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 Abstract

Amikacin (AMIK) is an aminoglycoside antibiotic that possesses considerable nephrotoxic adverse effects. This study examined the protective effects of vitamin E (VIT. E) or rosuvastatin (ROSU) against AMIK-induced nephrotoxicity. For this purpose, eight groups of rats were used. Two control groups received saline and vehicle, AMIK group (1.2 g/kg, i.p.), VIT. E group (1000 mg/kg; p.o.), ROSU group (10 mg/kg; p.o.), AMIK + VIT. E group, AMIK + ROSU group, and combination group. The results showed that AMIK significantly increased serum levels of urea and creatinine. Meanwhile, serum levels of total protein and albumin were decreased. The kidney content of malondialdehyde was increased, whereas glutathione content and catalase activity were decreased. Tumor necrosis factor-α and nuclear transcriptional factor levels were increased. Conversely, administration of VIT. E and/or ROSU with AMIK ameliorated such damage and reduced DNA fragmentation, apoptosis, and necrosis. In conclusion, co-administration of VIT. E, ROSU, or their combination alleviated AMIK-induced nephrotoxicity.

 

IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental Autoimmune Encephalomyelitis

Posted by D Ksiazek-Winiarek, P Szpakowski, M Turniak, et al. on 2017-10-27 00:41:18

Abstract

Multiple sclerosis is an autoimmune, neurodegenerative disease, affecting mostly young adults and resulting in progressive disability. It is a multifactorial disorder, with important involvement of both cellular and epigenetic components. Among the epigenetic factors, microRNAs are currently intensively investigated in the context of multiple sclerosis. It has been shown that their biogenesis and function may be regulated by various cytokines. IL-17, a hallmark cytokine of Th17 cells, has been thought to function predominantly as a pro-inflammatory factor, leading to increased disease symptoms. However, there are several studies indicating its protective role during inflammatory process. In this work, we have assessed the impact of high-dose IL-17 administration on microRNAs’ expression profile during the preclinical stage of EAE. For selected microRNA, we have performed computational analysis of its potential target mRNAs and cellular pathways. Based on results obtained from in silico analysis, we have chosen genes from neurotrophin signaling pathway for further experiments—BDNF, HRAS, and BCL2. Results obtained in this study suggested that high dose of IL-17 exerts protective activity via miR-155-5p downregulation. Increased expression of all studied genes, especially BCL2, indicated a potential anti-apoptotic function of IL-17 during the preclinical phase of EAE.

Effect of cardamonin on hepatic ischemia reperfusion induced in rats: Role of nitric oxide

Posted by Y Atef, H M.Ei-Fayoumi, M F.Mahmoud, et al. on 2017-10-19 18:51:41

Abstract

Ischemia reperfusion (I/R) injury is a cellular damage in a hypoxic organ following the restoration of oxygen delivery. It may occur during organ transplantation, trauma and hepatectomies. Nitric oxide (NO) effects during hepatic I/R are complicated. The iNOS-derived NO has a deleterious effect, whereas eNOS-derived NO has a protective effect in liver I/R. Cardamonin (CDN) is an anti-inflammatory molecule and a novel iNOS inhibitor, and Nω-Nitro-L-arginine (L-NNA) is a NOS inhibitor. L-Arginine is a precursor of NOS. This study was designed to investigate the possible protective effects of CDN on hepatic I/R and the role of NO. Wistar rats were randomly divided into 5 groups (Sham, I/R, CDN, L-NNA and L-arginine). Liver ischemia was induced for 45 min then reperfusion was allowed for 1 h. L-Arginine and CDN ameliorated the deleterious effects of I/R through reducing the oxidative stress and hepatocyte degeneration. Both molecules decreased the elevated inflammatory cytokines and increased the antiapoptotic marker, Bcl2. Both agents increased NO and eNOS expression and decreased iNOS expression. In conclusion, increased NO/eNOS and suppression of iNOS expression have protective effects on I/R injury. While inhibition of eNOS and reduction of NO have deleterious effects on I/R injury. For the first time, we demonstrated that cardamonin improved functional and structural abnormalities of the liver following I/R by improving oxidative stress and inflammation and increasing the availability of NO produced by eNOS. Treatment with cardamonin could be a promising strategy in patients with hepatic I/R injury in different clinical situations.

Resveratrol ameliorated the behavioral deficits in a mouse model of post-traumatic stress disorder

Posted by ZS Zhang, ZK Qiu, JL He, et al. on 2017-10-18 20:26:17

Abstract

Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40 mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15 mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40 mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40 mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction.

ITIH4: Effective Serum Marker, Early Warning and Diagnosis, Hepatocellular Carcinoma

Posted by XH Li, B Li, TS Guo, et al. on 2017-09-19 19:49:58

Abstract

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor evolved from cirrhosis. It is quite significant to seek accurate, easy markers for early warning and diagnosis of HCC. Through prospective cohort follow-up study and mass spectrometry, we discovered and verified a serum marker valuable for early warning and diagnosis. Follow-up observation was performed on cirrhosis patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was adopted to detect the serums of patients, and the serum polypeptides with a potential value in early HCC warning and diagnosis were screened. Electrospray ionization quadrupole time-of-flight tandem mass spectrometry (ESI-Q-TOF-MS/MS) was exploited to identify these screened polypeptides. Moreover, the serum marker concentration was determined by ELISA to validate the clinical value of the serum marker. Among 109 cirrhosis patients followed up for two years, 29 patients (26.6%) finally progressed into HCC. MALDI-TOF MS shows that the concentration of a 3155.66Da polypeptide was significantly different between the patients that progressed into HCC and those not. Through MS/MS identification, it is confirmed that the polypeptide is inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4). The serum ITIH4 concentrations in two groups were measured with ELISA and compared with Alpha-fetoprotein (AFP). Results show that serum ITIH4 and AFP concentrations were negatively correlated (r=−0.263, p=0.0006), and the ITIH4 concentration had a significant intergroup difference (p=0.000). Receiver operating characteristic (ROC) curve indicates that its predictive value (area under the curve, AUC) is 0.667, superior to AFP. For the patients progressing into HCC, serum samples were separately collected when they were recruited and diagnosed as cirrhosis. Measurement on these samples reveals that ITIH4 was declining during the progression of HCC (p=0.006). By virtue of mass spectrometry, we discovered and identified a biomarker valuable for early HCC warning and diagnosis. This marker overperforms the commonly used AFP, demonstrating a bright prospect.

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