Arginine induced acute pancreatitis was evaluated as a novel and distinct form of experimental pancreatitis with particular attention to the actin cytoskeleton and expression of heat shock or stress proteins. Arginine induced a dose related necrotising pancreatitis in rats, as shown by histological evaluation, and an increase in serum amylase. Severe pancreatitis induced by 4.5 g/kg arginine was accompanied by dramatic changes in the actin cytoskeleton, as visualised with rhodamine phallodin. Intermediate filaments were also disrupted, as visualised by cytokeratin 8/18 immunocytochemistry. Arginine pancreatitis was accompanied by a stress response with a large increase in the small heat shock protein HSP27, as well as HSP70, peaking at 24 hours and localised to acinar cells. There was a lower increase in HSP60 and HSP90 and no eVect on GRP78. HSP27 was also shifted to phosphorylated forms during pancreatitis. A lower dose of arginine (3.0 g/kg) induced less pancreatitis but a larger increase in HSP70 and HSP27 expression and phosphorylation of HSP27. Thus HSP expression can be overwhelmed by severe damage. The present work in conjunction with earlier work on caerulein induced pancreatitis indicates that changes in the actin cytoskeleton are an early component in experimental pancreatitis. (Gut 2001;49:241-250)

Background: Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC. Methods: The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XF e 96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay. Results: CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells. Conclusion: CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.

BackgroundPatients with ovarian cancer commonly have a poor prognosis, owing to its invasiveness and distant metastasis. Studies have found TM4SF1 participates in regulating tumor cell invasion and migration. Therefore, it is expected to become a target for anti-invasion and metastasis in ovarian cancer.MethodsThe expression of TM4SF1 in normal ovarian epithelial tissues, benign ovarian tumor tissues, primary foci of epithelial ovarian cancer and the matched lymph mode metastatic foci was detected using immunohistochemistry to analyze its association with prognosis. The expression of TM4SF1 in HO8910PM, SKOV3 was inhibited using RNAi, and the growth, proliferation, migration, invasion abilities of HO8910PM and SKOV3 cells and the growth of xenograft tumors in nude mice were examined.Results(1) The positive expression rate of TM4SF1 protein in epithelial ovarian cancer tissues (90.90%) was higher than that in benign ovarian tumor tissues (65.22%) and normal ovarian epithelial tissues (31.25%), and both differences were significant (P < 0.05). The expression of TM4SF1 protein was positive in all metastatic lymph node foci and matched primary foci (100%). (2) The level of TM4SF1 protein expression was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. However, The positive TM4SF1 protein expression was not an independent factor of prognosis (P > 0.05). (3) Silencing TM4SF1 expression did not affect growth, proliferation, or cell cycle distribution but inhibited the migration and invasion abilities of HO8910PM and SKOV3 cells. Silencing TM4SF1 expression inhibited the growth of xenograft tumors in nude mice.ConclusionTM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer.

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Liver disease is a major cause of illness and death worldwide. In China, liver diseases, primarily alcoholic and nonalcoholic fatty liver disease, and viral hepatitis, affect approximately 300 million people, resulting in a major impact on the global burden of liver diseases. The use of Liuweiwuling (LWWL), a traditional Chinese medicine formula, approved by the Chinese Food and Drug Administration for decreasing aminotransferase levels induced by different liver diseases. Our previous study indicated a part of the material basis and mechanisms of LWWL in the treatment of hepatic fibrosis. However, knowledge of the materials and molecular mechanisms of LWWL in the treatment of liver diseases remains limited. Using pharmacokinetic and network pharmacology methods, this study demonstrated that the active components of LWWL were involved in the treatment mechanism against liver diseases and exerted anti-apoptosis and anti-inflammatory effects. Furthermore, esculetin, luteolin, schisandrin A and schisandrin B may play an important role by exerting anti-inflammatory and hepatoprotective effects in vitro. Esculeti and luteolin dose-dependently inhibited H2O2-induced cell apoptosis, and luteolin also inhibited the NF-κB signaling pathway in bone marrow-derived macrophages. schisandrin A and B inhibited the release of ROS in acetaminophen (APAP)-induced acute liver injury in vitro. Moreover, LWWL active ingredients protect against APAP-induced acute liver injury in mice. The four active ingredients may inhibit oxidative stress or inflammation to exert hepatoprotective effect. In conclusion, our results showed that the novel component combination of LWWL can protect against APAP-induced acute liver injury by inhibiting cell apoptosis and exerting anti-inflammatory effects.

Background: TM4SF1 and DDR1 are expressed in many cancers, but their expression in ovarian cancer and the relationship between their expression and patient prognosis are still unclear. The present study aimed to explore the expression of TM4SF1 and DDR1 as well as their relationship with the prognosis of ovarian cancer.Methods: The Oncomine database and gene expression profile interactive analysis (GEPIA) were used to compare the different expression levels of TM4SF1 and DDR1 in ovarian cancer, and Kaplan–Meier plotter was used to analyse the relationship between gene expression and patient prognosis. The interacting proteins of TM4SF1 and DDR1 were analysed by STRING, which is an online protein interaction analysis tool, and enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways was conducted for these interacting proteins. Immunohistochemical staining was performed to detect the expression of TM4SF1 and DDR1 protein in ovarian cancer tissue and to analyse the relationship between the expression and prognosis.Results: Database and clinical sample analyses showed that the expression levels of TM4SF1 and DDR1 were significantly higher in ovarian cancer and that TM4SF1 and DDR1 were coexpressed in some cases. STRING analysis found that the TM4SF1 and DDR1 proteins had an interaction relationship. The overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients with TM4SF1 and DDR1 coexpression were significantly shorter than those of patients lacking TM4SF1 and DDR1 coexpression. Multivariate analysis showed that TM4SF1 and DDR1 protein coexpression was an independent prognostic factor.Conclusions: TM4SF1 and DDR1 proteins were coexpressed in some ovarian cancer tissues and were considered adverse prognostic factors for ovarian cancer. Our findings suggested that there might be an interaction or mutual regulatory mechanism of TM4SF1 and DDR1.

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