The Lin28/let-7a/c-Myc pathway plays a role in non-muscle invasive bladder cancer

We investigate the role of the Lin28/let-7a/c-Myc pathway in non-muscle invasive bladder cancer (NMIBC). Using RT-PCR, western blot and immunohistochemistry techniques, the levels of pre-let-7a, let-7a, Lin28 and c-Myc RNA and/or proteins were determined in samples of normal bladder tissue and bladder cancer. Expression of pre-let-7a was found to be negatively correlated with the pathological grade of bladder cancer, while let-7a showed a positive correlation with bladder cancer pathological grade. Expression of Lin28 RNA and protein was not significantly different between normal bladder tissue and low-grade transitional cell carcinoma of bladder (TCC) but the expression levels in high-grade TCC were remarkably increased. Expression of c-Myc RNA and protein was significantly higher in bladder cancer samples in comparison to normal bladder tissue without correlation with cancer differentiation. Expression of all the above RNAs and proteins showed no significant difference in Ta and T1 stages. The Lin28/let-7a/c-Myc pathway plays an important role in NMIBC. In particular, expression levels of let-7a correlate with the degree of cancer differentiation but not cancer stage.     

Synergistical effect of 20-HETE and high salt on NKCC2 protein and blood pressure via ubiquitin–proteasome pathway

We previously generated a cytochrome P450 4F2 (CYP4F2) transgenic mouse model and demonstrated that overexpressed CYP4F2 and overproduced 20-HETE in the kidneys contribute to the increase of blood pressure in the CYP4F2 transgenic mice with normal salt intake. We currently expect to elucidate a potential mechanism of salt-related hypertension whereby diverse levels of 20-HETE interact with dietary salt on Na⁺-K⁺-2Cl^? cotransporter, isoform 2 (NKCC2) in the kidneys of the transgenic and wild-type mice with high salt intake. High salt intake reduced about 85 % abundance of renal NKCC2 protein in the transgenic mice and about 24 % in the wild-type mice by Western blot. Furthermore, we first found that NKCC2 was ubiquitinated and interacted with Nedd4-2 by immunoprecipitation in the transgenic mice with high salt intake. In addition, inhibition of 20-HETE synthesis or proteasome activity reversed the reduction of NKCC2 expression induced by 20-HETE and high salt intake. These results suggest that 20-HETE and high salt intake synergistically decrease the expression of NKCC2 protein via Nedd4-2-mediated ubiquitin–proteasome pathway, and thereby modulate natriuresis and blood pressure. We propose that diverse levels of 20-HETE have diverse effects on blood pressure in different salt concentrations.     

A synonymous mutation in NOD2 gene was significantly associated with non-specific digestive disorder in rabbit

Nucleotide-binding oligomerization domain containing 2 (NOD2) plays a pivotal role in the host innate and adaptive immunity by recognizing the pathogenic agents. Therefore, its genetic polymorphisms and association with susceptibility to infectious diseases have been widely reported in human and farm animals. In the present study, we investigated the genetic polymorphisms in 3171 bp coding region of NOD2 gene and association with non-specific digestive disorder (NSDD) in rabbit. A total of four coding single-nucleotide polymorphisms (cSNPs) were detected. Among them, c.2961C>T was further genotyped for case (n = 176) and control (n = 130) based on association analysis, which revealed that C allele carried the potential protective role for susceptibility to NSDD with the odds ratio (OR) values of 0.52 (95% confidence interval (CI) 0.37–0.73, P < 0.01). Under the dominant inheritance model, CC genotype was associated with decreased susceptibility to NSDD (OR = 0.38, 95% CI 0.24–0.60, P < 0.01). Along with the aggravation of NSDD, we observed higher mRNA expression of NOD2 gene (P < 0.05). However, the mRNA expression pattern of CC genotype would be interacted by the different status of NSDD, which only showed the significantly increased level in severe NSDD group (P < 0.05). These results revealed by genetic association and gene expression analysis suggested that the NOD2 gene was associated with the susceptibility to NSDD in rabbit. However, the causative mutations linked to c.2961C>T and corresponding functional depiction should be further explored by performing exhaustive genetic studies.     

DcR3在甲状腺乳头状癌中的表达及临床意义

应用RT-PCR、Westem blot、免疫组化分别检测甲状腺乳头状癌组织与癌旁正常甲状腺组织标本中DcR3mRNA及蛋白的表达情况,探讨DcR3在甲状腺乳头状癌组织中的表达及,临床意义。RT-PCR检测显示,甲状腺乳头状癌中DcR3 mRNA的表达明显高于正常甲状腺组织（P〈0．05）：Western blot提示,DcR3蛋白在甲状腺乳头状癌中表达比正常甲状腺组织高（P〈0．05）;免疫组化显示,DcR3蛋白在甲状腺乳头状癌中高表达（P〈0．05）。DcR3mRNA及蛋白质在甲状腺乳头状癌及正常甲状腺组织间的表达差异有统计学意义（P〈0．05）。DcR3基因及蛋白在甲状腺乳头状癌中高表达,提示DcR3可能促进了甲状腺乳头状癌的发生发展。     

Bifunctional oligo(ethylene glycol) decorated surfaces which permit covalent protein immobilization and resist protein adsorption

In this article, surface coatings derived from homo-bifunctional tri(ethylene glycol) (EG₃) and hexa(ethylene glycol) (EG₆) molecules which have two terminal aldehyde groups are reported. These homo-bifunctional molecules can be used to functionalize amine-terminated surfaces through crosslinking one aldehyde group to surface amine groups, while leaving the other aldehyde group available for covalent immobilization of proteins. Best of all, after reducing remaining aldehyde groups on the surface with a reducing agent, sodium borohydride, the surface becomes oligo(ethylene glycol) (OEG)-terminated. The OEG-terminated surface can resist nonspecific protein adsorption, a feature that is often required for many biosensors and biomedical devices. Although some mixed self-assembled monolayers formed from two different organothiols also permit covalent protein immobilization and resist nonspecific protein adsorption, the procedure reported herein requires only one type of homo-bifunctional molecule and can be applied to both silicon and gold surfaces.     

Asymmetric Zinc‐Catalyzed Hydrosilylation of Ketones and the Effect of Carboxylate on the Enantioselectivity

Several chiral ligands containing (R,R)‐diaminocyclohexane moieties and pyrrole, furan, or benzene have been synthesized. These ligands were tested in enantioselective zinc‐catalyzed hydrosilylation reactions; excellent enantioselectivities were obtained when the ligands containing (R,R)‐diaminocyclohexane moieties and furan rings were used. For comparison, zinc chloride combined with different potassium carboxylate salts and ligands were also tested for catalytic hydrosilylation reactions. Chirality 25:275–280, 2013. © 2013 Wiley Periodicals, Inc.