Extracts of Feijoa Inhibit Toll-Like Receptor 2 Signaling and Activate Autophagy Implicating a Role in Dietary Control of IBD

Inflammatory bowel disease (IBD) is a heterogeneous chronic inflammatory disease affecting the gut with limited treatment success for its sufferers. This suggests the need for better understanding of the different subtypes of the disease as well as nutritional interventions to compliment current treatments. In this study we assess the ability of a hydrophilic feijoa fraction (F3) to modulate autophagy a process known to regulate inflammation, via TLR2 using IBD cell lines

Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation

The Glycan Shield of HIV Is Predominantly Oligomannose Independently of Production System or Viral Clade

The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide and vaccine design. The extent of cross-clade conservation of HIV oligomannose glycans is therefore a critical consideration for the development of HIV prophylaxes. We measured the oligomannose content of virion-associated gp120 from primary virus from PBMCs for a range of viral isolates and showed cross-clade elevation (62–79%) of these glycans relative to recombinant, monomeric gp120 (∼30%). We also confirmed that pseudoviral production systems can give rise to notably elevated gp120 oligomannose levels (∼98%), compared to gp120 derived from a single-plasmid viral system using the HIVLAI backbone (56%). This study highlights differences in glycosylation between virion-associated and recombinant gp120

Signal Detection on the Battlefield: Priming Self-Protection vs. Revenge-Mindedness Differentially Modulates the Detection of Enemies and Allies

Detecting signs that someone is a member of a hostile outgroup can depend on very subtle cues. How do ecology-relevant motivational states affect such detections? This research investigated the detection of briefly-presented enemy (versus friend) insignias after participants were primed to be self-protective or revenge-minded. Despite being told to ignore the objectively nondiagnostic cues of ethnicity (Arab vs. Western/European), gender, and facial expressions of the targets, both priming manipulations enhanced biases to see Arab males as enemies. They also reduced the ability to detect ingroup enemies, even when these faces displayed angry expressions. These motivations had very different effects on accuracy, however, with self-protection enhancing overall accuracy and revenge-mindedness reducing it. These methods demonstrate the importance of considering how signal detection tasks that occur in motivationally-charged environments depart from results obtained in conventionally motivationally-inert laboratory settings.National Institute of Mental Health (U.S.) (Grant MH64734)U.S. Army Research Institute for the Behavioral and Social Sciences (Grant W74V8H-05-K-0003)National Science Foundation (U.S.) (Grant BCS-0642873

Regulation of the JNK3 signaling pathway during islet isolation: JNK3 and c-fos as new markers of islet quality for transplantation.

Stress conditions generated throughout pancreatic islet processing initiate the activation of pro-inflammatory pathways and beta-cell destruction. Our goal is to identify relevant and preferably beta-specific markers to assess the activation of beta-cell stress and apoptotic mechanisms, and therefore the general quality of the islet preparation prior to transplantation. Protein expression and activation were analyzed by Western blotting and kinase assays. ATP measurements were performed by a luminescence-based assay. Oxygen consumption rate (OCR) was measured based on standard protocols using fiber optic sensors. Total RNA was used for gene expression analyzes. Our results indicate that pancreas digestion initiates a potent stress response in the islets by activating two stress kinases, c-Jun N-terminal Kinase (JNK) and p38. JNK1 protein levels remained unchanged between different islet preparations and following culture. In contrast, levels of JNK3 increased after islet culture, but varied markedly, with a subset of preparations bearing low JNK3 expression. The observed changes in JNK3 protein content strongly correlated with OCR measurements as determined by the Spearman's rank correlation coefficient rho [Formula: see text] in the matching islet samples, while inversely correlating with c-fos mRNA expression [Formula: see text]. In conclusion, pancreas digestion recruits JNK and p38 kinases that are known to participate to beta-cell apoptosis. Concomitantly, the islet isolation alters JNK3 and c-fos expression, both strongly correlating with OCR. Thus, a comparative analysis of JNK3 and c-fos expression before and after culture may provide for novel markers to assess islet quality prior to transplantation. JNK3 has the advantage over all other proposed markers to be islet-specific, and thus to provide for a marker independent of non-beta cell contamination

A model building exercise of mortality risk for Taiwanese women with breast cancer

Abstract Background The accurate estimation of outcome in patients with malignant disease is an essential component of the optimal treatment, decision-making and patient counseling processes. The prognosis and disease outcome of breast cancer patients can differ according to geographic and ethnic factors. To our knowledge, to date these factors have never been validated in a homogenous loco-regional patient population, with the aim of achieving accurate predictions of outcome for individual patients. To clarify this topic, we created a new comprehensive prognostic and predictive model for Taiwanese breast cancer patients based on a range of patient-related and various clinical and pathological-related variables. Methods Demographic, clinical, and pathological data were analyzed from 1 137 patients with breast cancer who underwent surgical intervention. A survival prediction model was used to allow analysis of the optimal combination of variables. Results The area under the receiver operating characteristic (ROC) curve, as applied to an independent validation data set, was used as the measure of accuracy. Results were compared by comparing the area under the ROC curve. Conclusions our model building exercise of mortality risk was able to predict disease outcome for individual patients with breast cancer. This model could represent a highly accurate prognostic tool for Taiwanese breast cancer patients.</p

Modulation of phosphofructokinase (PFK) from Setaria cervi, a bovine filarial parasite, by different effectors and its interaction with some antifilarials

<p>Abstract</p> <p>Background</p> <p>Phosphofructokinase (ATP: D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11, PFK) is of primary importance in the regulation of glycolytic flux. This enzyme has been extensively studied from mammalian sources but relatively less attention has been paid towards its characterization from filarial parasites. Furthermore, the information about the response of filarial PFK towards the anthelmintics/antifilarial compounds is lacking. In view of these facts, PFK from <it>Setaria cervi</it>, a bovine filarial parasite having similarity with that of human filarial worms, was isolated, purified and characterized.</p> <p>Results</p> <p>The <it>S. cervi </it>PFK was cytosolic in nature. The adult parasites (both female and male) contained more enzyme activity than the microfilarial (Mf) stage of <it>S. cervi</it>, which exhibited only 20% of total activity. The <it>S. cervi </it>PFK could be modulated by different nucleotides and the response of enzyme to these nucleotides was dependent on the concentrations of substrates (F-6-P and ATP). The enzyme possessed wide specificity towards utilization of the nucleotides as phosphate group donors. <it>S. cervi </it>PFK showed the presence of thiol group(s) at the active site of the enzyme, which could be protected from inhibitory action of para-chloromercuribenzoate (p-CMB) up to about 76% by pretreatment with cysteine or β-ME. The sensitivity of PFK from <it>S. cervi </it>towards antifilarials/anthelmintics was comparatively higher than that of mammalian PFK. With suramin, the Ki value for rat liver PFK was 40 times higher than PFK from <it>S. cervi</it>.</p> <p>Conclusions</p> <p>The results indicate that the activity of filarial PFK may be modified by different effectors (such as nucleotides, thiol group reactants and anthelmintics) in filarial worms depending on the presence of varying concentrations of substrates (F-6-P and ATP) in the cellular milieu. It may possess thiol group at its active site responsible for catalysis. Relatively, 40 times higher sensitivity of filarial PFK towards suramin as compared to the analogous enzyme from the mammalian system indicates that this enzyme could be exploited as a potential chemotherapeutic target against filariasis.</p

Incidence, patterns and severity of reported unintentional injuries in Pakistan for persons five years and older: results of the National Health Survey of Pakistan 1990–94

<p>Abstract</p> <p>Background</p> <p>National level estimates of injuries are not readily available for developing countries. This study estimated the annual incidence, patterns and severity of unintentional injuries among persons over five years of age in Pakistan.</p> <p>Methods</p> <p>National Health Survey of Pakistan (NHSP 1990–94) is a nationally representative survey of the household. Through a two-stage stratified design, 18, 315 persons over 5 years of age were interviewed to estimate the overall annual incidence, patterns and severity of unintentional injuries for males and females in urban and rural areas over the preceding one year. Weighted estimates were computed adjusting for complex survey design using <it>surveyfreq </it>and <it>surveylogistic </it>option of SAS 9.1 software.</p> <p>Results</p> <p>The overall annual incidence of all unintentional injuries was 45.9 (CI: 39.3–52.5) per 1000 per year; 59.2 (CI: 49.2–69.2) and 33.2 (CI: 27.0–39.4) per 1000 per year among males and females over five years of age, respectively. An estimated 6.16 million unintentional injuries occur in Pakistan annually among persons over five years of age. Urban and rural injuries were 55.9 (95% CI: 48.1–63.7) and 41.2 (95% CI: 32.2–50.0) per 1000 per year, respectively. The annual incidence of injuries due to falls were 22.2 (95% CI: 18.0–26.4), poisoning 3.3 (95%CI: 0.5–6.1) and burn was 1.5 (95%CI: 0.9–2.1) per 1000 per year. The majority of injuries occurred at home 19.2 (95%CI: 16.0–22.4) or on the roads 17.0 (95%CI: 13.8–20.2). Road traffic/street, school and urban injuries were more likely to result in handicap.</p> <p>Conclusion</p> <p>There is high burden of unintentional injuries among persons over five years of age in Pakistan. These results are useful to plan further studies and prioritizing prevention programs on injuries nationally and other developing countries with similar situation.</p