Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. However, there are only few data about remodelling of collagen fibers in healthy looking mucosa distant from the cancer. Using SHG imaging, electron microscopy and specialized softwares (CT-FIRE, CurveAlign and FiberFit), we objectively visualized and quantified changes in morphology and organization of collagen fibers and investigated possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that in the lamina propria this far from the colon cancer, there were changes in collagen architecture (width, straightness, alignment of collagen fibers and collagen molecules inside fibers), increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes (LOX and MMP2). Thus, the changes in organization of collagen fibers, which were already described in the cancer microenvironment, also exist in the mucosa far from the cancer, but smaller in magnitude. Extracellular matrix (ECM) is no longer considered as an inert substrate, a three-dimensional network which only "fills the spaces" between cells and provide mechanical support 1,2. Today, ECM is known to be a complex and dynamic structure, whose chemical and biophysical properties affect cell adhesion 3 , proliferation 4 morphology 5 , migration 6 , regulate tissue morphogenesis 7,8 and fluid volume in tissues 9. The most abundant component of ECM in the lamina propria of the colon mucosa is type I collagen. Remodelling of collagen fibers has been described in almost every solid cancer, including colorectal cancer. During tumor formation and progression, collagen remodelling is constantly carried out: degradation, synthesis, cross-linking of fibers, change of fiber orientation, and interaction of cells of the innate and acquired immune system with collagen fibers 10,11. Changes in morphology, representation, and organization of collagen fibers contribute to the formation of the microenvironment that favors tumor progression, primarily through its effect on cell migration and polarization 12. Also, remodelling of collagen fibers on premetastatic sites is of great importance in determination of survival and growth of disseminated cancer cells, and thus, formation of metastasis 13,14. Remodelling of collagen fibers may be a result of changes in synthesis, degradation or cross-linking. Main cells responsible for synthesis of collagen in colon mucosa are fibroblasts and myofibroblasts. The most important enzymes for degradation of collagen fibers are matrix metalloproteinases (MMPs). It has been shown that expression of MMP2 and MMP9 is increased in colorectal cancer and influences its progression and

We sought to investigate the relationship between blood pressure (BP) variability and left atrial (LA) phasic function assessed by volumetric and speckle tracking method in normal-weight, overweight and obese hypertensive patients. This cross-sectional study included 164 untreated hypertensive subjects who underwent a 24-h ambulatory BP monitoring and complete two-dimensional echocardiographic examination (2DE). All the patients were separated into three groups according to their body mass index (BMI): normal-weight patients (BMI < 25 kg/m(2)), overweight patients (25 ≤ BMI < 30 kg/m(2)), and obese patients (BMI ≥ 30 kg/m(2)). Daytime, nighttime and 24 h BP variability indices were higher in obese hypertensive subjects than in lean patients. Maximum and minimum LA volumes and volume indexes gradually and significantly increased, whereas pre-A LAV decreased, from normal-weight to obese subjects. Total and passive LA emptying fractions, representing LA reservoir and conduit function, gradually reduced from lean to obese individuals. Active LA EF, the parameter of LA booster pump function, increased in the same direction. Similar results were obtained by 2DE strain analysis. BP variability parameters were associated with structural, functional and mechanical parameters of LA remodeling in the whole study population. The parameters of LA reservoir function were negatively related with BP variability indices, whereas the parameters of LA pump function were positively related with BP variability indices. Obesity significantly impacts BP variability and LA phasic function in untreated hypertensive subjects. BP variability is associated with LA remodeling independent of BP, left ventricular systolic and diastolic function.

Preclinical Research Potassium (K ) channels have a key role in the maintenance of smooth muscle tone; a variety of agonists can modify the tone by altering K -channel activity. The aim of this study was assess the effects of the phenols, resveratrol, and naringenin on K -channels of the vascular smooth muscle. Segments of human umbilical vein (HUV) without endothelium were precontracted using serotonin (100 μM) or 100 mM K to derive cumulative concentration-response curves using increasing concentrations of resveratrol or naringenin. K -channel inhibitors were added in the bath before resveratrol (1-100 μM) or naringenin (0.01-1 mM) in assess the role of K -channels in their effects on HUV precontracted by serotonin. 4-Aminopiridine (4-AP; 1 mM), a nonselective blocker of voltage-dependent, tetraethylammonium (TEA; 1 mM) and barium chloride (1 mM), a nonselective blocker of Ca -dependent and inward rectifier K -channels (respectively) induced significant shifts to the right (P < 0.05) of resveratrol. concentration-response curves. The effect of naringenin was antagonized by 4-AP (1 mM). 4-AP-, TEA-, and barium chloride-sensitive K -channels are probably involved in the resveratrol vasodilatatory effect, while naringenin seems to affect 4-AP-sensitive K -channels. However, other mechanisms of vasodilation induced by polyphenols could not be excluded. Drug Dev Res, 2015. © 2015 Wiley Periodicals, Inc.