Effect of different therapies of Chinese medicine on the expressions of c-Fos and c-Jun proteins in hippocampus of rats with post-stroke depression

BACKGROUND ： c-fos and c-jun, the important immediate early genes （IEG）, are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression. OBJECTIVE： To observe the therapeutic effects of Bushen Yiqi （tonifying kidney to benefit qi）, Huoxue Huayu （promoting blood circulation to dissipate blood stasis） and Ditan Kaiqiao （eliminating phlegm for resuscitation） on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression （PSD）, and compare the results with those of fluoxetine, which is known to have definite effect on depression. DESIGN： A randomized controlled tna SETTING ： Zhejiang College of Traditional Chinese Medicine MATERIALS ： The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing （250±50） g, were randomly divided into 7 groups with 8 rats in each group： control group, model group, forced swimming group, Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang contained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Ditan Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/b METHODS： ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid artedes permanently. ② Rats in the control group, model group and forced swimming group were intragastncally perfused by saline （3 mL for each time）; those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group were intragastncally perfused with Bushen Yiqi Tang （18 g/kg）, Huoxue Huayu Tang （9 g/kg）, Ditan Kaiqiao Tang （9 g/kg） and fluoxetine （2.5 mg/kg） respectively, once a day. ③ At 55 days after model establishment, rats in the forced swimming group were managed according to the Porsolt＇s method. They were placed in water for 15 minutes, and then taken out and dned, no moving-time within 5 minutes was recorded at drying and 24 hours after drying. ④ Measurement of spontaneous behaviors： Except the forced swimming group, the spontaneous behaviors and activities （including horizontal and vertical movements） of rats were observed with the Open-Field method at 28, 42 and 56 days after administration in the other groups. ⑤ The expressions of c-Fos and coJun proteins in hippocampus were determined with the immunohistochemical method, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hip- pocampus were measured with the computerized image analytical system. MAIN OUTCOME MEASURES： The spontaneous behaviors of rats, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hippocampus were observed. RESULTS： Of the 56 rats, 1 died in the forced swimming group, and finally 55 rats were involved in the analysis of results. ① Results of spontaneous activities： At 28 days, the times of crossing movements were obviously fewer in the model group and fluoxetine group [（69.00±37.01）, （98.11 ±36.68） times/3 minutes] than in the control group [（128.44±16.85） times/3 minutes, P 〈 0.01, 0.05], but those in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group had no obvious differences as compared with those in the control group （P 〉 0.05）. At 42 and 56 days, the times of crossing movements were obviously more in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group [（106.44±31.24）, （117.20±23.95）, （134.80±28.18）, （136.36±40.95） times/3 minutes; （117.33±35.91）, （129.60 ±23.78）, （131.90 ±26.81）, （136.09±28.34） times/3 minutes] than in the model group [（64.00±17.51）, （72.86±20.68） times/3 minutes, P 〈 0.01]. The times of rearing movements had no obvious differences among the groups for the three times （P 〉 0.05）. ② The no moving-time within 5 minutes 24 hours after drying was obviously longer than that at drying in the forced swimming group. ③ The average objective gray values of c-Fos positive cells were not obviously different in the Bushen Yiqi group and Ditan Kaiqiao group from the control group （P 〉 0.05）, but lower in the model group than in the control group （69.84±9.82, 75.78±5.89, P 〈 0.01）, and higher in the forced swimming group than in the control group （85.97±10.99, P 〈 0.01）; all higher in the fluoxetine group, Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group （81.27±10.73, 74.04±8.34, 83.29±9.89, 70.14±4.92, P 〈 0.05-0.01）. The average objective gray values of c-Jun positive cells were obviously lower in the Bushen Yiqi group than in the control group （68.11 ±6.89, 79.58±5.86, P 〈 0.01）, but all higher in the other groups than in the control group （84.68±7.15, 81.34 ±8.36, 97.51±10.55, 85.68±9.25, 86.19±10.98, P 〈 0.05-0.01）; Those were obviously higher in the fluoxetine group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group （P 〈 0.05-0.01 ）, lower in the Bushen Yiqi group than in the model group （P 〈 0.05）, all obviously lower in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the fluoxetine group （P 〈 0.01）. The relative sectional area ratios of c-Fos and c-Jun positive cells had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： The methods of Bushen Yiqi, Huoxue Quyu and Ditan Kaiqiao can effectively treat PSD in rats, and the results were equivalent with those of fluoxetine, the actions of the above-mentioned drugs may correlated with their regulation to c-Fos and c-Jun expressions in hippocampus. PSD animal models can be successfully established by both permanent deligation of bilateral common carotid arteries and forced swimming, and the models induced by the former has similar basic cerebrovascular lesions as human stroke in clinic.

Effects of acute and chronic administration of MK-801 on c-Fos protein expression in mice brain regions implicated in schizophrenia and antagonistic action of clozapine

Objective To investigate the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice and an-tagonistic action of clozapine.Methods Immunohistochemistry was used to detect the expression of c-Fos protein.Results MK-801(0.6 mg·kg-1)acute administration produced a significant increase in the expression of c-Fos protein in the layers Ⅲ-Ⅳ of posterior cingulate and retrosplenial(PC/RS)cortex,which was consistent with the previous reports.Moreover,we presented a new finding that MK-801(0.6 mg·kg-1)chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex,prefrontal cortex(PFC)and hypothalamus of mice.Among that,c-Fos protein expression in the PC/RS cortex of mice was most significant.Compared acute administration with chronic administration,we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex,PFC and hypothalamus.Furthermore,pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration.Conclusions Marked expression of c-Fos protein induced by MK-801 is associated with neurotransmitters' change noted in our previous studies,and c-Fos protein,the marker of neuronal activation,might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist.

Expression of c-Fos protein and nitricoxide synthase in neurons of cerebral cortex from fetal rats in hypoxia and protective role of Angelica sinensis

BACKGROUND： Both c-Fos protein and nitricoxide synthase （NOS） have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE： To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN： Randomized control experiment.SETTING ： Department of Histology and Embryology, Luzhou Medical College.MATERIALS ： Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University （batch number： 01062310）. METHODS ： This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ①Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8： 00 am next day. On the 15^th conceiving day, all conceiving rats were divided randomly into three groups： control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group： Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group： Rats were injected with the same volume of saline. Control group： Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance （ANOVA） followed by q test. MAIN OUTCOME MEASURES： ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS：① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group （76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35±6.67, P 〈 0.05）, but those in Angelica group were less than those in hypoxia group （51.70±9.82, 35.65±8.37, P 〈 0.05）. CONCLUSION： Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.

大鼠癫痫持续状态血清C反应蛋白与海马C-FOS蛋白表达的动态观察

C反应蛋白（c-reactive protein,CRP）是体内非特异性炎症反应的敏感标志物之一,正常血清CRP浓度很低,当机体出现炎症或组织损伤时,其浓度可以在数小时内明显升高。尽管许多实验证实CRP与脑卒中、动脉粥样硬化等疾病明显相关,目前尚没有CRP与癫痫关系的正式文献报道。随着对癫痫发生机制的研究，发现癫痫为一种免疫相关性疾病，其发生发展与细胞因子更有着密切关联，以往研究发现在癫痫发生过程中具备cRP产生的相关细胞因子。

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

Expression of c-erbB-2 oncogene protein, epidermal growth factor receptor, and TGF-β1 in human pancreatic ductal adenocarcinoma

Objective: To detect the relations of c-erbB-2 onco-gene protein, epidermal growth factor receptor (EG-FR) and transforming growth factor-β1 (TGF-β1)to the progression or metastasis of pancreatic carci-noma.Methods: Using streptavidinbiotin complex (SABC)method, c-erbB-2 oncongene protein, we examinedimmunohistochemically EGFR and TGF-β1 expres-sions in wax-tissue sections from 10 individuals withnormal pancreas (NP), 13 patients with chronic pan-creatitis (CP) and 36 patients with pancreatic ductaladenocarcinoma (PC).Results: The positive expression rates of c-cerbB-2oncogene protein, EGFR and TGF-β1 in the NP, CPand PC groups were 0, 0, 10%; 7.7%, 7.7%,7.7%; and 41.7%, 50.0%, 44.4%, respectively.The positive expression rates of the three specific pro-teins increased more significantly in the PC groupthan in the NP and CP groups (P【0.05). The indi-vidual expression of c-erbB-2, EGFR and TGF-β1was not related to the age and sex of the patients aswell as the site, size and histopathological grade oftumors (P】0.05), but to the clinical stage of tumors(P【0.01). The coexpression rate of the three pro-teins was 27.8 % (10/36). This coexpression in thePC group was correlated with the histopathologicalgrades and clinical stages of tumors (P【0.01).Conclusion: Detection of c-erbB-2 oncogene protein,EGFR, and TGF-β1 expressions in pancreatic tissueis helpful to judge the malignancy, progression, andmetastasis of PC.

EXPRESSION AND SIGNIFICANCE OF ONCOPROTEIN p16 AND FOS IN OSTEOSARCOMA

Objective: To investigate p16, C-fos protein expression and their relationships in osteosarcoma. Methods: Immunohistochemical technique (SABC) was used to detect p16 and C-fos protein expression in 41 cases of osteosarcoma. Results: The positive rates of p16 and C-fos protein expression were 51.2% and 82.9% respectively. Their expression was not correlated to pathological subtype, but correlated to clinic grade, and the latter was associated with tumor metastasis. There was a negative correlation between p16 and C-fos protein expression. Conclusion: The alteration of p16 and C-fos protein expression may be related to the tumorigenesis and development of osteosarcoma, and C-fos proteins may take part in osteosarcoma metastasis. These data will offer useful helpness to determine the prognosis of osteosarcoma.

Response of Subcutaneous Xenografts of Endometrial Cancer in Nude Mice to Inhibitors of Phosphatidylinositol 3-Kinase/Akt and Mitogen-Activated Protein Kinase (MAPK) Pathways: An Effective Therapeutic Strategy for Endometrial Cancer

Objective: This study was designed to explore whether inhibition of the extracellular-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways can inhibit the growth of xenografts of endometrial cancer cell lines with different estrogen receptors (ER) profiles in vivo and to provide preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of the two pathways, especially to endometrial cancer with low ER status. Methods: Human endometrial cancer Ishikawa bearing ER and HEC-1Awith low ER status cells were subcutaneously injected into BALB/c nude mice to establish endometrial cancer xenograft tumor models. The effects of PI3K/Akt inhibitor LY294002, MAPK/ERK1/2 inhibitor PD-98059 and their combinations on the growth of the xenograft tumors and apoptotic state of Ishikawa and HEC-1Acells were tested in vivo using the inhibitory rate, the terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, H/E-stain. Western blot analysis was used to detect the alterations of activated ERK (P-ERK) and AKT (P-AKT) during this process. Results: LY294002, a PI3K/Akt pathway inhibitor, induced significant suppression in the growth of both Ishikawa and HEC-1Acell xenograft tumors, concomitant with increased apoptosis in xenografts as evidenced by TUNEL. A similar effect was also observed when the MAPK/ERK1/2 signaling pathway was inhibited by PD98059. Concurrent inhibition of the PI3K/Akt and MAPK/ERK1/2 pathways showed enhanced anti-tumor effects in vivo as indicated by increased apoptosis. At the same time, the levels of P-ERK and P-AKT in both xenograft tumors decreased, and their levels in combination group was the lowest. Conclusions: PD98059, LY294002 and their combinations showed remarkable inhibitory effects on xenograft tumors of endometrial carcinoma cell lines with different expression status of ER in vivo through blockage of PI3K/Akt and MAPK/ERK1/2 signaling pathways. This suggests that targeting these pathways may be an effective therapeutic strategy against endometrial carcinomas, especially for ER-negative cancers which show poor response to endocrinal therapy.

Research on Acupuncture Regulation of Visual Cortex c-Fos Protein Expression in Monocular Deprivation Cats

Objective: To explore the mechanism underlying acupuncture regulation of the visual cortex plasticity. Methods: Eighteen kittens of four weeks were randomly divided into 3 groups, a normal group, a model group and an acupuncture group, with six in each group. There was no treatment to those in the normal group. Unilateral eyelid suture method was used to establish the deprivation amblyopia cat model in the model group and the acupuncture group. After that, kittens in the model group didn't receive any treatment, but those in the acupuncture group were treated with acupuncture therapy of 12 weeks. Pattern Visual Evoked Potential (P-VEP) and c-Fos protein expression of visual cortex of kittens in each group were tested before and after acupuncture treatment. Results: P-VEP waveform changed significantly in kittens of the model group, the time value of P 100 was significantly delayed (P<0.01) and N 45 -P 100 amplitude was significantly lower (P<0.01) compared with the normal group. After treatment, the time value of P 100 in kittens of the acupuncture group was significantly shorter (P<0.01) and N 45 -P 100 amplitude was significantly higher (P<0.01) when compared with the model group. Expression of c-Fos positive neurons can be seen in the visual cortex layers II-IV of kittens in the acupuncture group, and the density and percentage of c-Fos immunoreactive neurons of cortex layers II-IV in kittens of the model group were significantly lower than those in the acupuncture group. Conclusion: Acupuncture has obvious improvement for abnormal changes of P-VEP waveform of monocular visual deprivation kittens; it can also increase the c-Fos protein expression in visual cortex after form- deprived.

Epidermal growth factor receptor and K-Ras in non-small cell lung cancer-molecular pathways involved and targeted therapies

Lung cancer is currently the leading cause of cancer death in Western nations.Non-small cell lung cancer(NSCLC)represents 80%of all lung cancers,and adenocarcinoma is the predominant histological type.Despite the intensive research carried out on this field and therapeutic advances,the overall prognosis of these patients remains unsatisfactory,with a 5-year overall survival rate of less than 15%.Nowadays,pharmacogenetics and pharmacogenomics represent the key to successful treatment.Recent studies suggest the existence of two distinct molecular pathways in the carcinogenesis of lung adenocarcinoma:one associated with smoking and activation of the K-Ras oncogene and the other not associated with smoking and activation of the epidermal growth factor receptor(EGFR).The K-ras mutation is mainly responsible for primary resistance to new molecules which inhibit tyrosine kinase EGFR(erlotinib and gefitinib)and most of the EGFR mutations are responsible for increased tumor sensitivity to these drugs.This article aims to conduct a systematic review of the literature regarding the molecular pathways involving the EGFR,K-Ras and EGFR targeted therapies in NSCLC tumor behavior.

Transretinoic acid inhibits rats gastric epithelial dysplasia induced by N-methyi-N-nitro-N-nitrosoguanidine:influences on cell apoptosis and expression of its regulatory genes

INTRODUCTIONGastric epithelial dysplasia (GED) hypothetically is a straight-forward concept: dysplastic epithelium replacing the normal gastric epithelium of the stomach [1].In the stomach ,like any other segment of the gut ,it is defined as an unequivocal non-invasive epithelial change[2,3].The observation of gastric dysplasia as a cancerous lesion was recognized over a century ago ,but it is only after the advent of gastroscopy that its clinical significance has been stressed[4-7].

Participation of Substance P in Noxious Stimulus-evoked c-fos Expression in Spinal Cord

It was reported that substance P (SP) is an excitatory neurotransmitter released from nociceptive primary afferent nerve terminals,and takes a double-effect part in modulation of pain transmission and analgesia in spinal cord.But

Gastrointestinal tumors in transplantation: Two case reports and review of literature

BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract.As most of them harbor a KIT mutation(75%),selective kinase inhibitors are the therapeutic option and show a sustained objective response among patients with metastatic or unresectable GISTs.A wellknown higher risk of neoplasm has been described among renal transplant recipients(RTRs).Nevertheless,only few cases of GIST onset among transplant patients have been reported in the literature.CASE SUMMARY Here,we describe 2 cases of gastric GIST occurring during the follow-up of RTRs.We also review the existing literature concerning GIST occurrence in transplant patients.In total and in association with our 2 cases,16 patients have been reported.The median age was 59.5 years and 69%were male.With a median tumor size of 45 mm,no patient displayed metastatic dissemination at diagnosis.Time from transplantation to diagnosis was highly variable between 5 mo and 21 years.Histopathological data mostly revealed high risk of progression(43%).Death increased to 29%during follow-up.Surgical treatment was systematically performed when the tumor was operable(94%).The use of adjuvant therapy was uncommon(19%).CONCLUSION GISTs represent rare but potentially severe malignant complication among transplant patients.

Role of NO in the inhibition of formalin-induced hyperalgesia after intraspinal injection of ACTH in rats

Objective: To study the role of nitric oxide (NO) in the inhibition of formalin-induced hyperalgesia aller intraspinal injection of adrenocorticotropic hormone (ATCH) in rats. Methods: NADPH-d histochemistry assay of the spinal cord, immuno-histochemical staining of c-fos protein (fos) and determination of the content of gama-aminobutyric acid (CABA) of ’ the spinal spinal cord tissue were performed Results: lntraspinal injection,of ACTH significantly inhibited the increase of nitrie oxide synthetase (NOS)positive . neurons, fos-positive neurons and the elevation of GABA level in the lumbar seg ment of the spinal cord which could be partially reversed with the adminnistration of 10 μmol L-arginine (Arg)Conclu- sion:The decrease of NO synthesis might play a part in the inhibition of formalin -induced hyperalgesia after intraspinal injec- tion of ACTH

Advances in BRAF gene mutations in papillary thyroid carcinoma

Thyroid cancer is the most common endocrine system tumor.Ultrasound guided fine needle puncture(FNA)can identify benign and malignant thyroid nodules.However,due to the limitation of cytological detection,some thyroid nodules are difficult to distinguish benign and malignant.BRAF gene mutation is a common human oncogenic mutation and the highest mutation frequency in papillary thyroid carcinoma.The combination of FNA and BRAF gene detection can significantly improve the diagnostic rate of benign and malignant thyroid nodules and make up for the deficiency of single diagnosis of cytology.Moreover,while the incidence of thyroid cancer is growing rapidly worldwide,its mortality remains stable.The problem of overdiagnosis and overtreatment of thyroid cancer is becoming more and more obvious.However,due to the limitations of current studies on BRAF genes,its prognostic value for papillary thyroid carcinoma remains controversial.Therefore,in order to reduce the adverse effects of overdiagnosis and treatment,the relationship between gene and tumor biological behavior needs further study in the future.

Efficacy of Ganshuang granules(肝爽颗粒)on non-alcoholic fatty liver and underlying mechanism:a network pharmacology and experimental verification

OBJECTIVE:To investigate the potential pharmacological mechanisms of Ganshuang granules(肝爽颗粒,GSG)in treating non-alcoholic fatty liver(NAFLD).METHODS:All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Protein-Protein interaction network,Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD.Then,the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG.The levels of interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α)and phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot,respectively.RESULTS:Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD.Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD.Further experiments showed that the significantly decreased alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,total cholesterol,triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment,as well as the expression levels of IL-6 and TNF-αin the liver.Furthermore,drug intervention increased the protein expression levels of phosphorylated-PI3K(P-PI3K)and P-AKT in the liver of the model group mice,and decreased the protein expression level of sterol regulatory element-binding protein 1.CONCLUSION:We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.

Mechanism of total glucosides from Chishao(Radix Paeoniae Rubra)on proliferation and apoptosis of hepatocellular carcinoma cells via phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol 3-kinase/protein kinase B signaling pathway

OBJECTIVE:To investigate the possible molecular mechanism of total glycosides of Chishao(Radix Paeoniae Rubra)(TG-RPR)on proliferation and apoptosis of hepatocellular carcinoma cells.METHODS:The proliferation of TG-RPR on Hep G2 cells was detected using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.The apoptosis of Hep G2 cells was measured by annexin V-FITC/double staining.The phosphatase and tensin homolog deleted on chromosome ten(PTEN)/phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(Akt)signaling pathway was evaluated by Western Blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS:TG-RPR can up-regulation the expression of pro-apoptotic factors such as PTEN and BCL2-Associated X(Bax),down-regulation the expression of anti-apoptotic factors including B-cell lymphoma-2(Bcl-2),PI3 K,and Akt.CONCLUSION:TG-RPR significantly inhibits the proliferation of Hep G2 cells in a dose-dependent manner and promotes apoptosis.These results demonstrated TG-RPR has significant inhibitory effect on Hep G2 cells.These results identify a critical role of TG-RPR in proliferation and apoptosis of Hep G2 cells via modulating PTEN/PI3 K/Akt signaling pathway.TG-RPR may offer a promise as a potential pharmaceutical therapy for hepatocellular carcinoma.

肝细胞生长因子／c—met系统与头颈肿瘤

肝细胞生长因子是一种多功能的细胞生长因子，其生物活性由c—met蛋白所介导，肝细胞生长因子通过与原癌基因c-met受体结合激活受体酪氨酸蛋白激酶活性调节细胞的分裂、增殖、分化、迁移等。故肝细胞生长因子／c—met信号传导在肿瘤的侵袭转移中发挥重要作用。人类许多肿瘤的生长、侵袭和转移与肝细胞生长因子／c—met系统密切相关。研究肝细胞生长因子／c-met系统与头颈部肿瘤侵袭、转移的关系，将对头颈肿瘤的诊断、治疗及预后有重要意义。

甲状腺髓样癌研究进展

甲状腺髓样癌（medullary thyroid carcinoma,MTC）来源于分泌降钙素和癌胚抗原的甲状腺滤泡旁细胞（又称C细胞）,且多因RET基因突变引发.它属于甲状腺癌中恶性程度较高的一类,预后相对较差.本文重点综述了近年来甲状腺髓样癌基础分子生物学研究、诊断、影像学检查及治疗方面的进展.

Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancer SiHa cells induced by arsenic trioxide

OBJECTIVE: To study the biological effect of arsenic trioxide (As2O3) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. METHODS: SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were established by transfecting SiHa cells with Bcl-2 expression vector. The sensitivities of SiHa and SiHa-Bcl2 cells to As2O3 were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. RESULTS: As2O3 inhibited the growth of SiHa cells and induced G2/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-Bcl2 cells partly resisted As2O3 induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c-myc gene expression. Nevertheless, As2O3 at a high concentration could still induce apoptosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightly inhibiting viral gene expression. CONCLUSION: As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As2O3 induced apoptosis, but the exact mechanism is unclear.