ABSTRACT:Objective To investigate the effects of poly ADP-ribose polymerase (PARP ) inhibitor 3-aminobenzene (3-AB)on the delayed development cerebral vasospasm (DCVS)after subarachnoid hemorrhage (SAH)and on the inflammatory factors,namely monocyte chemotactic protein 1 (MCP-1 )and hypersensitive c-reactive protein (hsCRP),and to explore the relationship between these and the signaling pathway of NF-kappa B (NF-κB).Methods Eighty male Sprague-Dawley rats were randomly divided into four groups:normal group (n =8),sham-operation group (n =8),SAH model group (n =32)and 3-AB group (n =32).We established 64 SAH model animals by double injection of blood into the cisterna magna.Half of the SAH model animals were treated with 3-AB by intraperitoneal injection (30 mg/kg).These rats were killed to obtain specimens respectively at days 3, 5,7 and 14 after the second blood injection.The morphological changes of basilar arteries were observed under the light microscope.The contents of PARP,MCP-1 and hsCRP in brain tissues were detected with enzyme-linked immunosorbent assay (ELISA).The expression of NF-κB in basilar arteries was determined by immunohistochemistry.
Results Compared with those in the sham-operation group,the degree of basilar artery spasm reached the peak [(30.47±3.89)%]at day 5 after established SAH model;the thickness and diameter of basilar artery were (1 6.44 ±1.32)μm and (1 78.21 ± 1 1.13)μm,respectively.Cerebral blood flow was reduced by nearly 60% (P <0.01 ). The expression of NF-κB in the cytoplasm and nucleus and PARP content in brain tissue were both increased significantly (P < 0.01 ).MCP-1 [(365.29 ± 28.08 )pg/mL ] and hsCRP [(402.1 6 ± 48.99 )ng/mL ] were significantly enhanced (P <0.01).Compared with the SAH group,after 5 days’intervention with 3-AB,there was obvious alleviation in the spasm degree of basilar artery [(22.65±3.21)%],the thickness [(14.89±1.27)μm]and diameter [(1 98.56±10.91)μm],respectively (P <0.01).Cerebral blood flow was significantly enhanced,but the expression of NF-κB in the cytoplasm and nucleus was decreased and PARP in brain tissue was significantly decreased (P < 0.01 ).MCP-1 [(126.5 1 ± 18.67 )pg/mL]and hsCRP [(285.39 ± 39.07 )ng/mL]in brain tissue were significantly declined,respectively (P <0.01).Conclusion PARP inhibitor 3-AB can alleviate DCVS and inhibit the inflammatory response in brain tissue after SAH.The mechanism may be related to NF-κB signaling pathway.

The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angio-genesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0 ? 1) among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0). It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated in the bladder. The radionuclide was completely metabolized within 24 h, and the distribution of radioactivity in rats was similar to normal levels. In our study, the specific marker 131I-Kringle 5 and SPECT/CT were suc-cessfully used to explore pharmacokinetic characteristics of Kringle 5 in rats. The study could provide a new evaluation platform of the specific, in vivo and real-time functional imaging and pharmacokinetics for the clinical application of 131I-Kringle 5.

Serine/arginine-rich splicing factors (SRSFs) refer to twelve RNA-binding proteins which regulate splice site recognition and spliceosome assembly during precursor messenger RNA splicing. SRSFs also participate in other RNA metabolic events, such as transcription, translation and nonsense-mediated decay, during their shuttling between nucleus and cytoplasm, making them indispensable for genome diversity and cellular activity. Of note, aberrant SRSF expression and/or mutations elicit fallacies in gene splicing, leading to the generation of pathogenic gene and protein isoforms, which highlights the therapeutic potential of targeting SRSF to treat diseases. In this review, we updated current understanding of SRSF structures and functions in RNA metabolism. Next, we analyzed SRSF-induced aberrant gene expression and their pathogenic outcomes in cancers and non-tumor diseases. The development of some well-characterized SRSF inhibitors was discussed in detail. We hope this review will contribute to future studies of SRSF functions and drug development targeting SRSFs.

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.