PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling

Plastin-3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T-classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan–Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit-8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol-3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.     

Exogenous maltose enhances Zebrafish immunity to levofloxacin-resistant Vibrio alginolyticus

Understanding the interplay between bacterial fitness, antibiotic resistance, host immunity and host metabolism could guide treatment and improve immunity against antibiotic-resistant pathogens. The acquisition of levofloxacin (Lev) resistance affects the fitness of Vibrio alginolyticus in vitro and in vivo. Lev-resistant (Lev-R) V. alginolyticus exhibits slow growth, reduced pathogenicity and greater resistance to killing by the host, Danio rerio (zebrafish), than Lev-sensitive (Lev-S) V. alginolyticus, suggesting that Lev-R V. alginolyticus triggers a weaker innate immune response in D. rerio than Lev-S V. alginolyticus. Differences were detected in the metabolome of D. rerio infected with Lev-S or Lev-R V. alginolyticus. Maltose, a crucial metabolite, is significantly downregulated in D. rerio infected with Lev-R V. alginolyticus, and exogenous maltose enhances the immune response of D. rerio to Lev-R V. alginolyticus, leading to better clearance of the infection. Furthermore, we demonstrate that exogenous maltose stimulates the host production of lysozyme and its binding to Lev-R V. alginolyticus, which depends on bacterial membrane potential. We suggest that exogenous exposure to crucial metabolites could be an effective strategy for treating and/or managing infections with antibiotic-resistant bacteria.     

Soluble expression, purification and functional identification of a disulfide-rich conotoxin derived from Conus litteratus

Conotoxins are a diverse array of small peptides mostly with multiple disulfide bridges. These peptides become an increasing significant source of neuro-pharmacological probes and drugs as a result of the high selectivity for ion channels and receptors. Usually, the analogue of natural conotoxins is produced by means of chemical synthesis. Here, we present a simple and fast strategy of producing disulfide-rich conotoxins via recombinant expression. By fused with thioredoxin and His tag, a novel O-superfamily conotoxin lt7a was successfully expressed in Escherichia coli and purified, resulting in a high yield of recombinant lt7a about 6 mg/l. The purity of target protein is up to 95% as identified by HPLC results. Whole cell patch-clamp recording revealed that the new conotoxin blocked voltage-sensitive sodium channels in rat dorsal root ganglion neurons, indicating it might be a novel microO-conotoxin.     

海南红厚壳花香气成分采集和TCT-GC-MS分析

用鲜花循环式动态顶空技术采集红厚壳鲜花的香气成分,TCT-GC-MS联用技术分析鉴定。4-羟基-2-丁酮,双烯酮,1、2-环氧-2-甲基丁烷,1、2-环氧-3-甲基丁烷,2-乙基戊烷,3-己醇,甲基环戊烷,2-丁醇等24个成分被检测出,占总离子流出峰面积的90.28%。并对结果进行了分析讨论。     

Adult Cardiac Progenitor Cell Aggregates Exhibit Survival Benefit Both In Vitro and In Vivo

Background

A major hurdle in the use of exogenous stems cells for therapeutic regeneration of injured myocardium remains the poor survival of implanted cells. To date, the delivery of stem cells into myocardium has largely focused on implantation of cell suspensions.

Methodology and Principal Findings

We hypothesize that delivering progenitor cells in an aggregate form would serve to mimic the endogenous state with proper cell-cell contact, and may aid the survival of implanted cells. Microwell methodologies allow for the culture of homogenous 3D cell aggregates, thereby allowing cell-cell contact. In this study, we find that the culture of cardiac progenitor cells in a 3D cell aggregate augments cell survival and protects against cellular toxins and stressors, including hydrogen peroxide and anoxia/reoxygenation induced cell death. Moreover, using a murine model of cardiac ischemia-reperfusion injury, we find that delivery of cardiac progenitor cells in the form of 3D aggregates improved in vivo survival of implanted cells.

Conclusion

Collectively, our data support the notion that growth in 3D cellular systems and maintenance of cell-cell contact improves exogenous cell survival following delivery into myocardium. These approaches may serve as a strategy to improve cardiovascular cell-based therapies.     

The association between ATM IVS 22-77 T>C and cancer risk: a meta-analysis

Background and Objectives

It has become increasingly clear that ATM (ataxia-telangiectasia-mutated) safeguards genome stability, which is a cornerstone of cellular homeostasis, and ATM IVS 22-77 T>C affects the normal activity of ATM proteins. However, the association between the ATM IVS 22-77 T>C genetic variant and cancer risk is controversial. Therefore, we conducted a systematic meta-analysis to estimate the overall cancer risk associated with the polymorphism and to quantify any potential between-study heterogeneity.

Methods

A total of nine studies including 4,470 cases and 4,862 controls were analyzed for ATM IVS 22-77 T>C association with cancer risk in this meta-analysis. Heterogeneity among articles and their publication bias were also tested.

Results

Our results showed that no association reached the level of statistical significance in the overall risk. Interestingly, in the stratified analyses, we observed an inverse relationship in lung and breast cancer.

Conclusion

Further functional research on the ATM mechanism should be performed to explain the inconsistent results in different cancer types.     

Novel potassium N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl]-L-amino acid dichloroplatinates(II) with high anti-tumor activity and low side reaction

To discover whether novel anti-tumor platinum agents are capable of selectively accumulating in tumor tissue, three novel potassium N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl]-L-amino acid dichloroplatinates(II) were prepared. At a dose of 1.67 μmol kg(-1) the in vivo anti-tumor potencies of two of the compounds were higher than that of oxaliplatin. The mortality analysis indicated that these compounds resulted in a 100% survival rate, whereas oxaliplatin lead to an 80% survival rate. The organ damage examination indicated that these compounds induced less damage than oxaliplatin. The platinum accumulation in the organs, blood and bone was significantly lower than that of oxaliplatin treated mice, while the platinum accumulation in the tumor tissue was significantly higher than that of the oxaliplatin treated mice.