Lycorine inhibits migration and proliferation of hepatocellular carcinoma cells by reducing transketonase expression.

Background: Previous studies have showed that lycorine can restrain the development of multiple tumor types, containing hepatocellular carcinoma (HCC), but the underlying mechanisms remain unknown. Methods: We assessed the impact of lycorine on hepatocellular cancer cell proliferation, migration, colony formation, cell cycle, and apoptosis. The possible inhibitory effect of lycorine on the activity of HCC cells was analyzed by RNA-seq, and transketolase (TKT) expression in HCC and nontumorous tissues was detected using RT-PCR. The expression of TKT protein in HCC and tumor adjacent non-cancerous tissues was detected by immunohistochemistry. We evaluated the association of expression of TKT in HCC tissues with prognosis, and investigated the inhibitory effect of lycorine on tumor growth in vivo. Results: Lycorine significantly inhibited the proliferation, invasion, migration, colony formation, cell cycle of HCC cells, but had no obvious impact on apoptosis. Twenty-eight genes were found to be down-regulated in HuH7 and HepG2 cells after lycorine treatment, and the difference of TKT gene expression was significantly. The expression of TKT protein was significantly higher in HCC than in non-tumorous tissues. The expression of TKT was correlated with tumor size, Edmondson grade, AFP, and overall survival. Survival analysis suggested that high expression of TKT was associated with a poor survival. The average tumor volume and weight were significantly reduced in the lycorine injection group, but the body weights of the mice did not change significantly. Conclusion: Lycorine can restrict the migration and proliferation of HCC cells by down-regulating TKT expression, and it may be a potential meaningful drug for the prevention and treatment of HCC.

Hypoxic Tumor-Derived Exosomal miR-199a-3p Promote Gastric Cancer Metastasis via MAP3K4.

Proximal gastrectomy is more frequently recommended for early upper gastric cancer and Siewert II gastroesophageal junction cancer less than 4 cm in length. After proximal gastrectomy, the anatomical structure of the gastroesophageal junction can be destroyed, and the anti-reflux effect of the cardia is lost. In recent years, as various anti-reflux reconstructions have been developed, some functions of the stomach are retained, and serious reflux esophagitis is avoided after proximal gastrectomy. In this article, we summarized the indications, advantages, and disadvantages of various classic reconstruction and latest improved reconstruction method including esophageal and residual stomach anastomosis, tubular gastroesophageal anastomosis, muscle flap anastomosis, jejunal interposition, and double-tract reconstruction.

The Functional Role of LncRNA UCA1 in Pancreatic Cancer: a mini-review.

Pancreatic cancer (PaC) is a common malignant tumor of the digestive tract, with a 5-year survival rate of less than 5% and high mortality rate in the world. LncRNAs have been showed to possess multiple biological functions in growth, differentiation, and proliferation, which play an important role in different biological processes and diseases, especially in the development of tumors. LncRNA UCA1, which is firstly identified in human bladder cancer, has been showed to be a tumor promoter in pancreatic cancer. Recent researches have showed that UCA1 might promote pancreatic carcinogenesis and progression, and correlate with drug resistance. In this review, we address the biological function and regulatory mechanism of UCA1 in pancreatic cancer, which might give a new approach for clinical diagnosis and treatment.

ZNF521 Is Correlated with Tumor Immune Cell Infiltration and Act as a Valuable Prognostic Biomarker in Gastric Cancer.

Aim: To explore the correlations between the expression of zinc finger protein 521 (ZNF521) with immune invasion and prognosis of gastric cancer. Methods: Expression of ZNF521 was examined by immunohistochemistry in gastric cancer cases. Kaplan-Meier plotter was used to determine the relationships between ZNF521 and prognosis. TIMER and GEPIA were used to analyze the correlation between ZNF521 expression and gene markers of immune cell infiltration. Results: The expression of ZNF521 was up-regulated in gastric cancer samples. Kaplan-Meier analysis indicated that higher expression of ZNF521 was associated with poor prognosis. The expression of ZNF521 was correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells in gastric cancer, which also correlated with diverse immune marker sets. Conclusions: ZNF521 is correlated significantly with immune cell infiltration and is a valuable biomarker for prognosis in gastric cancer.

Understanding reviewer characteristics in online reviews via network structural positions.

With the prevalence of online review websites, understanding online reviewer characteristics has become important, as such an understanding provides brand managers with opportunities to segment their markets, target influencers, and develop effective marketing strategies. Nonetheless, past studies have overlooked the role of network structural positions in the characteristics of online reviewers. Accordingly, using data from Yelp websites as samples, this study attempted to explore the differences in reviewer characteristics by network structural positions. The study used multiple data collection and analysis approaches, including web scraping, network analysis, and statistical analysis. The results of this study showed that compared to peripheral reviewers, core reviewers exhibited significantly more photos and brands reviewed and included a higher proportion of early reviewers. The study has significant theoretical and practical implications for researchers and brand managers who are interested in understanding online review markets.

Photoaged polystyrene microplastics serve as photosensitizers that enhance cimetidine photolysis in an aqueous environment.

Microplastics (MPs) have received much attention in recent years because of their continuous photoaging process in aquatic environments. However, little research has been conducted on the photochemistry of aged microplastics and the associated effects on coexisting pharmaceuticals. This study investigated the photodegradation of cimetidine via aged polystyrene microplastics (PS-MPs) with different aging times (0-7 d) under simulated sunlight irradiation (700 W/m2). PS-MPs with 5 d of aging time resulted in much faster cimetidine degradation (>99%) after 2 h of irradiation than pristine PS-MPs (<8%). The enhanced photodegradation of cimetidine by aged PS-MPs was related to the increase in chromophoric oxygenated groups (CO, C-O) followed by redshifted absorbance through the photoaging process, which induced the formation of the environmentally persistent free radicals (EPFRs) OH, 1O2 and 3PS*. However, only 1O2 and 3PS* contributed to enhanced cimetidine photodegradation, with 1O2 playing a more important role in our case. This work also demonstrated that other compounds that are susceptible to indirect photolysis, such as codeine and morphine, are likewise significantly degraded under irradiation in the presence of aged PS-MPs. Although previous studies have reported how MPs can increase the persistence of contaminants, this study demonstrates that MPs can serve as photosensitizers and alter the fate of coexisting pharmaceuticals in aquatic environments.

The role of NLRP3 inflammasome in digestive system malignancy.

Digestive system malignancies, the most common types of cancer and a major cause of death in the worldwide, are generally characterized by high morbidity, insidious symptoms and poor prognosis. NLRP3 inflammasome, the most studied inflammasome member, is considered to be crucial in tumorigenesis. In this paper, we reviewed its pro-tumorigenic and anti-tumorigenic properties in different types of digestive system malignancy depending on the types of cells, tissues and organs involved, which would provide promising avenue for exploring new anti-cancer therapies.

Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma.

AIMS: Lysine acetyltransferase 6B (KAT6B), is a histone acetyltransferase implicated to have a role in tumor suppression. However, the relationship between KAT6B and hepatocellular carcinoma (HCC) is unclear. The purpose of this study was to detect the expression of KAT6B in HCC tissues and analyze its connection with the clinicopathological features of HCC. METHODS: First, we performed immunohistochemical staining on 250 HCC tissues and 222 non-tumor liver tissues to examine the expression of KAT6B.Then the relation between KAT6B expression and clinicopathological parameters was analyzed by chi-square test, and the overall survival analysis was conducted by Kaplan-Meier survival method. In addition, based on the Oncomine expression array online and the UALCAN database, we compared KAT6B expression differences between normal liver tissues and HCC tissues more broadly. RESULTS: Compared with normal tissues, KAT6B expression was significantly lower in HCC tissues. Low KAT6B expression was found to be related to gender, AFP level, and tumor size. According to the online database, KAT6B expression was found to be decreased in HCC tissues and high in normal tissues. CONCLUSIONS: Lower expression of KAT6B is associated with poor prognosis of HCC, and KAT6B may be a potential tumor suppressor in liver cancer.

Clean water generation through a multifunctional activated carbon-TiO2 interfacial solar distillation system.

Solar distillation is emerging as an environmentally friendly and energy-effective technology for clean water generation. However, bulk water heating and the possibly complex composition of water matrices of source water could undermine the system efficacy. In this study, an interfacial evaporation device consisting of activated carbon combined with P25 TiO2 as the top layer and polyethylene foam as the bottom layer (AC-P25/foam device) was established. With the excellent optical absorbance of AC and the heat localization effect contributed by the PE foam, the evaporation rate (r evp) of the device (r evp = 2.1 kg m-2 h-1) was improved by 209% and 71% compared with that of the water-only (r evp = 0.68 kg m-2 h-1) and conventional evaporation (i.e., submerged AC-P25) systems (r evp = 1.23 kg m-2 h-1), respectively. The reusability test showed the stable evaporation performance of AC-P25/foam within 7 cycles; this interfacial evaporation was also found to be less affected by suspended solids in water due to a reduction in the influence of light scattering. The AC-P25/foam device not only possessed photothermal ability for water distillation but was also able to prevent enrichment of volatile organic compounds (i.e., phenol) with ∼95% removal efficiency through adsorption and photocatalytic reactions under illumination. Additionally, an outdoor solar distillation test performed with synthetic saline water demonstrated the desalination ability of the AC-P25/foam device, with the concentrations of all ions in the distilled water ≤3.5 mg L-1, far below the drinking water guideline value provided by the World Health Organization. The materials of the AC-P25/foam photothermal device are readily available and easily fabricated, showing the practical feasibility of this device for clean water generation.

Effects of a single bout of short-duration high-intensity and long-duration low-intensity exercise on insulin resistance and adiponectin/leptin ratio.

OBJECTIVES: Moderate-intensity exercise improves insulin sensitivity, which may depend on the intensity, duration, and frequency of exercise. We examined the effects of a single bout of short-duration high-intensity exercise (HIE) and long-duration lowintensity exercise (LIE) on insulin sensitivity and the adiponectin/leptin ratio in individuals with different body mass indices (BMIs) who do not exercise regularly. METHODS: We enrolled 42 healthy volunteers aged 20-64 years and divided them into two groups based on BMI: BMI <24 kg/m2 and BMI ≥27 kg/m2. They were randomly assigned to either the short-duration (20 min) HIE (70%-80% heart rate reserve, HRR) or long-duration (60 min) LIE training groups (30%-40% HRR). Glucose, insulin, adiponectin, and leptin levels were assessed before training and at 0, 30, 60, and 120 min after training. RESULTS: We finally analyzed 27 normal weight and 9 obese individuals. No significant differences were observed in the baseline information of both BMI groups. Homeostatic model assessment for insulin resistance significantly improved for both exercise patterns in the normal weight group and for the HIE pattern in the obese group (P < 0.01), whereas the adiponectin/leptin ratio increased significantly only among normal weight participants with the LIE intervention. CONCLUSION: Both exercise patterns in BMI <24 kg/m2 and BMI ≥27 kg/m2 benefit on insulin resistance. Therefore, people can choose the way they can fit to improve insulin resistance both short-duration high-intensity exercise and long-duration low-intensity exercise.

VSNL1 Promotes Gastric Cancer Cell Proliferation and Migration by Regulating P2X3/P2Y2 Receptors and Is a Clinical Indicator of Poor Prognosis in Gastric Cancer Patients.

PURPOSE: The aim of this study was to investigate the role of Visinin Like 1 (VSNL1) in the proliferation and migration of gastric cancer (GC) cells as well as its clinical prognostic significance. METHODS: To this end, we evaluated VSNL1 expression in GC tissues and cell lines by real-time PCR and immunohistochemistry. To further explore the effects of VSNL1, a lentiviral vector expressing a short hairpin RNA (shRNA) against VSNL1 was constructed and transduced into the GC cell lines BGC-823 and SGC-7901. The interference efficiency of VSNL1-shRNA was determined by western blot. The effects of VSNL1 on the migration and invasion of GC cells as well as the expression of P2X3/P2Y2 were explored using MTS, colony formation, migration, and western blot assays. RESULTS: VSNL1 mRNA and protein levels were increased in GC tissues and cell lines. Furthermore, VSNL1 expression was positively correlated with Lauren's classification, lymph node metastasis, distant metastasis, TNM stage, and prognosis. VSNL1 expression was inversely correlated with the 5-year survival rate of GC patients. VSNL1 expression was markedly reduced in cells transduced with lentivirus expressing shRNA against VSNL1, and inhibiting VSNL1 expression significantly suppressed cell growth, migration, and colony formation and reduced the expression of P2X3/P2Y2. CONCLUSION: VSNL1 may promote the proliferation and migration of GC cells by regulating P2X3 and P2Y2 expression. VSNL1 plays important roles in GC development and metastasis and may be correlated with patient prognosis.

Expression and Clinical Significance of MMP-28 in Bladder Cancer.

AIMS: The aim of this study to determine the expression of MMP-28 in bladder urothelial carcinoma and to analyze the correlation between MMP-28 and the clinicopathological characteristics of human bladder carcinoma, and its relationship with patient prognosis. METHODS: A total of 491 surgically resected bladder cancer samples and 80 normal tissue adjacent to the tumor were stained by immunohistochemistry. The expression of MMP-28 in these samples was quantitated, and the value of MMP-28 as a marker of bladder cancer and prognosis was assessed. RESULTS: The expression of MMP-28 in urinary bladder carcinoma was higher than in normal bladder mucosa. The high level of MMP-28 was significantly correlated with tumor histology grade, lymphatic metastasis, lymph node infiltration, and distant metastasis (P < 0.05). The upregulation of MMP-28 was also closely related to the risk of cancer progression and the survival of patients. Further analysis documented that high expression of MMP-28 was associated with decreased overall survival in bladder cancer patients. CONCLUSIONS: The abnormal expression of MMP-28 may be related to the initiation and development of urothelial carcinoma. The upregulation of MMP-28 can be used as one of the effective indicators to diagnose bladder cancer and predict tumor progression.

High expression of FOXO3 is associated with poor prognosis in patients with hepatocellular carcinoma.

The role of forkhead box O3 (FOXO3) as a tumor suppressor gene and its association with the human lifespan is well documented. However, several studies have indicated that high expression of FOXO3 is also significantly associated with tumorigenesis. The aim of the present study was to determine the clinical significance of FOXO3 in the development and prognosis of hepatocellular carcinoma (HCC). mRNA expression data of FOXO3 from The Cancer Genome Atlas database was analyzed through the UALCAN online tool to compare the expression of FOXO3 between HCC and normal liver tissues. Subsequently, the expression of FOXO3 at the protein level was investigated via immunohistochemical staining of 314 HCC and 150 non-cancerous liver tissue samples. The association between protein expression and clinicopathological parameters was analyzed using the χ2 test, and the effect of FOXO3 expression on survival was assessed via Kaplan-Meier analysis. The expression of FOXO3 mRNA was significantly higher in HCC in comparison with healthy tissues. High FOXO3 protein expression was revealed in 43/150 non-cancerous liver tissues, and in 238/314 HCC samples. A significant association was demonstrated between FOXO3 expression and metastasis, Tumor-Node-Metastasis stage, Edmondson grade, α-fetoprotein level and overall survival. In conclusion, the high expression of FOXO3 predicts a poor prognosis in patients with HCC, indicating this protein as a potential therapeutic target in HCC.

Decreased DC-SIGNR expression in hepatocellular carcinoma predicts poor patient prognosis.

Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin-related protein (DC-SIGNR) is a transmembrane receptor primarily involved in pathogen recognition by the innate immune system, with particular importance for viral recognition. DC-SIGNR may also be associated with tumorigenesis. The aim of the present study was to investigate the association between DC-SIGNR expression, development of hepatocellular carcinoma (HCC), and clinicopathological features. Immunohistochemistry was used to assess DC-SIGNR protein expression in HCC and paired non-cancerous tissue samples. DC-SIGNR expression was lower in HCC tissues compared with adjacent non-tumor tissue samples. The expression of DC-SIGNR was associated with small tumor size, low Edmondson grade and high patient long term survival rates. Bioinformatics analyses were performed on several datasets to assess the potential function of DC-SIGNR and related genes; the data revealed that DC-SIGNR mRNA expression was lower in HCC tissues compared with non-cancerous controls, and analyses of ten-year survival rates indicated patients with low DC-SIGNR expression exhibited shorter average survival times. In conclusion, decreased DC-SIGNR expression in HCC tissues may be a relevant predictive biomarker of clinical prognosis, in addition to being a viable therapeutic target for HCC treatment.

Low expression of citron kinase is associated with poor patient outcomes in hepatocellular carcinoma.

BACKGROUND: Citron kinase (CIT) is a protein related to cytokinesis and is an important abscission regulator. However, the relationship between CIT and hepatocellular carcinoma (HCC) is unclear. The aim of this study was to investigate the expression CIT in HCC tissues, and explore the connection between this expression and clinicopathological characteristics of HCC. METHODS: Immunohistochemistry staining on 235 HCC tissues and 96 non-tumorous liver tissues controls was performed to examine the CIT protein expression. We then analyzed the correlation between protein expression and clinicopathological parameters via χ2 tests, and we performed overall survival analyses via the Kaplan-Meier survival approach. Based on the online Oncomine Expression Array and UALCAN databases, we more broadly compared CIT mRNA expression between normal and HCC tissues. Finally, we compared CIT mRNA expression in these databases to protein expression in our study and explored potential sources for any observe differences. RESULTS: Compared to normal tissues, CIT expression was significantly lower in HCC tissues. Low CIT expression was found to be related to gender, tumor size, Edmondson Grade, Microvascular invasion, serum AFP levels and poor overall survival. Based on the online databases, CIT mRNA expression was found to be high in HCC tissues and decreased in normal tissues. We hypothesize that this unexpected result is due to a negative feedback loop whereby low protein CIT levels mediate increased CIT mRNA levels. CONCLUSIONS: Lower CIT protein levels are associated with a poorer prognosis in HCC patients, and lower CIT protein levels may mediate a negative feedback loop leading to increased CIT mRNA levels.

CAP2 is a Valuable Biomarker for Diagnosis and Prognostic in Patients with Gastric Cancer.

Cyclase-associated protein 2 (CAP2) protein is reported to be upregulated in hepatocellular carcinoma (HCC), human breast cancer, and malignant melanoma. However, its expression in gastric cancer remains unknown, this study was to investigate CAP2 expression and its prognostic significance in gastric cancer. Firstly, we analyzed the Oncomine databases to compare CAP2 mRNA expression in gastric cancer and normal tissues. CAP2 protein expression was analyzed in gastric cancer samples and non-tumor mucosa by RT-PCR and immunohistochemical analysis. Consequently, statistical analyses were performed to evaluate the clinicopathological significance of CAP2 expression in gastric cancer. CAP2 expression was significant higher in gastric cancer tissues than that in non-tumor mucosa at protein levels. CAP2 was up-regulated in 57.8% (252/436) of gastric cancer samples, while detected in only 10.9% (10/92) of non-tumor mucosa. Statistical analysis shows that the expression of CAP2 was correlated with tumor size, Lauren's classification, depth of invasion, lymph node and distant metastases, and regional lymph node stage, TNM stage, but not with age, sex, histology classification, and histologic differentiation. Kaplan-Meier analysis indicated that high CAP2 expression was associated with poor overall survival (78.7%) in 203 of 252 gastic cancer patients. In stage I, II, and III tumors, the 5-year survival rate was lower in those with high expression of CAP2 than those with low expression. In stage IV tumors, the expression of CAP2 did not correlate with the 5-year survival rate. Multiple Cox regression analysis indicated CAP2 as an independent predictor for overall survival [hazard ratio (HR) = 2.045, 95% confidence interval: 1.445-2.895, p < 0.01], while Lauren's classification, TNM stage, and expression of CAP2 were independent prognostic factors in patients with gastric cancer. For the first time, we found that CAP2 was upregulated in gastic cancer, and was associated with lymph node and distant metastases. CAP2 may serve as a prognostic indicator for patients with gastic cancer.

miR-199a-3p targets ETNK1 to promote invasion and migration in gastric cancer cells and is associated with poor prognosis.

PURPOSE: To investigate the prognostic significance of miR-199a-3p and its role in invasion and metastasis in gastric cancer. METHODS: miR-199a-3p expression in 436 formalin-fixed and 39 frozen gastric cancer tissues was investigated by in situ hybridization and RT-PCR, respectively. The role of miR-199a-3p in the migration and invasion of gastric cancer cells was determined in overexpression and inhibitor studies using transwell assays and the SGC-7901, BGC-823 and MGC-803 gastric cancer cells lines. The effect of miR-199a-3p expression on ethanolamine kinase 1 (ETNK1) levels was determined by western botting. RESULTS: miR-199a-3p was significantly up-regulated in AGS, SGC-7901, BGC-823 and MGC-803 gastric cancer cells, when compared with GES-1 non-malignant gastric epithelial cells. In situ hybridization studies revealed that human non-tumor gastric mucosa samples were negative for miR-199a-3p expression, while 162 of 436 (37.16%) cases of gastric cancer demonstrated positive expression. miR-199a-3p overexpression was associated with tumor size, Lauren classification, depth of invasion, lymph node and distant metastasis, TNM stage and prognosis. In patients with I, II and III stage tumors, high miR-199a-3p expression was associated with a significantly lower 5-year survival rate. miR-199a-3p overexpression was associated with increased cell migration and invasion. ETNK1 expression was inhibited following miR-199a-3p overexpression in BGC-823 and SGC-7901 cells, and elevated following miR-199a-3p suppression in MGC-803 cells. CONCLUSION: miR-199a-3p is highly expressed in gastric cancer, and correlates with invasion, metastasis and prognosis. miR-199a-3p regulates the invasion and migration of gastric cancer cells by targeting ETNK1. Consequently, miR-199a-3p may serve as a prognostic indicator in gastric cancer.

Decreased CRHBP expression is predictive of poor prognosis in patients with hepatocellular carcinoma.

Corticotropin releasing hormone binding protein (CRHBP) mediates the reaction between corticotropin releasing hormone (CRH) and corticotropin releasing hormone receptors (CRHRs). It is expressed in a number of organs, and the expression of CRHBP is associated with tumorigenesis and cancer progression. The aim of the present study was to investigate CRHBP expression levels in hepatocellular carcinoma (HCC) and its association with patient clinicopathological characteristics as well as prognosis. The expression of CRHBP was examined by immunohistochemistry in 169 HCC tissues and 151 adjacent non-tumorous tissues. The results were validated by western blotting using patient tissues and liver cancer cell lines. The association of CRHBP expression with clinicopathological patient characteristics and survival rate was analyzed statistically. Expression of CRHBP was detected in 142/151 (94.0%) non-tumorous liver tissues, and 84/169 (49.7%) HCC tissues (P<0.001). The expression of CRHBP was negatively associated with tumor size (P=0.013), Edmondson Grade (P=0.002), hepatitis B virus antigen (P=0.020), and α-fetoprotein levels (P=0.014). Patients exhibiting low CRHBP expression were associated with shorter survival time compared with those exhibiting high CRHBP expression (P=0.012). The results of western blotting analysis suggest that reduced CRHBP expression is frequently observable in patients with HCC. Low CRHBP expression in HCC tissues may be a predictor of clinical prognosis and a potential therapeutic target for HCC.

Metastasis-associated protein 1 (MTA1) in gastric cancer tissues is positively associated with poorer prognosis.

BACKGROUND: The present study examined the clinical significance of metastasis-associated protein 1 (MTA1) in the progression and patient survival of gastric cancer. METHODS: Paraffin-embedded resected tissues of gastric cancer mucosa (n = 436) and adjacent normal mucosa (n = 92) were assessed immunohistochemically for MTA1 protein, and scored according to the percentage of cells positively stained for MTA1 combined with stain intensity. Associations between MTA1 staining scores and clinicopathological factors, including survival time, were evaluated. RESULTS: The staining scores for MTA1 were significantly higher in gastric cancer tissues than in matched normal tissues. MTA1 scores positively correlated with tumor size, depth of invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distal metastasis, and advanced clinical staging. Patients with high MTA1 scores in gastric cancer tissues had a significantly lower five-year survival rate compared with patients with low MTA1 scores. The multivariate analysis indicated that MTA1 protein levels in resected gastric cancer tissues, as reflected by immunohistochemical staining, are an independent prognostic index of gastric carcinoma (P < 0.01). CONCLUSION: MTA1 immunopositivity was significantly associated with progression of gastric cancer, and may be helpful in gastric cancer prognosis.