Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4 inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine or vehicle. Flow cytometry of adipose tissue and liver, immunohistological analysis and glucose and insulin tolerance tests were performed to determine the effect of the treatment and diet. Although high fat diet feeding induced insulin resistance no significant effect was observed between the treatment groups. In addition no effect was found in leukocyte infiltration and activation in the adipose tissue and liver. Therefore we concluded that inhibition of neutrophil extracellular trap formation may have no clinical relevance for early obesity-mediated pathogenesis of the adipose tissue and liver

The mediating effect of green innovation on the relationship between green supply chain management and environmental performance

The emerging environmental awareness of the public, as well as the implementation of governmental regulations, force organisations to employ corporate environmental practices such as green supply chain management (GSCM) and green innovation. Accordingly, both practices are crucial to achieve professional improvement in the environmental performance of these organisations. However, research on the relationship of GSCM, green innovation, and environmental performance is relatively rare. Therefore, this study is aimed to provide empirical evidence showing that GSCM and green innovation practices significantly improve environmental performance in order to encourage organisations to implement these practices. In addition, this study investigates the relationship between GSCM and green innovation practices and the influence of these practices on the environmental performance in 123 manufacturing organisations with ISO 14001 certification. The results of PLS-SEM revealed that there is a significant and positive relationship between GSCM and green innovation, and the environmental performance. Moreover, green innovation had a positive effect on the environmental performance. Furthermore, green innovation had a mediating relationship between GSCM and environmental performance. Therefore, the present paper confirmed the significant influence of GSCM on boosting the green innovation of organisations and on the manufacturing establishments, which eventually improve the environment. In brief, the outcomes of this study provide enhanced understanding about the significant role of green innovation in the manufacturers for improving their GSCM and organisational environmental performance

Molecular Imaging for Efficacy of Pharmacologic Intervention in Myocardial Remodeling

ObjectivesUsing molecular imaging techniques, we examined interstitial alterations during postmyocardial infarction (MI) remodeling and assessed the efficacy of antiangiotensin and antimineralocorticoid intervention, alone and in combination.BackgroundThe antagonists of the renin-angiotensin-aldosterone axis restrict myocardial fibrosis and cardiac remodeling after MI and contribute to improved survival. Radionuclide imaging with technetium-99m–labeled Cy5.5 RGD imaging peptide (CRIP) targets myofibroblasts and indirectly allows monitoring of the extent of collagen deposition post-MI.MethodsCRIP was intravenously administered for gamma imaging after 4 weeks of MI in 63 Swiss-Webster mice and in 6 unmanipulated mice. Of 63 animals, 50 were treated with captopril (C), losartan (L), spironolactone (S) alone, or in combination (CL, SC, SL, and SCL), 8 mice received no treatment. Echocardiography was performed for assessment of cardiac remodeling. Hearts were characterized histopathologically for the presence of myofibroblasts and thick and thin collagen fiber deposition.ResultsAcute MI size was similar in all groups. The quantitative CRIP percent injected dose per gram uptake was greatest in the infarct area of untreated control mice (2.30 ± 0.14%) and decreased significantly in animals treated with 1 agent (C, L, or S; 1.71 ± 0.35%; p = 0.0002). The addition of 2 (CL, SC, or SL 1.31 ± 0.40%; p < 0.0001) or 3 agents (SCL; 1.16 ± 0.26%; p < 0.0001) demonstrated further reduction in tracer uptake. The decrease in echocardiographic left ventricular function, strain and rotation parameters, as well as histologically verified deposition of thin collagen fibers, was significantly reduced in treatment groups and correlated with CRIP uptake.ConclusionsRadiolabeled CRIP allows for the evaluation of the efficacy of neurohumoral antagonists after MI and reconfirms superiority of combination therapy. If proven clinically, molecular imaging of the myocardial healing process may help plan an optimal treatment for patients susceptible to heart failure

Antioxidant activities and polyphenolics from the shoots of Barringtonia racemosa (L.) Spreng in a polar to a polar medium system.

Solvents of different polarities (water, ethanol, ethyl acetate and hexane) were used for the extraction of antioxidants from the leaves and stems of the shoots of Barringtonia racemosa. The leaf water extracts had the highest polyphenol and ascorbic acid contents. Flavonoids and carotenoids were highest in the leaf ethyl acetate extracts. The leaf water extracts had the highest ferric reducing activities and scavenging activities against ABTS, DPPH and superoxide anion radicals. Antioxidant activities of these extracts were comparable to, if not higher than the antioxidants BHT, ascorbic acid, rutin and gallic acid. UHPLC analyses revealed the presence of gallic acid, protocatechuic acid, ellagic acid, quercetin and kaempferol in the leaves. Overall, the leaves contained more antioxidant compounds and higher antioxidant activities than the stems. This study demonstrates the polar nature of antioxidants in the shoots of B. racemosa. There is great potential for the plant as a natural source of antioxidants

Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions

Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the epigenomic enzyme Histone deacetylase 3 (Hdac3) in regulating the atherosclerotic phenotype of macrophages. Using conditional knockout mice, we found that myeloid Hdac3 deficiency promotes collagen deposition in atherosclerotic lesions and thus induces a stable plaque phenotype. Also, macrophages presented a switch to anti-inflammatory wound healing characteristics and showed improved lipid handling. The pro-fibrotic phenotype was directly linked to epigenetic regulation of the Tgfb1 locus upon Hdac3 deletion, driving smooth muscle cells to increased collagen production. Moreover, in humans, HDAC3 was the sole Hdac upregulated in ruptured atherosclerotic lesions, Hdac3 associated with inflammatory macrophages, and HDAC3 expression inversely correlated with pro-fibrotic TGFB1 expression. Collectively, we show that targeting the macrophage epigenome can improve atherosclerosis outcome and we identify Hdac3 as a potential novel therapeutic target in cardiovascular disease

Professional development and sustainable development goals

Professional development is defined as a consciously designed systematic process that helps professionals to attain, utilize, and retain knowledge, skills, and expertise. It is simply a process of obtaining skills, qualifications, and experience that help in advancement in one’s career. In the field of education, it is defined as the process of improving staff skills and competencies needed to produce outstanding performance of students. It also refers to a process of improving an organization’s staff capabilities through access to education and training opportunities for better output. Professional development can include a variety of approaches such as formal and informal education, vocational, specialized, or skill-based training, or advanced professional learning

Matrix-free interior point method for compressed sensing problems

We consider a class of optimization problems for sparse signal reconstruction which arise in the field of Compressed Sensing (CS). A plethora of approaches and solvers exist for such problems, for example GPSR, FPC AS, SPGL1, NestA, \ell_{1}_\ell_{s}, PDCO to mention a few. Compressed Sensing applications lead to very well conditioned optimization problems and therefore can be solved easily by simple first-order methods. Interior point methods (IPMs) rely on the Newton method hence they use the second-order information. They have numerous advantageous features and one clear drawback: being the second-order approach they need to solve linear equations and this operation has (in the general dense case) an $O(n^3)$ computational complexity. Attempts have been made to specialize IPMs to sparse reconstruction problems and they have led to interesting developments implemented in $\ell_1\_\ell_s$ and PDCO softwares. We go a few steps further. First, we use the matrix-free interior point method, an approach which redesigns IPM to avoid the need to explicitly formulate (and store) the Newton equation systems. Secondly, we exploit the special features of the signal processing matrices within the matrix-free IPM. Two such features are of particular interest: an excellent conditioning of these matrices and the ability to perform inexpensive (low complexity) matrix-vector multiplications with them. Computational experience with large scale one-dimensional signals confirms that the new approach is efficient and offers an attractive alternative to other state-of-the-art solvers