Long Non-Coding RNA MAFG-AS1 as a Potential Biomarker for Hepatocellular Carcinoma: Linkage with Tumor Features, Markers, Liver Functions, and Survival Profile.

Purpose: Long non-coding RNAs musculoaponeurotic fibrosarcoma oncogene family, protein G antisense 1 (lnc-MAFG-AS1) regulates hepatocellular carcinoma (HCC) progression and treatment resistance in multiple ways, while its engagement in HCC clinical management remains obscure. The current study aims to explore the relationship of lnc-MAFG-AS1 with tumor features, liver function indexes, tumor markers, and prognosis in HCC patients. Methods: One hundred and fifty-two surgical HCC patients who underwent tumor resection were retrospectively analyzed. Their tumor and adjacent tissues were acquired and then proposed to reverse transcription-quantitative polymerase chain reaction to detect lnc-MAFG-AS1 expression. Results: Lnc-MAFG-AS1 expression was increased in HCC tumor tissue than in adjacent tissue [median (interquartile range): 2.730 (1.685-4.198) vs. 0.990 (0.703-1.468), p < 0.001], with a high area under the curve [0.889, 95% confidence interval (CI): 0.854-0.924] to distinguish them via receiver operating characteristic curve analysis. Tumor lnc-MAFG-AS1 was linked with multifocal nodules (p < 0.001), increased Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.018), and elevated China Liver Cancer (CNLC) stage (p = 0.008), which also correlated with an abnormal alpha-fetoprotein (AFP) level (p = 0.004), However, lnc-MAFG-AS1 was not linked with other disease conditions, tumor properties, liver function indexes, or tumor markers (all ps > 0.05). In addition, patients with a high expression of lnc-MAFG-AS1 exhibited worse overall survival than those with a low expression of lnc-MAFG-AS1 [median (95% CI): 34.0 (24.5-43.5) vs. 48.0 (41.5-54.5) months] (p = 0.011), which was further validated by univariate Cox's analysis [hazard ratio (HR) = 1.827, p = 0.013] and multivariate Cox's analysis (HR = 1.697, p = 0.040). Conclusion: Lnc-MAFG-AS1 relates to multifocal nodules, increased BCLC stage, elevated CNLC stage, and abnormal AFP level and predicts pejorative prognosis in HCC patients.

Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

Detection of melatonin and homocysteine simultaneously in ulcerative colitis.

BACKGROUND: Oxidative stress could be a major contributing factor to the tissue injury that characterize inflammatory bowel disease (IBD). Homocysteine (HCY) could cause oxidative damage to the colon tissue in ulcerative colitis (UC) patients, melatonin (MLT) supplementation could reduce oxidative damage that caused by HCY in vitro and in vivo. In this study, we aimed to determine the levels of plasma HCY and MLT simultaneously in UC patients. METHODS: Collected the clinical data of 112 UC patients and 110 healthy controls (HC). The levels of plasma HCY and MLT were detected by HPLC-FD method. The levels of plasma folate, vitamin B(12) (VitB(12)) were detected by ELISA method. RESULTS: The levels of plasma HCY in UC patients were significantly higher than that in HC (11.27±7.26 µmol/L vs. 8.19±4.81 µmol/L, P=0.000). The levels of plasma MLT in UC patients were significantly lower than that in HC (49.06±31.40 pg/ml vs. 64.28±41.16 pg/ml, P=0.008). The levels of plasma folate and VitB(12) in UC patients were lower than that in HC (7.64±1.95 nmol/L vs. 9.14±1.23 nmol/L, 108.64±32.22 pmol/L vs. 112.64±33.33 pmol/L, P<0.05). The levels of plasma HCY and MLT in UC patients were not correlated with either the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) or the disease activity, localization and duration of UC (P>0.05). The change of increasing levels of plasma MLT but decreasing levels of plasma HCY was shown in UC patients, however, the association between the levels of plasma MLT and HCY were not statistically significant (P>0.05). CONCLUSIONS: The levels of plasma HCY were increased whereas the levels of plasma MLT were decreased in UC patients.

[Significance of plasmic homocysteine, folate and Vitamin B(12) in ulcerative colitis].

OBJECTIVE: To investigate the clinical significance of plasmic homocysteine (Hcy), folate (FA) and Vitamin B(12) (VitB(12)) in patients with ulcerative colitis (UC). METHODS: Plasmic Hcy in 112 cases of UC patients and 110 controls were detected by HPLC-FD method. Plasmic FA, VitB(12) in 76 cases of UC patients and 12 controls were detected by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The level of plasmic Hcy in UC patients was(11.27±7.26) µmol/L, significantly higher than that in controls[(8.19±4.81) µmol/L, P<0.05], and was not significantly correlated with disease index, extent and duration of UC(P>0.05). The level of FA and VitB(12) in UC patients were (7.64±1.95) nmol/L and (108.64±32.22) pmol/L respectively, lower than those in controls[(9.14±1.23) nmol/L and (112.64±33.33) pmol/L, P<0.05]. The level of plasmic Hcy was negatively correlated with the level of FA and VitB(12) in UC patients(P<0.05). The level of plasmic FA decreased to some extent with UC disease duration. CONCLUSION: Plasmic Hcy is elevated in UC patients, which may be related to the decrease of FA and VitB(12).

Involvement of cytochrome P450 3A4 and P-glycoprotein in first-pass intestinal extraction of omeprazole in rabbits.

AIM: To quantitatively evaluate in vivo first-pass intestinal extraction of omeprazole and to investigate the possible involvement of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in this process in rabbits. METHODS: Pharmacokinetic parameters were examined after intraduodenal (id), intraportal venous (ipv), and intravenous (iv) administration of omeprazole at various doses to intestinal and vascular access-ported rabbits. Extraction ratios in the liver and intestinal tract were determined from the area under the plasma concentration-time curve (AUC). In addition, omeprazole was administered by id or iv to rabbits alone or 30 min after the id administration of CYP3A4 or P-gp inhibitors (ketoconazole or verapamil, respectively). RESULTS: Pharmacokinetic parameters of omeprazole were dose-dependent after id, ipv, and iv administration at various doses. After id administration of 3 mg/kg omeprazole, the hepatic and intestinal extraction ratio was 57.18%+/-2.73% and 54.94%+/-1.85%, while the value was 59.29%+/-3.14% and 54.20%+/-1.53% after given 6 mg/kg, respectively. Compared with the control group, the presence of ketoconazole (60 mg/kg) or verapamil (9 mg/kg) significantly increased the area under the plasma concentration time curve (AUC) and the peak concentration (C(max)) of id-administered omeprazole, while it had no significant effect on omeprazole administered by iv. CONCLUSION: Oral omeprazole undergoes marked extraction in the small intestine, and increased bioavailability of the drug after id administration of ketoconazole and verapamil suggests that this increase results from inhibition of CYP3A4 and P-gp function in the intestine rather than the liver.