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1.
Int J Mol Sci ; 23(12)2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35743318

RESUMEN

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells.


Asunto(s)
Neoplasias de la Mama , Fibroblastos Asociados al Cáncer , Neoplasias de la Mama/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Medios de Cultivo Condicionados/metabolismo , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Inflamación/patología , Células del Estroma/metabolismo , Microambiente Tumoral
2.
Int J Mol Sci ; 22(10)2021 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-34067929

RESUMEN

Cutaneous melanoma (CM) tissue represents a network constituted by cancer cells and tumor microenvironment (TME). A key feature of CM is the high structural and cellular plasticity of TME, allowing its evolution with disease and adaptation to cancer cell and environmental alterations. In particular, during melanoma development and progression each component of TME by interacting with each other and with cancer cells is subjected to dramatic structural and cellular modifications. These alterations affect extracellular matrix (ECM) remodelling, phenotypic profile of stromal cells, cancer growth and therapeutic response. The stromal fibroblast populations of the TME include normal fibroblasts and melanoma-associated fibroblasts (MAFs) that are highly abundant and flexible cell types interacting with melanoma and stromal cells and differently influencing CM outcomes. The shift from the normal microenvironment to TME and from normal fibroblasts to MAFs deeply sustains CM growth. Hence, in this article we review the features of the normal microenvironment and TME and describe the phenotypic plasticity of normal dermal fibroblasts and MAFs, highlighting their roles in normal skin homeostasis and TME regulation. Moreover, we discuss the influence of MAFs and their secretory profiles on TME remodelling, melanoma progression, targeted therapy resistance and immunosurveillance, highlighting the cellular interactions, the signalling pathways and molecules involved in these processes.


Asunto(s)
Fibroblastos/fisiología , Melanoma/metabolismo , Microambiente Tumoral/fisiología , Fibroblastos Asociados al Cáncer/metabolismo , Comunicación Celular , Plasticidad de la Célula/fisiología , Matriz Extracelular/metabolismo , Humanos , Melanoma/patología , Melanoma/fisiopatología , Transducción de Señal , Neoplasias Cutáneas/patología , Células del Estroma/metabolismo , Melanoma Cutáneo Maligno
3.
Semin Cancer Biol ; 59: 187-207, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31362075

RESUMEN

Cutaneous melanoma (CM) represents one of the most metastasizing and drug resistant solid tumors. CM is characterized by a remarkable metabolic plasticity and an important connection between oncogenic activation and energetic metabolism. In fact, melanoma cells can use both cytosolic and mitochondrial compartments to produce adenosine triphosphate (ATP) during cancer progression. However, the CM energetic demand mainly depends on glycolysis, whose upregulation is strictly linked to constitutive activation of BRAF/MAPK pathway affected by BRAFV600E kinase mutant. Furthermore, the impressive metabolic plasticity of melanoma allows the development of resistance mechanisms to BRAF/MEK inhibitors (BRAFi/MEKi) and the adaptation to microenvironmental changes. The metabolic interaction between melanoma cells and tumor microenvironment affects the immune response and CM growth. In this review article, we describe the regulation of melanoma metabolic alterations and the metabolic interactions between cancer cells and microenvironment that influence melanoma progression and immune response. Finally, we summarize the hallmarks of melanoma therapies and we report BRAF/MEK pathway targeted therapy and mechanisms of metabolic resistance.


Asunto(s)
Metabolismo Energético , Melanoma/metabolismo , Animales , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Metabolismo Energético/efectos de los fármacos , Glucólisis , Humanos , Melanoma/tratamiento farmacológico , Melanoma/etiología , Melanoma/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/metabolismo , Terapia Molecular Dirigida , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos
4.
Int J Mol Sci ; 21(21)2020 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-33114386

RESUMEN

Cardiac adverse remodeling is characterized by biological changes that affect the composition and architecture of the extracellular matrix (ECM). The consequently disrupted signaling can interfere with the balance between cardiogenic and pro-fibrotic phenotype of resident cardiac stromal primitive cells (CPCs). The latter are important players in cardiac homeostasis and can be exploited as therapeutic cells in regenerative medicine. Our aim was to compare the effects of human decellularized native ECM from normal (dECM-NH) or failing hearts (dECM-PH) on human CPCs. CPCs were cultured on dECM sections and characterized for gene expression, immunofluorescence, and paracrine profiles. When cultured on dECM-NH, CPCs significantly upregulated cardiac commitment markers (CX43, NKX2.5), cardioprotective cytokines (bFGF, HGF), and the angiogenesis mediator, NO. When seeded on dECM-PH, instead, CPCs upregulated pro-remodeling cytokines (IGF-2, PDGF-AA, TGF-ß) and the oxidative stress molecule H2O2. Interestingly, culture on dECM-PH was associated with impaired paracrine support to angiogenesis, and increased expression of the vascular endothelial growth factor (VEGF)-sequestering decoy isoform of the KDR/VEGFR2 receptor. Our results suggest that resident CPCs exposed to the pathological microenvironment of remodeling ECM partially lose their paracrine angiogenic properties and release more pro-fibrotic cytokines. These observations shed novel insights on the crosstalk between ECM and stromal CPCs, suggesting also a cautious use of non-healthy decellularized myocardium for cardiac tissue engineering approaches.


Asunto(s)
Matriz Extracelular/metabolismo , Insuficiencia Cardíaca/patología , Células Madre Mesenquimatosas/citología , Adulto , Anciano , Animales , Supervivencia Celular , Células Cultivadas , Técnicas de Cocultivo , Citocinas/genética , Citocinas/metabolismo , Matriz Extracelular/genética , Femenino , Fibrosis , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad
5.
J Cell Mol Med ; 23(6): 4256-4268, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30980516

RESUMEN

Induced pluripotent stem cells (iPSCs) are adult somatic cells genetically reprogrammed to an embryonic stem cell-like state. Notwithstanding their autologous origin and their potential to differentiate towards cells of all three germ layers, iPSC reprogramming is still affected by low efficiency. As dermal fibroblast is the most used human cell for reprogramming, we hypothesize that the variability in reprogramming is, at least partially, because of the skin fibroblasts used. Human dermal fibroblasts harvested from five different anatomical sites (neck, breast, arm, abdomen and thigh) were cultured and their morphology, proliferation, apoptotic rate, ability to migrate, expression of mesenchymal or epithelial markers, differentiation potential and production of growth factors were evaluated in vitro. Additionally, gene expression analysis was performed by real-time PCR including genes typically expressed by mesenchymal cells. Finally, fibroblasts isolated from different anatomic sites were reprogrammed to iPSCs by integration-free method. Intriguingly, while the morphology of fibroblasts derived from different anatomic sites differed only slightly, other features, known to affect cell reprogramming, varied greatly and in accordance with anatomic site of origin. Accordingly, difference also emerged in fibroblasts readiness to respond to reprogramming and ability to form colonies. Therefore, as fibroblasts derived from different anatomic sites preserve positional memory, it is of great importance to accurately evaluate and select dermal fibroblast population prior to induce reprogramming.


Asunto(s)
Reprogramación Celular , Fibroblastos/clasificación , Fibroblastos/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Mesenquimatosas/citología , Piel/citología , Abdomen/crecimiento & desarrollo , Adulto , Apoptosis , Mama/citología , Mama/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Femenino , Fibroblastos/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Cuello/crecimiento & desarrollo , Piel/metabolismo , Muslo/crecimiento & desarrollo , Transcriptoma
6.
Clin Anat ; 32(2): 183-195, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30113088

RESUMEN

We aimed to establish the prevalence of the musculocutaneous nerve (MCN) variations and the probability of the variation being pure or mixed in the same plexus. We applied the principles of evidence-based anatomy to find, appraise, and synthesize data through a meta-analysis of anatomical studies. The variations were grouped based on the presence and location of the communicating branch with the median nerve and the origin of branches to anterior arm muscles. Forty-three cadaveric studies met the inclusion criteria, providing data from 4124 plexuses. The overall pooled prevalence of plexuses with MCN variations was 20%. Based on the classification applied in our study, the pooled prevalence of variations was 17% in region 1A, 20% in region 1B, 36% in region 2 and 49% in region 3. Importantly, 64.58% of variations in region 1A and 74.14% of variations in region 1B were mixed, that is, associated with a variation in another region. The odds of finding another variation in the presence of a variation in region 2 or 3 were equal 0.37 and 0.52, respectively, demonstrating a significantly lower probability of finding mixed variations involving these regions, when compared with region 1A. Variations of the MCN are most common in the part distal to the exit from within or beneath the coracobrachialis muscle. Proximal variations are more often associated with another variation located along the nerve. These findings can assist health care professionals in the treatment of brachial plexus lesions. Clin. Anat. 32:183-195, 2019. © 2018 Wiley Periodicals, Inc.


Asunto(s)
Brazo/inervación , Músculo Esquelético/inervación , Nervio Musculocutáneo/anatomía & histología , Cadáver , Femenino , Humanos , Masculino
7.
J Heart Valve Dis ; 23(2): 145-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25076542

RESUMEN

BACKGROUND AND AIM OF THE STUDY: Synthetic materials used for pulmonary autograft (PA) reinforcement in the Ross procedure fail to match the demand for structural growth, have only a limited longevity, and do not guarantee adequate vascular compliance in high-pressure load systems. The study aim was to develop a resorbable reinforcement of a PA, tailored to provide structural support and to guide the process of wall structure modification for the preservation of graft viability. METHODS: An experimental model of translocation of the pulmonary trunk as an autograft in the aortic position was developed and performed under cardiopulmonary bypass in young lambs. The PA was left without reinforcement, reinforced with standard commercially available mesh, or reinforced with resorbable mesh of polyglactin and polydioxanone. RESULTS: Based on vessel diameter measurements by transesophageal echography at day 0 and at six months postoperatively, only the PA with resorbable reinforcement showed a behavior similar to that of the normal aorta in a growing lamb. With the non-resorbable reinforcement, transmural migration of the mesh was observed, accompanied by a conspicuous inflammatory infiltrate and fibrosis. CONCLUSION: The resorbable mesh allowed for histological wall modification, characterized by the presence of highly organized smooth muscle cells and elastic lamellae in the media. The mechanical and histological features of this resorbable mesh-reinforced PA may be crucial to the clinical long-term success of the Ross procedure.


Asunto(s)
Aorta/cirugía , Bioprótesis , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Polidioxanona , Poliglactina 910 , Arteria Pulmonar/trasplante , Mallas Quirúrgicas , Animales , Aorta/diagnóstico por imagen , Aorta/crecimiento & desarrollo , Aorta/patología , Autoinjertos , Puente Cardiopulmonar , Ecocardiografía Transesofágica , Supervivencia de Injerto , Modelos Animales , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/crecimiento & desarrollo , Arteria Pulmonar/patología , Ovinos , Factores de Tiempo
8.
Basic Res Cardiol ; 108(1): 320, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23224139

RESUMEN

Adult human heart hosts a population of cardiac primitive CD117-positive cells (CPCs), which are responsible for physiological tissue homeostasis and regeneration. While the bona fide stem cells express telomerase, their progenies are no longer able to preserve telomeric DNA; hence the balance between their proliferation and differentiation has to be tightly controlled in order to prevent cellular senescence and apoptosis of CPCs before their maturation can be accomplished. We have examined at cellular and molecular level the proliferation, apoptosis and commitment of CPCs isolated from normal (CPC-N) and age-matched pathological adult human hearts (CPC-P) with ischemic heart disease. In the CPC-P, genes related to early stages of developmental processes, nervous system development and neurogenesis, skeletal development, bone and cartilage development were downregulated, while those involved in mesenchymal cell differentiation and heart development were upregulated, together with the transcriptional activation of TGFß/BMP signaling pathway. In the pathological heart, asymmetric division was the prevalent type of cardiac stem cell division. The population of CPC-P consisted mainly of progenitors of cardiac cell lineages and less precursors; these cells proliferated more, but were also more susceptible to apoptosis with respect to CPC-N. These results indicate that CPCs fail to reach terminal differentiation and functional competence in pathological conditions. Adverse effects of underlying pathology, which disrupts cardiac tissue structure and composition, and cellular senescence, resulting from cardiac stem cell activation in telomere dysfunctional environment, can be responsible for such outcome.


Asunto(s)
Isquemia Miocárdica/patología , Miocardio/patología , Células Madre/fisiología , Adulto , Apoptosis , Diferenciación Celular , Linaje de la Célula , Proliferación Celular , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Proteínas Proto-Oncogénicas c-kit/análisis , Células Madre/citología , Factor de Crecimiento Transformador beta1/fisiología
9.
BMC Surg ; 13 Suppl 2: S55, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24267923

RESUMEN

PURPOSE: To evaluate the feasibility, efficacy and safety of strict prone posturing taken for 2 hours after operation in preventing the occurrence of unintentional retinal displacement in elderly patients operated on for retinal detachment (RD). METHODS: Twenty patients aged 60 or more with diagnosis of macula-off RD were asked to keep a strict face-down posturing for 2 hours after vitrectomy and 20% sulfur hexafluoride tamponade. IOP was measured immediately before and after surgery and after the 2-hour posturing. A questionnaire was administered to each patient to evaluate the rate of discomfort experienced because of the face-down posturing. Unintentional displacement of the retina was assessed by evaluating the presence of retinal vessel printings on fundus autofluorescence images taken 4 weeks after operation. RESULTS: The 2-hour posturing was generally well-tolerated. A mild neck pain was the most common reported symptom. Only a few patients experienced moderate breath shortness while posturing and none had to break the posturing because of respiratory problems. Intraocular pressure (IOP) measured before operation (11.7 ± 2.6 mmHg) was significantly different from IOP recorded at the end of surgery (18.9 ± 4.9 mmHg) and from IOP measured 2 hours after surgery (16.8 ± 4.7 mmHg, P<0.05, Friedman test). IOPs measured immediately and 2 hours after surgery did not differ significantly. Fundus autofluorescence imaging showed RVPs in 7 eyes. CONCLUSIONS: This study shows that a 2-hour face-down posturing is effective in reducing the rate of retinal displacement in patients operated on for rhegmatogenous retinal detachment using vitrectomy and SF6 20%. A 2-hour face-down posturing is feasible for elderly patients and does not appear to cause unwanted, post-operative IOP raises.


Asunto(s)
Posicionamiento del Paciente , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/patología , Posición Prona , Desprendimiento de Retina/cirugía , Enfermedades de la Retina/prevención & control , Vitrectomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo
10.
BMC Surg ; 13 Suppl 2: S46, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24267290

RESUMEN

Endothelial dysfunction or loss is the early event that leads to a host of severe cardiovascular diseases, such as atherosclerosis, hypertension, brain stroke, myocardial infarction, and peripheral artery disease. Ageing is regarded among the most detrimental risk factor for vascular endothelium and predisposes the subject to atheroscleorosis and inflammatory states even in absence of traditional comorbid conditions. Standard treatment to restore blood perfusion through stenotic arteries are surgical or endovascular revascularization. Unfortunately, ageing patients are not the most amenable candidates for such interventions, due to high operative risk or unfavourable vascular involvement. It has recently been suggested that the transplantation of autologous bone marrow-derived endothelial progenitor cells (EPCs) might constitute an alternative and viable therapeutic option for these individuals. Albeit pre-clinical studies demonstrated the feasibility of EPC-based therapy to recapitulate the diseased vasculature of young and healthy animals, clinical studies provided less impressive results in old ischemic human patients. One hurdle associated to this kind of approach is the senescence of autologous EPCs, which are less abundant in peripheral blood and display a reduced pro-angiogenic activity. Conversely, umbilical cord blood (UCB)-derived EPCs are more suitable for cellular therapeutics due to their higher frequency and sensitivity to growth factors, such as vascular endothelial growth factor (VEGF). An increase in intracellular Ca(2+) concentration is central to EPC activation by VEGF. We have recently demonstrated that the Ca(2+) signalling machinery driving the oscillatory Ca(2+) response to this important growth factor is different in UCB-derived EPCs as compared to their peripheral counterparts. In particular, we focussed on the so-called endothelial colony forming cells (ECFCs), which are the only EPC population belonging to the endothelial lineage and able to form capillary-like structures in vitro and stably integrate with host vasculature in vivo. The present review provides a brief description of how exploiting the Ca(2+) toolkit of juvenile EPCs to restore the repairative phenotype of senescent EPCs to enhance their regenerative outcome in therapeutic settings.


Asunto(s)
Calcio/fisiología , Enfermedades Cardiovasculares/cirugía , Senescencia Celular , Células Endoteliales/trasplante , Trasplante de Células Madre , Anciano , Células Endoteliales/fisiología , Humanos , Fenotipo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular
11.
BMC Surg ; 13 Suppl 2: S40, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24266895

RESUMEN

BACKGROUND: Nitric oxide is key to endothelial regeneration, but it is still unknown whether endothelial cell (EC) loss results in an increase in NO levels at the wound edge. We have already shown that endothelial damage induces a long-lasting Ca²âº entry into surviving cells though connexin hemichannels (CxHcs) uncoupled from their counterparts on ruptured cells. The physiological outcome of injury-induced Ca²âº inflow is, however, unknown. METHODS: In this study, we sought to determine whether and how endothelial scraping induces NO production (NOP) in the endothelium of excised rat aorta by exploiting the NO-sensitive fluorochrome, DAF-FM diacetate and the Ca²âº-sensitive fluorescent dye, Fura-2/AM. RESULTS: We demonstrated that injury-induced NOP at the lesion site is prevented in presence of the endothelial NO synthase inhibitor, L-NAME, and in absence of extracellular Ca²âº. Unlike ATP-dependent NO liberation, the NO response to injury is insensitive to BTP-2, which selectively blocks store-operated Ca²âº inflow. However, injury-induced NOP is significantly reduced by classic gap junction blockers, and by connexin mimetic peptides specifically targeting Cx37Hcs, Cx40HCs, and Cx43Hcs. Moreover, disruption of caveolar integrity prevents injury-elicited NO signaling, but not the accompanying Ca²âº response. CONCLUSIONS: The data presented provide the first evidence that endothelial scraping stimulates NO synthesis at the wound edge, which might both exert an immediate anti-thrombotic and anti-inflammatory action and promote the subsequent re-endothelialization.


Asunto(s)
Aorta/metabolismo , Prótesis Vascular , Calcio/fisiología , Endotelio Vascular/metabolismo , Óxido Nítrico/biosíntesis , Factores de Edad , Anciano , Animales , Aorta/cirugía , Endotelio Vascular/lesiones , Humanos , Ratas , Ratas Wistar
12.
J Cell Mol Med ; 16(4): 936-42, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21790971

RESUMEN

Although low-energy extracorporeal cardiac shock wave (ECSW) therapy represents an attractive non-invasive treatment option for ischaemic heart disease, the precise mechanisms of its action and influence on the cardiac tissue remain obscure. The goal of this study was to evaluate the effects of SW application on cardiac function and structure. Four-month-old Fisher 344 rats were subjected to ECSW therapy. Echocardiographic measurements of cardiac function were performed at baseline and at 1 and 3 months after treatment. Signs of inflammation, apoptosis and fibrosis were evaluated by immunohistochemistry in the control and treated hearts. ECSW application did not provoke arrhythmia or increase the troponin-I level. At all time points, the left ventricular ejection fraction and fractional shortening remained stable. Histological analysis revealed neither differences in the extracellular matrix collagen content nor the presence of fibrosis; similarly, there were no signs of inflammation. Moreover, a population of cardiac cells that responded eagerly to ECSW application in the adult heart was identified; c-kit-positive, Ki67-positive, orthochromatic cells, corresponding to cardiac primitive cells, were 2.65-fold more numerous in the treated myocardium. In conclusion, non-invasive ECSW therapy is a safe and effective way of activating cardiac stem cells and myocardial regeneration. Because many factors influence cellular turnover in the ischaemic myocardium during the course of ischaemic heart disease, cardiac remodelling, and heart failure progression, studies to identify the optimal treatment time are warranted.


Asunto(s)
Isquemia Miocárdica/terapia , Animales , Masculino , Isquemia Miocárdica/fisiopatología , Ratas , Ratas Endogámicas F344 , Regeneración
13.
Methods Mol Biol ; 2454: 675-684, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33730354

RESUMEN

The generation of pluripotent stem cells from adult somatic cells by cell reprogramming has put a whole new perspective on stem cell biology and stem cell-based regenerative medicine. Cell reprogramming acts through the introduction of key genes that regulate and maintain the pluripotent cell state. In this chapter, we describe the optimized protocol for the efficient isolation of fibroblasts from a skin punch biopsy and the subsequent easy and effective generation of integration-free induced pluripotent stem cell (iPSC) colonies forcing the expression of specific factors by non-modified RNAs.


Asunto(s)
Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Adulto , Diferenciación Celular/genética , Reprogramación Celular/genética , Fibroblastos/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes/metabolismo , ARN/metabolismo
14.
Cancers (Basel) ; 14(17)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36077709

RESUMEN

Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs.

15.
J Basic Clin Physiol Pharmacol ; 33(5): 655-663, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35647906

RESUMEN

BACKGROUND: Several pre-participation screening algorithms (PPSAs) have been proposed to assess sports eligibility in different populations. They are usually based on self-administered questionnaires, without further medical assessment if no risk factors are documented. The Med-Ex "Formula Benessere" worksite program includes a complete cardiovascular (CV) screening for all participants. The purpose of this study was to assess PPSAs accuracy in detecting medical and/or CV abnormalities in the general population, comparing the results with the date derived from Med-Ex program. METHODS: The Med-Ex medical evaluation, consisting of medical history, physical examination (including body composition), resting electrocardiogram (ECG) and exercise stress test in 464 male subjects (38.4 aged) was analyzed and matched to several PPSAs - Physical Activity Readiness Questionnaire (PAR-Q) (2002-2020), American Heart Association (AHA)/American College of Sport Medicine (ACSM) (1998-2009-2014-2015), European Association of Cardiovascular Prevention and Rehabilitation (EACPR) (2011) - retrospectively simulated. RESULTS: Five-hundred and 67 abnormalities were detected though Med-Ex medical evaluation, and one-fourth (24%) would have been undetected applying PPSA alone. In particular 28% of high blood pressure, 21% of impaired fasting glycaemia, 21% of high Body Mass Index (BMI) values and 19% of ECG abnormalities would have been missed, on average, by all PPSAs. CONCLUSIONS: The simulation analysis model performed in this study allowed to highlight the limits of PPSAs in granting sport eligibility, compared to a medical-guided CV screening. These findings emphasize the importance of a more balanced approach to pre-participation screening that includes a thorough evaluation of the cost/benefit ratio.


Asunto(s)
Medicina Deportiva , Deportes , Anciano , Algoritmos , Electrocardiografía/métodos , Humanos , Masculino , Estudios Retrospectivos , Medicina Deportiva/métodos , Encuestas y Cuestionarios , Estados Unidos
16.
J Funct Morphol Kinesiol ; 6(3)2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34287311

RESUMEN

Official tests are used to assess the fitness status of soccer referees, and their results correlate with match performance. However, FIFA-approved tests expose the referees to high physical demands and are difficult to implement during the sportive year. The aim of our study was to evaluate the correlation between the 6 × 40-m sprint and Yo-Yo Intermittent Recovery Level 1 (IR1) official tests and other field-based tests that require no or little equipment, are not time-consuming, and impose low physical demands. All tests were performed by male referees from the Regional Section of the Italian Referee Association (n = 30). We observed a strong correlation between 6 × 40-m sprint and Illinois agility tests (r = 0.63, p = 0.001) and a moderate correlation between Yo-Yo IR1 and hand-grip strength in the dominant (r = 0.45, p = 0.014) and non-dominant hand (r = 0.41, p = 0.031). Interestingly, only a moderate correlation (r = -0.42, p = 0.025) was observed between the FIFA official tests, 6 × 40-m sprint and Yo-Yo IR1. These results suggest that Illinois agility and hand-grip tests could represent simple and low-physical-impact tools for repeated assessment and monitoring of referee fitness throughout the sportive season.

17.
Ann Anat ; 238: 151761, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34139280

RESUMEN

In Italy, recent legislation (Law No. 10/2020) has tuned regulations concerning the donation of one's postmortem body and tissues for study, training, and scientific research purposes. This study discusses several specific issues to optimise the applicability and effectiveness of such an important, novel regulatory setting. Critical issues arise concerning the learners, the type of training and teaching activities that can be planned, the position of academic anatomy institutes, the role of family members in the donation process, the time frame of the donation process, the eligibility of partial donation, or the simultaneous donation of organs and tissues to patients awaiting transplantation. In particular, a universal time limit for donations (i.e., one year) makes it impossible to plan the long-term use of specific body parts, which could be effectively preserved for the advanced teaching and training of medical students and surgeons. The abovementioned conditions lead to the limited use of corpses, thus resulting in the inefficiency of the whole system of body donation. Overall, the donors' scope for the donation of their body could be best honoured by a more flexible and tuneable approach that can be used on a case-by-case basis. Furthermore, it is deemed necessary to closely monitor the events scheduled for corpses in public nonacademic institutions or private enterprises. This paper presents useful insights from Italian anatomists with the hope of providing inspiration for drafting the regulations. In conclusion, this paper focuses on the critical issues derived from the recently introduced Italian law on the donation and use of the body after death and provides suggestions to lawmakers for future implementations.


Asunto(s)
Anatomistas , Estudiantes de Medicina , Obtención de Tejidos y Órganos , Cadáver , Humanos , Italia , Donantes de Tejidos
18.
J Mol Cell Cardiol ; 49(5): 719-27, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20566360

RESUMEN

Epithelial-mesenchymal transition is implicated in the remodelling of tissues during development and in the adult life. In the heart, it gives origin to progenitors of fibroblasts, coronary endothelium, smooth muscle cells, and cardiomyocytes. Moreover, epicardially-derived cells determine myocardial wall thickness and Purkinje fibre network. Recently, the presence of numerous cardiac stem cells in the subepicardium of the adult human heart has been described and the hypothesis that epicardially-derived cells can contribute to the population of cardiac stem cells in the adult heart has been advanced. In an effort to test this hypothesis and establish a possible link between epicardium, epicardially-derived cells and cardiac stem cells in the adult human heart we have examined epicardial mesothelial cells in the normal and pathological adult human heart with ischemic cardiomyopathy in vivo and we have induced and documented their epithelial-mesenchymal transition in vitro. Noticeably, epicardial cells were missing from the surface of pathological hearts and the cells with the expression of epithelial and mesenchymal markers populated thick subepicardial space. When the fragments of epicardium from the normal hearts were cultured on the specific substrate formed by extracellular matrix derived from cardiac fibroblasts, we obtained the outgrowth of the epithelial sheet with the mRNA and protein expression characteristic of epicardium. TGFß induced cellular and molecular changes typical of epithelial-mesenchymal transition. Moreover, the epicardially-derived cells expressed CD117 antigen. Thus, this study provides evidence that cardiac stem cells can originate from epithelial-mesenchymal transition of the epicardial cells in the adult human heart.


Asunto(s)
Células Madre Adultas/metabolismo , Transición Epitelial-Mesenquimal , Miocardio/patología , Pericardio/patología , Proteínas Proto-Oncogénicas c-kit/metabolismo , Adulto , Biomarcadores/metabolismo , Proliferación Celular , Supervivencia Celular , Epitelio/metabolismo , Matriz Extracelular/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Pericardio/metabolismo , Fenotipo
19.
Childs Nerv Syst ; 26(5): 621-6, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20191274

RESUMEN

PURPOSE: The goal of the present study was to develop a three-dimensional (3D) geometrical model based on pre- and post-dissection Digital Imaging and Communication in Medicine (DICOM) images of both transcranial and endonasal skull base approaches. Such model was structured for either teaching surgical anatomy and to evaluate the amount of bone removal over the skull base surface through a 3D digital perspective. METHODS: Twenty-five human cadaveric heads were dissected at the Laboratory of Surgical NeuroAnatomy (LSNA) of the University of Barcelona (Spain) between 2007 and 2009. Before and after each dissection, a computed tomography-scan (CT-scan) was obtained in order to create a 3D geometrical model of the same approach performed in the dissection laboratory. The model protocol was designed as follows: (1) preoperative CT-scan of the specimens; (2) creation of a computer-generated 3D model of the specimen using specific imaging software for visualization and manipulation of biomedical data; (3) dissection of the specimens; (4) development of a 3D CT-based model of the approach as a result of the overlapping of the DICOM data of the specimens before and after the dissection. RESULTS: The fusion of the pre- and post-dissection 3D models allowed evaluation of the amount of bone removal over the skull base surface. CONCLUSIONS: Measurements of the bony landmarks as well as the visual feedback of the drilled bone over the skull base provided by our 3D model gives the opportunity to improve the tailoring of each approach to the different skull base areas.


Asunto(s)
Imagenología Tridimensional/métodos , Base del Cráneo/anatomía & histología , Cirugía Asistida por Computador/métodos , Cadáver , Simulación por Computador , Humanos , Modelos Anatómicos , Neurocirugia/métodos , Procedimientos Neuroquirúrgicos/métodos
20.
J Funct Morphol Kinesiol ; 5(2)2020 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33467249

RESUMEN

Work-related stress represents a relevant public health issue and solution strategies are mandatory. Yoga is a common approach to manage stress and its effectiveness has been extensively confirmed. Therefore, this study aims systematically to review the effectiveness of Yoga interventions carried out at workplace on work-related stress among employees and to assess their impact quantitatively. Springerlink, MEDLINE, PubMed, CINAHL, Web of Science, Scopus, Cochrane CENTRAL and PEDro databases were searched. Clinical trials comparing workplace Yoga interventions to control groups, and evaluating perceived stress as outcome measure, were assessed for eligibility. All forms and styles of Yoga were considered for the analysis. Out of 3392 initially identified, 6 studies were included in the meta-analysis; 266 participants practicing Yoga interventions at worksite were compared to 221 subjects in control group. Included studies showed "some concerns" about different domains of source of bias. Quantitative analysis showed an overall effect size of -0.67 [95% confidence interval (CI): -0.86, -0.49] in favor of Yoga intervention in reducing stress outcome measures. Hence, workplace Yoga interventions were more effective when compared to no treatment in work-related stress management. Further high-quality studies are needed to improve the validity of these results and to specify more characteristics of the Yoga intervention, such as style, volume, and frequency.

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