TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1β enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils.     

Contribution of bacterial cells as nucleation centers in microbiologically induced CaCO3 precipitation—A mathematical modeling approach

The microbiologically induced calcite precipitation (MICP) has been extensively studied for geotechnical engineering through simultaneous action of natural phenomena and engineering processes. The focus of bacterial contribution to the MICP has been directed to calcium carbonate productivity, while the additional bacterial role as a crystal nucleation center was not explained especially from a mathematical prediction modeling point of view. Therefore, this study provides explanations and a mathematical modeling approach of bacterial influence on the MICP induced by newly-isolated ureolytic Bacillus strains and Sporosarcina pasteurii DSM 33. Using the obtained results of low-cost, rapid, and simple assays, artificial neural network modeling was applied for cell surface predispositions, pH changes as well as calcium-involved function in biofilm formation during the MICP, for the first time. Based on the obtained contribution of the alkalophilic/alkaloresistant bacteria, calcite precipitation can be significantly directed by the presence, of ureolytic bacterial cells as nucleation centers during CaCO₃ precipitation as well as their morphology, surface characteristics, potential to form a biofilm, and/or generate pH changes.     

Prognostic value of the PIK3CA,AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.     

Dark chocolate reduces endothelial dysfunction after successive breath-hold dives in cool water

Objective

The aim of this study is to observe the effects of dark chocolate on endothelial function after a series of successive apnea dives in non-thermoneutral water.

Methods

Twenty breath-hold divers were divided into two groups: a control group (8 males and 2 females) and a chocolate group (9 males and 1 female). The control group was asked to perform a series of dives to 20 m adding up to 20 min in the quiet diving pool of Conflans-Ste-Honorine (Paris, France), water temperature was 27 °C. The chocolate group performed the dives 1 h after ingestion of 30 g of dark chocolate. Flow-mediated dilatation (FMD), digital photoplethysmography, nitric oxide (NO), and peroxynitrite ONOO^?) levels were measured before and after each series of breath-hold dives.

Results

A significant decrease in FMD was observed in the control group after the dives (95.28 ± 2.9 % of pre-dive values, p < 0.001) while it was increased in the chocolate group (104.1 ± 2.9 % of pre-dive values, p < 0.01). A decrease in the NO level was observed in the control group (86.76 ± 15.57 %, p < 0.05) whereas no difference was shown in the chocolate group (98.44 ± 31.86 %, p > 0.05). No differences in digital photoplethysmography and peroxynitrites were observed between before and after the dives.

Conclusion

Antioxidants contained in dark chocolate scavenge free radicals produced during breath-hold diving. Ingestion of 30 g of dark chocolate 1 h before the dive can thus prevent endothelial dysfunction which can be observed after a series of breath-hold dives.     

Effect of a single, open-sea, air scuba dive on human micro- and macrovascular function

Purpose

Previous studies have shown that bubble formation induced endothelial damage on conduit arteries. We aim to evaluate the effect of diving on microvascular and macrovascular function.

Methods

Nine divers took part in a SCUBA dive at 30 msw (400 kPa), for 30 min of bottom time. Pre- and post-dive, they underwent an assessment of endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) microvascular function (laser Doppler flowmetry), as well as endothelial-dependent (flow-mediated dilation) and endothelial-independent (nitroglycerin-mediated dilation) function. Bubble grades were monitored with Doppler according to the Spencer grade.

Results

The mean KISS bubble score ranged from 21.10 ± 4.7 at rest to 55.03 ± 8.8 after knee flexion. The increase in cutaneous vascular conductance elicited by either acetylcholine (25.34 ± 6.71 to 7.63 ± 1.25 %, p = 0.021) or sodium nitroprusside (35.24 ± 8.75 to 7.61 ± 1.86 %, p = 0.017) was significantly reduced after diving. Similarly, both flow-mediated dilation (10.8 ± 0.9 to 5.4 ± 1.5 %, p = 0.002) and nitroglycerin-mediated dilation (15 ± 1.1 to 6.5 ± 1.6 %, p = 0.002) were also significantly decreased. There were no correlations between vascular parameters and bubble formation.

Conclusions

There appears to be a reduction in endothelium-dependent and endothelium-independent, macro- and microvascular function associated with diving. Our results suggest that in the process of vascular dysfunction during diving, functional changes in the vessel wall may not be limited to the endothelium and may be mediated by alterations in vascular smooth muscle.