Schnurri-3 drives tumor growth and invasion in cancer cells expressing interleukin-13 receptor alpha 2.

Interleukin 13 receptor alpha 2 (IL13Rα2) is a relevant therapeutic target in glioblastoma (GBM) and other tumors associated with tumor growth and invasion. In a previous study, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) is a key mediator of the IL-13/IL13Rα2 signaling pathway. PTP1B regulates cancer cell invasion through Src activation. However, PTP1B/Src downstream signaling mechanisms that modulate the invasion process remain unclear. In the present research, we have characterized the PTP1B interactome and the PTP1B-associated phosphoproteome after IL-13 treatment, in different cellular contexts, using proteomic strategies. PTP1B was associated with proteins involved in signal transduction, vesicle transport, and with multiple proteins from the NF-κB signaling pathway, including Tenascin-C (TNC). PTP1B participated with NF-κB in TNC-mediated proliferation and invasion. Analysis of the phosphorylation patterns obtained after PTP1B activation with IL-13 showed increased phosphorylation of the transcription factor Schnurri-3 (SHN3), a reported competitor of NF-κB. SHN3 silencing caused a potent inhibition in cell invasion and proliferation, associated with a down-regulation of the Wnt/ß-catenin pathway, an extensive decline of MMP9 expression and the subsequent inhibition of tumor growth and metastasis in mouse models. Regarding clinical value, high expression of SHN3 was associated with poor survival in GBM, showing a significant correlation with the classical and mesenchymal subtypes. In CRC, SHN3 expression showed a preferential association with the mesenchymal subtypes CMS4 and CRIS-B. Moreover, SHN3 expression strongly correlated with IL13Rα2 and MMP9-associated poor prognosis in different cancers. In conclusion, we have uncovered the participation of SNH3 in the IL-13/IL13Rα2/PTP1B pathway to promote tumor growth and invasion. These findings support a potential therapeutic value for SHN3.

Status of Ecosystem Services in Abandoned Mining Areas in the Iberian Peninsula: Management Proposal.

An abandoned sphalerite mining area in the southwest (SW) of the Iberian Peninsula was studied to evaluate the impact that the presence of metal(loid)s has on soil and ecosystem health. Five zones were delimited: sludge, dump, scrubland, riparian zone, and dehesa. Critical total levels of lead (Pb), zinc (Zn), thallium (Tl), and chromium (Cr), well above the limit indicative of toxicity problems, were found in the areas close to the sources of contamination. Pb-Zn concentrations were very high in the riparian zone, reaching values of 5875 mg/kg Pb and 4570 mg/kg Zn. The whole area is classifiable as extremely contaminated with Tl, with concentrations above 370 mg/kg in the scrubland. Cr accumulation mainly occurred in areas away from the dump, with levels up to 240 mg/kg in the dehesa. In the study area, several plants were found growing luxuriantly despite the contamination. The measured metal(loid)s content is the cause of a significant decrease in ecosystem services, resulting in unsafe soils for food and water production, so the implementation of a decontamination program is advisable. The plant species Retama sphaerocarpa, present in the sludge, scrubland, riparian zone, and dehesa, is postulated as suitable for use in phytoremediation.

Threats of metal mining on ecosystem services. Conservation proposals.

We have studied, in a protected area with intense hunting activity, the consequences of the abandonment of facilities and tailings of a metal mine. The area studied has the peculiarity of having a steep slope and containing a water reservoir for irrigation and human consumption. Soil, sludge, vegetation, and water samples were analyzed, in which many metal(loid)s exceeded the generic reference levels (NGR) established for the health of the ecosystem. The concentration of Tl in the soils ranged between 300 and 700 mg kg-1, because of continuous diffuse pollution, produced both by the alteration of sphalerite and the combustion products of a coal-fired power plant near the study area. Soil concentrations of Pb (250-1500 mg kg-1) and Zn (350-700 mg kg-1) from the tailings indicate extreme contamination in the areas adjacent to them and in the reservoir. The contamination affects the water quality of the stream running through the study area, with 64 µg L-1 of Tl and 9.1 µg L-1 of Zn having been detected in the reservoir water. To ensure protection of human and ecosystem health, the following is proposed: (i) soil stabilization for erosion control and reduction of diffuse pollution, (ii) monitoring of soils for agricultural use and water quality, and (iii) study the impact of contamination on wildlife, both hunting and non-game species. Given their capacity to accumulate heavy metals it is proposed to use Cistus ladanifer, Lavandula stoechas and Retama sphaerocarpa as phytoremedial species. The novelty of this research lies in two considerations. First, a proposal for the analysis of environmental compartments as an interconnected and interdependent network in terms of impacts and their repercussions on the ES. Secondly, the application of the model DPSIR, which assumes that anthropogenic activities have an impact on the environment.

A multicriteria decision analysis (MCDA) applied to three long-term prophylactic treatments for hereditary angioedema in Spain.

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LTP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.24-0.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE.

Dolor torácico y shock secundarios a perforación espontánea de esófago: síndrome de Boerhaave.

La perforación esofágica es la más letal de todas las perforaciones del aparato digestivo. Se presenta el caso de un varón de 65 años que acude a urgencias por un cuadro clínico de dolor torácico, vómitos e hipotensión. Se le realizó tomografía computarizada por sospecha de síndrome aórtico agudo, con hallazgos sugerentes de perforación esofágica. El síndrome de Boerhaave consiste en la rotura longitudinal del esófago sobre una pared macroscópicamente sana. Su tratamiento definitivo se realiza con cirugía durante las primeras 24 horas. El síndrome de Boerhaave debe considerarse como complicación posible en los pacientes con dolor epigástrico y vómitos, ya que es una emergencia quirúrgica con alta morbimortalidad.Esophageal perforation is the most lethal of all perforations of the digestive system. 65-year-old male who goes to the emergency department due to clinical symptoms of chest pain, vomiting and hypotension, who underwent CT scan for suspected acute aortic syndrome, with suggestive findings of esophageal perforation. Boerhaave syndrome consists of the longitudinal rupture of the esophagus on a macroscopically healthy wall. Its definitive treatment is performed with surgery during the first 24 hours. Boerhaave syndrome should be considered as a possible complication in patients with epigastric pain and vomiting, as it is a surgical emergency with high morbidity and mortality.