摘要:
Background: The interaction between leukocytes and vascular endothelial cells is ubiquitous in the occurrence and development of many diseases, especially in the body's defense response. The purpose of the present study was to investigate the effect of cornu bubali (CB) on the adhesion of leukocytes to endothelial cells. Materials and methods: Human leukemic cell line (HL-60) and human umbilical vein endothelial cells (HUVECs) were used to simulate the adhesion effect between cells. After HUVECs were treated with TNF-alpha (15 ng/mL) combined with different dose of CB (15, 30 and 60 mu mol/L) and dexamethasone (DEX, 2 mu g/ml) for 24 h, HL-60 cells were added into the coculture system for another 1 h. CCK8 assay was performed to investigate cell viability of HUVECs. HL-60 cells adhesion to HUVECs was quantified using Hoechst 33342 staining. Subsequently, the levels of adhesion molecules were detected by the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and ELISA, respectively. RT-qPCR and western blot were performed to assess the levels of inflammatory cytokines, chemokines and the expression of Notch signaling pathway. Results: Treatment with CB could reduce the adherence of HL-60 to HUVECs induced by TNF-alpha in a dose-dependent manner. CB inhibited the expression of ICAM-1, VCAM-1, CD44, IL-1 beta, COX-2 and CCL4 in HUVECs. Western blot and RT-qPCR analysis confirmed that CB prevented TNF-alpha-induced over-expression of Notch receptors (Notch1 and Notch2), Notch ligands (DLL1 and Jaggedly, signaling effectors (Hest) and adhesion related proteins (NF-kappa B/p65, p-I kappa B alpha and I kappa B alpha) in HUVECs. Conclusion: CB induces interactions between leukocytes and endothelial cells through the activation of Notch signaling pathway. These data contribute to further explain the protective effect of CB against development of inflammatory process of hemorrhage in acute leukemia.
摘要:
The Journal of Public Health (formerly the Journal of Public Health Medicine) focuses on current theory and practice within the whole spectrum of public health medicine. We aim to promote high standards of public health practice by publishing readable papers of high scientific quality. The journal looks in depth at the causes of disease and, in the light of this, how to prevent ill-health and promote good health. Disease trends are also monitored, as are outbreaks of environmental hazards. The journal also covers planning, provision and evaluation of health services.Coverage in the Journals@Ovid database for Journal of Public Health Medicine begins with the March 2001 issue.Coverage in the Journals@Ovid database for Journal of Public Health begins with the March 2004 issue.
期刊:
Frontiers in Neuroscience,2020年14:532068 ISSN:1662-4548
通讯作者:
Wang, Yang;Zhang, Wei;Ding, Chang-Song
作者机构:
[Zhou, Yan-Tao; Zheng, Fei] Hunan Univ, Coll Elect & Informat Engn, Changsha, Peoples R China.;[Wang, Yang; Luo, Jie-Kun; Hu, En; Tang, Tao; Li, Teng; Li, Peng-Fei] Cent South Univ, Inst Integrated Tradit Chinese & Western Med, Xiangya Hosp, Lab Ethnopharmacol, Changsha, Peoples R China.;[Zhang, Wei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ding, Chang-Song] Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
通讯机构:
[Wang, Yang] C;[Zhang, Wei; Ding, Chang-Song] H;Cent South Univ, Inst Integrated Tradit Chinese & Western Med, Xiangya Hosp, Lab Ethnopharmacol, Changsha, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
关键词:
Traumatic Brain Injury;Hippocampus and cortex;Metabolomics;LC-MS/MS;Subacute phase
摘要:
Traumatic brain injury (TBI) is a complex and serious disease as its multifaceted pathophysiological mechanisms remain vague. The molecular changes of hippocampal and cortical dysfunction in the process of TBI are poorly understood, especially their chronic effects on metabolic profiles. Here we utilize metabolomics-based liquid chromatography coupled with tandem mass spectrometry coupled with bioinformatics method to assess the perturbation of brain metabolism in rat hippocampus and cortex on day 7. The results revealed a signature panel which consisted of 13 identified metabolites to facilitate targeted interventions for subacute TBI discrimination. Purine metabolism change in cortical tissue and taurine and hypotaurine metabolism change in hippocampal tissue were detected. Furthermore, the associations between the metabolite markers and the perturbed pathways were analyzed based on databases: 64 enzyme and one pathway were evolved in TBI. The findings represented significant profiling changes and provided unique metabolite–protein information in a rat model of TBI following the subacute phase. This study may inspire scientists and doctors to further their studies and provide potential therapy targets for clinical interventions.
摘要:
Background: Hydroxyapatite (HAP) is the main component of bone mineral. The utility of using HAP-water decomposition technique with fast kilovoltage (KV)-switching dual-energy computed tomography (DECT) to detect abnormal edema in vertebral compression fractures (VCFs) has not been widely reported. Methods: A total of 31 consecutive patients with 80 VCFs who underwent DF,CT and magnetic resonance imaging (MRI) of the spine were retrospectively enrolled in our study between October 2018 and January 2019. VCFs in MR examinations served as the standard of reference. Two radiologists blindly and independently evaluated color-coded overlay virtual nonhydroxyapatite (VNHAP) images for the presence of abnormal edema. The inter-reader agreement, specificity, sensitivity, accuracy, and predictive values of VNHAP images for edema detection were calculated. The diagnostic accuracy of two readers was compared using McNemar's test. Two additional radiologists performed a quantitative analysis on VNHAP images, receiver operating characteristic (ROC) curve analysis was conducted, and the threshold was calculated. Results: MRI depicted 45 edematous and 35 nonedematous VCFs. For visual analysis, the VNHAP technique showed a sensitivity of 93.3%, a specificity of 97.1%, a positive predictive value (PPV) of 97.7%, a negative predictive value (NPV) of 91.9%, and an accuracy of 95.0%. The inter-reader agreement was almost perfect (k=0.90). The diagnostic accuracy of the two readers showed no significant differences in the assessment of VIII IA P images (P=1.00). Significant differences in CT numbers between vertebrae with and without bone marrow edema were found by quantitative analysis (P<0.01). The area under the curve (AUC) of the VNHAP images was estimated to be 0.917. The threshold of 1,003.2 mg/cm(3) yielded a sensitivity of 88.9% and a specificity of 82.9% for the differentiation of fresh and old VCFs. Conclusions: Fast KV-switching DECT HAP-water decomposition technique had excellent diagnostic performance for identifying acute and chronic VCFs in visual and quantitative analyses.
作者机构:
[Sun, Zhifang; Zheng, Jun] Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China;[Fan, Rong; Tang, Tao; Wang, Yang] Institute of Integrative Medicine, Key Laboratory of Hunan Province for Liver Manifestation of Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China;Key Laboratry of Materials Processing and Mold, Ministry of Education, Zhengzhou University, Zhengzhou, 450002, China;[Liu, Jiamiao; Yao, Honghui; Yan, Yujie] Xiangya School of Medicine, Central South University, Changsha, 410013, China;[Ran, Lu; Yi, Lunzhao] Yunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming, 650500, China
通讯机构:
[Yi Zhang] K;[Tao Tang; Yang Wang] I;Institute of Integrative Medicine, Key Laboratory of Hunan Province for Liver Manifestation of Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Key Laboratory of Hunan Province for Water Environment and Agriculture Product Safety, College of Chemistry and Chemical Engineering, Central South University, Changsha, China<&wdkj&>Institute of Integrative Medicine, Key Laboratory of Hunan Province for Liver Manifestation of Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, China
摘要:
Ischemic stroke is one of the leading causes of mortality and disability worldwide. However, there is a current lack of effective therapies available. As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses. In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the antiinflammatory M2 phenotype. The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke. It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke. In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia. Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke. The effects of autophagy on microglia polarization in ischemic stroke were also reviewed. Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.
作者机构:
[Tian, Xue-Fei; Deng, Zhe; Yunita, Fenny] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha 410208, Hunan, Peoples R China.;[Tian, Xue-Fei; Xu, Xiao-Yan] Hunan Univ Chinese Med, Hunan Key Lab Translat Res Formulas & Zheng Tradi, Changsha 410208, Hunan, Peoples R China.;[Zhou, Qing] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410208, Hunan, Peoples R China.;[Wu, Yong-Rong; Hu, Yu-Xing] Hunan Univ Chinese Med, Sch Basic Chinese Med Sci, Changsha 410208, Hunan, Peoples R China.;[Wang, Zhi-Qi] Hunan Univ Chinese Med, Coll Pharmaceut Sci, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Tian, Xue-Fei] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词:
Total ginsenosides;Curcumin;Liver cancer;Immune;Inflammation;Programmed cell death 1 ligand 1
摘要:
BACKGROUND Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality. The pathogenesis of liver cancer is closely associated with inflammation and immune response in the tumor microenvironment. New therapeutic agents for liver cancer, which can control inflammation and restore cellular immunity, are required. Curcumin (Cur) is a natural anti-inflammatory drug, and total ginsenosides (TG) are a commonly used immunoregulatory drug. Of note, both Cur and TG have been shown to exert anti-liver cancer effects. AIM To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer. METHODS A subcutaneous liver cancer model was established in BALB/c mice by a subcutaneous injection of hepatoma cell line. Animals were treated with Cur (200 mg/kg per day), TG (104 mg/kg per day or 520 mg/kg per day), the combination of Cur (200 mg/kg per day) and TG (104 mg/kg per day or 520 mg/kg per day), or 5-fluorouracil combined with cisplatin as a positive control for 21 d. Tumor volume was measured and the protein expression of programmed cell death 1 and programmed cell death 1 ligand 1 (PD-L1), inflammatory indicators Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B), and vascular growth-related factors nitric oxide synthases (iNOS) and matrix metalloproteinase 9 were analyzed by Western blot analysis. CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) were counted by flow cytometry. RESULTS The combination therapy of Cur and TG significantly inhibited the growth of liver cancer, as compared to vehicle-treated animals, and TG showed dose dependence. Cur combined with TG-520 markedly decreased the protein expression of PD-L1 (P < 0.0001), while CD4(+)CD25(+)Foxp3(+) Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1. Cur combined with TG-520 also inhibited the cascade action mediated by NF-kappa B (P < 0.0001), thus inhibiting the TLR4/NF-kappa B signalling pathway (P = 0.0088, P < 0.0001), which is associated with inflammation and acts on PD-L1. It also inhibited the NF-kappa B-MMP9 signalling pathway (P < 0.0001), which is associated with tumor angiogenesis. CONCLUSION Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-kappa B-mediated inflammation and angiogenesis.
期刊:
Evidence-Based Complementary and Alternative Medicine,2020年2020 ISSN:1741-427X
通讯作者:
Wang, Yang
作者机构:
[Wang, Yang; Luo, Jiekun; Yang, Zhaoyu; Zheng, Piao; Cui, Hanjin; Tang, Tao] Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Inst Integrat Med, Changsha 410008, Hunan, Peoples R China.;[Tian, Xuefei; Zheng, Piao; Zhang, Wei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Zhou, Jing] Shanxi Prov Hosp Tradit Chinese Med, Shanxi Prov Inst Tradit Chinese Med, Taiyuan 030012, Shanxi, Peoples R China.;[Zheng, Jun] Cent South Univ, Coll Chem & Chem Engn, Changsha 410083, Hunan, Peoples R China.
通讯机构:
[Wang, Yang] C;Cent South Univ, Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Inst Integrat Med, Changsha 410008, Hunan, Peoples R China.
摘要:
As a bioactive absorbed compound of rhubarb, Rhein is applied for the treatment of brain injury. However, the underlying pharmacological mechanisms remain unclear. In this study, we aimed to explore antineuroinflammatory functions and underlying mechanisms of Rhein in vitro. BV2 microglia cells were chosen and irritated by LPS. The influence of Rhein on cell viability was determined using MTT assay. We finely gauged the proinflammatory cytokines of TNF-alpha and IL-1 beta through tests of immunofluorescence staining, ELISA, RT-qPCR, and western blot. Additionally, mediators including IL-6, IL-12, iNOS, and IL-10 were surveyed by ELISA. Furthermore, protein levels of the underlying signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-kappa B) were tested adopting western blot. We found that Rhein reduced the secretion of pivotal indicators including TNF-alpha and IL-1 beta, effectively restraining their mRNA and protein expression in LPS-activated BV2 microglial cells. Besides, Rhein treatment demoted the production of IL-6, IL-12, and iNOS and promoted the excretion of IL-10. Subsequent mechanistic experiments revealed that Rhein obviously downregulated the phosphorylation levels of PI3K, Akt, p38, and ERK1/2 and simultaneously upregulated the PTEN expression. In addition, Rhein antagonized the increase of TLR4, p-I kappa B alpha, and NF-kappa B. In summary, Rhein suppresses neuroinflammation via multiple signaling pathways (PI3K/Akt, p38, ERK1/2, and TLR4/NF-kappa B) in LPS-stimulated BV2 microglia cells. This study highlights a natural agent for prevention and treatment of neuroinflammation.
期刊:
Australian Journal of Chemistry,2020年73(11):1074-1079 ISSN:0004-9425
通讯作者:
Tang, Qianli;Zhang, Xiaolu
作者机构:
[Tang, Qianli; Liao, Xianjiu] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Tang, Qianli; Liao, Xianjiu] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, Baise 533000, Guangxi, Peoples R China.;[Pan, Jianbin; Liao, Xianjiu] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210023, Peoples R China.;[Pan, Jianbin; Liao, Xianjiu] Nanjing Univ, Sch Chem & Chem Engn, Collaborat Innovat Ctr Chem Life Sci, Nanjing 210023, Peoples R China.;[Zhang, Xiaolu] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Neurosurg, Wuxi 214000, Jiangsu, Peoples R China.
通讯机构:
[Tang, Qianli] H;[Tang, Qianli] Y;[Zhang, Xiaolu] N;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inc, Baise 533000, Guangxi, Peoples R China.
摘要:
RNA interference (RNAi) is a powerful tool for silencing target genes in a variety of cells and has great therapeutic potential. It is triggered by small interfering RNAs (siRNAs) and by an RNA-binding protein (argonaute, Ago). In this manuscript, we designed a simple fluorescence sensor strategy for sensitive detection of argonaute2 (Ago2) based on the base pairing principle of Watson–Crick and Hoogsteen and the pyrene excimer switch. The sensing platform has extremely high sensitivity and a detection limit of 0.1 nM. It can be used to detect endogenous Ago2 in cancer cells and has great potential in clinical diagnosis and biomedical research.
摘要:
MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators. Some miRNAs, including the recently discovered miR-582–3p, have been implicated in leukemogenesis. This study aimed to reveal the biological function of miR-582–3p in acute myeloid leukemia (AML), which is one of the most frequently diagnosed hematological malignancies. The expression of miR-582–3p was determined using quantitative real-time PCR in blood samples from leukemia patients and in cell lines. Cell proliferation and cell cycle distribution were analyzed using the CCK-8, colony formation and flow cytometry assays. The target gene of miR-582–3p was verified using a dual-luciferase reporter assay. The G2/M phase arrest-related molecule contents were measured using western blotting analysis. We found miR-582–3p was significantly downregulated in the blood samples from leukemia patients and in the cell lines. MiR-582–3p overexpression significantly impaired cell proliferation and induced G2/M cell cycle arrest in THP-1 cells. Furthermore, cyclin B2 (CCNB2) was confirmed as a target gene of miR-582–3p and found to be negatively regulated by miR-582–3p overexpression. More importantly, CCNB2 knockdown showed suppressive effects on cell proliferation and cell cycle progression similar to those caused by miR-582–3p overexpression. The inhibitory effects of miR-582–3p overexpression on cell proliferation and cell cycle progression were abrogated by CCNB2 transfection. These findings indicate new functions and mechanisms for miR-582–3p in AML development. Further study could clarify if miR-582–3p and CCNB2 are potential therapeutic targets for the treatment of AML.
作者机构:
[Yan, Miao; Zhang, Min] Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;[Fan, Xin-Rong; Chen, Yan; Yang, Mei-ju; Zhang, Min] China Acad Chinese Med Sci, Inst Basic Theory Chinese Med, Beijing 100700, Peoples R China.;[Zhang, Min] Shaanxi Univ Chinese Med, Clin Med Coll 1, Xianyang, Peoples R China.;[Nie, Yu-Song; Fan, Xin-Rong; Zhang, Ling; Xie, Hui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构:
[Yan, Miao; Fan, Xin-Rong] C;Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China.;China Acad Chinese Med Sci, Inst Basic Theory Chinese Med, Beijing 100700, Peoples R China.
摘要:
The purpose of this study was to investigate the renal protective effect of celastrol on diabetic rats. Furthermore, the mechanism of its action was discussed whether it was related to MAPK/NF-kappaB signaling pathway. There were a total of 36 rats. Six rats were randomly chosen as the control group. The remaining 30 rats were given 1% streptozotocin intraperitoneal injection (50 mg/kg) and were randomly divided into five groups: the model control group, the low-dose celastrol group, the high-dose celastrol group, the Tripterygium wilfordii polyglycosides group, and the MAPK/NF-kappaB inhibitor group. After 4 weeks of continuous administration, 24-hr urine volume, urinary protein, blood urea nitrogen, and serum creatinine content were observed, and hematoxylin-eosin (HE) staining of the kidney and liver were evaluated. p38MAPK was designated by immunohistochemical method, and NF-kappaB p65 in renal tissue was detected by western blotting. Our results showed that celastrol could not only reduce contents of creatinine and urea nitrogen in blood but also reduce excretion of urinary protein in diabetic rats, improve renal pathological injury, and down-regulate the expression of p38MAPK and NF-kappaB p65. In conclusion, celastrol could protect kidney of diabetic rats by regulating the signal pathway of MAPK/NF-kappaB, inhibiting inflammation and delaying renal injury.