Autophagy is a cellular catabolic pathway that is essential for survival,differentiation,development and homeostasis.The dual roles of autophagy as a tumor-promoting mechanism and a tumor suppressor mechanism have been elucidated in the recent cancer research.The double function is accomplished by some neoplasms-associated signaling pathways which include mTOR-dependent signaling pathway,Beclin1 network,LKB1-AMPK signaling pathway,p53 and p53-related regulators of autophagy.Thus it can be seen that these signaling pathways function dependently and correlatively as inducing and inhibiting autophagy and play different roles in the process that involves growth and development of neoplasms.

Background Perineural invasion is an important biological character for adenoid cystic carcinoma (ACC) of lacrimal gland,which is different from those of other lacrimal gland tumors.As the important part of neurotrophic factors,glial-derived neurotrophic factor (GDNF) plays an important role in perineural invasion for ACC of salivary gland.GDNF regulation in the ACC cell biology function needs to be further explored.Objective This study was to investigate the effect of GDNF on proliferation and migration of ACC cells,and to explore the mechanism of neural invasion in ACC of lacrimal gland.Methods ACC-2 cell line was cultured and passaged in RPMI 1640 medium with 10％ fetal bovine serum,100 U/ml penicillin and 0.1 g/L streptomycin.Single-cell suspension was prepared with the density of 2×104/ml using logarithmic phase of cells and then incubated to 96-well plate.GDNF with the final concentration of 20,60,80,100 and 120 μg/L was added into the medium respectively in the experimental groups,and the cells were cultured in the medium without GDNF as the control group.The expression of GDNF in ACC-2 cells was detected by immunohistochemistry.MTT assay was employed to assay the absorbance value at the wavelength of 570 nm (A570) for the evaluation of proliferation of ACC-2 cells after cultured by different concentrations of GDNF for different time points.Meanwhile,transwell chamber was used to examine the cell migrated number.Results Immunochemistry assay exhibited that ACC-2 cells showed the positive response for GDNF with the brown staining in the cytoplasm.In 48 hours after culture,the A570 value was elevated with the increase of GDNF concentration,showing a significant difference among various groups (F =3.336,P =0.026),and the A570 value in various concentrations of GDNF groups was higher than that of 0 μg/L GDNF group (all P＜0.05).After action of 80 μg/L GDNF,the A570 value of the cells was gradually increased with the prolong of culture time (Ftime =39.979,P=0.000).In 30 minutes after GDNF cultured,the number of migrated cells increased with the increase of GDNF concentration (F=144.886,P=0.000).ACC-2 cells were cultured by 100 μg/L GDNF for 24,30 and 40 hours,the number of migrated cells were more as the time lapse,and more migrated cells were seen in GDNF group at various time points (Ftime =46.747,P =0.000 ; Fgroup =63.786,P =0.000).Conclusions GDNF can stimulate the proliferation and migration of ACC-2 cells in a dose-and time-dependent manner.

Aging ; psychology ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Wistar

Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Prognosis ; Staphylococcal Scalded Skin Syndrome ; diagnosis ; drug therapy

Glioma is the most common form of brain cancer. Despite recent advances in the treatment of solid tumors, there are few effective treatments for malignant gliomas due to its infiltrative nature. It has important significance to improve the treatment of glioma through in-depth understanding the intracerebral metabolic characteristics and pharmacokinetics of chemotherapeutics. Brain microdialysis (B-MD), an effective method to monitor central nervous system anticancer drug disposition, conditions of drugs through the blood-brain barrier, basic pathophysiologic metabolism, bioactive compounds and the changes of neurotransmitter in brain, provides the unique opportunity to allow the simultaneous determination of unbound concentrations of drugs in several tissues, and directly measure gliomas biochemistry continuously. B-MD has been able to monitor the change of brain drugs, metabolites and neurotransmitters, dynamic analysis of the drug concentration and pharmacological effect after administration, pharmacodynamic interaction between drugs, receptor mechanism of drug transport, as well as feedback information of internal environment. B-MD is expected to provide reference for clinical individual chemotherapy of glioma, but also provide powerful tools for the evaluation of new anticancer drugs in vivo. In this review, a comprehensive overview of B-MD for studies on glioma is elucidated with special emphasis on its application to neurochemistry and pharmacokinetic studies.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Blood-Brain Barrier ; Brain Neoplasms ; metabolism ; Glioma ; metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Metabolomics ; methods ; Microdialysis ; methods ; Neurotransmitter Agents ; pharmacokinetics ; Pharmaceutical Preparations ; metabolism ; Positron-Emission Tomography

Angiotensin II ; pharmacology ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Humans ; Myocytes, Smooth Muscle ; cytology ; Pulmonary Artery ; cytology

Acute Disease ; Asthma ; drug therapy ; Bronchodilator Agents ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infusions, Intravenous ; Male ; Theophylline ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

ObjectiveTo observe the clinical effect of sodium aescinate in the treatment of patients with stage Ⅰ - Ⅱ internal hemorrhoids.Methods177 patients with stage Ⅰ - Ⅱ internal hemorrhoids were randomly divided into two groups,the treated group( n =87 ) and the control group( n =90).Patients in the control group were treated with external hemorrhoids suppositories ( 1 per time,bid),while patients in the treated group took sodium aescinate orally(2 per time,Bid).After the 7-day course of treatment,the efficacy of sodium aescinate was determined.ResultsThere was significant difference between the two groups in the total obvious effective rate and the total effective rate(P ＜0.01 ).Compared with the control group,the symptoms of hematochezia and anal pain were more improved in the treated group( P ＜ 0.01 ).There was significant difference between the two groups in the hemorrhoidal mucosa,prolapse,the size of hemorrhoids and total score difference ( P ＜ 0.05 ).The total obvious effective rate and the total effective rate of the treated group were 87.4％ and 95.4％.ConclusionSodium aescinate had better clinical effect in the treatment of patients with stage Ⅰ - Ⅱ internal hemorrhoids.

ObjectiveTo investigate the changes and values of serum high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin I (cTnI) in patients with chronic heart failure.MethodsEighty patients with chronic heart failure (heart failure group) were divided into NYHA heart function Ⅲ grade ( 40 patients) and Ⅳ grade (40 patients).Eighty healthy people were included in control group.The levels of serum hs-CRP and cTnI were measured and compared.ResultsBefore treatment,the levels of hs-CRP and cTnI in heart failure group [ ( 11.56 ± 2.72) mg/L,(0.46 ± 0.11 ) μ g/L] were significantly higher than those in control group [ (2.31 ± 0.56) mg/L,(0.04 ± 0.13 ) μg/L ] (P ＜ 0.01 ).The levels of hs-CRP and cTnI in heart function Ⅳ grade patients [ ( 13.07 ± 4.31 ) mg/L,(0.57 ± 0.05 ) μg/L] were significantly higher than those in heart function Ⅲ grade patients [(10.04 ±3.12) mg/L,(0.35 ±0.09) μg/L](P＜0.01).After treatment,the levels of hs-CRP and cTnI in heart function Ⅲ grade and Ⅳ grade patients were significantly decreased compared with those before treatment(P＜ 0.01 ).ConclusionsThe levels of hs-CRP and cTnI in chronic heart failure patients are related to the inflammatory activities and myocardial damage.hs-CRP and cTnI may be effective factors to reflect the severity of heart failure.

Objective To investigate the influence of bushenhuoxue drug-containing serum on PI3K and Akt signaling pathway in purified retinal ganglion cell (RGCs) in vitro of Sprague-Dawley (SD) rats,and to explore the protective mechanisms of bushenhuoxue recipe on RGCs.Methods At first,bushenhuoxue drug-containing serum was prepared,and the RGCs of SD rats were purified;after the apoptotic model of pressurized and purified RGCs was established successfully in vitro using open pressure control system,RGCs were dealt with 50 g · L-1,100 g · L-1,200 g · L-1 concentration gradient of bushenhuoxue drug-containing serum.Then the subjected cells were divided into normal culture group (N group),control group (C group),50 g · L-1 bushenhuoxue group (50 g · L-1 BSHX group),100 g · L-1 bushenhuoxue group (100 g · L-1 BSHX group),200 g · L-1 bushenhuoxue group (200 g · L-1 BSHX group).Finally,cell apoptotic rate was detected by Annexin V-FITC/PI staining,while real-time quantitative PCR (qRT-PCR) and Western blot were used to detect the mRNA and protein expression of PI3K and Akt in each group respectively.Results The results of qRT-PCR detection showed that PI3K,Akt mRNA expression level in C group (0.04 ±0.01) was decreased compared with N group (1.00 ± 0.04),and the difference was statistically significant (all P＜0.05),while PI3K,Akt mRNA levels in 50 g · L-1,100 g · L-1 and 200 g · L-1 BXHX group (0.18 ±0.01,0.21 ±0.02,0.22 ±0.01,0.36 ±0.01,0.84 ±0.10,1.07 ± 0.17) were increased compared with the C group,and the difference was statistically significant (all P ＜0.05).The Western blot results of each group showed that PI3K,Akt protein expression level in C group was decreased compared with N group,with statistical difference (all P ＜ 0.05),while PI3 K,Akt protein expression levels in 50 g · L-1,100 g · L-1 and 200 g · L-1 BSHX group were increased compared with C group,with staffstical difference (all P ＜ 0.05).Conclusion Bushenhuoxue drug-containing serum may inhibit the RGCs apoptosis induced by pressure,which may be related to the activation of PBK/Akt signal transduction pathway.