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Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.
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In the present study, we employed the ddPCR and IHC techniques to assess the prevalence and roles of RAS and RAF mutations in a small batch of melanoma (n = 22), benign moles (n = 15), and normal skin samples (n = 15). Mutational screening revealed the coexistence of BRAF and NRAS mutations in melanomas and nevi and the occurrence of NRAS G12/G13 variants in healthy skin. All investigated nevi had driver mutations in the BRAF or NRAS genes and elevated p16 protein expression, indicating cell cycle arrest despite an increased mutational burden. BRAF V600 mutations were identified in 54% of melanomas, and NRAS G12/G13 mutations in 50%. The BRAF mutations were associated with the Breslow index (BI) (p = 0.029) and TIL infiltration (p = 0.027), whereas the NRAS mutations correlated with the BI (p = 0.01) and the mitotic index (p = 0.04). Here, we demonstrate that the "young" ddPCR technology is as effective as a CE-IVD marked real-time PCR method for detecting BRAF V600 hotspot mutations in tumor biopsies and recommend it for extended use in clinical settings. Moreover, ddPCR was able to detect low-frequency hotspot mutations, such as NRAS G12/G13, in our tissue specimens, which makes it a promising tool for investigating the mutational landscape of sun-damaged skin, benign nevi, and melanomas in more extensive clinical studies.
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Melanoma Cutáneo Maligno , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Humanos , Análisis Mutacional de ADN , Mutación , Nevo de Células Epitelioides y Fusiformes/genética , Proyectos Piloto , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Melanoma Cutáneo Maligno/genéticaRESUMEN
The skin is a complex organ that includes a wide variety of tissue types with different embryological origins [...].
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Early diagnosis is essential for completely eradicating skin cancer and maximizing patients' clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), optical coherence tomography (OCT), magnetic resonance imaging (MRI), near-infrared (NIR) bioimaging, positron emission tomography (PET), and their combinations provide non-invasive imaging data that may help in the early detection of cutaneous tumors and surgical planning. Hence, they seem appropriate for observing dynamic processes such as blood flow, immune cell activation, and tumor energy metabolism, which may be relevant for disease evolution. This review discusses the latest technological and methodological advances in imaging techniques that may be applied for skin cancer detection and monitoring. In the first instance, we will describe the principle and prospective clinical applications of the most commonly used imaging techniques, highlighting the challenges and opportunities of their implementation in the clinical setting. We will also highlight how imaging techniques may complement the molecular and histological approaches in sharpening the non-invasive skin characterization, laying the ground for more personalized approaches in skin cancer patients.
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Neoplasias Cutáneas , Humanos , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Tomografía de Coherencia Óptica/métodos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Microscopía Confocal/métodosRESUMEN
The outbreak of the coronavirus disease 2019 (COVID-19) has gathered 1 year of scientific/clinical information. This informational asset should be thoroughly and wisely used in the coming year colliding in a global task force to control this infection. Epidemiology of this infection shows that the available estimates of SARS-CoV-2 infection prevalence largely depended on the availability of molecular testing and the extent of tested population. Within molecular diagnosis, the viability and infectiousness of the virus in the tested samples should be further investigated. Moreover, SARS-CoV-2 has a genetic normal evolution that is a dynamic process. The immune system participates to the counterattack of the viral infection by pathogen elimination, cellular homoeostasis, tissue repair and generation of memory cells that would be reactivated upon a second encounter with the same virus. In all these stages, we still have knowledge to be gathered regarding antibody persistence, protective effects and immunological memory. Moreover, information regarding the intense pro-inflammatory action in severe cases still lacks and this is important in stratifying patients for difficult to treat cases. Without being exhaustive, the review will cover these important issues to be acknowledged to further advance in the battle against the current pandemia.
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Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Prueba de COVID-19 , COVID-19 , SARS-CoV-2 , Animales , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/inmunología , Humanos , Memoria Inmunológica , Mutación , Pandemias , SARS-CoV-2/genética , SARS-CoV-2/inmunologíaRESUMEN
Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner.In innate system, Toll-like receptor signaling is the main molecular event triggering effector functions. Various isoforms of PKC can be common to different TLRs, while some of them are specific for a certain type of TLR. Protein kinases involvement in innate immune cells are presented within the chapter emphasizing their coordination in many aspects of immune cell function and, as important players in immune regulation.In adaptive immunity T-cell receptor and B-cell receptor signaling are the main intracellular pathways involved in seminal immune specific cellular events. Activation through TCR and BCR can have common intracellular pathways while others can be specific for the type of receptor involved or for the specific function triggered. Various PKC isoforms involvement in TCR and BCR Intracellular signaling will be presented as positive and negative regulators of the immune response events triggered in adaptive immunity.
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Proteínas Quinasas , Transducción de Señal , Proteínas Portadoras , Inmunidad Innata , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Toll-LikeRESUMEN
Tumour microenvironment is a complex system comprising cells and molecules that will provide the necessary conditions for tumour development and progression. Cells residing in the tumour microenvironment gain specific phenotypes and specific functions that are pro-tumorigenic. Tumour progression is in fact a combination between tumour cell characteristics and its interplay with tumour microenvironment. This dynamic network will allow tumour cells to grow, migrate and invade tissues. In the present chapter, we are highlighting some traits that characterise tumour microenvironment in basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma. In skin cancers, there are some common tumour microenvironment characteristics such as the presence of tumour-associated macrophages and regulatory T lymphocytes that are non-tumour cells promoting tumorigenesis. There are also skin cancer type differences in terms of tumour microenvironment characteristics. Thus, markers such as macrophage migration inhibitory factor in melanoma or the extraordinary diverse genetic make-up in the cancer-associated fibroblasts associated to squamous cell carcinoma are just a few of specific traits in skin cancer types. New technological advances for evaluation of tumour environment are presented. Thus, non-invasive skin imaging techniques such as reflectance confocal microscopy can evaluate skin tumour inflammatory infiltrates for density and cellular populations. Analysing tumour micromedium in depth may offer new insights into cancer therapy and identify new therapy targets.
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Carcinogénesis , Neoplasias Cutáneas/patología , Microambiente Tumoral , Carcinogénesis/efectos de los fármacos , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacosRESUMEN
Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti-inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.
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Análisis de los Alimentos/métodos , Aceites Volátiles/química , Extractos Vegetales/química , Plantas/química , Rosmarinus/químicaRESUMEN
Herd immunity is a form of indirect protection that is offered to the community when a large proportion of individuals contained in the community are immune to a certain infection. This immunity can be due to vaccination or to the recovery post-disease. Effective herd immunity in SARS-CoV-2 infection has several hurdles upon achievement. Herd immunity cannot be obtained concomitantly in many geographical areas because the areas have different population density and the societal measures to contain the spreading are different. A proportion of 50-66% of the population needs to be immunized naturally or artificially in this SARS-Cov2 pandemic and this percentage is not easily achievable. The duration of herd immunity is another issue while information on the long-term immune response against SARS-CoV2 is yet scarce. Epitope stability, another issue to be solved when achieving herd immunity, is important. Mutation in the viral structure will call upon other sets of neutralizing antibodies and hence for other herd immunity type installment. The societal tactics to achieve the much-needed herd immunity should be developed keeping in mind the welfare of the population. Without being exhaustive, throughout our paper we will elaborate on each of the hurdles encountered in developing herd immunity to SARS-Cov2 infection.
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COVID-19/inmunología , COVID-19/prevención & control , Inmunidad Colectiva , Mutación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/epidemiología , Epítopos/química , Femenino , Geografía , Humanos , Inmunización Pasiva , Masculino , Modelos Teóricos , Pandemias/prevención & control , ARN Viral , Linfocitos T/inmunología , VacunaciónRESUMEN
Drug-induced liver injury (DILI) remains one of the challenges in the safety profile of both authorized and candidate drugs, and predicting hepatotoxicity from the chemical structure of a substance remains a task worth pursuing. Such an approach is coherent with the current tendency for replacing non-clinical tests with in vitro or in silico alternatives. In 2016, a group of researchers from the FDA published an improved annotated list of drugs with respect to their DILI risk, constituting "the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans" (DILIrank). This paper is one of the few attempting to predict liver toxicity using the DILIrank dataset. Molecular descriptors were computed with the Dragon 7.0 software, and a variety of feature selection and machine learning algorithms were implemented in the R computing environment. Nested (double) cross-validation was used to externally validate the models selected. A total of 78 models with reasonable performance were selected and stacked through several approaches, including the building of multiple meta-models. The performance of the stacked models was slightly superior to other models published. The models were applied in a virtual screening exercise on over 100,000 compounds from the ZINC database and about 20% of them were predicted to be non-hepatotoxic.
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Algoritmos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Bases de Datos Factuales/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Aprendizaje Automático , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Simulación por Computador , Humanos , Modelos Teóricos , Pronóstico , Relación Estructura-Actividad CuantitativaRESUMEN
Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients' survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.
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Capsaicina/farmacología , Capsaicina/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Phthalocyanines (Pc) and their metallated derivatives are strongly considered for photodynamic therapy (PDT) possessing unique properties as possible new photosensitizers (PS). We have used toxicological assessments, real-time monitoring of cellular impedance, and imagistic measurements for assessing the in vitro dark toxicity and PDT efficacy of Ga(III)-Pc in SHSy5Y neuroblastoma cells. We have established the non-toxic concentration range of Ga(III)-Pc, a compound which shows a high intracellular accumulation, with perinuclear distribution in confocal microscopy. By choosing Ga(III)Pc non-toxic dose, we performed in vitro experimental PDT hampering cellular proliferation. Our proposed Ga(III)-Pc could complete a future PS panel for neuroblastoma alternate therapy.
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Radioisótopos de Galio/farmacología , Indoles/farmacología , Neuroblastoma/radioterapia , Fármacos Fotosensibilizantes/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Humanos , Isoindoles , Fotoquimioterapia/métodosRESUMEN
Humans are exposed to multiple chemicals on a daily basis instead of to just a single chemical, yet the majority of existing toxicity data comes from single-chemical exposure. Multiple factors must be considered such as the route, concentration, duration, and the timing of exposure when determining toxicity to the organism. The need for adequate model systems (in vivo, in vitro, in silico and mathematical) is paramount for better understanding of chemical mixture toxicity. Currently, shortcomings plague each model system as investigators struggle to find the appropriate balance of rigor, reproducibility and appropriateness in mixture toxicity studies. Significant questions exist when comparing single-to mixture-chemical toxicity concerning additivity, synergism, potentiation, or antagonism. Dose/concentration relevance is a major consideration and should be subthreshold for better accuracy in toxicity assessment. Previous work was limited by the technology and methodology of the time, but recent advances have resulted in significant progress in the study of mixture toxicology. Novel technologies have added insight to data obtained from in vivo studies for predictive toxicity testing. These include new in vitro models: omics-related tools, organs-on-a-chip and 3D cell culture, and in silico methods. Taken together, all these modern methodologies improve the understanding of the multiple toxicity pathways associated with adverse outcomes (e.g., adverse outcome pathways), thus allowing investigators to better predict risks linked to exposure to chemical mixtures. As technology and knowledge advance, our ability to harness and integrate separate streams of evidence regarding outcomes associated with chemical mixture exposure improves. As many national and international organizations are currently stressing, studies on chemical mixture toxicity are of primary importance.
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Seguridad Química/métodos , Medición de Riesgo/métodos , Pruebas de Toxicidad/métodos , Animales , Simulación por Computador , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Modelos Biológicos , Modelos Teóricos , Reproducibilidad de los ResultadosRESUMEN
Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1) outline the state-of-the art knowledge on BBB passage, 2) address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3) highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nanosystem with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease.
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Barrera Hematoencefálica/metabolismo , Encefalopatías/tratamiento farmacológico , Preparaciones de Acción Retardada/metabolismo , Matriz Extracelular/metabolismo , Nanopartículas/metabolismo , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/patología , Encefalopatías/metabolismo , Encefalopatías/patología , Sistemas de Liberación de Medicamentos/métodos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/patología , Humanos , NeurofarmacologíaRESUMEN
Building the future of precision medicine is the main focus in cancer domain. Clinical trials are moving toward an array of studies that are more adapted to precision medicine. In this domain, there is an enhanced need for biomarkers, monitoring devices, and data-analysis methods. Omics profiling using whole genome, epigenome, transcriptome, proteome, and metabolome can offer detailed information of the human body in an integrative manner. Omes profiles reflect more accurately real-time physiological status. Personalized omics analyses both disease as a whole and the main disease processes, for a better understanding of the individualized health. Through this, multi-omic approaches for health monitoring, preventative medicine, and personalized treatment can be targeted simultaneously and can lead clinicians to have a comprehensive view on the diseasome.
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Epigenómica , Metaboloma , Medicina de Precisión/métodos , Proteoma/análisis , Transcriptoma/genética , Biomarcadores/análisis , Ensayos Clínicos como Asunto , HumanosRESUMEN
Psoriasis vulgaris is a chronic, immune-mediated, inflammatory, polygenic skin disorder affecting approximately 2% of the population. It has a great impact on quality of life; patients often experience depression, anxiety, stigma as well as suicidal behavior. Even though psoriasis is one of the most studied dermatological conditions, the pathogenesis of the disease is still not completely elucidated. The complex interactions between keratinocytes, dendritic cells, T-lymphocytes, neutrophils and mast cells are responsible for the histopathological changes seen in psoriasis. The pathogenic model leading to the formation of psoriatic plaques has however evolved a lot over the years. There is now enough evidence to support the role of interleukin (IL) -23, IL-17, IL-22, T helper (Th) -17 cells, Th-22 cells, T regulatory cells, transforming growth factor (TGF)-ß1 and IL-10 in the pathogenesis of the disease. Moreover, several inflammatory and anti-inflammatory molecules are currently being investigated, some of them showing promising results. The aim of this paper is to look over the most recent advances in the immunological pathways involved in the pathogenesis of psoriasis vulgaris.
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Inmunidad , Psoriasis/etiología , Psoriasis/metabolismo , Biomarcadores , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Humanos , Mediadores de Inflamación/metabolismo , Psoriasis/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Células Th17/inmunología , Células Th17/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is one of the most frequent cancers, and to date, there have been very few drugs available that can improve survival, the most well-known being sorafenib. The pathogenesis of HCC is complex, involving multiple processes including abnormal cell and tissue regeneration, angiogenesis, genomic instability, cellular proliferation, and signaling pathway alterations. Capsaicin is a substance that holds increasingly high interest and is studied as a therapeutic option in a wide array of diseases. Several studies have investigated capsaicin roles in various stages of HCC oncogenesis. This paper aims to thoroughly detail the available information on the individual effects of capsaicin on the cellular mechanisms and pathways involved in HCC development, as well as investigate their possible cooperation and interferences. The synergistic antitumor effects of capsaicin and sorafenib are also addressed.
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Antineoplásicos Fitogénicos/farmacología , Capsaicina/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Capsaicina/química , Capsaicina/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Estrés Oxidativo , Transducción de Señal/efectos de los fármacos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Canales Catiónicos TRPV/agonistasRESUMEN
Aerogels are a special class of nanostructured materials with very high porosity and tunable physicochemical properties. Although a few types of aerogels have already reached the market in construction materials, textiles and aerospace engineering, the full potential of aerogels is still to be assessed for other technology sectors. Based on current efforts to address the material supply chain by a circular economy approach and longevity as well as quality of life with biotechnological methods, environmental and life science applications are two emerging market opportunities where the use of aerogels needs to be further explored and evaluated in a multidisciplinary approach. In this opinion paper, the relevance of the topic is put into context and the corresponding current research efforts on aerogel technology are outlined. Furthermore, key challenges to be solved in order to create materials by design, reproducible process technology and society-centered solutions specifically for the two abovementioned technology sectors are analyzed. Overall, advances in aerogel technology can yield innovative and integrated solutions for environmental and life sciences which in turn can help improve both the welfare of population and to move towards cleaner and smarter supply chain solutions.
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Geles/química , Nanoestructuras/química , PorosidadRESUMEN
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research. The outcome of this intense research field is the discovery that development, ageing, and stem-cell dependent regeneration but also several diseases including cancer are largely controlled by the epigenetic state of cells. Consequently, this research has already led to the first FDA approved drugs that exploit the gained knowledge to combat disease. In recent years, the ~150 modifications found in RNA have come to the focus of intense research. Here we provide a perspective on necessary and expected developments in the fast expanding area of RNA modifications, termed epitranscriptomics.
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ADN de Neoplasias , Epigénesis Genética , Epigenómica/normas , Perfilación de la Expresión Génica/normas , Regulación Neoplásica de la Expresión Génica , Neoplasias , ARN Neoplásico , Transcriptoma , ADN de Neoplasias/genética , ADN de Neoplasias/metabolismo , Europa (Continente) , Perfilación de la Expresión Génica/métodos , Humanos , Neoplasias/genética , Neoplasias/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismoRESUMEN
Chemical allergens are small molecules able to form a sensitizing complex once they bound to proteins. One of the most frequent manifestations of chemical allergy is contact hypersensitivity, which can have serious impact on quality of life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune disease, resulting in erythema and eczema. Chemical allergy is of considerable importance to the toxicologist, who has the responsibility of identifying and characterizing the allergenic potential of chemicals, and estimating the risk they pose to human health. This review aimed at exploring the phenomena of chemical-induced contact allergy starting from a mechanistic understanding, immunoregulatory mechanisms, passing through the potency of contract allergen until the hazard identification, pointing out the in vitro models for assessing contact allergen-induced cell activation and the risk prevention.