ObjectiveTo investigate the effect of Huaier extract on the proliferation, invasion, and ferroptosis pathways of colorectal cancer (CRC) cells. MethodsThe CRC cell line SW620 was cultured in vitro, and the cells were treated with Huaier extract solution at different concentrations (0, 5, 10, 20, and 50 mg/mL). The cell counting kit 8 was used to detect the proliferation of CRC cells at different concentrations to scree the test dose of the Huaier extract. The Transwell and the scratch assays were used to detect the cell invasion and migration. The reactive oxygen species (ROS), glutathione (GSH), and malondialdehyde (MDA) kits were used to detect the cellular oxidative stress level. The Western blot was used to detect the ferroptosis-related proteins levels, including glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (NRF2), and high mobility group box-1 (HMGB1). ResultsIn this study, it could statistically inhibit the proliferation of CRC cells after 48 h interfering with Huaier extract at 10, 20 mg/mL concentrations, so we chose 10, 20 mg/mL concentrations as the test dose, 0 mg/L as the control dose. Huaier extract effectively inhibited the migration and invasion abilities of SW620 cells in a dose-dependent manner (Transwell: F=480.0, P<0.001; scratch assay: F=24.3, P=0.001). The level of ROS in the SW620 cells increased with the increase of concentration in a dose-dependent manner (F=806.3, P<0.001). the level of GSH in the SW620 cells decreased with the increase of concentration in a dose-dependent manner (F=35.0, P=0.005), but the level of MDA was highest at 10 mg/mL (F=22.9, P=0.002) . Further the Huaier extract could effectively reduce the expressions of GPX4 (F=74.2, P<0.001), NRF2 (F=32.8, P=0.001), and HMGB1 (F=55.1, P<0.001) in a dose-dependent manner. ConclusionFrom the results of this study, Huaier extract at 10 and 20 mg/mL concentrations can inhibit the proliferation and invasion of CRC SW620 cells by inducing ferroptosis.
Objective To understand the research progress and future prospects of the growth arrest specific protein 6/Axl receptor tyrosine kinase (Gas6/Axl) signaling pathway in gastrointestinal malignant tumors. Method Retrieve relevant literature on the Gas6/Axl signaling pathway in gastrointestinal malignant tumors and analyze and summarize. Results The Gas6/Axl signaling pathway was abnormally upregulated and activated in gastrointestinal malignancies, leading to malignant cell proliferation, invasion, and metastasis, thereby promoting the occurrence and development of gastrointestinal malignancies. At present, in the field of gastrointestinal cancer, the research of Gas6/Axl signaling pathway mainly involved tumor angiogenesis, tumor drug resistance, mesenchymal epithelial transformation, and tumor microenvironment. Conclusions The Gas6/Axl signaling pathway plays a critical role in governing various cellular processes and downstream effects. Its aberrant expression contributes to the development and advancement of gastrointestinal malignancies through diverse mechanisms. Thoroughly exploring the involvement of the Gas6/Axl signaling pathway in gastrointestinal tumors is of utmost significance, as it holds the potential to unveil novel therapeutic targets for effective management of gastrointestinal malignancies.
ObjectiveTo understand the relation between blood glucose regulating hormones and gastric cancer, so as to provide some new ideas for diagnosis and treatment of gastric cancer. MethodBy reviewing and screening relevant domestic and foreign literatures, the latest researches on the relation between blood glucose regulating hormones and gastric cancer were summarized. ResultsThe insulin, glucagon, adrenaline, growth hormone, and the other blood glucose regulating hormones all played the roles in promoting the occurrence and development of gastric cancer. However, glucocorticoids and somatostatin were protective hormones that maintained gastric homeostasis and inhibited the proliferation of gastric cancer cells. ConclusionBlood glucose regulating hormones play some roles in diagnosis and treatment of gastric cancer, but specific mechanisms such as interaction between blood glucose regulating hormones, role of glucose metabolism in biological behavior of gastric cancer, and effect of blood glucose regulating hormones on oncogene initiation are unclear, so prospective clinical control studies still need to be studied.
ObjectiveTo explore the change of expression of oxygen-regulated protein 150 (ORP150) in pancreatic injury of rats with severe acute pancreatitis. MethodsForty male Wistar rats were randomly allocated into two groups: sham operation group (SO group， n=10) and severe acute pancreatitis model group （SAP group， 3 h, 6 h， and 12 h after modeling, each time n=10）. SO group rats were only turned over the pancreas, and the SAP group rats were induced by retrogradely infusing 5% sodium taurocholate into the biliopancreatic duct. SO group rats were killed at 12 h after sham operation, and the SAP group rats were killed at 3 h, 6 h, and 12 h after modeling. Blood samples were obtained for detecting the amylase (AMY) and alanine transarninase (ALT) levels. The quantity of ascites were collected and measured. Pancreatic tissue samples were stained with hematoxylin and eosin for histopathological evaluation. Pancreatic tissue was collected to detect the expressive quantity of ORP150 mRNA by RT-PCR. ResultsThe quantity of ascites, AMY and ALT levels, and histopathological evaluation were significantly higher in SAP group than those in SO group (Plt;0.05). AMY and ALT levels, histopathological detection, and expression of ORP150 mRNA in pancreatic rats among 3 h, 6 h, and 12 h after modeling were significantly different from each other (Plt;0.05), except for ascites. The ascites were not significantly different between 3 h and 6 h after modeling (Pgt;0.05), while 12 h were significantly higher than those at 3 h and 6 h (Plt;0.05). The expression of ORP150 mRNA was low in SO group, and were rise in subgroup SAP 12 h, 6 h, and 3 h gradually. Subgroup was statistical difference (Plt;0.05). ConclusionThe expressive quantity of ORP150 mRNA is high in pancreatic tissues with SAP rats, prompting that ORP150 may play a role in pancreatic injury with SAP.
Objective Observing the expressions of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） mRNA in lung tissues of rats with acute necrotizing pancreatitis （ANP） to explore the role of NOS in ANP associated-lung injury. Methods Forty Wistar rats were assigned into ANP group (n=30) and sham-operation group (SO group, n=10). ANP model was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Pathological changes of the lung tissue were observed under light microscope at 3 h, 6 h and 12 h after the ANP-model operation, and the expressions of iNOS mRNA and eNOS mRNA in lung tissue were assayed by RT-PCR. Results Different degrees of pathological changes of the lung tissue, such as hyperemia, edema, inflammatory cells infiltration, hemorrhage and necrosis, were found in the ANP group. The pathologic injury scores of lung tissue in ANP group were higher than that in SO group (Plt;0.05), and gradually increased with the duration extension of ANP (Plt;0.05). Compared with the SO group, the expressions of iNOS and eNOS mRNA in ANP group were all higher at 3 h, 6 h, and 12 h (Plt;0.05). Conclusions The overexpressions of iNOS and eNOS mRNA may play important roles in lung injury of ANP. This provides us a theory basis that lung injury of ANP could be relieved by inhibiting the expressions of iNOS and eNOS mRNA.
目的 探讨聚腺苷二磷酸核糖聚合酶-1（poly ADPribose polymerase-1,PARP-1） mRNA在重症急性胰腺炎(severe acute pancreatitis，SAP)大鼠肾脏中的表达及意义。方法 48只Wistar大鼠按随机数字表法分为SAP组和假手术组(SO)组，分别于造模术后1、3、6及12 h测定血清肌酐，观察胰腺和肾脏组织病理变化，并以RT-PCR法检测PARP-1 mRNA在肾脏中的表达水平。结果 SAP组大鼠术后血清肌酐逐渐升高，于3、6及12 h明显高于SO组(Plt;0.05)。SAP组大鼠术后胰腺出现腺体破坏、腺泡坏死、出血、炎性细胞浸润等病理损害，且呈进行性加重； SO组各时相胰腺组织基本正常。SAP组大鼠术后出现肾小管上皮细胞变性、坏死、肾小球瘀血、缺血等改变，并随时间延长逐渐加重，其损伤程度在3、6及12 h明显较SO组严重(Plt;0.05)。SO组大鼠肾脏组织仅表达少量PARP-1 mRNA，而SAP组大鼠随病程延长肾脏组织中PARP-1 mRNA表达逐渐增加，自3 h时起明显高于SO组（Plt;0.01）。结论 在SAP发病过程中，PARP-1 mRNA的表达在肾脏组织中逐渐增加，PARP-1可能参与了SAP相关肾损伤过程。
ObjectiveTo investigate the possible protective effect of zerumbone on pancreatic injury in severe acute pancreatitis (SAP) rats, and to provide a theoretical basis for prevention and treatmen of severe acute pancreatitis. MethodsSeventy male Wistar rats were randomly divided into four groups:normal control group (NC group, n=10), SAP group (n=40), Zerumbone pretreatment group (ZER group, n=10), and Zerumbone drug control group (ZER-CON group, n=10). Rats of SAP group were divided into four time points of 1 h, 3 h, 6 h, and 12 h (n=10 each time point). SAP models were induced by retrograde injection of 5% sodium taurocholate (0.1 mL/100 g) in biliopancreatic duct in SAP group and ZER group. Rats were injected isotonic saline solution instead of taurocholate as a control in NC group and ZER-CON group. Zerumbone solution (10 mg/kg) was administered via femoral vein half an hour prior to establishing models in ZER group and ZER-CON group. All rats except SAP group were sacrificed at 12 h time point after the induction of SAP. The rats in SAP group were sacrificed at 1 h, 1 h, 3 h, 6 h and 12 h time point after induction of SAP. The mortality, ascites, serum amylase (AMY), phospholipase, and pathological examination of pancreas were observated or detected. The expression of nuclear factor-kappa B (NF-κB) p65 in pancreatic tissues was evaluated by immunohistochemistry assay. ResultsThere were no difference of the levels of mortality, ascites, serum AMY, phospholipase, pathological examination, and NF-κB p65 location expression of pancreas between the ZER-CON group and NC group (P>0.05). The above indexes in SAP group were significantly higher than those in NC group (P<0.05). However, those in ZER group were significantly lower than in SAP group (P<0.05), and higher than in NC group (P<0.05). ConclusionsZerumbone can reduce the mortality and ascites, effectively alleviate the enzyme, pathological injury, and NF-κB p65 location expression in pancreatic tissue following SAP. It may indicate that zerumbone can protect pancreatic injury in SAP via NF-κB pathway.
ObjectiveTo study the effects of ATP citrate lyase (ACLY) gene on proliferation, apoptosis, invasion, and lipid metabolism of colon cancer cells.MethodsColon cancer cells HCT116 were transfected with lentiviral knockdown ACLY gene in vitro and divided into three groups according to cell treatment: HCT116 cells with ACLY gene knockdown as knockdown group, empty vector transfected cells as negative control group, and untreated colon cancer HCT116 cells as blank control group. After the stable new cell line was screened with puromycin, the expression of ACLY protein was detected by Western blot method, the lipid production of cells was detected by triglyceride test kit, the proliferation ability of cells was detected by CCK-8 method, the apoptosis rate was detected by flow cytometry, and the migration ability of cells was detected by cell scratch test.ResultsThe cell survival rate of the knockdown group was lower than those of the blank control group and the negative control group at 120 h, but there was no significant difference among the three groups at 24 h and 48 h. Compared with the negative control group and the blank control group, the apoptosis rate in the knockdown group increased, the 24 h migration ability and the level of intracellular triglyceride decreased.ConclusionACLY gene knockdown can inhibit the proliferation, apoptosis, and migration of colon cancer cells, and its mechanism may be related to the decrease of lipid synthesis ability of colon cancer cells.
ObjectiveTo investigate the protective effect of exogenous insulin on relative adrenal insufficiency (RAI) in rats with severe acute pancreatitis (SAP).MethodsEighty SPF SD rats were randomly divided into 5 groups (n=16): sham operation (SO) group, SAP group, low-dose insulin intervention (low-dose) group (0.05 U/100 g body weight), medium-dose insulin intervention (medium-dose) group (0.1 U/100 g body weight), and high-dose insulin intervention (high-dose) group (0.2 U/100 g body weight). The five groups were randomly divided into two subgroups: cosyntropin stimulation test (CST) subgroup and non-CST subgroup. SAP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. The rats were sacrificed 3 hours after the establishment of SAP model. The levels of amylase (AMY), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Ur) and creatinine (Cr) were detected by automatic biochemical analyzer. The serum levels of tumor necrosis factor-α (TNF-α) and corticosterone (Cor) were detected by ELISA kit. The pathological changes of pancreas and adrenal gland were observed under light microscope. The lipid content of adrenal gland was observed by oil red O staining.ResultsCompared with the SO group, the serum levels of Amy, ALT, AST, Ur, Cr, TNF-α and Cor in the SAP group were significantly increased (P<0.05), typical pathological damages occurred in pancreas and adrenal gland, and pathological scores were significantly increased (P<0.05). Compared with the SAP group, the levels of AMY, ALT, AST, Ur, Cr, TNF-α and Cor in the low-dose group were not significantly changed (P>0.05); the levels of AMY, ALT, AST, Ur, Cr and TNF-α in the medium-dose group and the high-dose group were significantly decreased (P<0.05), and Cor levels were significantly increased (P<0.05). Compared with the low-dose group, AMY, ALT, AST, Cr, TNF-α in the medium-dose group and the high-dose group were significantly decreased (P<0.05), Cor level were significantly increased (P<0.05), Ur level had no significant change. There were no significant difference in AMY, ALT, AST, Ur, Cr, TNF-α and Cor levels between the medium-dose group and the high-dose group (P>0.05). After CST intervention, there were no significant change in serum Cor levels in the SAP group and the low-dose group (P>0.05), but the serum Cor levels in the SO group, the medium-dose group and the high-dose group were significantly increased (P<0.05).ConclusionAppropriate dose of exogenous insulin can improve SAP related adrenal injury and RAI, but the specific mechanism still needs further study.
Objective To investigate the protective effect of 4-phenylbutyric acid (PBA) on liver injury induced by severe acute pancreatitis (SAP) in rats and its possible mechanism. Methods Twenty-four SPF adult male Sprague Dawley rats were randomly divided into three groups: shame operation group (SO group,n=8), SAP group (n=8), and PBA group (n=8). SAP model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) in biliopancreatic duct in SAP group and PBA group. PBA solution (50 mg/kg) was administeredvia intraperitoneal injection for 3 days prior to establishing models in PBA group. Rats were injected equivalent saline solution instead of PBA solution in SAP group and SO group. All rats were sacrificed at 12 h after modeling. Blood samples were collected by inferior vena cava puncture, and serum levels of amylase (AMY), alanine aminotransferase (ALT), and aspartate transaminase (AST) were measured using a fully automatic chemistry analyzer. The head of pancreas and right lobe of hepatic tissues were harvested and pathological examination was observed under the light microscope. Expressions of glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and Caspase-3 in hepatic tissues were evaluated by immunohistochemistry assay. Results Compared with SO group, the serum levels of AMY, ALT and AST were significantly increased in SAP group (P＜0.05). The serum levels of ALT and AST in PBA group were significantly lower than those in SAP group (P＜0.05). There was no difference of the serum levels of AMY between in PBA group and SAP group (P＞0.05). Compared with SO group, the damages of the pancreas and liver tissues and the expressions of GRP78, CHOP and Caspase-3 in hepatic tissues were significantly increased in SAP group (P＜0.05). And the above indices in PBA group were significantly decreased when compared with SAP group. Conclusions PBA can alleviate severe acute pancreatitis-induced liver injury, and the mechanism may be associated with inhibition of endoplasmic reticulum stress (ERS) and reduction of hepatocyte apoptosis.