Easy approach to detect cell immunity to COVID vaccines in common variable immunodeficiency patients.

BACKGROUND: Patients with primary antibody deficiencies, such as Common Variable Immunodeficiency (CVID), have some problems to assess immune response after coronavirus disease (COVID) vaccination. Cutaneous delayed-type hypersensitivity (DTH) has the potential to be used as a useful, simple, and cheaper tool to assess T-cell (T lymphocyte) function. METHODS: Seventeen patients with CVID, a rare disease, received two doses of the mRNA-based Pfizer-BioNTech COVID-19 vaccine. Humoral Immune Response (HIR) was determined by measuring specific immunoglobulin G (IgG) antibodies, and Cellular Immune Response (CIR) was evaluated using an ex vivo interferon-gamma release assay (IGRA) and in vivo by DTH skin test. RESULTS: Two weeks after the second dose of the vaccine, 12 out of 17 CVID patients have high optical density (OD) ratios of specific anti-spike protein (S) IgG whereas five patients were negative or low. Ex vivo CIR was considered positive in 14 out of 17 S1-stimulated patients. Unspecific stimulation was positive in all 17 patients showing no T-cell defect. A positive DTH skin test was observed in 16 CVID patients. The only patient with negative DTH also had negative ex vivo CIR. CONCLUSIONS: The use of DTH to evaluate CIR was validated with an optimal correlation with the ex vivo CIR. The CIR after vaccination in patients with antibody deficiencies seems to have high precision and more sensitivity to antibodies-based methods in CVID. CLINICAL IMPLICATIONS: There is a remarkable correlation between cutaneous DTH and ex vivo IGRA after COVID vaccination. A COVID-specific skin DTH test could be implemented in large populations. CAPSULE SUMMARY: Cutaneous delayed-type hypersensitivity has the potential to be used as a useful, simple, and cheaper tool to assess T-cell functioning.

A novel application of delayed-type hipersensitivity reaction to measure cellular immune response in SARS-CoV-2 exposed individuals.

OBJECTIVE: To understand the anti-virus adaptive immune response occurring during SARS-Cov-2 infection is necessary to have methods to investigate cellular and humoral components. The goal of this study has been to investigate the utility of a specific spike-DTH test using a coronavirus recombinant protein in COVID-19 patients. METHODS: DTH studies were performed by intradermal injection of a commercial recombinant spike protein from SARS-CoV-2 along with conventional serology studies. RESULTS: Fifty-one COVID-19 patients were studied showing 84,3% of concordance with spike-DTH and anti-RBD-IgG. Spike-DTH was superior to identify seven more COVID-19 individuals. A high specificity was found with no positive spike DTH reactions in the non-sick individuals. The skin test also showed more stable results over time while specific anti-RBD-IgG decreased gradually. Clinical severity groups also showed a progressive gradient of larger positive spike-DTH. CONCLUSION: Specific spike DTH test seems to be an easy method to study cell immune response.

Community perception of malaria in a vulnerable municipality in the Colombian Pacific.

BACKGROUND: Malaria primarily affects populations living in poor socioeconomic conditions, with limited access to basic services, deteriorating environmental conditions, and barriers to accessing health services. Control programmes are designed without participation from the communities involved, ignoring local knowledge and sociopolitical and cultural dynamics surrounding their main health problems, which implies imposing decontextualized control measures that reduce coverage and the impact of interventions. The objective of this study was to determine the community perception of malaria in the municipality of Olaya Herrera in the Colombian Pacific. METHODS: A 41-question survey on knowledge, attitudes, and practices (KAP) related to malaria, the perception of actions by the Department of Health, and access to the health services network was conducted. RESULTS: A total of 134 adults were surveyed, in whose households a total of 671 people lived. According to the survey data, about 80% of the household members included teenagers and children, out of which 61% had malaria at one time, and for 75.3%, this disease is a persistent problem. In spite of this, 57.2% of people who fell ill due to malaria were never visited by health personnel for a follow up. This population claimed that responsibility for who should prevent the disease is shared between each person and the Department of Health. However, personal actions were focused on using mosquito nets, ignoring other important practices to prevent bites. Despite campaigns by the Department of Health, 11.9% of respondents did not know how malaria was transmitted, and 8.96% thought it was transmitted through water. Also, 43.5% said that the Department of Health did not do any work to control malaria and 16% did not know if any action was taken. CONCLUSIONS: In spite of the knowledge about malaria and the efforts of the Department of Health to prevent it, the community actions do not seem to be consistent with this knowledge, as the number of cases of malaria is still high in the area.

Treatment of food waste digestate using microalgae-based systems with low-intensity light-emitting diodes.

Anaerobic digestion of food wastes coupled with digestate post-treatment using microalgae-based systems could recover large amounts of energy and nutrients worldwide. However, the development of full-scale implementations requires overcoming microalgae inhibition by high ammonia concentrations and low light transmittances affecting photosynthesis. This study evaluated the potential of microalgae-based reactors supplied with red light-emitting diodes (LEDs) at low intensity (660 nm and 15 µmol·m-2·s-1) to treat food waste digestate. LED reactors were compared with control reactors exposed to solar radiation. From a range of species in the inoculum, Chlorella vulgaris showed high adaptation to both lighting regimes and digestate environmental conditions, characterized by a C:N:P ratio of 74:74:1. Removal efficiencies for control and LED reactors were 84.0% and 95.8% for soluble chemical oxygen demand (COD) and 89.4% and 53.0% for ammonia, respectively. Approximately 50% of ammonia in control reactor and 15% in LED reactor was lost from the systems, whereas 17% and 36% of ammonia was transformed to organic nitrogen in control and LED reactors, respectively. Low-intensity LEDs maintained microalgae growth in levels similar to solar radiation and supported efficient digestate treatment, showing a potential for further application in optimization of full scale reactors at a relatively low energy cost.

Craniofacial primary well-differentiated low-grade central osteosarcoma in a paediatric patient: a case report.

Osteosarcoma is a primary malignant tumour that accounts for less than 1% of cancers diagnosed annually in the United States and 3% of all cancers in paediatric patients. Surgical treatment and adjuvant chemotherapy are essential to improve short- and long-term survival. In this report, we present the case of an 11-month-old female patient referred to the first level of care for a suspected tumour in the left orbit, who underwent biopsy and tumour resection surgery by the maxillofacial surgery service and underwent adjuvant chemotherapy in a specialised centre. Timely detection of cancer in the paediatric population, as well as multidisciplinary management and close surveillance, improves the survival and quality of life of patients.

Wastewater-based epidemiology for COVID-19 using dynamic artificial neural networks.

Global efforts in vaccination have led to a decrease in COVID-19 mortality but a high circulation of SARS-CoV-2 is still observed in several countries, resulting in some cases of severe lockdowns. In this sense, wastewater-based epidemiology remains a powerful tool for supporting regional health administrations in assessing risk levels and acting accordingly. In this work, a dynamic artificial neural network (DANN) has been developed for predicting the number of COVID-19 hospitalized patients in hospitals in Valladolid (Spain). This model takes as inputs a wastewater epidemiology indicator for COVID-19 (concentration of RNA from SARS-CoV-2 N1 gene reported from Valladolid Wastewater Treatment Plant), vaccination coverage, and past data of hospitalizations. The model considered both the instantaneous values of these variables and their historical evolution. Two study periods were selected (from May 2021 until September 2022 and from September 2022 to July 2023). During the first period, accurate predictions of hospitalizations (with an overall range between 6 and 171) were favored by the correlation of this indicator with N1 concentrations in wastewater (r = 0.43, p < 0.05), showing accurate forecasting for 1 day ahead and 5 days ahead. The second period's retraining strategy maintained the overall accuracy of the model despite lower hospitalizations. Furthermore, risk levels were assigned to each 1 day ahead prediction during the first and second periods, showing agreement with the level measured and reported by regional health authorities in 95 % and 93 % of cases, respectively. These results evidenced the potential of this novel DANN model for predicting COVID-19 hospitalizations based on SARS-CoV-2 wastewater concentrations at a regional scale. The model architecture herein developed can support regional health authorities in COVID-19 risk management based on wastewater-based epidemiology.

Segregation of a haplotype encompassing FEB1 with genetic epilepsy with febrile seizures plus in a Colombian family.

Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (θ) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus.

MAGE-I proteins and cancer-pathways: A bidirectional relationship.

Data emerged from the last 20 years of basic research on tumor antigens positioned the type I MAGE (Melanoma Antigen GEnes - I or MAGE-I) family as cancer driver factors. MAGE-I gene expression is mainly restricted to normal reproductive tissues. However, abnormal re-expression in cancer unbalances the cell status towards enhanced oncogenic activity or reduced tumor suppression. Anomalous MAGE-I gene re-expression in cancer is attributed to altered epigenetic-mediated chromatin silencing. Still, emerging data indicate that MAGE-I can be regulated at protein level. Results from different laboratories suggest that after its anomalous re-expression, specific MAGE-I proteins can be regulated by well-known signaling pathways or key cellular processes that finally potentiate the cancer cell phenotype. Thus, MAGE-I proteins both regulate and are regulated by cancer-related pathways. Here, we present an updated review highlighting the recent findings on the regulation of MAGE-I by oncogenic pathways and the potential consequences in the tumor cell behavior.

Environmental Dissemination of SARS-CoV-2 in a University Hospital during the COVID-19 5th Wave Delta Variant Peak in Castile-León, Spain.

The dominant SARS-CoV-2 Delta variant (B.1.617.2) became the main circulating variant among countries by mid 2021. Attention was raised to the increased risk of airborne transmission, leading to nosocomial outbreaks even among vaccinated individuals. Considering the increased number of COVID-19 hospital admissions fueled by the spread of the variant, with Spain showing the highest COVID-19 rates in mainland Europe by July 2021, the aim of this study was to assess SARS-CoV-2 environmental contamination in different areas of a University Hospital in the region of Castile-León, Spain, during the peak of the 5th wave of COVID-19 in the country (July 2021). Air samples were collected from sixteen different areas of the Hospital using a Coriolis® µ air sampler. Surface samples were collected in these same areas using sterile flocked plastic swabs. RNA extraction followed by a one-step RT-qPCR were performed for detection of SARS-CoV-2 RNA. Of the 21 air samples, only one was positive for SARS-CoV-2 RNA, from the emergency waiting room. Of the 40 surface samples, 2 were positive for SARS-CoV-2 RNA, both from the microbiology laboratory. These results may be relevant for risk assessment of nosocomial infection within healthcare facilities, thus helping prevent and minimize healthcare staff's exposure to SARS-CoV-2, reinforcing the importance of always wearing appropriate and well-fit masks at all times and proper PPE when in contact with infected patients.

Quantification and Whole Genome Characterization of SARS-CoV-2 RNA in Wastewater and Air Samples.

Wastewater-based epidemiology has emerged as a promising and efficacious surveillance system for SARS-CoV-2 and other infectious diseases in many nations. The process typically involves wastewater concentration, nucleic acid extraction, amplification of selected genomic segments, and detection and quantification of the amplified genomic segment. This methodology can similarly be leveraged to detect and quantify infectious agents, such as SARS-CoV-2, in air samples. Initially, SARS-CoV-2 was presumed to spread primarily through close personal contact with droplets generated by an infected individual while speaking, sneezing, coughing, singing, or breathing. However, a growing number of studies have reported the presence of SARS-CoV-2 RNA in the air of healthcare facilities, establishing airborne transmission as a viable route for the virus. This study presents a composite of established protocols to facilitate environmental detection, quantification, and sequencing of viruses from both wastewater and air samples.

Long Term Cell Immune Response to COVID-19 Vaccines Assessment Using a Delayed-Type Hypersensitivity (DTH) Cutaneous Test.

OBJECTIVE: As we progress with mass vaccination against SARS-CoV-2, there are key questions about the immunogenicity of COVID-19 vaccines that still are not answered. Conventional methods to measure cellular immune responses are complex and expensive in a pandemic situation. PATIENTS AND METHODS: Forty healthy healthcare workers accepted to participate during the vaccination schedule with a mRNA vaccine against SARS-CoV-2. Measurement of Delayed-Type Hypersensitivity (DTH) cutaneous response after intradermal test of protein S of SARS-CoV-2 at day 35 and day 200 was performed. At the same time, a specific anti-RBD IgG using a classic ELISA before vaccination, and on days 0, 35, and 200 was performed. RESULTS: All 40 individuals had a positive DTH skin response at day 35, whereas 39 participants had a positive skin test at day 200. Moreover, although all 40 individuals showed a positive humoral response of specific IgG against spike protein at day 35, with most of them having significantly lower levels at day 200. CONCLUSION: DTH could be proposed as an ideal and easy method to predict cellular immunity response to mRNA vaccines 200 days after starting an immunization schedule with mRNA vaccine for COVID-19.

Salmonella Typhi Vaccination Response as a Tool for the Stratification of Risk in Patients with Predominantly Antibody Deficiencies.

Predominantly antibody deficiencies are the most frequent type of primary immunodeficiency (PID). Diagnosis requires evaluation of the immune function by distinguishing the presence or absence of a response against polysaccharide antigens. Salmonella enterica serovar Typhi-based vaccines have proved to be a suitable tool. We studied a group of patients with suspicion of primary immunodeficiency and classified them by final diagnosis. We analyzed the vaccination response to S. Typhi and other immune biomarkers and clinical data. The aim of this study was to classify patients regarding the intensity of their immune response measured as the difference between specific immunoglobulin G levels before and after vaccination and antibody levels in the post-vaccination sample in order to improve clinical decisions regarding follow up and treatment of immunodeficiency patients. We established four groups of response: Non responders (NR), Low responders (LR), Intermediate responders (IR), and High responders (HR), where we found differences in IgG, IgG1, IgG2, IgG4, IgA, IgA1, IgA2, and IgM, and where the finally achieved diagnosis was also different and corresponding to the level of vaccination response.

Sociodemographic and clinical characteristics related to the final condition of patients intoxicated by paraquat in a hospital in southwestern Colombia / Características sociodemográficas y clínicas relacionadas con la condición final de pacientes intoxicados por paraquat en un hospital del suroccidente de Colombia.

Introduction: Paraquat is an agrochemical that constitutes the first cause of death by poisoning in different countries. Objective: To relate sociodemographic and clinical characteristics with the final condition of patients intoxicated by paraquat in a hospital in southwestern Colombia. Materials and methods: This was an observational, descriptive, analytical, crosssectional, and retrospective study. We reviewed the medical records of patients diagnosed with paraquat poisoning at a level III hospital in Pasto, Colombia, from 2013 to 2018. We collected the data regarding their final condition (alive or deceased) and their sociodemographic, clinical, and paraclinical information. We established group comparisons and designed a binary logistic regression model. Results: We reviewed 299 records and, after the exclusion, we analyzed 160 cases. The characteristics related to the final condition of the patients were length of stay (OR = 0.124; 95% CI: 0.03-0.6; p = 0.009), heart rate (OR = 35.65; 95% CI: 1.44-884.78; p = 0.029), and initial creatinine (OR = 1.73; 95% CI: 1.23-2.44; p = 0.002). Conclusion: The proportion of case fatality was higher in patients with short hospital stay times and elevated heart rates and admission creatinine levels. This report may be useful as a rationale for the creation of a severity scale for the early detection of patients with adverse outcomes and their timely treatment.

Introducción. El herbicida paraquat constituye la primera causa de decesos por intoxicaciones en distintos países. Objetivo. Relacionar las características sociodemográficas y clínicas con la condición final de pacientes intoxicados por paraquat atendidos en un hospital del suroccidente de Colombia. Materiales y métodos. En este estudio observacional, descriptivo, analítico, transversal y retrospectivo, se revisaron las historias clínicas de pacientes atendidos por intoxicación con paraquat en una institución de tercer nivel de complejidad en Pasto (Colombia) entre el 2013 y el 2018. Se recolectó la información sobre la condición final (vivo o fallecido) de cada paciente, así como los datos sociodemográficos, clínicos y de los exámenes paraclínicos. Se establecieron comparaciones por grupos y se diseñó un modelo de regresión logística binaria. Resultados. Se filtró la información de 299 registros y se analizaron finalmente 160 casos. Las características relacionadas con la condición final de los pacientes fueron el tiempo de estancia (OR=0,124; IC95% 0,03-0,6; p=0,009), la frecuencia cardiaca (OR=35,65; IC95% 1,44-884,78; p=0,029) y la creatinina inicial (OR=1,73; IC95% 1,23-2,44; p=0,002). Conclusiones. La proporción de la letalidad fue mayor entre los pacientes con estancia hospitalaria corta, taquicardia y elevación de la concentración sérica de creatinina al ingreso. Este reporte puede ser útil como fundamento de una escala de gravedad para detectar a los pacientes con resultados adversos en la fase temprana para que puedan recibir una intervención oportuna.

Effect of digestate loading rates on microalgae-based treatment under low LED light intensity.

Low red-LED irradiances are an attractive alternative for enhancing microalgae photobioreactors treating digestate due to their potential contribution in decreasing area footprints with low energy consumptions. However, more information is required regarding the influence of digestate load on treatment performance and biomass valorisation when low-intensity red-LEDs are applied. Thus, this study assessed microalgae-based photobioreactors treating food waste digestate under different concentrations (5%, 25%, 50%, and 75%, v/v) at low red-LED irradiance (15 µmol·m-2·s-1). The removal efficiencies of soluble chemical oxygen demand (sCOD) at the end of the experiment ranged from 45% to 75% when treating influent loads between 5.3 and 79.1 g sCOD·m-3·d-1 (5% and 75%-digestate), respectively. Total ammonia nitrogen (TAN) was applied in loading rates between 3.2 and 48.5 g TAN·m-3·d-1 (5% and 75%, respectively) and removed with maximum efficiencies of 90%-100% in all trials. Nitrification-denitrification was proportionally more relevant when treating 5%-digestate, whereas volatilisation was the primary process in 25%, 50% and 75% concentrations. Microalgae presented adequate yields in all treatments, except in 75%-digestate, likely due to the blocking of light by the high solids concentrations. The assessment of the microalgae community and chlorophyll-a and carotenoids suggested that chlorophytes, mainly Dictyosphaerium pulchellum and Scenedesmus sp. grew autotrophically, whereas cyanobacteria Pseudanabaena sp. grew mixotrophically. Moreover, the sustainability of red LED lighting applications can be increased by anaerobic digestion or agricultural valorisation of the biomass, enabled by its high N and P contents. Low-intensity red-LEDs may have promissory applications in the treatment of high-strength wastewaters.

Centralized and decentralized wastewater-based epidemiology to infer COVID-19 transmission - A brief review.

Wastewater-based epidemiology has shown to be a promising and innovative approach to measure a wide variety of illicit drugs that are consumed in the communities. In the same way as for illicit drugs, wastewater-based epidemiology is a promising approach to understand the prevalence of viruses in a community-level. The ongoing coronavirus disease 2019 (COVID-19) pandemic created an unprecedented burden on public health and diagnostic laboratories all over the world because of the need for massive laboratory testing. Many studies have shown the applicability of a centralized wastewater-based epidemiology (WBE) approach, where samples are collected at WWTPs. A more recent concept is a decentralized approach for WBE where samples are collected at different points of the sewer system and at polluted water bodies. The second being particularly important in countries where there are insufficient connections from houses to municipal sewage pipelines and thus untreated wastewater is discharged directly in environmental waters. A decentralized approach can be used to focus the value of diagnostic tests in what we call targeted-WBE, by monitoring wastewater in parts of the population where an outbreak is likely to happen, such as student dorms, retirement homes and hospitals. A combination of centralized and decentralized WBE should be considered for an affordable, sustainable, and successful WBE implementation in high-, middle- and low-income countries.

T cell activity in successful treatment of chronic urticaria with omalizumab.

Omalizumab, a humanized monoclonal anti-IgE antibody has the potential to alter allergen processing. Recently, it has been postulated the assessment of PHA-stimulated adenosine triphosphate (ATP) activity as maker of CD4+ T cells activity in peripheral blood cells. We present the case report of a 35-year-old woman with a history of chronic idiopathic urticaria and angioedema of 8 years of development with poor response to treatment. The patient was partially controlled with cyclosporine at doses of 100 mg/12 h. However, she was still developing hives daily. Finally treatment with omalizumab was started at dose of 300 mg every 2 weeks. The patient experienced a decrease in urticarial lesions 2 days after starting therapy. We also evaluated the effects of omalizumab therapy on the activity of peripheral blood CD4+ T cells from the patient, in order to determine the potential modification of anti-IgE therapy on the process of antigen presentation-recognition. Activity of CD4+ cells by ATP release was clearly increased demonstrating an enlarged CD4 activity. Omalizumab may be useful in the treatment of severe chronic urticaria. ATP activity of peripheral blood CD4+ T cells might be a non-subjective method to assess Omalizumab activity.

The Beauty of Simplicity: Delayed-Type Hypersensitivity Reaction to Measure Cellular Immune Responses in RNA-SARS-Cov-2 Vaccinated Individuals.

BACKGROUND: Monitoring cellular immune responses elicited in vaccinated individuals is highly complicated. METHODS: 28 individuals participated during the vaccination process with 12 BNT162b2 mRNA (Pfizer) vaccine. Specific anti-RBD IgG using a classic ELISA was performed in days 10 and 20 (after one dose of the vaccine) and on day 35 (after two vaccine doses) in serum samples of all participants. In parallel, DTH (delayed-type hypersensitivity) Skin Test using S protein was performed before (11/28) and after two doses (28/28) of the vaccine. RESULTS: 6/28 individuals were considered positive for the specific anti-RBD IgG positive at day 10, whereas all 28 individuals were positive at day 20. Moreover, 28/28 individuals increased the OD ratios at day 36 (2 doses). DTH cutaneous test was performed on 11/28 participants at day 20 (1 dose) showing 8/11 a positive reaction at 12 h. DTH of all participants was performed on day 36 (2 doses), showing 28/28 positive reactions at 12 h. CONCLUSION: This report describes the first publication of the results obtained using an in vivo method, the classical DTH response to the Spike protein to assess T-cell immune responses in vaccinated individuals. This affordable and simple test would help to answer basic immunogenicity questions on large-scale population vaccine studies.

Optimizing a Protocol to Assess Immune Responses after SARS-CoV-2 Vaccination in Kidney-Transplanted Patients: In Vivo DTH Cutaneous Test as the Initial Screening Method.

Previously, the delayed-type hypersensitivity (DTH) cutaneous test with the spike protein of SARS-CoV-2 has been shown to be a simple in vivo method to measure T-cell functionality after natural infection and in vaccinated individuals. METHODS: Twenty-five kidney-transplanted recipients were immunized with two doses of the mRNA-based Pfizer-BioNTech COVID19 vaccine three weeks apart. Cell-immune response (CIR) was evaluated ten weeks later using an in vivo DTH skin test and in vitro with an interferon gamma release assay (IGRA). Humoral Immune Response (HIR) was determined by the measurement of specific IgG anti-S1 SARS-CoV-2. RESULTS: Ten weeks after the second dose of the vaccine, 23 out of 25 transplanted patients had a positive DTH skin test, while in vitro CIR was considered positive in 20 patients. Unspecific stimulation was positive in all 25 patients, showing no T-cell defect. Seven out of twenty-five patients had a negative specific anti-spike IgG. CIR was positive in all immune-competent control patients. CONCLUSIONS: DTH is a useful, simple, and cheaper tool that can be used to assess cellular immune response, with an excellent correlation with the in vitro CIR. CIR assessment after vaccination in these immunocompromised patients is an excellent complement to HIR-based methods. This skin test could be used if classical in vitro methods cannot be applied.

MageC2 protein is upregulated by oncogenic activation of MAPK pathway and causes impairment of the p53 transactivation function.

Normal-to-tumor cell transition is accompanied by changes in gene expression and signal transduction that turns the balance toward cancer-cell phenotype, eluding by different mechanisms, the response of tumor-suppressor genes. Here, we observed that MageC2, a MAGE-I protein able to regulate the p53 tumor-suppressor, is accumulated upon MEK/ERK MAPK activation. Overexpression of H-RasV12 oncogene causes an increase in MageC2 protein that is prevented by pharmacologic inhibition of MEK. Similarly, decrease in MageC2 protein levels is shown in A375 melanoma cells (which harbor B-RafV600E oncogenic mutation) treated with MEK inhibitors. MageC2 protein levels decrease when p14ARF is expressed, causing an Mdm2-independent upregulation of p53 transactivation. However, MageC2 is refractory to p14ARF-driven downregulation when H-RasV12 is co-expressed. Using MageC2 knockout A375 cells generated by CRISPR/CAS9 technology, we demonstrated the relevance of MageC2 protein in reducing p53 transcriptional activity in cells containing hyperactive MEK/ERK signaling. Furthermore, gene expression analysis performed in cancer-genomic databases, supports the correlation of reduced p53 transcriptional activity and high MageC2 expression, in melanoma cells containing Ras or B-Raf driver mutations. Data presented here suggest that MageC2 can be a functional target of the oncogenic MEK/ERK pathway to regulate p53.