Coffee consumption and prostate cancer risk: further evidence for inverse relationship

<p>Abstract</p> <p>Background</p> <p>Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.</p> <p>Results</p> <p>Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.</p> <p>Conclusion</p> <p>Coffee consumption reduces the risk of aggressive PC but not the overall risk.</p

Evolutionary response of Caragana (Fabaceae) to Qinghai-Tibetan Plateau uplift and Asian interior aridification

Caragana is endemic to temperate Asia, with most species distributed on the Qinghai-Tibetan Plateau (QTP) and in Northwestern China. Consequently its biogeography should be hypothesized to have been affected by QTP uplift. To examine the biogeography of Caragana in relation to QTP uplift and consequent interior aridification, we conducted molecular dating analyses based on three genes (ITS, cpDNA trnS-trnG and rbcL). Results from relaxed Bayesian BEAST, relaxed Bayesian Multidivtime, and PL (penalized likelihood) indicate that QTP uplift, especially the onset of Himalayan motion at 21-17 Ma, triggered the origin of Caragana (with estimated ages 16-14 Ma). The subsequent QTP rapid uplift at 8 Ma is inferred to have driven the evolution and diversification of the three major clades of Caragana: section Caragana (northern China and the Junggar-Altai-Sayan region), section Frutescentes (Central Asia), and sections Bracteolatae and Jubatae, centered in the QTP. A rapid and active speciation process occurring in the QTP intense uplift at 3.4-1.8 Ma, is indicated by the chronogram

Acidosis, a fundamental regulator of bone cell function

Previous work has demonstrated that bone cells are highly sensitive to extracellular acidification. Low pH is a key osteoclast activation factor, and reduces bone formation by inhibiting mineralisation of the matrix. The aim of this thesis was to investigate further the roles played by pH in modulating bone cell function. Transient receptor potential (TRP) channels detect protons within the pathophysiological range, so are potential candidates for mediating the observed effects of acid on bone cells. I found that TRPV1 agonists/antagonists had no effect on osteoclast formation and activation or bone mineralisation by osteoblasts. Additionally, TRPV1-/- osteoclasts demonstrated no functional differences from wildtypes. Furthermore, agonists/antagonists for TRPM8, TRPV4 and TRPV3 were without effect. Pyrophosphate (PPi) a fundamental inhibitor of mineralisation in the bone microenvironment is generated from extracellular nucleotides by ecto-nucleotidases such as E-NPP1. I showed that E-NPP1 mRNA and protein were up-regulated in osteoblasts cultured at pH 6.9; total E-NPP activity was also increased. To determine the role of acidification in tumour-induced osteolysis, I devised an in vitro model to investigate interactions of osteoclasts with breast cancer cells, which metastasise to bone, sometimes causing osteolytic disease. Surprisingly, the overall effect of breast cancer cells on osteoclasts was inhibitory; however, resorption was significantly stimulated relative to buffered controls when breast cancer cells were allowed to acidify the culture medium. These results suggest that local acidification in tumour settings in vivo could be an important factor in determining the degree of osteolysis that occurs. Finally, I investigated whether two key cytokines implicated in the vicious cycle model of tumour-mediated osteolysis, B-cell activating factor (BAFF) and activin A influence osteoclast function. In all experiments only acidosis stimulated osteoclast resorption. These results provide further evidence for the fundamental role of acid as a regulator of bone cell function

Phylogeny of Salsoleae s.l. (Chenopodiaceae) based on DNA sequence data from ITS, psbB-psbH, and rbcL, with emphasis on taxa of northwestern China

To reconstruct phylogeny and verify the monophyly of major subgroups, a total of 52 species representing almost all species of Salsoleae s.l. in China were sampled, with analysis based on three molecular markers (nrDNA ITS, cpDNA psbB psbH and thcL), using maximum parsimony, maximum likelihood, and Bayesian inference methods Our molecular evidence provides strong support for the following: (1) Camphorosmeae is nested within Salsoleae s.l. instead of the previously suggested sister relationship. (2) Tribe Salsoleae s.I is monophyletic and is composed of three monophyletic subunits, Caroxyloneae, the Kali clade, and Salsoleae s.str (3) Climacoptera is separated from Salsola s I It does not form a monophyletic group but is split into two monophyletic parts, Climacoptera I and Chmacoptera II (4) Halogeton is clearly polyphyletic, as are Anabasis and the genus Salsola s.l. (5) Caroxylon, Halo.xylon, Kali, and Petrosnnonia are well-supported monophyletic genera. Additional evidence is needed regarding the monophyly of Halimocnemis, which remains unclear

Thiol-Functionalized Mesoporous Silica for Effective Trap of Mercury in Rats

The chance of exposure to heavy metal for human being rises severely today due to the increasing water contamination and air pollution. Here, we prepared a series of thiol-functionalized mesoporous silica as oral formulation for the prevention and treatment of heavy metal poisoning. The successful incorporation of thiol was verified by the FTIR spectra. SBA15-SH-10 was used for the study as it is of uniform mesopores and fine water dispersibility. In simulated gastrointestinal fluid, the thiol-functionalized mesoporous silica can selectively capture heavy metal, showing a very high affinity for inorganic mercury (II). The blood and urine mercury levels of rats fed with a diet containing Hg (II) and material were significantly lower than those of rats fed with the metal-rich diet only. On the contrary, the mercury content in fecal excretion of the treatment group increased more than twice as much as that of the control group. This result indicated that SBA15-SH-10 could effectively remove mercury (II) in vivo and the mercury loaded on SBA15-SH-10 would be excreted out. Hence, SBA15-SH-10 has potential application in preventing and treating heavy metal poisoning via digestive system

Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole

Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m-2; 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m-2; 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m -2; and 43.3 (23.0-81.7, n=16) when 6535.0 kg m-2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patient

Rare coding variants and X-linked loci associated with age at menarche

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P&lt;5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the &apos;missing heritability&apos; of this complex trait

Increasing vegetable intakes: rationale and systematic review of published interventions

Purpose While the health benefits of a high fruit and vegetable consumption are well known and considerable work has attempted to improve intakes, increasing evidence also recognises a distinction between fruit and vegetables, both in their impacts on health and in consumption patterns. Increasing work suggests health benefits from a high consumption specifically of vegetables, yet intakes remain low, and barriers to increasing intakes are prevalent making intervention difficult. A systematic review was undertaken to identify from the published literature all studies reporting an intervention to increase intakes of vegetables as a distinct food group. Methods Databases—PubMed, PsychInfo and Medline—were searched over all years of records until April 2015 using pre-specified terms. Results Our searches identified 77 studies, detailing 140 interventions, of which 133 (81 %) interventions were conducted in children. Interventions aimed to use or change hedonic factors, such as taste, liking and familiarity (n = 72), use or change environmental factors (n = 39), use or change cognitive factors (n = 19), or a combination of strategies (n = 10). Increased vegetable acceptance, selection and/or consumption were reported to some degree in 116 (83 %) interventions, but the majority of effects seem small and inconsistent. Conclusions Greater percent success is currently found from environmental, educational and multi-component interventions, but publication bias is likely, and long-term effects and cost-effectiveness are rarely considered. A focus on long-term benefits and sustained behaviour change is required. Certain population groups are also noticeably absent from the current list of tried interventions