摘要：
Mycoplasma genitalium adhesion protein (MgPa) is a major adhesin of M. genitalium, a human pathogen associated with a series of genitourinary tract diseases. MgPa plays a very important role in M. genitalium adhering to the host cells. However, the exact receptor peptides or proteins of MgPa are still poorly understood so far. Three polypeptides (V-H-W-D-F-R-Q-W-W-Q-P-S), (D-W-S-S-W-V -Y-R-D-P-Q-T) and (H-Y-I-D-F-R-W) were previously screened from a phage display random peptide library using recombinant MgPa (rMgPa) as a target molecule. In this study, three polypeptides were artificially synthesized and investigated as to whether they are potential receptors of MgPa. We found that rMgPa specifically bound to three synthesized polypeptides as determined via an indirect enzyme-linked immunosorbent assay (ELISA). Moreover, three polypeptides were further identified by indirect immunofluorescence microscopy (IFM). We confirmed that rMgPa and M. genitalium can adhere to SV-HUC-1 cells in vitro and that anti-rMgPa antibody and three synthesized polypeptides can partially inhibit the adherence of rMgPa and M. genitalium to SV-HUC-1 cells. In summary, these three polypeptides may be the essential receptor peptides of MgPa, and may aid in enhancing the understanding of biological function of MgPa and the possible pathogenic mechanism of M. genitalium.
作者机构：
[Tang, SS; Mo, Zhongcheng; Ou, Hanxiao; Tang, Shengsong; Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.;[Liu, Chuhao; Xiao, Xinwen; Feng, Wenjie] Univ South China, Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Tang, SS; Mo, ZC] U;[Tang, Shengsong] H;Univ South China, Inst Pharm & Pharmacol, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Peoples R China.;Hunan Univ Med, Ctr Life Sci, Huaihua 418000, Peoples R China.
关键词：
adenosine monophosphate-activated protein kinase;autophagy;lipid metabolism;atherosclerosis-associated cell;atherosclerosis
摘要：
Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.
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：
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.
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.
作者：
Li, Shuihong;Mou, Qianqian;Xu, Xinya*;Qi, Shuhua;Leung, Polly H. M.
期刊：
ROYAL SOCIETY OPEN SCIENCE,2018年5(5):172466 ISSN：2054-5703
通讯作者：
Xu, Xinya
作者机构：
[Li, Shuihong] Univ South China, Inst Pathogen Biol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Med Coll, Hengyang 421001, Peoples R China.;[Xu, Xinya; Qi, Shuhua] Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Guangdong, Peoples R China.;[Mou, Qianqian; Leung, Polly H. M.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong 999077, Hong Kong, Peoples R China.
通讯机构：
[Xu, Xinya] C;Chinese Acad Sci, South China Sea Inst Oceanol, Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Guangdong, Peoples R China.
摘要：
Penicillenol A2 (isolated from deep-sea fungus Penicillium biourgeianum DFFSCS023) has good antibacterial activity against methicillin-sensitive Staphylococcus aureus and in combination with beta-lactam antibiotics it could significantly decrease methicillin-resistant Staphylococcus aureus (MRSA) survival, which provides a novel treatment consideration for MRSA-caused infections.
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.
摘要：
Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors.
作者机构：
[Tang, Xiao-Qing; Huang, Hong-Lin; Wei, Le] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Chun-Yan; Tang, Xiao-Qing; Zou, Wei; Kan, Li-Yuan; Wei, Le; Zeng, Hai-Ying; Tang, Yi-Yun; Xie, Ming; Zhang, Ping] Univ South China, Med Coll, Dept Physiol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wang, Chun-Yan; Tang, Xiao-Qing; Zou, Wei; Kan, Li-Yuan; Wei, Le; Zeng, Hai-Ying; Tang, Yi-Yun; Xie, Ming; Zhang, Ping] Univ South China, Med Coll, Inst Neurosci, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Tang, Xiao-Qing; Kan, Li-Yuan; Xie, Ming] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;[Zou, Wei; Zeng, Hai-Ying; Zhang, Ping] Univ South China, Nanhua Affiliated Hosp, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Huang, Hong-Lin; Tang, Xiao-Qing] H;Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Institute of Pharmacy and Pharmacology, University of South China, 28 West Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.;Department of Physiology and Institute of Neuroscience, Medical College, University of South China, 28 W Changsheng Road, Hengyang, 421001, Hunan, People's Republic of China.;Department of Neurology, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
摘要：
Our previous works have shown that hydrogen sulfide (H2S) significantly attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and hippocampal endoplasmic reticulum (ER) stress. Brain-derived neurotrophic factor (BDNF) generates an antidepressant-like effect by its receptor tyrosine protein kinase B (TrkB). We have previously found that H2S upregulates the expressions of BDNF and p-TrkB in the hippocampus of CUMS-exposed rats. Therefore, the present work was to explore whether BDNF/TrkB pathway mediates the antidepressant-like role of H2S by blocking hippocampal ER stress. We found that treatment with K252a (an inhibitor of BDNF/TrkB pathway) significantly increased the immobility time in the forced swim test and tail suspension test and increased the latency to feed in the novelty-suppressed feeding test in the rats cotreated with sodium hydrosulfide (NaHS, a donor of H2S) and CUMS. Similarly, K252a reversed the protective effect of NaHS against CUMS-induced hippocampal ER stress, as evidenced by increases in the levels of ER stress-related proteins, glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12. Taken together, our results suggest that BDNF/TrkB pathway plays an important mediatory role in the antidepressant-like action of H2S in CUMS-exposed rats, which is by suppression of hippocampal ER stress. These data provide a novel mechanism underlying the protection of H2S against CUMS-induced depressive-like behaviors.
