Jianjun Yu

The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.

BACKGROUND: The aims of this study were to detect the level of histone crotonylation in prostate cancer (PCa) tissues, analyze the correlations between its level and clinical stage and grade, and explore the effects of bromodomain-containing protein 4 (BRD4) inhibitors and sodium crotonate on the histone crotonylation in PCa cell lines and on the functions of PCa cells. METHODS: PCa tissues from 72 patients and adjacent tissues from 7 patients were collected, and immunohistochemistry was used to measure the level of histone crotonylation. Three human PCa cell lines, PC-3, LNCaP, and C42B, were selected and treated with IC50 value of I-BET762, I-BET726, and CPI-203, respectively. Next, short hairpin RNA (shRNA) transient knockdown was used to inhibit BRD4 expression. Histone crotonylation level and the expression of acetylase were determined by Western blotting. Finally, cell proliferation, migration, and invasion were measured with Cell Counting Kit-8 assay, scratch test, and Transwell test respectively. RESULTS: The level of histone crotonylation in PCa tissue was higher than that in adjacent tissues, and histone lysine crotonylation (Kcr) increased with the increasing malignancy of PCa. Treatments with I-BET762, I-BET726, and CPI-203 could inhibit the proliferation, migration, and invasion of PCa cell lines including PC-3, LNCaP, and C42B, and could also regulate the histone crotonylation and androgen receptor signaling pathways via the regulation of BRD4 expression. CONCLUSIONS: PCa is closely related to histone crotonylation. Inhibition of BRD4 expression can inhibit the proliferation, migration, and invasion of PCa cells.

Long-term exposure to UVB (280–320 nm) can cause oxidative skin damage, inflammatory injury, and skin cancer. Research on nicotinamide mononucleotide (NMN) and lactic acid bacteria (LAB) with regard to antioxidation, anti-inflammation, and prevention of other age-related diseases has received increasing attention. In the present study, the in vitro antioxidant analysis showed that NMN combined with Lactobacillus fermentum TKSN041 ( L. fermentum TKSN041) has a high scavenging ability on hydroxyl (OH), 2, 2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and it also possess a good total antioxidant capacity. The animal experimental results show that NMN combined with LAB maintained normal liver morphology of mice and reduced pathological damage to murine skin. NMN combined with LAB significantly increased the serum levels of total superoxide dismutase (T-SOD), catalase (CAT), and interleukin (IL)-10, but reduced the levels of malondialdehyde, advanced glycation end products, tumor necrosis factor (TNF)-α, and IL-6. NMN combined with LAB increased T-SOD, CAT, IL-10, Na + -K + -ATPase, and NAD + levels in the skin, but reduced TNF-α level in the skin. NMN combined with LAB increased the mRNA expression levels of SOD1, CAT, glutathione (GSH), inhibitor of NF-κB (IκB-α), IL-10, AMP-activated protein kinase (AMPK), adaptor protein, phosphotyros ineinteraction, PH domain and leucine zipper containing 1 (APPL1), peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α), and forkhead transcription factor O (FOXO) in the skin and liver, but decreased the mRNA expression levels of nuclear factor (NF)-κBp65, TNF-α, IL-6, and rapamycin target protein (mTOR). NMN combined with LAB increased the protein expression levels of AMPK, IκB-α, SOD1, and CAT in the skin tissues and reduced protein expression of NF-κBp65. NMN combined with L. fermentum TKSN041 improved murine skin damage caused by UVB irradiation, and the protective mechanism may be related to activation of the AMPK signaling pathway. The results of this study are expected to provide a reference for preventing and the treating skin photoaging.

PURPOSE: Myocardial infarction is a major cause of mortality and heart failure worldwide. One of the most effective methods of this injury is direct delivery of cardioprotective drugs to ischemia-reperfusion (IR) myocardium. The aim of the present study was to fabricate an adenosine (Ade) prodrug-based, atrial natriuretic peptide (ANP)-modified nanosystem for the treatment of myocardial infarction. MATERIALS AND METHODS: Oleate adenosine prodrug (Ade-OA) and ANP-distearoylphosphatidylethanolamine-polyethylene glycol were synthesized. ANP-modified Ade-loaded lipid nanocarriers (ANP Ade/LNCs) were then self-assembled by using solvent evaporation method. In vitro drug release in the presence of plasma was evaluated. In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics were investigated in rats with ischemic myocardium after intravenous injection. RESULTS: In vivo inhibition effect on infarct size, tissue distribution, and pharmacokinetics studies in acute myocardial infarction (AMI) rats showed that ANP Ade/LNCs exhibited better efficiency than non-modified Ade/LNCs and free Ade in all respects. CONCLUSION: These results indicated that the ANP Ade/LNCs can be used as a promising system for the treatment of cardiovascular diseases.