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Mitochondrial dysfunction in proximal tubular epithelial cells is a key event in acute kidney injury (AKI), which is a risk factor for the development of chronic kidney disease (CKD). Apelin is a bioactive peptide that protects against AKI by alleviating inflammation, inhibiting apoptosis, and preventing lipid oxidation, but its role in protecting against mitochondrial damage remains unknown. Herein, we examined the protective effects of apelin on mitochondria in cisplatin-stimulated human renal proximal tubular epithelial cells and evaluated its therapeutic efficacy in cisplatin-induced AKI mice. In vitro, apelin inhibited the cisplatin-induced mitochondrial fission factor (MFF) upregulation and the fusion-promoting protein optic atrophy 1 (OPA1) downregulation. Apelin co-treatment reversed the decreased levels of the deacetylase, Sirt3, and the increased levels of protein acetylation in mitochondria of cisplatin-stimulated cells. Overall, apelin improved the mitochondrial morphology and membrane potential in vitro. In the AKI model, apelin administration significantly attenuated mitochondrial damage, as evidenced by longer mitochondrial profiles and increased ATP levels in the renal cortex. Suppression of MFF expression, and maintenance of Sirt3 and OPA1 expression in apelin-treated AKI mice was also observed. Finally, exogenous administration of apelin normalized the serum level of creatinine and urea nitrogen and the urine levels of NGAL and Kim-1. We also confirmed a regulatory pathway that drives mitochondrial homeostasis including PGC-1α, ERRα and Sirt3. In conclusion, we demonstrated that apelin ameliorates renal functions by protecting tubular mitochondria through Sirt3 upregulation, which is a novel protective mechanism of apelin in AKI. These results suggest that apelin has potential renoprotective effects and may be an effective agent for AKI treatment to significantly retard CKD progression.

Information on systematic analysis of olfactory memory-related proteins is poor. In this study, the odor discrimination task to investigate olfactory recognition memory of adult male C57BL/6J mice was used. Subsequently, olfactory bulbs (OBs) were taken, proteins extracted, and run on two-dimensional gel electrophoresis with in-gel-protein digestion, followed by mass spectrometry and quantification of differentially expressed proteins. Dual specificity mitogen-activated protein kinase kinase 1 (MEK1), dihydropyrimidinase-related protein 1 (DRP1), and fascin are related with Lemon odor memory. Microtubule-associated protein RP/EB family member 3 is related to Rose odor memory. Hypoxanthine-guanine phosphoribosyltransferase is related with both Lemon and Rose odors memory. MEK1 and DRP1 levels were increased, while microtubule-associated protein RP/EB family member 3, fascin and hypoxanthine-guanine phosphoribosyltransferase levels were decreased during olfactory memory. In summary, neurogenesis, signal transduction, cytoskeleton, and nucleotide metabolism are involved in olfactory memory formation and storage of C57BL/6J mice.

Sensitive and specific biomarkers for identifying early stage of non-small cell lung cancer (NSCLC) are urgently needed to improve the therapeutic outcome and reduce the mortality. Small non-coding microRNAs (miRNAs) are key components of cancer development and are considered as potential biomarkers for cancer diagnosis and for monitoring treatment. The aim of this study was to determine whether aberrant miRNA expression can be used as a marker in peripheral blood mononuclear cells (PBMC) for the diagnosis of NSCLC.The levels of two mature miRNAs (miR-143 and miR-150) were detected by probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in PBMC of 64 patients with NSCLC and 26 healthy individuals, and the relationship between miR-143 and miR-150 levels and clinical and pathological factors was explored.All endogenous miRNAs were present in peripheral blood in a remarkably stable form and detected by RT-qPCR. MiR-143 expression in the PBMC specimens was significantly lower in NSCLC patients than in healthy individuals (P0.0001). MiR-150 expression in the PBMC specimens was not significantly different between NSCLC patients and healthy individuals (P = 0.260). MiR-150 expression was significantly higher in lung adenocarcinoma patients than in healthy individuals (P = 0.001). There was a very strong difference in the expression level of miR-150 between lung adenocarcinoma patients and lung squamous cell carcinoma patients (P0.0001). In receiver operating characteristic curve (ROC) analysis, low expression of miR-143 showed the area under the ROC (AUC) of 0.885 for distinguishing cancer patients from healthy subjects. High expression of miR-150 had an AUC of 0.834 for distinguishing lung adenocarcinoma patients from healthy subjects. High expression of miR-150 had an AUC of 0.951 for distinguishing lung adenocarcinoma from lung squamous cell carcinoma. The miR-150 level was significantly associated with distant metastasis (P = 0.014).It is indicated that there is a potential for using miR-143 as a novel diagnostic biomarker for NSCLC. Moreover, miR-150 can be a highly accurate marker for differentiating adenocarcinoma from squamous cell carcinoma.

Studying fear extinction is a major topic in neuroscience. No information on systematic studies on the linkage of contextual fear conditioning (cFC) with hippocampal protein levels is available and we were therefore interested in protein differences between animals with poor and good extinction. cFC was carried out in C57BL/6J mice, hippocampi were taken and proteins were run on two-dimensional gel electrophoresis with subsequent quantification of protein spots. In-gel digestion with trypsin and identification by ion trap MS/MS (high-capacity ion trap) was used for the identification of significantly different hippocampal proteins between mice with good and poor performance of extinction. Signaling protein ras-related protein rab-7A and septin 8 levels were significantly higher in hippocampus of poor extinguishers, whereas ubiquitin carboxyterminal hydrolase isozyme L1 showed higher levels in animals with good extinction performance. A series of additional proteins showed significantly different levels between groups but the abovementioned were confirmed by immunoblotting. The abovementioned proteins have never been reported to be linked to extinction, memory, or learning and herein evidence for the involvement of several proteins in extinction mechanism as well as probably representing pharmaceutical targets is provided. Moreover, it is intriguing to demonstrate the differences between good and poor extinction performance at the protein level.

The Multiple T-maze (MTM) and the Barnes maze (BM) are land mazes used for the evaluation of spatial memory. The observation that mice are performing differently in individual mazes made us test the hypothesis that differences in cognitive performances in the two land mazes would be accompanied by differences in hippocampal protein levels. C57BL/6J mice were tested in the BM and in the MTM, hippocampi were extirpated 6 h following the probe trials each, and proteins were extracted for gel-based proteomic analysis. Mice learned the task in both paradigms. Levels of hippocampal proteins from several pathways including signaling, chaperone, and metabolic cascades were significantly different between the two spatial memory tasks. Protein levels were linked to spatial memory specifically as yoked controls were used.