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Objective: This study aimed to investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation., Methods: Five-week-old ZDF rats and Zucker lean (ZL) rats were fed a high-fat diet (HFD) for 18 weeks. A baseline BOLD-MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD-MRI scan, Hypoxyprobe-1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed., Results: HFD feeding led to a significant increase in VAT BOLD-MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct-positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation., Conclusions: This work demonstrated the feasibility of BOLD-MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD-MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity., (© 2018 The Obesity Society.)

Heme oxygenase-1 (HO-1) is an inducible and cytoprotective enzyme that provides a defense against oxidant damage. The present study screened 137 HO-1/interacting proteins using a profound co-immunoprecipitation (Co-IP) coupled with proteomics, and profiled the global HO-1 interactome network, including oxidative phosphorylation, endoplasmic reticulum and transport vesicle functions. Among these molecules, we observed that a novel interactor, emopamil-binding protein (EBP), is closely related to the cholesterol metabolism process. This study demonstrated that cholesterol promotes excessive oxidative stress and alters the energy metabolism in cardiomyocytes, further triggering numerous cardiovascular diseases. We observed that cholesterol caused the overexpression of EBP and HO-1 by the activation of AKT and Nrf2/mTOR pathways. In addition, HO-1 and EBP performed a myocardial protective function. The overexpression of HO-1 alleviated the cholesterol-induced excessive oxidative stress status by inhibition of the carbohydrate metabolism. Notably, we also confirmed that the loss of partial HO-1 activity aggravated the oxidative damage and cardiac systolic function induced by a high-fat diet in HO-1 heterozygous (HO-1+/-) mice. These findings indicate that the HO-1/EBP interaction plays a protective role in alleviating the dysfunction of oxidative stress and cardiac systolic function induced by cholesterol stimulation.

The blind mole rat (BMR), Spalax galili, is an excellent model for studying mammalian adaptation to life underground and medical applications. The BMR spends its entire life underground, protecting itself from predators and climatic fluctuations while challenging it with multiple stressors such as darkness, hypoxia, hypercapnia, energetics and high pathonecity. Here we sequence and analyse the BMR genome and transcriptome, highlighting the possible genomic adaptive responses to the underground stressors. Our results show high rates of RNA/DNA editing, reduced chromosome rearrangements, an over-representation of short interspersed elements (SINEs) probably linked to hypoxia tolerance, degeneration of vision and progression of photoperiodic perception, tolerance to hypercapnia and hypoxia and resistance to cancer. The remarkable traits of the BMR, together with its genomic and transcriptomic information, enhance our understanding of adaptation to extreme environments and will enable the utilization of BMR models for biomedical research in the fight against cancer, stroke and cardiovascular diseases.

Objective: To investigate the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) in evaluating human visceral adipose tissue (AT) oxygenation induced by salt loading/depletion and its association with changes in circulating monocyte subsets., Methods: A dietary intervention study was performed in 23 healthy volunteers beginning with a 3-day usual diet followed by a 7-day high-salt diet (≥15 g NaCl/day) and a 7-day low-salt diet (≤5 g NaCl/day). BOLD-MRI was used to evaluate oxygenation in perirenal AT., Results: Salt loading led to a consistent AT hypoxia (increase in the R2* signal, 25.2 ± 0.90 s(-1) vs. baseline 21.5 ± 0.71 s(-1) , P < 0.001) and suppression of circulating renin-angiotensin-aldosterone system (RAAS), as well as an expansion of the CD14++CD16+ monocytes and monocyte pro-inflammatory activation. In salt depletion phase, the hypoxic state of AT and the expanded CD14++CD16+ monocyte pool were regressed to baseline levels, accompanied by a rebound activation of RAAS. Moreover, AT oxygenation level was positively correlated with the CD14++CD16+ monocytes (r = 0.419, P < 0.001)., Conclusions: This work provides proof-of-principle evidence supporting the feasibility of BOLD-MRI in monitoring visceral AT oxygenation in humans induced by dietary salt loading/depletion. In addition, the CD14++CD16+ monocytes may participate in the pathogenesis of high-salt intake induced AT hypoxia., (Copyright © 2014 The Obesity Society.)

To investigate the feasibility of blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) in evaluating human subcutaneous and visceral adipose tissue (AT) oxygenation status, as well as their responses to dietary salt loading/depletion, we enrolled 16 healthy subjects [mean body mass index (BMI): 24.8 ± 2.7 kg/m(2)] to conduct a dietary intervention study, beginning with a 3-day run-in period for usual diet, followed by a 7-day high-salt diet (≥ 15 g NaCl/day) and a 7-day low-salt diet (≤ 5 g NaCl/day). Abdominal BOLD-MRI scan was performed to evaluate oxygenation in waist subcutaneous and perirenal (visceral) AT. Two subjects with lower BMI were excluded because of the difficulty to identify subcutaneous AT. High salt diet led to a consistent increase in R2* signal (a parameter for increased hypoxia) both in subcutaneous and visceral AT (all P < 0.0001), which was completely regressed to baseline levels by low salt diet. In addition, subcutaneous AT R2* values at any time points, were all higher than that of visceral AT (all P < 0.0001). Pearson correlation analysis revealed that the visceral AT R2* levels were negatively associated obesity indicators (waist circumference, waist-to-hip ratio and BMI). On the contrary, although a trend towards negative associations between the subcutaneous AT R2* and obesity indicators was observed, none of the associations reached statistical significances. Thus, our data demonstrate the possibility of simultaneous detection of human subcutaneous and visceral AT oxygenation status using BOLD-MRI. In addition, there is a more close relationship visceral AT oxygenation status and the development of obesity.

Graphical abstract Abstract Wound dressings with multiple functions are required to meet the complexity of the wound healing process. The multifunctionality often leads to an increase in the complexity and difficulty in dressing preparation. To surmount this problem, we used a facile preparation and fabrication process to fabricate a multi-functional dressing by integrating four widely accessible materials: plain gauze, sodium alginate (SA), Ca2+ and Co2+. Firstly, mixed Ca2+/Co2+ ion solutions with different concentration were applied to gauzes. After drying, SA solution was added to ionized gauze and Co2+-Ca2+/Gauze/SA (Ion-GSA) composite dressings were formed easily. In vitro results showed that all Ion-GSA dressings exhibited strong mechanical properties, uniform dispersion and sustained release of Ca2+ and Co2+, and the ability to retain moisture and absorb wound exudate. Besides the above advantages, dressings prepared with 0.25 g/L Co2+ and 4 g/L Ca2+ (Co2+0.25-Ca2+4 GSA composite dressings) exhibited the best overall effect for inducing a hypoxia-like response, and favorable cytocompatibility, hemostatic property and antibacterial activity. In vivo wound healing assays revealed that Co2+0.25-Ca2+4 GSA composite dressings inhibited bacterial growth, increased local Hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) protein expression, and accelerated full-thickness skin wound healing in mouse bacterial-infected wound model. The quick healing wounds had improved angiogenesis, macrophages regulation, re-epithelialization and dense collagen deposition. Collectively, our results indicated that Co2+0.25-Ca2+4 GSA composite dressings promote wound healing. Statement of Significance Wound dressings with integrated functionalities are required to meet complex clinical requirements. However, there is often a trade-off between reducing preparation complexity and increasing the multifunctionality of the dressing's properties. In this study, we prepared multifunctional composite dressings by a facile preparation process using widely accessible materials. The composite dressings possessed the mechanical strength of gauze, had the effective wound exudate absorption, moisture maintenance and hemostatic property capacity of calcium alginate hydrogels, and had the hypoxia-like induction and the antimicrobial effects of Co2+. These functions all together promote bacteria-infected wound healing. Thus, we believed that the composite dressings can be widely applied in skin wound repair duo to their facile preparation method and good therapeutic effect. [ABSTRACT FROM AUTHOR]