Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of tumors. The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies. AIM: To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs (LMR-lncRNAs) and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC. METHODS: Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs. Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs. Nile red staining was employed to observe intracellular lipid levels. The interaction between RP11-817I4.1, miR-3120-3p, and ATP citrate lyase (ACLY) was validated through the performance of dual-luciferase reporter gene and RIP assays. RESULTS: Three LMR-lncRNAs (negative regulator of antiviral response, RNA transmembrane and coiled-coil domain family 1 antisense RNA 1, and RP11-817I4.1) were identified as predictive markers for HCC patients and were utilized in the construction of risk models. Additionally, proliferation, migration, and invasion were reduced by RP11-817I4.1 knockdown. An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis. CONCLUSION: LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients, and the discovery of a novel LMR-lncRNAs, RP11-817I4.1, revealed its role in promoting lipid accumulation, thereby accelerating the onset and progression of HCC.

Protective effects of L-carnitine on intestinal ischemia/reperfusion injury in a rat model.

BACKGROUND: Ischemia/reperfusion (IR) injury of the intestine is a major problem in abdominal pathological condition and is associated with a high morbidity and mortality. The purpose of the study is to determine whether the L-carnitine can prevent the harmful effects of small intestinal IR injury in rats. METHODS: Thirty Sprague-Dawley rats were randomly divided into three groups. Sham operated group (S), for shamoperated, the IR group for rats submitted to 45-minute of intestinal ischemia and 2-hour reperfusion, and IR+L group for those IR group treated with L-carnitine before reperfusion. All the rats were given EmGFP labelled E. coli DH5α through gavage 2-hour before the operative procedure. Afterwards the bacterial translocation (BT) from mesenteric lymph nodes (MLN), liver, spleen, lung and portal vein blood were detected. And the colony forming units/g (CFU/g) were counted. The TNF-α, IL-1ß, IL-6, and IL-10 in serum were measured by ELISA. The morphometric study was measured by Chius classification. RESULTS: The levels of BT were higher in the IR group than IR+L group (P < 0.05). The E. coli DH5α was hardly detected in the S group. The IR+L rats had enhancement of IL-10 and suppressed production of serum TNF-α, IL-1ß and IL-6, compared to IR group rats (P < 0.05). The degree of pathological impairment in small intestine was lighter in IR+L than IR group (P < 0.05). CONCLUSIONS: The L-carnitine pretreatment has a positive effect on reducing levels of BT, on inhibiting secretion of proinflammatory cytokines, and on lessening intestinal mucosa injury during small intestinal IR injury. KEYWORDS: L-carnitine; Ischemia/reperfusion injury; Intestine.

Hepatocyte growth factor protects human embryonic stem cell derived-neural progenitors from hydrogen peroxide-induced apoptosis.

Promoting human embryonic stem cell (hESC)-derived-neural progenitor survival in the pro-apoptotic niche is pivotal for stem cell replacement therapy. The present study was designed to investigate the protective effect of hepatocyte growth factor (HGF) on hESC-derived neural progenitor injured by hydrogen peroxide (H(2)O(2)) exposure. Treatment of hESC-derived neural progenitor cells with HGF prior to H(2)O(2) exposure conferred protective effect against oxidative stress-induced apoptosis. HGF treatment increased both phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation. However, selective inhibition of each pathway supported that the activation of PI3K/AKT, but not ERK1/2, provides survival advantage to the neural progenitor cells. Further investigation indicated that HGF pretreatment could attenuate the decrease of the expression of Bcl-2 protein induced by H(2)O(2), whereas the level of Bax was not affected. Additionally, we observed that H(2)O(2)-induced decrease of mitochondrial transmembrane potential, release of cytochrome c and increase of caspase-3 activation were alleviated by HGF pretreatment. These effects of HGF could be reversed by inhibition of the PI3K/Akt and ERKs pathways, indicating PI3K/Akt and ERKs signaling might be involved in HGF-mediated regulation of mitochondrial apoptotic pathway mediated by H(2)O(2). The neuroprotective effect of HGF might potentially be useful in stem cell-based therapies for neurodegenerative disorders.

Relief of abdominal pain by morphine without altering physical signs in acute appendicitis.

BACKGROUND: Abdominal pain is a common symptom among patients with acute appendicitis, yet these patients have long been denied relief from suffering because of widespread misconceptions associated with the use of opioids. We determined whether morphine hydrochloride masked the physical signs in adults with acute appendicitis and assessed the efficacy of morphine in relieving abdominal pain. METHODS: A prospective, double-blind, placebo controlled, clinical trial was conducted with 106 adult patients between 16 and 70 years old with acute appendicitis. Patients were randomly divided into a morphine group (n=54) or a normal saline group (n=52). All patients presented with acute abdominal pain with onset within 3 days. The morphine group received hypodermic injection of morphine (0.15 mg/kg; maximum 20 mg) and the control group members were given an equivalent volume of normal saline solution. The clinical symptoms, physical signs, and patients' cooperation during physical examination were assessed before and after 30 minutes of morphine or normal saline administration. RESULTS: Abdominal pain was significantly relieved and the patients' cooperation was improved in the morphine group after 30 minutes treatment compared with the control group and before morphine administration (P<0.05). The physical signs were unaffected by either treatment (P>0.05). CONCLUSIONS: Morphine relieved abdominal pain and improved the patients' cooperation for treatment and care. Furthermore, the morphine did not mask the physical signs of acute appendicitis.

[Protection of hepatocyte growth factor against hydrogen peroxide-induced mitochondria-mediated apoptosis in rat cortical neurons.].

Hepatocyte growth factor (HGF) pretreatment could protect multiple cell types from apoptosis induced by various damages including oxidative stress. The present study was designed to investigate the protective effect of HGF on rat cortical neurons against apoptosis induced by hydrogen peroxide (H2O2) in culture, and then to explore whether HGF could influence the mitochondrial pathway of apoptosis. Primary rat cortical neurons were isolated from Sprague-Dawley rats and cultured in serum free medium containing 2% B27 and Neurobasal-A. To mimic the oxidative stress damage, cortical neurons were exposed to 100 mumol/L H2O2 for 4 h. To explore the effects of HGF on the neurons subjected to H2O2 injury, cells were pretreated with HGF 15, 30, 60 ng/mL for 24 h, respectively, and then exposed to 100 mumol/L H2O2 for 4 h. The cell viability was measured by MTT colorimetric assay and cell injury was evaluated by lactate dehydrogenase (LDH) leakage rate. Apoptotic cells were detected by Hoechst 33258 staining and Annexin V-FITC/PI double labeled flow cytometry. The caspase-3 activity was assessed by colorimetry. The alteration of transmembrane potential of mitochondria was determined by confocal laser scanning microscopy. The expression of cytochrome C protein was measured by Western blot analysis. The results showed that H2O2 treatment significantly decreased the cell viability, increased LDH leakage rate and the percentage of apoptotic cells. Pretreatment of HGF at different concentrations (15-60 ng/mL) could remarkably increase the cell viability of neurons. Compared with that of H2O2 group (53.4%+/-7.4%), the cell viabilities of neurons treated with 15, 30, and 60 ng/mL HGF significantly increased to (69.3+/-6.4)%, (77.5+/-6.1)% and (82.9+/-9.3)% (P<0.05), respectively. HGF preincubation also evidently decreased the LDH leakage rate in cortical neurons damaged by H2O2. The results of Hoechst staining revealed that HGF pretreatment could significantly reduce the apoptotic rate of neurons. The apoptotic rate of H2O2 group was (62.8+/-7.1)%, while that of HGF groups decreased significantly to (34.8+/-8.4)%, (23.5+/-3.2)% and (18.6+/-4.5)% (P<0.05), respectively. The data from caspase-3 activity assay indicated that HGF preconditioning could also remarkably decrease the caspase-3 activity of neurons. In addition, in the presence of various concentrations of HGF, the decrease of transmembrane potential of mitochondria in neurons caused by H2O2 injury could be reversed. Moreover, as detected by Western blot analysis, HGF downregulated the expression of cytochrome C protein in neurons. These results suggest that HGF has a protective effect on rat cortical neurons against apoptosis induced by H2O2, which might be related to the inhibition of the mitochondrial apoptotic pathway and the suppression of the caspase-3 activity.

Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice.

AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo. METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model was established successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method. RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P < 0.05), whereas there were no significant differences (P > 0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group. CONCLUSION: rhGH does not accelerate the proli-feration of human gastric cancer cell in vivo.

In vitro effects of recombinant human growth hormone on growth of human gastric cancer cell line BGC823 cells.

AIM: To study the effects of recombinant human growth hormone (rhGH) on growth of human gastric cancer cell line in vitro. METHODS: Experiment was divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cell inhibitory rate, cell cycle, cell proliferation index (PI) and DNA inhibitory rate of human gastric cancer line BGC823, at different concentrations of rhGH treatment were studied by cell culture, MTT assay and flow cytometry. RESULTS: The distinctly accelerated effects of rhGH on multiplication of BGC823 cell line were not found in vitro. There was no statistical significance between rhGH group and control group, or between rhGH+L-OHP group and L-OHP group (P>0.05). The cell growth curve did not rise. Cell inhibitory rate and cells arrested in G(0)-G(1) phase were obviously increased. Meanwhile, cells in S phase and PI were distinctly decreased and DNA inhibitory rate was obviously increased in rhGH+L-OHP group in comparison with control group and rhGH group, respectively (P<0.01). Cell inhibitory rate showed an increasing trend and PI showed a decreasing trend in rhGH+L-OHP group compared with L-OHP group. CONCLUSION: In vitro rhGH does not accelerate the multiplication of human gastric cancer cells. It may increase the therapeutic efficacy when it is used in combination with anticancer drugs.