Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system

Background: Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Autoantibodies to tumor-associated proteins in the serum profile, as new biomarkers, may improve the early detection of HCC. Methods: In this study, we interrogated a HCC cDNA T7 phage library for tumor-associated proteins using biopan enrichment techniques with HCC patient and normal sera. The enrichment of tumor-associated proteins after biopanning was tested using plaque assay and immunochemical detection. The putative tumor-associated phage clones were collected for PCR and sequencing analysis. Identities of those selected sequences were revealed through the sequence BLAST program. The identified phage-expressed proteins were then used to develop phage protein ELISA to measure matching autoantibodies using 70 HCC patients, 50 chronic hepatitis patients, and 70 normal serum samples. The logistic regression model and leave-one-out validation were used to evaluate predictive accuracies with a single marker as well as with combined markers. Results: Twenty-six phage-displayed proteins have sequence identity with known or putative tumor-associated proteins. Immunochemical reactivity of patient sera with phage-expressed proteins showed that the autoantibodies to phage-expressed protein CENPF, DDX3, HSPA4, HSPA5, VIM, LMNB1, and TP53 had statistical significance in HCC patients. Measurements of the seven autoantibodies combined in a logistic regression model showed that combined measurements of these autoantibodies was more predictive of disease than any single antibody alone, underscoring the importance of identifying multiple potential markers. Conclusion: Autoantibody in the serum profiling is a promising approach for early detection and diagnosis of HCC. The panel of autoantibodies appears preferable to achieve superior accuracy rather than an autoantibody alone, and may have significant relevance to tumor biology, novel drug development, and immunotherapies.     

Involvement of Agrobacterium tumefaciens Galacturonate Tripartite ATP-Independent Periplasmic (TRAP) Transporter GaaPQM in Virulence Gene Expression

Monosaccharides capable of serving as nutrients for the soil bacterium Agrobacterium tumefaciens are also inducers of the vir regulon present in the tumor-inducing (Ti) plasmid of this plant pathogen. One such monosaccharide is galacturonate, the predominant monomer of pectin found in plant cell walls. This ligand is recognized by the periplasmic sugar binding protein ChvE, which interacts with the VirA histidine kinase that controls vir gene expression. Although ChvE is also a member of the ChvE-MmsAB ABC transporter involved in the utilization of many neutral sugars, it is not involved in galacturonate utilization. In this study, a putative tripartite ATP-independent periplasmic (TRAP) transporter, GaaPQM, is shown to be essential for the utilization of galacturonic acid; we show that residue R169 in the predicted sugar binding site of the GaaP is required for activity. The gene upstream of gaaPQM (gaaR) encodes a member of the GntR family of regulators. GaaR is shown to repress the expression of gaaPQM, and the repression is relieved in the presence of the substrate for GaaPQM. Moreover, GaaR is shown to bind putative promoter regions in the sequences required for galacturonic acid utilization. Finally, A. tumefaciens strains carrying a deletion of gaaPQM are more sensitive to galacturonate as an inducer of vir gene expression, while the overexpression of gaaPQM results in strains being less sensitive to this vir inducer. This supports a model in which transporter activity is crucial in ensuring that vir gene expression occurs only at sites of high ligand concentration, such as those at a plant wound site.     

番茄皂苷A对小鼠血脂及肝脏脂肪的作用

该研究以ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠为对象,采用药理学方法研究了番茄皂苷A对血脂及肝脏脂肪的调节作用。在ApoE基因缺陷小鼠和高脂饲料诱导的高血脂症模型小鼠中,通过灌胃给予番茄皂苷A:取血,测定血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素氮(BUN)、肌酐(Cr)、葡萄糖(Glu)的含量和活性;处死小鼠后,取肝脏称重,计算肝脏指数;精确称取一部分肝脏,测定肝脏脂质的含量。结果表明:番茄皂苷A对ApoE基因缺陷小鼠可以降低血清TC、HDLC、LDLC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以降低ApoE基因缺陷小鼠血中胆固醇含量,对血糖没有影响,对肝肾功能无影响;对高脂饲料诱导的高血脂症模型小鼠,可以降低血清TC、HDLC的含量,可以降低肝脏TC的含量,对ALT、AST、BUN、Cr、Glu没有影响,说明番茄皂苷A可以改善高脂饲料诱导的高血脂症模型小鼠的脂质代谢,且对肝肾功能无影响。该研究结果表明番茄皂苷A具有一定的降低胆固醇的作用,且不影响肝肾功能。     

High-Performance Tunable Multichannel Absorbers Coupled with Graphene-Based Grating and Dual-Tamm Plasmonic Structures

Plasmonics - We present a hybrid Tamm system targeting the tunable multichannel absorber. The proposed optical absorber is analyzed and investigated by using the transfer matrix method (TMM). The...     

A trade-off between primary and secondary seed dispersal by wind

Plant Ecology - The seeds of most plant species are dispersed by multiple mechanisms. Whether functional traits mediate positive correlations or negative correlations (trade-offs) between different...     

Synthesis,evaluation and quantitative structure–activity relationship (QSAR) analysis of Wogonin derivatives as cytotoxic agents

A novel series of 49 wogonin derivatives were synthesized by introducing group at 7-, 8- or B ring of wogonin. The cytotoxic activities against HepG2, A549 and BCG-823 cancer cell lines were also investigated in vitro. Several of them showed obvious cytotoxic activities and compound 3h possessed the highest potency against HepG2, A549, and BCG-823 with IC₅₀ values of 1.07 μM, 1.74 μM and 0.98 μM, respectively. A quantitative structure-activity relationship (QSAR) study of these synthetic derivatives as well as wogonin indicated that high solubility and low octanol/water partition coefficient are favorable, and excessive electrostatic properties and refractivity are unfavorable for the cytotoxic activities of these wogonin derivatives. These findings and results provide a base for further investigations.