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1.
Cell Mol Life Sci ; 81(1): 163, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38570362

RESUMO

Proteolytic release of transmembrane proteins from the cell surface, the so called ectodomain shedding, is a key process in inflammation. Inactive rhomboid 2 (iRhom2) plays a crucial role in this context, in that it guides maturation and function of the sheddase ADAM17 (a disintegrin and metalloproteinase 17) in immune cells, and, ultimately, its ability to release inflammatory mediators such as tumor necrosis factor α (TNFα). Yet, the macrophage sheddome of iRhom2/ADAM17, which is the collection of substrates that are released by the proteolytic complex, is only partly known. In this study, we applied high-resolution proteomics to murine and human iRhom2-deficient macrophages for a systematic identification of substrates, and therefore functions, of the iRhom2/ADAM17 proteolytic complex. We found that iRhom2 loss suppressed the release of a group of transmembrane proteins, including known (e.g. CSF1R) and putative novel ADAM17 substrates. In the latter group, shedding of major histocompatibility complex class I molecules (MHC-I) was consistently reduced in both murine and human macrophages when iRhom2 was ablated. Intriguingly, it emerged that in addition to its shedding, iRhom2 could also control surface expression of MHC-I by an undefined mechanism. We have demonstrated the biological significance of this process by using an in vitro model of CD8+ T-cell (CTL) activation. In this model, iRhom2 loss and consequent reduction of MHC-I expression on the cell surface of an Epstein-Barr virus (EBV)-transformed lymphoblastoid cell line dampened activation of autologous CTLs and their cell-mediated cytotoxicity. Taken together, this study uncovers a new role for iRhom2 in controlling cell surface levels of MHC-I by a dual mechanism that involves regulation of their surface expression and ectodomain shedding.


Assuntos
Proteínas de Transporte , Infecções por Vírus Epstein-Barr , Animais , Humanos , Camundongos , Proteína ADAM17/genética , Proteína ADAM17/metabolismo , Proteínas de Transporte/metabolismo , Herpesvirus Humano 4 , Complexo Principal de Histocompatibilidade , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Knockout
2.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37686355

RESUMO

Neural stem cells (NSCs) were described for the first time more than two decades ago for their ability to differentiate into all neural cell lineages. The isolation of NSCs from adults and embryos was carried out by various laboratories and in different species, from mice to humans. Similarly, no more than two decades ago, cancer stem cells were described. Cancer stem cells, previously identified in hematological malignancies, have now been isolated from several solid tumors (breast, brain, and gastrointestinal compartment). Though the origin of these cells is still unknown, there is a wide consensus about their role in tumor onset, propagation and, in particular, resistance to treatments. Normal and neoplastic neural stem cells share common characteristics, and can thus be considered as two sides of the same coin. This is particularly true in the case of the Zika virus (ZIKV), which has been described as an inhibitor of neural development by specifically targeting NSCs. This understanding prompted us and other groups to evaluate ZIKV action in glioblastoma stem cells (GSCs). The results indicate an oncolytic activity of this virus vs. GSCs, opening potentially new possibilities in glioblastoma treatment.


Assuntos
Glioblastoma , Infecção por Zika virus , Zika virus , Adulto , Humanos , Animais , Camundongos , Glioblastoma/terapia , Células-Tronco Neoplásicas , Encéfalo
3.
Int J Mol Sci ; 24(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38139100

RESUMO

Pancreatic cancer (PCa) is the fifth leading cause of cancer mortality. Recently, our group and others have demonstrated the oncolytic activity of the Zika virus (ZIKV) against glioblastoma. The peculiar features of this virus offer the opportunity to use an agent already tested in vivo through natural transmission, with minimal effects on adults, to specifically target a tumor such as glioblastoma. This remarkable specificity prompted us to explore the potential use of ZIKV oncolytic action against other tumor types. In particular, we focused on the subgroup of pancreatic tumors with a neuroendocrine origin known as neuroendocrine tumors (NETs). We found that ZIKV exerts its oncolytic activity by specifically infecting NET cells, leading to growth inhibition and cell death. We also assessed whether the oncolytic action could be extended to pancreatic tumors different from NETs. However, as expected, the viral specificity is limited to NETs and is not applicable to adenocarcinoma tumors, indicating a narrow spectrum of action for this virus. These findings support the potential use of ZIKV in therapeutic approaches not only in glioblastoma, but also against other tumors, such as neuroendocrine pancreatic tumors.


Assuntos
Glioblastoma , Tumores Neuroendócrinos , Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias Pancreáticas , Infecção por Zika virus , Zika virus , Adulto , Humanos , Zika virus/fisiologia , Glioblastoma/terapia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Hormônios Pancreáticos
4.
Int J Mol Sci ; 23(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36499373

RESUMO

At present, there is a lack of clinical evidence about the impact and long-term durability of the immune response induced by the third dose of mRNA vaccines. In this study, we followed up the B cell compartment behavior in a cohort of immunocompetent individuals three and six months after the third dose of vaccine. During this period, some subjects contracted the virus. In uninfected vaccinated subjects, we did not report any changes in serum spike-specific IgG levels, with a significant reduction in IgA. Instead, subjects recovered from natural infection showed a significant increase in both specific IgG and IgA. Moreover, we showed a time-related decrease in IgG neutralizing potential to all SARS-CoV-2 variants of concern (VOC) in uninfected compared to recovered subjects, who displayed an increased neutralizing ability, particularly against the omicron variant. Finally, we underlined the presence of a pool of SARS-CoV-2-specific B cells in both groups that are prone to respond to restimulation, as demonstrated by their ability to differentiate into plasma cells and to produce anti-SARS-CoV-2-specific immunoglobulins. These data lead us to assert the long-term effectiveness of the BNT162b2 vaccine in contrasting the severe form of the pathology and prevent COVID-19-associated hospitalization.


Assuntos
COVID-19 , Células B de Memória , Humanos , SARS-CoV-2 , Vacina BNT162 , COVID-19/prevenção & controle , RNA Mensageiro/genética , Imunoglobulina G , Anticorpos Antivirais
5.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055049

RESUMO

Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.


Assuntos
Âmnio/citologia , Células-Tronco Mesenquimais/metabolismo , Transcriptoma , Biomarcadores , Técnicas de Cultura de Células , Diferenciação Celular , Separação Celular , Células Cultivadas , Biologia Computacional/métodos , Epigênese Genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Imunofenotipagem , Células-Tronco Mesenquimais/citologia , Anotação de Sequência Molecular , Medicina Regenerativa
6.
Nature ; 522(7554): 94-7, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25849774

RESUMO

Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-ß activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.


Assuntos
Morte Celular , Células Epiteliais/citologia , Folículo Piloso/citologia , Fagocitose , Nicho de Células-Tronco/fisiologia , Células-Tronco/citologia , Animais , Apoptose , Derme/citologia , Derme/metabolismo , Células Epiteliais/metabolismo , Folículo Piloso/metabolismo , Homeostase , Camundongos , Fagócitos/citologia , Regeneração , Transdução de Sinais , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta/metabolismo , beta Catenina/metabolismo
7.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466583

RESUMO

Mesenchymal stromal/stem cells (MSCs) are multipotent adult stem cells that support homeostasis during tissue regeneration. In the last decade, cell therapies based on the use of MSCs have emerged as a promising strategy in the field of regenerative medicine. Although these cells possess robust therapeutic properties that can be applied in the treatment of different diseases, variables in preclinical and clinical trials lead to inconsistent outcomes. MSC therapeutic effects result from the secretion of bioactive molecules affected by either local microenvironment or MSC culture conditions. Hence, MSC paracrine action is currently being explored in several clinical settings either using a conditioned medium (CM) or MSC-derived exosomes (EXOs), where these products modulate tissue responses in different types of injuries. In this scenario, MSC paracrine mechanisms provide a promising framework for enhancing MSC therapeutic benefits, where the composition of secretome can be modulated by priming of the MSCs. In this review, we examine the literature on the priming of MSCs as a tool to enhance their therapeutic properties applicable to the main processes involved in tissue regeneration, including the reduction of fibrosis, the immunomodulation, the stimulation of angiogenesis, and the stimulation of resident progenitor cells, thereby providing new insights for the therapeutic use of MSCs-derived products.


Assuntos
Células-Tronco Mesenquimais/citologia , Medicina Regenerativa/métodos , Animais , Meios de Cultivo Condicionados/metabolismo , Exossomos/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Comunicação Parácrina
8.
Biochem Biophys Res Commun ; 531(2): 223-227, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798016

RESUMO

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive malignancy that accounts for the majority of deaths from all thyroid cancers. ATC exhibits invasiveness and highly resistance to conventional therapies which include cytotoxic chemotherapy, the combination of BRAF and MEK inhibition and, more recently, immunotherapies, that have shown promising but still limited results. A growing knowledge on ATC tumor biology is needed for developing more effective therapies with significant better survival. Researchers have begun to utilize 3D models to culture cancer cells for in vitro studies. In this work, C643 ATC cell line was cultured on polymeric scaffolds with high-interconnected porous matrix. They exhibited distinct viability, proliferation and 3D morphology similar to an in vivo solid tumor mass. We also carried out quantitative real-time PCR experiments for monitoring Cancer Stem Cells enrichment, since they are most probably the cause of tumor resistance, reoccurrence and metastasis. The same tests were performed after cell treatment with the chemotherapic Doxorubicin. An up-regulation of the analyzed stem-cell markers confirmed the high resistance to treatment of these cell line with respect to conventional drugs. In conclusion, 3D scaffolds could be an ideal platform for studying the mechanisms that regulate ACT growth and survival and also improving novel therapeutic approaches for treatment-resistant thyroid cancer.


Assuntos
Progressão da Doença , Polímeros/química , Carcinoma Anaplásico da Tireoide/patologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Alicerces Teciduais/química
9.
Int J Mol Sci ; 21(12)2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32560261

RESUMO

The NLRP3 inflammasome is a multi-protein complex that initiates innate immunity responses when exposed to a wide range of stimuli, including pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). Inflammasome activation leads to the release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18 and to pyroptotic cell death. Over-activation of NLRP3 inflammasome has been associated with several chronic inflammatory diseases. A deep knowledge of NLRP3 inflammasome biology is required to better exploit its potential as therapeutic target and for the development of new selective drugs. To this purpose, in the past few years, several tools have been developed for the biological characterization of the multimeric inflammasome complex, the identification of the upstream signaling cascade leading to inflammasome activation, and the downstream effects triggered by NLRP3 activation. In this review, we will report cellular models and cellular, biochemical, and biophysical assays that are currently available for studying inflammasome biology. A special focus will be on those models/assays that have been used to identify NLRP3 inhibitors and their mechanism of action.


Assuntos
Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Alarminas/metabolismo , Animais , Humanos , Imunidade Inata , Modelos Biológicos , Moléculas com Motivos Associados a Patógenos/metabolismo , Piroptose , Transdução de Sinais
10.
Adv Exp Med Biol ; 1169: 81-93, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487020

RESUMO

Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mature thyrocytes and functional follicles for the treatment of thyroid diseases in mice. In addition, the discovery of resident thyroid progenitor cells, along with other sources of stem cells, has defined in detail the mechanisms responsible for tissue repair upon moderate or severe organ injury.In this chapter, we highlight in detail the current state of research on thyroid stem cells by focusing on (1) the description of the first experiments performed to obtain thyroid follicles from embryonic stem cells, (2) the identification of resident stem cells in the thyroid gland, and (3) the definition of the current translational in vivo and in vitro models used for thyroid tissue repair and regeneration.


Assuntos
Células-Tronco Embrionárias , Glândula Tireoide , Animais , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Humanos , Camundongos , Pesquisa/tendências , Glândula Tireoide/citologia
11.
Monaldi Arch Chest Dis ; 89(1)2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30968657

RESUMO

A key factor in cardiovascular prevention is the detection and appropriate management of preclinical heart failure (HF), but information on the subject is scarce. We designed VASTISSIMO as a prospective, observational study to investigate Outpatient Clinic Cardiologists' skills in detecting and managing preclinical HF in Italy. Quality scores were used to assess the appropriateness of clinical management according to guideline recommendations. The feasibility of making a diagnosis of preclinical HF in a cardiology outpatient clinical setting, cardiologists' awareness of preclinical HF and consistency between physician's perceived risk of HF and the patient's classification into the preclinical HF Stages A [(SAHF) or B (SBHF)] have been investigated. Consistency was defined acceptable if the concordance between perceived risk and actual risk was >70%. Out of 3322 patients included in the study data necessary for identifying SBHF were collected in 2106 (63.4%). Many SBHF patients had their risk underestimated: 16.2% of those with previous acute myocardial infarction (AMI), 23.1% with left ventricular hypertrophy (LVH) at ECG/echocardiography, 30% with systolic/diastolic dysfunction, and 14.3% with valve disease. Cardiologists' awareness of preclinical HF in the outpatient setting should be improved. This is a critical area of cardiovascular prevention that requires attention to improve good clinical practice and adherence to guidelines.


Assuntos
Assistência Ambulatorial/métodos , Cardiologistas/estatística & dados numéricos , Insuficiência Cardíaca/diagnóstico , Guias de Prática Clínica como Assunto , Idoso , Assistência Ambulatorial/normas , Instituições de Assistência Ambulatorial , Cardiologistas/normas , Doenças Cardiovasculares/prevenção & controle , Competência Clínica , Ecocardiografia/métodos , Eletrocardiografia/métodos , Feminino , Fidelidade a Diretrizes , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
12.
Nature ; 487(7408): 496-9, 2012 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-22763436

RESUMO

Tissue development and regeneration depend on cell-cell interactions and signals that target stem cells and their immediate progeny. However, the cellular behaviours that lead to a properly regenerated tissue are not well understood. Using a new, non-invasive, intravital two-photon imaging approach we study physiological hair-follicle regeneration over time in live mice. By these means we have monitored the behaviour of epithelial stem cells and their progeny during physiological hair regeneration and addressed how the mesenchyme influences their behaviour. Consistent with earlier studies, stem cells are quiescent during the initial stages of hair regeneration, whereas the progeny are more actively dividing. Moreover, stem cell progeny divisions are spatially organized within follicles. In addition to cell divisions, coordinated cell movements of the progeny allow the rapid expansion of the hair follicle. Finally, we show the requirement of the mesenchyme for hair regeneration through targeted cell ablation and long-term tracking of live hair follicles. Thus, we have established an in vivo approach that has led to the direct observation of cellular mechanisms of growth regulation within the hair follicle and that has enabled us to precisely investigate functional requirements of hair-follicle components during the process of physiological regeneration.


Assuntos
Folículo Piloso/citologia , Regeneração/fisiologia , Células-Tronco/citologia , Animais , Divisão Celular , Movimento Celular , Sobrevivência Celular , Rastreamento de Células , Derme/citologia , Terapia a Laser , Mesoderma/citologia , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica
13.
Eur Heart J Suppl ; 20(Suppl F): F1-F74, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29867293

RESUMO

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

14.
Immunol Cell Biol ; 95(6): 531-537, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28294139

RESUMO

Biomedical imaging in recent decades has clarified our understanding of normal and pathological cellular processes in vivo. In particular, this approach recently provided insights into processes occurring at a molecular or genetic level rather than at the anatomical level. The evolution of this discipline by engineering have led to its integration into biomedical research to (1) increase sensitivity and resolution imaging and to (2) improve tissue and cell specificity. Currently, imaging approaches are used in three different biomedical areas: (a) identification of cellular processes in physiological and disease state; (b) in vivo single-cell imaging; and (c) identification of new prognostic and therapeutical strategies. In this review, we will focus on the state of art of biomedical imaging in cancer. Specifically, we will highlight the most important advances in imaging tools available for basic and translational cancer research, with a particular emphasis on solid tissue malignancies.


Assuntos
Diagnóstico por Imagem/métodos , Imagem Molecular/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/etiologia , Neoplasias/patologia , Animais , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Humanos , Oncologia , Terapia de Alvo Molecular , Imagem Multimodal/métodos , Neoplasias/terapia , Células-Tronco Neoplásicas/metabolismo , Imagem Óptica/métodos , Pesquisa
15.
Eur Heart J Suppl ; 19(Suppl D): D3-D54, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28751833

RESUMO

Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.

16.
Monaldi Arch Chest Dis ; 82(3): 165-70, 2014 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-26058269

RESUMO

Non steroid anti-inflammatory drugs (NSAIDs) are largely used for treatment of acute and chronic pain, even for long periods of time (months or years). While it is known that their use is frequently associated with gastrointestinal damage, including major bleedings from peptic ulcer, the risk of cardiovascular events related to NSAID has received much less attention. However, there is a large body of evidence showing that NSAIDs (both "traditional", such as diclofenac or indobufen, and selective cyclooxygenase inhibitors, COX-2) are associated with a significant increase of risk of cardiovascular events, both fatal and nonfatal. Consequently, several options have been proposed for the treatment of pain, including the use of analgesic drugs with different mechanisms of action, such as the opiates. Of interest, the Italian Drug Agency (AIFA) published a few years ago a warning (Nota 66) on the careful prescription of NSAIDs in patients with overt heart disease, such as coronary artery disease and heart failure. Aim of this paper is to present the current status of knowledge on the proper use of NSAIDs and other analgesic drugs in the management of acute and chronic pain.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Cardiotoxicidade , Humanos , Dor/tratamento farmacológico , Risco
17.
J Clin Med ; 13(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892964

RESUMO

Background: Cardiovascular (CV) disease is the leading cause of death in women, but few of them are aware of the CV risks (CVRs). Most women are not aware of all the CV risk factorsand their knowledge often still does not improve their lifestyle. Methods: The Carin Women is a survey conducted among Italian women by filling out a questionnaire in the waiting rooms of clinics. The aim was to determine the level of awareness of women's cardiovascular risk, knowledge of risk factors, and lifestyle. A total of 5590 questionnaires were completed in two different periods. Results: Median age was 56 (IQR 46-65); BMI was 25 (IQR 22-29). Schooling, marital status, and rate of risk conditions were assessed; 311 women (5.57%) had already suffered a cardiovascular event. The relationship between the CV events and the number of traditional risk factors was significant. A similar curve, but without significant differences, was reported for non-traditional risk factors. From the total number of women, 23% with a high CVR and 62% with a very high CVR underestimated thei risk regardless of their level of education. Up to 43% of women underestimated female CV risk compared to male risk. Women showed a good knowledge of traditional risk factors, but only a few of them had a healthy lifestyle: 21.86% were smokers, only 45.88% performed sufficient physical activity, 27.55% did not recognize they were overweight, and only 30.4% consumed more than two daily portions of fruit and vegetables. Most women (86%) need more information about CVR. Conclusions: Italian women underestimate female CVRs and their own CVR.

18.
Front Cell Dev Biol ; 12: 1385712, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882056

RESUMO

Mesenchymal stromal/stem cells (MSCs) are a heterogeneous population of multipotent cells that can be obtained from various tissues, such as dental pulp, adipose tissue, bone marrow and placenta. MSCs have gained importance in the field of regenerative medicine because of their promising role in cell therapy and their regulatory abilities in tissue repair and regeneration. However, a better characterization of these cells and their products is necessary to further potentiate their clinical application. In this study, we used unbiased high-resolution mass spectrometry-based proteomic analysis to investigate the impact of distinct priming strategies, such as hypoxia and IFN-γ treatment, on the composition and therapeutic functionality of the secretome produced by MSCs derived from the amniotic membrane of the human placenta (hAMSCs). Our investigation revealed that both types of priming improved the therapeutic efficacy of hAMSCs, and these improvements were related to the secretion of functional factors present in the conditioned medium (CM) and exosomes (EXOs), which play crucial roles in mediating the paracrine effects of MSCs. In particular, hypoxia was able to induce a pro-angiogenic, innate immune response-activating, and tissue-regenerative hAMSC phenotype, as highlighted by the elevated production of regulatory factors such as VEGFA, PDGFRB, ANGPTL4, ENG, GRO-γ, IL8, and GRO-α. IFN-γ priming, instead, led to an immunosuppressive profile in hAMSCs, as indicated by increased levels of TGFB1, ANXA1, THBS1, HOMER2, GRN, TOLLIP and MCP-1. Functional assays validated the increased angiogenic properties of hypoxic hAMSCs and the enhanced immunosuppressive activity of IFN-γ-treated hAMSCs. This study extends beyond the direct priming effects on hAMSCs, demonstrating that hypoxia and IFN-γ can influence the functional characteristics of hAMSC-derived secretomes, which, in turn, orchestrate the production of functional factors by peripheral blood cells. This research provides valuable insights into the optimization of MSC-based therapies by systematically assessing and comparing the priming type-specific functional features of hAMSCs. These findings highlight new strategies for enhancing the therapeutic efficacy of MSCs, particularly in the context of multifactorial diseases, paving the way for the use of hAMSC-derived products in clinical practice.

19.
Int J Cardiol Cardiovasc Risk Prev ; 21: 200267, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38638196

RESUMO

Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE). Results: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus. Conclusion: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.

20.
Monaldi Arch Chest Dis ; 80(3): 118-25, 2013 Sep.
Artigo em Italiano | MEDLINE | ID: mdl-24818318

RESUMO

OBJECTIVES: To offer a snapshot of the personal health habits of Italian cardiologists, the Survey on Cardiac Risk Profile and Lifestyle Habits in a Cohort of Italian Cardiologists (SOCRATES) study was undertaken. BACKGROUND: Cardiologists' cardiovascular profile and lifestyle habits are poorly known worldwide. METHODS: A Web-based electronic self-reported survey, accessible through a dedicated website, was used for data entry, and data were transferred via the web to a central database. The survey was divided in 4 sections: baseline characteristics, medical illnesses and traditional cardiovascular risk factors, lifestyle habits and selected medication use. The e-mail databases of three national scientific societies were used to survey a large and representative sample of Italian cardiologists. RESULTS: During the 3-month period of the survey, 1770 out of the 5240 cardiologists contacted (33.7%) completed and returned one or more sections of the questionnaire. More than 49% of the participants had 1 out of 5 classical risk factors (e.g. hypertension, hypercholesterolemia, active smoking, diabetes and previous vascular events). More than 28% of respondents had 2 to 5 risk factors and only 22.1% had none and therefore, according to age and sex, could be considered at low-intermediate risk. Despite the reported risk factors, more than 90% of cardiologists had a self-reported risk perception quantified as mild, such as low or intermediate. Furthermore, overweight/obesity, physical inactivity and stress at work or at home were commonly reported, as well as a limited use of cardiovascular drugs, such as statins or aspirin. CONCLUSIONS: The average cardiovascular profile of Italian cardiologist is unlikely to be considered ideal or even favorable according to recent statements and guidelines regarding cardiovascular risk. Thus, there is a large room for improvement and a need for education and intervention.


Assuntos
Cardiologia , Doenças Cardiovasculares/epidemiologia , Médicos/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Feminino , Hábitos , Inquéritos Epidemiológicos , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Itália/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Fumar/epidemiologia , Inquéritos e Questionários
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