Rapamycin inhibits IGF-1 stimulated cell motility through PP2A pathway.

Serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) has been implicated as a novel component of the mammalian target of rapamycin (mTOR) signaling pathway. Recently we have demonstrated that mTOR regulates cell motility in part through p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) pathways. Little is known about the role of PP2A in the mTOR-mediated cell motility.

Effects of genistein and equol on human and rat testicular 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 activities.

The objective of the present study was to investigate the effects of genistein and equol on 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) in human and rat testis microsomes. These enzymes (3beta-HSD and 17beta-HSD3), along with two others (cytochrome P450 side-chain cleavage enzyme and cytochrome P450 17alpha-hydroxylase/17-20 lyase), catalyze the reactions that convert the steroid cholesterol into the sex hormone testosterone. Genistein inhibited 3beta-HSD activity (0.

Reducing nanotube cytotoxicity using a nano-combinatorial library approach.

Carbon nanotubes (CNTs) have a great potential for applications in medicine. However, their biocompatibility and toxicity cause a great concern. Due to the large surface area of CNTs, chemical modification can dramatically alter their physiochemical properties and hence biological activity.

Natural product-inspired synthesis of thiazolidine and thiazolidinone compounds and their anticancer activities.

Nature makes many pharmacologically active compounds containing thiazolidine and thiazolidinone scaffolds. These privileged structures have been identified in many random screening assays. Molecules containing these core structures have been designed and synthesized, and they show a broad range of anticancer activities in vitro and in vivo.

The antitumor activity of the fungicide ciclopirox.

Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture.

Mechanism of impaired baroreflex sensitivity in Wistar rats fed a high-fat and -carbohydrate diet.

Both high-fat and high-carbohydrate diets have been considered in association with the impairment of baroreflex sensitivity. However, the mechanisms are unclear. In the present study, the effects of a complex high-fat and high-carbohydrate diet (HFCD) on baroreflex circuitry were investigated.

Hydrogen peroxide inhibits mTOR signaling by activation of AMPKalpha leading to apoptosis of neuronal cells.

Oxidative stress results in apoptosis of neuronal cells, leading to neurodegenerative disorders. However, the underlying molecular mechanism remains to be elucidated. Here, we show that hydrogen peroxide (H(2)O(2)), a major oxidant generated when oxidative stress occurs, induced apoptosis of neuronal cells (PC12 cells and primary murine neurons), by inhibiting the mammalian target of rapamycin (mTOR)-mediated phosphorylation of ribosomal p70 S6 kinase (S6K1) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1).

[Experimental study of treating Duchenne muscular dystrophy with myoblast transplantation].

Objective: To investigate the effect of myoblast transplantation on duchenne muscular dystrophy (DMD) and to explore the method and feasibility of applying gene therapy to DMD.

Methods: Myoblast of C57/BL10 mice were cultured using multiple-step enzyme digestion method and differential velocity adherent technique. The morphology of the cells was observed with inverted phase contrast microscope.

[Correlation of cardiovascular risk factors versus glomerular filtration rate in healthy population].

Objective: To evaluate the relationship between cardiovascular risk factors and glomerular filtration rate in healthy population.

Methods: A community-based cross-sectional study was conducted in Shenyang. The Framingham sex-specific risk equation was employed to evaluate the cardiovascular risk factors of 501 healthy study objects, calculate Framingham risk score and estimate the risk of 10-year coronary heart disease (CHD).

Use of cyclohexylisocyanide and methyl 2-isocyanoacetate as convertible isocyanides for microwave-assisted fluorous synthesis of 1,4-benzodiazepine-2,5-dione library.

A new protocol in which cyclohexylisocyanide and methyl 2-isocyanoacetate are used as convertible isocyanides for Ugi/de-Boc/cyclization/Suzuki synthesis of biaryl-substituted 1,4-benzodiazepine-2,5-diones has been developed. Ugi reactions of Boc-protected anthranilic acids, fluorous benzaldehydes, amines, and cyclohexylisocyanide or methyl 2-isocyanoacetate were carried out at room temperature. Microwave-promoted de-Boc/cyclization reactions afforded 1,4-benzodiazepine-2,5-diones (BZDs).

Microwave-assisted fluorous synthesis of a 1,4-benzodiazepine-2,5-dione library.

Fluorous displaceable linker-facilitated synthesis of 1,4-benzodiazepine-2,5-dione library has been developed. Perfluorooctanesulfonyl protected 4-hydroxy benzaldehydes were used as the limiting agent for Ugi four-component reactions to form condensed products. Postcondensation reactions of the Ugi products generated 1,4-benzodiazepine-2,5-dione ring skeleton.

Advances in preclinical small molecules for the treatment of NSCLC.

Background: NSCLC accounts for 85% of all lung cancer cases and is the leading cause of cancer mortality. Advances in the knowledge of molecular events governing oncogenesis have led to a number of novel therapeutic agents targeting specific pathways critical for tumor growth.

Objective: To summarize the recent preclinical developments of small molecules for NSCLC therapy.

The (+)- and (-)-gossypols potently inhibit both 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase 3 in human and rat testes.

Androgen deprivation is commonly used in the treatment of metastatic prostate cancer. The (-)-gossypol enantiomer has been demonstrated as an effective inhibitor of Bcl-2 in the treatment of prostate cancer. However, the mechanism of gossypol as an inhibitor of androgen biosynthesis is not clear.

Evaluation of efficacy and safety of anterior corpus callosotomy with keyhole in refractory seizures.

Purpose: This study was conducted to evaluate the efficacy and safety of anterior corpus callosotomy with a keyhole approach on refractory seizures and to evaluate this procedure for drop attacks (DAs) and generalized tonic-clonic seizures (GTCSs).

Methods: All refractory seizure patients underwent anterior corpus callosotomy (n=31) without other epilepsy surgery. Seizure response and procedure complications were evaluated.

Functionalized carbon nanotubes specifically bind to alpha-chymotrypsin's catalytic site and regulate its enzymatic function.

Although carbon nanotubes (CNTs) have been shown to nonspecifically bind proteins through charge complementary, pi-pi stacking or hydrophobic interactions, they have not been shown to bind to a specific site on proteins. By generating surface molecular diversity, we created functionalized CNTs that recognize and bind to the catalytic site of alpha-chymotrypsin and inhibit its enzymatic activity competitively.

Bone marrow mesenchymal stem cells upregulate transient outward potassium currents in postnatal rat ventricular myocytes.

Bone marrow mesenchymal stem cell (BMSC) transplantation has been shown to effectively improve cardiac function in experimental animals and patients with myocardial infarction and heart hypertrophy. BMSCs exert potent effects on cardiomyocytes through the inhibition of cardiac apoptosis, the attenuation of cardiac inflammation, etc. However, novel biological actions of BMSCs on cardiomyocytes remain to be explored.

The (+)- and (-)-gossypols potently inhibit human and rat 11beta-hydroxysteroid dehydrogenase type 2.

Gossypol has been proven to be a very effective male contraceptive. However, clinical trials showed that the major side effect of gossypol was hypokalemia. Gossypol occurs naturally as enantiomeric mixtures of (+)-gossypol and (-)-gossypol.

Transsulcal approach supported by navigation-guided neurophysiological monitoring for resection of paracentral cavernomas.

Objectives: The aim of the study is to evaluate tools that can improve surgical precision and minimize surgical trauma for removal of cavernomas in the paracentral area. Moreover, the surgical strategies for the treatment of symptomatic epilepsy in cavernoma patients are discussed.

Patients And Methods: Between June 2000 and July 2007, 17 patients suffering from paracentral cavernoma underwent surgery via a transsulcal approach with the aid of neuronavigation, functional mapping and neurophysiological intraoperative monitoring.

[Effect of p38 MAPK on elemene-induced cell cycle arrest in C6 glioblastoma cells].

Objective: To observe the effect of elemene on cell cycle of rat C6 glioblastoma cells.

Methods: Cell cycle analysis and expression of p38 in C6 glioblastoma cells under elemene treatment were measured by flow cytometry and Western blot. Flow cytometry and MTT assay were used to examine cell cycle and cell proliferation while C6 glioblastoma cells were pretreated with p38 inhibitor and DN-p38 plasmids.

A nano-combinatorial library strategy for the discovery of nanotubes with reduced protein-binding, cytotoxicity, and immune response.

We have discovered functionalized multiwalled carbon nanotubes with reduced protein-binding, cytotoxicity, and immune response and the associated structure-activity relationships using in silico surface molecular diversity design, combinatorial library synthesis, and multiple biological screenings. Our results demonstrated the general utility of the nanocombinatorial library approach in nanomedicine and nanotoxicity research.

Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells.

Ten cytoselective compounds have been identified from 372 thiazolidinone analogues by applying iterative library approaches. These compounds selectively killed both non-small cell lung cancer cell line H460 and its paclitaxel-resistant variant H460 taxR at an IC 50 between 0.21 and 2.

Microwave-assisted fluorous synthesis of 2-aryl-substituted 4-thiazolidinone and 4-thiazinanone libraries.

A straightforward two-step protocol for the synthesis of 2-aryl-substituted 4-thiazolidinone and 4-thiazinanone libraries has been developed. The one-pot, three-component reactions of fluorous benzaldehydes with amines and mercaptoacetic acid or mecaptopropanoic acid produce the heterocyclic systems. Intermediates purified by fluorous solid-phase extraction are subject to microwave-assisted palladium-catalyzed coupling reactions to simultaneously cleave the fluorous tag and introduce the biaryl and thioaryl functional groups to the 2-position of 4-thiazolidinones and 4-thiazinanones.

[Present and future of clinical application of myoblast].

Objective: To introduce the current situation and future of myoblast transfer therapy (MTT) in clinical application.

Methods: The latest fifteen-year literatures were extensively reviewed, concerning gene therapy for Duchenne's muscular dystrophy, Parkinson's disease, myelopathy, permanent facial paralysis, angiocardiopathy, injuries of bone, joint and muscle, hematopathy, and pituitary dwarf.

Results: In medical field, MTT is an ideal method to treat some common diseases.