Application of GC-MS coupled with chemometrics for scanning serum metabolic biomarkers from renal fibrosis rat.

Renal interstitial fibrosis closely relates to chronic kidney disease and is regarded as the final common pathway in most cases of end-stage renal disease. Metabolomic biomarkers can facilitate early diagnosis and allow better understanding of the pathogenesis underlying renal fibrosis. Gas chromatography-mass spectrometry (GC/MS) is one of the most promising techniques for identification of metabolites. However, the existence of the background, baseline offset, and overlapping peaks makes accurate identification of the metabolites unachievable. In this study, GC/MS coupled with chemometric methods was successfully developed to accurately identify and seek metabolic biomarkers for rats with renal fibrosis. By using these methods, seventy-six metabolites from rat serum were accurately identified and five metabolites (i.e., urea, ornithine, citric acid, galactose, and cholesterol) may be useful as potential biomarkers for renal fibrosis.

[Retracted] MicroRNA­379 acts as a tumor suppressor in non­small cell lung cancer by targeting the IGF­1R­mediated AKT and ERK pathways.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell migration and invasion assay data shown in Figs. 2F, 5D and 6D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 38: 1857­1866, 2017; DOI: 10.3892/or.2017.5835].

Fluorofenidone attenuates diabetic nephropathy and kidney fibrosis in db/db mice.

BACKGROUND/AIMS: Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of the present study was to investigate the effects of AKF-PD on diabetic nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of action. METHODS: We administered AKF-PD to diabetic db/db mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations. RESULTS: AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the db/db mice. The upregulated expression of α1(I)- and α1(IV)-collagen and fibronectin mRNAs, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins was inhibited by AKF-PD treatment in the renal cortex of db/db mice. The maximal effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the upregulated expression of α1(I)- and α1(IV)-collagens, TGF-ß1, TIMP-1 and α-SMA induced by high glucose concentrations in cultured mesangial cells. CONCLUSIONS: Our data indicate that AKF-PD diminishes the abnormal accumulation of mesangial matrix through the inhibition of upregulated expression of TGF-ß target genes in kidneys of db/db mice, resulting in attenuation of renal fibrosis and amelioration of renal dysfunction despite persistent hyperglycemia. Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the treatment of diabetic nephropathy.

[Impact of rosuvastatin on atherosclerosis lesions in apolipoprotein E knockout mice].

OBJECTIVE: To investigate the effect of rosuvastatin on atherosclerosis in apoE-knockout (apoE-/-) mice. METHODS: Eighteen 6-week-old apoE-/- mice fed with high fat diet were used as atherosclerosis models, twelve 6-week-old C57BL/6 mice fed with normal diet were used as control. After twelve weeks, six apoE-/- mice were used to observe the formation of atherosclerosis. Another 12 apoE-/- mice were divided into placebo treated group (n = 6) and rosuvastatin group (n = 6, 10 mg×kg(-1)×d(-1) per gavage) and treated for 12 weeks. Then, blood was collected for measuring lipid, aorta was prepared for morphologic study (HE, Oil red O, Masson) and immunohistochemical analysis (α-smooth active protein, transforming growth factor ß(1), macrophage surface molecule-3). RESULTS: Serum cholesterol and low density lipoprotein levels were significantly higher in apoE-/- mice fed with high fat diet than in C57/BL6 mice(all P < 0.01)while triglyceride level was similar between the two groups, these were not affected by rosuvastatin. Similarly, atherosclerotic lesion area in apoE-/- mice fed with high fat diet was also not significantly reduced by rosuvastatin, while lipid deposition could be significantly reduced and collagen deposition could be significantly increased in the aortic atherosclerotic lesions by treatment with rosuvastatin. Upregulated TGF-ß(1) and Mac-3 expression in the aortic atherosclerotic lesions in apoE-/- mice fed with high fat diet could also be significantly reduced by rosuvastatin (all P < 0.01), suggesting reduce inflammatory responses in the atherosclerotic lesion and stable atherosclerotic plaque post rosuvastatin treatment. CONCLUSION: Reducing inflammatory responses and stabilizing plaque properties might contribute to the anti-atherosclerosis effects of rosuvastatin in mice high fat diet fed apoE-/- mice.

MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF­1R-mediated AKT and ERK pathways.

Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR­379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR­379 was downregulated in both NSCLC tissue and cell lines. Low miR­379 expression in NSCLC tissues was significantly correlated with TNM stage and lymph node metastasis. In addition, functional experiments revealed that restoring the expression of miR­379 inhibited cell proliferation, migration and invasion of NSCLC. The insulin-like growth factor receptor-1 (IGF­1R) was identified as a direct target of miR­379 in NSCLC. IGF­1R was highly expressed in NSCLC tissues and inversely correlated with miR­379 expression. Downregulation of IGF­1R had tumor suppressive roles similar to that of miR­379 overexpression on NSCLC cell proliferation, migration and invasion. Moreover, the upregulation of IGF­1R effectively rescued the tumor suppressive roles induced by miR­379 overexpression in NSCLC. The resumption of the expression of miR­379 inhibited the activation of AKT and ERK signaling pathways in NSCLC. These findings suggested that miR­379 acts as a tumor suppressor in NSCLC by directly targeting IGF­1R and indirectly regulating AKT and ERK signaling pathways. miR­379 provides novel therapeutic targets for the treatment of patients with this disease.