Preparation,Safety, Pharmacokinetics,and Pharmacodynamics of Liposomes Containing <Emphasis Type="Italic">Brucea javanica</Emphasis> Oil

Brucea javanica oil-loaded liposomes (BJOL) were prepared through thin film hydration method and characterized by transmission electron microscope, dynamic light scattering, and differential scanning calorimetry. Acute toxicity of B. javanica oil (BJO) in liposomes was assessed by determining the number of deaths of Kunming mice over intravenous treatment for 2 weeks. The pharmacokinetic behavior of the main active component (oleic acid) was studied in SD rats. The pharmacodynamics of BJOL was investigated using MMC-7721 cell lines and mice with Lewis lung cancer. The commercial emulsion of BJO (BJOE) was used as a reference. The data showed that BJOL had an average diameter of 108.2 nm with a zeta potential of −57.0 mV, drug loading of 3.60%, and entrapment efficiency of 92.40%. The area under curve of BJO in liposomes and emulsions were 2.31 and 1.15 mg min/ml, respectively. Compared with BJOE, mean residence time and elimination half-time (t _1/2) increased 2.8- and 4.0-fold, respectively, and the clearance (CL) decreased 0.5-fold. In the acute toxicity test, the median lethal dose (LD₅₀) of BJOE was 7.35 g/kg. In contrast, all mice treated with liposomes survived even at the highest dosage (12.70 g/kg). The IC₅₀ value of BJOL group was one third of that of BJOE group (p < 0.01), and a less weight loss was observed in the BJOL-treated animals (p < 0.05). In conclusion, the present study suggests that BJOL significantly decreased toxicity of BJO and enhance the antitumor activity. Therefore, liposomes may be a potential effective delivery vehicle for this lipophilic antitumor drug.     

Isolation of mitochondrial DNA sequences that distinguish male-sterility-inducing cytoplasms in Sorghum bicolor (L.) Moench

We have demonstrated that sorghum DNA sequences of mitochondrial origin can be used to distinguish different male-sterility-inducing cytoplasms. Six DNA clones containing single-copy mitochondrial sequences were hybridized on Southern blots to restriction enzyme-digested DNA of 28 sorghum lines representing sources of different cytoplasmic male-sterility (CMS) groups. Four cytoplasmic types were defined on the basis of the pattern of DNA fragments detected. Similar analyses of 50 additional diverse sorghum accessions suggested that three of the four cytoplasmic types may be diagnostic for CMS. Also, three other cytoplasmic types were discovered. These and other mitochondrial DNA clones may be useful molecular tools for “fingerprinting” sterility-inducing cytoplasms in breeding programs, determining cytoplasmic diversity among germ plasm accessions, and identifying new sources of cytoplasm that induce male sterility.     

Silibinin induced-autophagic and apoptotic death is associated with an increase in reactive oxygen and nitrogen species in HeLa cells

Silibinin, as the major active constituent of silymarin, has its various biological effects. Here, we investigated the inhibitory effects of silibinin on HeLa cell growth in relation to autophagy and apoptosis induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. Silibinin dose and time-dependently decreased cell growth cultured in medium containing 10% fetal bovine serum or in serum free media (SFM) with an IC(50) of approximately 80-100 and 40-60 μM at 24 h, respectively. Silibinin induced autophagy at 12 h, confirmed by monodansylcadervarine (MDC) staining and up-regulation of beclin-1, and induced apoptosis at 24 h, detected by observation of apoptotic bodies and activation of caspase-3. 3-methyladenine (3-MA) inhibited silibinin-induced autophagy and attenuated the silibinin's inhibitory effect on cell viability, suggesting that autophagy enhanced silibinin-induced cell death. Silibinin increased ROS levels at 12 h, and ROS scavenger, N-acetylcysteine (NAC), significantly reversed the cytotoxicity of silibinin through inhibiting both autophagy and apoptosis. Specific antioxidants were applied and results indicated that hydroxyl radical (·OH) was the major ROS induced by silibinin, and OH scavenger glutathione (GSH) inhibited apoptosis and autophagy. Silibinin also generated RNS production in the cells at 12 h. High concentration of N omega-nitro-l-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor attenuated the cytotoxicity of silibinin by decreasing ROS levels, leading to down-regulation of apoptosis. Silibinin also could interrupt the respiring functions of mitochondria, leading to ROS production and oxidative damage.     

60 Years of Development of the Journal of Integrative Plant Biology

In celebration of JIPB's 60^th anniversary, this paper summarizes and reviews the development process of the journal. To start, we offer our heartfelt thanks to JIPB's pioneer Editors-in-Chief who helped get the journal off the ground and make it successful. Academic achievement is the soul of academic journals, and this paper summarizes JIPB's course of academic development by analyzing it in four stages: the first two stages are mostly qualitative analyses, and the latter two stages are dedicated to quantitative analyses. Most-cited papers were statistically analyzed. Improvements in editing, publication, distribution and online accessibility—which are detailed in this paper—contribute to JIPB's sustainable development. In addition, JIPB's evaluation index and awards are provided with accompanying pictures. At the end of the paper, JIPB's milestones are listed chronologically. We believe that JIPB's development, from a national journal to an international one, parallels the development of the Chinese plant sciences.     

Association of 8q24 rs13281615A > G polymorphism with breast cancer risk: evidence from 40,762 cases and 50,380 controls

The association between a single nucleotide polymorphism rs13281615A > G located in the 8q24 and breast cancer risk is still controversial and ambiguous. Hence, we performed a more convincing and precise estimation of the relationship between 8q24 and breast cancer by meta-analyzing the currently available evidence from literature. PubMed, Ovid, Medline, and Web of Science databases were searched. A total of 10 publications containing 11 studies including 40,762 cases and 50,380 controls were identified. Crude odds ratio with 95 % confidence interval was used to assess the strength of association. We observed that the 8q24 rs13281615A > G polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta analysis. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for all genetic models. For mixed ethnicities, significantly increased risks were found for all genetic models except for the allele contrast model. However, no significantly increased risk was found among Africans for all genetic models. Interestingly, when stratified by BRCA1 mutation carriers status, significantly decreased breast cancer risk was found for allele contrast model. But significantly increased breast cancer risk was found in the BRCA2 mutation carriers for all genetic models except for the recessive model. There was no evidence for significant association between 8q24 rs13281615A > G polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparable models. In conclusion, this meta-analysis suggests that the 8q24 rs13281615A > G polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.     

High level secretory expression of murine OCIL by CHO cells and action of OCIL on osteoclast differentiation

Receptor activator of nuclear factor-kB ligand (RANKL), a well-known membrane-bound molecule expressed on osteoblasts and bone marrow stromal cells, is believed to induce osteoclast differentiation and activation by binding to the receptor activator of nuclear factor-kB (RANK), which is expressed on the surface of osteoclast lineage cells. This induction is inhibited by osteoprotegerin (OPG) that is secreted by osteoblast lineage and acts as a decoy receptor of RANKL. Currently the essential role of the OPG/RANKL/RANK system in the process of osteoclast maturation, as well as activation, has been well established, and the majority of bone resorption regulators control osteoclast formation and activation through their effects on this system and especially on the relative expression levels of RANKL and OPG [1].     

Development and evaluation of an efficient and real-time monitoring system for the vector mosquitoes,Aedes albopictus and Culex quinquefasciatus

BackgroundThe surveillance of vector mosquitoes is essential for prevention and control of mosquito-borne diseases. In this study, we developed an internet-based vector mosquito monitor, MS-300, and evaluated its efficiency for the capture of the important vector mosquitoes, Aedes albopictus and Culex quinquefasciatus, in laboratory and field trials.Methodology/Principal findingsThe linear sizes of adult Ae. albopictus and Cx. quinquefasciatus were measured and an infrared window was designed based on these data. A device to specifically attract these two species and automatically transmit the number of captured mosquitoes to the internet was developed. The efficiency of the device in capturing the two species was tested in laboratory, semi-field and open field trials. The efficiency results for MS-300 for catching and identifying Ae. albopictus in laboratory mosquito-net cages were 98.5% and 99.3%, and 95.8% and 98.6%, respectively, for Cx. quinquefasciatus. In a wire-gauze screened house in semi-field trials, the efficiencies of MS-300 baited with a lure in catching Ae. albopictus and Cx. quinquefasciatus were 54.2% and 51.3%, respectively, which were significantly higher than 4% and 4.2% without the lure. The real-time monitoring data revealed two daily activity peaks for Ae. albopictus (8:00–10:00 and 17:00–19:00), and one peak for Cx. quinquefasciatus (20:00–24:00). During a 98-day surveillance trial in the field, totals of 1,118 Ae. albopictus and 2,302 Cx. quinquefasciatus were captured by MS-300. There is a close correlation between the number of captured mosquitoes and the temperature in the field, and a positive correlation in the species composition of the captured samples among the mosquitoes using MS-300, BioGents Sentinel traps and human landing catches.Conclusions/SignificanceThe data support the conclusion that MS-300 can specifically and efficiently capture Ae. albopictus and Cx. quinquefasciatus, and monitor their density automatically in real-time. Therefore, MS-300 has potential for use as a surveillance tool for prevention and control of vector mosquitoes.     

Enhanced Trafficking of Tetrameric Kv4.3 Channels by KChIP1 Clamping

The cytoplamsic auxiliary KChIPs modulate surface expression and gating properties of Kv4 channels. Recent co-crystal structure of Kv4.3 N-terminus and KChIP1 reveals a clamping action of the complex in which a single KChIP1 molecule laterally binds two neighboring Kv4.3 N-termini at different locations, thus forming two contact interfaces involved in the protein–protein interaction. In the second interface, it functions to stabilize the tetrameric assembly, but the role it plays in channel trafficking remains elusive. In this study, we examined the effects of KChIP1 on Kv4 protein trafficking in COS-7 cells expressing EGFP-tagged Kv4.3 channels using confocal microscopy. Mutations either in KChIP1 (KChIP1 L39E-Y57A-K61A) or Kv4.3 (Kv4.3 E70A-F73E) that disrupt the protein–protein interaction within the second interface can reduce surface expression of Kv4 channel proteins. Kv4.3 C110A, the Zn²⁺ binding site mutation in T1 domain, that disrupts the tetrameric assembly of the channels can be rescued by WT KChIP1, but not the KChIP1 triple mutant. These results were further confirmed by whole cell current recordings in oocytes. Our findings show that key residues of second interface involved in stabilizing tetrameric assembly can regulate the channel trafficking, indicating an intrinsic link between tetrameric assembly and channel trafficking. The results also suggest that formation of octameric Kv4 and KChIP complex by KChIPs clamping takes place before their trafficking to final destination on the cell surface. Special issue article in honor of Dr. Ji-Sheng Han.