Reactive oxygen species (ROS) generation inhibited by aporphine and phenanthrene alkaloids semi-synthesized from natural boldine.

Four phenanthrene and one aporphine alkaloids semi-synthesized from boldine were evaluated for their inhibitory effect on reactive oxygen species (ROS) generation. ROS generation by neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine was inhibited in a concentration dependent manner. Alkaloids exerted similar inhibitory effect in the hypoxanthine-xanthine oxidase system than in stimulated neutrophils, which could be attributed to a direct ROS scavenging activity. None of the alkaloids assayed had any effect on xanthine oxidase activity. Therefore the synthesized alkaloids might constitute an alternative therapy in inflammation disorders in which ROS generation is involved.

Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study

[EN] Matrix-assisted autologous chondrocyte implantation (MACI) has shown promising results for cartilage repair, combining cultured chondrocytes and hydrogels, including alginate. The ability of chondrocytes for MACI is limited by different factors including donor site morbidity, dedifferentiation, limited lifespan or poor proliferation in vitro. Mesenchymal stem cells could represent an alternative for cartilage regeneration. In this study, we propose a MACI scaffold consisting of a mixed alginate-agarose hydrogel in combination with human dental pulp stem cells (hDPSCs), suitable for cartilage regeneration. Scaffolds were characterized according to their rheological properties, and their…

IFT46 Expression in the Nasal Mucosa of Primary Ciliary Dyskinesia Patients: Preliminary Study

Este artículo se encuentra disponible en la siguiente URL: https://journals.sagepub.com/doi/pdf/10.1177/2152656721989288 Background: Primary ciliary dyskinesia (PCD) is characterised by an imbalance in mucociliary clearance leading to chronic respiratory infections. Cilia length is considered to be a contributing factor in cilia movement. Recently, IFT46 protein has been related to cilia length. Therefore, this work aims to study IFT46 expression in a PCD patients cohort and analyse its relationship with cilia length and function, as it was not previously described. Materials and methods: The expression of one intraflagellar transport (IFT46) and two regulating ciliary architecture (FOXJ1 a…

Human platelet-rich plasma improves the nesting and differentiation of human chondrocytes cultured in stabilized porous chitosan scaffolds

[EN] The clinical management of large-size cartilage lesions is difficult due to the limited regenerative ability of the cartilage. Different biomaterials have been used to develop tissue engineering substitutes for cartilage repair, including chitosan alone or in combination with growth factors to improve its chondrogenic properties. The main objective of this investigation was to evaluate the benefits of combining activated platelet-rich plasma with a stabilized porous chitosan scaffold for cartilage regeneration. To achieve this purpose, stabilized porous chitosan scaffolds were prepared using freeze gelation and combined with activated platelet-rich plasma. Human primary articular chond…

A cell-free approach with a supporting biomaterial in the form of dispersed microspheres induces hyaline cartilage formation in a rabbit knee model

The objective of this study was to test a regenerative medicine strategy for the regeneration of articular cartilage. This approach combines microfracture of the subchondral bone with the implant at the site of the cartilage defect of a supporting biomaterial in the form of microspheres aimed at creating an adequate biomechanical environment for the differentiation of the mesenchymal stem cells that migrate from the bone marrow. The possible inflammatory response to these biomaterials was previously studied by means of the culture of RAW264.7 macrophages. The microspheres were implanted in a 3 mm-diameter defect in the trochlea of the femoral condyle of New Zealand rabbits, covering them wi…

High-Speed Video Microscopy for Primary Ciliary Dyskinesia Diagnosis: A Study of Ciliary Motility Variations with Time and Temperature

Este artículo se encuentra disponible en la siguiente URL: https://www.mdpi.com/2075-4418/11/7/1301 Este artículo de investigación pertenece al número especial "Progress in Diagnosing and Managing Primary Ciliary Dyskinesia". Primary ciliary dyskinesia (PCD) is a rare disease resulting from a defect in ciliary function that generates, among other issues, chronic upper and lower respiratory tract infections. European guidelines recommend studying ciliary function (pattern (CBP) and frequency (CBF)), together with characteristic clinical symptoms, as one of the definitive tests. However, there is no “gold standard”. The present study aims to use high-speed video microscopy to describe how CBF…

Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro

Background/Objective Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on prolifer…

Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo.

AbstractAngiotensin-II (Ang-II) has inflammatory activity and is involved in different diseases associated with the cardiovascular system. This study has evaluated the effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us, secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant neutrophil accumulation, which was maximal at 4–8 h. BM inhibited neutrophil infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%, respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM inhibited the release of cytokine-inducible neutrophil chemoattractant/ke…

In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem c…

Cartilage Regeneration and Tissue Engineering

Abstract Articular cartilage in synovial joints is a hyaline cartilage highly hydrated with a rigorous order of cells and fibers and a specific content of proteoglycans and glycoproteins. It provides a low-friction surface, participates in the lubrication of the synovial joints, and distributes the forces to the underlying bone. It is an avascular and aneural tissue where small metabolites diffuse to and from cells. Unlike hyaline cartilage in other locations, articular cartilage lacks perichondrium, a layer of fibrous tissue around it that serves as the source of new cartilage cells. Thus, although extracellular matrix undergoes continuous remodeling throughout life, the ability to repair …

Effect of two phenanthrene alkaloids on angiotensin II-induced leukocyte-endothelial cell interactionsin vivo

The present study has evaluated the effect of two phenanthrene alkaloids, uvariopsine and stephenanthrine, on angiotensin II (Ang-II)-induced leukocyte–endothelial cell interactions in vivo and the mechanisms involved in their activity. Intravital microscopy within the rat mesenteric microcirculation was used. A 60 min superfusion with 1 nM Ang-II induced a significant increase in the leukocyte–endothelial cell interactions that were completely inhibited by 1 μM uvariopsine cosuperfusion. A lower dose of 0.1 μM significantly reduced Ang-II-induced leukocyte adhesion by 75%. When Ang-II was cosuperfused with 1 and 0.1 μM stephenanthrine, Ang-II-induced leukocyte responses were significantly …

Tenofovir-induced toxicity in renal proximal tubular epithelial cells

OBJECTIVE In-vivo studies suggest that mitochondria is involved in tenofovir (TFV)-induced renal toxicity, but the underlying mechanisms are still unclear. The aim of the present study was to assess the effects of TFV and its prodrug, TFV disoproxil fumarate, on mitochondrial function and cell survival/viability in a renal proximal tubular cell line. DESIGN AND METHODS We evaluated parameters of cellular proliferation/survival (cell count, cell cycle, viability) and mitochondrial function (oxygen consumption, mitochondrial membrane potential, reactive oxygen species production) in NRK-52E cells. Intracellular TFV was measured by HPLC and expression of antioxidant genes was analysed by real-…

Use of decellularized tracheas for airways engineering

Background/Objective: Tracheal stenosis produces serious dyspnea. In some cases, a defective correction or timely intervention can lead to the death of the patient. The Hospital Clinico Universitario de Valencia is a reference hospital for the treatment of patients with airway problems exhibiting complex tracheal stenosis. Surgery is limited to a maximum length of 6-7 cm and it is not exempt of mortality (3-5%). In this study we have study the useful of decellularized porcine tracheas to be used in airway regenerative medicine. Methods: Three porcine tracheas were cut in 3 cm rings and exposed to SDS 2% for up to four weeks. Cell content was evaluated by fluorescence microscopy (DAPI) weekl…

PGC-1α Induction in Pulmonary Arterial Hypertension

Idiopathic Pulmonary arterial hypertension (IPAH) is characterized by the obstructive remodelling of pulmonary arteries, and a progressive elevation in pulmonary arterial pressure (PAP) with subsequent right-sided heart failure and dead. Hypoxia induces the expression of peroxisome proliferator activated receptorγcoactivator-1α(PGC-1α) which regulates oxidative metabolism and mitochondrial biogenesis. We have analysed the expression of PGC-1α, cytochrome C (CYTC), superoxide dismutase (SOD), the total antioxidant status (TAS) and the activity of glutathione peroxidase (GPX) in blood samples of IPAH patients. Expression of PGC-1αwas detected in IPAH patients but not in healthy volunteers. Th…

Optimization of a decellularized protocol of porcine tracheas. Long-term effects of cryopreservation. A histological study

[EN] Objective: The aim of this study was to optimize a decellularization protocol in the trachea of Sus scrofa domestica (pig) as well as to study the effects of long-term cryopreservation on the extracellular matrix of decellularized tracheas. Methods: Porcine tracheas were decellularized using Triton X-100, SDC, and SDS alone or in combination. The effect of these detergents on the extracellular matrix characteristics of decellularized porcine tracheas was evaluated at the histological, biomechanical, and biocompatibility level. Morphometric approaches were used to estimate the effect of detergents on the collagen and elastic fibers content as well as on the removal of chondrocytes from …

FP187MITOCHONDRIAL DYSFUNCTION INDUCED BY TENOFOVIR IN RENAL CELLS. POTENTIATION OF THE EFFECTS BY CO-STIMULATION WITH ANGIOTENSIN II

Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients’ …