Investigation of the effects of ellagic, vanillic and rosmarinic acid on reperfusion-induced renal injury.

INTRODUCTION: The aim of this study was to investigate the effects of ellagic, vanillic and rosmarinic acid on reperfusion-related kidney damage, developed in an experimental lower-extremity ischaemia/reperfusion (I/R) model. METHODS: Forty-eight female Sprague-Dawley rats were divided into six groups. A median laparotomy and dissection were performed. In the I/R group, 60 minutes of ischaemia followed by 120 minutes of reperfusion was achieved. In addition one group was given 100 mg/kg ellagic acid, one group was given 12 mg/kg vanillic acid, one group was given 50 mg/kg rosmarinic acid and one group was given all three drugs 15 minutes before clamp removal. Bilateral kidney and blood samples were taken in all groups. RESULTS: Tubular epithelial degeneration, necrosis of the tubule epithelium and vessel wall thickening were significantly higher in the I/R group. Some parameters in the groups that were given drugs were found to be lower than in the I/R group and close to that of the control group. Total oxidant status (TOS) and oxidative stress index (OSI) were significantly higher and total antioxidant status (TAS) was significantly lower in the I/R group. Although not statistically significant in the groups given drugs, TAS was higher, and TOS and OSI were lower than in the I/R group. CONCLUSION: The antioxidant effect of ellagic, vanillic and rosmarinic acid administration may have beneficial effects on renal damage after reperfusion in acute lower-extremity ischaemia. This study is expected to provide information for future clinical trials.

Association of MG53 with presence of type 2 diabetes mellitus, glycemic control, and diabetic complications.

OBJECTIVES: Mitsugumin 53 (MG53) is a myokine that acts as a membrane repair protein in tissues. Data on the effect of MG53 on insulin signaling and type 2 diabetes mellitus (T2 DM) are still unknown; most are from preclinical studies. Nevertheless, some researchers have argued that it may be a new pathogenic factor, and therapies targeting MG53 may be a new avenue for T2 DM. Our study aims to evaluate the relationship of circulating MG53 levels with the presence of diabetes, diabetic complications, and glycemic control. METHODS: We conducted a case-control study with 107 patients with T2 DM and 105 subjects without insulin resistance-related disease. Concurrent blood samples were used for serum MG53 levels and other biochemical laboratory data. MG53 concentration was measured using Human-MG53, an enzyme-linked immunosorbent assay kit (Cat# CSB-EL024511HU). RESULTS: We found no difference in MG53 levels between the diabetic and control groups (p = 0.914). Furthermore, when the subjects were divided into tertiles according to their MG53 levels, we did not find any difference between the groups in terms of the presence of diabetes (p = 0.981). Additionally, no correlation was observed between weight, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, albumin excretion in the urine, e-GFR levels, and MG53. Finally, MG53 levels were similar between the groups with and without microvascular and macrovascular complications of diabetes. CONCLUSION: Our research finding provides insightful clinical evidence of lack of association between the levels of MG53 and T2 DM or glycemic control, at least in the studied population of Turkeys ethnicity. However, further clinical studies are warranted to establish solid evidence of the link between MG53, insulin resistance and glycemic control in a wider population elsewhere in the world.

Comparative Investigation of Anti-Inflammatory Effect of Platelet-Rich Fibrin after Mandibular Wisdom Tooth Surgery: A Randomized Controlled Study.

This study evaluated the anti-inflammatory effect of platelet-rich fibrin (PRF) applied to the extraction socket after impacted mandibular third molar surgery with subjective and objective parameters. Forty-eight patients with impacted wisdom teeth in bilateral and similar positions were included in the study. The control group was formed with the standard surgery and the PRF group was formed with local PRF application in addition to standard procedure (n = 96). The anti-inflammatory activity of PRF on postoperative 2nd and 7th days was evaluated subjectively by clinical parameters and objectively by biochemical parameters. Postoperative 2nd- and 7th-day follow-up data of pain, edema, and trismus in the PRF group were found to be statistically significantly lower. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were found to be statistically significantly lower in the PRF group than the control in the postoperative 2nd-day follow-up period (p < 0.001). There was no statistically significant difference in interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) parameters when the PRF group and the control group were compared in both follow-up periods (p > 0.05). The study has demonstrated the effectiveness of locally applied PRF after ITM surgery via clinical parameters and objective data. The quantitative analysis of CRP and ERS can be an effective parameter in determining the amount of inflammation after ITM surgery.

Effects of acrylamide on protein degradation pathways in human liver-derived cells and the efficacy of N-acetylcysteine and curcumin.

Acrylamide is a harmful chemical, and its metabolism occurs mainly in the liver. Acrylamide can form adducts on proteins. Protein homeostasis is vital for metabolic and secretory functions of the liver. No study has investigated the effect of acrylamide on the ubiquitin-proteasome system (UPS). Also, the effect of acrylamide on autophagy and its regulation is not fully known. We aimed to investigate the effects of acrylamide on the UPS, autophagy, mammalian target of rapamycin (mTOR), and heat shock protein 70 (HSP70) in HepG2 cells as well as to examine the effects of N-acetylcysteine and curcumin on these parameters in acrylamide-treated cells. HepG2 cells were initially treated with variable concentrations of acrylamide (0.01-0.1-1-10 mM) for 24 hours. Then, HepG2 cells were treated with 5 mM N-acetylcysteine and 6.79 µM curcumin in the presence of 10 mM acrylamide for 24 hours. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Ubiquitinated protein, mTOR, microtubule-associated proteins 1 A/1B light chain 3B-II (LC3B-II), and HSP70 levels were measured by immunoblotting. Acrylamide at 10 mM concentration, without any significant change at lower concentrations, caused an increase in ubiquitinated protein, LC3B-II, and HSP70 levels and a decrease in mTOR phosphorylation. Furthermore, 5 mM N-acetylcysteine caused a decrease in ubiquitinated protein and HSP70 levels; however, 6.79 µM curcumin did not affect 10 mM in acrylamide-treated cells. Our study showed that acrylamide at high concentration inhibits UPS and mTOR, activates autophagy, and increases HSP70 levels in HepG2 cells, and N-acetylcysteine reduces UPS inhibition and HSP70 levels in acrylamide-treated cells.

Pericardial SCUBE1 levels may help predict postoperative results in patients operated on for coronary artery bypass graft surgery.

INTRODUCTION: Signal peptide-CUB epidermal growth factorlike domain-containing protein (SCUBE1) is a newly described, secretable and measurable cellular surface protein associated with atherosclerotic lesions in humans, which may be involved in hypertension and cardiovascular pathologies. We aimed to detect normal SCUBE1 levels in pericardial fluid and investigate the effects of SCUBE1 values on postoperative outcomes after coronary artery bypass surgery. METHODS: Between February 2016 and March 2017, 184 consecutive patients were included in the study. Group 1 consisted of patients with unstable angina pectoris, group 2 of patients with non-ST-elevation myocardial infarction, group 3 of patients with ST-elevation myocardial infarction, and group 4 consisted of patients operated on due to non-coronary reasons. Pericardial fluid and arterial blood SCUBE1 values, demographic variables and postoperative results were noted and compared. RESULTS: Normal SCUBE1 level in pericardial fluid was 0.049 ± 0.061 ng/ml. Arterial SCUBE1 levels of smokers were higher. Pericardial SCUBE1 levels were higher in patients requiring postoperative intra-aortic balloon pump support and patients needing peri-operative temporary cardiac pacing. High pericardial SCUBE1 values did not correlate with postoperative stroke, prolonged intensive care unit stay and mortality. CONCLUSIONS: High levels of pericardial SCUBE1 may help us predict the need for postoperative intra-aortic balloon pump support and the need for temporary cardiac pacing, however they were not helpful in predicting prolonged intensive care unit stay and early postoperative mortality.

Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

BACKGROUND: Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. AIMS: To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. STUDY DESIGN: In vitro experimental study. METHODS: HepG2 cells were incubated with 0 (control), 10, 50 and 200 µM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. RESULTS: We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. CONCLUSION: Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

Effect of lipoic acid on paraoxonase-1 and paraoxonase-3 protein levels, mRNA expression and arylesterase activity in liver hepatoma cells.

Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 µM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

Increased Fibrinogen to Albumin Ratio in Ischemic Retinal Vein Occlusions.

PURPOSE: To demonstrate the relationship between ischemia and plasma fibrinogen and serum albumin levels in cases of retinal vein occlusion (RVO). METHODS: This study included 44 patients with central RVO (CRVO), 68 patients with branch RVO (BRVO), and 54 age- and sex-matched controls, for a total of 166 subjects. All of the subjects underwent full ophthalmologic examinations and complete physical examinations, including a detailed medical history and blood count, and biochemical parameters. RESULTS: The mean fibrinogen to albumin ratios were 92.5 ± 36.1 for the patients with CRVO, 84.5 ± 31.5 for the patients with BRVO, and 68.4 ± 12.2 for the control group. Overall, the patients with CRVO and patients with BRVO with ischemia had higher fibrinogen to albumin ratios and higher fibrinogen levels. Moreover, significant positive correlations were found between ischemia and the fibrinogen to albumin ratio (r = 0.732, p = 0.001) and the fibrinogen level (r = 0.669, p = 0.001). CONCLUSIONS: The fibrinogen to albumin ratio is significantly associated with ischemic RVO. Instead of complicated and invasive methods, such as a retinal angiogram, the fibrinogen to albumin ratio could be a useful initial diagnostic test to predict ischemia in RVO.