lncRNA PCAT-1 interacting with FZD6 contributes to the malignancy of acute myeloid leukemia cells through activating Wnt/ß-catenin signaling pathway.

Accumulating evidence has suggested the involvement of long noncoding RNAs (lncRNAs) on the acute myeloid leukemia (AML). Therefore, this study aimed to investigate the unknown function of lncRNA Prostate cancer-associated transcript-1 (PCAT-1) in AML cells. Our data found that PCAT-1 was highly expressed in AML-M1/2 and AML-M3 patients than normal controls and its expression was significantly up-regulated in AML cell lines Kasumi-6 and HL-60. The functional experiments demonstrated that knockdown of PCAT-1 remarkably inhibited proliferation, arrested cell cycle progression and triggered apoptosis of AML cells. Mechanistically, we revealed that PCAT-1 could directly interact with FZD6 protein to regulate its stability. Overexpression of FZD6 partly abolished the effects of PCAT-1 silencing on AML cells. Our integrated experiments then suggested that PCAT-1 could activate the Wnt/ß-catenin signaling pathway in an FZD6-dependent manner. Taken together, the present study indicated that PCAT-1 interacting with FZD6 to activate Wnt/ß-catenin signaling, which may play an important role in the pathogenesis of AML.

Exploring the pharmacological effects and potential targets of paeoniflorin on the endometriosis of cold coagulation and blood stasis model rats by ultra-performance liquid chromatography tandem mass spectrometry with a pattern recognition approach.

This study was employed to explore the potential biomarkers of endometriosis of cold coagulation and blood stasis (ECB) model rats and the effective mechanism of action of paeoniflorin (PF). The serum metabolomics approach was carried out using the UPLC-MS technique with a pattern recognition approach to prove the possible biomarkers of the ECB model rats and the perturbed pathways. Subsequently, the mechanism of PF treatment of this disease model was elucidated. The results revealed that the serum metabolism profiles in two groups were also separated significantly. Moreover, 8 biomarkers were found in the positive mode, and 5 biomarkers were found in the negative mode. Totally, 13 biomarkers participated in the metabolism of phenylalanine, arachidonic acid, etc. After treatment with PF, 10 biomarkers were regulated. Among the 10 biomarkers, 4 were statistically significant: l-phenylalanine, l-tryptophan, LysoPC (18:4(6Z,9Z,12Z,15Z)), and LysoPC (16:1(9Z)). We initially confirmed that PF could significantly regulate the metabolic expression of multiple metabolic pathways in the ECB model rats. For the first time, this study explored the mechanism of action of PF treatment based on the metabolic pathways of the organism and demonstrated the potential of the metabolomics techniques for the study of drug action mechanisms.

High-throughput metabolomics used to identify potential therapeutic targets of Guizhi Fuling Wan against endometriosis of cold coagulation and blood stasis.

Metabolomics is an emerging and robust discipline and involves the comprehensive evaluation of small molecule endogenous metabolites and enables the exploration of the pathogenesis of diseases. For example, endometriosis - a common disease which mostly occurs in women of childbearing age. A cure for endometriosis of cold coagulation and blood stasis (ECB) is highly sought after. This study was conducted to discover the potential biomarkers of ECB and the effective mechanism undertaken by Guizhi Fuling Wan (GFW) in treating ECB in rats. Urinary metabolomics were performed by using UPLC-Q-TOF-MS with pattern recognition methods to evaluate the changes in metabolic profiles and to identify biomarkers for elucidating the mechanism of the treatment of ECB with GFW. The results showed that urinary metabolism in the two groups were distinctly separated on the 28th day, and a total of 20 differential biomarkers (16 in the positive mode, 4 in the negative mode) were confirmed involving several key metabolic pathways which included phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism and the citrate cycle. Following the oral administration of GFW, certain pathways were affected; these included the following: phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, glyoxylate and dicarboxylate metabolism, tyrosine metabolism, citrate cycle, steroid hormone biosynthesis, tryptophan metabolism, phenylalanine metabolism, primary bile acid biosynthesis, and aminoacyl-tRNA biosynthesis. This study also demonstrated that the administration of GFW affected the levels of urine endogenous metabolites, thereby laying a foundation for further study of the pharmacodynamical mechanism of GFW.

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.

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.

Myofibrotic malformation vessels: unique angiodysplasia toward the progression of hemorrhoidal disease.

BACKGROUND: The etiology and pathogenesis of hemorrhoids is unclear, although hemorrhoids are a worldwide disease in men and women, with peak prevalence at 45-65 years of age. Hemorrhoidal cushions as the anal venous plexi are normal anatomical structures from infancy. This study attempts to reveal the angiodysplasia and other pathological changes in association with different degrees of symptomatic hemorrhoids. MATERIALS AND METHODS: A total of 281 patients with internal hemorrhoids from degree I to IV underwent hemorrhoidectomy. The vascular changes were analyzed by microscopic assessment and software analysis, with Masson's trichrome, CD34, and smooth muscle actin. RESULTS: The hemorrhoidal tissues exhibited abnormal vessels in the mucosae and submucosae that we termed them as myofibrotic malformation vessels (MMVs). MMVs are not ascribed to arteries or veins because they exhibit enlarged and tortuous lumens with smooth muscle dysplasia and fibrotic deposition in the walls without overlying mucosal ulceration. The muscularis mucosae also showed smooth muscle dysplasia and fibrosis, even if it were interrupted by the intruding MMVs. The statistical data indicated that the severity of all the changes correlate positively with the progression of hemorrhoids (P<0.001). Hemorrhoidal patients are prone for reoccurrence even with prolapsing hemorrhoid when compared with the conventional hemorrhoidectomy. Multiple logistic regression analysis showed that MMVs in mucosal propria, mean thickness of mucosal muscularis layer, and fibrotic changes in MMV were independent risk factors for MMVs in hemorrhoidal disease. CONCLUSION: MMVs and muscularis mucosae dysplasia reciprocally contribute to hemorrhoidal exacerbation. The novel findings of this study propose that the characteristic features of MMVs and muscularis mucosae dysplasia of the anorectal tube ultimately cause symptomatic hemorrhoids, which could affect the clinical management of hemorrhoidal disease through the use of surgery to target the malformed vessels.