【Abstract】 Objective To investigate the protective role of recombinant human growth hormone (rhGH )in ischemic reperfusion injury of rat liver and its mechanism. Methods One hundred Male rats were randomly divided into two groups: the rhGH group and the control group. In the rhGH group, rhGH were injected （0.2U/100g weight） to rats seven days before the ischemic reperfusion injury, and in the control group, normal saline was injected instead. Serum levels of ALT， TNF-α and IL-1α were tested. Hepatic tissue was sectioned for to detect the level of EC and MDA, the expression of NF-κB and ICAM-1 mRNA on SEC. Ultrastructural characteristics histopathological characteristics were determined also. Results Serum levels of ALT, TNF-α, IL-1α and the contents of MDA in the control group were significantly higher than those in the rhGH group （P＜0.05）. Comparied with control group, rhGH also decreased NF-κB activation, and reduced the expression of ICAM-1 mRNA of SEC in the liver cells （P＜0.05）. Electronic microscopic revealed that the hepatic sinusoidal endothelial cells and the hepatocellular mitochondria were injured in the control group. Pretreatment with the rhGH was able to significantly improved the pathological changes. Conclusion rhGH might confer the protection to ischemic reperfusion injury of rat liver through reducing the expression of NF-κB to down-regulate cytokine (IL-1α,TNF-α), MDA and inhibition the expression of ICAM-1 mRNA.
Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (Plt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (Plt;0.05), but not to gender, age, or lymph node metastasis (Pgt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (Pgt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (Plt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.
ObjectiveTo investigate the effects of naringenin on the production of chemokines and its mechanism in human bronchial epithelial (HBE) cells. MethodsHBE cells were divided into a control group, a TNF-αgroup, a low-dose naringenin group, a moderate-dose naringenin group and a high-dose naringenin group. The Naringenin groups were incubated with different doses of naringenin (10, 5 and 2.5μmol/L, respectively) for 2 h. Then the naringenin groups and the TNF-αgroup were incubated with TNF-α. After 24 h of incubation, the levels of eotaxin and RANTES were determined by ELISA method, and IκBαdegradtion was detected by Western blot method. After incubated with TNF-αfor 30 min, NF-κB DNA-binding activity was detected by EMSA method. ResultsCompared with the control group, the levels of eotaxin and RANTES were significantly increased in the HBE cells stimulated with TNF-α. Naringenin had inhibitory effects on the expression of these chemokines. Naringenin abolished IκBαdegradation and reduced the DNA-binding activity of NF-κB. ConclusionNaringenin may inhibit the production of chemokines through inhibiting NF-κB pathway.
OBJECTIVE: To review the role of thyroid hormone in the peripheral nerve regeneration. METHODS: The recent literatures of experimental study and clinical application on the role of thyroid hormone in nerve regeneration were reviewed. The researches on expression, isoform and changes of thyroid hormones in rat sciatic nerve in normal or injury were summarized. The effect of thyroid hormone on local rat sciatic nerve was studied, too. RESULTS: Nuclear thyroid hormone receptors expressed in numerous nuclei of sciatic nerve during a limited period of development extending from the third week of embryonic life to the end of the second postnatal week and after injury of adult sciatic nerve. A single and local administration of thyroid hormone at the level of the transected sciatic nerve produced a lasting effect on peripheral nerve regeneration. CONCLUSION: The beneficial effects of thyroid hormones upon injured peripheral nerve may have considerable therapeutic potential.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
Mutations in optic atrophy (OPA) genes can lead to a similar phenotype, namely optic atrophy, which can manifest as isolated optic atrophy or be accompanied by other systemic symptoms, mostly related to the nervous system. Currently, a total of 13 OPA genes have been discovered, covering a variety of inheritance patterns, including chromosomal dominant inheritance, autosomal recessive inheritance, and X-linked inheritance. Through genetic testing and analysis of patients, it is possible to accurately determine whether they carry mutation genes related to optic atrophy, and predict the progression of the disease and potential complications accordingly. This not only provides valuable genetic counseling and fertility planning guidance for patients and their families, but also helps better understand the disease, discover new therapeutic targets, and lay the foundation for developing more precise and effective drugs or gene therapies in the future.
ObjectiveTo explore the relationship between nuclear factor κB (NFκB) and the occurrence, metastasis, and treatment of colon cancer. MethodsThe literature on the structure and the property of molecular biology of NFκB, the relationship between NFκB and apopotosis, malignant tumor and colon cancer were reviewed.ResultsNFκB had action of antiapopotosis. The occurrence of malignant tumor had close relation with the oncogene by NFκB, the metastasis of malignant tumor was that cell of cancer escaped the killing and supervising of immunity by NFκB. NFκB affected the occurrence and metastasis of colon cancer by regulating cmyc, Cox2, ICAM1.Conclusion NFκB has important action in the occurrence and metastasis of colon cancer. It will become a new target of treatment.
Objective The usefulness of measurement of nuclear DNA content elevation for diagnosis of early hepatocellular carcinoma was evaluated by a study of 186 patients with liver cirrhosis. Methods Nuclear DNA content was measured using an automatic image analysis system.Results ①Hepatocellular carcinoma was found in 37 patients during 10 years follow-up, the cumulative incidence of hepatocellular carcinoma was 19.89%. ②The incidence of hepatocellular carcinoma increased with the increase of the patterns of α-fetoprotein (AFP), 5c exceeding rate (5cER), FORM PE, but positive predictive value of 5cER was the highest of three parameters, the difference among all groups was significant by the χ2 test (Ｐ＜0.05). ③When 5cER joined AFP for monitoring development of hepatocellular carcinoma, the incidence of hepatocellular carcinoma was 72.00%, which was significantly higher than that of 5cER or AFP alone, the difference between groups was highly significant (Ｐ＜0.01). Conclusion Patients who had 5cER levels of 3%-5% or more, who had transient increases in 5cER or who had both, should be treated as being in a super-highrisk group for hepatocellular carcinoma. Frequent and careful examination by ultrasonography of such patients is recommended. It is important that measurement of 5cER join with AFP in cirrhotic patients monitored for early development of hepatocellular carcinoma.
Objective To summarize the role of nuclear factor kappa B (NF-κB) in the occurrence and progression of various sorts of liver injury. Methods Literatures on the structures, property of molecular biology and function of NF-κB, as well as its relationships with liver injury were collected and reviewed. Results NF-κB was an important nuclear factor existed in cells widely distributed in most cell types. The activation of NF-κB was induced by various sorts of liver injury. The activated NF-κB could affect the liver injury by regulating cytokines, adhesion molecules, and activating factor involving in immunologic reaction， inflammatory reaction and the apoptosis. Conclusion NF-κB plays an important role during the occurrence and progression of liver injury， and may become a new target in the treatment of liver injury.