摘要:
Circular RNA (circRNA) is a class of RNA with the 5' and 3' ends connected covalently to form a closed loop structure and characterized by high stability, conserved sequences and tissue specificity, which is caused by special reverse splicing methods. Currently, it has become a hot spot for research. With the discovery of its powerful regulatory functions and roles, the molecular mechanisms and future value of circRNA in participating in and regulating biological and pathological processes are becoming increasingly apparent. Among them is the increasing prevalence of cardiovascular diseases (CVDs). Many studies have elucidated that circRNA plays a crucial role in the development and progression of CVDs. Therefore, circRNA shows its advantages and brilliant expectations in the field of CVDs. In this review, we describe the biogenesis, bioinformatics detection and function of circRNA and discuss the role of circRNA and its effects on CVDs, including atherosclerosis, myocardial infarction, cardiac hypertrophy and heart failure, myocardial fibrosis, cardiac senescence, pulmonary hypertension, and diabetic cardiomyopathy by different mechanisms. That shows circRNA advantages and brilliant expectations in the field of CVDs.
期刊:
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY,2023年227:106199 ISSN:0960-0760
通讯作者:
Guo, Zifen
作者机构:
[Guo, Zifen; Wen, Xiaosha; Pu, Huijie] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Luo, DiXian] Huazhong Univ Sci & Technol, Technol Union Shenzhen Hosp, Nanshan Hosp, Dept Lab Med, Wuhan 518000, Guangdong, Peoples R China.
通讯机构:
[Guo, Zifen] I;Institute of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address:
关键词:
Breast cancer;Endometrial cancer;Endometriosis;Progesterone;Progesterone receptor
摘要:
The uterus and breasts are hormone-responsive tissues. Progesterone and estradiol regulate gonadotropin secretion, prepare the endometrium for implantation, maintain pregnancy, and regulate the differentiation of breast tissue. Dysregulation of these hormones causes endometriosis, endometrial cancer, and breast cancer, damaging the physical and mental health of women. Emerging evidence has shown that progesterone resistance or elevated progesterone activity is the primary hormonal substrate of these diseases. Since progesterone acts through its specific nuclear receptor, the abnormal expression of the progesterone receptor (PR) dysregulates progesterone function. This review discusses the regulatory mechanisms of PR expression in patients with endometriosis, and endometrial or breast cancer, including estrogen, polymorphisms, transcription factors, epigenetics, and the ubiquitin-proteasome system. (1) Estrogen promotes the expression of PRA (a PR isoform) mRNA and protein through the interaction of estrogen receptors (ERs) and Sp1 with half-ERE/Sp1 binding sites. ERs also affect the binding of Sp1 and Sp1 sites to promote the expression of PRB (another PR isoform)(2) PR polymorphisms, mainly PROGINS and + 331 G/A polymorphism, regulate PR expression by affecting DNA methylation and transcription factor binding. (3) The influence of epigenetic alterations on PR expression occurs through DNA methylation, histone modification, and microRNA. (4) As one of the main protein degradation pathways in vivo, the ubiquitin-proteasome system (UPS) regulates PR expression by participating in protein degradation. These mechanisms may provide new molecular targets for diagnosing and treating endometriosis, endometrial, and breast cancer.
作者机构:
[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Tang, Hui-Fang; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan] Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;[Li, Chun-Quan; Qian, Feng-Cui] Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Li, CQ ; Tang, HF ; Tang, HF] U;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Key Lab Multiom & Artificial Intelligen, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
摘要:
Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.
摘要:
Alkaline phosphatase (ALP) is a group of enzymes that catalyze hydrolysis of phosphate esters at an alkaline pH, resulting in the generation of inorganic phosphate. These enzymes are widely distributed, and their activity is found in various tissues including bone, liver, intestine, and placenta. However, abnormalities in ALP expression and activity have been observed in certain types of cancer. In some cases, elevated serum levels of ALP are observed in patients with liver and bone metastasis. In other cases, increased levels of ALP have been observed in patients with pancreatic and lung cancer. On the other hand, low expression of ALP has also been associated with poor prognosis in patients with certain types of tumors, including colorectal cancer (CRC), breast cancer, and non-small cell lung cancer (NSCLC). In these cases, low ALP activity may be associated with decreased differentiation of cancer cells and increased cancer cell proliferation. Overall, the role of ALP in cancer is complex and context-dependent. This article reviews application progress of ALP in cancer, and we hypothesize that ALP might be a potential tumor biomarker, combined detection of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), bone-specific alkaline phosphatase (BSAP), carbohydrate antigen 19-9 (CA 19-9), lactate dehydrogenase (LDH) and ALP isozymes levels can be used for more accurate diagnosis of a particular tumor. Further research is needed to better understand the mechanisms underlying ALP dysregulation in cancer and to identify potential therapeutic targets.
作者机构:
[Yan, Qi; Song, Jiaqi; Wang, Jiyan; Chang, Hongkai; Sun, Huanran; Xie, Fei; Zhang, Han; Sun, Mingming; Shan, Changliang; Wang, Yingzhi; Qiao, Yaya] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin Key Lab Mol Drug Res, Tianjin 300350, Peoples R China.;[Li, Zhen; Li, Leilei] Jinan Univ, Biomed Translat Res Inst, Guangzhou 510632, Peoples R China.;[Lin, Shu-Hai; Niu, Yujia] Xiamen Univ, Innovat Ctr Cell Signaling Network, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Peoples R China.;[Tan, Junzhen; Lai, Sizhen; Zhao, Huifang; Yang, Chenxin; Zhang, Shuai] Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin 301617, Peoples R China.;[Li, Yanping] Jining Med Univ, Inst Precis Med, Dept Pathol, Jining 272067, Peoples R China.
通讯机构:
[Lin, S.-H.] S;State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China
摘要:
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein argi-nine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and a-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post -translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.(c) 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
摘要:
Mammalian autophagy-related protein Atg8, including the LC3 subfamily and GABARAP subfamily. Atg8 proteins play a vital role in autophagy initiation, autophagosome formation and transport, and autophagy-lysosome fusion. GABARAP subfamily proteins (GABARAPs) share a high degree of homology with LC3 family proteins, and their unique roles are often overlooked. GABARAPs are as indispensable as LC3 in autophagy. Deletion of GABARAPs fails autophagy flux induction and autophagy lysosomal fusion, which leads to the failure of autophagy. GABARAPs are also involved in the transport of selective autophagy receptors. They are engaged in various particular autophagy processes, including mitochondrial autophagy, endoplasmic reticulum autophagy, Golgi autophagy, centrosome autophagy, and dorphagy. Furthermore, GABARAPs are closely related to the transport and delivery of the inhibitory neurotransmitter γ-GABA(A) and the angiotensin II AT1 receptor (AT1R), tumor growth, metastasis, and prognosis. GABARAPs also have been confirmed to be involved in various diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In order to better understand the role and therapeutic potential of GABARAPs, this article comprehensively reviews the autophagic and non-autophagic functions of GABARAPs, as well as the research progress of the role and mechanism of GABARAPs in cancer, cardiovascular diseases and neurodegenerative diseases. It emphasizes the significance of GABARAPs in the clinical prevention and treatment of diseases, and may provide new therapeutic ideas and targets for human diseases. GABARAP and GABARAPL1 in the serum of cancer patients are positively correlated with the prognosis of patients, which can be used as a clinical biomarker, predictor and potential therapeutic target. GABARAP family proteins: autophagy and non-autophagy related functions in diseases. By Figdraw ( https://www.figdraw.com ).
作者机构:
[Li, Ao; He, Longwei; Liu, Yalan; Chen, Zhe; Li, Songjiao; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharm, Hengyang Med Sch,Hunan Prov Key Lab Tumor Microen, Hengyang 421001, Peoples R China.;[Zhong, Rongbin; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang 421002, Peoples R China.
通讯机构:
[Linxi Chen; Longwei He] S;School of Pharmacy, 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, 421001, PR China
作者机构:
[Chen, Hong-Fei; Yang, Ze-Hua; Gao, Cong-Xi; Wu, Ting-Juan; Peng, Ya-Ling; Liu, Qian-Wen; Tang, Cai-Hong; Hu, Yue; Liu, Mei-Ling; Zheng, Xing] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Prov Key Lab Tumor Microenvironm Respons Dr, Grp Lead Compound,Dept Pharm,Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Gao, Cong-Xi] Kunming Med Univ, Sch Pharm, Kunming 650500, Yunnan, Peoples R China.;[Gao, Cong-Xi] Kunming Med Univ, Yunnan Key Lab Nat Med Pharmacol, Kunming 650500, Yunnan, Peoples R China.
通讯机构:
[Ze-Hua Yang; Xing Zheng] G;Group of Lead Compound, Department of Pharmacy, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medicinal School, University of South China, Hengyang421001, China<&wdkj&>Group of Lead Compound, Department of Pharmacy, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medicinal School, University of South China, Hengyang421001, China
关键词:
Oleanolic acid derivatives;A ring modification;anticancer activity;C-28 site modification;mechanism of action
摘要:
Oleanolic acid (OA) is a five-ring triterpenoid compound, which is widely present in plants. Due to a wide range of pharmacological activities, oleanolic acid has attracted more and more attention. However, oleanolic acid is insoluble in water and has low bioavailability, which limits its clinical application. In this review, we focus on summarizing the anti-cancer activity and mechanism of the A ring or C-28 carboxyl modified derivatives of OA since 2015, to determine the strength of its anti-cancer effectiveness and evaluate whether it could be used as a clinical anti-cancer drug.
摘要:
Linezolid combined with rifampicin has shown excellent clinical outcomes against infection by multi-resistant Gram-positive bacteria. However, several studies have indicated that rifampicin reduces the plasma concentration of linezolid in patients with severe infection. Linezolid has been recommended for the treatment of patients with multidrug-resistant or extensively drug-resistant tuberculosis. However, studies on the interaction between linezolid and rifampicin in patients suffering from tuberculosis with infection are lacking. We evaluated the interaction between linezolid and rifampicin based on therapeutic drug monitoring (TDM). A retrospective analysis was undertaken for patients with tuberculosis and infection who were treated with linezolid and undergoing TDM. Patients were divided into the linezolid group and linezolid + rifampicin group. Data on demographic characteristics, disease, duration of linezolid therapy, and the plasma concentration of linezolid were used for statistical analyses. Eighty-eight patients with tuberculosis and infection were assessed. Values for the peak (Cmax) and trough (Cmin) concentrations of linezolid in plasma were available for 42 and 46 cases, respectively. Patients in the linezolid group had a significantly higher Cmax [15.76 (8.07–26.06) vs. 13.18 (7.48–23.64) mg/L, p = 0.048] and Cmin [8.38 (3.06–16.53) vs. 4.27 (0.45–10.47), p = 0.005] than those in the linezolid + rifampicin group. The plasma concentration of linezolid increased obviously in two patients after rifampicin discontinuation. However, the total efficiency and prevalence of hematologic adverse reactions were not significantly different in the linezolid group and linezolid + rifampin group. The plasma concentration of linezolid decreased upon combination with rifampicin, suggesting that TDM may aid avoidance of subtherapeutic levels of linezolid upon co-treatment with rifampicin.
摘要:
Formaldehyde (FA) has neurotoxic characteristics and causes neurodegenerative disease. Our previous study demonstrated the neuroprotective effects of hydrogen sulfide (H(2)S) on FA-induced neurotoxicity in HT22 cells. Emerging evidence have supported that ferroptosis is involved in FA-induced neurotoxicity. To understand the mechanism of the protection of H(2)S against FA-induced neurotoxicity, this study explored the regulatory effect of H(2)S on FA-induced ferroptosis and the underlying mechanisms. The researcher found that H(2)S (100, 200, and 400μM, 30min) reverses the ferroptosis induced by FA (100μM, 24h) in HT22 cells (a cell line of mouse hippocampal neurons), including decreases in free iron, reactive oxygen species (ROS), 4-hydroxy-2-trans-nominal (4-HNE), and malondialdehyde (MDA) contents, as well as an increase in glutathione (GSH) content. H(2)S (100, 200, and 400μM, 30min) also inhibited ferritinaphagy in FA-exposed HT22 cells, as evidenced by the downregulation of the ferritinophagy receptor nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1 light chain-3B (LC3B) as well as the upregulation of the main iron storage protein ferritin heavy chain 1 (FTH1) and p62. H(2)S (100, 200, and 400μM, 30min) also up-regulated the expression of growth differentiation factor-11 (GDF11) in FA-exposed HT22 cells. Furthermore, knockdown of GDF11 in HT22 cells cancelled the beneficial effects of H(2)S in FA-induced ferroptosis and ferritinaphagy. These data indicated that the protective mechanism underlying H(2)S-prevented neurotoxicity of FA is involved in alleviating FA-induced ferroptosis via inhibiting ferritinaphagy by upregulation of GDF11.
作者机构:
[Xie, Zhizhong; Lei, Xiaoyong; Sun, Xueyan; Tang, Guotao] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.;[Wang, Zhe; Wang, Z] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[Huang, Sheng] Jiuzhitang Co Ltd, Changsha 410007, Hunan, Peoples R China.
通讯机构:
[Wang, Z ; Tang, GT ] U;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hunan Prov Key Lab Tumor Microenvironm Respons Dru, Hengyang 421001, Hunan, Peoples R China.
摘要:
Tumor neovascularization provides abundant nutrients for the occurrence and development of tumors, and is also an important factor in tumor invasion and metastasis, which has attracted extensive attention in anti-tumor therapy. Sorafenib is a clinically approved multi-targeted anti-tumor drug that targets vascular endothelial growth factor receptor (VEGFR) and inhibits the formation of tumor angiogenesis, thereby achieving the purpose of suppressing tumor growth. Since the approval of sorafenib, N,N'-diarylureas have received extensive attention as the key pharmacophore in its chemical structure. And a series of N,N'-diarylureas were designed and synthesized to screen a new generation of anti-tumor drug candidates through chemical modification and structural optimization. Moreover, the rational design of targeted drugs is beneficial to reduce toxic side effects and drug resistance and improve the curative effect. Here, this article reviews the research progress in the design, classification, structure-activity relationship (SAR) and biological activity of N,N'-diarylureas, in order to provide some prospective routes for the development of clinically effective anti-tumor drugs.
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
关键词:
cancer;mercury;plant;ribosomal protein S27a;ubiquitin
摘要:
The ribosomal protein S27a (RPS27a) is cleaved from the fusion protein ubiquitin–RPS27a (Ub–RPS27a). Generally, Ub and RPS27a are coexpressed as a fusion protein but function independently after Ub is cleaved from RPS27a by a deubiquitinating enzyme. We reviewed the functions of RPS27 in various cancers, including colorectal cancer, liver cancer, chronic myeloid leukemia, and renal carcinoma. We also introduced a mechanism through which RPS27a affects the physiological processes in animals and plants. Abstract The ribosomal protein S27a (RPS27a) is cleaved from the fusion protein ubiquitin–RPS27a (Ub–RPS27a). Generally, Ub and RPS27a are coexpressed as a fusion protein but function independently after Ub is cleaved from RPS27a by a deubiquitinating enzyme. As an RP, RPS27a assembles into ribosomes, but it also functions independently of ribosomes. RPS27a is involved in the development and poor prognosis of various cancers, such as colorectal cancer, liver cancer, chronic myeloid leukemia, and renal carcinoma, and is associated with poor prognosis. Notably, the murine double minute 2/P53 axis is a major pathway through which RPS27a regulates cancer development. Moreover, RPS27a maintains sperm motility, regulates winged aphid indirect flight muscle degeneration, and facilitates plant growth. Additionally, RPS27a is a metalloprotein and mercury (Hg) biomarker. In the present review, we described the origin, structure, and biological functions of RPS27a.
作者机构:
[Sun, Shaowei; Tang, Yuehong; Sun, SW; Gao, Yi; Ye, Shiying] Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Tong, Wenjuan] Univ South China, Affiliated Hosp 1, Dept Gynecol & Obstet, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Tong, WJ ; Sun, SW ] U;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Gynecol & Obstet, Hengyang 421001, Hunan, Peoples R China.
关键词:
Central nervous system;Cholesterol homeostasis;Neurodegenerative diseases
摘要:
The brain is the most cholesterol-rich organ in mammals. However, cholesterol metabolism in the brain is completely independent of other tissues due to the presence of the blood-brain barrier (BBB). Neurons, astrocytes and oligodendrocytes are the main cells responsible for cholesterol synthesis in the brain. The cholesterol content in the brain is maintained at a relatively constant level under strict regulation of synthesis, transport, and turnover, that is, brain cholesterol homeostasis. Once this balance is disrupted, neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD) ensue. This review summarizes the processes controlling cholesterol homeostasis with respect to the synthesis, transport and turnover of cholesterol in the brain. We further focus on how cholesterol imbalance contributes to neurodegenerative diseases to explore the possibilities to modulate the key steps involved, which will provide clues for the development of therapies for the treatment of central nervous system (CNS) diseases.
摘要:
Long non-coding RNAs play important roles in cellular functions and disease development. H19, as a long non-coding RNA, is pervasively over-expressed in almost all kinds of human malignant tumors. Although many studies have reported that H19 is closely associated with tumor cell proliferation, apoptosis, invasion, metastasis, and chemoresistance, the role and mechanism of H19 in gene regulation and tumor development are largely unclear. In this review, we summarized the recent progress in the study of the major functions and mechanisms of H19 lncRNA in cancer development and progression. H19 possesses both oncogenic and tumor-suppressing activities, presumably through regulating target gene transcription, mRNA stability and splicing, and competitive inhibition of endogenous RNA degradation. Studies indicate that H19 may involve in cell proliferation and apoptosis, tumor initiation, migration, invasion, metastasis and chemoresistance and may serve as a potential biomarker for early diagnosis, prognosis, and novel molecular target for cancer therapy.
期刊:
JOURNAL OF MATERIALS CHEMISTRY B,2023年11(39):9459-9466 ISSN:2050-750X
通讯作者:
Cheng, D;Li, Songjiao;He, LW
作者机构:
[He, LW; Zeng, Jiayu; Li, Songjiao; He, Longwei; Jiang, Renfeng] Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421002, Hunan, Peoples R China.;[Cheng, Dan; Liu, Qian] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang 421002, Hunan, Peoples R China.
通讯机构:
[He, LW ; Cheng, D ; Li, SJ] U;Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang 421002, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421002, Hunan, Peoples R China.
摘要:
Hepatocellular carcinoma (HCC) is a type of cancer associated with a high rate of mortality and morbidity. In order to achieve precise HCC theranostics, it is important to develop excellent fluorescent probes. However, the existing probes are not sensitive or specific enough to accurately identify HCC margins and contours. For diagnosing HCC and identifying tumors during surgery, it is urgent to engineer highly sensitive and selective fluorescent probes. Liver tumor progression is closely associated with leucine aminopeptidase (LAP) overexpression, a biomarker of liver cancer. Herein, we have rationally designed a NIR fluorescent probe, NLAP, which is specially activated by LAP. The probe exhibited high sensitivity (detection limit = 6.8 mU L-1) and superior affinity (Km = 2.98 mu M) for LAP. With this probe, we distinguished cancer cells overexpressing LAP from normal cells and applied it intraoperatively to guide liver tumor excisions. Furthermore, NLAP was employed to successfully detect the LAP of intestinal and splenic metastatic tumors in orthotopic liver tumor mice by "in situ spraying" and good performances were demonstrated. Visualizing a LAP change in cancer cells and normal cells and guiding surgical resection of liver cancer by engineering an activated near-infrared fluorescent probe with high sensitivity and selectivity.
期刊:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2023年157:106392 ISSN:1357-2725
通讯作者:
Yuping Chen
作者机构:
[Chen, Yuping; Zhang, Jie; Xun, Min] Univ South China, Inst Pharm & Pharmacol, Sch Pharmaceut Sci, Hengyang 421001, Peoples R China.;[Chen, Yuping; Wu, Meichun] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Wu, Meichun] Univ South China, Sch Nursing, Hengyang 421001, Peoples R China.;[Chen, Yuping] Univ South China, Sch Pharmaceut Sci, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Yuping Chen] I;Institute of Pharmacy & Pharmacology, School of Pharmaceutical Science, University of South China, Hengyang 421001, China<&wdkj&>Hengyang Medical School, University of South China, Hengyang 421001, China
摘要:
The active proliferation and migration of vascular smooth muscle cells supports the healing of vessel damage while their abnormal aggression or destitution contribute to the aberrant intima-medial structure and function in various cardiovascular diseases, so the understanding of the proliferation disorders of vascular smooth muscle cell and the related mechanism is the basis of effective intervention and control for cardiovascular diseases. Recently, long non-coding RNAs have stood out as upstream switchers for multiple proliferative signaling pathways and molecules, and many of them have been shown to conduce to the dysregulated proliferation and apoptosis of vascular smooth muscle cells under various pathogenic stimuli. This article discusses the long non-coding RNAs disclosed and linked to atherosclerosis, pulmonary hypertension, and aneurysms, and focuses upon their modulation of vascular smooth muscle cell population affecting three deadly cardiovascular diseases.
摘要:
Alkaline phosphatase (ALP) is an indicator of sterilization efficacy of milk products and its activity monitoring is essential for ensuring food safety and controlling product quality. Here, a novel fluorometric method for the determination of ALP activity based on resorcinol monophosphate ester (RME) as a new substrate was proposed to verify pasteurization of milk products. RME was cheap and was simply and novelly synthesized by a two-step method using resorcinol (RC) as the raw material. The mechanism is, after dephosphorylation, RME was transformed to RC, which subsequently react with dopamine (DA) to form a strong fluorescent product, azamonardine. It has a fluorescence emission wavelength at 461 nm under the optimal excitation at 418 nm. The results show that under the optimum conditions, there is a good linear relationship between & UDelta;F (the variation of fluorescence intensity) and ALP activity over 0-5000 mU/L. High sensitivity was achieved (detection limit of 17.34 mU/L) because of high quantum yield of the products and catalytic activity of ALP and the recovery rate is 96.8-106.1%. Compared with national and international standard methods, the detection procedures are simple, just adding RME and DA solution to milk with buffer solution. Our method was successfully applied for ALP activity detection in milk products. Moreover, the catalyst of ALP and the reaction of RME and dopamine are pH dependent, and thus the reaction time could be kept identical by terminating the reaction through adding acids. With high sensitivity, high selectivity, simple operation, and wide linear range, our assay will find more practical applications in food analysis.
期刊:
Sensors and Actuators B-Chemical,2023年379:133253 ISSN:0925-4005
通讯作者:
He, LW;Cheng, D
作者机构:
[He, LW; Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;[Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构:
[He, LW ; Cheng, D ] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch, Dept Pharm & Pharmacol, Hengyang, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
摘要:
Hypochlorous acid (HClO) is a key signal molecule involved in various physiological and pathological processes as well as the immune system. Recent study demonstrated that excess HClO in the body is closely related to diabetes since it can induce stress in the endoplasmic reticulum (ER). Unfortunately, up to now, developing a near-infrared (NIR) fluorescent probe that can detect ER HClO remains a challenge. Herein, we designed and synthesized NIR-ER-HClO, which stains ER with high selectivity, sensitivity, and hypotoxicity. The probe could accurately monitor exogenous and endogenous HClO variations in living cells. Besides, NIR-ER-HClO was successfully used to image HClO in a diabetic mice model. Compared with the control group, NIR-ER-HClO showed a stronger NIR fluorescence signal in diabetic mice and in the blood of people with diabetes. Thus, NIR-ER-HClO provides an effective method for diagnosing ER HClO in related diseases.