The Leptin Gene Family and Colorectal Cancer: Interaction with Smoking Behavior and Family History of Cancer

Background

Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin.

Methodology/Principal Findings

A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13–1.76) and 1.74 (95%CI 1.08–2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82×10⁻¹⁰).

Conclusions/Significance

Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.     

Peptide mimotopes of pneumococcal capsular polysaccharide of 6B serotype: a peptide mimotope can bind to two unrelated antibodies

Two groups of bacteriophage clones displaying the antigenic properties of serotype 6B pneumococcal capsular polysaccharide (PS) were obtained from different phage libraries expressing random heptameric peptides. One group, biopanned with a mouse mAb (Hyp6BM1), is comprised of 17 phage clones expressing 10 unique sequences of linear peptides. The other group, selected with another mAb (Hyp6BM8), contained six clones, all of which expressed the identical circular peptide. Phage clones expressing the linear peptides (e.g., PhaM1L3) bound only to Hyp6BM1, but not other 6B PS-specific mAb, and their binding could be inhibited with pneumococcal capsular type 6B PS only. In contrast, a phage clone expressing the circular peptide (PhaM8C1) cross-reacted with several other 6B PS-specific mAbs, and their binding could be inhibited with pneumococcal capsular PS of 6A and 6B serotypes. Two short peptides, PepM1L3 and PepM8C1, reflecting the peptide inserts of the corresponding phage clones, could inhibit the binding of the two clones to their respective mAb. Interestingly, the peptide insert in PhaM8C1 was identical to that in PhaB3C4, a previously reported mimotope of alpha(2-->8) polysialic acid, Neisseria meningitidis group B PS. Indeed, PhaM8C1 bound to HmenB3 (a meningococcal Ab), and their association could be inhibited with alpha(2-8) polysialic acid, but not with 6B PS. Conversely, alpha(2-8) polysialic acid could not inhibit the binding of PhaM8C1 to Hyp6BM8. The two-dimensional nuclear magnetic resonance studies indicate that PepM8C1 peptide can assume several conformations in solution. The ability of this peptide to assume multiple conformations might account for its ability to mimic more than one Ag type.     

Improved biological characteristics of poly(L-lactic acid) electrospun membrane by incorporation of multiwalled carbon nanotubes/hydroxyapatite nanoparticles

Significant effort has been devoted to fabricating various biomaterials to satisfy specific clinical requirements. In this study, we developed a new type of guided tissue regeneration (GTR) membrane by electrospinning a suspension consisting of poly( l-lactic acid), multiwalled carbon nanotubes, and hydroxyapatite (PLLA/MWNTs/HA). MWNTs/HA nanoparticles were uniformly dispersed in the membranes, and the degradation characteristics were far improved. Cytologic research revealed that the PLLA/MWNTs/HA membrane enhanced the adhesion and proliferation of periodontal ligament cells (PDLCs) by 30% and inhibited the adhesion and proliferation of gingival epithelial cells by 30% also, compared with the control group. After PDLCs were seeded into the PLLA/MWNTs/HA membrane, cell/membrane composites were implanted into the leg muscle pouches of immunodeficient mice. Histologic examinations showed that PDLCs attached on the membranes functioned well in vivo. This new type of membrane shows excellent dual biological functions and satisfied the requirement of the GTR technique successfully in spite of a monolayer structure. Compared with other GTR membranes on sale or in research, the membrane can simplify the manufacturing process, reduce the fabrication cost, and avoid possible mistakes in clinical application. Moreover, it does not need to be taken out after surgery. PLLA/MWNTs/HA membranes have shown great potential for GTR and tissue engineering.     

Microsatellite Markers and Genetic Diversity of Four Scleractinian Corals

Russian Journal of Marine Biology - Eighteen microsatellite sequences were isolated from Platygyra acuta through magnetic bead hybridization enrichment method, and the site primers were used to...     

松山自然保护区各功能区植被动态及变化格局

作为全球生态保育的基石,保护区管理和设计成为研究热点。本研究旨在描述不同功能区在相应保护措施下植被的差异性变化。运用遥感和GIS技术以及景观分析手段,利用两期Landsat5TM影像提取出北京松山国家级自然保护区1987、2001年的归一化差值植被指数(NormalizedDifferenceVegetationIndex,NDVI)信息,对植被动态进行分析,并按变化率分为减少、无变化和增加3种类型,利用景观指数刻画出变化格局,就植被动态及其变化格局在不同功能区的空间分异性进行比较。得到以下主要结论:(1)保护区建立后植被大体稳定并有所改善,形成核心区>缓冲区>实验区的植被覆盖梯度。(2)在绝对保护措施下,核心区植被稳定性高并得到进一步改善。植被稳定类型集中于区域中心,增加类型聚集在区域边缘,减少类型与自然植被动态特征相符呈随机分布状态。(3)受经营、开发措施影响,实验区稳定性低,变化面积大、变幅大、增加与衰退共存,植被覆盖居全保护区最低且有退化趋势。(4)缓冲区植被动态呈现出一定的随机分布格局。     

MicroRNA profile analysis of a feline kidney cell line before and after infection with mink enteritis virus

MicroRNAs (miRNAs) are small regulatory RNAs that play a significant role in eukaryotes by targeting mRNAs for cleavage or translational repression. Recent studies have also shown them to be associated with cellular changes following viral infection. Mink enteritis virus (MEV) is one of the most important viral pathogens in the mink industry. To study the involvement of miRNAs in the MEV infection process, we used Illumina's ultrahigh throughput approach to sequencing miRNA libraries from the feline kidney (F81) cell line before and after infection with MEV. Using this bioinformatics approach we identified 196 known mammalian miRNA orthologs belonging to 152 miRNA families in F81 cells. Additionally, 97 miRNA*s of these miRNAs were detected. As well as known miRNAs, 384 and 398 novel miRNA precursor candidates were identified in uninfected and MEV-infected F81 cells respectively that have not been reported in other mammals. In MEV-infected cells 3 miRNAs were significantly down-regulated and 4 up-regulated including 3 significantly. The majority (12 of 16) of randomly selected miRNA expression profiles by qRT-PCR were consistent with those identified by deep sequencing. A total of 88 miRNAs were predicted to target interferon-associated genes; 6 appear to target the 3′UTR of MEV-specific receptor transferring receptor mRNAs; and 8 to target the MEV mRNA coding region. No miRNAs coded by MEV itself were detected.     

MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor,feline transferrin receptor

Mink enteritis virus (MEV) is one of the most important pathogens in the mink industry. Recent studies have shed light into the role of microRNAs (miRNAs), small noncoding RNAs of length ranging from 18–23 nucleotides (nt), as critical modulators in the host-pathogen interaction networks. We previously showed that miRNA miR-181b can inhibit MEV replication by repression of viral non-structural protein 1 expression. Here, we report that two other miRNAs (miR-320a and miR-140) inhibit MEV entry into feline kidney (F81) cells by downregulating its receptor, transferrin receptor (TfR), by targeting the 3′ untranslated region (UTR) of TfR mRNA, while being themselves upregulated.