Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

Publication date: Available online 15 March 2018
Source:Cell Metabolism
Author(s): Meenakshi Ravichandran, Steffen Priebe, Giovanna Grigolon, Leonid Rozanov, Marco Groth, Beate Laube, Reinhard Guthke, Matthias Platzer, Kim Zarse, Michael Ristow
Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase (GCAT, EC 2.3.1.29). Impairing gcat expression promotes the lifespan of C. elegans by interfering with threonine catabolism to promote methylglyoxal (MGO; CAS 78-98-8) formation in an amine oxidase-dependent manner. MGO is a reactive dicarbonyl inducing diabetic complications in mammals by causing oxidative stress and damaging cellular components, including proteins. While high concentrations of MGO consistently exert toxicity in nematodes, we unexpectedly find that low-dose MGO promotes lifespan, resembling key mediators of gcat impairment. These were executed by the ubiquitin-proteasome system, namely PBS-3 and RPN-6.1 subunits, regulated by the stress-responsive transcriptional regulators SKN-1/NRF2 and HSF-1. Taken together, GCAT acts as an evolutionary conserved aging-related gene by orchestrating an unexpected nonlinear impact of proteotoxic MGO on longevity.

Graphical abstract

Teaser

Ravichandran et al. show that the gcat gene is downregulated during normal aging in different species, and show that impairment of GCAT delays aging by promoting formation of methylglyoxal. This diabetes-related and toxic compound unexpectedly also extends healthspan at low concentrations. Both interventions converge at stress-response and proteostasis pathways.


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Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes

Publication date: Available online 15 March 2018
Source:Cell Metabolism
Author(s): Alexandra Moraru, Janica Wiederstein, Daniel Pfaff, Thomas Fleming, Aubry K. Miller, Peter Nawroth, Aurelio A. Teleman
The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.

Graphical abstract

Teaser

Moraru et al. find that elevated levels of the reactive metabolite methylglyoxal in a Drosophila model recapitulate the progression of type 2 diabetes, causing flies to become obese, insulin resistant, and hyperglycemic. This raises the question of whether elevated methylglyoxal might be a cause of type 2 diabetes.


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Confucian Culture as Determinants of Consumers' Food Leftover Generation: Evidence from Chengdu, China

Abstract

Food waste is a worldwide problem due to its effects on carbon emission, water pollution, and arable lands. Previous studies of food waste generation and reduction focus on demographic, psychological, and situational factors, whereas the effects of culture in different countries have been ignored. This paper investigates the influence of Confucian culture on behaviors that waste food, considering additional factors of face saving and group conformity. We used an integrated behavioral intention model combining the TPB model and Lee's modified Fishbein model. The results show that including the constructors of Confucian culture increases the predictive power of the model. Face saving and group conformity are found to significantly influence attitude toward food waste reduction. Face saving can greatly reduce the intention to pack leftovers, and group conformity has a significant effect on the ordering of small portion sizes. Based on these results, we give a discussion and put forward with suggestions to the government and the catering industry. Limitations and implications for future research are provided accordingly.

http://ift.tt/2FXjTVi

Production-scale fibronectin nanofibers promote wound closure and tissue repair in a dermal mouse model

Publication date: June 2018
Source:Biomaterials, Volume 166
Author(s): Christophe O. Chantre, Patrick H. Campbell, Holly M. Golecki, Adrian T. Buganza, Andrew K. Capulli, Leila F. Deravi, Stephanie Dauth, Sean P. Sheehy, Jeffrey A. Paten, Karl Gledhill, Yanne S. Doucet, Hasan E. Abaci, Seungkuk Ahn, Benjamin D. Pope, Jeffrey W. Ruberti, Simon P. Hoerstrup, Angela M. Christiano, Kevin Kit Parker
Wounds in the fetus can heal without scarring. Consequently, biomaterials that attempt to recapitulate the biophysical and biochemical properties of fetal skin have emerged as promising pro-regenerative strategies. The extracellular matrix (ECM) protein fibronectin (Fn) in particular is believed to play a crucial role in directing this regenerative phenotype. Accordingly, Fn has been implicated in numerous wound healing studies, yet remains untested in its fibrillar conformation as found in fetal skin. Here, we show that high extensional (∼1.2 ×10⁵ s⁻¹) and shear (∼3 ×10⁵ s⁻¹) strain rates in rotary jet spinning (RJS) can drive high throughput Fn fibrillogenesis (∼10 mL/min), thus producing nanofiber scaffolds that are used to effectively enhance wound healing. When tested on a full-thickness wound mouse model, Fn nanofiber dressings not only accelerated wound closure, but also significantly improved tissue restoration, recovering dermal and epidermal structures as well as skin appendages and adipose tissue. Together, these results suggest that bioprotein nanofiber fabrication via RJS could set a new paradigm for enhancing wound healing and may thus find use in a variety of regenerative medicine applications.



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Physical evolution of the Three Gorges Reservoir using advanced SVM on Landsat images and SRTM DEM data

Abstract

The Three Gorges Reservoir (TGR) is one of the largest hydropower reservoirs in the world. However, changes of the important physical characteristics of the reservoir covering pre-, during-, and post- dam have not been well studied. This study analyzed the lengths and water surface areas of the TGR using advanced support vector machine method (SVM) combined Landsat images with the Shuttle Radar Topography Mission (SRTM) digital elevation model (DEM), which showed an increasing trend of lengths and surface areas with variable growth rates from pre-dam period to post-dam period. The highest water level (ca. 171.5 m) was reported in 1st Jan, 2015, with the longest length of 687.8 km and largest water surface area of 1106.2 km² during the study period. The lowest increasing magnitude of the reservoir length occurred in the first stage (2000–2005) but with the fastest magnitude of water surface area increase. The third stage (2010–2015) showed highest increase magnitude of length and lowest increase magnitude of water surface area. Meanwhile, the increased reservoir areas were mainly from cultivated land, forest land, and building land, with the biggest increase rate of cultivated land regardless of periods. Specifically, cultivated land contributed 39.1–46.0% to increased reservoir water area; the proportions were 22.6–29.6%, 22.1–24.1%, and 5.6–9.4% for forest, building land, and grassland, respectively. The study provides important data for the TGR physical evolution in the Holocene.

http://ift.tt/2pdFaka

Magnetically actuated mechanical stimuli on Fe3O4/mineralized collagen coatings to enhance osteogenic differentiation of the MC3T3-E1 cells

Publication date: Available online 15 March 2018
Source:Acta Biomaterialia
Author(s): Junjun Zhuang, Suya Lin, Lingqing Dong, Kui Cheng, Wenjian Weng
Mechanical stimuli at the bone–implant interface are considered to activate the mechanotransduction pathway of the cell to improve the initial osseointegration establishment and to guarantee clinical success of the implant. However, control of the mechanical stimuli at the bone–implant interface still remains a challenge. In this study, we have designed a strategy of a magnetically responsive coating on which the mechanical stimuli is controlled because of coating deformation under static magnetic field (SMF). The iron oxide nanoparticle/mineralized collagen (IOP-MC) coatings were electrochemically codeposited on titanium substrates in different quantities of IOPs and distributions; the resulting coatings were verified to possess swelling behavior with flexibility same as that of hydrogel. The relative quantity of IOP to collagen and the IOP distribution in the coatings were demonstrated to play a critical role in mediating cell behavior. The cells present on the outer layer of the distributed IOP-MC (O-IOP-MC) coating with a mass ratio of 0.67 revealed the most distinct osteogenic differentiation activity being promoted, which could be attributed to the maximized mechanical stimuli with exposure to SMF. Furthermore, the enhanced osteogenic differentiation of the stimulated MC3T3-E1 cells originated from magnetically actuated mechanotransduction signaling pathway, embodying the upregulated expression of osteogenic-related and mechanotransduction-related genes. This work therefore provides a promising strategy for implementing mechanical stimuli to activate mechanotransduction on the bone–implant interface and thus to promote osseointegration.Statement of significanceThe magnetically actuated coating is designed to produce mechanical stimuli to cells for promoting osteogenic differentiation based on the coating deformation. Iron oxide nanoparticles (IOPs) were incorporated into the mineralized collagen coatings (MC) forming the composite coatings (IOP-MC) with spatially distributed IOPs, and the IOP-MC coatings with outer distributed IOPs (O-IOPs-MC) shows the maximized mechanical stimuli to cells with enhanced osteogenic differentiation under static magnetic field. The upregulated expression of the associated genes reveals that the enabled mechanotransduction signaling pathway is responsible for the promoted cellular osteogenic differentiation. This work therefore provides a promising strategy for implementing mechanical stimuli to activate mechanotransduction on the bone–implant interface to promote osseointegration.

Graphical abstract

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Fatigue of soft fibrous tissues: multi-scale mechanics and constitutive modeling

Publication date: Available online 15 March 2018
Source:Acta Biomaterialia
Author(s): Kevin Linka, Markus Hillgärtner, Mikhail Itskov
In recent experimental studies a possible damage mechanism of collagenous tissues mainly caused by fatigue was disclosed. In this contribution, a multi-scale constitutive model ranging from the tropocollagen (TC) molecule level up to bundles of collagen fibers is proposed and utilized to predict the elastic and inelastic long-term tissue response. Material failure of collagen fibrils is elucidated by a permanent opening of the triple helical collagen molecule conformation, triggered either by overstretching or reaction kinetics of non-covalent bonds. This kinetics is described within a probabilistic framework of adhesive detachments of molecular linkages providing collagen fiber integrity. Both intramolecular and interfibrillar linkages are considered. The final constitutive equations are validated against recent experimental data available in literature for both uniaxial tension to failure and the evolution of fatigue for subsequent loading cycles. All material parameters of the proposed model have a clear physical interpretation.Statement of significanceIrreversible changes take place at different length scales of soft fibrous tissues tissues under supra-physiological loading and alter their macroscopic mechanical properties. Understanding the evolution of those histologic pathologies under loading and incorporating them into a continuum mechanical framework appears to be crucial in order to predict long-term evolution of various diseases and to support the development of tissue engineering.

Graphical abstract

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Cutaneous Barriers and Skin Immunity: Differentiating A Connected Network

Publication date: Available online 15 March 2018
Source:Trends in Immunology
Author(s): Stefanie Eyerich, Kilian Eyerich, Claudia Traidl-Hoffmann, Tilo Biedermann
The skin is the outermost barrier of the organism that ensures protection from external harm. Lately, our view of the skin has evolved from an inert mechanical barrier to an active organ that can sense danger signals and mount perfectly adapted defense measures in response to invading pathogens. This Review highlights the different levels of the cutaneous barrier (the microbiome, chemical, physical, and immune barriers), their characteristics, and functional, highly interconnected network of cells and mediators that allow balanced defense measures to protect the body and maintain barrier integrity.



http://ift.tt/2IrhQr6

Excitation energy dependence of the life time of orange emission from Mn-doped ZnS nanocrystals

Publication date: July 2018
Source:Journal of Luminescence, Volume 199
Author(s): N.T. Tuan, D.Q. Trung, N.V. Quang, N.D. Hung, N.T. Khoi, P.T. Huy, Philippe F. Smet, Katrien W. Meert, Dirk Poelman
Mn-doped ZnS nanocrystals were prepared by co-precipitation method. X-ray diffraction analysis indicates pure cubic zinc blende structure. We report for the first time experimental observation of the dependence of the decay time of Mn²⁺ emission from Mn-doped ZnS nanocrystals on excitation energy. Photon energy smaller than the ZnS bandgap induces faster decay time compared to the one equal to the bandgap energy. In addition, while the decay spectra of orange emission indicate both sub μs and ms, the time-resolved luminescence measurement suggests that the sub μs component belongs to the tail of the blue emission.

Graphical abstract

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Assessment of biochemical alterations in the neotropical fish species Phalloceros harpagos after acute and chronic exposure to the drugs paracetamol and propranolol

Abstract

Over time, many pollutants of anthropogenic origin have caused the contamination of aquatic ecosystems. Among several characteristics, these compounds can reach the trophic chain, causing deleterious interactions with the biota. Pharmaceutical substances can be included in this scenario as emerging contaminants that reach the aquatic environment because of direct human and veterinary usage, and release by industrial effluents, as well as through domestic dumping of surplus drugs. The effects of these compounds on exposed organisms have been studied since the 1990s, but ecotoxicological data for such chemicals are still scarce especially concerning aquatic organisms from tropical regions. Paracetamol and propranolol were selected for this study since they are frequently found in surface waters. Paracetamol is a drug used as analgesic and antipyretic, while propranolol, a β-blocker, is used in the treatment of hypertension. The objective of this study was to assess the toxic effects of these substances on the neotropical freshwater fish Phalloceros harpagos after acute (96 h) and chronic (28 days) exposures. In order to understand the effects of these drugs on P. harpagos, biochemical markers were selected, including the enzymes involved in oxidative stress, xenobiotic metabolism, and neurotransmission (catalase, glutathione-S-transferase, and cholinesterase activities, respectively). After acute exposure, no significant alterations were observed for catalase activity, suggesting the absence of oxidative stress. On the contrary, significant alterations in glutathione-S-transferases activity were described for the higher concentrations of both pharmaceuticals after acute exposure. In addition, acute exposure to paracetamol caused a significant increase of cholinesterase activity. None of the tested pharmaceuticals caused significant changes in catalase or cholinesterase activities after chronic exposure. Glutathione S-transferases activity was significantly increased for propranolol following chronic exposure, indicating the potential involvement of phase II detoxification pathway.

http://ift.tt/2tQjsYf

Hydroxychavicol, a key ingredient of Piper betle induces bacterial cell death by DNA damage and inhibition of cell division

Publication date: Available online 15 March 2018
Source:Free Radical Biology and Medicine
Author(s): Deepti Singh, Shwetha Narayanamoorthy, Sunita Gamre, Ananda Guha Majumdar, Manish Goswami, Umesh Gami, Susan Cherian, Mahesh Subramanian
Antibiotic resistance is a global problem and there is an urgent need to augment the arsenal against pathogenic bacteria. The emergence of different drug resistant bacteria is threatening human lives to be pushed towards the pre-antibiotic era. Botanical sources remain a vital source of diverse organic molecules that possess antibacterial property as well as augment existing antibacterial molecules. Piper betle, a climber, is widely used in south and south-east Asia whose leaves and nuts are consumed regularly. Hydroxychavicol (HC) isolated from Piper betle has been reported to possess antibacterial activity. It is currently not clear how the antibacterial activity of HC is manifested. In this investigation we show HC generates superoxide in E. coli cells. Antioxidants protected E. coli against HC induced cell death while gshA mutant was more sensitive to HC than wild type. DNA damage repair deficient mutants are hypersensitive to HC and HC induces the expression of DNA damage repair genes that repair oxidative DNA damage. HC treated E. coli cells are inhibited from growth and undergo DNA condensation. In vitro HC binds to DNA and cleaves it in presence of copper. Our data strongly indicates HC mediates bacterial cell death by ROS generation and DNA damage. Damage to iron sulfur proteins in the cells contribute to amplification of oxidative stress initiated by HC. Further HC is active against a number of Gram negative bacteria isolated from patients with a wide range of clinical symptoms and varied antibiotic resistance profiles.

Graphical abstract

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The dual role of ROS in autoimmune and inflammatory diseases: evidence from preclinical models

Publication date: Available online 15 March 2018
Source:Free Radical Biology and Medicine
Author(s): Markus H. Hoffmann, Helen Griffiths
Reactive oxygen species (ROS) are created in cells during oxidative phosphorylation by the respiratory chain in the mitochondria or by the family of NADPH oxidase (NOX) complexes. The first discovered and most studied of these complexes, NOX2, mediates the oxidative burst in phagocytes. ROS generated by NOX2 are dreadful weapons: while being essential to kill ingested pathogens they can also cause degenerative changes on tissue if production and release are not balanced by sufficient detoxification. In the last fifteen years evidence has been accumulating that ROS are also integral signalling molecules and are important for regulating autoimmunity and immune-mediated inflammatory diseases. It seems that an accurate redox balance is necessary to sustain an immune state that both prevents the development of overt autoimmunity (the bright side of ROS) and minimizes collateral tissue damage (the dark side of ROS). Herein, we review studies from rodent models of arthritis, lupus, and neurodegenerative diseases that show that low NOX2-derived ROS production is linked to disease and elaborate on the underlying cellular and molecular mechanisms and the translation of these results to disease in humans.



http://ift.tt/2GyqPXa

The bilingual language network: Differential involvement of anterior cingulate, basal ganglia and prefrontal cortex in preparation, monitoring, and execution

Publication date: 1 July 2018
Source:NeuroImage, Volume 174
Author(s): Roy Seo, Andrea Stocco, Chantel S. Prat
Research on the neural bases of bilingual language control has largely overlooked the role of preparatory processes, which are central to cognitive control. Additionally, little is known about how the processes involved in global language selection may differ from those involved in the selection of words and morpho-syntactic rules for manipulating them. These processes were examined separately in an fMRI experiment, with an emphasis on understanding how and when general cognitive control regions become activated. Results of region-of-interest analyses on 23 early Spanish-English bilinguals showed that the anterior cingulate cortex (ACC) was primarily engaged during the language preparation phase of the task, whereas the left prefrontal (DLPFC) and pre-supplementary motor areas showed increasing activation from preparation to execution. Activation in the basal ganglia (BG), left middle temporal lobe, and right precentral cortical regions did not significantly differ throughout the task. These results suggest that three core cognitive control regions, the ACC, DLPFC, and BG, which have been previously implicated in bilingual language control, engage in distinct neurocognitive processes. Specifically, the results are consistent with the view that the BG "keep track" of the target language in use throughout various levels of language selection, that the ACC is particularly important for top-down target language preparation, and that the left prefrontal cortex is increasingly involved in selection processes from preparation through task execution.



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Maturation trajectories of cortical resting-state networks depend on the mediating frequency band

Publication date: 1 July 2018
Source:NeuroImage, Volume 174
Author(s): Sheraz Khan, Javeria A. Hashmi, Fahimeh Mamashli, Konstantinos Michmizos, Manfred G. Kitzbichler, Hari Bharadwaj, Yousra Bekhti, Santosh Ganesan, Keri-Lee A. Garel, Susan Whitfield-Gabrieli, Randy L. Gollub, Jian Kong, Lucia M. Vaina, Kunjan D. Rana, Steven M. Stufflebeam, Matti S. Hämäläinen, Tal Kenet
The functional significance of resting state networks and their abnormal manifestations in psychiatric disorders are firmly established, as is the importance of the cortical rhythms in mediating these networks. Resting state networks are known to undergo substantial reorganization from childhood to adulthood, but whether distinct cortical rhythms, which are generated by separable neural mechanisms and are often manifested abnormally in psychiatric conditions, mediate maturation differentially, remains unknown. Using magnetoencephalography (MEG) to map frequency band specific maturation of resting state networks from age 7 to 29 in 162 participants (31 independent), we found significant changes with age in networks mediated by the beta (13–30 Hz) and gamma (31–80 Hz) bands. More specifically, gamma band mediated networks followed an expected asymptotic trajectory, but beta band mediated networks followed a linear trajectory. Network integration increased with age in gamma band mediated networks, while local segregation increased with age in beta band mediated networks. Spatially, the hubs that changed in importance with age in the beta band mediated networks had relatively little overlap with those that showed the greatest changes in the gamma band mediated networks. These findings are relevant for our understanding of the neural mechanisms of cortical maturation, in both typical and atypical development.



http://ift.tt/2FTBcXB

Cortical and subcortical responses to biological motion

Publication date: 1 July 2018
Source:NeuroImage, Volume 174
Author(s): Dorita H.F. Chang, Hiroshi Ban, Yuji Ikegaya, Ichiro Fujita, Nikolaus F. Troje
Using fMRI and multivariate analyses we sought to understand the neural representations of articulated body shape and local kinematics in biological motion. We show that in addition to a cortical network that includes areas identified previously for biological motion perception, including the posterior superior temporal sulcus, inferior frontal gyrus, and ventral body areas, the ventral lateral nucleus, a presumably motoric thalamic area is sensitive to both form and kinematic information in biological motion. Our findings suggest that biological motion perception is not achieved as an end-point of segregated cortical form and motion networks as often suggested, but instead involves earlier parts in the visual system including a subcortical network.



http://ift.tt/2FXBKvC

Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology

Publication date: Available online 15 March 2018
Source:Cell Stem Cell
Author(s): Michael J. Ziller, Juan A. Ortega, Katharina A. Quinlan, David P. Santos, Hongcang Gu, Eric J. Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y. Meltzer, Andreas Gnirke, C.J. Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing. We find defects in neuralization and MN differentiation in DNMT3A knockouts (KO) that can be rescued by the targeting of DNAme to key developmental loci using catalytically inactive dCas9. We also find decreased dendritic arborization and altered electrophysiological properties in DNMT3A KO MNs. Our work provides a list of DNMT3A-regulated targets and a mechanistic link between de novo DNAme, cellular differentiation, and human MN function.

Graphical abstract

Teaser

Kiskinis and colleagues demonstrate that DNA methylation dynamics play a central role in the differentiation of human pluripotent stem cells toward highly specialized motor neurons. Through a combination of molecular and functional analysis they identify key transcriptional mediators of these effects and link DNA methylation to neuronal patterning and function.


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Adiposity Results in Metabolic and Inflammation Differences in Premenopausal and Postmenopausal Women Consistent with the Difference in Breast Cancer Risk

Abstract

Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese. Expression levels of 21 target genes were determined using a TaqMan Low Density Array procedure. Breast tissue estradiol levels were measured by a liquid chromatography-tandem mass spectrometry procedure, and serum estradiol and follicle-stimulating hormone (FSH) were measured by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. We found that in postmenopausal women, serum and tissue estradiol levels were increased in those who were overweight, and serum FSH levels were decreased in obese status. Interestingly, RPS6KB1, an AMPK downstream-responsive gene for protein synthesis and cell growth, and estrogen receptor α (encoded by the ESR1 gene) and its target gene GATA3 were significantly decreased in rFNA of premenopausal, obese women. In postmenopausal women, RPS6KB1, ESR1, and GATA3 expression remained unchanged in relation to adiposity. However, prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin D1 (CCND1), and another ESR1 target gene, TFF1, were elevated in rFNA of obese postmenopausal women. Thus, as bodyweight increases, gene expression is indicative of increased proliferation in postmenopausal women but decreased proliferation in premenopausal women. Overall, our data reveal a novel process by which obesity promotes the risk of breast cancer in postmenopausal but not premenopausal women.

http://ift.tt/2FWmSxr

Intravenous injection of artificial red cells and subsequent dye laser irradiation causes deep vessel impairment in an animal model of port-wine stain

Abstract

Our previous study proposed using artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment for port-wine stains (PWSs). Dye laser photons are absorbed by red blood cells (RBCs) and hemoglobin (Hb) mixture, which potentially produce more heat and photocoagulation and effectively destroy endothelial cells. Hb-Vs combination therapy will improve clinical outcomes of dye laser treatment for PWSs because very small vessels do not contain sufficient RBCs and they are poor absorbers/heaters of lasers. In the present study, we analyzed the relationship between vessel depth from the skin surface and vessel distraction through dye laser irradiation following intravenous Hb-Vs injection using a chicken wattle model. Hb-Vs were administered and chicken wattles underwent high-energy irradiation at energy higher than in the previous experiments. Hb-Vs location in the vessel lumen was identified to explain its photosensitizer effect using human Hb immunostaining of the irradiated wattles. Laser irradiation with Hb-Vs can effectively destroy deep vessels in animal models. Hb-Vs tend to flow in the marginal zone of both small and large vessels. Increasing laser power combined with Hb-Vs injection contributed for deep vessel impairment because of the synergetic effect of both methods. Newly added Hb tended to flow near the target endothelial cells of the laser treatment. In Hb-Vs and RBC mixture, heat transfer to endothelial cells from absorbers/heater may increase. Hb-Vs function as photosensitizers to destroy deep vessels within a restricted distance that the photon can reach.

http://ift.tt/2FFsc9e

LED session prior incremental step test enhance VO 2max in running

Abstract

This study aimed to investigate the effect of prior LED sessions on the responses of cardiorespiratory parameters during the running incremental step test. Twenty-six healthy, physically active, young men, aged between 20 and 30 years, took part in this study. Participants performed two incremental load tests after placebo (PLA) and light-emitting diode application (LED), and had their gas exchange, heart rate (HR), blood lactate, and rating of perceived exertion (RPE) monitored during all tests. The PLA and LED conditions were compared using the dependent Student t test with significance set at 5%. The T test showed higher maximum oxygen uptake (VO_2max) (PLA = 47.2 ± 5.7; LED = 48.0 ± 5.4 ml kg⁻¹ min⁻¹, trivial effect size), peak velocity (V_peak) (PLA = 13.4 ± 1.2; LED = 13.6 ± 1.2 km h⁻¹, trivial effect size), and lower maximum HR (PLA = 195.3 ± 3.4; LED = 193.3 ± 3.9 b min⁻¹, moderate effect size) for LED compared to PLA conditions. Furthermore, submaximal values of HR and RPE were lower, and submaximal VO₂ values were higher when LED sessions prior to the incremental step test were applied. A positive response of the previous LED application in the blood lactate disappearance was also demonstrated, especially 13 and 15 min after the test. It is concluded that LED sessions prior to exercise modify cardiorespiratory response by affecting running tolerance during the incremental step test, metabolite clearance, and RPE. Therefore, LED could be used as a prior exercise strategy to modulate oxidative response acutely in targeted muscle and enhance exercise tolerance.

http://ift.tt/2DuN6C0

Has the time come to include low-level laser photobiomodulation as an adjuvant therapy in the treatment of impaired endometrial receptivity?

Abstract

Low-level laser therapy (LLLT) has been used in photobiomodulation to promote healing, regenerate, and restore tissue function. Women with persistent thin endometrium were assumed to encounter diminished activity in the regenerative and functional capacity of their endometrium. The aim of this study was to examine the ability of LLLT in 635 nm wavelength to enhance the proliferation and gene expression of in vitro cultured endometrial cells. Single (SE) versus multiple exposures (ME) to LLLT were examined in the study groups and compared to controls. A fluence dose of 4.27 J/cm² for 16 min was given once in the SE or divided in three equal sessions in days 2, 4, and 6 of the culture in ME. Cellular response was evaluated by measuring viable cell numbers and surface area. Pattern of MUC1, ITGA5, ITGB3, LIF, and PTEN gene expression was assessed using the qRT-PCR. Greater numbers of cells were found in both study groups (P < 0.001) as compared to controls. The surface area of cells at the end of culture phase was highly significant (P < 0.001) in ME when compared to SE and controls. A statistically significant difference was found in terms of gene expression in both irradiated groups (P < 0.001) as compared to controls, although greater difference in PTEN tumour suppressor gene (Phosphatase and tensin homolog) expression was toward ME. The introduction of LLLT to the armamentarium of infertility will serve as a new adjuvant therapy in this field. The current study proofed that LLLT was able to increase the proliferative and functional capacity of cultured endometrial cells.

http://ift.tt/2pe5gmX