Borregaardklinge1878

Obesity represents a global health problem. Excessive caloric intake promotes the release of inflammatory mediators by hypertrophic adipocytes and obesity-induced inflammation is now recognized as a risk factor for the development of several diseases, such as cardiovascular diseases, insulin resistance, type-II diabetes, liver steatosis and cancer. Since obesity causes inflammation, we tested the ability of acetylsalicylic acid (ASA), a potent anti-inflammatory drug, in counteracting this inflammatory process and in mitigating obesity-associated health complications.

Mice were fed with standard (SD) or high fat diet (HFD) for 3months and then treated with acetylsalicylic acid for the subsequent two months. We then analyzed the metabolic and inflammatory status of their adipose and liver tissue by histological, molecular and biochemical analysis.

Although ASA did not exert any effect on body weight, quantification of adipocyte size revealed that the drug slightly reduced adipocyte hypertrophy, however not sufficient so as to induce weight loss. Most importantly, ASA was able to improve insulin resistance. Gene expression profiles of pro- and anti-inflammatory cytokines as well as the expression of macrophage and lymphocyte markers revealed that HFD led to a marked macrophage accumulation in the adipose tissue and an increase of several pro-inflammatory cytokines, a situation almost completely reverted after ASA administration. In addition, liver steatosis caused by HFD was completely abrogated by ASA treatment.

ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue.

ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue.Klotho is a novel renoprotective anti-aging protein available in membrane-bound or soluble form. Klotho is expressed in brain, pancreas, and other solid organs but shows highest expression levels in the kidney. Klotho sustains normal kidney physiology but Klotho regulation also contributes to the progression of kidney disease. Systemic and intrarenal levels of Klotho fall drastically during acute kidney injury, kidney fibrosis, diabetic nephropathy, and other forms of chronic kidney disease, etc. Moreover, exogenous supplementation or overexpression of endogenous Klotho attenuates kidney disease. The regulation of endogenous Klotho expression involves epigenetic as well as non-epigenetic mechanisms. The epigenetic modifications such as DNA methylation, post-translational histone modifications, miRNAs regulate the change in Klotho expression in kidney disease. Non-epigenetic mechanisms such as ER stress, Wnt signaling, activation of the renin angiotensin system (RAS), excessive reactive oxygen species and cytokine generation, albumin overload, and PPAR-γ signaling also contribute to Klotho regulation. Evolving evidence highlight the capacity of natural products to regulate Klotho expression in kidney disease. All these preclinical data suggest that Klotho could be a novel biomarker as well as therapeutic target. Here we review the different mechanisms of Klotho regulation in the context of Klotho as a biomarker and potential therapeutic agent.Although somatic cells play an integral role in animal gametogenesis, their organization and function are usually poorly characterized, especially in non-model systems. One such example is a peculiar cell found in leech ovaries - the apical cell (AC). A single AC can be found at the apical tip of each ovary cord, the functional unit of leech ovaries, where it is surrounded by other somatic and germline cells. The AC is easily distinguished due to its enormous size and its numerous long cytoplasmic projections that penetrate the space between neighboring cells. It is also characterized by a prominent accumulation of mitochondria, Golgi complexes and electron-dense vesicles. Tofacitinib order ACs are also enriched in cytoskeleton, mainly in form of intermediate filaments. Additionally, the AC is connected to neighboring cells via junctions that structurally resemble hemidesmosomes. In spite of numerous descriptive data about the AC, its functions remain poorly understood. Its suggested functions include a role in forming skeleton for the germline cells, and a role in defining a niche for germline stem cells. The latter is more speculative, since germline stem cells have not been identified in leech ovaries. Somatic cells with similar morphological properties to those of the AC have been found in gonads of nematodes - the distal tip cell - and in insects - Verson's cell, hub cells and cap cells. In the present article we summarize information about the AC structure and its putative functions. AC is compared with other well-described somatic cells with potentially similar roles in gametogenesis.Although the plan of the retina is well conserved in vertebrates, there are considerable variations in cell type diversity and number, as well as in the organization and properties of the tissue. The high ratios of retinal ganglion cells (RGCs) to cones in primate fovea and bird retinas favor neural circuits essential for high visual acuity and color vision. The role that cell metabolism could play in cell fate decision during embryonic development of the nervous system is still largely unknown. Here, we describe how subtle changes of mitochondrial activity along the pathway converting uncommitted progenitors into newborn RGCs increase the recruitment of RGC-fated progenitors. ATOH7, a proneural protein dedicated to the production of RGCs in vertebrates, activates transcription of the Hes5.3 gene in pre-committed progenitors. The HES5.3 protein, in turn, regulates a transient decrease in mitochondrial activity via the retinoic acid signaling pathway few hours before cell commitment. This metabolic shift lengthens the progression of the ultimate cell cycle and is a necessary step for upregulating Atoh7 and promoting RGC differentiation.

Diffusion magnetic resonance imaging (dMRI) is a popular non-invasive imaging technique applied for the study of nerve fibers in vivo, with diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI) as the commonly used dMRI methods. However, DTI cannot resolve complex fiber orientations in a local area and HARDI lacks a solid physical basis.

We introduce a diffusion coefficient orientation distribution function (DCODF). It has a clear physical meaning to represent the orientation distribution of diffusion coefficients for Gaussian and non-Gaussian diffusion. Based on DCODF, we then propose a new HARDI method, termed as diffusion coefficient orientation distribution transform (DCODT), to estimate the orientation distribution of nerve fibers in voxels.

The method is verified on the simulated data, ISMRM-2015-Tracto-challenge data, and HCP datasets. The results show the superior capability of DCODT in resolving the complex distribution of multiple fiber bundles effectively.

The method is compared to other common model-free HARDI estimators.