摘要:
BACKGROUND: We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. METHODS: The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8(+) T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8(+) T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. RESULTS: KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3'-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8(+) T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8(+) T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. CONCLUSIONS: LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.
摘要:
Objective To observe the effects and possible mechanism of Ziyin Mingmu Pills (滋阴明目丸) on retinal pigment epithelial (RPE) cells after light injury. Methods A total of 60 SD rats were divided into Ziyin Mingmu Pills low,medium and high dose groups and a blank group,with 15 rats in each group. The groups of different Ziyin Mingmu Pills dosages were respectively administered with the suspension of Ziyin Mingmu Pills at a concentration of 0.39,0.78,and 1.56 g /ml. The gavage volume was 34 ml /(kg·d),and the blank group was given 34 ml /(kg·d) of normal saline for gavage,each group was administered for 7 days. The drug-containing serum was prepared in the end of the gavage,and the concentration of the drug-containing serum in the subsequent experiment was screened by the MTT method. The selected cells for experiment were divided into a blank group (without drugcontaining serum),serum group (with drug-containing serum),model group (light damage modeling,no drug-containing serum),and Chinese medicine group (light damage modeling with drug-containing serum). After 24 hours of culture,the in vitro RPE cell light damage models of model group and the Chinese medicine group were established. The apoptosis rate of each group was measured,and the expression of caspase-1,caspase-3 and mRNA were measured. Results The medium dose serum was the optimal dose,and it was used in subsequent experiments. Compared with the blank group,the apoptosis rate,expression of Caspase-1 and Caspase-3 protein and mRNA in serum group were not statistically significant (P > 0.05). The apoptosis rate,Caspase-1 and Caspase-3 protein and mRNA expression in the model group increased significantly (P < 0.05). Compared with the model group,the apoptosis rate,Caspase-1 and Caspase-3 protein and mRNA expression in the Chinese medicine group were significantly decreased (P < 0.05). Conclusion Ziyin Mingmu Pills can effectively inhibit the apoptosis of RPE cells after light injury. The mechanism may be related to the inhibition of the expression of Caspase-1,Caspase-3 protein and its mRNA.
摘要:
Acute pancreatitis (AP) is defined as an acute inflammation of pancreas that may cause damage to other tissues and organs depending upon the severity of symptoms. The diagnosis of AP is usually made by detection of raised circulating pancreatic enzyme levels, but there are occasional false positive and false negative diagnoses and such tests are often normal in delayed presentations. More accurate biomarkers would help in such situations. In this study, the global metabolites' changes of AP patients (APP) were profiled by using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition techniques were used to establish the classification models to distinguish APP from healthy participants (HP). Some significant metabolites including 3-hydroxybutyric acid, phosphoric acid, glycerol, citric acid, D-galactose, D-mannose, D-glucose, hexadecanoic acid and serotonin were selected as potential biomarkers for helping clinical diagnosis of Ap. Furthermore, the metabolite changes in APP with severe and mild symptoms were also analyzed. Based on the selected biomarkers, some relevant pathways were also identified. Our results suggested that GC-MS based serum metabolomics method can be used in the clinical diagnosis of AP by profiling potential biomarkers. (C) 2017 LAP and EPC. Published by Elsevier B.V. All rights reserved.
作者机构:
School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, 410208;The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007;The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053;[刘灿; 周芝根; 杨茜芸; 常小荣; 刘迈兰] School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, 410208;[李波] The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007
通讯机构:
[Mai-lan Liu] S;School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, China
关键词:
Acupuncture Therapy;Point, Zusanli (ST 36);Central Mechanism;Functional Magnetic Resonance Imaging;Specificity of Acupoints;Research on Acupoints
摘要:
The contents about the central action mechanisms of needling Zusanli (ST 36) were sorted by summarizing the relevant literatures published in the past 10 years, and it was found that: by comparing acupuncture at Zusanli (ST 36), other acupoints or sham points, most studies showed that Zusanli (ST 36) had relatively specific characteristics in the brain function response; studies on the central action mechanisms of Zusanli (ST 36) were mainly focused on sequelae of cerebral apoplexy, pain, gastrointestinal diseases, weight loss and drug addiction withdrawal and so on; acupuncture manipulations, stimulation methods, individual differences, stimulation quantity, and stimulation duration, etc. could also induce different brain function responses; acupuncture at Zusanli (ST 36) had an after-working effect, also called long-term effect, but with poor repeatability. So, it was suggested that the future studies should focus on the factors that affect the clinical efficacies and experimental results, including the compatibility effects of the acupoints, reproducibility of research results, sample size, acupuncture methods, long-term effects and disease entities.
作者机构:
[常小荣; 刘迈兰; 周芝根; 刘灿; 杨茜芸] College of Acupuncture-Moxibustion and Massage, Hunan University of CM, Changsha 410208, China;[李波] the First Affiliated Hospital of Hunan University of CM
作者机构:
School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, 410208;School of Information Science and Engineering, Central South University, Changsha, 410002;Radiology Department, the First Hospital of Hunan University of Chinese Medicine, Changsha, 410007;[刘迈兰; 刘灿; 周芝根; 郁洁; 常小荣] School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, 410208;[吴静; 戴培山] School of Information Science and Engineering, Central South University, Changsha, 410002
通讯机构:
[Jie Yu; Xiao-rong Chang] S;School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>School of Acupuncture, Moxibustion & Tuina, Hunan University of Chinese Medicine, Changsha, China
摘要:
Objective: To compare and analyze functional brain response characteristics by applying acupuncture or moxibustion to Zusanli (ST 36) in patients with functional dyspepsia (FD) and investigate the differences of central action mechanism resulting from acupuncture or moxibustion. Methods: A total of eligible 24 FD cases were divided into two blood-oxygen-level dependent (BOLD) sequences for functional magnetic resonance imaging (fMRI) scan. The amplitude of low frequency fluctuation (ALFF) analyses were conducted on the data of location phase, structure phase, resting state before acupuncture/moxibustion, working state during acupuncture/moxibustion and resting state after acupuncture/moxibustion using Data Processing Assistant for Resting-State fMRI (DPARSF) software. Results: Acupuncture and moxibustion produced significant differences in functional brain response. The working state during acupuncture/moxibustion mainly decreased ALFF values in the right supramarginal gyrus, right superior parietal lobule, right frontal gyrus, upper right occipital lobe, right precuneus and right cingulate gyrus. At the same time, it increased ALFF values in the left cerebellum, right caudate nucleus, right cerebellum and left inferior gyrus. The differences during the resting state after acupuncture/moxibustion were significantly smaller than the working state in intensity and size. It mainly resulted in decrease in ALFF values in the right postcentral gyrus and right supramarginal gyrus and increase in ALFF values in the left precuneus, orbital part of inferior frontal gyrus and right cerebellar peduncles. Conclusion: Needling and moxibustion at Zusanli (ST 36) can produce significant differences in immediate functional brain response.