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Background: Treatment of cancer pain remains suboptimal worldwide. In Italy, a law requires that pain be regularly assessed and reported in both medical and nursing records. Aim: To provide a homogeneous form to get exhaustive clinical information in the clinical report according to Italian legislation. Methods: A board, including oncologists and pain therapists, designed a form to report the pain characteristics of cancer patients in Italy in clinical records. The form was voted on through a Delphi process among directors of 18 clinical oncology specialization schools in Italy to obtain agreement on its content. Results: A form useful for collecting and reporting comprehensive and homogeneous information on pain among oncologists in Italy was produced. Conclusion: The development of common strategies for pain management can be improved by using this tool.
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Oncologia , Neoplasias , Humanos , Medição da Dor , Dor/diagnóstico , Dor/etiologia , Manejo da Dor , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Itália/epidemiologiaRESUMO
BACKGROUND: Copper oxide (CuO) nanoparticles (NPs) are known to trigger cytotoxicity in a variety of cell models, but the mechanism of cell death remains unknown. Here we addressed the mechanism of cytotoxicity in macrophages exposed to CuO NPs versus copper chloride (CuCl2). METHODS: The mouse macrophage cell line RAW264.7 was used as an in vitro model. Particle uptake and the cellular dose of Cu were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The deposition of Cu in lysosomes isolated from macrophages was also determined by ICP-MS. Cell viability (metabolic activity) was assessed using the Alamar Blue assay, and oxidative stress was monitored by a variety of methods including a luminescence-based assay for cellular glutathione (GSH), and flow cytometry-based detection of mitochondrial superoxide and mitochondrial membrane potential. Protein aggregation was determined by confocal microscopy using an aggresome-specific dye and protein misfolding was determined by circular dichroism (CD) spectroscopy. Lastly, proteasome activity was investigated using a fluorometric assay. RESULTS: We observed rapid cellular uptake of CuO NPs in macrophages with deposition in lysosomes. CuO NP-elicited cell death was characterized by mitochondrial swelling with signs of oxidative stress including the production of mitochondrial superoxide and cellular depletion of GSH. We also observed a dose-dependent accumulation of polyubiquitinated proteins and loss of proteasomal function in CuO NP-exposed cells, and we could demonstrate misfolding and mitochondrial translocation of superoxide dismutase 1 (SOD1), a Cu/Zn-dependent enzyme that plays a pivotal role in the defense against oxidative stress. The chelation of copper ions using tetrathiomolybdate (TTM) prevented cell death whereas inhibition of the cellular SOD1 chaperone aggravated toxicity. Moreover, CuO NP-triggered cell death was insensitive to the pan-caspase inhibitor, zVAD-fmk, and to wortmannin, an inhibitor of autophagy, implying that this was a non-apoptotic cell death. ZnO NPs, on the other hand, triggered autophagic cell death. CONCLUSIONS: CuO NPs undergo dissolution in lysosomes leading to copper-dependent macrophage cell death characterized by protein misfolding and proteasomal insufficiency. Specifically, we present novel evidence for Cu-induced SOD1 misfolding which accords with the pronounced oxidative stress observed in CuO NP-exposed macrophages. These results are relevant for our understanding of the consequences of inadvertent human exposure to CuO NPs.
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Macrófagos , Nanopartículas Metálicas , Nanopartículas , Superóxido Dismutase-1 , Animais , Morte Celular/efeitos dos fármacos , Cobre , Glutationa/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Nanopartículas Metálicas/toxicidade , Camundongos , Nanopartículas/química , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Estresse Oxidativo , Dobramento de Proteína/efeitos dos fármacos , Células RAW 264.7 , Superóxido Dismutase-1/metabolismo , SuperóxidosRESUMO
BACKGROUND: Communicating strategically is a key issue for health organizations. Over the past decade, health care communication via social media and websites has generated a great deal of studies examining different realities of communication strategies. However, when it comes to systematic reviews, there is fragmentary evidence on this type of communication. OBJECTIVE: The aim of this systematic review was to summarize the evidence on web institutional health communication for public health authorities to evaluate possible aim-specific key points based on these existing studies. METHODS: Guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, we conducted a comprehensive review across 2 electronic databases (PubMed and Web of Science) from January 1, 2011, to October 7, 2021, searching for studies investigating institutional health communication. In total, 2 independent researchers (AN and SS) reviewed the articles for inclusion, and the assessment of methodological quality was based on the Kmet appraisal checklist. RESULTS: A total of 78 articles were selected. Most studies (35/78, 45%) targeted health promotion and disease prevention, followed by crisis communication (24/78, 31%), general health (13/78, 17%), and misinformation correction and health promotion (6/78, 8%). Engagement and message framing were the most analyzed aspects. Few studies (14/78, 18%) focused on campaign effectiveness. Only 23% (18/78) of the studies had an experimental design. The Kmet evaluation was used to distinguish studies presenting a solid structure from lacking studies. In particular, considering the 0.75-point threshold, 36% (28/78) of the studies were excluded. Studies above this threshold were used to identify a series of aim-specific and medium-specific suggestions as the communication strategies used differed greatly. CONCLUSIONS: Overall, the findings suggest that no single strategy works best in the case of web-based health care communication. The extreme variability of outcomes and the lack of a unitary measure for assessing the end points of a specific campaign or study lead us to reconsider the tools we use to evaluate the efficacy of web-based health communication.
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Comunicação em Saúde , Saúde Pública , Promoção da Saúde , Humanos , Internet , Projetos de PesquisaRESUMO
The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by flow cytometry. BEAS-2B cells cultured under serum-free conditions were exposed to NM100 (anatase, 50-150nm), NM101 (anatase, 5-8nm) and NM103 (rutile, 20-28nm) for 3, 24 or 48h mainly at concentrations 1-30 µg/ml. In the mini-gel comet assay (eight gels per slide), we included analysis of (i) DNA strand breaks, (ii) oxidised bases (Fpg-sensitive sites) and (iii) light-induced DNA damage due to photocatalytic activity. Furthermore, MN assays were used and we compared the results of more high-throughput MN scoring with flow cytometry to that of cytokinesis-block MN cytome assay scored manually using a microscope. Various methods were used to assess cytotoxic effects and the results showed in general no or low effects at the doses tested. A weak genotoxic effect of the tested TiO2 materials was observed with an induction of oxidised bases for all three materials of which NM100 was the most potent. When the comet slides were briefly exposed to lab light, a clear induction of DNA strand breaks was observed for the anatase materials, but not for the rutile. This highlights the risk of false positives when testing photocatalytically active materials if light is not properly avoided. A slight increase in MN formation for NM103 was observed in the different MN assays at the lower doses tested (1 and 5 µg/ml). We conclude that mini-gel comet assay and MN scoring using flow cytometry successfully can be used to efficiently study cytotoxic and genotoxic properties of nanoparticles.
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Ensaio Cometa , Dano ao DNA , Células Epiteliais/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Brônquios/efeitos dos fármacos , Linhagem Celular , DNA/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Nanopartículas Metálicas/química , Titânio/farmacologia , Titânio/toxicidadeRESUMO
We have considered nanoparticles (NPs) of Fe, Co and Ni, three transition metals sharing similar chemical properties. NP dissolution, conducted by radioactive tracer method and inductively coupled plasma mass spectrometry, indicated that NiNPs and FeNPs released in the medium a much smaller amount of ions than that released by Co NPs. The two considered methodological approaches, however, gave comparable but not identical results. All NPs are readily internalized by the cells, but their quantity inside the cells is less than 5%. Cytotoxicity and gene expression experiments were performed on SKOV-3 and U87 cells. In both cell lines, CoNPs and NiNPs were definitely more toxic than FeNPs. Real-time polymerase chain reaction experiments aimed to evaluate modifications of the expression of genes involved in the cellular stress response (HSP70, MT2A), or susceptible to metal exposure (SDHB1 and MLL), or involved in specific cellular processes (caspase3, IQSEC1 and VMP1), gave different response patterns in the two cell lines. HSP70, for example, was highly upregulated by CoNPs and NiNPs, but only in SKOV-3 cell lines. Overall, this work underlines the difficulties in predicting NP toxicological properties based only on their chemical characteristics. We, consequently, think that, at this stage of our knowledge, biological effects induced by metal-based NPs should be examined on a case-by-case basis following studies on different in vitro models. Moreover, with the only exception of U87 exposed to Ni, our results suggest that metallic NPs have caused, on gene expression, similar effects to those caused by their corresponding ions.
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Cobalto/toxicidade , Ferro/toxicidade , Nanopartículas Metálicas/toxicidade , Níquel/toxicidade , Transporte Biológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobalto/química , Cobalto/metabolismo , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ferro/química , Ferro/metabolismo , Nanopartículas Metálicas/química , Níquel/química , Níquel/metabolismo , Tamanho da Partícula , Solubilidade , Propriedades de Superfície , Fatores de TempoRESUMO
We thank Dr. Lissing and colleagues for providing us with these helpful comments [...].
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Acute porphyrias are a group of metabolic disorders resulting in defective porphyrin synthesis and reduced heme production, which carries a risk of malignancy. Porphyrias are inborn defects in the heme biosynthesis pathway resulting in neurovisceral manifestations and cutaneous photosensitivity attacks with multi-systemic involvement. Its estimated prevalence nears 5 per 100,000 patients worldwide. Subclinical liver disease is common, which can progress into transaminitis, fibrosis, cirrhosis, and malignancy. However, data on the incidence of primary liver cancer are lacking. We aim to determine the risk of hepatocellular carcinoma (HCC) in patients with porphyria. A systematic review and pooled analysis were conducted through 2021 on studies assessing blood tests, imaging, cancer development, liver transplant, surgical resection, and outcomes in porphyria. In total, 19 studies, which included 7381 patients with porphyria (3476 females), were considered for the final review. In eight studies, alpha-fetoprotein levels were elevated between 200 and 1000 IU/mL. Of the total cohort of patients with porphyria, primary liver cancer was diagnosed in 351 patients (4.8%), of whom 243 (3.3% of the total) were found to have HCC. A subset of patients was found to have cholangiocarcinoma (n = 18; 0.3% of the total). Interestingly, advanced liver disease or cirrhosis was not a prerequisite for the formation of HCC in a small group of patients. Of the total cohort, 30 patients underwent liver resection, 48 patients underwent liver transplantation, and 327 patients died. Patients with porphyria are at risk of developing primary liver malignancy. Further studies should aim to develop diagnostic and prognostic models aimed at the early detection of HCC in porphyria.
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Anthocyanins represent the major red, purple, and blue pigments in many flowers, fruits, vegetables, and cereals. They are also recognized as important health-promoting components in the human diet with protective effects against many chronic diseases, including cardiovascular diseases, obesity, and cancer. Anthocyanin biosynthesis has been studied extensively, and both biosynthetic and key regulatory genes have been isolated in many plant species. Here, we will provide an overview of recent progress in understanding the anthocyanin biosynthetic pathway in plants, focusing on the transcription factors controlling activation or repression of anthocyanin accumulation in cereals and fruits of different plant species, with special emphasis on the differences in molecular mechanisms between monocot and dicot plants. Recently, new insight into the transcriptional regulation of the anthocyanin biosynthesis, including positive and negative feedback control as well as epigenetic and post-translational regulation of MYB-bHLH-WD40 complexes, has been gained. We will consider how knowledge of regulatory mechanisms has helped to produce anthocyanin-enriched foods through conventional breeding and metabolic engineering. Additionally, we will briefly discuss the biological activities of anthocyanins as components of the human diet and recent findings demonstrating the important health benefits of anthocyanin-rich foods against chronic diseases.
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Frailty represents a state of vulnerability to multiple internal physiologic factors, as well as external pressures, and has been associated with clinical outcomes. We aim to understand the impact of frailty on patients admitted with hepatocellular carcinoma (HCC) by using the validated Hospital Frailty Risk Score, which is implemented in several hospitals worldwide. We conducted a nation-wide retrospective cohort study to determine the effect of frailty on the risk of in-patient mortality, hepatic encephalopathy, length of stay and cost. Frailty was associated with a 4.5-fold increased risk of mortality and a 2.3-fold increased risk of hepatic encephalopathy. Adjusted Cox regression showed that frailty was correlated with increased risk of in-patient mortality (hazard ratio: 2.3, 95% CI 1.9-2.8, p < 0.001). Frail HCC patients had longer hospital stay (median 5 days) vs. non-frail HCC patients (median 3 days). Additionally, frail patients had higher total costs of hospitalization ($40,875) compared with non-frail patients ($31,667). Frailty is an independent predictor of hepatic encephalopathy and in-patient mortality. Frailty is a surrogate marker of hospital length of stay and cost.
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The increased use of nanoparticles (NPs) requires efficient testing of their potential toxic effects. A promising approach is to use reporter cell lines to quickly assess the activation of cellular stress response pathways. This study aimed to use the ToxTracker reporter cell lines to investigate (geno)toxicity of various metal- or metal oxide NPs and draw general conclusions on NP-induced effects, in combination with our previous findings. The NPs tested in this study (n = 18) also included quantum dots (QDs) in different sizes. The results showed a large variation in cytotoxicity of the NPs tested. Furthermore, whereas many induced oxidative stress only few activated reporters related to DNA damage. NPs of manganese (Mn and Mn3O4) induced the most remarkable ToxTracker response with activation of reporters for oxidative stress, DNA damage, protein unfolding and p53-related stress. The QDs (CdTe) were highly toxic showing clearly size-dependent effects and calculations suggest surface area as the most relevant dose metric. Of all NPs investigated in this and previous studies the following induce the DNA damage reporter; CuO, Co, CoO, CdTe QDs, Mn, Mn3O4, V2O5, and welding NPs. We suggest that these NPs are of particular concern when considering genotoxicity induced by metal- and metal oxide NPs.
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Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1ß release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale® system, and NPs were deposited on the co-culture using XposeALI®. No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1ß, IL-6, TNFα, MCP-1) were observed after exposure of the co-culture in ALI (max 5 µg/cm2) or submerged (max 22 µg/cm2) conditions. In contrast, CeO2 NPs cause clear IL-1ß release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.
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Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.
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An increasing use of cobalt (Co)-based nanoparticles (NPs) in different applications and exposures at occupational settings triggers the need for toxicity assessment. Improved understanding regarding the physiochemical characteristics of Co metal NPs and different oxides in combination with assessment of toxicity and mechanisms may facilitate decisions for grouping during risk assessment. The aim of this study was to gain mechanistic insights in the correlation between NP reactivity and toxicity of three different Co-based NPs (Co, CoO, and Co3O4) by using various tools for characterization, traditional toxicity assays, as well as six reporter cell lines (ToxTracker) for rapid detection of signaling pathways of relevance for carcinogenicity. The results showed cellular uptake of all NPs in lung cells and induction of DNA strand breaks and oxidative damage (comet assay) by Co and CoO NPs. In-depth studies on the ROS generation showed high reactivity of Co, lower for CoO, and no reactivity of Co3O4 NPs. The reactivity depended on the corrosion and transformation/dissolution properties of the particles and the media highlighting the role of the surface oxide and metal speciation as also confirmed by in silico modeling. By using ToxTracker, Co NPs were shown to be highly cytotoxic and induced reporters related to oxidative stress (Nrf2 signaling) and DNA strand breaks. Similar effects were observed for CoO NPs but at higher concentrations, whereas the Co3O4 NPs were inactive at all concentrations tested. In conclusion, our study suggests that Co and CoO NPs, but not Co3O4, may be grouped together for risk assessment.
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Cobalto/toxicidade , Nanopartículas Metálicas/toxicidade , Óxidos/toxicidade , Células A549 , Quebras de DNA/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Nickel (Ni) compounds are classified as carcinogenic to humans but the underlying mechanisms are still poorly understood. Furthermore, effects related to nanoparticles (NPs) of Ni have not been fully elucidated. The aim of this study was to investigate genotoxicity and mutagenicity of Ni and NiO NPs and compare the effect to soluble Ni from NiCl2 . We employed different models; i.e., exposure of (1) human bronchial epithelial cells (HBEC) followed by DNA strand break analysis (comet assay and γ-H2AX staining); (2) six different mouse embryonic stem (mES) reporter cell lines (ToxTracker) that are constructed to exhibit fluorescence upon the induction of various pathways of relevance for (geno)toxicity and cancer; and (3) mES cells followed by mutagenicity testing (Hprt assay). The results showed increased DNA strand breaks (comet assay) for the NiO NPs and at higher doses also for the Ni NPs whereas no effects were observed for Ni ions/complexes from NiCl2 . By employing the reporter cell lines, oxidative stress was observed as the main toxic mechanism and protein unfolding occurred at cytotoxic doses for all three Ni-containing materials. Oxidative stress was also detected in the HBEC cells following NP-exposure. None of these materials induced the reporter related to direct DNA damage and stalled replication forks. A small but statistically significant increase in Hprt mutations was observed for NiO but only at one dose. We conclude that Ni and NiO NPs show more pronounced (geno)toxic effects compared to Ni ions/complexes, indicating more serious health concerns. Environ. Mol. Mutagen. 59:211-222, 2018. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
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Ensaio Cometa/métodos , Proteínas de Fluorescência Verde/metabolismo , Histonas/metabolismo , Hipoxantina Fosforribosiltransferase/metabolismo , Nanopartículas Metálicas/toxicidade , Testes de Mutagenicidade/métodos , Níquel/toxicidade , Animais , Bioensaio , Brônquios/efeitos dos fármacos , Brônquios/patologia , Sobrevivência Celular , Células Cultivadas , Dano ao DNA , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Genes Reporter , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Mutagênicos/toxicidade , Mutação , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND: Application of nanoenzymes, based on D-amino acid oxidase (DAAO) conjugated to magnetic nanoparticles (NPs), as anticancer system requires improvement of the synthesis protocol and in vivo distribution evaluation. RESULTS: A new and more efficient synthesis via EDC-NHS produced an Fe3O4NP-APTES-DAAO system with a specific activity of 7 U/mg NPs. IR spectroscopy showed that all Fe3O4 NP sites are saturated with APTES and all available NH2 sites with DAAO. The acute cytotoxicity of the new system does not differ from that of the previous one. In vivo experiments showed that the system did not cause adverse effects, cross the brain-blood barrier and accumulate in the heart. CONCLUSIONS: Our results support the possibility to use enzymes conjugated to magnetic NPs for cancer treatment. Besides, we think that enzymes and other biological molecules efficiently conjugated to magnetic NPs might constitute a category of 'bionanoparticles' to be exploited, not only in medical, but also in industrial biotechnology.
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AIM: The authors propose a new magnetic nanoparticle-enzyme system for cancer therapy capable of targeting the enzyme and consequently decreasing the adverse effects, meanwhile improving the patient's life quality. MATERIALS & METHODS: The authors have functionalized Fe3O4 nanoparticles with 3-amino-propyltriethoxysilane (APTES) and conjugated it to yeast D-amino acid oxidase (DAAO) by coupling this with glutaraldehyde. RESULTS & CONCLUSION: The authors have tested the Fe3O4-APTES-DAAO system on three tumor cell lines. Exposed cells show, at the electron microscope level, nanoparticles on the surface of the plasma membrane and inside endocytic vesicles. Fe3O4-APTES-DAAO caused a substantial decrease of cell viability greatly augmented when D-alanine, a DAAO substrate, was added. Fe3O4-APTES-DAAO was demonstrated to be more effective than free DAAO, confirming the validity of the system in cancer therapy.
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D-Aminoácido Oxidase/química , Nanopartículas/química , Neoplasias/terapia , Sobrevivência Celular/fisiologia , Células HCT116 , Humanos , Microscopia Eletrônica de Transmissão , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In the search for noninvasive diagnostic techniques and new therapies, "nanosystems", which are capable of binding and targeting bioactive molecules, are becoming increasingly important. In this context, biocompatible coatings are gaining interest, not only for their biological effects but also because they are considered capable to mask nanoparticle toxicity. In this work, we have compared the toxicity of nanoparticles coated with heparin and carboxymethylchitosan in the SKOV-3 cell line. Our results indicate that heparin and carboxymethylchitosan coatings do not guarantee the decrease of nanoparticle intrinsic toxicity which is often envisaged. Nonetheless, these coatings provide the opportunity for further functionalization with a variety of biomolecules for their use in theranostics.