Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity.

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.

The diagnostic significance of circulating miRNAs and metabolite profiling in early prediction of breast cancer in Egyptian women.

OBJECTIVE: Breast cancer (BC) is one of the most commonly diagnosed solid malignancies in women worldwide. PURPOSE: Finding new non-invasive circulating diagnostic biomarkers will facilitate the early prediction of BC and provide valuable insight into disease progression and response to therapy using a safe and more accessible approach available every inspection time. Therefore, our present study aimed to investigate expression patterns of potentially circulating biomarkers that can differentiate well between benign, malignant, and healthy subjects. METHODS: To achieve our target, quantitative analyses were performed for some circulating biomarkers which have a role in the proliferation and tumor growth, as well as, glutamic acid, and human epidermal growth receptor 2 (HER2) in blood samples of BC patients in comparison to healthy controls using qRT-PCR, liquid chromatography/mass spectrometry (LC/MS/MS), and ELISA. RESULTS: Our findings showed that the two miRNAs (miRNA-145, miRNA-382) were expressed at lower levels in BC sera than healthy control group, while miRNA-21 was expressed at higher levels in BC patients than control subjects. Area under ROC curves of BC samples revealed that AUC of miRNA-145, miRNA-382, miRNA-21, and glutamic acid was evaluated to equal 0.99, 1.00, 1.00 and 1.00, respectively. Besides, there was a significantly positive correlation between miRNA-145 and miRNA-382 (r = 0.737), and a highly significant positive correlation between miRNA-21 and glutamic acid (r = 0.385). CONCLUSION: Based on our results, we conclude that the detection of serum miRNA-145, -382 and -21 as a panel along with glutamic acid, and circulating HER2 concentrations could be useful as a non-invasive diagnostic profiling for early prediction of breast cancer in Egyptian patients. It can provide an insight into disease progression, discriminate between malignancy and healthy control, and overcome the use limitations (low sensitivity and specificity, repeated risky exposure, and high cost) of other detecting tools, including mammography, magnetic resonance imaging, and ultrasound.

Possible Role of microRNA-122 in Modulating Multidrug Resistance of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a hypervascular primary liver cancer characterized by rapid progression, besides, resistance to traditional chemotherapeutic agents. It has been shown that microRNAs play critical roles in regulation of tumor cell sensitivity to drugs through modulating the expression of genes involved in drug transport. The present study investigated whether restoration of miR-122 in HCC cells could alter the cell cycle distribution and the expression of multidrug resistance (MDR)-related genes (ABCB1, ABCC1, ABCG2 and ABCF2). After overexpression of miR-122 in HepG2 cells treated or untreated with doxorubicin doses, total RNAs and protein extracts were isolated for application of QRT-PCR and western blotting techniques. Moreover, cell cycle distribution was monitored by flow cytometry. Our results revealed that, the over expression of miR-122 in HepG2 cells treated or untreated with doxorubicin could modulate the sensitivity of cells to chemotherapeutic drug through downregulation of MDR-related genes, ABCB1 and ABCF2. Interpretation of cell cycle distribution revealed that, the anti-proliferative effect of miR-122 is associated with the accumulation of cells in G0/G1 phase. Moreover, treatment with miR-122 and doxorubicin resulted in high percentage of HCC cells in G0/G1 phase. Taken together, our findings revealed that, overexpression of miR-122 inhibited HCC cell growth by inducing cell cycle arrest and this arrest is associated with down-regulation of MDR-related genes.

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

BACKGROUND: The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. METHODS: Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. RESULTS: A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). CONCLUSION: This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.