Long noncoding RNA ZFAS1 promotes hepatocellular carcinoma proliferation by epigenetically repressing miR-193a-3p.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Long noncoding RNAs (lncRNAs) play important roles in many diseases. Therefore, the aim of this study was to investigate the role of lncRNA ZFAS1 in the development of HCC and to explore its underlying mechanism. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to detect ZFAS1 expression in tissue samples of HCC patients. Subsequently, Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and EdU incorporation assay were performed to detect the function of ZFAS1 in vitro. Furthermore, mechanism assays were performed to explore the interaction between ZFAS1 and miR-193a-3p. RESULTS: ZFAS1 was significantly highly expressed in HCC tissues than that of adjacent normal tissues. The growth ability of HCC cells was markedly inhibited after ZFAS1 was silenced. However, the growth ability of HCC cells was remarkably promoted after ZFAS1 overexpression. Moreover, RT-qPCR results revealed that miR-193a-3p was significantly down-regulated via the overexpression of ZFAS1. However, miR-193a-3p was significantly up-regulated via the knockdown of ZFAS1. Further experiments showed that miR-193a-3p was a direct target of ZFAS1 in HCC. CONCLUSIONS: ZFAS1 could enhance the proliferation of HCC cells by suppressing miR-193a-3p, which might be a potential therapeutic target in HCC.

Protective effect of erythropoietin against lipopolysaccharide induced inflammation and mitochondrial damage in liver.

Recent studies have shown that liver dysfunction is an early event in sepsis. Pre-existing liver dysfunction is a risk factor for progression of infection to sepsis. However, the mechanism of the liver immune response in promoting sepsis and the importance of liver function are not completely understood. In the present study, we investigated the protective effect of erythropoietin (EPO) against mitochondrial dysfunction in a lipopolysaccharide (LPS)-induced sepsis model, and examined the underlying signaling mechanisms. Enzyme linked immunosorbent assay (ELISA) and reactive oxygen species (ROS) analysis were used to evaluate the levels of interleukin (IL)-1ß and ROS. The effects of EPO on hepatic mitochondrial function were studied by detecting the mitochondrial DNA (mtDNA) copy number using real-time PCR (RT-PCR). To explore the mechanism of action of EPO in sepsis, protein expressions of IL-1ß, caspase-1 and NLRP3 were assessed by Western blotting; liver histopathology and ultrastructure of liver mitochondria was examined by transmission electron microscopy. We found that LPS treatment increased serum IL-1ß and ROS levels, the effect of which was attenuated by EPO. Moreover, LPS treatment also increased the mtDNA copy number and the protein expressions of IL-11ß, caspase-1, and NLRP3, which were suppressed by EPO. Histological examination of liver showed LPS-induced cellular edema in hepatic lobules, lymphocytic infiltration and hepatocellular necrosis; these changes were also alleviated by EPO treatment. On electron microscopy, the size of hepatocellular mitochondria in the LPS group was smaller than that in the control group, and the changes were reversed by EPO in the LPS+EPO group. Our results suggest that EPO alleviated liver and mitochondrial damage induced by LPS, possibly via inhibition of NLRP3 signaling.

Expression of dopamine transporter in the different cerebral regions of methamphetamine-dependent rats.

OBJECTIVES: To observe the expression of the dopamine transporter (DAT) in six cerebral regions of a methamphetamine (MA)-dependent rat, which were frontal cortex, nucleus accumbens septi, striatum, hippocampus, substantia nigra and ventral tegmental area. METHODS: The rats were administrated intraperitoneally with 10 mg/kg/day of MA for 10 days consecutively; the behaviour changes were measured via the conditioned place preference (CPP), and the scores of stereotyped behaviour (SB) were used to confirm animal addiction. Then, the animals were further injected with MA respectively for 1, 2, 4 and 8 weeks to establish different periods of MA-dependent models. The expressions of DAT and DAT messenger RNA in six cerebral regions were detected. RESULTS: The results of CPP and SB scores were significant different when comparing all four experimental groups with the control group (p < 0.05). Comparing between different experimental groups, the expression of DAT mainly decreased and had dynamic changes in the same regions (p < 0.05). Comparing the different regions with each other in the same experimental group, the expression of DAT also had significant difference in several regions p < 0.05). CONCLUSIONS: The expression of DAT mainly decreased and had different in the six cerebral regions at the same MA-dependent time period as well as at different time periods in the same cerebral region. It was speculated that DAT might play a crucial role in the mechanism of MA dependence.

Effects of electro-acupuncture on the expression of c-jun and c-fos in spared dorsal root ganglion and associated spinal laminae following removal of adjacent dorsal root ganglia in cats.

This study evaluated the plastic changes of c-jun and c-fos in the right sixth lumbar dorsal root ganglion (L6 DRG), Rexed's lamina II in representative spinal segments L3, L5, and L6 and in the nucleus dorsalis (ND) at L3 segments after electro-acupuncture (EA) in cats subjected to removal of L1-L5 and L7-S2 DRG. Following dorsal root ganglionectomy, there was a significant increase in the density of c-jun immunoreactivity in the neurons and glia in spinal lamina II and in the ND; there was also marked elevation in the expression of c-fos in ND. In both cases there was no change in the c-jun and c-fos immunoreactivity in the DRG. After EA in the operated animals, there was an up-regulation in the expression of c-jun in the L6 DRG and the associated spinal lamina II; however, increased c-fos expression was detected only in the L6 DRG. Western blot and RT-PCR were also performed to quantitatively explore the mRNA and protein expression changes in the spinal dorsal horn and associated DRG. Following partial deafferentation, there was a significant increase in the protein level of both c-jun and c-fos in the dorsal horn, while, in both cases there was no change in c-jun and c-fos protein and mRNA in the DRG. After EA in the operated animals, both c-jun protein and its mRNA in the L6 DRG as well as the associated dorsal horn of L6 spinal segment were upregulated, but increased c-fos protein and its mRNA was observed only in the L6 DRG. These findings suggested that c-jun and c-fos might be related to the acupuncture promoted spinal cord plasticity as reported previously.

[Research of ultra-structural pathological changes of nervous, endocrine and immune system in heroin addicts].

OBJECTIVE: To investigate ultrastructural pathological changes of Heroin-Addicts. METHODS: Heroin-Addicts' central nervous system, endocrine system, immune system and reproductive system in 4 cases are observed by using transmission electron microscope(TEM). RESULTS: The changes of central nervous system are mitochondrion swelling, crista fragmentation and disappear. Endoplasmic reticulum dilation, nervous fibres and cell organelles reduction; mitochondrion swelling, Partial crista fragmentation and endoplasmic reticulum dilation are also found in endocrine system; Lymphocytes reduction, cytoplasm ingredient reduction and dead lymphocytes increase in immune system; in reproductive system, spermatogenic cells and cell organelles are reduced in the male and follicle disappeared in the female. CONCLUSION: Ultra-structural pathological changes of heroin-addicts are presented acute, chronic oxygen deficiency degeneration and necrosis.

The diagnostic significance of carbohydrate antigen CA 19-9 in serum and pancreatic juice in pancreatic carcinoma.

CA 19-9 is a carbohydrate antigen isolated from human colon carcinoma cell line, and is reportedly a tumor marker for pancreatic carcinoma. In this study we determined serum CA 19-9 in 71 normal subjects, 103 patients with benign digestive diseases, 85 patients with periampullary cancers, and 160 patients with other digestive cancers. Serum CA 19-9 was elevated only in 2.3% of normals and benign digestive disease patients, whereas it was increased in 72.7%, 86.4%, and 89.5% of pancreatic, ampullary, and choledochal carcinoma patients, respectively. Of other digestive cancer patients, it was elevated in 23.8%. In addition, very high serum CA 19-9 (greater than 120 u/m) was more often observed in patients with pancreatic, ampullary, and biliary cancer patients than in GL cancer patients (54.1% vs 9.4%, p less than 0.001). In 18 normal subjects and 68 patients with benign and malignant diseases, it was found that CA 19-9 content in the pancreatic juice was significantly increased in pancreatic, ampullary, and choledochal cancer patients, whereas in chronic pancreatitis patients it was normal, indicating that it is a specific and valuable tumor marker in differential diagnosis of pancreatic cancer.

Effect of vasoactive intestinal peptide, somatostatin, neurotensin, cholecystokinin octapeptide, and secretin on intestinal absorption of amino acid in rat.

The effects of vasoactive intestinal peptide (VIP), somatostatin (SRIF), neurotensin (NT), cholecystokinin octapeptide (CCK-8), and secretin (SEC) on the intestinal absorption of amino acid were investigated. Six groups of Wistar rats were studied: (1) controls; (2) VIP treated; (3) SRIF treated; (4) NT treated; (5) CCK-8 treated; (6) SEC treated. [3H]Leucine was given intraluminally through a cannula at the ligament of Treitz, a number of blood samples were obtained through a superior mesenteric vein catheter 1-60 min after administration of [3H]leucine, and the radioactivity of plasma was measured to evaluate the absorption of [3H]leucine. It was shown that VIP and SRIF significantly inhibited the absorption of [3H]leucine (by 59.1% and 38.7%, respectively), whereas NT, CCK-8, and SEC significantly enhanced absorption (by 44.2%, 49.6%, and 39.1%, respectively). Radioimmunoassays of VIP, SRIF, and NT showed that at least some of the hormones or peptides exerted their effects on absorption of leucine at or near their physiological concentrations.