelin/APJ system in vascular diseases, such as atherosclerosis, hypertension, and chronic kidney disease (CKD) from the point of VSMC. Above all, apelin/APJ system is a promising target for managing vascular disease.
作者机构：
[Tang Mingzhu; Lu Liqun; Huang Zhen; Chen Linxi] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,Learning Key Laboratory for Pharmacoproteomics, Hengyang, 421001
通讯机构：
[Chen, L.] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang, China
关键词：
线粒体;动力学;机制;病理;信号;蛋白质;关键酶;荧光灯
摘要：
Acta Biotheoretica is devoted to the promotion of theoretical biology, encompassing mathematical biology and the philosophy of biology, paying special attention to the methodology of formation of biological theory. Papers on all kind of biological theories are welcome. Interesting subjects include philosophy of biology, biomathematics, computational biology, genetics, ecology and morphology. The process of theory formation can be presented in verbal or mathematical form. Moreover, purely methodological papers can be devoted to the historical origins of the philosophy underlying biological theories and concepts. Papers should contain clear statements of biological assumptions, and where applicable, a justification of their translation into mathematical form and a detailed discussion of the mathematical treatment. The connection to empirical data should be clarified. Acta Biotheoretica also welcomes critical book reviews, short comments on previous papers and short notes directing attention to interesting new theoretical ideas. Coverage in the Journals@Ovid database begins with the first 1997 issue.
摘要：
A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC50 values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.
作者机构：
[Liqun Lu; Mingzhu Tang] 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, 421001, China;[Feng Xie] 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, 421001, China. 764136587@qq.com;[Linxi Chen] 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, 421001, China. lxchen6@126.com
通讯机构：
[Feng Xie; Linxi Chen] I;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<&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：
Critical Mechanism;Neuronal Function;Fragile X Mental Retardation Protein (FMRP);Small Ubiquitin-like Modifier (SUMO);methyl-CpG-binding Protein 2 (MeCP2)
摘要：
Recently,Khayachi et al.showed that fragile X mental retardation protein (FMRP) is an active substrate of the small ubiquitin-like modifier (SUMO) pathway in neurons.FMRP SUMOylation is induced by the activation of metabotropic glutamate receptors (mGlu5Rs).FMRP SUMOylation is required for dissociating FMRP from dendritic RNA granules and controlling spine density and proper maturation.Mechanically,the SUMOylation process is triggered by the activation of mGlu5Rs,thereby contributing to maintaining FMRP-mediated neuronal function.In fact,some proteins that mediate synaptic plasticity,neurotransmitter release,and neuronal network formation,are mostly regulated by SUMOylation.Therefore,SUMOylation has emerged as an essential posttranslational modification in the nervous system.This novel discovery first provides evidence to support the idea that FMRP is a novel substrate of SUMOylation and acts as an essential regulator in the developing brain.Clearly,it also expands the biological ramifications of FMRP modification,since FMRP was previously supposed to be modulated by phosphorylation and dephosphorylation.Together,their research reveals that the rapid SUMOylation of FMRP results from the activation of mGlu5Rs and activity-dependent FMRP SUMOylation is a novel target for affecting neuronal functions.
摘要：
Olfactory receptors (ORs) are mainly distributed in olfactory neurons and play a key role in detecting volatile odorants, eventually resulting in the production of smell perception. Recently, it is also reported that ORs are expressed in non-olfactory tissues including heart, lung, sperm, skin, and cancerous tissues. Interestingly, ectopic ORs are associated with the development of diseases in non-olfactory tissues. For instance, ectopic ORs initiate the hypoxic ventilatory responses and maintain the oxygen homeostasis of breathing in the carotid body when oxygen levels decline. Ectopic ORs induce glucose homeostasis in diabetes. Ectopic ORs regulate systemic blood pressure by increasing renin secretion and vasodilation. Ectopic ORs participate in the process of tumor cell proliferation, apoptosis, metastasis, and invasiveness. Ectopic ORs accelerate the occurrence of obesity, angiogenesis and wound-healing processes. Ectopic ORs affect fetal hemoglobin levels in sickle cell anemia and thalassemia. Finally, we also elaborate some ligands targeting for ORs. Obviously, the diversified function and related signal pathway of ectopic ORs may play a potential therapeutic target in non-olfactory tissues. Thus, this review focuses on the latest research results about the diversified function and therapeutic potential of ectopic ORs in non-olfactory tissues.
摘要：
Macrophage autophagy contributes to the hydrolysis of cholesteryl ester into free cholesterol mainly for ATP-binding cassette transporter A1 (ABCA1)-dependent efflux. Interferon-stimulated gene 15 (ISG15) has been shown to regulate autophagy in multiple types of cells. The present study aimed to examine the effects of ISG15 on autophagy and cholesterol efflux in THP-1 macrophage-derived foam cells and to explore the underlying molecular mechanisms. Our results showed that overexpression of ISG15 promoted autophagy and cholesterol efflux and inhibited lipid accumulation without impact on ABCA1 expression. Inhibition of autophagy by 3-methyladenine (3-MA) abrogated the enhancing effects of ISG15 on cholesterol efflux. Both bioinformatics analysis and dual luciferase reporter assay identified Beclin-1 as a direct target of miR-17-5p. Moreover, ISG15 overexpression markedly decreased miR-17-5p levels and upregulated Beclin-1 expression. ISG15-induced enhancement of autophagy and cholesterol efflux was reversed by pretreatment with either miR-17-5p mimic or Beclin-1 siRNA. In conclusion, these findings suggest that ISG15 reduces miR-17-5p levels and thereby promotes Beclin-1-mediated autophagy, resulting in increased cholesterol efflux from THP-1 macrophage-derived foam cells.
摘要：
beta2-microglobulin (B2M), the light chain of major histocompatibility complex class I (MHC I) molecules, has been found to impair hippocampal neurogenesis. Based on the crucial role of hippocampal neurogenesis disturbance in the process of depression and anxiety, the aim of the present study is to investigate whether B2M leads to depressive- and anxiety-like behaviors. We found that 6 days after intracerebroventricular injection with B2M (0.3 mug), the immobility times of rats in the tail suspension test and the forced swimming test were increased, the swimming and climbing time in the forced swimming test was decreased, and the latency to feed in the novelty-suppressed feeding test was increased, indicating that B2M induces depressive-like behaviors. In addition, in the elevated plus maze test, B2M-treated rats displayed obvious decline in the number of entries into and the proportion of time spent in the open arm, while the number of total arm entries was no change, which indicated that B2M induces anxiety-like behaviors. Our present findings suggest that target B2M might represent a novel approach for treatment of depression and anxiety.
摘要：
Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease.
通讯机构：
[Li, LF; Chen, LX] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
The P2X7 receptor;Myocardial ischemia-reperfusion injury;Dilated cardiomyopathy;Autoimmune myocarditis;Atherosclerosis;Diabetic retinopathy
摘要：
The P2X7 purinergic receptor, a calcium permeable cationic channel, is activated by extracellular ATP. Most studies show that P2X7 receptor plays an important role in the nervous system diseases, immune response, osteoporosis and cancer. Mounting evidence indicates that P2X7 receptor is also associated with cardiovascular disease. For example, the P2X7 receptor activated by ATP can attenuate myocardial ischemia-reperfusion injury. By contrast, inhibition of P2X7 receptor decreases arrhythmia after myocardial infarction, prolongs cardiac survival after a long term heart transplant, alleviates the dilated cardiomyopathy and the autoimmune myocarditis process. The P2X7 receptor also mitigates vascular diseases including atherosclerosis, hypertension, thrombosis and diabetic retinopathy. This review focuses on the latest research on the role and therapeutic potential of P2X7 receptor in cardiovascular diseases.
摘要：
The present review describes the advantages and updated applications of the T7 phage display system in bioscience and medical science. Current phage display systems are based on various bacteriophage vectors, including M13, T7, T4 and f1. Of these, the M13 phage display is the most frequently used, however, the present review highlights the advantages of the T7 system. As a phage display platform, M13 contains single-stranded DNA, while the T7 phage consists of double-stranded DNA, which exhibits increased stability and is less prone to mutation during replication. Additional characteristics of the T7 phage include the following: The T7 phage does not depend on a protein secretion pathway in the lytic cycle; expressed peptides and proteins are usually located on the C-terminal region of capsid protein gp10B, which avoids problems associated with steric hindrance; and T7 phage particles exhibit high stability under various extreme conditions, including high temperature and low pH, which facilitates effective high-throughput affinity elutriation. Recent applications of the T7 phage display system have been instrumental in uncovering mechanisms of molecular interaction, particularly in the fields of antigen discovery, vaccine development, protein interaction, and cancer diagnosis and treatment.
