Intersectin is an evolutionarily conserved multifunctional adaptor protein with multifunctional domains. These domains interact with components of the endocytic and exocytic pathways, such as the clathrin mediating synaptic vesicle recycling, the protein related to endocytosis via caveolae, the with-no-lysine kinases related to the regulation of renal outer medullar potassium, and the Cdc42 mediating exocytic pathway. Recently, the understanding of intersectin function in the pathogenesis of endocrine tumor and many neurodegenerative diseases such as Down syndrome, Alzheimer disease has been deepened. This article reviewed the structure and roles in endocytosis/exocytosis and diseases of intersectin.
Adaptor Proteins, Vesicular Transport ; physiology ; Endocytosis ; Exocytosis ; Humans ; Synaptic Vesicles ; physiology

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice.Methods Single i.p.injection with puromycin aminonucleoside (PA,0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control.Animals were examined for urine protein,blood pressure,kidney weight/body weight (KW/BW),renal histology at 2,4,8,12, 30,60 and 90 dpp (n=6～9 for each group).Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1,CD31,VEGF,Flk-1,Ang-1,Ang-2,Tie-1 and Tie-2.Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4,8,12 dpp when compared with NS controls.Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection.PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp.Significantly increased systolic blood pressure was detected at 60 dpp in PA mice.Compared with NS injection,PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1,without obvious changes of VEGF at 2 dpp.Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli,leading to abnormal development of glomerular capillaries,and subsequent proteinuria,hypertension and glomerulosclerosis.

Objective To observe the effects of cyclosporin A on the expression of phosphorylated AKT in hepatocytes, and to investigate the mechanism of insulin resistance caused by cyclosporin A. Methods This study included two parts. 1. In vitro experiment:Human hepatocyte HL77022 cell line was cultured at different concentrations of cyclosporin A (0?1 μmol/L, 1 μmol/L, 5 μmol/L) for 48 hours. The expressions of phosphorylated AKT ( P?AKT) in HL77022 cells were measured by Western blot assay. 2. Rat in vivo experiment: SD rats were randomly divided into 2 groups. The rats in the control group were administrated with distilled water 1 mL/Kg/d. The rats in the cyclosporine group were administrated with cyclosporine 25 mg/Kg/d. The total experiment time was 5 months. The levels of fasting blood glucose and insulin were tested at the end of the experiment. The insulin resistance index and insulin sensitivity index were calculated. The expression of P?AKT in the rat hepatocytes was measured by immunohistochemistry. Results 1. Each group of the HL7702 cells treated by CsA ( 0?1 μmol/L, 1 μmol/L, 5 μmol/L ) showed a significantly decreased expression of P?AKT (P<0?05, P<0?01, and P<0?01). 2. After 5 months of therapy, the fasting blood glucose level of rats in the cyclosporine group was 9?28 mmol/L, indicating that cyclosporine?induced diabetic rat models were established. The insulin sensitivity index in the cyclosporine group was lower than that in the control group ( P<0?05 ) . The expression of P?AKT in liver in the cyclosporine group was significantly lower than that in the control group ( P <0?05) . Conclusions Therapeutic dose of cyclosporine has hyperglycemic effects on rats. Cyclosporine can reduce the expression of phosphorylated AKT in hepatic tissue in rats and also decrease the expression of P?AKT in human hepatocyte HL77022 cells, which indicate that cyclosporine may cause insulin resistance by interfering PI3K/AKT signal transduction pathway.

OBJECTIVE: To explore the effect of nitric oxide (NO) on the gene expression of hepatic TNF-α and IL-1β by crush injury of rat's soft tissues. METHODS: Rats were randomly divided into sham group, crush group, crush+aminoguanidine (AG) group, and crush+L-arginine (L-Arg) group. Activities of ALT and AST as well as NO level in serum were measured. Gene expressions of TNF-α and IL-1β were detected with RT-PCR. RESULTS: Obvious increase in TNF-α and IL-1β mRNA expression was detected in the crush group compared with the sham group (P<0.05). After pretreated L-Arg, expressions of TNF-α and IL-1β mRNA were markedly increased (P<0.05). After pretreated AG, those indices obviously decreased (P<0.05). Activities of ALT and AST enhanced and NO level increased in the crush group compared with the sham group (P<0.05). Pretreatment with L-Arg or AG led to substantial increased or reduced activities of ALT and AST as well as NO levels, respectively. CONCLUSION Endogenous NO mediated TNF-α, IL-1β mRNA up expression in liver induced by increased production of NO after crush injury of rat's soft tissues.
Animals ; Gene Expression ; Interleukin-1beta/metabolism* ; Liver ; Nitric Oxide/physiology* ; RNA, Messenger ; Rats ; Tumor Necrosis Factor-alpha/metabolism* ; Wounds and Injuries

Guanylate-binding protein 1 (GBP1) is an interferon induced protein, that belongs to the guany late-binding protein family. GBP1 is widely involved in anti-infection immune responses, anti-tumor activity and various biological reactions. Recent studies have proved that IFN-alpha, IFN-beta, IFN-gamma, IL1alpha, IL1beta, TNF-alpha and LPS can induce GBP1 expression; hence, the diverse biological functions of GBP1 have been gradually deduced and exploited. Many studies have been performed over recent years to understand the exact mechanisms that underlie the anti-infection and anti-tumor properties of GBP1. This review describes the molecular structure, biological activity, anti-infective properties and other functions of GBP1, in order to provide insights into the divergent roles of GBP1 in the regulation of various biological processes.
Animals ; Antineoplastic Agents ; metabolism ; Antiviral Agents ; metabolism ; GTP-Binding Proteins ; chemistry ; genetics ; metabolism ; Humans ; Interferons ; genetics ; metabolism

The aim was to prepare a novel ocular cationic microemulsion-in situ gel (CM-ISG) system with vitamin A palmitate (VAP) as model drug, and investigate the corneal retention behavior and corneal irritation of the system. VAP/CM was prepared by a process based on supply of energy, and the before-and-after gelation rheology of VAP/CM-ISG was investigated. In vitro VAP release and gel dissolution of both VAP/CM-ISG and Oculotect Gel was determined. And in vitro corneal retention behavior of both formulations was evaluated by captive bubble technique. Ocular irritation test was carried out based on the Draize method. Images of TEM showed that homogenous VAP/CM was made, and no significant differences of particle size were found between the VAP/CM and VAP/CM in Poloxamer 407 gel. Rheology study illustrated that VAP/CM reduced the phase transition temperature of Poloxamer 407 gel by 1.5 degrees C, and the elastic modulus increased about 15.7 times. The in vitro release and gel dissolution profile of both formulations exhibited the characteristics of zero order kinetics. Comparing with Oculotect Gel, desorption kinetics study of VAP/CM-ISG exhibited longer corneal retention time and smaller contact angle. Irritation test showed a good ocular compatibility of VAP/CM-ISG. Therefore, VAP/CM-ISG combined both advantages of the cationic microemulsion and in situ gel system, provided better wettability and longer ocular retention time. It might be a promising ocular drug delivery system.
Animals ; Cornea ; drug effects ; metabolism ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Ophthalmic Solutions ; Poloxamer ; chemistry ; Rabbits ; Random Allocation ; Viscosity ; Vitamin A ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; toxicity

Adenocarcinoma, Follicular ; pathology ; physiopathology ; Female ; Humans ; Kidney Diseases ; pathology ; physiopathology ; Kidney Neoplasms ; physiopathology ; Thyroid Neoplasms ; pathology ; physiopathology ; Young Adult

OBJECTIVETo observe the clinical effects and explore the mechanism of the integrated traditional Chinese and Western medicine in treating atopic dermatitis (AD).

METHODSForty-seven patients with AD were randomly assigned to two groups, the control group and the treated group, they were treated with conventional Western medicine (10 mg Loratadine tablet, once daily) and with integrated medicine additionally given modified Jiawei Danggui Decection besides Western medicine respectively for 4 weeks. Double-sandwich ELISA was used to detect the levels of interleukin- 4, -10 and -12 (IL-4, IL-10 and IL-12) before and after treatment.

RESULTSThe total effective rate in the treated group was 56% (14/25 cases), better than that in the control group (22.7%, 5/22 cases), showing significant difference between the two groups (X2 = 5.38, P < 0.05). Before treatment the serum levels of IL-4, IL-10 were significantly higher and level of IL-12 was lower in AD patients as compared with those in healthy persons (P < 0.01); they all restored to normal in the treated group after treatment but unchanged in the control group, showing significant difference between the two groups (P < 0.01).

CONCLUSIONThe clinical effect of integrated traditional Chinese and Western medicine is ascertainable, its mechanism might be associated with the regulation on related cytokines.

Adolescent ; Adult ; Cytokines ; blood ; Dermatitis, Atopic ; blood ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Integrative Medicine ; Loratadine ; therapeutic use ; Male ; Young Adult

To optimize indices of molecular identification for authentication of Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix, four indices, including sequence similarity, specific positions, genetic distance and phylogenetic tree, were compared based on trnL-trnF sequences. Total DNA was extracted from Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix, and trL-trnF sequences were amplified and sequenced. Sequence similarity was calculated by BLAST analysis. Specific positions were compared by DNAman software. Genetic distance and phylogenetic tree were analyzed by Mega software. The results showed that the inter-specific and intra-specific similarity of P. ginseng and P. quinquefolius respectively was 100% and 99. 6%. There were four specific positions at G153A, T463A, C732G and T818C. The inter-specific genetic distance (0) of trL-trnF sequences was lower than intra-specific genetic distance (0. 004). P. ginseng can be distinguished from P. quinquefolius based on the phylogenetic tree. It is concluded that Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix can be authenticated by identification indices of sequence similarity, specific positions, genetic distance and phylogenetic tree. Index of specific positions based on trnL-trnF sequences is the most efficient index to authenticate Ginseng Radix et Rhizoma and Panacis Quinquefolii Radix.
Chloroplasts ; genetics ; DNA Barcoding, Taxonomic ; methods ; Panax ; classification ; genetics ; Phylogeny ; Plant Proteins ; genetics ; Rhizome ; classification ; genetics

Objective To observe the efficacy and safety of oxcarbazepine combined with selective serotonin re-uptake inhibitor (SSRI) in the treatment of outpatients with agitated depression. Methods Thirty-two outpatients with agitated symptoms meeting CCMD-3 depression criteria were treated with oxcarbazepine combined with SSRI for 8 w: the dosage of oxcarbazepine changed dairy (1st and 2nd d, 0.3 g; 3rd d, 0.6 g; 7th and 8th, 1.2-1.5 g). The efficacy and side effects were assessed by Hamilton depression scale, Hamilton anxiety rating scale and Young manic-state rating scale. Results The mean dosage of oxcarbazepine in 32 patients was (1020±65) mg/d. Their mean effective rate and full remission rate 87.5% and 65.6%,respectively. The mean effective rate and full remission rate 1, 2, 4 and 8 w after the treatment were 28.1% (9/32) and 6.3% (2/32), 37.5% (12/32) and 12.5% (4/32), 46.9% (15/32) and 31.3% (10/32), and 90.6% (29/32) and 65.6% (21/32), respectively. The scores of the above scales 1, 2, 4 and 8 w after the treatment were significantly different with those before the treatment (P<0.05). Phase inversion was not found in these 32 patients. Conclusion The oxcarbazepine combined with SSRI maybe one of the better ways in the treatment of patients with agitated depression.