Mesenteric ischaemia in a case of acute anterior myocardial infarction: overlap of ischaemic types.

Acute mesenteric ischaemia is divided into different clinical entities which are usually considered separately. Here we report a case of acute mesenteric ischaemia complicated with acute anterior myocardial infarction. The clinical picture suggested that non-occlusive mesenteric ischaemia and acute mesenteric arterial thrombosis were both present in this case. Thus, non-occlusive and occlusive ischaemia may coexist in a coordinated and perceptible pattern.

Protective Effects of Relaxin 2 (RLXH2) against Hypoxia-Induced Oxidative Damage and Cell Death via Activation of The Nrf2/HO-1 Signalling Pathway in Gastric Cancer Cells.

OBJECTIVE: This study aims to investigate the potential role of relaxin, a peptide hormone, in preventing cellular deterioration and death in gastric carcinoma cells under hypoxic conditions. It explores the effects of recombinant relaxin 2 (RLXH2) on growth, cell differentiation, invasive potential, and oxidative damage in these cells. MATERIALS AND METHODS: In this experimental study, the NCI-N87 cell line was cultured under normal conditions and then subjected to hypoxia using cobalt chloride (CoCl2). The cells were treated with RLXH2, and various assays were performed to assess cellular deterioration, death, and oxidative stress. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to measure the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1, and the translocation of Nrf2 to the nucleus was confirmed through Western blot analysis. RESULTS: This study demonstrates, for the first time, that RLXH2 significantly reduces the formation of reactive oxygen species (ROS) and the release of lactate dehydrogenase (LDH) in gastric cancer cells under hypoxic conditions. RLXH2 also enhances the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), leading to a decrease in hypoxia-induced oxidative damage. RLXH2 promotes the translocation of Nrf2 to the nucleus, resulting in HO-1 expression. CONCLUSION: Our findings suggest that RLXH2 plays a significant protective role against hypoxia-induced oxidative damage in gastric carcinoma cells through the Nrf2/HO-1 signalling pathway. This research contributes to a better understanding of the potential therapeutic applications of RLXH2 in gastric cancer treatment.

Transferrin-Modified Mangiferin-Loaded SLNs: Preparation, Characterization, and Application in A549 Lung Cancer Cell.

Introduction: Mangiferin is a plant antitumor compound with poor water solubility and low bioavailability. In this study, transferrin-modified mangiferin-loaded solid lipid nanoparticles (Tf-modified MGF-SLNs) were prepared to overcome the above defects. Methods: Tf-modified MGF-SLNs were prepared by the emulsification-solvent evaporation method. The physicochemical properties of Tf-MGF-SLNs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of Tf-MGF-SLNs in lung cancer. Results: The mean hydrodynamic diameter of the Tf-MGF-SLNs was 121.8±2.9 nm with a polydispersity index of 0.134±0.03. According to TEM micrographs, Tf-MGF-SLNs are spherical and uniform, and the EE% was found to be 72.5±2.4%. In vitro release, we identified an initial burst effect release, followed by controlled release, in SLNs at both pHs and the Tf-MGF-SLNs drug accumulation release percentages reached over 68% at pH 4.0 and 72% at pH 7.4 in 6 hours, respectively. In vivo studies showed that depending on surface modification, Tf-MGF-SLNs, which suggested that cell internalization was changed and more drugs entered the cells successfully. Discussion: Tf-MGF-SLNs were highly efficient in suppressing the tumor growth in xenograft tumor model. Sustained release of the drug delivery system and Tf-modified MGF-SLNs played a major role. Tf-MGF-SLNs would be a promising formulation for the treatment of lung cancer.

Notum palmitoleoyl-protein carboxylesterase regulates Fas cell surface death receptor-mediated apoptosis via the Wnt signaling pathway in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is one of the most common types of malignancy and accounts for >3 million deaths worldwide each year. The present study aimed to evaluate the role of notum palmitoleoyl-protein carboxylesterase (NOTUM) in in vivo and in vitro, and to identify the relationship between NOTUM and the apoptosis of COAD. Moreover, the present study aimed to investigate whether NOTUM regulated Fas cell surface death receptor (FAS)-mediated apoptosis was affected by the Wnt signaling pathway. Gene expression profiling interactive analysis (GEPIA) was used to predict the potential function of NOTUM. Western blotting and reverse transcription-quantitative PCR were conducted to detect the protein and mRNA expression levels of NOTUM in different tissues or cell lines. The occurrence and development of COAD was detected after NOTUM knockdown lentivirus administration. The apoptosis of COAD was also observed. SKL2001 was applied to examine whether the role of NOTUM was regulated by Wnt. GEPIA analysis demonstrated that NOTUM expression in COAD tumor tissue was higher compared with in normal tissues. Pair-wise gene correlation analysis identified a potential relationship between NOTUM and Wnt. NOTUM protein and mRNA expression levels in colon carcinoma tissues and RKO cells were increased. NOTUM knockdown lentivirus serves a role in inhibiting COAD development by reducing tumor proliferation, reducing tumor size, and increasing the level of apoptosis in vitro and in vivo. Moreover, NOTUM could increase apoptosis in COAD, which was regulated by FAS, and SKL2001 blocked the progress of apoptosis after NOTUM regulation by NOTUM knockdown lentivirus in vitro and in vivo. Collectively, the present results suggested that NOTUM may be able to regulate the apoptosis of COAD, and that Wnt may be the down-stream target signaling of NOTUM in apoptosis.

Circular RNA Paired-Related Homeobox 1 Promotes Gastric Carcinoma Cell Progression via Regulating MicroRNA-665/YWHAZ Axis.

BACKGROUND: Gastric carcinoma (GC) is a ubiquitous malignant tumor worldwide. Circular RNA paired-related homeobox 1 (circ-PRRX1), one kind of non-coding RNAs, has been reported to act as a promoter in tumor growth. This study aims to explore the effects of circ-PRRX1 on proliferation, apoptosis, and metastasis in GC and the underlying regulatory mechanisms. METHODS: The expression of circ-PRRX1, miR-665, and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze YWHAZ protein expression. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-Htetrazolium bromide (MTT), flow cytometry, and transwell assay were carried out to assess the viability, apoptosis, migration, and invasion in GC cells. The interaction between miR-665 and circ-PRRX1 or YWHAZ was predicted by StarBase v2.0 and identified by dual-luciferase reporter system. Xenograft mouse model was employed to determine the effects of circ-PRRX1 knockdown on GC growth in vivo. RESULTS: Compared with normal tissues and cells, circ-PRRX1 and YWHAZ levels were upregulated, and miR-665 was downregulated in GC tissues and cells. Functionally, circ-PRRX1 knockdown inhibited the viability, migration, and invasion and promoted apoptosis in GC cells, whereas anti-miR-665 abolished these effects. Mechanistically, circ-PRRX1 was confirmed as a sponge of miR-665 to regulate YWHAZ expression. Xenograft mouse model suggested that circ-PRRX1 knockdown reduced GC cells growth in vivo. CONCLUSION: Circ-PRRX1 knockdown suppressed GC development by targeting miR-665 to inhibit YWHAZ expression, and the potential molecular mechanism may provide a theoretical basis for GC therapy.

MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN.

Recent studies have shown that miR-494-3p is oncogene and has a central role in many solid tumors; however, the role of miR-494-3p in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, it was found that miR-494-3p was up-regulated in HCC tissues. The high level of miR-494-3p in HCC tumors was correlated with aggressive clinicopathological characteristics and predicted poor prognosis in HCC patients. Functional study demonstrated that miR-494-3p significantly promoted HCC cell metastasis in vitro and vivo. Since phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) signaling is a basic oncogenic driver in HCC, a potential role of miR-494-3p was explored as well as its target genes in PI3K/AKT activation. Of all the predicted target genes of miR-494-3p, the tumor-suppressor phosphatase and tensin homolog (PTEN) were identified. In conclusion, the data we collected could define an original mechanism of PI3K/AKT hyperactivation and sketch the regulatory role of miR-494-3p in suppressing the expression of PTEN. Therefore, targeting miR-494-3p could provide an effective therapeutic method for the treatment of the disease.

Combination of acoustic radiation force impulse imaging, serological indexes and contrast-enhanced ultrasound for diagnosis of liver lesions.

AIM: To assess the value of combined acoustic radiation force impulse (ARFI) imaging, serological indexes and contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant liver lesions. METHODS: Patients with liver lesions treated at our hospital were included in this study. The lesions were divided into either a malignant tumor group or a benign tumor group according to pathological or radiological findings. ARFI quantitative detection, serological testing and CEUS quantitative detection were performed and compared. A comparative analysis of the measured indexes was performed between these groups. Receiver operating characteristic (ROC) curves were constructed to compare the diagnostic accuracy of ARFI imaging, serological indexes and CEUS, alone or in different combinations, in identifying benign and malignant liver lesions. RESULTS: A total of 112 liver lesions in 43 patients were included, of which 78 were malignant and 34 were benign. Shear wave velocity (SWV) value, serum alpha-fetoprotein (AFP) content and enhancement rate were significantly higher in the malignant tumor group than in the benign tumor group (2.39 ± 1.20 m/s vs 1.50 ± 0.49 m/s, 18.02 ± 5.01 ng/mL vs 15.96 ± 4.33 ng/mL, 2.14 ± 0.21 dB/s vs 2.01 ± 0.31 dB/s; P < 0.05). The ROC curve analysis revealed that the areas under the curves (AUCs) of SWV value alone, AFP content alone, enhancement rate alone, SWV value + AFP content, SWV value + enhancement rate, AFP content + enhancement rate and SWV value + AFP content + enhancement rate were 85.1%, 72.1%, 74.5%, 88.3%, 90.4%, 82.0% and 92.3%, respectively. The AUC of SWV value + AFP content + enhancement rate was higher than those of SWV value + AFP content and SWV value + enhancement rate, and significantly higher than those of any single parameter or the combination of any two of parameters. CONCLUSION: The combination of SWV, AFP and enhancement rate had better diagnostic performance in distinguishing between benign and malignant liver lesions than the use of any single parameter or the combination of any two of parameters. It is expected that this would provide a tool for the differential diagnosis of benign and malignant liver lesions.

Low-level miR-646 in colorectal cancer inhibits cell proliferation and migration by targeting NOB1 expression.

Aberrant expression of microRNA (miRNA) is important in the progression of various human cancers, however further investigation is required in order to fully elucidate mechanisms of and validate actions of endogenous non-coding RNAs. The present study demonstrated that the expression of miR-646 was downregulated in colorectal cancer tissues and cell lines. Notably, it was observed that miR-646, a tumor suppressor, inhibited colorectal cancer cell progression through directly targeting Nin one binding protein (NOB1) expression, which possesses anti-tumor properties in colorectal cancer. Furthermore, knockdown of NOB1 expression was responsible for the tumor-suppressive effect of miR-646. The findings suggest that miR-646 may act as a therapeutic target for the treatment of colorectal cancer.

Liver reserve function assessment by acoustic radiation force impulse imaging.

AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse (ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase (ALT), aspartate aminotransferase (AST), serum albumin (ALB), total bilirubin (T-Bil), and other indicators were observed. Liver stiffness (LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green (ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh (CP) scores were carried out based on patient's preoperative biochemical tests and physical condition. Correlations among CP scores, ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. Kruskal-Wallis test was used to compare LS values of CP scores, and the receiver-operator characteristic (ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant (2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B (1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C (1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15 (r = 0.617, P < 0.01) and CP score (r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K (r = -0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively correlated with LS (P < 0.05). The ROC curve revealed that the when the LS value was 2.34 m/s, the Youden index was at its highest point, sensitivity was 69.2% and specificity was 92.1%. CONCLUSION: For patients with liver tumors, ARFI imaging is a useful tool for assessing liver reserve function.

Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition.

AIM: To identify the mechanisms of chemokine ligand 20 (CCL20)-induced hepatocellular carcinoma (HCC) metastasis and evaluate it as a prognostic marker. METHODS: Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels of epithelial-mesenchymal transition (EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide (MTT) and Transwell assays. RESULTS: CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level (P = 0.043), tumor size (P = 0.000), tumor number (P = 0.008), vascular invasion (P = 0.014), and tumor differentiation (P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression (both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability (P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, ß-catenin and vimentin, and decreased E-cadherin expression (P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression (13.33%, 4/30), and positively correlated with vimentin (90.0%, 27/30), ß-catenin (96.67%, 29/30) and p-AKT (76.67%, 23/30) expression. CONCLUSION: CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/ß-catenin pathways.

Prognostic value of CD133 expression in cancer patients treated with chemoradiotherapy: a meta-analysis.

Many studies evaluated the correlations of CD133 expression with the clinical outcomes in patients treated with chemoradiotherapy (CRT) but yielded controversial results. This meta-analysis was performed to identify the impacts of CD133 expression on the prognosis of cancer patients treated with CRT. Electronic databases updated up to March 2014 were searched to find relevant studies. Relevant literatures without any language restrictions were searched via electronic databases as follows: Web of Science (1945 ~ 2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966 ~ 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), and the Chinese Biomedical Database (CBM) (1982 ~ 2013). STATA software was used for the current meta-analysis. Hazard ratios (HR) and its corresponding 95% confidence interval (95% CI) were calculated. Six studies were identified with a total of 470 cancer patients treated with CRT. The meta-analysis results showed that CD133-positive patients had poorer overall survival (OS) than that of CD133-negative patients (HR = 2.13, 95% CI = 1.20 ~ 3.07, P < 0.001). Furthermore, CD133-positive patients displayed shorter disease-free survival (DFS) than that of CD133-negative patients (HR = 1.74, 95% CI = 0.08 ~ 3.40, P = 0.039). Ethnicity-stratified analysis indicated that CD133 expression positively correlated with shorter OS among the Japanese, Chinese, and Spanish populations (all P < 0.05). In conclusion, our findings suggest that CD133 expression may be positively correlated with poorer prognosis in cancer patients treated with CRT.