Can renalase be a novel candidate biomarker for distinguishing renal tumors?

Renalase (RNLS) is synthesized mainly in renal tissues. The function of RNLS in cancerous renal tissues has not been investigated. We investigated the synthesis of RNLS in chromophobe renal cell carcinoma, papillary renal cell carcinoma and clear cell renal cell carcinoma with Fuhrman grades (FG): FG1, nucleoli are absent or inconspicuous and basophilic; FG2, nucleoli are conspicuous and eosinophilic and visible but not prominent; FG3, nucleoli are conspicuous and eosinophilic; FG4, extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation. We used 90 tissue samples including 15 healthy controls, 15 chromophobe renal cell carcinoma tissues and 10 papillary renal cell carcinoma renal tissues: 12 FG1, 14 FG 2, 14 FG 3 and 10 FG4. RNLS in the tissue samples was measured using enzyme linked immunosorbent assay and immunostaining of RNLS in these tissues. RNLS was significantly greater in the chromophobe renal cell carcinoma and papillary renal cell carcinoma tissues than the control. The least amount of RNLS was found in the renal tissues of clear cell renal cell carcinoma FG1; the amount of RNLS increased as the FG grades increased. Because RNLS increased significantly in renal tissues due to cancer, except for clear cell renal cell carcinoma FG1, RNLS may be useful biomarker for distinguishing grades of renal cancer. Because RNLS increases cell survival, anti-RNLS preparations may be useful for treating cancer in the future.

Effects of iloprost and sildenafil treatment on elabela, apelin-13, nitric oxide, and total antioxidant and total oxidant status in experimental enzyme-positive acute coronary syndrome in rats.

Despite significant advances in medicine, mortality due to cardiovascular disease is not yet preventable. We investigated the amounts of elabela (ELA) and apelin, synthesized by cardiomyocytes, and changes of these compounds in cardiac tissue and circulation after administration of iloprost (ILO) and sildenafil (SIL) in rats with induced myocardial ischemia (MI). We also investigated a connection with circulating troponin-I, creatine kinase (CK), creatine kinase-myocardial band (CK-MB) and nitric oxide (NO), and total anti-oxidant (TAS)/total oxidant status (TOS). We established eight study groups of five rats each. Group 1, sham, was given only physiologic serum; group 2, ILO; group 3, SIL; group 4, ILO + SIL; group 5, MI; group 6, MI + ILO; group 7, MI + SIL; group 8, MI + ILO + SIL. Troponin-I, CK, CK-MB and TAS-TOS were investigated using an autoanalyzer. NO, ELA and apelin were analyzed by ELISA. Tissue apelin and ELA expressions and localizations were determined by immunohistochemistry. The MI group compared to the control (sham) group showed that ELA, apelin, troponin-I, CK, CK-MB, NO and TOS levels were elevated significantly. Concentrations of these factors increased in MI, but decreased after ILO and SIL administration. The largest decrease of TOS was identified in the ILO + SIL group. ELA and apelin may be novel indicators of MI and administration of ILO and SIL, individually or together, may be useful for treating MI.

A promising biomarker to distinguish benign and malignant renal tumors: ELABELA.

AIM: The aim of this study was to investigate ELABELA (ELA) expression in benign and malignant renal tissues and expression differences in different nuclear grades of clear cell carcinomas. MATERIALS AND METHODS: Patients that underwent surgery due to renal masses between the years of 2007 and 2017 were used. Control renal tissues (n = 23), papillary RCC (n = 23), clear cell RCC (CcRCC) [Fuhrman Grade1 (n = 23), Fuhrman Grade2 (n = 23), Fuhrman Grade3 (n = 23), Fuhrman Grade4 (n = 23)], and chromophobe RCC (n = 23) were included to the study. The Independent samples t-test was used for 2-point intergroup assessments and the one-way analysis of variance and posthoctukey test was used for the others. Values of P < 0.05 were considered statistically significant. RESULTS: ELA immunoreactivity was observed in proximal and distal tubules in the kidney, but not in glomeruli in control tissues. When compared with control kidney tissue, a statistically significant increase was observed in ELA immunoreactivity in renal oncocytoma. In the chromophobe RCC, ELA immunoreactivity was significantly lower than control kidney tissue, whereas papillary RCC did not show ELA immunoreactivity. However, compared with control kidney tissue, ELA immunoreactivity was not observed in Fuhrman Grade 1 and Grade 2 CcRCC. Also, there was a significant decrease at Fuhrman Grade 3 and Grade 4 CcRCC compared with control kidney tissues. In the statistical analysis of ELA immunoreactivity among the Fuhrman nuclear grades of CcRCCs, The ELA immunoreactivity was higher at Grade 4 CcRCC than Grade 1, Grade 2, and Grade 3. CONCLUSION: ELA is a usefull molecule to differentiate benign and malign renal tumors. But further broad and comprehensive studies are needed to investigate cellular and molecular mechanisms of ELAs on malign transformation.

Does hepcidin play a role in the pathogenesis of aphthae in Behçet's disease and recurrent aphthous stomatitis?

BACKGROUND: Aphthae constitute one of the major signs in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS). No scientific study has yet explored the relationship of hepcidins, which have antimicrobial effects, with RAS and BD. OBJECTIVES: In this study, we aimed to evaluate by immunohistochemistry whether hepcidin is synthesized by the salivary glands and to measure levels of prohepcidin and hepcidin (an antibacterial peptide) in the serum and saliva of patients with BD and RAS. METHODS: The study included 25 BD patients and 30 RAS patients, as well as a control group comprising 25 healthy individuals. Serum and saliva samples were collected at the same time from all subjects. Levels of prohepcidin and hepcidin were measured by ELISA. The presence of hepcidin in salivary glands was assessed by immunohistochemistry. RESULTS: Hepcidin was localized in the striated ducts of the sublingual and parotid glands. Saliva prohepcidin and hepcidin levels were correlated with blood levels. Saliva prohepcidin levels were found to be lower in RAS patients than in BD patients and healthy controls (P < 0.001 and P = 0.007 respectively). In addition, RAS patients had lower saliva hepcidin levels than did the control group (P = 0.03). CONCLUSIONS: The lower serum and saliva prohepcidin and hepcidin concentrations found in RAS and BD patients indicate that hepcidin may be involved in the aetiopathogenesis of these diseases. Because it can be obtained non-invasively and easily, saliva may provide a useful alternative to serum in quantifying prohepcidin and hepcidin concentrations.

Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma.

BACKGROUND: T lymphocytes induce the transformation of fibroblasts into myofibroblasts, the main mediators of fibrogenesis. The inosine 5'-monophosphate dehydrogenase inhibitor mycophenolate mofetil (MMF) and the anti-CD25 monoclonal antibody daclizumab (DCZ) have been reported to suppress the proliferation of T lymphocytes. AIM: To evaluate the preventive effects of MMF and DCZ in early stages of bleomycin (BLM)-induced scleroderma. METHODS: This study involved five groups of Balb/c mice (n = 10 per group). Mice in four of the groups were injected subcutaneously (SC) with BLM [100 µg/day in 100 µL phosphate-buffered saline (PBS)] for 4 weeks; the remaining (control) group received only 100 µL PBS. Three of the BLM-treated groups also received either intraperitoneal MMF 50 or 150 mg/kg/day, or SC DCZ 100 µg/week. At the end of the fourth week, all mice were killed, and blood and tissue samples were obtained for further analysis. RESULTS: In the BLM-treated group, increases were seen in inflammatory-cell infiltration, α-smooth muscle actin-positive (α-SMA+) fibroblastic cell count, tissue hydroxyproline content, and dermal thickness. Dermal fibrosis was histopathologically prominent. In BLM-treated mice also given MMF or DCZ, inflammatory-cell infiltration, tissue hydroxyproline content and dermal thickness were decreased. In the MMF groups, decreases were also noted in α-SMA+ fibroblastic cell count. CONCLUSION: In this BLM-induced dermal fibrosis model, MMF and DCZ treatments prevented the development of dermal fibrosis. Further studies are needed to evaluate whether targeting T lymphocytes is effective in resolving pre-existing fibrosis in human scleroderma.

Heterotopic gastric mucosa (inlet patch): endoscopic prevalence, histopathological, demographical and clinical characteristics.

OBJECTIVE: Heterotopic gastric mucosa (HGM) is found in the cervical oesophagus, just below the upper oesophageal sphincter, and has generally been overlooked by endoscopists. The objective of the present study is to determine endoscopic prevalence and histopathological and clinical characteristics of HGM and to classify patients according to their clinicopathological features. METHOD: A total of 911 consecutive patients (436 M and 475 F) who were admitted to our Endoscopy Unit were examined. HGM type and the presence of Helicobacter pylori (Hp) either in the stomach or in the HGM were histopathologically evaluated. RESULTS: Of the 911 patients, 33 (25 M and 8 F) were found to have HGM. HGM prevalence was determined to be 3.6%. On the basis of HGM patients' symptoms, only dysphagia was significantly correlated with the size of HGM (p < 0.05). Hp was positive in 29.2% of HGM. Clinicopathological classification of the patients showed that 20 patients were HGM type 1 and 13 were HGM type 2. None of the patients had HGM type 3, 4 or 5. CONCLUSION: Prevalence of HGM was 3.6%. Dysphagia was found related with the size of HGM. This may be associated with larger HGMs' causing more acid secretion.