Tetramethylpyrazine attenuates oleic acid-induced acute lung injury/acute respiratory distress syndrome through the downregulation of nuclear factor-kappa B (NF-kB) activation in rats

The aim of this study was to investigate the anti-inflammatory activities of tetramethylpyrazine (TMP) in the mice model of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) induced by oleic acid (0.15 ml/kg, intravenous (i.v.)). We report here that TMP (given at 160 mg/kg intraperitoneal (i.p.)) exerts potent anti-inflammatory effects in this model. After 4, 8 and 12 h, animal model reaction was observed and bronchoalveolar lavage fluid was obtained to measure proinflammatory cytokines (tumor necrosis factor α, interleukin 1β) and proteins by enzyme-linked immunosorbent assay and bicinchoninic acid protein assay kit, respectively. The protein expression of NF-kB in the lung was measured by immunohistochemistry and Western blotting. The results showed an increase in tumor necrosis factor α and interleukin 1β in the ALI/ARDS rat models. The activation of NF-kB was suppressed by TMP in the ALI/ARDS rats. The suppression of those molecules is controlled by NF-kB. These findings support the hypothesis that TMP inhibits the inflammatory process in the lung tissue through the suppression of NF-kB activation. Nevertheless, further investigations are required to determine the potential clinical usefulness of TMP in the adjunctive therapy for ARDS.Key words: Tetramethylpyrazine, acute lung injury/acute respiratory distress syndrome, inflammatory factors, NF-kB

Molecular cloning, characterization and functional analysis of a 3-hydroxy-3- methylglutaryl coenzyme A reductase gene from Jatropha curcas

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR, EC: 1.1.1.34) catalyzes the first committed step in mevalonic acid (MVA) pathway for biosynthesis of isoprenoids. The full-length cDNA encoding HMGR was isolated from Jatropha curcas for the first time (designated as JcHMGR), which contained a 1950 bp ORF encoding 584 amino acids. The JcHMGR genomic DNA sequence was also obtained, revealing JcHMGR had 4 exons and 3 introns. The deduced JcHMGR protein showed high identity to other plant HMGRs and contained 2 transmembrane domains and a catalytic domain. The potential significance of JcHMGR gene was also discussed

Quality of Life in Younger versus Older Breast Cancer Survivors

poster abstractBackground: Breast cancer is one of the most frequently occurring cancers in the developing world, but with earlier detection and better treatment, the majority of breast cancer survivors will live many years after diagnosis. Breast cancer survivors may experience many symptoms that impact their quality of life, and these symptoms may vary by age. The purpose of this study is to compare breast cancer survivors who were diagnosed at 45 and under (n=469) with survivors diagnosed at 55 to 70 (n=584) years of age. Materials and methods: Participants were identified through a large cooperative group (Eastern Cancer Cooperative Group). Eligibility criteria included use of chemotherapy at initial diagnosis, being 3 to 8 years from diagnosis, and not having a recurrence of breast cancer. The mean current age of younger survivors was 45.2 and for older survivors was 66.7. Women who agreed to participate were sent a survey and informed consent which was completed and returned via mail. Overall, 80% of eligible women contacted by researchers agreed to participate. Measures included physical, psychological, social, spiritual, and overall quality of life constructs. All measurements had good reported validity and reliability. A total of 469 younger and 584 older breast cancer survivors are included. Linear regression was used to compare the two groups on continuous outcomes while adjusting for the following potentially confounding covariates: marital status (married versus not), years of education, and total household income, and years since diagnosis. Results: Younger survivors scored significantly worse than older survivors on gynecological problems, sexual enjoyment, attention function, and overall reported symptoms. Psychologically, younger survivors demonstrated greater symptom distress, greater depression, and greater state and trait anxiety than older survivors. Younger survivors had lower marital satisfaction scores. Younger survivors reported greater fear of recurrence and less favorable body image. Younger survivors reported lower perceived social support from their partners and greater social constraint. Older survivors held higher spiritual beliefs and behaviors as compared to younger survivors. Perceived self efficacy for dealing with problems related to cancer survivorship was lower in younger survivors as compared to older survivors. For overall quality of life measures, younger survivors reported lower index of well being scores than older survivors and reported that breast cancer had a greater impact on their life. Health care service use was greater for younger as opposed to older survivors both during and after treatment. Conclusions: Younger survivors reported significantly more problems on several, physical, psychological, social and generic quality of life issues as compared to older survivors. Results indicate a need to proactively assess quality of life issues in younger women at time of diagnosis

The Decade of the Dendritic NMDA Spike

In the field of cortical cellular physiology, much effort has been invested in understanding thick apical drites of pyramidal neurons and the regenerative sodium and calcium spikes that take place in the apical trunk. Here we focus on thin dendrites of pyramidal cells (basal, oblique, and tuft dendrites), and we discuss one relatively novel form of an electrical signal (“NMDA spike”) that is specific for these branches. Basal, oblique, and apical tuft dendrites receive a high density of glutamatergic synaptic contacts. Synchronous activation of 10–50 neighboring glutamatergic synapses triggers a local dendritic regenerative potential, NMDA spike/plateau, which is characterized by significant local amplitude (40–50 mV) and an extraordinary duration (up to several hundred milliseconds). The NMDA plateau potential, when it is initiated in an apical tuft dendrite, is able to maintain a good portion of that tuft in a sustained depolarized state. However, if NMDA-dominated plateau potentials originate in proximal segments of basal dendrites, they regularly bring the neuronal cell body into a sustained depolarized state, which resembles a cortical up state. At each dendritic initiation site (basal, oblique, and tuft) an NMDA spike creates favorable conditions for causal interactions of active synaptic inputs, including the spatial or temporal binding of information, as well as processes of short-term and long-term synaptic modifications (e.g., long-term potentiation or long-term depression). Because of their strong amplitudes and durations, local dendritic NMDA spikes make up the cellular substrate for multisite independent subunit computations that enrich the computational power and repertoire of cortical pyramidal cells. We propose that NMDA spikes are likely to play significant roles in cortical information processing in awake animals (spatiotemporal binding, working memory) and during slow-wave sleep (neuronal up states, consolidation of memories

How do event zones influence visitor behaviour and engagement with host destinations? : A longitudinal study of the Cambridge half marathon (2017–2020)

© 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)This work identifies important influencing factors that affect event visitor behaviour in and beyond event zones, utilising a four-year, mixed-method, longitudinal study (n=6212) of the Cambridge Half Marathon (2017–2020). We counter a commonly held view that visitors naturally spill out into local cultural and business precincts, arguing that event zones represent cities within cities that spatially segregate visitors from the host destination; only 7% of the sample engaged in longer and deeper cultural stays. Quantitative data reveals statistically significant demographic and tripographic factors that increase the likelihood of visitors venturing beyond the event zone, whilst qualitative data reveals the behavioural and organisational factors that encourage or discourage engagement. Managerial tactics and strategies for encouraging visitors to venture beyond event zones, across host destinations, to optimise local economic benefits across the host destination are presented.Peer reviewe

Intense vortex pinning enhanced by semicrystalline defect traps in self-aligned nanostructured MgB2

In this work, we report the discovery of a vortex pinning source: semicrystalline defect wells in self-aligned nanostructured MgB2. It is demonstrated that these aperiodic regions trap numerous crystal defects migrating along nanodomain boundaries during self-alignment and act as intense vortex pinning centers that significantly enhance the high-field performance of MgB2. This suggests that the density of trapped defects in the wells is much greater than that found in other vortex pinning sources