Protein-protein interactions (PPI) are involved in a variety of biological processes, including cell-to-cell interactions, metabolism and development control. The misregulation, post-translational modification and interference of PPI are related to a variety of human diseases, making the regulation of these interactions a very attractive field of drug discovery. In recent years, the interaction between MDM2 and p53 has become a research hotspot, which plays an important role in the treatment of tumors. But unfortunately there are no such inhibitors approved all over the world. In this view, recent advances of MDM2-p53 inhibitors were briefly described and its inhibitors with potential therapeutic activities in clinical studies were introduced.

Objective To investigate the injury characteristics of Beagle dogs after warship multi cabin explosion.Methods Forty-eight adult male Beagle dogs were placed in the simulated blast-cabin and adjacent cabin (24 each),and ammunitions respectively containing 0.75kg TNT and 3.50kg TNT were then detonated in the blast-cabin.The survival situation,fluctuation of vital signs,morphological changes of organs and the incidence of various types of injury of the dogs were observed immediately after the explosion to 24h after injury,and the neurological functions score was performed.Results Twenty dogs died immediately after the explosion,and another 9 dogs died 24h after the explosion.The total mortality was 60.42％(29/48),and the mortalities in blastcabin and adjacent cabin were 79.17％(19/24) and 41.67％(10/24),respectively.The dog's skull was penetrated by bomb fragments,and congestion and bleeding were observed in brain tissue,lung,heart,stomach,bowels,liver and kidneys.Extremities fracture,soft tissue contusions,perforation and rupture were also checked out after explosion.The fatality rate of bomb fragment injury,blast injury and combined bomb fragment-blast injury was 27.59％(8/29),17.24％(5/29) and 55.17％(16/29),respectively.Conclusions The combined bomb fragment-blast injury show high incidence and make high fatality rate and serious injury.Combatants should effectually shield themselves with occluded objects as far as possible to avoid damage and reduce fatality.The key of early treatment is to treat the multiple injuries promptly.Intravenous fluid therapy should be practiced after hemodynamic monitoring.

OBJECTIVETo detect the expression of CBX7 in human glioma and investigate the potential regulatory effect of abnormally expressed microRNAs on CBX7 expression.

METHODSSemi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot were applied to detect the expression pattern of CBX7 in 2 human normal brain tissues, 9 glioma tissues, and 3 glioma cell lines. Miranda algorithm and Ensemble Machine Learning algorithm were combined to predict miRNAs that target human CBX7. The expression of miR-9 in those tissues and cell lines were detected by real-time PCR. After miR-9 overexpression in 293ET and miR-9 knock-down in T98G, luciferase assay and Western blot were used to confirm the effect of miR-9 on CBX7 expression. MTT assay and flow cytometry were applied to detect the effect of miR-9 knock-down on T98G cells.

RESULTSNo obvious difference in the CBX7 mRNA level between normal and tumor tissues was observed, while the protein level of CBX7 was abrogated or markedly reduced in glioma tissues and cell lines. Several miRNAs including miR-9 may target CBX7 by bioinformatics prediction. MiR-9 was up-regulated in glioma tissues and cell lines. In 293ET cell, luciferase activity of CBX7-3'UTR reporter was decreased to 24% after miR-9 overexpression. After miR-9 knock-down in T98G cell, the luciferase activity was increased by 1.8 fold and there was no change of CBX7 mRNA, while the protein level of endogenous CBX7 was significantly increased. The number of survival T98G cells increased and cells in G1 phase decreased after miR-9 knock-down.

CONCLUSIONIn human glioma, CBX7 is down-regulated by the inhibition of miR-9 at posttranscriptional level.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Blotting, Western ; Brain ; metabolism ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Child ; Female ; Flow Cytometry ; Glioma ; genetics ; metabolism ; Humans ; In Vitro Techniques ; Male ; MicroRNAs ; genetics ; physiology ; Middle Aged ; Polycomb Repressive Complex 1 ; Repressor Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

OBJECTIVETo study the correlation of homocysteine (Hcy) in plasma with nitric oxide synthetase (NOS) and endogenous carbon monoxide (CO) in the penile corpus cavernosum of type 2 diabetic rats.

METHODSThis study included 40 male Wistar rats, 10 as controls (Group A) and the other 30 as diabetes mellitus (DM) models. Four weeks after the model establishment, the model rats were divided into a DM group (Group B, n = 10), an insulin treated group (Group C, n = 10), and a folic acid and vitamin B12 treated group (Group D, n = 10). All the rats were injected with apomorphine and observed for penile erection at 8 and 12 weeks, and the levels of total plasma Hcy (tHcy), NOS and CO in the penile corpus cavernosum were measured at 12 weeks.

RESULTSCompared with Group A, the level of tHcy was significantly increased, while NOS and CO activities in the penile cavernous tis-sue and erectile function remarkably decreased in Group B (P < 0.01). The incidence rate of high Hcy was 55% in the DM rats. In comparison, the level of tHcy was obviously decreased, and the NOS activity and erectile function markedly increased in Groups C and D (P < 0.01). The Hcy level showed a significant negative correlation with NOS activity (rA = -0.89, rB = -0.76, rc = -0.91, rD = -0.91) and CO content (TA = -0.82, r, = -0.77, rc = -0.93, rD = -0.81).

CONCLUSIONHigh plasma Hcy can decrease NOS and CO activities in the penile corpus cavernosum, and consequently induce erectile dysfunction in DM rats, while insulin, folic acid and vitamin B12 can improve their penile erectile function by increasing NOS and CO activities.

Animals ; Carbon Monoxide ; metabolism ; Diabetes Mellitus, Experimental ; blood ; physiopathology ; Diabetes Mellitus, Type 2 ; blood ; physiopathology ; Folic Acid ; pharmacology ; Homocysteine ; blood ; Insulin ; pharmacology ; Male ; Nitric Oxide Synthase ; metabolism ; Penis ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Vitamin B 12 ; pharmacology

OBJECTIVETo investigate the correlation between expression of A-kinase anchoring protein 95 (AKAP95) and protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.

METHODSFifty-one cases of lung cancer were included in the study. The protein expression of AKAP95, cyclin E1, and cyclin D1 were measured by immunohistochemistry.

RESULTSThe protein expression of cyclin E1 in lung cancer tissues was significantly higher than that in para-cancerous tissues (positive rate: 75.56%vs 20%, P < 0.01); its expression showed no relationship with histopathological type, lymph node metastasis, and cellular differentiation (P > 0.05). The protein expression of cyclin D1 in lung cancer tissues was higher than that in para-cancerous tissues (positive rate: 69.39% vs 14.29%); its expression showed a significant relationship with histopathological type (P < 0.05). The expression of AKAP95 was correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissues (P < 0.01).

CONCLUSIONCyclin E1 and cyclin D1 are highly expressed in lung cancer tissue, suggesting that they play an important role in the development and progression of lung cancer. The protein expression of cyclin E1 has no relationship with cellular differentiation, lymph node metastasis, and histopathological type of lung cancer, and the protein expression of cyclin D1 has a significant relationship with histopathological type. The expression of AKAP95 is correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.

A Kinase Anchor Proteins ; metabolism ; Adult ; Aged ; Cyclin D1 ; metabolism ; Cyclin E ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Middle Aged ; Oncogene Proteins ; metabolism

Objective To establish a rat model of craniocerebral blast injury caused by the shock wave of cabin explosion.Methods Fifty male adult Sprague-Dawley rats were randomly divided into 5 groups (10 each):3g,5g,8g TNT with vest groups,5g TNT without vest group and control group.Uncased explosives of different equivalent were suspended in the cabin center.After anesthesia,with exception of control group,the rats were placed in prone position about 31 cm below the explosive,facing the explosive with or without vest.After the explosion,the survived rats were observed,serological and pathological examinations were performed at 3h,1d and 3d after the explosion.Results In terms of tissue damage and mortality,compared with the control group,no obvious injury formed in rats of the 3g TNT with vest group,and all of them survived;Rats in 5g TNT with vest group showed mild lung injury,brain tissue edema,enlarged blood vessel,patchy hemorrhage on the brain surface,and with a mortality of 30％;Rats in 8g TNT with vest group showed serious organ damage with a mortality of 80％;Rats in 5g TNT without vest group suffered from severe lung injury,almost all died right after the explosion.Therefore,rats in 5g TNT with vest group were more in line with the experimental needs.Further serum and pathologic examinations showed that the brain water content increased,the serum neuron specific enolase (NSE) and S-100β protein also increased markedly,and necrotic or apoptotic changes happened in the cortex and hippocampus neurons.Conclusion A stable animal model of craniocerebral blast injury may be established with rats in the case of chest and abdomen protected and then exposed to 5g TNT explosion in cabin.

Shaoyao Gancaotang, first seen in Treatise on Febrile and Miscellaneous Diseases, is composed of Paeoniae Radix Alba and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle in equal proportion.It has the functions of preserving Yin to nourish blood, harmonizing liver and spleen, relieving spasm and pain.This formula is applied in leg and foot spasm and abdominal pain caused by blood deficiency, body fluid consuming and the unmoistened muscles and veins.It has been highly praised and used by medical experts throughout the ages and has extended its application scope.Modern pharmacological studies have shown that Shaoyao Gancaotang has significant effects in antispasmodic, analgesic, antitussive and other areas, and is used to treat spastic diseases, painful diseases, inflammatory diseases and so on.This paper will systematically elaborate the historical evolution, compatibility analysis, pharmacological and pharmacodynamic studies, modern clinical application of Shaoyao Gancaotang, in order to provide theoretical basis and reference for the development of this famous classical formula.