Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.     

A Lack of GD3 Synthase Leads to Impaired Renal Expression of Connexins and Pannexin1 in St8sia1 Knockout Mice

The aim of this study was to determine the effects of altered ganglioside composition on the expression of Cx37, Cx40, Cx43, Cx45, and Panx1 in different kidney regions of St8sia1 gene knockout mice (St8sia1 KO) lacking the GD3 synthase enzyme. Experiments were performed in twelve male 6-month-old mice: four wild-type (C57BL/6-type, WT) and eight St8sia1 KO mice. After euthanasia, kidney tissue was harvested, embedded in paraffin wax, and processed for immunohistochemistry. The expression of connexins and Panx1 was determined in different regions of the kidney: cortex (CTX.), outer stripe of outer medulla (O.S.), inner stripe of outer medulla (IN.S.), and inner medulla (IN.MED.). We determined significantly lower expression of Cx37, Cx40, Cx45, and Panx1 in different parts of the kidneys of St8sia1 KO mice compared with WT. The most consistent decrease was found in the O.S. where all markers (Cx 37, 40, 45 and Panx1) were disrupted in St8si1 KO mice. In the CTX. region, we observed decrease in the expression of Cx37, Cx45, and Panx1, while reduced expression of Cx37 and Panx1 was more specific to IN.S. The results of the present study suggest that deficiency of GD3 synthase in St8sia1 KO mice leads to disruption of renal Cx expression, which is probably related to alteration of ganglioside composition.     

Effective Natural Killer Cell Degranulation Is an Essential Key in COVID-19 Evolution

NK degranulation plays an important role in the cytotoxic activity of innate immunity in the clearance of intracellular infections and is an important factor in the outcome of the disease. This work has studied NK degranulation and innate immunological profiles and functionalities in COVID-19 patients and its association with the severity of the disease. A prospective observational study with 99 COVID-19 patients was conducted. Patients were grouped according to hospital requirements and severity. Innate immune cell subpopulations and functionalities were analyzed. The profile and functionality of innate immune cells differ between healthy controls and severe patients; CD56dim NK cells increased and MAIT cells and NK degranulation rates decreased in the COVID-19 subjects. Higher degranulation rates were observed in the non-severe patients and in the healthy controls compared to the severe patients. Benign forms of the disease had a higher granzymeA/granzymeB ratio than complex forms. In a multivariate analysis, the degranulation capacity resulted in a protective factor against severe forms of the disease (OR: 0.86), whereas the permanent expression of NKG2D in NKT cells was an independent risk factor (OR: 3.81; AUC: 0.84). In conclusion, a prompt and efficient degranulation functionality in the early stages of infection could be used as a tool to identify patients who will have a better evolution.     

Eco-Sustainable Silk Fibroin/Pomegranate Peel Extract Film as an Innovative Green Material for Skin Repair

Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases.     

Hematites Precipitated in Alkaline Precursors: Comparison of Structural and Textural Properties for Methane Oxidation

Hematite (α-Fe₂O₃) catalysts prepared using the precipitation methods was found to be highly effective, and therefore, it was studied with methane (CH₄), showing an excellent stable performance below 500 °C. This study investigates hematite nanoparticles (NPs) obtained by precipitation in water from the precursor of ferric chloride hexahydrate using precipitating agents NaOH or NH₄OH at maintained pH 11 and calcined up to 500 °C for the catalytic oxidation of low concentrations of CH₄ (5% by volume in air) at 500 °C to compare their structural state in a CH₄ reducing environment. The conversion (%) of CH₄ values decreasing with time was discussed according to the course of different transformation of goethite and hydrohematites NPs precursors to magnetite and the structural state of the calcined hydrohematites. The phase composition, the size and morphology of nanocrystallites, thermal transformation of precipitates and the specific surface area of the NPs were characterized in detail by X-ray powder diffraction, transmission electron microscopy, infrared spectroscopy, thermal TG/DTA analysis and nitrogen physisorption measurements. The results support the finding that after goethite dehydration, transformation to hydrohematite due to structurally incorporated water and vacancies is different from hydrohematite α-Fe₂O₃. The surface area SBET of Fe₂O₃_NH-70 precipitate composed of protohematite was larger by about 53 m²/g in comparison with Fe₂O₃_Na-70 precipitate composed of goethite. The oxidation of methane was positively influenced by the hydrohematites of the smaller particle size and the largest lattice volume containing structurally incorporated water and vacancies.     

Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma

Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.     

The Origin of the High Voltage in DPM12/P3HT Organic Solar Cells

Organic solar cells made using a blend of DPM12 and P3HT are studied. The results show that higher V_oc can be obtained when using DPM12 in comparison to the usual mono‐substituted PCBM electron acceptor. Moreover, better device performances are also registered when the cells are irradiated with sun‐simulated light of 10–50 mW cm^?2 intensity. Electrochemical and time‐resolved spectroscopic measurements are compared for both devices and a 100‐mV shift in the density of states (DOS) is observed for DPM12/P3HT devices with respect to PCBM/P3HT solar cells and slow polaron‐recombination dynamics are found for the DPM12/P3HT devices. These observations can be directly correlated with the observed increase in V_oc, which is in contrast with previous results that correlated the higher V_oc with different ideality factors obtained using dark‐diode measurements. The origin for the shift in the DOS can be correlated to the crystallinity of the blend that is influenced by the properties of the included fullerene.     

Polymerizable Skin Hydrogel for Full Thickness Wound Healing

The skin is the largest organ in the human body, comprising the main barrier against the environment. When the skin loses its integrity, it is critical to replace it to prevent water loss and the proliferation of opportunistic infections. For more than 40 years, tissue-engineered skin grafts have been based on the in vitro culture of keratinocytes over different scaffolds, requiring between 3 to 4 weeks of tissue culture before being used clinically. In this study, we describe the development of a polymerizable skin hydrogel consisting of keratinocytes and fibroblast entrapped within a fibrin scaffold. We histologically characterized the construct and evaluated its use on an in vivo wound healing model of skin damage. Our results indicate that the proposed methodology can be used to effectively regenerate skin wounds, avoiding the secondary in vitro culture steps and thus, shortening the time needed until transplantation in comparison with other bilayer skin models. This is achievable due to the instant polymerization of the keratinocytes and fibroblast combination that allows a direct application on the wound. We suggest that the polymerizable skin hydrogel is an inexpensive, easy and rapid treatment that could be transferred into clinical practice in order to improve the treatment of skin wounds.     

Intra- and interspecific mineral composition variability of commercial instant coffees and coffee substitutes: Contribution to mineral intake

The present paper reports the amount and estimated daily mineral intake of nine elements (Ca, Mg, K, Na, P, Fe, Mn, Cr and Ni) in commercial instant coffees and coffee substitutes (n = 49). Elements were quantified by high-resolution continuum source flame (HR-CS-FAAS) and graphite furnace (HR-CS-GFAAS) atomic absorption spectrometry, while phosphorous was evaluated by a standard vanadomolybdophosphoric acid colorimetric method.Instant coffees and coffee substitutes are rich in K, Mg and P (>100 mg/100 g dw), contain Na, Ca and Fe in moderate amounts (>1 mg/100 g), and trace levels of Cr and Ni. Among the samples analysed, plain instant coffees are richer in minerals (p < 0.001), except for Na and Cr. Blends of coffee substitutes (barley, malt, chicory and rye) with coffee (20–66%) present intermediate amounts, while lower quantities are found in substitutes without coffee, particularly in barley.From a nutritional point of view the results indicate that the mean ingestion of two instant beverages per day (total of 4 g instant powder), either with or without coffee, cannot be regarded as important sources of minerals to the human diet, although providing a supplementation of some minerals, particularly Mg and Mn in instant coffees. Additionally, and for authentication purposes, the correlations observed between some elements and the coffee percentage in the blends, with particular significance for Mg amounts, provides a potential tool for the estimation of coffee in substitute blends.