摘要：
BACKGROUND AND AIMS: Fargesin mainly functions in the improvement of lipid metabolism and the inhibition of inflammation, but the role of fargesin in atherogenesis and the molecular mechanisms have not been defined. We aimed to explore if and how fargesin affects atherosclerosis by regulating lipid metabolism and inflammatory response. METHODS AND RESULTS: ApoE(-/-) mice were fed a high-fat diet to form atherosclerotic plaques and then administrated with fargesin or saline via gavage. Oil Red O, HE and Masson staining were performed to assess atherosclerostic plaques in apoE(-/-) mice. [(3)H] labeled cholesterol was used to detect cholesterol efflux and reverse cholesterol transport (RCT) efficiency. Enzymatic methods were performed to analyze plasma lipid profile in apoE(-/-) mice. Immunohistochemistry was used to analyze macrophage infiltration. THP-1-derived macrophages were incubated with fargesin or not. Both Western blot and qRT-PCR were applied to detect target gene expression. Oil Red O staining was applied to examine lipid accumulation in THP-1-derived macrophages. ELISA and qRT-PCR were used to examine the levels of inflammatory mediotors. We found that fargesin reduced atherosclerotic lesions by elevating efficiency of RCT and decreasing inflammatory response via upregulation of ABCA1 and ABCG1 expression in apoE(-/-) mice. Further, fargesin reduced lipid accumulation in THP-1-derived macrophages. Besides, fargesin increased phosphorylation of CEBPalpha in Ser21 and then upregulated LXRalpha, ABCA1 and ABCG1 expression in THP-1-derived macrophages. In addition, fargesin could reduce ox-LDL-induced inflammatory response by inactivation of the TLR4/NF-kappaB pathway. CONCLUSION: These results suggest that fargesin inhibits atherosclerosis by promoting RCT process and reducing inflammatory response via CEBPalpha(S21)/LXRalpha and TLR4/NF-kappaB pathways, respectively.
期刊：
International Journal of Antimicrobial Agents,2020年55(5):105951 ISSN：0924-8579
通讯作者：
Tang, Chao-Ke;Tang, Shi-Lin
作者机构：
[Tang, Chao-Ke; Liu, Shang-Ming; Li, Heng; Tang, Shi-Lin] Univ South China, Affiliated Hosp 1, Hengyang Med Coll,Dept Intens Care Unit,Hunan Pro, Med Res Expt Ctr,Inst Cardiovasc Dis,Key Lab Arte, Hengyang 421001, Hunan, Peoples R China.;[Yu, Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Hainan, Peoples R China.;[Tang, Chao-Ke] Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shi-Lin] Univ South China, Dept Intens Care Unit, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, Chao-Ke; Tang, Shi-Lin] U;Univ South China, Affiliated Hosp 1, Hengyang Med Coll,Dept Intens Care Unit,Hunan Pro, Med Res Expt Ctr,Inst Cardiovasc Dis,Key Lab Arte, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Cardiovasc Dis, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Dept Intens Care Unit, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
摘要：
Coronavirus disease 2019 (COVID-19) originated in the city of Wuhan, Hubei Province, Central China, and has spread quickly to 72 countries to date. COVID-19 is caused by a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [previously provisionally known as 2019 novel coronavirus (2019-nCoV)]. At present, the newly identified SARS-CoV-2 has caused a large number of deaths with tens of thousands of confirmed cases worldwide, posing a serious threat to public health. However, there are no clinically approved vaccines or specific therapeutic drugs available for COVID-19. Intensive research on the newly emerged SARS-CoV-2 is urgently needed to elucidate the pathogenic mechanisms and epidemiological characteristics and to identify potential drug targets, which will contribute to the development of effective prevention and treatment strategies. Hence, this review will focus on recent progress regarding the structure of SARS-CoV-2 and the characteristics of COVID-19, such as the aetiology, pathogenesis and epidemiological characteristics. (C) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
摘要：
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases. With the aim to find reagents that reduce oxidative stress, a phage display library was screened for peptides mimicking α2,6-sialyllactose (6'-SL), which is known to beneficially influence neural functions. Using Sambucus nigra lectin, which specifically binds to 6'-SL, we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids. Mimetic peptide, reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin. Indeed, lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide, but not by the reverse or scrambled peptides, showing that this peptide mimics 6'-SL. Functionally, mimetic peptide, but not the reverse or scrambled peptides, increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells, and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H(2)O(2)-induced oxidative stress. The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis, thus raising hopes for the treatment of neurodegenerative diseases. This study was approved by the Medical Ethics Committee of Shantou University Medical College, China (approval No. SUMC 2014-004) on February 20, 2014.
摘要：
Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.
摘要：
Multiple sclerosis (MS) is an immune-mediated demyelinated disease of the central nervous system. Activation of microglia is involved in the pathogenesis of myelin loss. This study is focused on the role of Hv1 in regulating demyelination and microglial activation through reactive oxygen species (ROS) production after lysophosphatidylcholine (LPC)-mediated demyelination. We also explored autophagy in this process. A model of demyelination using two-point LPC injection into the corpus callosum was established. LFB staining, immunofluorescence, Western blot, and electron microscopy were used to study the severity of demyelination. Microglial phenotype and autophagy were detected by immunofluorescence and Western blot. Morris water maze was used to test spatial learning and memory ability. We have identified that LPC-mediated myelin damage was reduced by Hv1 deficiency. Furthermore, we found that ROS and autophagy of microglia increased in the demyelination region, which was also inhibited by Hv1 knockout. These results suggested that microglial Hv1 deficiency ameliorates demyelination through inhibition of ROS-mediated autophagy and microglial phenotypic transformation.
期刊：
KAOHSIUNG JOURNAL OF MEDICAL SCIENCES,2020年36(9):741-749 ISSN：1607-551X
通讯作者：
Li, Yan
作者机构：
[Ruan, Zhong-Fan; Lan, Fang; Wan, Juan; Xie, Ming] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang City, Hunan, Peoples R China.;[Gui, Shu-Jia] Univ South China, Affiliated Nanhua Hosp, Dept Neurol, Hengyang City, Hunan, Peoples R China.;[Li, Yan] Univ South China, Affiliated Nanhua Hosp, Dept Anesthesiol, 336 Dongfeng South Rd, Hengyang City, Hunan, Peoples R China.
通讯机构：
[Li, Yan] U;Univ South China, Affiliated Nanhua Hosp, Dept Anesthesiol, 336 Dongfeng South Rd, Hengyang City, Hunan, Peoples R China.
关键词：
MiR-370;Nrf2/ARE signal pathway;SIRT6;cerebral ischemia reperfusion injury
摘要：
Cerebral ischemia reperfusion (CIR) is one of the highly lethal diseases in the world. MicroRNA-370 (miR-370) exerts multiple functions in different diseases. However, further research is needed to investigate the potential role of miR-370 in CIR injury. The in vivo middle cerebral artery occlusion (MCAO) rat model and in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) SH-SY5Y cell model were successfully established to mimic CIR injury. The infarct sizes of brain tissues from rats were evaluated. The relationship between miR-370 and silencing information regulatory protein 6 (SIRT6) was confirmed by luciferase activity assay. The cell viability and apoptosis were determined by CCK-8 assay and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining. In this study, miR-370 was upregulated in brain tissues of MCAO rats and knockdown of miR-370 decreased cerebral infarction volume of MCAO rats and it alleviated CIR injury in vivo. The in vitro experiments indicated that knockdown of miR-370 promoted cell viability and alleviated OGD/R-induced SH-SY5Y cell apoptosis. Additionally, the TargetScan predicted that SIRT6 was a target of miR-370 and confirmed by luciferase activity assay. Moreover, miR-370 inhibited SIRT6 expression and regulated Nrf2/ARE signal pathway, whereas overexpression of SIRT6 partly reversed the effect of miR-370 on OGD/R-induced SH-SY5Y cell injury. Thus, we could conclude that miR-370 accelerated CIR injury via targeting SIRT6 and regulating Nrf2/ARE signal pathway, which might provide novel therapeutic targets for CIR injury treatment.
作者机构：
[Lu, Chunxue; Wu, Yimou; Li, Yumeng; Chen, Yuqing; Zheng, Kang; Tan, Yuan; Yan, Xiaoliang; Wang, Chuan; Xiao, Jian] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang, Peoples R China.;[Lu, Chunxue; Wu, Yimou; Li, Yumeng; Chen, Yuqing; Zheng, Kang; Tan, Yuan; Yan, Xiaoliang; Wang, Chuan; Xiao, Jian] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.;[Wang, Shuzhi] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.;[Yu, Jian] Univ South China, Hengyang Med Coll, Dept Expt Zool, Hengyang 421001, Peoples R China.;[Wu, Yimou] Univ South China, Hengyang Med Coll, Pathogen Biol Inst, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, Yimou] U;Univ South China, Hengyang Med Coll, Pathogen Biol Inst, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
C. psittaci;Pgp3;Multiepitope;Vaccine;Protective immunity
摘要：
Chlamydia psittaci is the pathogen of psittacosis, and it has emerged as a significant public health threat. Because most infections are easily overlooked, a vaccine is recognized as the best solution to control the spread of C. psittaci. Our previous study showed that Pgp3 protein is efficacious as a subunit vaccine while not the best candidate due to the negative effects. Thus, in this study, we tested the ability of a tandem epitope vaccine candidate designated SP based on Pgp3-dominant epitopes to induce protective immunity against pulmonary chlamydial infection. BALB/c mice were intraperitoneally inoculated with multiepitope peptide antigens followed by intranasal infection with C. psittaci. We found that the multiepitope peptide antigens induced strong humoral and cellular immune responses with high Th1-related (IFN-gamma and IL-2) and proinflammatory (IL-6) cytokine levels. Meanwhile, the pathogen burden and inflammatory infiltration were significantly reduced in lungs of SP-immunized mice after chlamydial challenge. In addition, the IFN-gamma and IL-6 secretion levels in the infected lungs were substantially reduced. Overall, our findings demonstrate that the peptide vaccine SP plays a significant role with good immunogenicity and protective efficacy against C. psittaci lung infection in BALB/c mice, providing important insights towards understanding the potential of peptide vaccines as new vaccine antigens for inducing protective immunity against chlamydial infection.
作者机构：
[Yang, Hui-xian] Univ South China, Med Coll, Inst Cardiovasc Dis, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Liao, Duan-fang; Chen, Jian-xiong; Tuo, Qin-hui] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Tian, Ying; Long, Shi-yin; Yang, Hui-xian; Zhang, Cai-ping; Zhang, Min; Liao, DF] Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Jian-xiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, University, MS 38677 USA.
通讯机构：
[Zhang, CP; Liao, DF] U;Univ South China, Med Coll, Dept Biochem & Mol Biol, 28 W Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Dyslipidemia;IDOL;LDL-C;LDLR;PCSK9;SREBP2
摘要：
The SREBP2/LDLR pathway is sensitive to cholesterol content in the endoplasmic reticulum (ER), while membrane low-density lipoprotein receptor (LDLR) is influenced by sterol response element binding protein 2 (SREBP2), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and inducible degrader of LDLR (IDOL). LDL-C, one of the risk factors in cardiovascular disease, is cleared through endocytosis recycling of LDLR. Therefore, we propose that a balance between LDLR endocytosis recycling and PCSK9-mediated and IDOL-mediated lysosomal LDLR degradation is responsible for cholesterol homeostasis in the ER. For statins that decrease serum LDL-C levels via cholesterol synthesis inhibition, the mechanism by which the statins increase the membrane LDLR may be regulated by cholesterol homeostasis in the ER.
摘要：
This current study explored the effects of fine particulate matter (PM2.5) on deoxyribonucleic acid methylation in human bronchial epithelial cells. Human bronchial epithelial cells were exposed to PM2.5 for 24 h after which, deoxyribonucleic acid samples were extracted, and the differences between methylation sites were detected using methylation chips. Subsequent gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the differential methylation sites. Functional epigenetic modules analysis of the overall differential methylation site interactions was also conducted. A total of 127 differential methylation sites in 89 genes were screened in the PM2.5 10 mu g/ml group, of which 55 sites demonstrated increased methylation, with methylation levels decreasing in a further 72 sites. Following an exposure of 50 mu g/ml PM2.5, a total of 238 differentially methylated sites were screened in 168 genes, of which methylation levels increased in 127 sites, and decreased in 111. KEGG analysis showed that the top 10 enrichment pathways predominantly involve hepatocellular carcinoma pathways and endometrial cancer pathways, whereas functional epigenetic modules analysis screened eight genes (A2M, IL23A, TPIP6, IL27, MYD88, ILE2B, NLRC4, TNF) with the most interactions. Our results indicate that exposure to PM2.5 for 24 h in human bronchial epithelial cells induces marked changes in deoxyribonucleic acid methylation of multiple genes involved in apoptosis and carcinogenesis pathways, these findings can provide a new direction for further study of PM2.5 carcinogenic biomarkers.
作者机构：
[Li, Yu-kun; Zou, Juan; Ye, Dong-mei; Zeng, Xi] Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Ying] Univ South China, Sch Nursing, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Xi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Luo, Gui-fang; Chen, Chang-ye] Univ South China, Affiliated Hosp 1, Dept Gynecol, Hengyang 410011, Hunan, Peoples R China.
通讯机构：
[Zeng, Xi; Luo, Gui-fang] U;Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Gynecol, Hengyang 410011, Hunan, Peoples R China.
关键词：
Apoptosis;Cancer;EMT;PAK5;Proliferation
摘要：
An oncogenic role, p21-activated kinase 5 (PAK5), has proven as a significant mediator for many cellular progression, which is expressed highly in human organs such as lung, liver, kidney, blood vessels endothelial cells and inflammatory cells. PAK5 was primitively detected in the cerebrum and accelerated the filopodia formation in neurocytes. It can reverse the effect of Rho and adjust its activity to mediate maintenance and development of nerve axon by binding with Cdc42-GTP. Moreover, PAK5 has been suggested to mediate protean, multitudinous and inscrutable functions in cancer. Currently, many researches indicated that PAK5 was dysregulated in ovarian cancer, cervical cancer, melanoma, osteosarcoma, renal carcinoma, breast cancer, gastric cancer and so on, which was involved in cell proliferation, apoptosis, migration and invasion. This review focuses the latest knowledge on the structure, expression, signalling pathway of PAK5, emphasizing its function in cancer.
摘要：
Cervical cancer (CC) is regarded as the second serious threat to women's health worldwide; it's associated with certain viruses that are transmitted through sexual intercourse. Therefore, the pathogenesis of CC remains to be studied. The identified long non-coding RNAs (lncRNAs) as a key genomic product were found to be commonly dysregulated in CC and to exert significant effects in the initiation, migration, invasion and therapeutic response of CC. Therefore lncRNAs may be used as tumor suppressor genes or oncogenes to interact with DNA, RNA or proteins for the regulation of gene expression and cell signaling pathways. The relationship between single lncRNA and CC has been discovered. However, full-scale reviews on the lncRNAs function in CC are deficiency. In this review, we describe the recent reports on the dysregulated patterns regulation of lncRNAs in CC. We also conclude the recent advances on biologic functions and molecular regulation mechanism and potential clinical application of lncRNAs in CC.
摘要：
Gastric cancer (GC) is the fifth most common primary malignancy in humans. Rho GDP dissociation inhibitor 2 (RhoGDI2) is overexpressed in multiple cancer types, but the role of RhoGDI2 in GC has not been elucidated. This study aims to determine the level of RhoGDI2 in GC and to confirm the effect of its inhibition or overexpression on GC cell migration, invasion and chemosensitivity. RhoGDI2 level is significantly enhanced in human GC tissue samples in comparison with normal gastric epithelium and corresponding para-cancerous samples. The expression of RhoGDI2 is correlated with clinicopathological parameters and prognosis. Transfection in combination with miRNA targeting of RhoGDI2 in GC cell lines remarkably downregulates GC cell migration and invasion and reduces the mRNA levels of Rac1, Pak1 and LIMK1. The inhibition of RhoGDI2 downregulates GC cell migration and invasion by attenuating the EMT cascade via the Rac1/Pak1/LIMK1 pathway. Knockdown of RhoGDI2 is a potential therapeutic strategy for GC.
期刊：
MOLECULAR MEDICINE REPORTS,2020年22(2):1507-1517 ISSN：1791-2997
通讯作者：
Zou, Juan;Tong, Wen-Juan
作者机构：
[Zeng, Juan] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Hunan, Peoples R China.;[Zou, Juan; Li, Yu-Kun; Zeng, Tian] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Quan, Fei-Fei] Foshan First Peoples Hosp, Dept Gynecol, Foshan 528000, Guangdong, Peoples R China.;[Quan, Fei-Fei; Chen, Chang-Ye] Univ South China, Affiliated Hosp 1, Dept Gynecol, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Xin] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zou, Juan; Tong, Wen-Juan] U;Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Obstet, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
ovarian cancer;propofol;bioinformatics analysis;microRNA-125a-5p;lin-28 homolog B
摘要：
Propofol, a commonly used intravenous anesthetic agent during surgery, has relatively widespread pharmacological actions. Previous studies have reported that propofol may act as an antitumor drug in several cancer types, such as pancreatic cancer, lung cancer and gastric cancer. However, the underlying mechanism in ovarian cancer remain unknown. Therefore, the present study investigated the pharmacological effect ofpropofol on microRNAs (miRNAs) in ovarian cancer treatment. Propofol (1, 5 or 10µg/ml) was used to treat A2780 and SKOV3 ovarian cancer cells for 1, 2, 3, 4 or 5days. The MTT assay was used to detect cell viability, while wound healing and Transwell assays were utilized to assess the invasive and migratory abilities. The bioinformatics prediction approach identified differentially expressed miRNAs(miRs) that were used in Gene Ontology, Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes analyses. The expression levels of miR‑125a‑5p and lin‑28 homologB(LIN28B) were evaluated by reverse transcription‑quantitative PCR(RT‑qPCR). A luciferase assay was performed to identify the relationship between miR‑125a‑5p and LIN28B. Western blotting was conducted to measure the protein expression of LIN28B. It was demonstrated that propofol significantly upregulated miR‑125a‑5p to exert its antitumor activity. RT‑qPCR results suggested that propofol could upregulate miR‑125a‑5p and LIN28B expression levels in ovarian cancer cell lines. Western blot analysis also indicated that propofol could enhance the expression of LIN28B in ovarian cancer cell lines. The luciferase assay identified that miR‑125a‑5p could directly inhibit the expression of LIN28B to suppress proliferation and metastasis in ovarian cancer. In conclusion, these results suggested that propofol inhibited ovarian cancer proliferation and metastasis by enhancing miR‑125a‑5p, which targets LIN28B.
