Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants.

Background: CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 families are rare and lack a systematic investigation of their phenotype.

Methods: All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL).

Mitochondrial DNA response to high altitude: a new perspective on high-altitude adaptation.

Mitochondria are the energy metabolism centers of the cell. More than 95% of cellular energy is produced by mitochondrial oxidative phosphorylation. Hypoxia affects a wide range of energy generation and consumption processes in animals.

Exploring the genetic characteristics of two recombinant inbred line populations via high-density SNP markers in maize.

Understanding genetic characteristics can reveal the genetic diversity in maize and be used to explore evolutionary mechanisms and gene cloning. A high-density linkage map was constructed to determine recombination rates (RRs), segregation distortion regions (SDRs), and recombinant blocks (RBs) in two recombinant inbred line populations (RILs) (B73/By804 and Zong3/87-1) generated by the single seed descent method. Population B73/By804 containing 174 lines were genotyped with 198 simple sequence repeats (SSRs) markers while population Zong3/87-1 comprised of 175 lines, were genotyped with 210 SSR markers along with 1536 single nucleotide polymorphism (SNP) markers for each population, spanning 1526.

On the interplay of telomeres, nevi and the risk of melanoma.

The relationship between telomeres, nevi and melanoma is complex. Shorter telomeres have been found to be associated with many cancers and with number of nevi, a known risk factor for melanoma. However, shorter telomeres have also been found to decrease melanoma risk.

[The efficacy of antihypertensive treatment on diabetes mellitus or impaired glucose tolerance patients with blood pressure below 140/90 mm Hg: a meta-analysis].

Objective: To investigate whether antihypertensive treatment is beneficial to patients with diabetes mellitus when their blood pressure (BP) is below 140/90 mm Hg (1 mm Hg = 0.133 kPa).

Methods: MEDLINE, EMBASE, IPA database and secondary resources were searched with terms including blood pressure, hypertension and anti-hypertension drug.

Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer.

Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. We analyzed 270 breast cancer cases included in a population-based breast cancer case-control study conducted in Poland.

Genome-wide association study dissects the genetic architecture of oil biosynthesis in maize kernels.

Maize kernel oil is a valuable source of nutrition. Here we extensively examine the genetic architecture of maize oil biosynthesis in a genome-wide association study using 1.03 million SNPs characterized in 368 maize inbred lines, including 'high-oil' lines.

Natural variation in the sequence of PSY1 and frequency of favorable polymorphisms among tropical and temperate maize germplasm.

Provitamin A (Pro-VA) is necessary for human vision and immune system health, especially in growing children. The first committed step in the maize carotenoid biosynthesis pathway is catalyzed by phytoene synthase 1 (encoded by PSY1) which controls the flux of substrates into the pathway. The flow of these substrates could be directed into production of the β-branch carotenoids (the step controlled largely by the lycopene epsilon cyclase gene), but terminated after the production of β-carotene, rather than allowing it to be converted into the next metabolite (the step controlled largely by the β-carotenoid hydroxylase gene).

[Analysis of a family affected with familial male-limited precocious puberty due to a Ala568Val mutation in LHCGR gene].

Objective: Familial male-limited precocious puberty (FMPP) is due to constitutive activation of a mutant luteinizing hormone/choriogonadotropin receptor (LH/CGR) leading to elevated testosterone synthesis in testicular Leydig cells. In the present study, we have analyzed the LHCGR gene for members of a Chinese FMPP family.

Methods: Physical examinations have included assessment of penile length, testicular volume and pubic hair.

LINE-1 methylation in peripheral blood and the risk of melanoma in melanoma-prone families with and without CDKN2A mutations.

Cutaneous malignant melanoma (CMM) is an etiologically heterogenous disease with genetic, environmental (sun exposure), and host (pigmentation/nevi) factors and their interactions contributing to risk. Recently, epigenetic changes involving reduced levels of global DNA methylation in blood have been associated with genomic instability and cancer risk. We thus examined whether global methylation was associated with CMM risk in individuals from melanoma-prone families with and without CDKN2A germline mutations.

Effect of Sanqi Oral Liquid on the expressions of CD4⁺, CD8⁺ and CD68⁺ cells in 5/6 nephrectomized rats with chronic renal failure.

Objective: To explore the mechanisms of Chinese herbal medicine Sanqi Oral Liquid, composed of Astragalus membranaceus and Panpax notoginseng, in alleviating renal injury by observing its effect on the expressions of CD4(+), CD8(+) and CD68(+) cells in 5/6 nephrectomized rats with chronic renal failure.

Methods: A total of 102 SD rats were randomly divided into six groups: three treatment groups were administrated with high, medium and low dosage of Sanqi Oral Liquid respectively by gavage; a normal group, a 5/6 nephrectomized model group, and a group treated with coated aldehyde oxygenstarch were used as controls. Following oral administration of Sanqi Oral Liquid for 12 weeks, the general condition and renal pathological changes were observed, and the renal function, platelet count (PLT) and the expressions of CD4(+), CD8(+) and CD68(+) cells were determined for each group.

Dissecting tocopherols content in maize (Zea mays L.), using two segregating populations and high-density single nucleotide polymorphism markers.

Background: Tocopherols, which are vitamin E compounds, play an important role in maintaining human health. Compared with other staple foods, maize grains contain high level of tocopherols.

Results: Two F(2) populations (K22/CI7 and K22/Dan340, referred to as POP-1 and POP-2, respectively), which share a common parent (K22), were developed and genotyped using a GoldenGate assay containing 1,536 single nucleotide polymorphism (SNP) markers.

Karyotype and DNA-Methylation Responses in Myelodysplastic Syndromes following Treatment with Traditional Chinese Formula Containing Arsenic.

We have previously shown that arsenic-containing Chinese herbal formula, Qing-Huang powder capsule (containing tetraarsenic tetrasulfide, As(4)S(4)), is effective in the treatment of myelodysplastic syndrome (MDS); yet the underlined mechanisms remain unclear. In this study, using standard cytogenetic analysis (G-banded) and global DNA methylation method (ChIP-on-chip assays), we aimed to determine the effect of arsenic-containing Chinese herbal formula on karyotype status and the genomic methylation level in primarily diagnosed MDS patients. Correlation of aberrant DNA methylation and chromosome aberrations in MDS was also investigated.

Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma.

Aim: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines.

Methods: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepatocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5-diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro) and tumor metastasis assay (in vivo) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis.

Results: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo.

Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma.

Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro.

Large-surface mesoporous TiO2 nanoparticles: synthesis, growth and photocatalytic performance.

This study demonstrates a facile and effective method to generate mono-dispersed titanium dioxide spheres at ambient conditions. The size of the colloids can be controlled from 60 to 500 nm by optimizing experimental parameters (e.g.

Characterization of diverse antimicrobial peptides in skin secretions of Chungan torrent frog Amolops chunganensis.

We have cloned, synthesized, and characterized 11 novel antimicrobial peptides from a skin derived cDNA library of the Chungan torrent frog, Amolops chunganensis. Seven of the 11 antimicrobial peptides were present in authentic A. chunganensis skin secretions.

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-D-glucose gold nanoparticles in vivo.

We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-D-glucose (6-FDG) to gold nanoparticles (6-FDG-GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG-GNPs in vivo using a murine model. At 2 h, following intravenous injection of 6-FDG-GNPs into the murine model, approximately 30% of the 6-FDG-GNPs were distributed to three major organs: the liver, the spleen and the kidney.

Design and synthesis of a series of pyrido[2,3-d]pyrimidine derivatives as CCR4 antagonists.

A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b was proven to be a potent CCR4 antagonist that can block cell chemotaxis induced by macrophage-derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and CKLF1, the natural ligands of CCR4.

Induction of antigen-specific immune responses in mice by recombinant baculovirus expressing premembrane and envelope proteins of West Nile virus.

Background: West Nile Virus (WNV) is an emerging arthropod-born flavivirus with increasing distribution worldwide that is responsible for a large proportion of viral encephalitis in humans and horses. Given that there are no effective antiviral drugs available for treatment of the disease, efforts have been directed to develop vaccines to prevent WNV infection. Recently baculovirus has emerged as a novel and attractive gene delivery vehicle for mammalian cells.

A transposable element insertion within ZmGE2 gene is associated with increase in embryo to endosperm ratio in maize.

Most of the maize kernel oil is located in the embryo while the majority of starch is located in the endosperm. Maize kernel composition and value are affected significantly by the ratio of the embryo size to the endosperm size; however, the genetic regulation of embryo to endosperm ratio (EER) in maize is unknown. Here we identified ZmGE2 gene, which encodes a cytochrome p450 protein, as a gene associated with EER variation in maize.

Design, synthesis, and preliminary biological evaluation of 6-O-glucose-azomycin adducts for diagnosis and therapy of hypoxic tumors.

Several 2-nitroimidazole-based molecules (NIs) are used as clinical hypoxic tumor radiodiagnostics, but they are not effective as radiosensitizers/radiochemotherapeutics. These NIs permeate tumor cells nonselectively via diffusion, and in therapy, where high doses are required, their dose limiting toxicities preclude success. The synthesis and preliminary in vitro evaluations of three glucoazomycins, members of a novel class of C6-O-glucose-linked-azomycin conjugates that are putative substrates of glucose transport proteins (GLUTs) and possess hypoxia-selective radiosensitization features, are now reported.

VEGF upregulates VEGF receptor-2 on human outer root sheath cells and stimulates proliferation through ERK pathway.

Vascular endothelial growth factor (VEGF) is a key regulator of physiological and pathological angiogenesis. The biological effects of VEGF are mediated by receptor tyrosine kinases. VEGF receptor-2, the primary receptor for VEGF, is thought to mediate most functional effects.

Characterization of QTL for oil content in maize kernel.

Kernel oil content in maize is a complex quantitative trait. Phenotypic variation in kernel oil content can be dissected into its component traits such as oil metabolism and physical characteristics of the kernel, including embryo size and embryo-to-endosperm weight ratio (EEWR). To characterize quantitative trait loci (QTL) for kernel oil content, a recombinant inbred population derived from a cross between normal line B73 and high-oil line By804 was genotyped using 228 molecular markers and phenotyped for kernel oil content and its component traits [embryo oil content, embryo oil concentration, EEWR, embryo volume, embryo width, embryo length, and embryo width-to-length ratio (EWLR)].