1. The role of angiotensin-converting enzyme (ACE) 2 is likely to balance the status of the renin-angiotensin system (RAS) by degrading angiotensin (Ang) II and generating Ang-(1-7). Earlier demonstrations that ACE2 is insensitive to ACE inhibitors prompted us to evaluate the effect of ACE inhibitors on ACE2 expression. 2. Liver fibrosis was induced in rats with 40% CCl(4) (2.5 mL/kg, s.c., twice per week). Half the rats were further treated with perindopril (2 mg/kg, p.o., daily). After 2 and 4 weeks treatment, ACE2 immunoreactivity was assessed by immunohistochemical staining, ACE2 protein expression was determined by western blot and mRNA expression of ACE2 and the Ang-(1-7) receptor Mas was determined by reverse transcription-polymerase chain reaction (RT-PCR). 3. As an in vitro study, hepatic stellate cells (HSC) were treated with AngII (0.1-10 micromol/L) alone or in combination with the synthesized peptide ACEI (Sigma-Aldrich). Western blot and RT-PCR were used to evaluate ACE2 expression and Mas mRNA levels. Furthermore, after treatment of HSC with the Mas antagonist A779 (1 micromol/L), the protein expression of connective tissue growth factor (CTGF) was detected to evaluate the interaction between AngII, ACEI and the ACE2-Mas axis. 4. Expression of both ACE2 mRNA and protein and Mas mRNA was markedly upregulated in both CCl(4)-injured rat liver and AngII-treated HSC. Further significant upregulation was observed following additional administration of ACEI. In addition, ACEI treatment of HSC inhibited AngII-induced overexpression of connective tissue growth factor and this effect was ameliorated by blockade of the Mas receptor with A779. 5. The findings of the present study suggest that ACE inhibitors are able to upregulate ACE2 under conditions of liver injury both in vivo and in vitro, which may indicate potential benefits of ACE inhibitors in the therapeutic treatment of liver fibrosis.

Translationally controlled tumor protein (TCTP) plays a major role in a broad array of biological processes. However, the TCTP-related biological process and interactive proteins still remain poorly characterized. In the present study, we found that knockdown of TCTP inhibited proliferation, migration, and invasion activities of LoVo cells in vitro and in vivo. The whole-cell proteomes were compared by 2D gel electrophoresis before and after knockdown of TCTP. Alterations in 27 proteins were detected and their identities were revealed by mass spectrometry analysis. Components of Ubiquitin-Proteasome System, proteins involved in the cytoskeleton biosynthesis and tumor metastasis were found to be changed upon TCTP removal. These results imply that TCTP might play at least a partial role in colon adenocarcinoma progression.

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Glioma has been identified as one of the most aggressive primary tumors. Long non-coding RNAs (lncRNAs), with length larger than 200 bp, have drawn increasing attention to their abnormal expression and regulation function in carcinogenesis. However, the role of lncRNAs in glioma remains largely unknown. Maternally expressed gene 3 (MEG3), also known as gene-trap locus 2 (GTL2), is an imprinted gene, and is encoded by the MEG3 transcript of the DLK1/MEG3 locus on human chromosome, or Meg3 on mouse chromosome. In this study, we found that lncRNA MEG3 was significantly downregulated in malignant glioma tissues and cell lines. The employment of the loss-of and gain-of functions assays presented that MEG3 suppressed glioma cells proliferation and induced cell-cycle arrest. Furthermore, our findings showed that highly expressed MEG3 could weaken Wnt/β-catenin signaling in glioma. Collectively, our findings revealed that downregulated lncRNA MEG3 could promote glioma cell proliferation through targeting Wnt/β-catenin signaling, which mainly influenced cell cycle.

Functional regression of the mammary gland is partly reflected by proteolysis of milk protein and tissue protein. The involvement of the plasminogen activation system in degradation of milk protein and mammary tissue damage has been demonstrated under inflammatory conditions. In this study, mammary secretion from 23 dairy goats primarily grouped as lactation (milking twice daily) or involution (milking once daily or less) was used to determine the ratio of gravity-precipitated casein to total milk protein (casein ratio) as an index of caseinolysis, and activities of components of plasminogen activation system as well as their expressions on somatic cells. Based on the casein ratio, lactation goats were subcategorized as very active (71.8 +/- 1.0%) or less active (29.9 +/- 1.0%) in mammary function; involution goats were subcategorized as gradual (21.7 +/- 1.0%) or acute (5.9 +/- 0.2%) involution. This result suggests that caseinolysis occurred during regular lactation as well as during involution. On the other hand, activities of components of the plasminogen activation system in mammary secretion were increased along with the decreasing casein ratio, in contrast to the similar activities of their counterparts in circulation throughout various mammary statuses. Correlation analysis between casein ratio and activities of plasminogen activation system of goat milk indicated a significant negative relationship for plasmin (r = -0.64), plasminogen (r = -0.69), and urokinase-type plasminogen activator (uPA; r = -0.78) during involution but not during lactation. As for the cellular components of plasminogen activation system, there was an increase in immunoreactivity on somatic cells toward both monoclonal antibodies of human uPA and human uPA receptor under involution conditions suggesting their upregulation relative to lactation condition. Collectively, these results suggest that plasminogen activation system within the mammary gland differentially contribute to milk caseinolysis along the various stages of goat lactation. Meanwhile, a somatic cell-mediated local elevation of plasmin activity may be committed to extensive caseinolysis during involution.

Loss of β‐cell number and function is a hallmark of diabetes. β‐cell preservation is emerging as a promising strategy to treat and reverse diabetes. Here, we first found that Pdia4 was primarily expressed in β‐cells. This expression was up‐regulated in β‐cells and blood of mice in response to excess nutrients. Ablation of Pdia4 alleviated diabetes as shown by reduced islet destruction, blood glucose and HbA1c, reactive oxygen species (ROS), and increased insulin secretion in diabetic mice. Strikingly, this ablation alone or in combination with food reduction could fully reverse diabetes. Conversely, overexpression of Pdia4 had the opposite pathophysiological outcomes in the mice. In addition, Pdia4 positively regulated β‐cell death, dysfunction, and ROS production. Mechanistic studies demonstrated that Pdia4 increased ROS content in β‐cells via its action on the pathway of Ndufs3 and p22phox. Finally, we found that 2‐β‐D‐glucopyranosyloxy1‐hydroxytrideca 5,7,9,11‐tetrayne (GHTT), a Pdia4 inhibitor, suppressed diabetic development in diabetic mice. These findings characterize Pdia4 as a crucial regulator of β‐cell pathogenesis and diabetes, suggesting Pdia4 is a novel therapeutic and diagnostic target of diabetes.

Circular RNAs (circRNAs) are involved in the regulation of gene expression in different physiological and pathological processes. These macromolecules can act as microRNA (miRNA) sponges and play an important role as gene regulators throughout the circRNA‐miRNA pathway. In this study, we established a radioresistance model with the nasopharyngeal carcinoma cell line CNE‐2, and then analyzed the differences in the circRNAs between radioresistant and normal nasopharyngeal carcinoma cell lines using a high‐throughput microarray. Tested circRNAs included 1042 upregulated and 1558 downregulated circRNAs. Relevant signaling pathways associated with the circRNAs and their target miRNAs were analyzed using bioinformatics analysis to determine the radioresistance of the differentially expressed circRNAs. Curcumin was used to treat irradiated cell lines, and changes in the circRNA before and after curcumin treatment were analyzed to investigate the radiosensitization effects of curcumin. The results showed that curcumin could regulate the circRNA‐miRNA‐messenger RNA network and inhibit the epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3), and growth factor receptor‐bound protein 2 (GRB2) to achieve radiosensitization. Thus, circRNA acted as a miRNA sponge and regulated the expression of miRNA, thereby affecting EGFR, STAT3, and GRB2 expression and radiosensitization.