Glycosaminoglycan sulodexide modulates inflammatory pathways in chronic venous disease.

Inflammation represents an important epiphenomenon in the etiopathogenesis of chronic venous disease, a worldwide debilitating condition affecting millions of subjects. The pathophysiology of chronic venous disease (CVD) is based on the hemodynamic abnormalities in conjunction to alterations in cellular and extracellular matrix biocompounds. The endothelial dysfunction results from early perturbation in the endothelium linked to glycocalyx injury and promoted by inflammatory cells and mediators (such as matrix metalloproteinases and interleukins), which lead to progressive dilation of the vein resulting in chronic venous insufficiency.

Omics profiles in chronic venous ulcer wound fluid: innovative applications for translational medicine.

Chronic venous disease represents a healthcare problem due to high prevalence and recurrence rates. Studies on chronic venous ulcer wound fluid (CVUWF) have demonstrated increased inflammation and proteolysis which can cause tissue destruction and delayed healing. This review discusses: nearly all known metabolites discovered in the past 25 years in CVUWF studies; the omics approaches characterizing the microenvironment of human venous leg ulcers; and the use of biocompounds as prognostic biomarkers and as possible targets for therapeutic approaches.

Morphogenesis of rat myotendinous junction.

Myotendinous junction (MTJ) is the highly specialized complex which connects the skeletal muscle to the tendon for transmitting the contractile force between the two tissues. The purpose of this study was to investigate the MTJ development and rat EDL was chosen as a model. 1, 15, 30 day animals were considered and the junctions were analyzed by light and electron microscopy.

Further considerations on in vitro skeletal muscle cell death.

The present review discusses the apoptotic behavior induced by chemical and physical triggers in C2C12 skeletal muscle cells, comparing myoblast to myotube sensitivity, and investigating it by means of morphological, biochemical and cytofluorimetric analyses. After all treatments, myotubes, differently from myoblasts, showed a poor sensitivity to cell death. Intriguingly, in cells exposed to staurosporine, etoposide and UVB radiation, apoptotic and normal nuclei within the same fibercould be revealed.

Mitohormesis in muscle cells: a morphological, molecular, and proteomic approach.

Low-level oxidative stress induces an adaptive response commonly defined as hormesis; this type of stress is often related to reactive oxygen species (ROS) originating from the mitochondrial respiratory chain (mitochondrial hormesis or mitohormesis). The accumulation of transient low doses of ROS either through chronic physical activity or caloric restriction influences signaling from the mitochondrial compartment to the cell, reduces glucose metabolism, induces mitochondrial metabolism, increases stress resistance and ultimately, increases lifespan. Mitochondrial formation of presumably harmful levels (chronic and/or excessive) of ROS within skeletal muscle has been observed in insulin resistance of obese subjects, type 2 diabetes mellitus, as well as in impaired muscle function associated with normal aging.

Development and use of sulodexide in vascular diseases: implications for treatment.

Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium.

Sulodexide down-regulates the release of cytokines, chemokines, and leukocyte colony stimulating factors from human macrophages: role of glycosaminoglycans in inflammatory pathways of chronic venous disease.

Chronic venous disease (CVeD) is a debilitating condition that affects millions of individuals worldwide. The condition can result in varicose veins, or advance to severe skin changes and venous ulceration. The fundamental basis for CVeD is inflammation within the venous circulation and that it is subjected to increased hydrostatic pressure resulting in increased ambulatory venous pressure.

Weight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding.

Background: Bladder dysfunction has one of the highest prevalences as a comorbidity of obesity in industrialized countries. The aetiopathogenesis of obesity-associated bladder dysfunction is still obscure, but there is growing evidence that general metabolic changes in obese patients may be in part responsible. As demonstrated recently, high fat diet (HFD) significantly alters the protein expression in the urinary bladder, activates multiple signalling pathways associated with cell survival and inflammation and ultimately provokes bladder fibrosis in an obese rat model.

Putative miRNAs for the diagnosis of dyslexia, dyspraxia, and specific language impairment.

Disorders of human communication abilities can be classified into speech and language disorders. Speech disorders (e.g.

Aluminium, carbonyls and cytokines in human nipple aspirate fluids: Possible relationship between inflammation, oxidative stress and breast cancer microenvironment.

The human breast is likely exposed to Al (aluminium) from many sources including diet and personal care products. Underarm applications of aluminium salt-based antiperspirant provide a possible long-term source of exposure, especially after underarm applications to shaved and abraded skin. Al research in breast fluids likely reflects the intraductal microenvironment.

Understanding breast cancer stem cell heterogeneity: time to move on to a new research paradigm.

Human breast cancer (BC) is one of the leading causes of death for women worldwide, and is characterized by a group of highly heterogeneous lesions. The morphological and biomolecular heterogeneity of BC cells, accompanied by dynamic plasticity of the BC microenvironment and the presence of stem-like cells, make tumor categorization an urgent and demanding task.The major limitations in BC research include the high flexibility rate of breast cancer stem cells (BCSCs) and the difficulty of their identification.

Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome.

Background: One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific.

Anti-apoptotic activity of hydroxytyrosol and hydroxytyrosyl laurate.

Hydroxytyrosol (HyT) is a polyphenol primarily released in olive mill wastewater and in olive oil. In animal and cell model studies, HyT and its metabolites have strong antioxidant and antimicrobial activities, as well as beneficial effects on the cardiovascular system and in several human diseases. Differently, many researchers reported that HyT down-regulates tumor cell viability and cell cycle progression, and induces reactive oxygen species (ROS) production and apoptosis.

Deciphering the single-cell omic: innovative application for translational medicine.

Traditional technologies to investigate system biology are limited by the detection of parameters resulting from the averages of large populations of cells, missing cells produced in small numbers, and attempting to uniform the heterogeneity. The advent of proteomics and genomics at a single-cell level has set the basis for an outstanding improvement in analytical technology and data acquisition. It has been well demonstrated that cellular heterogeneity is closely related to numerous stochastic transcriptional events leading to variations in patterns of expression among single genetically identical cells.

Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases.

We evaluated the effects of the glycosaminoglycan sulodexide (SDX; antithrombotic/profibrinolytic drug) on the activity and release of matrix metalloproteinases (MMPs) in human blood. This was a prospective non-randomized study, analyzing by zymography and ELISA the in vitro effects of SDX on pro-enzyme, complexed, and active MMP forms in plasma and serum from 60 healthy donors, and in U-937 leukemia cell line. The levels and zymographic profile of MMP-2 did not show significant changes among samples and during SDX treatments.

Nuclear localization of matrix metalloproteinases.

Matrix metalloproteinases (MMPs) were originally identified as matrixin proteases that act in the extracellular matrix. Recent works have uncovered nontraditional roles for MMPs in the extracellular space as well as in the cytosol and nucleus. There is strong evidence that subspecialized and compartmentalized matrixins participate in many physiological and pathological cellular processes, in which they can act as both degradative and regulatory proteases.

Hypoxia and neural stem cells: from invertebrates to brain cancer stem cells.

Oxygen is a fundamental element for all living organisms, and modifications in its concentration influence several physiological and pathological events such as embryogenesis, development and also aging. Regulation of oxygen levels is an important factor in neural stem cell biology (e.g.

What does matrix metalloproteinase-1 expression in patients with breast cancer really tell us?

Molecular and biochemical expressions of matrix metalloproteinases in breast cancer tissue and cells offers promise in helping us understand the breast cancer microenvironment, and also in the future it is hoped this will improve its detection, treatment and prognosis. In a retrospective study recently published in BMC Cancer, microenvironment predisposing to breast cancer progression, metastatic behavior and the expression of matrix metalloproteinase-1 (MMP-1) and its correlation with well-known biochemical, molecular and clinicopathologic factors in breast cancer cells and cancer-associated stromal cells was examined; this study also analyzed patient survival in different breast cancer subtypes. The positive correlation in breast tumor and stromal cells between MMP-1 expression and several markers of tumor grade and stage provide us with some useful new insights into important questions about the molecular profiling of the stromal microenvironment in metastatic breast cancer.

Analysis of aluminium content and iron homeostasis in nipple aspirate fluids from healthy women and breast cancer-affected patients.

Aluminium is not a physiological component of the breast but has been measured recently in human breast tissues and breast cyst fluids at levels above those found in blood serum or milk. Since the presence of aluminium can lead to iron dyshomeostasis, levels of aluminium and iron-binding proteins (ferritin, transferrin) were measured in nipple aspirate fluid (NAF), a fluid present in the breast duct tree and mirroring the breast microenvironment. NAFs were collected noninvasively from healthy women (NoCancer; n = 16) and breast cancer-affected women (Cancer; n = 19), and compared with levels in serum (n = 15) and milk (n = 45) from healthy subjects.

Iron-binding proteins and C-reactive protein in Nipple Aspirate Fluids: role of Iron-driven inflammation in breast cancer microenvironment?

Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess metabolic activity in breast microenvironment. Premalignant and malignant cell alterations may produce biochemical signals that deliver inflammatory proteins to the site.

Natural and artificial radioactivity determination of some medicinal plants.

Several medicinal plants used in Italy were analysed to determine natural and artificial radioactivity in those parts (leaves, fruits, seeds, roots, peduncles, flowers, barks, berries, thallus) used generally as remedies. The radionuclides were determined by alpha ((238)U, (210)Po) and gamma ((214)Pb-Bi, (210)Pb, (40)K and (137)Cs) spectrometry. (238)U ranged between <0.

Detection of superoxide dismutase-1 in nipple aspirate fluids: a reactive oxygen species-regulating enzyme in the breast cancer microenvironment.

Introduction: Analysis of nipple aspirate fluid (NAF) allows the noninvasive identification of both cellular and biomolecular markers of human breast cancer, the most common female malignancy in developed countries. Cytosolic superoxide dismutase (SOD-1) represents a detoxifying enzyme able to regulate the balance between oncogenic and oncosuppressor reactive oxygen species.

Patients And Methods: We analyzed SOD-1 expression in 126 NAF samples collected from 67 women with and 59 without breast cancer, using enzyme-linked immunosorbent assay, immunoprecipitation, Western blotting, and immunocytochemistry.

Intake of 210Po, 234U and 238U radionuclides with wine in Italy.

238U, 234U and 210Po activity concentration was determined in 70 samples of red and white wine coming from 16 Italian regions. The radionuclides were determined by alpha spectrometry after separation. The results show that the mean concentrations of 238U, 234U and 210Po were 3.

The Collaborative Interactions Scale: a new transcript-based method for the assessment of therapeutic alliance ruptures and resolutions in psychotherapy.

The authors present a new transcript-based method for the assessment of therapeutic alliance ruptures and resolutions in psychotherapy-the Collaborative Interaction Scale (CIS)-and discuss the structure and theoretical background of the scale and the rating procedure. To assess interrater reliability, three raters independently evaluated 32 psychotherapy sessions (2,984 patient utterances and 2,984 therapist utterances) using the CIS, which demonstrated good interrater reliability (average kappa=.66-.

Intracrinology of breast microenvironment: hormonal status in nipple aspirate fluid and its relationship to breast cancer.

Breast cancer, a complex and multifactorial disease, is the most commonly diagnosed malignancy affecting women. Methods currently available for breast cancer detection have well-described limitations; in this respect, the intraductal approaches directly assess the microenvironment of the breast. Nipple aspirate fluid (NAF) can be noninvasively obtained from the breast in most women and represents a promising biological tool to assess metabolic, hormonal and molecular changes occurring in the cells lining the ducts, from which breast cancer arises.