Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.
Antineoplastic Agents ; Autophagy ; Humans ; Neoplasms ; physiopathology

Drug-induced immune hemolytic anemia has complicated manifestations and pathogenesis, and therefore clinicians should know its etiology and pathogenesis for safe medication. In this paper, we made a discuss on the etiology and pathogenesis of drug-induced immune hemolytic anemia from both traditional Chinese and western medicine viewpoint hoping to provide references for clinical physicians.

Epithelial-mesenchymal transition (EMT) refers to tne transition during which epithelial cells undergo the loss of apical-basal polarity, acquisition of migration capability and transformation into mesenchymal cells. EMT induces breast cancer in situ to developing into metastasis and associates with the drug resistence. The multiple elements including signal pathways, transcriptional factors and downstream genes orchestrate the transition. Among them, the transforming growth factor β (TGF-β) signaling pathway plays a key role in the regulation of EMT in breast cancer. And this paper reviews the development of TGF-β signaling pathway induced EMT in breast cancer.
Breast Neoplasms ; metabolism ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Humans ; Signal Transduction ; Transcription Factors ; Transforming Growth Factor beta ; physiology

Background The tissue-engineered cornea is becoming the hot spot in the ophthalmologic field,while the research of corneal substitute is in the ascendant,because it is more similar to the corneal morpha and easy to survive in vivo.Objective This study was to investigate the biocompatibility of recombinant human type-Ⅲ collagen/poly9 ( 3-( methacryloylamino ) propyl dimethyl ( 3-sulfopropyl ) ammonium hydroxide ) ( PMPDSAH ) interpenetrating polymer network (IPN) (RHC-Ⅲ/PMPDSAH IPN) hydrogel as a tissue-engineered cornea in rabbit eye and its feasibility as the corneal substitute.Methods One hundred and eight rabbits were randomly divided into experimental group( 90 rabbits) and normal control group ( 3 rabbits),and 15 rabbits ( 30 eyes ) used as the donor corneas.RHC-Ⅲ/PMPDSAH IPN,NGF PMPDSAH IPN and corneal grafts were lamellarly transplanted into the right eyes in RHC-Ⅲ/PMPDSAH IPN group,NGF PMPDSAH IPN group and allograft group respectively.The corneal transparency and neovascularization were examined and scored under the slim lamp and compared among three groups using Kraskal-Wallis H test.The corneal epithelization time was observed and compared among these three groups using one way analysis of variance and LSD-t test.The histological examination of corneas was performed at the 3rd day,1st and 2nd week,1 st,3rd and 6th month after the surgery.The immunohistochemistry was used to detect the expression of K3 in cornea at the 6th month.Results The grafts were well attached in RHC-Ⅲ/PMPDSAH IPN group,NGF PMPDSAH IPN group and allograft group,and no rejection reaction was found throughout 6-month following up.Compared with normal control group,no significant differences were found in the scores of corneal opacification and neovescularization in these three groups (x2 =4.34,P =0.23 ;x2 =2.60,P =0.46 ) at the 6th month.NGF PMPDSAH IPN group achieved reepithelialization in (4.97±0.63) days and was obviously shorted than that in RHC-Ⅲ/PMPDSAH IPN group and allograft group ( t =11.97,P =0.00; t =5.80,P =0.00).The re-epithelialization time in RHC-Ⅲ/PMPDSAH IPN was (6.86±0.71) days,and that of allograft group was (5.87±0.43 ) days,showing a significant difference ( t =6.32,P =0.00).Hematoxylin-eosin staining results demonstrated that implanted materials integrated into the host corneal tissue well and support corneal epithelialization.Part of the material degraded at the 2nd week and degraded completely 1 month later.Regular alignment and distribution of collagen fibers were seen in the regenerated cornea and were similar to those of the normal stroma in 6 months.Immunohistochemistry showed the positive expression of keratin-3 in corneal epithelial cells.Conclusions RHC-Ⅲ/PMPDSAH IPN has a good biocompatibility without toxicity to corneal tissue.Furthermore,NGF can promote the corneal wound-healing and re-epithelialization.The material can be used as safe and reliable corneal substitute after improving the mechanical strength.

Animals ; Decompression ; Decompression Sickness ; physiopathology ; Electrocardiography ; Electroencephalography ; Electromyography ; Electrophysiology ; Male ; Rabbits

OBJECTIVE To explore the effects of perinatal inflammation on the expression of proin-flammatory cytokines and DMEs (drug metabolism enzymes) in offspring mice. METHODS C57BL/6 maternal mice were administrated with single dose 100 μg·kg-1LPS(lipopolysaccharide)or saline(vehicle) during gestation (day 10 after fertilization). Offspring mice were sacrificed at 30 d after birth and liver samples were collected.Real-time PCR was adopted to test the mRNA expression of proinflammatory cytokines (Nrlp3 and IL-1β), nuclear receptors (Pxr and Car), and DMEs (Cyp3a11, 2b10, 1a2, and Ugt1a1).RESULTS Gender different expression of candidate genes was observed.The expression of Car,in the maternal injection of LPS groups,was significantly decreased in both female and male offspring (n=3-8/group, P<0.01). Concomitantly, a significantly lower expression of Cyp3a11 was found in both female and male offspring (P<0.01, P<0.05, respectively). Furthermore, the expression of Ugt1a1 was reduced in male offspring following maternal administration of LPS (P<0.01). In male offspring, Nrlp3 expression was specially decreased(P<0.05).Interestingly,there was an approximately 66% reduction in mRNA level of Cyp1a2 in female offspring (P<0.01), while in male offspring Cyp1a2 expression showed an increased trend (P>0.05) compared with vehicle group. The expression of Pxr, Cyp2b10, and IL-1β was no difference between LPS treatment group and vehicle group(P>0.05).CONCLUSION Maternal LPS administration affects the expression of proinflammatory cytokines, nuclear receptors and DMEs in mouse offspring.

OBJECTIVE To demonstrate the long-or short-term impacts of neonatal Pxr(pregnane X receptor) agonists exposureon DMEs (drug metabolism enzymes) expression in adulthood. METHODS C57BL/6 mice(day 5,postnatal)were injected with different doses(0,50,100,150,200 mg·kg-1·d-1, constitutive 4 d)of PCN(pregnenolone-16a-carbonitrile).Mice at different ages(day 5,10,15,25,postna-tal)were administrated with 200 mg·kg-1·d-1PCN in constitutive 4 d.All mice were sacrificed at day 60 after birth. Liver samples were collected for detecting the expression of Pxr target genes. RESULTS Compared with vehicle group, the significant inductions of Cyp2b10, Cyp3a11 and Pxrwere observed in high dose groups (150, 200 mg·kg-1·d-1, 5-8 d after birth) both in male and female mice (n=4-9/group,P<0.05).Furthermore,high dose groups(200 mg·kg-1·d-1,5-8 d after birth)were found to have higher mRNA expression levels of Cyp2a4,Ugt1a1,Abcc4,and Oatpla4 in female mice,while Papss2 in male mice compared with vehicle groups (n= 4-9/group, P<0.05). Interestingly, a decreased mRNA expression of Sult2a1 was identified in 200 (5-8 d) groups (n=4-9/group, P<0.05). Consistent with these results, the protein expression of Cyp3a11 was only increased in 200 (5-8 d) groups compared with the vehicle groups(n=3/group,P<0.05).Importantly,the persistent impacts on DMEs only occurred in day 5 and day 25 treatment groups,not day 10 and day 15 groups(n=4/group).CONCLUSION Neonatal Pxr activation has a long-term effect on the expression of DMEs in C57BL/6 mice.Dose and treatment exposure time are two key factors involved in this permanent alteration procedure.

Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.
CDC2 Protein Kinase ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; G1 Phase ; drug effects ; Hep G2 Cells ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; Thiazoles ; pharmacology

Objective To analyze the CT features of renal cell carcinoma,so as to improve the diagnostic accuracy of renal cell carcinoma.Methods Three hundred cases of renal cell carcinoma proved by pathology were examined by means of CT.There were 214 male and 86 female in this group.Their age ranged from 9 to 81 years,with a mean of 53.7 years.Their CT features were retrospectively reviewed. Results The masses were 1.5—16.0 cm(mean,4.8 cm)in greatest dimension,125 masses on left kidney and 175 masses on right kidney.According to WHO histological classification of tumours of the kidney in 2004,there were 238 cases of clear cell renal cell carcinoma,6 cases of multilocular clear cell renal cell carcinomas,23 cases of papillary renal cell carcinoma,14 cases of chromophobe renal cell carcinoma and 19 cases of renal cell carcinoma,unclassified.The above subtype of renal cell carcinoma demonstrated characteristic features.Clear cell renal cell carcinoma exhibited inhomogenous(due to hemorrhage,necrosis or cystic degeneration)and hypervaseular.Multilocular clear cell renal cell carcinoma presented as a multilocular cystic mass lacking an,expansile nodule,and with regular thin cyst wall and septa.Papillary renal cell carcinoma exhibited inhomogenous and hypovascular.Chromophobe renal cell carcinoma was relatively homogenous and hypovascular.Renal cell carcinoma,unclassified showed inhomogenous and hypervascular,and was more invading growth compared to clear cell renal cell carcinoma. Conclusion Common subtype of renal cell carcinoma demonstrated characteristic features in CT and it is helpful for differentiation.

Objective To explore the effects of early interventions on growth associated protein-43(GAP-43) and neuron apoptosis in brain of neonatal rats.Methods According to matched-pairs design,30 rats from the same materal rats were divided into two groups:intervention group and control group randomly.The intervention group received the neonatal handling for 14 d and then were kept in an enriched environment for another 14 d.The expression of GAP-43 and the number of neurons apoptosis were detected by immunohistochemistry and TUNEL staining respectively in forehead cortex and hippocampus of rats.The brain functional outcomes of rats were evaluated by water-maze test.Results In prefrontal cortex and hippocampus,the level of GAP-43 immuno-positive response in intervention group was significantly higher than that of control group(P