Non-coding RNAs in cardiomyocyte proliferation and cardiac regeneration: Dissecting their therapeutic values.

Cardiovascular diseases are associated with high incidence and mortality, contribute to disability and place a heavy economic burden on countries worldwide. Stimulating endogenous cardiomyocyte proliferation and regeneration has been considering as a key to repair the injured heart caused by ischaemia. Emerging evidence has proved that non-coding RNAs participate in cardiac proliferation and regeneration. In this review, we focus on the observation and mechanism that microRNAs (or miRNAs), long non-coding RNAs (or lncRNAs) and circular RNA (or circRNAs) regulate cardiomyocyte proliferation and regeneration to repair a damaged heart. Furthermore, we highlight the potential therapeutic role of some non-coding RNAs used in stimulating CMs proliferation. Finally, perspective on the development of non-coding RNAs therapy in cardiac regeneration is presented.

Potential prognostic value of circulating levels of vascular endothelial growth factor-A in patients with gastric cancer.

OBJECTIVE: The aim of this study was to evaluate the potential prognostic value of the circulating levels of vascular endothelial growth factor-A (VEGF-A) in patients with gastric cancer. MATERIALS AND METHODS: An ELISA was used to quantify the serum and plasma levels of VEGF-A in 135 patients with gastric cancer and 48 controls with benign gastric diseases diagnosed by gastroendoscopy and histology of the biopsied specimens. Serum VEGF-A levels were assayed in controls (n = 10) and patients with gastric cancer (n = 10) prior to surgery. Further samples from 16 patients with gastric cancer, 3 weeks after tumour excision, were collected. RESULTS: VEGF-A levels were significantly higher in both serum and plasma from patients with gastric cancer than those from the controls (serum: 342.1 pg/ml vs. 80.0 pg/ml, p < 0.01; plasma: 74.1 pg/ml vs. 23.7pg/ml, p < 0.01). In both cancer patients prior to surgery and controls, serum VEGF-A levels appeared to be unchanged over a 7-day period. However, examination of paired samples from 16 cancer patients collected prior to surgery and 3 weeks post-surgery showed that tumor excision resulted in a significant decrease in VEGF-A levels (Paired t-test, t = 5.4, p < 0.0001). CONCLUSION: Serum and plasma VEGF-A levels were significantly higher in patients with gastric cancer than in the controls. Serum VEGF-A levels correlated with tumour burden, as VEGF-A levels were significantly lowered following tumour excision in patients with gastric cancer.

[Distribution of Helicobacter pylori in stomach before and after the administration of Lansoprazole].

OBJECTIVE: To investigate the effect of the acid inhibitor-Lansoprazole on the distribution of Helicobacter pylori (H.pylori) in stomach. METHODS: Biopsy specimens were taken from the duodenal ulcer patients who underwent gastroscopy before and after the treatment of Lansoprazole. The biopsy specimens were taken from the lesser curvature of the antrum and the greater curvature of the corpus respectively. H&E and Warthin-Starry staining were used for detecting the changing of active gastritis and the positive rate of H.pylori. RESULTS: (1)The positive rates of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment, in the lesser curvature of the antrum were 93.02%, 58.14%, and 86.05%, respectively. The positive rate and density of H.pylori 4 weeks after treatment were greatly decreased compared with those before treatment (P<0.001) and also lower than those 3 months after treatment (P<0.05). (2) The positive rate of H.pylori before treatment, 4 weeks after treatment and 3 months after treatment in greater curvature had differences without statistical significance. However, the density of H.pylori 4 weeks after treatment was increased compared with that before treatment. CONCLUSION: Lansoprazole can change the colonization site of H.pylori in the stomach, decrease the positive rate and the density of H.pylori in lesser curvature of the antrum, but increase the density of H.pylori in the greater curvature of the corpus. This effect is most obvious in one month after treatment. Active gastritis is related to H.pylori.

[Pioglitazone, a peroxisome proliferators-activated receptor gamma ligand, inhibits dimethylhydrazine (DMH) induced aberrant crypt foci in rats].

OBJECTIVE: To investigate the chemopreventive effects of pioglitazone (exogenous PPAR gamma ligand) on rat colon aberrant crypt foci, a rat carcinogenesis model induced by dimethylhydrazine (DMH), and to compare pioglitazone with sulindac (a NSAID). METHODS: Thirty-two, 8-week-old, female Sprague-Dawley rats were randomly divided into four groups (n = 8 each). Group 1 rats were injected with DMH alone (120 mg.kg-1, single subcutaneous injection). Group 2 rats were injected with saline alone. Group 3 rats were pre-treated with sulindac (320 mg.kg-1) for 7 days before DMH initiation. Group 4 rats were treated with pioglitazone (100 mg.kg-1). The animals were killed at the end of the experiment (week 5) and the colons were stained with methylene blue. The aberrant crypt foci (ACF) of the colonic mucosa were assessed. RESULTS: In Group 1 rats (DMH only), the average numbers of ACF/colon and AC/colon were (182 +/- 93) and (263 +/- 198), respectively. In Group 2 (saline group) rats, no ACF were found. In Group 3 (sulindac group) rats, the average numbers of ACF/colon and AC/colon were (91 +/- 49) and (140 +/- 69), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). In Group 4 (pioglitazone group) rats, the average numbers of ACF/colon and AC/colon were (97 +/- 23) and (148 +/- 31), respectively. Both of them were decreased significantly compared with the values in Group 1 (P < 0.01 and P < 0.05). No difference was found in the values of Group 3 and Group 4. CONCLUSION: These results suggest that pioglitazone have chemopreventive effects against rat colon carcinogenesis induced by DMH, whose effect is similar to that of sulindac.

[Effect of recombinant human trefoil factor on protection of gastric mucosa and healing of chronic gastric ulcer in rats].

OBJECTIVE: To study the effect of recombinant human intestinal trefoil factor ( rhITF) on the healing of rat chronic gastric ulcer, protect gastric mucosal and mechanisms are involved. METHODS: (1) Acute gastric mucosal injury was induced by ethanol, stress, aspirin and pylorusl ligation. The injury index,MDA, GMBL,hexosamine (Hex) and acid output were measure. (2) Chronic gastric ulcer was induced in rats by application of 50% glacial acetic acid to the serosa of the glandular stomach. After injury, rats received by rhITF or vehicle orally twice daily for 11 days. On day 12, gastric mucosal blood flow GMBF was measured under ether anesthesia. Then the pylorus was ligated for 3 hours and each stomach removed. The gastric acid output, ulcer index, Hex and nitric oxide(NO) content in gastric mucosa, as well as iNOSmRNA in the ulcer bed were determined. RESULTS: (1) rhITF protected gastric mucosa from the acute lesion, and increased Hex content in gastric mucosa. (2) rhITF treatment significantly decreased the ulcer index and gastric acid output, but increased the GMBF, Hex and NO content in comparison with the control groups. In addition, rhITF also stimulated iNOSmRNA expression in the ulcer bed by situ hybridization analysis. CONCLUSION: rhITF can protect gastric mucosa against acute lesion, and enhance the healing of chronic gastric ulcer in the rats. This action may result from the inhibition of gastric acid output, increase of GMBF.Hex and NO content and rhITF stimulated iNOSmRNA expression.

[The roles of dopamine 4 receptor in MPTP-induced gastrointestinal mucosal injury in rats].

OBJECTIVE: Using the dopamine 4 receptor (D(4)) agonist quinpirole (Q.) and antagonist clozapine (C.) to investigate the role of D(4) in MPTP induced gastrointestinal injury in rat. METHODS: SD rats were randomly divided into 8 groups (n = 5 approximately 9 each group): NS as control; Q. 0.5 mg/kg; Q. 1 mg/kg; C. 10 mg/kg; Q. 0.5 mg/kg + MPTP; Q. 1 mg/kg + MPTP; and MPTP l mg/100 g. After treated with the different chemicals, the gastric and duodenal mucosa lesion index (LI) was recorded. Gastric and duodenal mucosa was collected to assay NO and iNOS by spectrophotometer. RESULTS: (1) MPTP peritoneal injection induced significant gastro-duodenal mucosa injury; both gastric and duodenal LI were 5 approximately 6-fold higher than control group (P < 0.01). (2) Q. or C. used alone showed no effect on gastro-duodenal mucosa, Q. used before MPTP could resist the MPTP-induced mucosa injury, especially in duodenum (P < 0.01). This effectiveness is dose dependent. C. had no effect on gastro-duodenal mucosa protection. (3) The mucosal NO concentration and iNOS activity in MPTP group were lower than that in control, especially in duodenum (P < 0.05). They were negative correlated with LI. CONCLUSION: MPTP peritoneal injection induced significant gastro-duodenal mucosa injury in rat, mediated partially by decreasing the activity of mucosa iNOS and NO concentration. D(4) agonist Q. could resist the effectiveness of MPTP-induced mucosa injury, while the antagonist C. had no effect.

Effects of san qi on gastric secretion and protective factors of gastric mucosa in the rat with precancerous lesion of stomach.

In the model rat with precancerous lesion of stomach induced by the combined method of insertion of a spring into the pylorus and high salt hot paste, effects of San Qi ([symbol: see text] Radix Notoginseng) on gastric secretion and protective factors of stomach were investigated. The results indicated that gastric secretion, gastric mucosal blood flow (GMBF) and aminohexose content lowered significantly, and malondialdehyde (MDA) increased significantly (P < 0.01) in the model group as compared with the normal group; after treatment with San Qi Powder for 12 weeks, both gastric secresion and GMBF increased, and MDA content decreased as compared with the negative control group (P < 0.01), with no significant increase of aminohexose content. It is suggested that San Qi ([symbol: see text] Radix Notoginseng) may improve gastric secretion, and that increase of GMBF and antagonism against the lesion of oxygen free radicals are possibly one of its mechanisms.

Factors influencing intercellular spaces in the rat esophageal epithelium.

AIM: To evaluate the effect of acute stress, hydrochloric acid, ethanol, aspirin, and prednisolone on the intercellular spaces of the esophageal epithelium. METHODS: Part I, male Sprague-Dawley rats were randomly divided into eight groups and treated with the damaging or control factors. The esophagus of each rat was macroscopically inspected. Histological changes in mucosal biopsies were examined by light microscopy, and the widths of intercellular spaces were determined by transmission electron microscopy (TEM). Part II, in part I, we found that acute stress and aspirin induced dilated intercellular spaces (DIS) of the esophageal epithelium. Therefore, the effect of acid suppression pretreatment with esomeprazole on esophageal epithelial DIS induced by water immersion and restraint stress (WRS) and aspirin was further investigated to determine the association of DIS with acid reflux. After administration of 0.9% sodium chloride solution or esomeprazole solution orally for five days, rats underwent WRS or intragastric administration of aspirin solution. Esophageal epithelial intercellular spaces were investigated by TEM. RESULTS: (1) The five damaging factors produced no lesions or inflammation in esophageal mucosa of rats under either gross or routine histological inspections. Esophageal epithelial intercellular space diameters in stress and aspirin groups were significantly greater, nearly three or two-fold respectively, than those in their corresponding control groups (stress model: 0.38 + or - 0.05 microm vs 0.13 + or - 0.02 microm, P < 0.01; aspirin model: 0.32 + or - 0.12 microm vs 0.19 + or - 0.05 microm, P < 0.01). Neither intragastric administration of hydrochloric acid or ethanol, nor hypodermic injection of prednisolone produced DIS compared with their corresponding control groups (hydrochloric acid model: 0.24 + or - 0.03 microm vs 0.19 + or - 0.05 microm, P > 0.05; ethanol model: 0.25 + or - 0.10 microm vs 0.19 + or - 0.05 microm, P > 0.05; prednisolone model: 0.20 + or - 0.03 microm vs 0.14 + or - 0.03 microm, P > 0.05); and (2) No significant difference in the intercellular space diameters was observed between the group pretreated with esomeprazole and the control group, in both the stress and aspirin models (stress model: 0.35 + or - 0.05 microm vs 0.37 + or - 0.05 microm, P > 0.05; aspirin model: 0.24 + or - 0.02 microm vs 0.27 + or - 0.03 microm, P > 0.05). CONCLUSION: Acute stress and aspirin can induce DIS of the esophageal epithelium in rats, and it is not correlated with acid reflux.