Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds

Identifying patient concerns during consultations in tertiary burns services: development of the Adult Burns Patient Concerns Inventory

ObjectivesIdentifying the issues and concerns that matter most to burns survivors can be challenging. For a number of reasons, but mainly relating to patient empowerment, some of the most pressing concerns patients may have during a clinical encounter may not naturally be the focal point of that encounter. The Patient Concerns Inventory (PCI) is a tried and tested concept initially developed in the field of head and neck cancer that empowers patients during a clinical encounter through provision of a list of prompts that allows patients to self-report concerns prior to consultation. The aim of this study was to develop a PCI for adult burns patients.DesignContent for the PCI was generated from three sources: burns health-related quality of life tools, thematic analysis of one-to-one interviews with 12 adult burns patients and 17 multidisciplinary team (MDT) members. Content was refined using a Delphi consensus technique, with patients and staff members, using SurveyMonkey.SettingWithin outpatient secondary care.ParticipantsTwelve adult burns patients and MDT members from two regional burns centres.ResultsA total of 111 individual items were generated from the three sources. The Delphi process refined the total number of items to 58. The main emergent domains were physical and functional well-being (18 items), psychological, emotional and spiritual well-being (22 items), social care and social well-being (7 items) and treatment-related concerns (11 items).ConclusionsThe Adult Burns Patient Concerns Inventory is a 58-item, holistic prompt list, designed to be used in the outpatient clinic. It offers a new tool in burn care to improve communication between healthcare professionals and patients, empowering them to identify their most pressing concerns and hence deliver a more focused and targeted patient-centred clinical encounter

Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B Leukemic Cells

<p>Abstract</p> <p>Background</p> <p>Cucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood.</p> <p>Methods</p> <p>BJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site.</p> <p>Results</p> <p>Herein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis.</p> <p>Conclusions</p> <p>Taken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression.</p

The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation

The fruit of the date palm (Phoenix dactylifera L.) is a rich source of dietary fibre and polyphenols. We have investigated gut bacterial changes induced by the whole date fruit extract (digested date extract; DDE) and its polyphenol-rich extract (date polyphenol extract; DPE) using faecal, pH-controlled, mixed batch cultures mimicking the distal part of the human large intestine, and utilising an array of microbial group-specific 16S rRNA oligonucleotide probes. Fluorescence microscopic enumeration indicated that there was a significant increase in the growth of bifidobacteria in response to both treatments, whilst whole dates also increased bacteroides at 24 h and the total bacterial counts at later fermentation time points when compared with DPE alone. Bacterial metabolism of whole date fruit led to the production of SCFA, with acetate significantly increasing following bacterial incubation with DDE. In addition, the production of flavonoid aglycones (myricetin, luteolin, quercetin and apigenin) and the anthocyanidin petunidin in less than 1 h was also observed. Lastly, the potential of DDE, DPE and metabolites to inhibit Caco-2 cell growth was investigated, indicating that both were capable of potentially acting as antiproliferative agents in vitro, following a 48 h exposure. This potential to inhibit growth was reduced following fermentation. Together these data suggest that consumption of date fruits may enhance colon health by increasing beneficial bacterial growth and inhibiting the proliferation of colon cancer cells. This is an early suggestion that date intake by humans may aid in the maintenance of bowel health and even the reduction of colorectal cancer development

Estimation of the reinforcement factor xi for calculating the transverse stiffness E2 with the Halpin-Tsai equations using the finite element method

In this work, an estimation of the reinforcement factor n of the Halpin Tsai equations used to calculate the transverse stiffness E2 is provided. An improved estimation of the value xi=2 originally proposed by Halpin and Tsai is given through a set of finite element analyses that consider randomly distributed unidirectional fibers for different volume fractions. The analysis overcomes the original hypothesis of a square array distribution of fibers in the transverse plane. It is concluded that a value of xi=1.5 is a better estimation for the usual volume fractions found in practice for a unidirectional lamina of fiber reinforced composites.The authors wish to thank the Ministerio de Economia y Competitividad for the support received in the framework of the project DPI2013-46641-R and the Generalitat Valenciana, Programme PROMETEO 2012/023. The authors also gratefully acknowledge the collaboration of Mr. Vicente Franco Parra.Giner Maravilla, E.; Vercher Martínez, A.; Marco, M.; Arango Villegas, C. (2015). Estimation of the reinforcement factor xi for calculating the transverse stiffness E2 with the Halpin-Tsai equations using the finite element method. Composite Structures. 124:402-408. https://doi.org/10.1016/j.compstruct.2015.01.008S40240812

Controls on the composition and lability of dissolved organic matter in Siberia's Kolyma River basin

High-latitude northern rivers export globally significant quantities of dissolved organic carbon (DOC) to the Arctic Ocean. Climate change, and its associated impacts on hydrology and potential mobilization of ancient organic matter from permafrost, is likely to modify the flux, composition, and thus biogeochemical cycling and fate of exported DOC in the Arctic. This study examined DOC concentration and the composition of dissolved organic matter (DOM) across the hydrograph in Siberia's Kolyma River, with a particular focus on the spring freshet period when the majority of the annual DOC load is exported. The composition of DOM within the Kolyma basin was characterized using absorbance-derived measurements (absorbance coefficienta330, specific UV absorbance (SUVA254), and spectral slope ratio SR) and fluorescence spectroscopy (fluorescence index and excitation-emission matrices (EEMs)), including parallel factor analyses of EEMs. Increased surface runoff during the spring freshet led to DOM optical properties indicative of terrestrial soil inputs with high humic-like fluorescence, SUVA254, and low SRand fluorescence index (FI). Under-ice waters, in contrast, displayed opposing trends in optical properties representing less aromatic, lower molecular weight DOM. We demonstrate that substantial losses of DOC can occur via biological (∼30% over 28 days) and photochemical pathways (>29% over 14 days), particularly in samples collected during the spring freshet. The emerging view is therefore that of a more dynamic and labile carbon pool than previously thought, where DOM composition plays a fundamental role in controlling the fate and removal of DOC at a pan-Arctic scale

COVID-19 Scenario Projections: The Emergence of Omicron in the US - January 2022

As of January 6, 2021, the highly-transmissible SARS-CoV-2 Omicron variant is driving the largest COVID-19 wave in the US to date. The numbers of new cases and hospitalizations continue to rise, straining healthcare systems around the country. On December 16, 2021, we posted projections for the emergence of the Omicron variant under 18 plausible scenarios [1]. At that time, many of Omicron's epidemiological characteristics were uncertain. Recent studies suggest that the Omicron variant is more transmissible, more immune evasive, and less severe than the Delta variant. In this report, we present updated scenario projections that reflect our current understanding of Omicron transmission and severity in the US. Using a stochastic compartmental model that tracks population-level immunity against the Delta and Omicron variants derived from infections, primary vaccines, and booster vaccines, we project COVID-19 cases, hospitalizations, and deaths over a six month period beginning on January 1, 2022 under eight different scenarios.Integrative Biolog

COVID-19 Scenario Projections: The Emergence of Omicron in the US

On November 24, 2021, South African scientists announced the rapid spread of a new SARS-CoV-2 variant. Within days, the WHO named the variant Omicron and classified it as a variant of concern (VOC). As of December 15, 2021, many of Omicron's epidemiological characteristics remain uncertain, including its intrinsic transmissibility, ability to evade vaccine-acquired and infection-acquired immunity, and severity. To support situational awareness and planning in the United States, we simulated the emergence and spread of Omicron in the US across a range of plausible scenarios. Using a stochastic compartmental model that tracks population-level immunity against the Delta and Omicron variants derived from infections, primary vaccines, and booster vaccines, we project COVID-19 cases, hospitalizations and deaths over a six month period beginning on December 1, 2021 under 18 different scenarios.Integrative Biolog