Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway.

Epithelial-to-mesenchymal transition (EMT), a biologic process in which tubular cells lose their epithelial phenotypes and acquire new characteristic features of mesenchymal properties, is increasingly recognized as an integral part of renal tissue fibrogenesis. Recent studies indicate that resveratrol, a botanical compound derived mainly from the skins of red grapes, may have anti-fibrotic effects in many tissues, but the potential molecular mechanism remains unknown. In the present study, we identified that resveratrol inhibits the induction of EMT and deposition of extracellular matrix (ECM) through antagonizing the hedgehog pathway in vitro and in vivo.

Design, synthesis and pharmacological evaluation of 2-(thiazol-2-amino)-4-arylaminopyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors.

A series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) was developed by incorporation of a substituted 2-aminothiazole component as the C-2 substituent of the center pyrimidine core. Compound 5i showed highest potency of 12.4 nM against ALK and 24.

Hepatic stellate cell is activated by microRNA-181b via PTEN/Akt pathway.

Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. MicroRNAs have been shown to play a pivotal role in regulating HSC functions such as cell proliferation, differentiation, and apoptosis. Recently, miR-181b has been reported to promote HSCs proliferation by targeting p27.

Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma.

Background: Asthma is a common immune disorder characterized by increased IgE levels. The interleukin (IL)-4 and IL-13 pathway is central for IgE regulation, and previous studies have reported many genetic variants of IL-4/IL-13 signaling in relation to asthma, but few have focused on the gene-to-gene interactions that are likely to contribute to disease complexity.

Objective: To assess the combined effects of 7 functional single-nucleotide polymorphisms (SNPs) on asthma susceptibility, total serum IgE levels, and gene expression in children.

Single-shot dual-wavelength phase unwrapping in parallel phase-shifting digital holography.

We propose a single-shot phase-unwrapping method using two wavelengths in parallel phase-shifting digital holography (PPSDH). The proposed method enables one to solve the phase ambiguity problem in PPSDH. We conducted an experiment of the proposed method using two lasers whose wavelengths are 473 and 532 nm.

Efficacy and safety of phosphodiesterase-5 inhibitors for treating erectile dysfunction in kidney transplant recipients: a meta-analysis.

Objectives: Erectile dysfunction is common after kidney transplant. The phosphodiesterase-5 inhibitors are the primary drugs for the treatment of erectile dysfunction. The purpose of this study was to evaluate the efficacy and safety of these drugs in the treatment of erectile dysfunction after kidney transplant.

Novel 2,4-Diarylaminopyrimidine Analogues (DAAPalogues) Showing Potent c-Met/ALK Multikinase Inhibitory Activities.

By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.

SOMCL-863, a novel, selective and orally bioavailable small-molecule c-Met inhibitor, exhibits antitumor activity both in vitro and in vivo.

Deregulation of HGF/c-Met signaling and its driven neoplastic phenotype are associated with a variety of human malignancies. We herein reported SOMCL-863 as a novel selective c-Met inhibitor which effectively abrogated c-Met signaling pathways, thereby leading to substantial impairment of c-Met-dependent cell proliferation, migration, invasion, cell scattering and invasive growth. In EBC-1 and NCI-H1993 xenografts, SOMCL-863 exerted significant anti-tumor efficacy through anti-proliferative effects and antiangiogenic mechanisms, including reduction of tumor cell proliferation and reductions of microvessel density and secretion of proangiogenic factor IL-8.

Aurora A orchestrates entosis by regulating a dynamic MCAK-TIP150 interaction.

Entosis, a cell-in-cell process, has been implicated in the formation of aneuploidy associated with an aberrant cell division control. Microtubule plus-end-tracking protein TIP150 facilitates the loading of MCAK onto the microtubule plus ends and orchestrates microtubule plus-end dynamics during cell division. Here we show that TIP150 cooperates with MCAK to govern entosis via a regulatory circuitry that involves Aurora A-mediated phosphorylation of MCAK.

Discovery of novel type II c-Met inhibitors based on BMS-777607.

Twenty-two new analogs based on the structure of BMS-777607 were designed, synthesized, and evaluated to determine their biological activities. Compounds bearing a cyclic sulfonamide or α-chloropiperidone scaffold exhibited good activity, which may provide a new basis for further structural optimization. Quinoline-containing analogs exhibited better results than did their counterparts with an aminopyrimidine, aminopyridine, or pyrrolopyridine unit.

Discovery of novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent inhibitory activities against both wild-type and mutant ALK kinases.

We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.

Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

Evaluation of hemilaminectomy use in microsurgical resection of intradural extramedullary tumors.

The aim of this study was to investigate the microsurgical techniques of hemilaminectomy, used in the excision of intradural extramedullary (IDEM) tumors, and to illustrate its clinical effects. Clinical data obtained from 16 patients (seven males, nine females) with IDEM tumors, which were treated at the China-Japan Union Hospital between January 2009 and December 2011, were retrospectively analyzed. The mean age of patients was 49 years, ranging from 34-72 years.

Effect on eNOS/NO Pathway in MIRI rats with preconditioning of GFPC from Dang Gui Si Ni decoction.

Objective: In order to discover whether the eNOS/NO (endothelial nitric oxide synthase/nitric oxide) pathway is involved in the protective mechanisms of ischemic myocardium of DGSND (Dang Gui Si Ni Decoction) in MIRI (myocardial ischemia-reperfusion injury) SD rats.

Materials And Methods: We made I/R (ischemia-reperfusion) model by ligating the left anterior-descending branch of the coronary artery (LAD) for 30 min and releasing the ligature for 120 min. eNOS (nitric oxide synthase) mRNA (message ribonucleic acid) and iNOS (inducible nitric oxide synthase) mRNA were measured by the methods of real-time RT-PCR (Real time Polychainase Chain Reaction), peNOS (phosphorylated eNOS) and iNOS protein were measured by the means of western blot.

Assessment of renal tissue elasticity by acoustic radiation force impulse quantification with histopathological correlation: preliminary experience in chronic kidney disease.

Objectives: Chronic kidney disease (CKD), a progressive and irreversible pathological syndrome, is the major cause of renal failure. Renal fibrosis is the principal process underlying the progression of CKD. Acoustic radiation force impulse (ARFI) quantification is a promising noninvasive method for assessing tissue stiffness.

Effects of low-intensity pulsed ultrasound on integrin-FAK-PI3K/Akt mechanochemical transduction in rabbit osteoarthritis chondrocytes.

The effect of low-intensity pulsed ultrasound (LIPUS) on extracellular matrix (ECM) production via modulation of the integrin/focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been investigated in previous studies in normal chondrocytes, but not in osteoarthritis (OA). Therefore, we investigated the LIPUS-induced integrin β1/FAK/PI3K/Akt mechanochemical transduction pathway in a single study in rabbit OA chondrocytes. Normal and OA chondrocytes were exposed to LIPUS, and mRNA and protein expression of cartilage, metalloproteinases and integrin-FAK-PI3K/Akt signal pathway-related genes was determined by quantitative reverse transcription polymerase chain reaction and Western blotting, respectively.

The progression of the tubulointerstitial fibrosis driven by stress-induced "proliferation-death" vicious circle.

Several hypotheses have been developed to interpret the progression of tubulointerstitial fibrosis (TF), including senescence, epithelial-mesenchymal transition, inflammation, chronic hypoxia, and reactive oxygen species. All of these hypotheses are based on persistent cell injury and localized cell death. Proliferation of neighboring renal tubular epithelial cells (RTECs) is beneficial for organ function recovery from acute injury.

Novel self-assembled micelles based on palmitoyl-trimethyl-chitosan for efficient delivery of harmine to liver cancer.

Background: Polymeric micelles is a safe and effective delivery system, which belong to the targeted delivery system (TDS). An anticancer drug, harmine(HM) is a hydrophobic drug with much adverse effects when used for treatment of liver cancer. Chitosan (CS) is a polysaccharide and can be modified to be an amphiphilic polmer which could self-assemble into micelles and be applied for delivery of hydrophobic drugs.

Mitochondrial DNA levels in blood and tissue samples from breast cancer patients of different stages.

Aims: Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer.

Methods: Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features.

Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold.

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.

Asparagine depletion potentiates the cytotoxic effect of chemotherapy against brain tumors.

Unlabelled: Targeting amino acid metabolism has therapeutic implications for aggressive brain tumors. Asparagine is an amino acid that is synthesized by normal cells. However, some cancer cells lack asparagine synthetase (ASNS), the key enzyme for asparagine synthesis.

[The application of genotyping in the complicated ABO blood group type].

Objective: To investigate the application of ABO blood group genotyping in complicated ABO blood group type.

Methods: Ten specimens of complicated ABO blood group were genotyped by sequence specific primer PCR (PCR -SSP), and confirmed by DNA sequencing and alignment. Six hundred and ten blood samples typed by ABO immunoassay were as control of genotyping.

Detection of aberrant hypermethylated spastic paraplegia-20 as a potential biomarker and prognostic factor in gastric cancer.

The aim of this study was to evaluate hypermethylation of the spastic paraplegia-20 promoter as a potential biomarker and prognostic factor in gastric cancer. Four human gastric cancer cell lines, 41 primary gastric cancer tissue samples and corresponding peripheral blood samples, and blood samples of 21 healthy individuals were analyzed using methylation-specific polymerase chain reaction. Additionally, the expression of Spartin, the protein product encoded by spastic paraplegia-20, was analyzed in tissues from 119 gastric cancer patients who underwent radical gastrectomy at Xi'an Jiaotong University between 2005 and 2010.

[Study on KIR gene polymorphisms in 416 renal transplantation recipients from southern Zhejiang].

Objective: To investigate polymorphisms of killer cell immunoglobulin-like receptor gene (KIR) in renal transplant recipients from southern Zhejiang.

Methods: KIR genotypes were analyzed by PCR-SSP in 416 renal transplant recipients, and the genotype frequencies were compared with populations from Eastern China and worldwide.

Results: All 16 known KIR genes were detected in the renal transplant recipients, and KIR2DL4, 3DL2-3, 3PD1 were found in all.