The effects of a training program encompassing cold exposure, breathing exercises, and meditation on plasma metabomics during experimental human endotoxemia
Project description:ObjectivesThe aim of our study was to assess the effect of short-term cold exposure, typical in subarctic climate, on cardiac electrical function among untreated middle-aged hypertensive men.MethodsWe conducted a population-based recruitment of 51 hypertensive men and a control group of 32 men without hypertension (age 55-65 years) who underwent whole-body cold exposure (15 min exposure to temperature -10°C, wind 3 m/s, winter clothes). Conduction times and amplitudes, vectorcardiography, arrhythmias, and heart rate variability (autonomic nervous function) were assessed.ResultsShort-term cold exposure increased T-peak to T-end interval from 67 to 72 ms (p<0.001) and 71 to 75 ms (p<0.001) and T-wave amplitude from 0.12 to 0.14 mV (p<0.001) and from 0.17 to 0.21 mV (p<0.001), while QTc interval was shortened from 408 to 398 ms (p<0.001) and from 410 to 401 ms (p<0.001) among hypertensive men and controls, respectively. Cold exposure increased both low (from 390 to 630 ms2 (p<0.001) and 380 to 700 ms2 (p<0.001), respectively) and high frequency heart rate variability (from 90 to 190 ms2 (p<0.001) and 150 to 300 ms2 (p<0.001), respectively), while low-to-high frequency-ratio was reduced. In addition, the frequency of ventricular ectopic beats increased slightly during cold exposure. The cold induced changes were similar between untreated hypertensive men and controls.ConclusionsShort-term cold exposure with moderate facial and mild whole body cooling resulted in prolongation of T-peak to T-end interval and higher T-wave amplitude while QTc interval was shortened. These changes of ventricular repolarization may have resulted from altered cardiac autonomic regulation and were unaffected by untreated hypertension.Trial registrationClinicalTrials.gov NCT02007031.
Project description:IntroductionSkin cancer is often fatal, which motivates new therapy avenues. Recent advances in cancer treatment are indicative of the importance of combination treatments in oncology. Previous studies have identified small molecule-based therapies and redox-based technologies, including photodynamic therapy or medical gas plasma, as promising candidates to target skin cancer.ObjectiveWe aimed to identify effective combinations of experimental small molecules with cold gas plasma for therapy in dermato-oncology.MethodsPromising drug candidates were identified after screening an in-house 155-compound library using 3D skin cancer spheroids and high content imaging. Combination effects of selected drugs and cold gas plasma were investigated with respect to oxidative stress, invasion, and viability. Drugs that had combined well with cold gas plasma were further investigated in vascularized tumor organoids in ovo and a xenograft mouse melanoma model in vivo.ResultsThe two chromone derivatives Sm837 and IS112 enhanced cold gas plasma-induced oxidative stress, including histone 2A.X phosphorylation, and further reduced proliferation and skin cancer cell viability. Combination treatments of tumor organoids grown in ovo confirmed the principal anti-cancer effect of the selected drugs. While one of the two compounds exerted severe toxicity in vivo, the other (Sm837) resulted in a significant synergistic anti-tumor toxicity at good tolerability. Principal component analysis of protein phosphorylation profiles confirmed profound combination treatment effects in contrast to the monotherapies.ConclusionWe identified a novel compound that, combined with topical cold gas plasma-induced oxidative stress, represents a novel and promising treatment approach to target skin cancer.
Project description:Pockels-based Mueller polarimetry is presented as a novel diagnostic technique for studying time and space-resolved and in-situ the interaction between an organic sample (a layer of onion cells) and non-thermal atmospheric pressure plasma. The effect of plasma is complex, as it delivers electric field, radicals, (UV) radiation, non-uniform in time nor in space. This work shows for the first time that the plasma-surface interaction can be characterized through the induced electric field in an electro-optic crystal (birefringence caused by the Pockels effect) while at the same moment the surface evolution of the targeted sample is monitored (depolarization) which is attached to the crystal. As Mueller polarimetry allows for separate detection of depolarization and birefringence, it is possible to decouple the entangled effects of the plasma. In the sample three spatial regions are identified where the surface evolution of the sample differs. This directly relates to the spatial in-homogeneity of the plasma at the surface characterized through the detected electric field. The method can be applied in the future to investigate plasma-surface interactions for various targets ranging from bio-films, to catalytic surfaces and plastics/polymers.
Project description:Cold Atmospheric Plasma (CAP) is a novel promising tool developed in several biomedical applications such as cutaneous wound healing or skin cancer. Nevertheless, in vitro studies are lacking regarding to CAP effects on cellular actors involved in healthy skin healing and regarding to the mechanism of action. In this study, we investigated the effect of a 3 minutes exposure to CAP-Helium on human dermal fibroblasts and Adipose-derived Stromal Cells (ASC) obtained from the same tissue sample. We observed that CAP treatment did not induce cell death but lead to proliferation arrest with an increase in p53/p21 and DNA damages. Interestingly we showed that CAP treated dermal fibroblasts and ASC developed a senescence phenotype with p16 expression, characteristic morphological changes, Senescence-Associated β-galactosidase expression and the secretion of pro-inflammatory cytokines defined as the Senescence-Associated Secretory Phenotype (SASP). Moreover this senescence phenotype is associated with a glycolytic switch and an increase in mitochondria content. Despite this senescence phenotype, cells kept in vitro functional properties like differentiation potential and immunomodulatory effects. To conclude, we demonstrated that two main skin cellular actors are resistant to cell death but develop a senescence phenotype while maintaining some functional characteristics after 3 minutes of CAP-Helium treatment in vitro.
Project description:The purpose of the study was to examine the effects of exercise on total leukocyte count and subsets, as well as hormone and cytokine responses in a thermoneutral and cold environment, with and without an individualized pre-cooling protocol inducing low-intensity shivering. Nine healthy young men participated in six experimental trials wearing shorts and t-shirts. Participants exercised for 60 min on a treadmill at low (LOW: 50% of peak VO2) and moderate (MOD: 70% VO2peak) exercise intensities in a climatic chamber set at 22°C (NT), and in 0°C (COLD) with and without a pre-exercise low-intensity shivering protocol (SHIV). Core and skin temperature, heart rate and oxygen consumption were collected continuously. Blood samples were collected before and at the end of exercise to assess endocrine and immunological changes. Core temperature in NT was greater than COLD and SHIV by 0.4±0.2°C whereas skin temperature in NT was also greater than COLD and SHIV by 8.5±1.4°C and 9.3±2.5°C respectively in MOD. Total testosterone, adenocorticotropin and cortisol were greater in NT vs. COLD and SHIV in MOD. Norepinephrine was greater in NT vs. other conditions across intensities. Interleukin-2, IL-5, IL-7, IL-10, IL-17, IFN-γ, Rantes, Eotaxin, IP-10, MIP-1β, MCP-1, VEGF, PDGF, and G-CSF were elevated in NT vs. COLD and/or SHIV. Furthermore, IFN-γ, MIP-1β, MCP-1, IL-10, VEGF, and PDGF demonstrate greater concentrations in SHIV vs. COLD, mainly in the MOD condition. This study demonstrated that exercising in the cold can diminish the exercise-induced systemic inflammatory response seen in a thermoneutral environment. Nonetheless, prolonged cooling inducing shivering thermogenesis prior to exercise, may induce an immuno-stimulatory response following moderate intensity exercise. Performing exercise in cold environments can be a useful strategy in partially inhibiting the acute systemic inflammatory response from exercise but oppositely, additional body cooling may reverse this benefit.
Project description:ObjectiveWe previously showed that a training intervention comprising a combination of meditation, exposure to cold, and breathing exercises enables voluntary activation of the sympathetic nervous system, reflected by profoundly increased plasma epinephrine levels, and subsequent attenuation of the lipopolysaccharide (LPS)-induced inflammatory response. Several elements of the intervention may contribute to these effects, namely, two different breathing exercises (either with or without prolonged breath retention) and exposure to cold. We determined the contribution of these different elements to the observed effects.MethodsForty healthy male volunteers were randomized to either a short or an extensive training in both breathing exercises by either the creator of the training intervention or an independent trainer. The primary outcome was plasma epinephrine levels. In a subsequent study, 48 healthy male volunteers were randomized to cold exposure training, training in the established optimal breathing exercise, a combination of both, or no training. These 48 participants were subsequently intravenously challenged with 2 ng/kg LPS. The primary outcome was plasma cytokine levels.ResultsBoth breathing exercises were associated with an increase in plasma epinephrine levels, which did not vary as a function of length of training or the trainer (F(4,152) = 0.53, p = .71, and F(4,152) = 0.92, p = .46, respectively). In the second study, the breathing exercise also resulted in increased plasma epinephrine levels. Cold exposure training alone did not relevantly modulate the LPS-induced inflammatory response (F(8,37) = 0.60, p = .77), whereas the breathing exercise led to significantly enhanced anti-inflammatory and attenuated proinflammatory cytokine levels (F(8,37) = 3.80, p = .002). Cold exposure training significantly enhanced the immunomodulatory effects of the breathing exercise (F(8,37) = 2.57, p = .02).ConclusionsThe combination of cold exposure training and a breathing exercise most potently attenuates the in vivo inflammatory response in healthy young males. Our study demonstrates that the immunomodulatory effects of the intervention can be reproduced in a standardized manner, thereby paving the way for clinical trials.Trial Registration:ClinicalTrials.gov identifiers: NCT02417155 and NCT03240497.
Project description:Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.
Project description:In insects and other ectotherms, cold temperatures cause a coma resulting from loss of neuromuscular function, during which ionic and metabolic homeostasis are progressively lost. Cold adaptation improves homeostasis during cold exposure, but the ultimate targets of selection are still an open question. Cold acclimation and adaptation remodels mitochondrial metabolism in insects, suggesting that aerobic energy production during cold exposure could be a target of selection. Here, we test the hypothesis that cold adaptation improves the ability to maintain rates of aerobic energy production during cold exposure by using 31 P NMR on live flies. Using lines of Drosophila melanogaster artificially selected for fast and slow recovery from a cold coma, we show that cold exposure does not lower ATP levels and that cold adaptation does not alter aerobic ATP production during cold exposure. Cold-hardy and cold-susceptible lines both experienced a brief transition to anaerobic metabolism during cooling, but this was rapidly reversed during cold exposure, suggesting that oxidative phosphorylation was sufficient to meet energy demands below the critical thermal minimum, even in cold-susceptible flies. We thus reject the hypothesis that performance under mild low temperatures is set by aerobic ATP supply limitations in D. melanogaster, excluding oxygen and capacity limitation as a weak link in energy supply. This work suggests that the modulations to mitochondrial metabolism resulting from cold acclimation or adaptation may arise from selection on a biosynthetic product(s) of those pathways rather than selection on ATP supply during cold exposure.
Project description:Pathogen contamination is a severe problem in maintaining food safety in the cold chain. Cold plasma (CP) is a novel non-thermal disinfection method that can be applied for the bacterial inactivation of food in appropriate contexts. Currently, research on CP used on food at cold chain temperatures is rare. This work investigated the bacterial inactivation effect of CP on beef at typical cold storage temperatures of 4 and -18 °C and room temperature (25 °C). The reactive species in CP were indirectly tested by evaluating O3, NO3- and NO2- in cold plasma-activated water (PAW), which indicated the highest concentrations of reactive species in CP at 25 °C and the lowest at -18 °C. The bactericidal efficacy of CP treatment against beef inoculated with Escherichia coli at -18 °C, 4 °C, and 25 °C was 30.5%, 60.1%, and 59.5%, respectively. The 4 °C environment was the most appropriate treatment for CP against beef, with the highest bactericidal efficacy and a minor influence on beef quality. The indirect CP treatment had no significant effect on the texture, color, pH, or cooking loss of beef at -18 °C. CP shows significant potential for the efficient decontamination of food at cold chain temperatures.
Project description:BackgroundEvidence indicates that healthy individuals who follow a training program comprised hyperventilatory breathing exercises and cold exposure can voluntarily activate their sympathetic nervous system and attenuate their systemic inflammatory response during experimental endotoxemia (intravenous administration of bacterial endotoxin). Furthermore, trained participants reported less endotoxemia-induced flu-like symptoms. However, it remained to be determined whether the effects on symptoms are due to the mitigated inflammatory response or involve direct analgesic effects of (elements of) the training program.MethodsIn the present study, we used Nijmegen-Aalborg Screening Quantitative sensory testing (NASQ) to objectively map pain sensitivity using non-invasive stimuli to address this question. First, NASQ parameters were evaluated in 20 healthy volunteers before, during, and after the conduct of the hyperventilatory breathing exercise. Second, NASQ measurements were performed before and after 48 healthy volunteers followed different modalities of the training program: breathing exercise training, cold exposure training, the combination of both, or no training. Lastly, NASQ measurements were performed in these 48 subjects during experimental endotoxemia.ResultsElectrical pain detection thresholds increased during the breathing exercise (p = 0.001) as well as four hours afterwards (p = 0.03). Furthermore, cold exposure training resulted in lower VAS scores during hand immersion in ice water (p < 0.001). Systemic inflammation induced by administration of endotoxin nullified the decreased pain perception during the ice water test in subjects trained in cold exposure.ConclusionA hyperventilatory breathing exercise decreases pain perception induced by an electrical stimulus. Furthermore, cold exposure training may decrease pain perception induced by hand immersion in ice water.