Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal ...epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out.
Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel).
A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome.
We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.
A direct extraction of volatile organic compounds (VOC) using HS-SPME method was proposed. The identification and quantification of VOC of six dry-cured meat products were developed using gas ...chromatography-single mass spectrometry technique. This method allowed obtaining high sensitive, repeatable and reproducible results using a simple and fast analysis. The compounds were organized according to their chemical family to facilitate their presentation, due to some of them can have different origins. The possible origins were discussed in text. The VOC detected in the present research could be divided into three different groups: The first group included typical volatile derived from chemical reactions that take place during dry-cured stage, mainly lipid oxidation and amino acid degradation. Some VOC in the first group having high influence in the overall aroma were alcohols (1-penten-3-ol, 1-octen-3-ol and 1-hexanol), aldehydes (butanal, 2- and 3-methyl, propanal, 2-methyl, hexanal, octanal and nonanal), acids (acetic acid, butanoic acid and butanoic acid, 2- and 3-methyl), furan, 2-penthyl, ketones (acetoin) or ethyl esters. The second group included terpenes and some sulphur compounds derived from spices used in the meat product formulation. Finally, the third group included furans, phenols, pyrazines and pyridines derived from smoking process. As a general conclusion, the results indicated that the use of HS-SPME-GC/MS is an adequate method for VOC analysis in dry-cured meat products.
Extractive metallurgy has recently turned its attention to waste treatment for the recovery of precious metals through innovative metallurgical processes, such as ion flotation. This work studied the ...influence of several chemical and physical factors, such as the concentration of xanthate x, frother agent e, dithiophosphate xl, pH, superficial gas velocity Jg, percentage of gas holdup Eg, bubble diameter (Db) calculated with the drift flux model, and the type of sparger, in the efficiency of silver(I) recovery by the ion flotation technique in sub-aerated cells. The results obtained indicate a 90.7% v/v recovery of silver(I) under conditions of 3.77 × 10−4 M x, 1.25 × 10−4 M e, Jg 0.5 cm/s, Jl 0.19 cm/s, Eg of 4.1% v/v, and Optimal Db of 0.11 cm, with a rigid bubble generator, achieving an apparent flotation kinetics of 4.16 1/min. The use of combinations x–xl achieve a silver(I) recovery of 86.9% with a Jg of 1.0 cm/s. The best recovery efficiencies achieved 93% w/w silver(I) are with pH 8.0, e of 1.25 × 10−4, Jl of 0.19 (cm/s) and a rigid sparger compared to a flexible one.
The translocation of nanomaterials or complex delivery systems into the cytosol is a major challenge in nanobiotechnology. After receptor‐mediated endocytosis, most nanomaterials are sequestered and ...undergo degradation, therapy inactivation, or exocytosis. Herein we explore a novel surface particle coating made of adsorbed carbon nanotubes that provides coated materials with new properties that reproduce the viral cell‐invasive mechanisms, namely, receptor‐mediated endocytosis, endolysosomal escape, and cytosolic particle release preserving cell viability. This novel biomimetic coating design will enable the intracytoplasmic delivery of many different functional materials endowed with therapeutic, magnetic, optical, or catalytic functionalities, thus opening the door to a wide array of chemical and physical processes within the cytosolic or nuclear domains, and supporting new developments in the biotechnological, pharmaceutical, and biomedical industries.
A clean getaway: An engineered nanocoating composed of carbon nanotubes enabled particles with nano/micrometer dimensions to break through lysosomal membranes and invade the intracellular realm (see picture). The coated materials resemble viruses in terms of their structure and reproduce the viral cell‐invasive mechanisms of receptor‐mediated endocytosis, endolysosomal escape, and cytosolic particle release with the preservation of cell viability.
Up to 22 June 2022, 508 confirmed cases of monkeypox (MPX) have been reported in the Madrid region of Spain, 99% are men (n = 503) with a median age of 35 years (range: 18-67). In this ongoing ...outbreak, 427 cases (84.1%) reported condomless sex or sex with multiple partners within the 21 days before onset of symptoms, who were predominantly men who have sex with men (MSM) (n = 397; 93%). Both the location of the rash, mainly in the anogenital and perineal area, as well as the presence of inguinal lymphadenopathy suggest that close physical contact during sexual activity played a key role in transmission. Several cases reported being at a sauna in the city of Madrid (n = 34) or a mass event held on the Spanish island of Gran Canaria (n = 27), activities which may represent a conducive environment for MPX virus spread, with many private parties also playing an important role. Because of the rapid implementation of MPX surveillance in Madrid, one of the largest outbreaks reported outside Africa was identified. To minimise transmission, we continue to actively work with LGBTIQ+ groups and associations, with the aim of raising awareness among people at risk and encouraging them to adopt preventive measures.
Genistein is an isoflavone present in soybeans and is considered a bioactive compound due to its widely reported biological activity. We have previously shown that intraperitoneal genistein ...administration and diet supplementation activates the thermogenic program in rats and mice subcutaneous white adipose tissue (scWAT) under multiple environmental cues, including cold exposure and high‐fat diet feeding. However, the mechanistic insights of this process were not previously unveiled. Uncoupling protein 1 (UCP1), a mitochondrial membrane polypeptide responsible for dissipating energy into heat, is considered the most relevant thermogenic marker; thus, we aimed to evaluate whether genistein regulates UCP1 transcription. Here we show that genistein administration to thermoneutral‐housed mice leads to the appearance of beige adipocyte markers, including a sharp upregulation of UCP1 expression and protein abundance in scWAT. Reporter assays showed an increase in UCP1 promoter activity after genistein stimulation, and in silico analysis revealed the presence of estrogen (ERE) and cAMP (CRE) response elements as putative candidates of genistein activation. Mutation of the CRE but not the ERE reduced genistein‐induced promoter activity by 51%. Additionally, in vitro and in vivo ChIP assays demonstrated the binding of CREB to the UCP1 promoter after acute genistein administration. Taken together, these data elucidate the mechanism of genistein‐mediated UCP1 induction and confirm its potential applications in managing metabolic disorders.
Genistein induces the thermogenic program in white adipose tissue via cAMP/PKA/CREB pathway to promote Ucp1 transcription. This mechanism of beige remodeling is independent of sympathetic nervous system activation.
The aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs).
We ...retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor).
Sixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05).
Positivity in a readily available autoantibody battery may be associated with the occurrence of irAEs.
KEY MESSAGES
Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events.
Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.
Immune checkpoint blockade (ICB) with antibodies has shown durable clinical responses in a wide range of cancer types, but the overall response rate is still limited. Other effective therapeutic ...modalities to increase the ICB response rates are urgently needed. New bispecific antibody (bsAb) formats combining the ICB effect and a direct action on cancer cells could improve the efficacy of current immunotherapies. Here, we report the development of a PD-L1/EGFR symmetric bsAb by fusing a dual-targeting tandem trimmer body with the human IgG1 hinge and Fc regions. The bsAb was characterized in vitro and the antitumor efficacy was evaluated in humanized mice bearing xenografts of aggressive triple-negative breast cancer and lung cancer. The IgG-like hexavalent bsAb, designated IgTT-1E, was able to simultaneously bind both EGFR and PD-L1 antigens, inhibit EGF-mediated proliferation, effectively block PD-1/PD-L1 interaction, and induce strong antigen-specific antibody-dependent cellular cytotoxicity activity in vitro. Potent therapeutic efficacies of IgTT-1E in two different humanized mouse models were observed, where tumor growth control was associated with a significantly increased proportion of CD8
+
T cells. These results support the development of IgTT-1E for the treatment of EGFR
+
cancers.
Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We ...performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range IQR, 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% 55/396 versus 23.9% 16/67; hazard ratio HR, 0.51 95% confidence interval, 0.27 to 0.96;
= 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 95% confidence interval, 0.048 to 0.65). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% 42/310 versus 15.1% 13/86; odds ratio OR, 0.880 95% confidence interval, 0.449 to 1.726;
= 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.
PDF
