Cardiac Specific Overexpression of Mitochondrial Omi/HtrA2 Induces Myocardial Apoptosis and Cardiac Dysfunction.

Myocardial apoptosis is a significant problem underlying ischemic heart disease. We previously reported significantly elevated expression of cytoplasmic Omi/HtrA2, triggers cardiomyocytes apoptosis. However, whether increased Omi/HtrA2 within mitochondria itself influences myocardial survival in vivo is unknown. We aim to observe the effects of mitochondria-specific, not cytoplasmic, Omi/HtrA2 on myocardial apoptosis and cardiac function. Transgenic mice overexpressing cardiac-specific mitochondrial Omi/HtrA2 were generated and they had increased myocardial apoptosis, decreased systolic and diastolic function, and decreased left ventricular remodeling. Transiently or stably overexpression of mitochondria Omi/HtrA2 in H9C2 cells enhance apoptosis as evidenced by elevated caspase-3, -9 activity and TUNEL staining, which was completely blocked by Ucf-101, a specific Omi/HtrA2 inhibitor. Mechanistic studies revealed mitochondrial Omi/HtrA2 overexpression degraded the mitochondrial anti-apoptotic protein HAX-1, an effect attenuated by Ucf-101. Additionally, transfected cells overexpressing mitochondrial Omi/HtrA2 were more sensitive to hypoxia and reoxygenation (H/R) induced apoptosis. Cyclosporine A (CsA), a mitochondrial permeability transition inhibitor, blocked translocation of Omi/HtrA2 from mitochondrial to cytoplasm, and protected transfected cells incompletely against H/R-induced caspase-3 activation. We report in vitro and in vivo overexpression of mitochondrial Omi/HtrA2 induces cardiac apoptosis and dysfunction. Thus, strategies to directly inhibit Omi/HtrA2 or its cytosolic translocation from mitochondria may protect against heart injury

Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation

Effects of the graphene nanoplatelets reinforced interphase on mechanical properties of carbon fibre reinforced polymer – A multiscale modelling study

Mechanical properties of carbon fibre reinforced polymer (CFRP) are greatly affected by an interphase between fibre and matrix. Coating fibre with nanofillers has been suggested to improve the interphase properties. In this paper, a multiscale modelling framework was developed to investigate how graphene nanoplatelets (GnPs) influence the mechanical properties of CFRP laminate by reinforcing the interphase. At the nanoscale, the Mori-Tanaka homogenisation method was used to determine effective properties of the GnPs reinforced interphase. GnPs reinforced interphase properties at different GnPs orientations, and volume fractions were examined. At the microscale, a 3-D representative volume element (RVE) model based on obtained interphase properties was used to predict the elastic constants of CFRP unidirectional lamina. This RVE model consisted of three phases: carbon fibre, epoxy resin and the GnPs reinforced interphase. The incorporation of GnPs in the interphase increased both longitudinal and transverse lamina moduli. Finally, simulations of the three-point bending test were performed on the macroscale CFRP laminate. The macroscale modelling based on predicted lamina properties was found to reproduce experimentally measured flexural modulus well. It was found that the GnPs coating on fibre has a positive influence on the mechanical properties of CFRP, and the enhancement varied with orientation and local volume fraction of GnPs. In the presence of GnPs coating, 0° and 90° flexural moduli of CFRP laminate increased by 6.1% and 28.3% respectively.University of Derb

Mechanical Properties of Eco-Friendly, Lightweight Flax and Hybrid Basalt/Flax Foam Core Sandwich Panels

Greener materials, particularly in sandwich panels, are in increasing demand in the transportation and building sectors to reduce environmental impacts. This shift is driven by strict environmental legislation and the need to reduce material costs and fuel consumption, necessitating the utilisation of more sustainable components in the transportation and construction sectors, with improved load-bearing capabilities and diminished ecological footprints. Therefore, this study aims to analyse and evaluate the structural performance of polyethylene terephthalate (PET) core and flax or basalt/flax FRP sandwich panels as an alternative to conventional synthetic materials. The novel eco-friendly sandwich panels were manufactured using the co-curing technique. Four-point bending, edgewise compression and core shear tests were performed and insights into how the skin properties affect the strength, stiffness and failure mode of specimens were provided. The stress–strain behaviour, facing modulus and strength, flexural rigidity, core shear strength and failure modes were evaluated. The flexural facing modulus of the flax and flax/basalt sandwich skins were found to be 5.1 GPa and 9.8 GPa, respectively. The flexural rigidity of the eco-friendly sandwich panel was compared with published results and demonstrated a promising structural performance. The environmental benefits and challenges were outlined and critically evaluated focusing on transportation and construction applications

Thioredoxin reductase was nitrated in the aging heart after myocardial ischemia/reperfusion.

The age-related loss of anti-oxidant defense reduces recovery from myocardial ischemia/reperfusion injury (MI/R) in aged people. Our previous data showed that inactivation of thioredoxin (Trx) was involved in enhanced aging MI/R injury. Thioredoxin reductase (TrxR), the enzyme known to regulate Trx, is less efficient with age. The aim of the current study was to determine why TrxR activity was reduced and whether reduced TrxR activity contributed to enhanced aging MI/R injury. Both Trx and TrxR activity were decreased in the aging heart, and this difference was further amplified after MI/R. However, MI/R injury did not change TrxR expression between young and aging rats. Increased nitrogen oxide (NOx) but decreased nitric oxide (NO) bioavailability (decreased phosphorylated vasodilator-stimulated phosphoprotein) was observed in aging hearts. Peroxynitrite (ONOO⁻) was increased in aging hearts and was further amplified after MI/R. TrxR nitration in young and aging hearts was detected by immunoprecipitation (anti-nitrotyrosine) followed by immunoblotting (anti-TrxR). Compared with young hearts, TrxR nitration was increased in the aging hearts, and this was further intensified after MI/R. The ONOO⁻ decomposition catalyst (FeTMPyp) reduced TrxR nitration and increased TrxR and Trx activity. More importantly, FeTMPyp attenuated the MI/R injury in aging hearts as evidenced by decreased caspase-3 and malondialdehyde (MDA) concentration and increased cardiac function. Increased ONOO⁻ nitrated TrxR in the aging heart as a post-translational modification, which may be related to the enhanced MI/R injury of aging rats. Interventions that inhibit nitration and restore TrxR activity might be a therapy for attenuating enhanced MI/R injury in aging heart

Acupuncture and Moxibustion for Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background. Inflammatory bowel diseases (IBD) are recurrent and refractory which include ulcerative colitis (UC) and Crohn’s disease (CD). Clinical researches about acupuncture and moxibustion treatments for IBD are increasing, while systematic reviews about their efficacy remains in a shortage. This study sought to evaluate the efficacy of acupuncture and moxibustion for IBD. Methods. Seven significant databases both in and abroad were searched for randomized controlled trials (RCTs) which compared acupuncture and moxibustion as the main intervention to pharmacotherapy in treating IBD. A meta-analysis was performed. Results. A total of 43 RCTs were included. Among the 43 included trials, 10 trials compared oral sulphasalazine (SASP) with acupuncture and/or moxibustion treatments. A meta-analysis of the 10 trials indicated that acupuncture and moxibustion therapy was superior to oral SASP. Conclusion. Acupuncture and moxibustion therapy demonstrates better efficacy than oral SASP in treating IBD. However, given the limitations of this systematic review and the included literature, definitive conclusions regarding the exact efficacy of acupuncture and moxibustion treatment for IBD cannot be drawn. Extant RCTs still cannot provide sufficient evidence and multicentre, double-blind RCTs with large sample sizes are needed to provide higher-quality evidence

The progression rate of spinocerebellar ataxia type 3 varies with disease stage

Background: In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions. Methods: Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models. Results: An acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available. Conclusions: We first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp

Metabolomics analysis unveils important changes involved in the salt tolerance of Salicornia europaea

Salicornia europaea is one of the world’s salt-tolerant plant species and is recognized as a model plant for studying the metabolism and molecular mechanisms of halophytes under salinity. To investigate the metabolic responses to salinity stress in S. europaea, this study performed a widely targeted metabolomic analysis after analyzing the physiological characteristics of plants exposed to various NaCl treatments. S. europaea exhibited excellent salt tolerance and could withstand extremely high NaCl concentrations, while lower NaCl conditions (50 and 100 mM) significantly promoted growth by increasing tissue succulence and maintaining a relatively stable K+ concentration. A total of 552 metabolites were detected, 500 of which were differently accumulated, mainly consisting of lipids, organic acids, saccharides, alcohols, amino acids, flavonoids, phenolic acids, and alkaloids. Sucrose, glucose, p-proline, quercetin and its derivatives, and kaempferol derivatives represented core metabolites that are responsive to salinity stress. Glycolysis, flavone and flavonol biosynthesis, and phenylpropanoid biosynthesis were considered as the most important pathways responsible for salt stress response by increasing the osmotic tolerance and antioxidant activities. The high accumulation of some saccharides, flavonoids, and phenolic acids under 50 mM NaCl compared with 300 mM NaCl might contribute to the improved salt tolerance under the 50 mM NaCl treatment. Furthermore, quercetin, quercetin derivatives, and kaempferol derivatives showed varied change patterns in the roots and shoots, while coumaric, caffeic, and ferulic acids increased significantly in the roots, implying that the coping strategies in the shoots and roots varied under salinity stress. These findings lay the foundation for further analysis of the mechanism underlying the response of S. europaea to salinity

Mechanisms Underlying the Analgesic Effect of Moxibustion on Visceral Pain in Irritable Bowel Syndrome: A Review

Irritable bowel syndrome (IBS) is a functional bowel disorder that causes recurrent abdominal (visceral) pain. Epidemiological data show that the incidence rate of IBS is as high as 25%. Most of the medications may lead to tolerance, addiction and toxic side effects. Moxibustion is an important component of traditional Chinese medicine and has been used to treat IBS-like abdominal pain for several thousand years in China. As a mild treatment, moxibustion has been widely applied in clinical treatment of visceral pain in IBS. In recent years, it has played an irreplaceable role in alternative medicine. Extensive clinical studies have demonstrated that moxibustion for treatment of visceral pain is simple, convenient, and inexpensive, and it is being accepted by an increasing number of patients. There have not been many studies investigating the analgesic mechanisms of moxibustion. Studies exploring the analgesic mechanisms have mainly focused on visceral hypersensitivity, brain-gut axis neuroendocrine system, and immune system. This paper reviews the latest developments in moxibustion use for treatment of visceral pain in IBS from these perspectives. It also evaluates potential problems in relevant studies on the mechanisms of moxibustion therapy to promote the application of moxibustion in the treatment of IBS

The Internal-Collision-Induced Magnetic Reconnection and Turbulence (ICMART) Model of Gamma-Ray Bursts

The recent Fermi observation of GRB 080916C shows that the bright photosphere emission associated with a putative fireball is missing, which suggests a Poynting-flux-dominated outflow. We propose a model of gamma-ray burst (GRB) prompt emission in the Poynting-flux-dominated regime, namely, the Internal-Collision-induced MAgnetic Reconnection and Turbulence (ICMART) model. It is envisaged that the GRB central engine launches an intermittent, magnetically-dominated wind, and that in the GRB emission region, the ejecta is still moderately magnetized. Similar to the internal shock (IS) model, the mini-shells interact internally at the traditional internal shock radius. Most of these early collision have little energy dissipation, but serve to distort the ordered magnetic field lines. At a certain point, the distortion of magnetic field configuration reaches the critical condition to allow fast reconnection seeds to occur, which induce relativistic MHD turbulence in the interaction regions. The turbulence further distorts field lines easing additional magnetic reconnections, resulting in a runway release of the stored magnetic field energy (an ICMART event). Particles accelerated in the ICMART region radiate synchrotron photons that power the observed gamma-rays. Each ICMART event corresponds to a broad pulse in the GRB lightcurve, and a GRB is composed of multiple ICMART events. This model retains the merits of the IS and other models, but may overcome several difficulties/issues faced by the IS model (e.g. low efficiency, fast cooling, electron number excess, Amati/Yonetoku relation inconsistency, and missing bright photosphere). It predicts two-component variability time scales, and a decreasing Ep and polarization degree during each ICMART event. The model may be applied to most Fermi LAT GRBs that have time-resolved, featureless Band-function spectra (abridged).Comment: ApJ, in press (submitted on May 6, 2010). 27 emulateapj pages, 4 figures. Minor changes to match the published versio