摘要:
Background: Ischemic stroke is the obstruction of cerebral blood flow with a high morbidity. Microglial polarization is a contributing factor for ischemic strokeinduced injury. Here, we focused on function and mechanism of RNA binding protein RPS3 in microglial polarization after ischemic stroke. Methods: Transient middle cerebral artery occlusion (tMCAO) was conducted in SD rats. Infarct area was detected by TTC staining and neurological score was assessed. Fluorescence staining tested neuronal apoptosis and microglial differentiation. Oxygen and glucose deprivation/reoxygenation (OGD/R) was applied for treating microglia. Levels of RPS3, SIRT1, M1 and M2 polarization markers (CD86, iNOS, CD206, Arg-1) were determined by RT-qPCR. Western blot detected RPS3, SIRT1, NLRP3, ASC and Cleaved-caspase-1 expression. RIP assay validated that RPS3 interacted with SIRT1. CCK-8 measured cell viability. Flow cytometry and ELISA assessed M1 and M2 polarization markers. LDH release was detected using colorimetric CytoTox 96 Cytotoxicity kit. Results: RPS3 depletion improved neurological dysfunction and reduced infarction area in rats after tMCAO. Knockdown of RPS3 resulted in increased SIRT1 expression and decreased NLRP3 inflammasome activation, and induced microglia M2 polarization after ischemia-reperfusion (I/R). Besides, RPS3 directly targeted SIRT1 and reduced its expression in microglia. RPS3 silencing suppressed OGD/R-triggered neuronal and microglial cell death through SIRT1. Moreover, RPS3 activated NLRP3 inflammasome and regulated microglial polarization via SIRT1. Conclusion: RPS3 regulates microglial polarization and neuronal injury through SIRT1/NLRP3 pathway, suggesting a novel target for ischemic stroke treatment.Keywords: Ischemic stroke-Microglial polarization-NLRP3 inflammasome-(c) 2023 Elsevier Inc. All rights reserved.
摘要:
High altitude exposure leads to various cognitive impairments. The cerebral vasculature system plays an integral role in hypoxia-induced cognitive defects by reducing oxygen and nutrition supply to the brain. RNA N6-methyladenosine (m6A) is susceptible to modification and regulates gene expression in response to environmental changes, including hypoxia. However, the biological significance of m6A in endothelial cell performance under hypoxic conditions is unknown. Using m6A-seq, RNA immunoprcipitation-seq, and transcriptomic co-analysis, the molecular mechanism of vascular system remodeling under acute hypoxia is investigated. A novel m6A reader protein, proline-rich coiled-coil 2B (PRRC2B), exists in endothelial cells. PRRC2B knockdown promoted hypoxia-induced endothelial cell migration by regulating alternative splicing of the alpha 1 chain of collagen type XII in an m6A-dependent manner and the decay of matrix metallopeptidase domain 14 and ADAM metallopeptidase domain 19 mRNA in an m6A-independent manner. In addition, conditional knockout of PRRC2B in endothelial cells promotes hypoxia-induced vascular remodeling and cerebral blood flow redistribution, thus alleviating hypoxia-induced cognitive decline. Therefore, PRRC2B is integral in the hypoxia-induced vascular remodeling process as a novel RNA-binding protein. These findings provide a new potential therapeutic target for hypoxia-induced cognitive decline.
通讯机构:
[Huan He; Pingkun Zhou] D;Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China<&wdkj&>NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China<&wdkj&>Department of Radiation Toxicology and Oncology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing, China<&wdkj&>School of Medicine, University of South China, Hengyang, China
关键词:
TAB182;EGFR;Cell invasion;Cell migration;EMT;Lung cancer cells
摘要:
BACKGROUND: TAB182 is overexpressed in cancerous tissues and correlated with poor overall survival in lung cancer patients. Mechanistically, TAB182 participates in DNA damage repair and endows tumour cells with radio- and chemoresistance. However, its role in non-small cell lung cancer (NSCLC) remains unclear. METHODS AND RESULTS: Cells with stable TAB182 knockdown (KD) were generated using A549 NSCLC cells, and we demonstrated that depleting TAB182 inhibits cell EMT, proliferation, colony formation, migration and invasion. Analysis of the TCGA database showed a positive correlation between TAB182 and EGFR, a well-established NSCLC oncoprotein. Then, we verified that silencing TAB182 decreases EGFR expression at both the mRNA and protein levels. Moreover, both TAB182 and EGFR were reported to restore ionizing radiation (IR)-triggered DNA damage. We validated that IR elevates the protein level of EGFR and that silencing TAB182 can alleviate IR-induced EGFR upregulation. Furthermore, overexpressing EGFR abrogates the inhibitory effects of TAB182 KD on EMT, migration, and invasion in A549 cells. CONCLUSIONS: Our data demonstrated that EGFR expression is regulated by TAB182 and downregulation of TAB182 has a novel function to repress EMT, migration and invasion by decreasing EGFR, indicating TAB182 could regulate the malignant progression of NSCLC.
作者机构:
[Li, Weiwei; Wu, Yimou; Yu, Maoying; Liu, Zhaoping; Li, Sijia; He, Zhangping; Tang, Yuanyuan; Xu, Man; Liu, Jie; Xu, M; Guo, Ningyuan; Yang, Hongyu; Wang, Jianye; Wu, YM] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang, Peoples R China.;[Li, Weiwei; Xie, Dongde] Second Peoples Hosp Foshan, Dept Clin Lab, Foshan, Peoples R China.;[Wang, Jianye] Tianjin Med Univ, Sch Basic Med Sci, Dept Immunol, Key Lab Immune Microenvironm & Dis,Minist Educ, Tianjin, Peoples R China.;[Zheng, Kang] Hengyang Cent Hosp, Dept Clin Lab, Hengyang, Peoples R China.
通讯机构:
[Xu, M; Wu, YM ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang, Peoples R China.
摘要:
Tp92 impedes the activation of procaspase‐3 via the ERK MAPK, PI3K/Akt, and NF‐κB signaling pathways, consequently suppressing caspase‐3 activity within hPMNs, and thereby preventing hPMNs apoptosis. These findings provide valuable insights into the molecular mechanisms underlying Treponema pallidum infection and suggest potential therapeutic targets for syphilis treatment. Abstract Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram‐negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short‐lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase‐3 via the ERK MAPK, PI3K/Akt, and NF‐κB signaling pathways, consequently suppressing caspase‐3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti‐apoptotic protein Mcl‐1, stimulating IL‐8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.
期刊:
JMIR PUBLIC HEALTH AND SURVEILLANCE,2023年9(1):e49291- ISSN:2369-2960
通讯作者:
Wang, J
作者机构:
[Wang, Jian; Guo, Qulian; Song, Zongbin; Hou, Xinran; Zhu, Maoen; Wang, J] Cent South Univ, Xiangya Hosp, Dept Anesthesiol, 87 Xiangya Rd, Changsha 410008, Peoples R China.;[Wang, Jian; Guo, Qulian; Song, Zongbin; Zhang, Chengliang; Hou, Xinran; Zhu, Maoen] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.;[Xu, Wei] Univ South China, Hunan Prov Maternal & Child Hlth Care Hosp, Dept Anesthesiol, Changsha, Peoples R China.;[Zhang, Chengliang] Cent South Univ, Xiangya Hosp, Dept Cardiovasc Surg, Changsha, Peoples R China.
通讯机构:
[Wang, J ] C;Cent South Univ, Xiangya Hosp, Dept Anesthesiol, 87 Xiangya Rd, Changsha 410008, Peoples R China.
关键词:
serum chloride;all-cause mortality;cause-specific mortality;National Health and Nutrition Examination Survey;National Death Index
摘要:
BACKGROUND: Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. OBJECTIVE: This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. METHODS: Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. RESULTS: A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). CONCLUSIONS: In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.
作者机构:
[Zhang, Qi; Lu, Yiming; Lu, Hao; Zhao, Xi; Hao, Rongjiao; Han, Huihui; Li, Yuanfeng; Zhou, Gangqiao; Jiang, Siao; Xing, Shuang; Quan, Cheng; Chen, Hongxia; Yu, Zuyin] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing, Beijing, Peoples R China.;[Wang, Qianqian; Yang, Wei] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Radiat Oncol, Beijing, Peoples R China.;[Zhang, Qi; Zhou, Gangqiao] Univ South China, Sch Med, Hengyang, Hunan, Peoples R China.;[Lu, Yiming; Hao, Rongjiao; Zhou, Gangqiao; Jiang, Siao] Univ Hebei, Sch Life Sci, Baoding, Hebei, Peoples R China.;[Feng, Changjiang] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Thorac Surg, Beijing, Peoples R China.
通讯机构:
[Zhou, GQ ; Lu, YM] B;Beijing Inst Radiat Med, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing, Beijing, Peoples R China.;Univ South China, Sch Med, Hengyang, Hunan, Peoples R China.;Univ Hebei, Sch Life Sci, Baoding, Hebei, Peoples R China.;Nanjing Med Univ, Sch Publ Hlth, Collaborat Innovat Ctr Personalized Canc Med, Ctr Global Hlth, Nanjing, Jiangsu, Peoples R China.
摘要:
Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m(6)A) levels showed significant alteration after acute irradiation. The m(6)A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m(6)A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m(6)A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m(6)A in radiation accidents management and clinical applications. Radiation dosimetry are critical for the medical management of individuals exposed to ionizing radiation (IR). Here, authors show that the RNA m6A levels of Ncoa4, Ate1 and Fgf22 genes in peripheral blood cells could serve as dosimetry of IR exposure.
作者机构:
[Peng, Jie; Jiang, Yuyang; Gao, Dan; Chen, Yulin] Tsinghua Univ, Tsinghua Shenzhen Int Grad Sch, State Key Lab Chem Oncogen, Guangdong Prov Key Lab Chem Biol, Shenzhen 518055, Guangdong, Peoples R China.;[Zhu, Qingyun] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Chu, Bizhu] Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Peoples R China.;[Wang, Jian] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Thorac Surg, Shenzhen 518020, Guangdong, Peoples R China.;[Wang, Jian; Liu, Liping] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China.
通讯机构:
[Dan Gao] S;State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, China
作者机构:
[金良; 陈勇军; 陈语婕] Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China
关键词:
基因变异;发育性和癫痫性脑病;OMIM数据库;精准治疗
摘要:
发育性和癫痫性脑病(developmental and epileptic encephalopathy,DEE)是一组临床和遗传异质的年龄依赖性神经系统疾病,其特征是在婴儿期或儿童早期出现难治性癫痫发作,且受影响的个体...展开更多 发育性和癫痫性脑病(developmental and epileptic encephalopathy,DEE)是一组临床和遗传异质的年龄依赖性神经系统疾病,其特征是在婴儿期或儿童早期出现难治性癫痫发作,且受影响的个体有精神运动发育迟缓或倒退。随着二代测序技术的发展,尤其是全外显子测序技术的应用,越来越多的基因被发现与DEE相关。这些发现将为临床工作中DEE致病基因的检测提供依据,同时将有助于加深对DEE发病机制的理解。本文主要对DEE的遗传学病因及诊疗的相关研究进展展开综述,以期帮助临床医生早期识别相关基因突变,从而加快疾病诊断并及时实施最佳治疗。收起
作者机构:
[Xiang, Z.; Li, Q.; Fang, X.; Liu, F.] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Radiol, Hengyang 421001, Hunan, Peoples R China.;[Zhou, J.] Jiangsu Univ, Affiliated Hosp, Zhenjiang 212001, Jiangsu, Peoples R China.;[Yang, X.] Sichuan Sci City Hosp, Mianyang 621000, Sichuan, Peoples R China.;[Lin, H.] GE Healthcare, Dept Pharmaceut Diag, Changsha 410005, Peoples R China.;[Yang, Q.] Univ South China, Ctr Mol Imaging Probe, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Fang, X ; Yang, Q ] U;Univ South China, Hengyang Med Sch, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol,Ctr, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Dept Radiol, Hengyang Med Sch, 30 Jiefang Rd, Hengyang 421001, Hunan, Peoples R China.
摘要:
AIM: To explore the value of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics model for predicting the degree of pathological differentiation in non-small-cell lung cancer (NSCLC).MATERIALS AND METHODS: Clinical characteristics of 182 NSCLC patients from four centres were collected, and radiomics features were extracted from 18F-FDG PET/CT images. Three logistic regression prediction models were established: clinical model; radiomics model; and nomogram combining radiomics signatures and clinical features. The predictive ability of the models was assessed using receiver operating characteristics curve analysis. RESULTS: Patients from centre 1 were assigned randomly to the training and internal validation cohorts (7:3 ratio); patients from centres 2-4 served as the external validation cohort. The area under the curve (AUC) values for the clinical model in the training, internal validation, and external validation cohort were 0.74 (95% confidence interval [CI] = 0.64-0.84), 0.64 (95% CI = 0.46-0.81), and 0.74 (95% CI = 0.60-0.88), respectively. In the training (AUC: 0.84 [95% CI = 0.77-0.92]), internal validation (AUC: 0.81 [95% CI = 0.67-0.95]), and external validation cohorts (AUC: 0.74 [95% CI = 0.58-0.89]), the radiomics model showed good predictive ability for differentiation. Compared to the clinical and radiomics models, the nomogram has relatively better diagnostic performance, and the AUC values for nomogram in the training, internal validation, and external validation cohort were 0.86 (95% CI = 0.78-0.93), 0.83 (95% CI = 0.70-0.96), and 0.77 (95% CI = 0.62-0.92), respectively.CONCLUSIONS: The 18F-FDG PET/CT-based radiomics model showed good ability for predicting the degree of differentiation of NSCLC. The nomogram combining the radiomics signature and clinical features has relatively better diagnostic performance. (c) 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
作者机构:
[Zhang, Yang; Yuan, Mei; Sun, Wenjie] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang, Hunan, Peoples R China.;[Wan, Teng] Shenzhen Univ, Huazhong Univ Sci & Technol, Union Shenzhen Hosp, Dept Neurol,Affiliated Hosp 6,Hlth Sci Ctr, Shenzhen 518060, Peoples R China.;[Guo, Weiming] Shenzhen Univ, Huazhong Univ Sci & Technol, Union Shenzhen Hosp, Dept Sports Med,Affiliated Hosp 6,Hlth Sci Ctr, Shenzhen 518060, Peoples R China.;[Jiang, Weiwei; Xia, Beibei; Wan, Teng; Shen, Xiangru; Fu, Mingyuan] Univ South China, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Teng Wan; Mei Yuan] D;Department of Neurology, Huazhong University of Science and Technology Union Shenzhen Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China<&wdkj&>Hengyang Medical College, University of South China, Hengyang, China<&wdkj&>Department of Neurology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
摘要:
Apelin is a natural ligand for the G protein-coupled receptor APJ, and the apelin/APJ system is widely distributed in vivo. Among the apelin family, apelin-13 is the major apelin isoform in the central nervous system and cardiovascular system, and is involved in the regulation of various physiopathological mechanisms such as apoptosis, neuroinflammation, angiogenesis, and oxidative stress. Apelin is currently being extensively studied in the nervous system, and apelin-13 has been shown to be associated with the onset and progression of a variety of neurological disorders, including stroke, neurodegenerative diseases, epilepsy, spinal cord injury (SCI), and psychiatric diseases. This study summarizes the pathophysiological roles of apelin-13 in the development and progression of neurological related diseases.
期刊:
PATHOLOGY RESEARCH AND PRACTICE,2023年248:154634 ISSN:0344-0338
通讯作者:
Cao, JY;Dai, T
作者机构:
[Cao, Jingying] Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, Changsha 410013, Hunan, Peoples R China.;[Cao, Renxian] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Liu, Yiqi] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Dai, Tao] Cent South Univ, Xiangya Sch Med, Hunan Canc Hosp, Affiliated Canc Hosp,Dept Urol, Changsha 410013, Hunan, Peoples R China.;[Cao, Jingying; Cao, JY] Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
通讯机构:
[Dai, T ; Cao, JY ] C;Cent South Univ, Xiangya Hosp 3, Dept Med Clin Lab, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;Cent South Univ, Xiangya Sch Med, Hunan Canc Hosp, Affiliated Canc Hosp,Dept Urol, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.
关键词:
AKT;CPNE1;Glycolysis;PI3K;Triple-negative breast cancer
摘要:
CPNE1 regulates multiple signaling pathways and can stimulate cell proliferation and differentiation by activating the AKT-mTOR signaling pathway. In addition, CPNE1 is associated with various cancers; however, its role in breast cancer, particularly in TNBC, has not been fully elucidated. Our study aimed to reveal the impact of the CPNE1/PI3K/AKT/HIF-1α axis on TNBC. We first measured the expression of CPNE1 in the tumor tissues of TNBC patients and examined its prognostic value. Subsequently, we used sh-CPNE1 and overexpression vectors to transfect TNBC cell lines and analyzed cell viability, migration, and invasive abilities using colony formation and CCK-8 assays. Metabolites were analyzed through metabolomics. We found that higher expression of CPNE1 predicted poor prognosis in TNBC patients. Knockdown of CPNE1 reduced the viability, migration, invasion, and proliferation capabilities of TNBC cells. Furthermore, metabolomics analysis showed that glucose metabolism was the most dominant pathway, and knockdown of CPNE1 significantly limited the glycolytic activity of TNBC cells. We verified these conclusions in mouse models. Additionally, we overexpressed CPNE1 and treated TNBC cell lines with a PI3K inhibitor (LY294002). The results indicated that CPNE1 promoted aerobic glycolysis in TNBC cells through the PI3K/AKT/HIF-1α signaling pathway. This suggests that CPNE1 regulates cell glycolysis and participates in the development of TNBC. Our study may provide a new therapeutic target for TNBC treatment.
摘要:
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease with high incidence in the elderly population. MicroRNAs have been reported to abnormally expressed in patients with AD. In this study, we investigated the role of inflammation-related miR-511-3p in AD patients and AD cell models. METHOD: The level of miR-511-3p was quantified by Real-Time PCR. The diagnostic value was evaluated by receiver operating characteristic curve (ROC) analysis. The correlation between miR-511-3p expression levels and ini-mental state examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) scores and inflammatory factors was analyzed. The concentrations of IL-1β, IL-6 and TNF-α were measured by Enzyme-Linked Immunosorbent Assay (ELISA) in AD cell model and serum from AD patients. RESULT: Serum miR-511-3p expression was decreased in AD patients and correlated with MMSE score, MoCA score and inflammatory response. MiR-511-3p mimics significantly reversed the effects of Aβ (1)(-)(40) on inflammation in AD cells. ROC curve results showed that miR-511-3p had high diagnostic accuracy in distinguishing normal controls from AD patients. CONCLUSION: Our results show that miR-511-3p is down-regulated in AD patients and has high diagnostic value. MiR-511-3p may participate in the development of AD by regulating the levels of neuroinflammatory factors in AD cells. MiR-511-3p may provide a new perspective for the prevention and pathogenesis of AD.
作者机构:
[Zhou, Zhou; Chen, Chen; Zou, JianJun; Zhao, Zheng] Nanjing Med Univ, Nanjing Hosp 1, Dept Clin Pharmacol, Nanjing, Peoples R China.;[Lu, Wei] China Pharmaceut Univ, Sch Basic Med & Clin Pharm, Nanjing, Peoples R China.;[Xiang, Liang; Guo, LeHeng; Shan, YaJie; Zhang, Cheng; Xiang, Lan; Zhao, ZhiHong; Li, XueMei] Hunan Normal Univ, Affiliated Hosp 1, Peoples Hosp Hunan Prov, Dept Neurol, Changsha, Peoples R China.;[Chen, Chen; Zou, JianJun; Zhao, Zheng] China Pharmaceut Univ, Nanjing Hosp 1, Dept Pharm, Nanjing, Peoples R China.;[Wang, BiJun] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.
通讯机构:
[JianJun Zou; XiaoMing Dai; ZhiHong Zhao] D;Department of Clinical Pharmacology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China<&wdkj&>Department of Pharmacy, Nanjing First Hospital, China Pharmaceutical University, Nanjing, China<&wdkj&>Department of Hepatobiliary Surgery, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China<&wdkj&>Department of Neurology, The First Affiliated Hospital (People’s Hospital of Hunan Province), Hunan Normal University, Changsha, China
摘要:
OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is an aggressive disease with higher mortality rate in the elderly population. Unfortunately, the previous models for predicting clinical prognosis are still not accurate enough. Therefore, we aimed to construct and validate a visualized nomogram model to predict online the 3-month mortality in elderly aSAH patients undergoing endovascular coiling. METHOD: We conducted a retrospective analysis of 209 elderly aSAH patients at People's Hospital of Hunan Province, China. A nomogram was developed based on multivariate logistic regression and forward stepwise regression analysis, then validated using the bootstrap validation method (n = 1000). In addition, the performance of the nomogram was evaluated by various indicators to prove its clinical value. RESULT: Morbid pupillary reflex, age, and using a breathing machine were independent predictors of 3-month mortality. The AUC of the nomogram was 0.901 (95% CI: 0.853-0.950), and the Hosmer-Lemeshow goodness-of-fit test showed good calibration of the nomogram (p = 0.4328). Besides, the bootstrap validation method internally validated the nomogram with an area under the curve of the receiver operator characteristic (AUROC) of 0.896 (95% CI: 0.846-0.945). Decision curve analysis (DCA) and clinical impact curve (CIC) indicated the nomogram's excellent clinical utility and applicability. CONCLUSION: An easily applied visualized nomogram model named MAC (morbid pupillary reflex-age-breathing machine) based on three accessible factors has been successfully developed. The MAC nomogram is an accurate and complementary tool to support individualized decision-making and emphasizes that patients with higher risk of mortality may require closer monitoring. Furthermore, a web-based online version of the risk calculator would greatly contribute to the spread of the model in this field.
通讯机构:
[Tan, SJ ; Zeng, P] U;Univ South China, Sch Basic Med, Hengyang Med Sch, Dept Histol & Embryol, Hengyang, Peoples R China.
摘要:
Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.
摘要:
Human papillomavirus (HPV) E7 protein as an important viral factor was involved in the progression of cervical cancer by mediating the cellular signaling pathways. Daxx (Death domain-associated protein) can interact with a variety of proteins to affect the viral infection process. However, the interaction and its related function between HPV16 E7 and Daxx have not been adequately investigated. Here, it was found that HPV16 E7 can interact with Daxx in HeLa or C33A cells by co-immunoprecipitation. HPV16 E7 protein treatment can up-regulate Daxx protein expression, while the interference in Daxx expression and the agonists for JNK can both reduce the antagonistic effects of HPV16 E7 on TNF-α-induced apoptosis, suggesting that Daxx/JNK pathway may be involved in the anti-apoptotic activity of HPV16 E7.
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Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.
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.