Abstract.Oleuropein is a polyphenol, that is found in extra-virgin olive oil. Previous studies have shown that oleuropein inhibits cell proliferation and induces apoptosis in breast cancer, colorectal cancer and thyroid cancer. The aim of the present study was to investigate the effects of oleuropein in hepatocellular carcinoma (HCC) cells. The results of Cell Counting Kit 8 and flow cytometric analysis indicated that oleuropein effectively inhibited cell viability and induced apoptosis in HepG2 human hepatoma cells in a dose-dependent manner, through activation of the caspase pathway. Proapoptotic Bcl-2 family members, BAX and Bcl-2, were involved in oleuropein-induced apoptosis. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was also shown to be involved in this process. Oleuropein was demonstrated to suppress the expression of activated AKT. In addition, AKT overexpression promoted cell survival following treatment with oleuropein, while inhibition of AKT promoted cell death. Furthermore, the data demonstrated that oleuropein induces the production of reactive oxygen species (ROS) and that the function of oleuropein is, at least partially, ROS-dependent. These results suggest that oleuropein may be a promising novel chemotherapeutic agent in hepatocellular carcinoma. IntroductionHepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality (1). The predominant risk factors for HCC development are infection with hepatitis B or C virus, obesity and excess alcohol intake. The incidence and mortality of HCC is increasing as a result of the current obesity epidemic and rise in alcohol consumption (2). However, only 10-20% of patients with HCC are eligible for surgical resection, due to poorly preserved liver function, portal vein invasion or extrahepatic spread. Furthermore, the risk of recurrence following HCC resection is high (3,4). The available chemotherapeutic and radiotherapeutic treatment options for patients with advanced HCC are also extremely limited. Therefore, it is necessary to develop effective and practical chemotherapeutic agents with minimal cytotoxicity for use in this disease.A number of previous studies have shown that regular consumption of coffee, vitamin E and fish oil may be associated with a reduced risk of developing HCC (5-7). Ecological studies have investigated the association between dietary fat and certain types of cancer (8,9). Hursting et al (8) demonstrated that the intake of saturated or polyunsaturated fats was associated with incidence of breast and prostate cancer. A causal relationship was identified between cholesterol intake and colon cancer (9). Olive oil is the oil obtained from the fruit of the olive tree (Olea europaea Sativa) and its consumption is associated with lower overall mortality patterns, which are observed in Mediterranean populations (10). The primary component of olive leaf extract is oleuropein. Andreadou et al reported that oleuropein is involved in cardiomyocyte metabolism through the activati...

IntroductionMicrofibril-associated protein 2 (MFAP2) is an extracellular matrix protein that interacts with fibrillin to modulate the function of microfibrils. MFAP2 has been reported to play a significant role in obesity, diabetes, and osteopenia, and has been shown to be upregulated in head and neck squamous cell carcinoma. However, the molecular function and prognostic value of MFAP2 have never been reported in gastric cancer (GC) or any other tumors.MethodsThe current study investigated the expression patterns, prognostic significance, functional role, and possible mechanisms of MFAP2 in GC.ResultsWe demonstrated that MFAP2 was overexpressed in GC tissues, and its overexpression was significantly correlated with poor overall and disease-free survival in patients with GC. Moreover, we found that MFAP2 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) phenotype in GC cells. MFAP2 might modulate EMT of GC cells by activating the TGF-β/SMAD2/3 signaling pathway.ConclusionThese findings provide novel evidence that MFAP2 plays a crucial role in the progression of GC. Therefore, MFAP2 may be a promising prognostic marker and a potent anticancer agent.

Multiplex assays, involving the simultaneous use of multiple circulating tumor DNA (ctDNA) markers, can improve the performance of liquid biopsies so that they are highly predictive of cancer recurrence. We have developed a single-tube methylation-specific quantitative PCR assay (mqMSP) that uses 10 different methylation markers and is capable of quantitative analysis of plasma samples with as little as 0.05% tumor DNA. In a cohort of 179 plasma samples from colorectal cancer (CRC) patients, adenoma patients, and healthy controls, the sensitivity and specificity of the mqMSP assay were 84.9% and 83.3%, respectively. In a head-to-head comparative study, the mqMSP assay also performed better for detecting early-stage (stage I and II) and premalignant polyps than a published SEPT9 assay. In an independent longitudinal cohort of 182 plasma samples (preoperative, postoperative, and follow-up) from 82 CRC patients, the mqMSP assay detected ctDNA in 73 (89.0%) of the preoperative plasma samples. Postoperative detection of ctDNA (within 2 wk of surgery) identified 11 of the 20 recurrence patients and was associated with poorer recurrence-free survival (hazard ratio, 4.20; P = 0.0005). With subsequent longitudinal monitoring, 14 patients (70%) had detectable ctDNA before recurrence, with a median lead time of 8.0 mo earlier than seen with radiologic imaging. The mqMSP assay is cost-effective and easily implementable for routine clinical monitoring of CRC recurrence, which can lead to better patient management after surgery.

With regards to colon cancer, resistance to 5-fluorouracil (5-FU)-based chemotherapy and cancer stem cells (CSCs) are considered important factors underlying therapy failure. Metastasis-associated colon cancer 1 (MACC1) has been associated with poor prognosis and the promotion of metastasis within several types of cancer. However, the biological behavior of MACC1 in chemoresistance and CSC-like properties remains unclear. In the present study, various methods including gene knockdown, gene overexpression, western blotting, quantitative polymerase chain reaction and MTT assay, have been adopted. According to the results of the present study, MACC1 was depleted in two colon cancer cell lines resistant to 5-FU; subsequently, CSC-like properties and 5-FU sensitivity were investigated. Within 5-FU-resistant cells, cell death was facilitated by MACC1 knockdown. Furthermore, sphere formation and the expression levels of pluripotent markers, including cluster of differentiation (CD) 44, CD133 and Nanog were reduced due to MACC1 depletion. Additionally, it was indicated that the phosphoinositide 3-kinase/protein kinase B signaling pathway may be associated with 5-FU resistance and CSC-like properties via MACC1.

DAP is a novel lipopeptide antibiotic that it exhibits excellent in vitro activity against most clinically relevant Gram-positive bacteria, and the investigations on its pharmaceutical action mode of DAP have dramatically increased in the past decade due to its unique antimicrobial mechanism. However, the target molecules of DAP acting on the infectious bacteria, are far from clear. The state-of-the-art quantitative proteomic technologies provide new avenues to uncover underlying mechanism of antibiotics. Our research main aims to identify bacterial proteome profiling of host strain S. aureus response to DAP treatment through an iTRAQ-based quantitative proteomic analysis, which contributes to understand DAP efficient antibacterial activity and the microbial-antibiotic interactions.

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Procyanidins, a subclass of flavonoids found in commonly consumed foods, possess potential anti-inflammatory activity. Manipulation of M1/M2 macrophage homeostasis is an effective strategy for the treatment of metabolic inflammatory diseases. The objective of this study was to determine the effect of procyanidins on macrophage polarization. Procyanidin B2 (PCB2), the most widely distributed natural procyanidins, enhanced the expressions of M2 macrophage markers (Arg1, Ym1, and Fizz1). PCB2 activated peroxisome proliferator-activated receptor γ (PPARγ) activity and increased the expressions of PPARγ target genes (CD36 and ABCG1) in macrophages. Inhibition of PPARγ using siRNA or antagonist GW9662 attenuated the PCB2-induced expressions of M2 macrophage markers. In addition, we identified cognate PPAR-responsive elements (PPREs) within the 5'-flanking regions of the mouse Arg1, Ym1, and Fizz1 genes. Furthermore, macrophages isolated from db/db diabetic mice showed lower expressions of M2 markers. PCB2 effectively restored the Arg1, Ym1, and Fizz1 expressions in a PPARγ-dependent manner. These findings support the notion that PCB2 regulated macrophage M2 polarization via the activation of PPARγ. Our results provide a new mechanism by which procyanidins exert their beneficial anti-inflammatory effects.

The aim of this study was to evaluate the effect of electroacupuncture (EA) on postoperative pain management in patients undergoing thoracic surgery. A randomized study was conducted. Ninety-two thoracic surgical patients were randomly divided into an EA group and a sham group. Postoperative intravenous analgesia was applied with a half dose of the conventional drug concentration in both groups. In the EA group, EA treatment was administered for three consecutive days after the surgery with 6 sessions of 30 min each. Compared with the sham group, patients in the EA group had a lower visual analogue scale (VAS) score at 2, 24, 48, and 72 hours and consumed less analgesic after surgery. The incidence of opioid-related adverse effects of nausea was lower in the EA group. The time to first flatus and defecation was also shorter in the EA group. Furthermore, the plasma β-endorphin (β-EP) level was higher by radioimmunoassay and the plasma 5-hydroxytryptamine (5-HT) level was lower in the EA group by enzyme-linked immunosorbent assay during the first 72 hr after thoracic surgery. Therefore, EA is suitable as an adjunct treatment for postoperative pain management after thoracic surgery.