Biological Response Profiling Reveals the Functional Differences of Main Alkaloids in Rhizoma Coptidis.

Rhizoma Coptidis (RC) is a widely used traditional Chinese medicine. Although modern research has found that some alkaloids from RC are the pharmacologically active constituents, the differences in their biological effects are not completely clear. This study analyzed the differences in the typical alkaloids in RC at a systematic level and provided comprehensive information on the pharmaceutical mechanisms of the different alkaloids. The ethanol RC extract (RCE) was characterized using HPLC assay. HepG2, 3T3-L1, and RAW264.7 cells were used to detect the cytotoxicity of alkaloids. Transcriptome analyses were performed to elucidate the cellular pathways affected by RCE and alkaloids. HPLC analysis revealed that the typical alkaloids of RCE were berberine, coptisine, and palmatine. Coptisine and berberine displayed a stronger inhibitory effect on cell proliferation than palmatine. The overlapping ratios of differentially expressed genes between RCE and berberine, coptisine, and palmatine were 70.8%, 52.6%, and 42.1%, respectively. Pathway clustering analysis indicated that berberine and coptisine possessed a certain similarity to RCE, and both compounds affected the cell cycle pathway; moreover, some pathways were uniquely enriched by berberine or coptisine. Berberine and coptisine had different regulatory effects on genes involved in lipid metabolism. These results provide comprehensive information on the pharmaceutical mechanisms of the different RC alkaloids and insights into their better combinatory use for the treatment of diseases.

Long noncoding RNA PP7080 promotes hepatocellular carcinoma development by sponging mir-601 and targeting SIRT1.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults, ranking the second leading cause of cancer-related death. To date, the underlying mechanisms of HCC pathogenesis are still unclear. Recently, more and more studies have reported that long noncoding RNAs (lncRNAs) are involved in the occurrence and development of HCC. This study aims to investigate the expressions, clinical significance and roles of lncRNA PP7080 in HCC. We analyzed the transcriptome data of HCC cancer tissue (n = 369) and normal tissue (n = 50) in the TCGA database. We used the qRT-PCR method to detect the expression levels of lncRNA PP7080 in 40 pairs of HCC and adjacent tissues. The survival curve was drawn by KM-plotter. The changes of migration, invasion and proliferation of HCC cells were detected by transwall, CCK8 and colony forming assays, respectively. For the interaction between genes, we performed the luciferase activity assay to analyze. The expression of lncRNA PP7080 and miR-601 in cancer tissues of 40 cancer patients was analyzed by Pearson correlation. LncRNA PP7080 was highly expressed in HCC and predicted a poor prognosis. Luciferase activity assay identified lncRNA PP7080 as a molecular sponge for miR-601 in HCC cells. LncRNA PP7080 promoted HCC cells proliferation, migration and invasion by miR-601/SIRT1 signal axis. These results revealed lncRNA PP7080 effect in regulating miR-601/SIRT1 signal axis in the progression of HCC, indicating the important role of miR-601 in HCC pathogenesis.

Biological-Profiling-Based Systematic Analysis of Rhizoma Coptidis from Different Growing Regions and Its Anticholesterol Biosynthesis Activity on HepG2 Cells.

Rhizoma Coptidis is a widely cultivated traditional Chinese herb. Although the chemical profiles of Rhizoma Coptidis have been established previously, the biological profiling of Rhizoma Coptidis has not been conducted yet. In this study, we collected Rhizoma Coptidis varieties from four distinct growing regions and performed genome-wide biological response fingerprinting (BioReF) on HepG2 cells using a gene expression array. Similar biological pathways were affected by extracts of all four Rhizoma Coptidis varieties but not by their analogue, Mahoniae Caulis. Among these pathways, the terpenoid backbone biosynthesis pathway was highly enriched, and six genes in the mevalonate (MVA) pathway were all down-regulated. However, the expression, maturation, as well as the specific DNA binding capacity of their coordinate transcription factor, sterol response element binding protein 2 (SREBP2), was not affected by Rhizoma Coptidis extract (RCE) or its typical active alkaloid berberine. Cellular cholesterol content tests further verified the cholesterol-lowering function of RCE in vitro, which supplements evidence for the use of Rhizoma Coptidis in hyperlipidemia treatment. This is the first described example of evaluating the quality of Rhizoma Coptidis with BioReF and a good demonstration of using BioReF to uncover the mechanisms of herbs at a systematic level.

Autophagy and ER stress in LPS/GalN­induced acute liver injury.

Numerous mechanisms and factors have been implicated in liver damage; however, the involvement of autophagy and endoplasmic reticulum (ER) stress during early­stage liver injury remains to be fully elucidated. The present study was conducted to determine the expression of autophagy and ER­stress­associated proteins in hepatic tissues following injury. A murine model of liver injury was induced by intraperitoneally injecting lipopolysaccharide (LPS) and D­galactosamine (GalN), and control mice were similarly injected with normal saline. The gross and histological appearance of the liver was examined, serum alanine aminotransferase (ALT) levels were detected, and protein expression evaluated via Western blot analysis. Co­administration of LPS and GalN effectively induced liver injury in mice, with severe liver damage manifesting at 6 h following induction. Furthermore, upregulation of autophagy­associated proteins, including microtubule­associated protein 1 light chain 3 (MAP1 LC3 or, briefly, LC3­II) and Beclin 1, were detected 3 h following liver injury. Consistently, the expression of the ER stress factor CCAAT/enhancer binding protein (C/EBP)­homologous protein decreased after 1 h, but increased 3 h after liver damage. Autophagy and ER stress occurred in early­stage liver injury induced by LPS­GalN administration in mice. Induction of autophagy may act as a compensatory mechanism during early liver injury.

Prevalence, awareness, treatment, and control of hypertension among China's Sichuan Tibetan population: A cross-sectional study.

BACKGROUND: Our aim is to investigate the prevalence, awareness, treatment, and control status of hypertension and explore the associated factors among Sichuan Tibetan population. METHODS: A cross-sectional investigation was conducted in the Sichuan Tibetan region from to September 2013 to March to 2014. Three thousand two hundred and forty persons were included in the study through a multi-stage stratified clustering sampling. Participants received questionnaires and physical examination. Blood pressure (BP) was recorded three times after 5 min of rest with the mean taken as the final BP. Hypertension was defined according the 2010 Chinese guidelines for the management of hypertension. RESULTS: Prevalence of hypertension was 45.7%. The proportion of different stages (1-3) of hypertension was 31.7%, 9.2%, and 7.6% for males and 26.3%, 9.5%, and 6.0% for females. The rate of awareness, treatment, and control of hypertension were 4.9%, 21.3%, and 3.0% for males and 7.5%, 24.5%, and 3.1% for females. Multiple-factor analysis found that age, overweight or obesity (odds ratio(OR)=1.16), drinking alcohol (OR = 1.29, 95% confidence interval (CI):1.07-1.54), increased waist circumference (OR = 1.81, 95%CI: 1.39-2.36), family history of hypertension (OR = 1.51, 95%CI; 1.28-1.78), higher salt intakes (OR = 1.62, 95%CI: 1.24-2.11), long duration of sleep (OR = 1.05, 95%CI: 1.01-1.09), rural area (OR = 1.99, 95%CI: 1.64-2.41), and drinking coffee at times (OR = 0.71, 95%CI:0.57-0.87) were related to hypertension. CONCLUSION: Prevalence of hypertension in Sichuan Tibetan was significantly higher than the national level with low rates of awareness, treatment, and control of hypertension. Intervention measurements are needed to change some unhealthy lifestyles, behaviors, and habits in this region.