Search

As the global aging process accelerates, the health challenges posed by sarcopenia among middle-aged and older adults are becoming increasingly prominent. However, the available evidence on the adverse effects of air pollution on sarcopenia is limited, particularly in the Western Pacific region. This study aimed to explore relationships of multiple air pollutants with sarcopenia and related biomarkers using the nationally representative database. Totally, 6585 participants aged over 45 years were enrolled from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 3443 of them were followed up until 2015. Air pollutants were estimated from high-resolution satellite-based spatial-temporal models. In the cross-sectional analysis, we used generalized linear regression, unconditional logistic regression analytical and restricted cubic spline (RCS) methods to assess the single-exposure and non-linear effects of multiple air pollutants on sarcopenia and related surrogate biomarkers (serum creatinine and cystatin C). Several popular mixture analysis techniques such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression, and quantile-based g-computation (Qgcomp) were further used to examinate the combined effects of multiple air pollutants. Logistic regression was used to further analyze the longitudinal association between air pollution and sarcopenia. Each interquartile range increase in PM 2.5 , PM 10 and NO 2 was significantly associated with an increased risk of sarcopenia, with adjusted odds ratios (aORs) of 1.09 [95 % confidence interval (CI): 1.01, 1.20], 1.24 (95 % CI: 1.14, 1.35) and 1.18 (95 % CI: 1.08, 1.28), respectively. Our findings also showed that five air pollutants were significantly associated with the sarcopenia index. In addition, employing a mixture analysis approach, we confirmed significant combined effects of air pollution mixtures on sarcopenia risk and associated biomarkers, with PM 10 and PM 2.5 identified as major contributors to the combined effect. The results of the exposure-response (E-R) relationships, subgroup analysis, longitudinal analysis and sensitivity analysis all showed the unfavorable impact of air pollution on sarcopenia risk and related vulnerable populations. Single-exposure and co-exposure to multiple air pollutants were positively associated with sarcopenia among middle-aged and older adults in China. Our study provided new evidence that air pollution mixture was significantly associated with sarcopenia related biomarkers. [Display omitted] • Ambient PM 2.5 , PM 10 , and NO 2 were positively associated with risk of sarcopenia. • Positive joint effect of air pollution mixtures with sarcopenia risk was revealed. • Both individual and mixed air pollutants were negatively associated with sarcopenia index. • PM 10 and PM 2.5 dominated the joint effects on sarcopenia and sarcopenia index. • New findings were based on nationally representative Chinese adults (age ≥ 45 years). [ABSTRACT FROM AUTHOR]

[Display omitted] • A reverse emulsion is utilized to form iron-polypyrrole (Fe-PPy) precursor. • Melt-salt-mediated pyrolysis of Fe-PPy constructs onion-like Co/CoO@FeNC. • Co/CoO@FeNC consists of Co/CoO nanoparticles embedded in graphitic carbon shells. • Co/CoO@FeNC proves reversable oxygen catalytic performance with a Δ E of 0.695 V. • Co/CoO@FeNC catalyst improves the durability and power density of Zinc-air battery. A melt-salt-assisted method is utilized to construct an onion-like hybrid with Co/CoO nanoparticles embedded in graphitic Fe-N-doped carbon shells (Co/CoO@FeNC) as a bifunctional electrocatalyst. The iron-polypyrrole (Fe-PPy) is firstly prepared with a reverse emulsion. Direct pyrolysis of Fe-PPy yields turbostratic Fe-N-doped carbon (FeNC) with excellent oxygen reduction reaction (ORR) electrocatalysis, while the melt salt (CoCl 2) mediated pyrolysis of Fe-PPy obtains onion-like Co/CoO@FeNC with a reversible overvoltage value of 0.695 V, largely superior to Pt/C and IrO 2 (0.771 V) and other Co-based catalysts reported so far. The ORR activity is mainly due to the graphitic FeNC and further enhanced by Co N x bonds, whereas the oxygen evolution reaction (OER) activity is principally due to the Co/CoO composite. Concurrently, Co/CoO@FeNC as cathode catalyst enables Zn-air battery with a high open circuit voltage of 1.42 V, a peak power density of 132.8 mW cm−2, a specific capacity of 813 mAh g Zn −1, and long-term stability. [ABSTRACT FROM AUTHOR]

In this work, the variational method of the Pekar type is used to theoretically study the temperature effects on the bound polaron in the triangular quantum dot (QD) qubit subjected to an electromagnetic field. We analyze and discuss in detail the numerical results and show that the relationships of the ground and first excited state energies, the electron probability density and the electron oscillation period in the superposition state of the ground state and the first-excited state with the temperature, the cyclotron frequency, the electron-phonon coupling constant, the electric field strength, the confinement strength and the Coulomb impurity potential, respectively. [ABSTRACT FROM AUTHOR]

Rapidly and correctly identifying endocrine-disrupting chemicals (EDCs) is an important issue in environmental risk assessment. Major EDCs are associated with the androgen receptor (AR) and oestrogen receptors (ERs). Because of the high cost and time-consuming nature of experimental tests, in silico methods are valuable alternative tools for the identification of EDCs. In this study, a large dataset related to EDCs was constructed. Each molecule was represented with seven fingerprints, and computational models were subsequently developed to predict AR and ER binders via machine learning methods including k-nearest neighbour (k NN), C4.5 decision tree (C4.5 DT), naïve Bayes (NB), and support vector machine (SVM) algorithms. The best model for predicting AR binders was PubChem Fingerprint-SVM, which exhibited an accuracy of 0.84. For ER binders, the best method was Extended Fingerprint-SVM with an accuracy of 0.79. Moreover, several representative substructure alerts for characterizing EDCs, such as phenol, trifluoromethyl, and annelated rings, were identified using the combination of information gain and substructure frequency analysis. Our study involved a systematic computational assessment of EDCs related to AR and ERs, and provides significant information on the structural characteristics of these chemicals, which are a great help in identifying EDCs. [ABSTRACT FROM AUTHOR]

Prorocentrum donghaiense , a marine dinoflagellate, causes harmful algal blooms (HABs) characterised by the highest outbreak frequency and most extensive coverage among similar species in the East China Sea. Highly efficient and ecofriendly biocontrol strategies should be developed for HAB control. Prodigiosin is an efficient biological algicide that demonstrated strong algicidal activity towards P. donghaiense. However, the mechanism of its toxicity to P. donghaiense is unknown. These factors were investigated to evaluate potential use of prodigiosin for control of P. donghaiense blooms. Photosynthetic electron transport rate, maximum quantum yield and respiration rate of P. donghaiense decreased significantly upon exposure to prodigiosin, indicating that prodigiosin rapidly exerted adverse effects on the chloroplasts and mitochondria. Furthermore, a significant increase in dichlorofluorescein fluorescence intensity indicated an overproduction of reactive oxygen species (ROS). The antioxidant system of P. donghaiense scavenged ROS; however, an increase in malondialdehyde concentrations indicated that excessive ROS were still able to initiate lipid peroxidation. Thus, ROS production resulted in the formation of lipids with a reduced degree of unsaturation. Lipid peroxidation decreased lipid fluidity and rigidified the membrane system, causing serious functional destruction of the membrane. Flow cytometry analysis indicated that prodigiosin arrested the cell cycle of P. donghaiense. However, surviving algal cells were able to repair the damaged functions and resume the cell cycle after prodigiosin was removed by photodegradation. Otherwise, P. donghaiense cells lost their membrane integrity and died. To begin an evaluation of ecological safety of prodigiosin, we tested four marine organisms at various trophic levels. The results of these tests indicated that Chlorella vulgaris, Photobacterium phosphoreum, Artemia salina and Lateolabrax japonicus were less sensitive to prodigiosin than P. donghaiense. Toxicity to all five organisms declined after prodigiosin was exposed to sunlight for 6 h. Considering the toxic doses of prodigiosin to various organisms and its photodegradation characteristics, we suggest that prodigiosin has potential in controlling P. donghaiense blooms but should be applied at night, in small doses, with multiple applications. [Display omitted] • Prodigiosin damaged the photosynthetic and respiratory function of P. donghaiense. • Prodigiosin changed the fatty acid composition of P. donghaiense. • Prodigiosin blocked the cell cycle of algal cells. • The toxicities of prodigiosin to several aquatic species were assessed. • The growth recovery of algal cells under prodigiosin stress was investigated. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of iron-regulated cell death implicated in ischemic heart disease. Our previous study revealed that Sirtuin 3 (SIRT3) is associated with ferroptosis and cardiac fibrosis. In this study, we tested whether the knockout of SIRT3 in cardiomyocytes (SIRT3cKO) promotes mitochondrial ferroptosis and whether the blockade of ferroptosis would ameliorate mitochondrial dysfunction. Mitochondrial and cytosolic fractions were isolated from the ventricles of mice. Cytosolic and mitochondrial ferroptosis were analyzed by comparison to SIRT3loxp mice. An echocardiography study showed that SIRT3cKO mice developed heart failure as evidenced by a reduction of EF% and FS% compared to SIRT3loxp mice. Comparison of mitochondrial and cytosolic fractions of SIRT3cKO and SIRT3loxp mice revealed that, upon loss of SIRT3, mitochondrial, but not cytosolic, total lysine acetylation was significantly increased. Similarly, acetylated p53 was significantly upregulated only in the mitochondria. These data demonstrate that SIRT3 is the primary mitochondrial deacetylase. Most importantly, loss of SIRT3 resulted in significant reductions of frataxin, aconitase, and glutathione peroxidase 4 (GPX4) in the mitochondria. This was accompanied by a significant increase in levels of mitochondrial 4-hydroxynonenal. Treatment of SIRT3cKO mice with the ferroptosis inhibitor ferrostatin-1 (Fer-1) for 14 days significantly improved preexisting heart failure. Mechanistically, Fer-1 treatment significantly increased GPX4 and aconitase expression/activity, increased mitochondrial iron‑sulfur clusters, and improved mitochondrial membrane potential and Complex IV activity. Inhibition of ferroptosis ameliorated cardiac dysfunction by specifically targeting mitochondrial aconitase and iron‑sulfur clusters. Blockade of mitochondrial ferroptosis may be a novel therapeutic target for mitochondrial cardiomyopathies. • SIRT3cKO in mice causes severe cardiac dysfunction similar to the mitochondrial cardiomyopathy seen in Friedreich's ataxia • SIRT3cKO mice exhibit mitochondrial iron dysregulation and mitochondrial ferroptosis • Ferrostatin-1 improves cardiac function in SIRT3cKO mice by targeting mitochondrial iron-sulfur clusters and aconitase [ABSTRACT FROM AUTHOR]

The presence of some types of N -nitrosamines in water bodies is of great concern worldwide due to their carcinogenic risks and harmful mutagenic effects on human health. In the present study, eight N -nitrosamines and their formation potentials (FPs) were primarily investigated in Yangtze River surface water to evaluate their spatial distribution, mass loads, and ecological risks. The results showed that of the eight N -nitrosamines investigated, NDMA (<1.5–17 ng/L), NDEA (<1.4–9.5 ng/L), NDPA (1.0 ng/L), NMOR (<1.0–1.3 ng/L), NPIP (<2.1–3.7 ng/L), and NDBA (<3.6–30 ng/L) were detected. The FPs of NDMA (<27–130 ng/L), NDEA (<0.9–2.3 ng/L), NDPA (<1.2–1.9 ng/L), NPYR (<1.4–2.9 ng/L), NMOR (<1.0 ng/L), and NDBA (<1.1–14 ng/L) were significantly identified. NDBA was predominantly observed in surface water, while NDMA was noticeably detected in chloraminated water samples. It was estimated that approximately 5.4 t/y of N -nitrosamines were carried by the Yangtze River to the East China Sea, whereas the input flux of N -nitrosamine precursors was estimated to be approximately 69.5 t/y. Spatial variations were observed due to the input of N -nitrosamines from the upstream dams and lakes. The origin of N -nitrosamine precursors was not associated with the presence of sediment in river water. NDEA could be introduced into river water by the discharge of wastewater. NDBA and its precursors could originate from industrial and aquaculture activities. NDMA and its precursors could result from both of the aforementioned sources. Moreover, the wastewater discharge from small cities, pH value, wastewater treatment ratio, and dilution could be the key factors that influence the occurrence of N -nitrosamines along the Yangtze River. More attention should be paid to the cancer risks posed by N -nitrosamines. The ecological risks posed by N -nitrosamines in the Yangtze River can be ignored. • Uneven spatial distribution of NDMA was observed in the Yangtze River. • A high correlation between NDMA and NDMA-FP was first identified. • The distributions of N -nitrosamines were affected by lakes and reservoirs. • The occurrences of N -nitrosamines were affected by pH. [ABSTRACT FROM AUTHOR]

Adolescence and young adulthood are critical periods of human growth and development. Phthalates are environmental endocrine disruptors, and their health hazards in adolescents and young adults cannot be ignored. This study was undertaken to assess phthalate exposure and determine the associations between lifestyle behaviors and phthalate metabolite levels in Chinese adolescents and young adults. Four hundred and seventy-eight adolescents and young adults aged 16–20 years were included in this study. The levels of mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-carboxmethyl)-hexyl phthalate (MCMHP) in the subjects' urine were measured by high-performance liquid chromatography-tandem mass spectrometry. The estimated daily intake (EDI) and hazard index (HI) of phthalates were calculated based on urinary metabolite levels. Relevant information on the subjects was collected via questionnaires. The associations between phthalate metabolite levels and lifestyle behaviors were examined using the independent-sample t- test, Mann-Whitney test and multiple linear regression. In this study, the detection rates of all seven metabolites were >98%. The highest median metabolite concentration was MBP, which was 43.00 μg/L (33.11 μg/g creatinine). The highest median EDI was for di-(2-ethylhexyl) phthalate (DEHP), which was 2.40 μg/kg-bw/day (volume-based) and 1.51 μg/kg-bw/day (creatinine-based). 2.7% (volume-based) and 1.0% (creatinine-based) of the subjects showed excessive HI TDI (HI of the tolerable daily intake) values, which indicated the cumulative risk of anti-androgenic effects. Furthermore, factors significantly associated with phthalate metabolite levels included the use of plastic food packages (DEHP metabolites), physical exercise (MEOHP), the frequency of fast food consumption (MBP), and the frequency of skin care cosmetics and color cosmetics use (MEP). Our results suggest that Chinese adolescents and young adults are widely exposed to phthalates and their metabolite levels are influenced by lifestyle behaviors. • Chinese adolescents and young adults are widely exposed to DEP, DBP, and DEHP. • MBP was the metabolite with highest median concentration in subjects' urine. • DEHP was the phthalate with highest estimated median daily intake. • Approximately 3% of subjects showed a cumulative risk of anti-androgenic effects. • The levels of phthalate metabolites was associated with lifestyle behaviors. [ABSTRACT FROM AUTHOR]

A new bisepoxylignan dendranlignan A (A 1) and the known compound lantibeside D (D 2) was isolated from Chrysanthemum Flower, the dried capitulum of Dendranthema morifolium (Ramat.) kitam. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-NMR, 2D-NMR and MS data. Additionally, A1 and D2 were evaluated for their effects on the production of inflammatory mediators in H9c2 cardiomyocytes stimulated with lipopolysaccharide (LPS). Results demonstrated that A1 and D2 decreased LPS-induced production of inflammatory cytokines TNF-α, IL-2 and IFN-γ in H9c2 cells. Both compounds also decreased the nuclear localization of c-JUN, p-P65 and p -IRF3, but did not affect the level of TLR4. Molecular docking indicated that A1 and D2 occupied the ligand binding sites of TLR4-MD2. In the present study, we for the first time discovered a new bisepoxylignan compound A1, and found that this compound has a potential to inhibit inflammation by inhibiting TLR4 signaling. [ABSTRACT FROM AUTHOR]

Chronic heart failure is associated with increased interleukin-1β (IL-1β), leukocyte infiltration, and fibrosis in the heart and lungs. Here we further studied the role of IL-1β in the transition from left heart failure to pulmonary hypertension and right ventricular hypertrophy in mice with existing left heart failure produced by transverse aortic constriction. We demonstrated that transverse aortic constriction-induced heart failure was associated with increased lung inflammation and cleaved IL-1β, and inhibition of IL-1β signaling using blocking antibodies of clone B122 effectively attenuated further decrease of left ventricular systolic function in mice with existing heart failure. We found that inhibition of IL-1β attenuated lung inflammation, inflammasome activation, fibrosis, oxidative stress, and right ventricular hypertrophy. IL-1β blocking antibodies of clone B122 also significantly attenuated lung T cell activation. Together, these data indicate that IL-1β signaling exerts a causal role for heart failure progression, or the transition from left heart failure to lung remodeling and right heart hypertrophy. A diagram shows left ventricle pressure overload-induced heart failure causes profound lung leukocyte infiltration, T cell activation, fibrosis, oxidative stress and inflammasome activation and selective inhibition of IL-1β signaling effectively attenuated above changes and the associated right ventricle hypertrophy/fibrosis in mice with existing heart failure. Unlabelled Image • IL-1β blocking attenuates lung inflammation, fibrosis, as well as RV hypertrophy in mice with existing LV failure. • IL-1β blocking antibodies could effectively attenuate heart failure-induced lung T cell activation. • Inhibition of IL-1β signaling effectively suppressed lung inflammasome activation. [ABSTRACT FROM AUTHOR]

This study designed a composite material with internal synergistic effects among multiple components to achieve highly selective adsorption of Cu (II). Through controlled synthesis, the Fe 3 O 4 /MnO 2 (3 1 0)/ZIF-67 composite was successfully fabricated, leading to significant improvement in adsorption selectivity, capacity, and adsorption rate. The experimental results showed that the composite is of outstanding selectivity in the adsorption of Cu (II), with a partition coefficient K of Cu (II) that was 2.2–5.3 times higher than that of other coexisting ions. Moreover, the composite exhibited a remarkable adsorption capacity of 1261.0 mg g−1 and a fast adsorption rate of 840.7 mg g−1 h−1 at 298 K. Additionally, its magnetic property facilitated easy separation from wastewater, thereby enhancing its potential for commercial applications. The synergetic effect mechanism was analyzed through characterizations and DFT calculations. Furthermore, the recyclability of the composite was investigated, which showed that after seven cycles, the adsorption efficiency remained at 85% of its initial efficiency. It can be concluded that Fe 3 O 4 /MnO 2 (3 1 0)/ZIF-67 has potential to address challenges posed by heavy metal pollution in copperplating effluents. • A composite with the desired synergistic effect is developed for the adsorption of Cu2+. • The adsorption of Cu2+ is enhanced by the synergistic effect of MnO 2 (3 1 0) and ZIF-67. • The adsorption of Cu2+ is highly selective with a capacity of 1261.0 mg g−1. • Selective adsorption of Cu2+ is revealed by DFT calculations. [ABSTRACT FROM AUTHOR]

Adenosine exerts numerous protective actions in the heart, including attenuation of cardiac hypertrophy. Adenosine kinase (ADK) converts adenosine to adenosine monophosphate (AMP) and is the major route of myocardial adenosine metabolism, however, the impact of ADK activity on cardiac structure and function is unknown. To examine the role of ADK in cardiac homeostasis and adaptation to stress, conditional cardiomyocyte specific ADK knockout mice (cADK−/−) were produced using the MerCreMer-lox-P system. Within 4 weeks of ADK disruption, cADK−/− mice developed spontaneous hypertrophy and increased β-Myosin Heavy Chain expression without observable LV dysfunction. In response to 6 weeks moderate left ventricular pressure overload (transverse aortic constriction;TAC), wild type mice (WT) exhibited ~60% increase in ventricular ADK expression and developed LV hypertrophy with preserved LV function. In contrast, cADK−/− mice exhibited significantly greater LV hypertrophy and cardiac stress marker expression (atrial natrurietic peptide and β-Myosin Heavy Chain), LV dilation, reduced LV ejection fraction and increased pulmonary congestion. ADK disruption did not decrease protein methylation, inhibit AMPK, or worsen fibrosis, but was associated with persistently elevated mTORC1 and p44/42 ERK MAP kinase signaling and a striking increase in microtubule (MT) stabilization/detyrosination. In neonatal cardiomyocytes exposed to hypertrophic stress, 2-chloroadenosine (CADO) or adenosine treatment suppressed MT detyrosination, which was reversed by ADK inhibition with iodotubercidin or ABT-702. Conversely, adenoviral over-expression of ADK augmented CADO destabilization of MTs and potentiated CADO attenuation of cardiomyocyte hypertrophy. Together, these findings indicate a novel adenosine receptor-independent role for ADK-mediated adenosine metabolism in cardiomyocyte microtubule dynamics and protection against maladaptive hypertrophy. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract We concretely report feasible synthesis procedures of colloidal Cu 2 ZnSn(S 1- x ,Se x) 4 -Au (CZTSSe-Au) nano-heterostructured composites, and creatively employ them as the counter electrodes (CEs) of all-solid-state solar cells with inorganic CsSnI 2.95 F 0.05 perovskite hole conductor. Acquired optical characterization indicates that integration of noble metal nanoparticles with cuprum-chalcogenide could heighten light absorption within visible-band due to localized surface plasmon resonance (LSPR) generated by Au, and the forbidden gap of nanocomposites gets adjustment accordingly. It is demonstrated that this novel photocathode alternative with favorable conductivity can not only match the energy level within the device band structure construction, but also restrain recombination so that accelerate charge transfer and extraction occurring on the photocathode. The photocurrent and photoelectric conversion efficiency (PCE) of cells conjugating CZTS-Au photocathodes turn to be respectively 43% and 25% higher than those using pure CZTS. Moreover, it has been demonstrated that CZTS-Au, coupling very well with inorganic perovskite, owns comparable electrocatalytic performance and even higher output photocurrent with respect to platinum CEs, which portends a potential substitution for conventional costly photocathodes. A comprehensive analysis on impedance spectroscopy data is subsequently carried out for the sake of deep understanding charge accumulation and transfer response at CsSnI 2.95 F 0.05 /CE interface, attempting to orient further optimization of device performance. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease have an increased cardiovascular morbidity and mortality. It has been recognized that the traditional cardiovascular risk factors could only partially explain the increased cardiovascular morbidity and mortality in patients with chronic kidney disease. Asymmetric dimethylarginine (ADMA) and N -monomethy l -arginine (L-NMMA) are endogenous inhibitors of nitric oxide synthases that attenuate nitric oxide production and enhance reactive oxidative specie generation. Increased plasma ADMA and/or L-NMMA are strong and independent risk factor for chronic kidney disease, and various cardiovascular diseases such as hypertension, coronary artery disease, atherosclerosis, diabetes, and heart failure. Both ADMA and L-NMMA are also eliminated from the body through either degradation by dimethylarginine dimethylaminohydrolase-1 (DDAH1) or urine excretion. This short review will exam the literature of ADMA and L-NMMA degradation and urine excretion, and the role of chronic kidney diseases in ADMA and L-NMMA accumulation and the increased cardiovascular disease risk. Based on all available data, it appears that the increased cardiovascular morbidity in chronic kidney disease may relate to the dramatic increase of systemic ADMA and L-NMMA after kidney failure. [ABSTRACT FROM AUTHOR]

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability and can increase production of NOS derived reactive oxidative species. Increased plasma ADMA is a one of the strongest predictors of mortality in patients who have had a myocardial infarction or suffer from chronic left heart failure, and is also an independent risk factor for several other conditions that contribute to heart failure development, including hypertension, coronary artery disease/atherosclerosis, diabetes, and renal dysfunction. The enzyme responsible for ADMA degradation is dimethylarginine dimethylaminohydrolase-1 (DDAH1). DDAH1 plays an important role in maintaining nitric oxide bioavailability and preserving cardiovascular function in the failing heart. Here, we examine mechanisms of abnormal NO production in heart failure, with particular focus on the role of ADMA and DDAH1. [ABSTRACT FROM AUTHOR]

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2min, each separated by 2min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (P<0.05). Despite reduced regional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. [ABSTRACT FROM AUTHOR]

Abstract: AMP-activated protein kinase (AMPK) is an energy sensing metabolic switch in mammalian cells. Here, we report our novel finding that AMPK is lost in all immune cells of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of Central Nervous System (CNS). AMPKα1 is predominantly expressed in T cells and antigen presenting cells (APCs), which are primarily involved in EAE disease progression. AMPK is lost at protein level in spleen macrophages, total T cells and their subsets (CD4, CD8 and regulatory T cells) isolated from EAE afflicted animals compared to control, without affecting its mRNA levels suggesting that the loss of AMPK protein is the result of posttranscriptional modification. To examine its pathological relevance in inflammatory disease, EAE was induced in wild type (+/+) and AMPKα1 null mice (−/−) using MOG35–55 peptide. AMPKα1−/− mice exhibited severe EAE disease with profound infiltration of mononuclear cells compared to wild type mice however, AMPKα2 is not involved in enhancing the severity of the disease. Spleen cells isolated from AMPKα1−/− immunized mice exhibited a significant induction in the production of IFNγ. Our study identifies AMPK as a down regulated target during disease in all immune cells and possibly restoring AMPK may serve as a novel therapeutic target in autoimmune diseases like multiple sclerosis (MS). [Copyright &y& Elsevier]