ABSTRACT
OBJECTIVE: Hyperglycemia-induced inflammation and subsequent endothelial injuries ultimately lead to the pathogenesis of cardiovascular diseases associated with high mortality, such as atherosclerosis. Maslinic acid (MA) is a phytochemical with anti-inflammatory activity. However, it remains unknown whether it can inhibit diabetes-associated cardiovascular inflammation. The present study aimed to determine the effect of MA on high glucose-induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs) and to explore the underlying mechanism. METHODS: HUVECs were treated with high glucose to induce inflammation and apoptosis. Apoptosis was determined by flow cytometry. CCK-8 assay was used to examine cell viability. Production levels of cytokines were detected by quantitative realtime PCR (qPCR) and ELISA. Protein expression levels and signaling pathways activation were detected by Western blotting. RNA immunoprecipitation and qPCR were used to determine the N6-methyladenosine (m6A) levels of target mRNAs. RESULTS: MA promoted the recruitment of RNA demethylase ALKBH5 to TXNIP mRNA, and subsequently enhanced its m6A demethylation. By this means, MA decreased the stability of TXNIP mRNA and downregulated its expression level. Subsequently, reactive oxygen species (ROS) and production of pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1ß, were inhibited. And high glucose-induced apoptosis in HUVECs was inhibited by MA. CONCLUSION: MA ameliorates high glucose-induced endothelial inflammation and injury, serving as a new potential therapeutic application for protecting against diabetes-associated atherosclerosis and other inflammatory diseases.
Subject(s)
Atherosclerosis , Inflammation , Humans , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/genetics , Human Umbilical Vein Endothelial Cells , Cytokines/metabolism , Glucose/adverse effects , Glucose/metabolism , RNA, Messenger/metabolism , Atherosclerosis/metabolism , Carrier Proteins/geneticsABSTRACT
Treatment with sorafenib remains the firstline therapy for patients with advanced stage hepatocellular carcinoma (HCC), however, it has limited effect due to the acquired resistance of HCC. Elucidating the potential mechanism can assist in developing promising strategies to overcome this resistance. In the present study, a sorafenibrefractory HCC cell was established from the Huh7 parental cell line, which was resistant to sorafenib mediatedcytotoxicity in vitro. The cell inhibition rate and apoptosis of cells were determined by MTT assay and flow cytometry, respectively. Electronic microscopy was used to detect autophagy in cells. The expression levels of endoplasmic reticulum stress (ERS)related protein, apoptosisrelated protein and cFLIP were examined by western blot analysis. Coimmunoprecipitation was used to examine the ubiquitination of cFLIP. It was found that sustained exposure to sorafenib activated ERS in the HCC cells. The ERS inhibitor partly increased sorafenibinduced cell death in these cells. In addition, ERSinduced autophagy was important in resistance to sorafenib, as inhibiting autophagy led to the resistant HCC cells becoming more sensitive to sorafenib. However, ERSinduced apoptosis did not differ between sorafenibsensitive HCC cells and sorafenibrefractory HCC cells. The knockdown of cFLIP reversed the acquired sorafenib resistance by activating caspase8 and inhibiting activated ERS in the sorafenibresistant HCC cells. Mechanistically, a sustained increased in cFLIP was found to be dependent on USP2induced deubiquitination. In conclusion, cFLIP was identified as a potential target for overcoming the acquired sorafenib resistance in HCC. These effects occurred partially through reducing ERSrelated autophagy in HCC.
Subject(s)
Autophagy , Biomarkers, Tumor/metabolism , CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism , Carcinoma, Hepatocellular/pathology , Drug Resistance, Neoplasm , Endoplasmic Reticulum Stress/drug effects , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Proliferation/drug effects , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Niacinamide/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Sorafenib , Tumor Cells, CulturedABSTRACT
PURPOSE: Complementary and alternative medicine (CAM) has been widely used by cancer patients but rarely discussed by oncologists. This study was designed to evaluate the communication gap between China's oncologists and cancer patients on CAM. METHODS: Two parallel cross-sectional studies assessed 83 oncologists and 402 cancer patients on CAM communication between patients and oncologists, and attitudes toward CAM use and clinical decisions about CAM. RESULTS: A majority (75.1%) of the cancer patients (302/402) were identified as CAM users within the most recent three months while 77.6% of the cancer patients (312/402) were identified as CAM users since diagnosis of cancer. Oncologists and patients responded differently ( P < .001) on CAM communications. Both oncologists and patients expected that CAM could improve the immune system. They both agreed that oncologists usually discouraged their patients from using CAM. Regarding the effectiveness of CAM, cancer patients were more likely to believe that CAM was effective while oncologists had more concerns about adverse effects of CAM use. CAM use by patients was predicted by disease duration (≥9 months) in the multivariable logistic regression model. CONCLUSION: China's oncologists and cancer patients may hold discrepant views on CAM. China's oncologists are encouraged to improve their knowledge on CAM and to initiate more discussions with their patients regarding effective and the safe use of CAM.
Subject(s)
Complementary Therapies/psychology , Neoplasms/psychology , Neoplasms/therapy , Oncologists/psychology , Attitude of Health Personnel , China , Communication , Cross-Sectional Studies , Female , Hospitals, General/methods , Humans , Male , Medical Oncology/methods , Middle Aged , Surveys and QuestionnairesABSTRACT
OBJECTIVE: In China, people have relied on traditional Chinese medicine (TCM) for thousands of years to keep healthy and treat diseases. TCM also plays an important role in military health services and now forms a new discipline called military Chinese medicine (MCM). However, the type, quality and focus of research articles about MCM have not been reported. The present study was performed to analyze the growing trends of MCM and investigate China's contribution to military health services. METHODS: China's MCM publications were retrieved from the PubMed database, as well as China National Knowledge Infrastructure, Wanfang Data and Chongqing VIP database from 2005 to 2014. RESULTS: The study found that the number of published articles increased markedly from 2005 to 2014. Basic research studies comprised a small percentage of the literature. Among these studies, military training injury and special military environmental medicine were the most common research subjects in MCM. Military hospitals were the main institutions generating MCM literature. CONCLUSION: The quality of MCM research is generally low, as indicated by the proportion of publications in core journals. Studies on MCM still lack high-quality publications and international cooperation.