A Survey of Alkylphenols,Bisphenols, and Triclosan in Personal Care Products from China and the United States

Exposure of humans to environmental phenolic compounds such as bisphenol A (BPA) and alkylphenols is a matter of concern, due to these compounds’ ubiquitous occurrence and estrogenic potencies. Little is known about the levels of environmental phenolics in personal care products (PCPs). In this study, nonylphenol, two octylphenols, eight bisphenols (BPA and its analogs), and triclosan (TCS) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in PCP samples (n = 231) collected from China and the United States (U.S.). The concentrations of 4-n-nonylphenol (4-NP), 4-n-octylphenol (4-OP), 4-tert-octylphenol (4-t-OP), and TCS were in the ranges of <0.5–39,100 [geometric mean (GM): 21.5], <0.5–315 (0.680), <1.0–10,100 (2.69), and <0.5–53,900 (3.03) ng/g, respectively. The GM concentrations of individual bisphenols, including BPA, bisphenol S (BPS), and bisphenol F (BPF), were generally at sub-nanogram per gram levels. No significant differences in concentrations of the target compounds were found among various PCP categories or between China and the U.S. The estimated GM daily intakes of 4-NP, ∑OPs (sum of 4-OP and 4-t-OP), ∑BPs (sum of eight bisphenols), and TCS through dermal absorption from the use of PCPs were 0.932, 0.093, 0.072, and 0.016 μg/day, respectively, for adult Chinese women and 0.340, 0.054, 0.120, and 0.068 μg/day, respectively, for adult U.S. women. Body lotions, face creams, and liquid foundations accounted for the majority (>85 %) of the dermal exposure doses of the target phenolics.     

Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) −174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 −174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32–0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) −174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00–1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55–0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37–0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59–3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 −174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.     

Opposing effects of pro‐ and anti‐inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study

In an earlier study, the genotypes associated with higher level of transforming growth factor‐β1 (TGF‐β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro‐ and anti‐inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single‐nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL‐4 (IL‐4 C‐590T; rs2243250), IFN‐γ (IFN‐G A + 874T; rs2430561) and MCP‐1 (MCP‐1 A‐2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL‐4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37–0.98) was seen similar to that seen in TGF‐B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP‐1 or IFN‐γ. In individuals positive for three or more alleles associated with higher levels of either pro‐ or anti‐inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF‐B1 & IL‐4, OR = 0.33, 95% CI 0.12–0.87; for IFN‐G & MCP‐1, OR = 2.29, 95% CI 0.95–5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti‐inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.     

Regulation of E-kinase mediated cell-adhesion molecule(s) function by E-NTPase(s): imminent regulatory inter-dependency for cell adhesion

E-NTPase is a cell membrane bound enzyme, suggested to play a role in maintaining the [NTP](o) and cell adhesion. Attempts to purify this enzyme resulted identification of many proteins co-purifying with E-NTPase. The amino acid sequence of chicken gizzard smooth muscle E-NTPase has been shown to have considerable amino acid sequence homology with mammalian CD39. On the other hand, the purified rat cardiac sarcolemmal E-NTPase showed identical sequence homology with platelet CD36. In this communication, an effort was made to provide rationale for the functional relevance of E-NTPase with reference to cell-adhesion process.     

ProKinO: A Unified Resource for Mining the Cancer Kinome

Protein kinases represent a large and diverse family of evolutionarily related proteins that are abnormally regulated in human cancers. Although genome sequencing studies have revealed thousands of variants in protein kinases, translating “big” genomic data into biological knowledge remains a challenge. Here, we describe an ontological framework for integrating and conceptualizing diverse forms of information related to kinase activation and regulatory mechanisms in a machine readable, human understandable form. We demonstrate the utility of this framework in analyzing the cancer kinome, and in generating testable hypotheses for experimental studies. Through the iterative process of aggregate ontology querying, hypothesis generation and experimental validation, we identify a novel mutational hotspot in the αC‐β4 loop of the kinase domain and demonstrate the functional impact of the identified variants in epidermal growth factor receptor (EGFR) constitutive activity and inhibitor sensitivity. We provide a unified resource for the kinase and cancer community, ProKinO, housed at http://vulcan.cs.uga.edu/prokino .     

Dendrimer-enabled DNA delivery and transformation of Chlamydia pneumoniae

The chlamydiae are important human pathogens. Lack of a genetic manipulation system has impeded understanding of the molecular bases of virulence for these bacteria. We developed a dendrimer-enabled system for transformation of chlamydiae and used it to characterize the effects of inserting the C. trachomatis plasmid into C. pneumoniae, which lacks any plasmids. The plasmid was cloned into modified yeast vector pEG(KG) and the clone complexed to polyamidoamine dendrimers, producing 50–100 nm spherical particles. HEp-2 cell cultures were infected with C. pneumoniae strain AR-39. Twenty-four hours later, medium was replaced for 3 hours with dendrimer-plasmid complexes, then removed and the medium replaced. Cultures were harvested at various times post-transformation. Real-time PCR and RT-PCR of nucleic acids from transformed cultures demonstrated plasmid replication and gene expression. The cloned plasmid was replicated and expressed in transformants over 5 passages. This system will allow study of chlamydial gene function, allowing development of novel dendrimer-based therapies.From the Clinical EditorThis team of investigators developed a dendrimer-enabled system for transformation of chlamydiae and successfully utilized it to characterize the effects of inserting the C. trachomatis plasmid into C. pneumonia. This system will allow study of chlamydial gene function, allowing development of novel dendrimer-based therapies.     

BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine

Virus-neutralizing antibody and B cell responses to influenza A viruses were measured in 35 aged and 28 middle-aged individuals following vaccination with the 2012 and 2013 trivalent inactivated influenza vaccines. Antibody responses to the vaccine strains were lower in the aged. An analysis of B cell subsets by flow cytometry with stains for immunoregulators showed that B cells of multiple subsets from the aged as compared to younger human subjects showed differences in the expression of the co-inhibitor B and T lymphocyte attenuator (BTLA). Expression of BTLA inversely correlated with age and appears to be linked to shifting the nature of the response from IgM to IgG. High BTLA expression on mature B cells was linked to higher IgG responses to the H1N1 virus. Finally, high BTLA expression on isotype switched memory B cells was linked to better preservation of virus neutralizing antibody titers and improved recall responses to vaccination given the following year.     

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127

Magnetic nanoparticles are promising molecular imaging agents due to their relatively high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co‐polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell‐culture model were quantified using concurrent assaying: a lactate dehydrogenase assay to determine cytotoxicity and a 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium, inner salt assay to determine viability for a 24 h incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents needs to be carefully constructed to avoid interference and erroneous results. Copyright © 2010 John Wiley & Sons, Ltd.