Identification of lncRNAs-gene interactions in transcription regulation based on co-expression analysis of RNA-seq data.

Long noncoding RNAs (lncRNA) play important roles in gene expression regulation in diverse biological contexts. Numerous studies have indicated that lncRNA-gene interactions are closely related to the occurrence and development of cancers. Thus, it is important to develop an effective method for the identification of target genes of lncRNA. Meanwhile, the high throughput sequencing data provide tremendous information about regulation correlation, by which the new target genes could be detected from known lncRNA regulated genes. In this study, we developed a method for elucidating lncRNA-gene interactions by using a biclustering approach, which allows for the identification of particular expression patterns across multiple datasets, indicating networks of lncRNA and gene interactions. A p-value strategy is followed to link co-expression patterns to certain lncRNAs. The method was applied on the breast cancer RNA-seq datasets along with a set of known lncRNA regulated genes. The evaluation indicated that the method can detect some new targets but fail to obtain higher coverage. We believe that this developed method will provide useful information for future studies on lncRNAs.

[Induction study of CYP3A2 in male rats by zolmitriptan].

In our preliminary studies, we observed zolmitriptan (ZOL) treatment led to induction of CYP3A2 in male not female rats. To figure out the reason is of great significance for drug-drug interactions and personalized administration. Since growth hormone (GH) is known as the major mechanistic determinant of sexually-dimorphic gene expression like CYP3A2 in rat liver, the impacts of ZOL on both plasma GH levels in non monosodium glutamate (MSG)-treated rats and CYP3A2 expression in GH depleted MSG-treated rats were studied. ZOL was shown to partially suppress GH levels in both genders. Furthermore, CYP3A2 protein and mRNA level declined in male not female MSG-treated rats. In order to study the possible molecular events involved in the depression of GH and gender-selective induction on rat CYP3A2 by ZOL, the mRNA and protein level(whole protein and nuclear protein) of hepatocyte nuclear factor 4α (HNF4α) was investigated. Nuclear accumulation of HNF4α was observed in the normal male not female rat liver tissue following ZOL treatment. However, this kind of nuclear translocation did not occur in rat hepatocytes and MSG-treated rats. These findings demonstrated CYP3A2 inducibility by ZOL was gender-selective. GH and HNF4α may play an important role in CYP3A2 induction.

Pharmacokinetics and plasma protein binding of rutin deca (H-) sulfate sodium.

Rutin deca (H-) sulfate sodium (RDS) possesses very good activity as an inhibitor of the complement system of warm-blooded animals and HIV. An ion-pair coupled with solid-phase extraction technique (IP-SPE) was developed to extract RDS from rat plasma, urine, bile and protein solution samples. The assay was applied to pharmacokinetics of RDS, including plasma pharmacokinetics, excretion and protein binding studies. After i.v. 5, 20 and 100 mg x kg(-1) RDS via tail vein in rats, the plasma concentration-time profiles were fitted using 3P97 software. The average terminal half-life (t(1/2)) was 3.432 +/- 0.185 2 h. The relationship of dose and AUC of RDS was linear within the dosage range. This suggested that the disposition of RDS in rats belong to linear kinetics and the pharmacokinetic parameters of RDS were dose independent. After iv RDS 20 mg x kg(-1) in rats, the biliary excretion amount of parent drug amount was only 0.3181% +/- 0.2087% of given dosage, and the urinary excretion was 86.0% +/- 6.1% in 36 h. Ultrafiltration techniques were applied to determine the protein binding of RDS in plasma (from SD rat, Beagle dog and human), human serum albumin (HSA) and human alpha1-acid glycoprotein (AGP). The mean protein binding rate in plasma of SD rat, Beagle dog and human plasma of RDS were 80%-90%, in which the range of concentration of RDS was 5 to 100 microg x mL(-1). The protein binding to HSA was 85.7% +/- 1.3% and 14.0% +/- 3.2% to AGP.

Stereoselective behavior of a novel biodegradable racemic ketoprofen injectable implant in rats.

The stereoselectivity of release of ketoprofen (KET) enantiomers from a biodegradable injectable implant containing racemic KET (rac-KET) was investigated in vivo. A pre-column chiral derivatization RP-HPLC method was employed to assay diastereoisomeric derivatives of R- and S-KET. The rac-KET injectable implant, once injected subcutaneously in rats, produced long-lasting plasma levels of S-KET, which were always greater than those of R-KET. The difference in enantiomer concentration was to be related to stereoselective release, due to stereoselective interaction between D,L-PLG in the implant and KET enantiomers, as well as the chiral inversion of KET in vivo. The rac-KET injectable implant provided the sustained release of S-KET with effective plasma levels maintained for about 8 wk after a single injection.

A novel partner for Dictyostelium filamin is an alpha-helical developmentally regulated protein.

The filamins are a family of highly homologous actin-crosslinking proteins that stabilize three-dimensional actin networks, link them to membrane proteins and direct intracellular signaling reactions to the actin scaffold through interaction with various binding partners. Here, we describe the first Dictyostelium filamin-interacting protein to be isolated--FIP, a 229.8 kDa protein with two alpha-helical coiled coil domains. FIP was identified in a yeast two-hybrid screen using the rod domain of filamin as bait. FIP can also be coimmunoprecipitated with filamin from cellular extracts. Deletion analysis located the interaction domain of FIP to a C-terminal region; by contrast, in filamin rods, repeats 2-4 interacted with the recombinant FIP protein. The 7 kb transcript of FIP is upregulated during early development. Monoclonal antibodies raised against a bacterially expressed FIP polypeptide recognize a 230 kDa developmentally regulated protein in western blots. Immunofluorescence analysis shows a punctate staining pattern in the cytosol and, in cell fractionation experiments, FIP is mainly found in the cytosolic fraction. A fusion protein composed of GFP and the C-terminal part localizes to the plasma membrane and is associated with the cytoskeleton. Expression of the fusion protein affects development and influences the size of the multicellular aggregates and the phototactic behavior of slugs. Thus, FIP might provide a candidate link between the dynamic actin cytoskeleton and signal transduction events during the multicellular stages of Dictyostelium amoebae.