Search results for "etica."

Calcium Polyphosphate Nanoparticles Act as an Effective Inorganic Phosphate Source during Osteogenic Differentiation of Human Mesenchymal Stem Cells

2019

The ability of bone-marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to differentiate into osteoblasts makes them the ideal candidate for cell-based therapies targeting bone-diseases. Polyphosphate (polyP) is increasingly being studied as a potential inorganic source of phosphate for extracellular matrix mineralisation. The aim of this study is to investigate whether polyP can effectively be used as a phosphate source during the in vitro osteogenic differentiation of human BM-MSCs. Human BM-MSCs are cultivated under osteogenic conditions for 28 days with phosphate provided in the form of organic &beta

NOTCH3 expression is linked to breast cancer seeding and distant metastasis

2018

Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF…

The hallmarks of ovarian cancer: proliferation and cell growth

2020

Epithelial ovarian cancer (EOC) is a heterogeneous group of diseases with distinct biological and clinical behaviour. Despite the differences between them, the capability of tumour cells to continuously proliferate and avoid death is maintained among histotypes. This ability is the result of alterations at different levels, causing the deregulation of cell cycle and proliferative-related pathways. Even if the leading role is played by RB and TP53, changes in other molecular pathways are involved in the development of EOC. This ability can be exploited to generate in vitro and in vivo models resembling the conditions of tumour development in a patient. In vivo models, such as patient-derived…

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

2018

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A(2A) receptor (A(2A)R) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A(2A)R and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A(2A)R-CB1R heteromeric complexes. However, th…

Inflammatory Response Mechanisms of the Dentine–Pulp Complex and the Periapical Tissues

2021

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The fron…

Pathophysiology of Peripheral Arterial Disease (PAD): A Review on Oxidative Disorders

2020

Peripheral arterial disease (PAD) is an atherosclerotic disease that affects a wide range of the world’s population, reaching up to 200 million individuals worldwide. PAD particularly affects elderly individuals (>65 years old). PAD is often underdiagnosed or underestimated, although specificity in diagnosis is shown by an ankle/brachial approach, and the high cardiovascular event risk that affected the PAD patients. A number of pathophysiologic pathways operate in chronic arterial ischemia of lower limbs, giving the possibility to improve therapeutic strategies and the outcome of patients. This review aims to provide a well detailed description of such fundamental issues as physical exe…

CD40/CD40L and Related Signaling Pathways in Cardiovascular Health and Disease—The Pros and Cons for Cardioprotection

2020

The CD40–CD40 ligand (CD40L) dyad represents a scientific and clinical field that has raised many controversies in the past and cannot be clearly defined as being an either beneficial or harmful pathway. Being crucially involved in physiological immunological processes as well as pathological inflammatory reactions, the signaling pathway has been recognized as a key player in the development of both autoimmune and cardiovascular disease. Even though the possibilities of a therapeutic approach to the dyad were recognized decades ago, due to unfortunate events, detailed in this review, pharmacological treatment targeting the dyad, especially in patients suffering from atherosclerosis, is not …

2020

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to ev…

Tight Junctions as a Key for Pathogens Invasion in Intestinal Epithelial Cells

2021

Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions’ attack by pathogens, including…

Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

2016

Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within …