Hyper-inflammatory responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major cause of disease severity and death. Predictive prognosis biomarkers to guide ...therapeutics are critically lacking. Several studies have indicated a "cytokine storm" with the release of interleukin-1 (IL-1), IL-6, and IL-8, along with tumor necrosis factor alpha (TNFα) and other inflammatory mediators. Here, we proposed to assess the relationship between IL-6 and outcomes of patients with coronavirus disease 2019 (COVID-19). Our cohort consisted of 46 adult patients with PCR-proven SARS-CoV-2 infection admitted in a COVID-19 ward of the Hospital de Braga (HB) from April 7 to May 7, 2020, whose IL-6 levels were followed over time. We found that IL-6 levels were significantly different between the disease stages. Also, we found a significant negative correlation between IL-6 levels during stages IIb and III, peripheral oxygen saturation (SpO
), and partial pressure of oxygen in arterial blood (PaO
), showing that IL-6 correlates with respiratory failure. Compared to the inflammatory markers available in the clinic routine, we found a positive correlation between IL-6 and C-reactive protein (CRP). However, when we assessed the predictive value of these two markers, IL-6 behaves as a better predictor of disease progression. In a binary logistic regression, IL-6 level was the most significant predictor of the non-survivors group, when compared to age and CRP. Herein, we present IL-6 as a relevant tool for prognostic evaluation, mainly as a predictor of outcome.
The rise of emerging contaminants in waters challenges the scientific community and water treatment stakeholders to design remediation techniques that are simple, practical, inexpensive, effective, ...and environmentally friendly. Emerging contaminants include antibiotics, hormones, illicit drugs, endocrine disruptors, cosmetics, personal care products, pesticides, surfactants, industrial products, microplastics, nanoparticles, and nanomaterials. Removing those contaminants is not easy because classical wastewater treatment systems are not designed to handle emerging contaminants, and contaminants often occur as traces in complex organo-mineral mixtures. Here, we review advanced treatments for the removal of emerging contaminants in wastewater, with focus on adsorption-oriented processes using non-conventional adsorbents such as cyclodextrin polymers, metal–organic frameworks, molecularly imprinted polymers, chitosan, and nanocellulose. We describe biological-based technologies for the degradation and removal of emerging contaminants. Then, we present advanced oxidation processes as the most promising strategies because of their simplicity and efficiency.
Cells are subjected to endogenous e.g., reactive oxygen species (ROS), replication stress and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the ...synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.
This work reports on the design, development, and characterization of novel magneto-plasmonic elastic liposomes (MPELs) of DPPC:SP80 (85:15) containing Mg
Ca
Fe
O
nanoparticles coupled with gold ...nanorods, for topical application of photothermal therapy (PTT). Both magnetic and plasmonic components were characterized regarding their structural, morphological, magnetic and photothermal properties. The magnetic nanoparticles display a cubic shape and a size (major axis) of 37 ± 3 nm, while the longitudinal and transverse sizes of the nanorods are 46 ± 7 nm and 12 ± 1.6 nm, respectively. A new methodology was employed to couple the magnetic and plasmonic nanostructures, using cysteine as bridge. The potential for photothermia was evaluated for the magnetic nanoparticles, gold nanorods and the coupled magnetic/plasmonic nanoparticles, which demonstrated a maximum temperature variation of 28.9 °C, 33.6 °C and 37.2 °C, respectively, during a 30 min NIR-laser irradiation of 1 mg/mL dispersions. Using fluorescence anisotropy studies, a phase transition temperature (T
) of 35 °C was estimated for MPELs, which ensures an enhanced fluidity crucial for effective crossing of the skin layers. The photothermal potential of this novel nanostructure corresponds to a specific absorption rate (SAR) of 616.9 W/g and a maximum temperature increase of 33.5 °C. These findings point to the development of thermoelastic nanocarriers with suitable features to act as photothermal hyperthermia agents.
Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection ...that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis. This is required to prevent the development of hypoglycemia that otherwise compromises disease tolerance to sepsis. FTH overexpression or ferritin administration establish disease tolerance therapeutically. In conclusion, disease tolerance to sepsis relies on a crosstalk between adaptive responses controlling iron and glucose metabolism, required to maintain blood glucose within a physiologic range compatible with host survival.
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•Ferritin is required to establish disease tolerance to sepsis•Iron heme represses liver G6Pase during sepsis•Ferritin counters G6Pase repression and sustains blood glucose levels after sepsis•Liver gluconeogenesis is required to establish disease tolerance to sepsis
Disease tolerance to sepsis depends on a crosstalk between iron and glucose- metabolic responses that maintain blood glucose levels within a dynamic range compatible with host survival.
Abstract
Expression of the transcription factor SOX4 is often elevated in human cancers, where it generally correlates with tumor-progression and poor-disease outcome. Reduction of SOX4 expression ...results in both diminished tumor-incidence and metastasis. In breast cancer, TGF-β-mediated induction of SOX4 has been shown to contribute to epithelial-to-mesenchymal transition (EMT), which controls pro-metastatic events. Here, we identify SMAD3 as a novel, functionally relevant SOX4 interaction partner. Genome-wide analysis showed that SOX4 and SMAD3 co-occupy a large number of genomic loci in a cell-type specific manner. Moreover, SOX4 expression was required for TGF-β-mediated induction of a subset of SMAD3/SOX4-co-bound genes regulating migration and extracellular matrix-associated processes, and correlating with poor-prognosis. These findings identify SOX4 as an important SMAD3 co-factor controlling transcription of pro-metastatic genes and context-dependent shaping of the cellular response to TGF-β. Targeted disruption of the interaction between these factors may have the potential to disrupt pro-oncogenic TGF-β signaling, thereby impairing tumorigenesis.
The picture-word interference (PWI) paradigm allows us to delve into the process of lexical access in language production with great precision. It creates situations of interference between target ...pictures and superimposed distractor words that participants must consciously ignore to name the pictures. Yet, although the PWI paradigm has offered numerous insights at all levels of lexical representation, in this work we expose an extended lack of control regarding the variable animacy. Animacy has been shown to have a great impact on cognition, especially when it comes to the mechanisms of attention, which are highly biased toward animate entities to the detriment of inanimate objects. Furthermore, animate nouns have been shown to be semantically richer and prioritized during lexical access, with effects observable in multiple psycholinguistic tasks. Indeed, not only does the performance on a PWI task directly depend on the different stages of lexical access to nouns, but also attention has a fundamental role in it, as participants must focus on targets and ignore interfering distractors. We conducted a systematic review with the terms "picture-word interference paradigm" and "animacy" in the databases PsycInfo and Psychology Database. The search revealed that only 12 from a total of 193 PWI studies controlled for animacy, and only one considered it as a factor in the design. The remaining studies included animate and inanimate stimuli in their materials randomly, sometimes in a very disproportionate amount across conditions. We speculate about the possible impact of this uncontrolled variable mixing on many types of effects within the framework of multiple theories, namely the Animate Monitoring Hypothesis, the WEAVER++ model, and the Independent Network Model in an attempt to fuel the theoretical debate on this issue as well as the empirical research to turn speculations into knowledge.
Several millions of individuals are estimated to develop post-acute sequelae SARS-CoV-2 condition (PASC) that persists for months after infection. Here we evaluate the immune response in convalescent ...individuals with PASC compared to convalescent asymptomatic and uninfected participants, six months following their COVID-19 diagnosis. Both convalescent asymptomatic and PASC cases are characterised by higher CD8
T cell percentages, however, the proportion of blood CD8
T cells expressing the mucosal homing receptor β7 is low in PASC patients. CD8 T cells show increased expression of PD-1, perforin and granzyme B in PASC, and the plasma levels of type I and type III (mucosal) interferons are elevated. The humoral response is characterized by higher levels of IgA against the N and S viral proteins, particularly in those individuals who had severe acute disease. Our results also show that consistently elevated levels of IL-6, IL-8/CXCL8 and IP-10/CXCL10 during acute disease increase the risk to develop PASC. In summary, our study indicates that PASC is defined by persisting immunological dysfunction as late as six months following SARS-CoV-2 infection, including alterations in mucosal immune parameters, redistribution of mucosal CD8
β7Integrin
T cells and IgA, indicative of potential viral persistence and mucosal involvement in the etiopathology of PASC.
Despite the promising pharmacological properties of curcumin, the transport and effective release of curcumin is still a challenge. The advances in functionalized nanocarriers for curcumin have also ...been motivated by the anticancer activity of this natural compound, aiming at targeted therapies. Here, stealth (aqueous and solid) magnetoliposomes containing calcium-substituted magnesium ferrite nanoparticles, Ca
Mg
Fe
O
(with
= 0.25, 0.50, 0.75) were developed as nanocarriers for curcumin. The magnetic nanoparticles exhibit superparamagnetic properties and crystalline structure, with sizes below 10 nm. The magnetoliposomes based on these nanoparticles have hydrodynamic diameters around or below 150 nm and a low polydispersity. The influence of an alternating magnetic field (AMF) on drug release over time was evaluated and compared with curcumin release by diffusion. The results suggest the potential of drug-loaded magnetoliposomes as nanocarriers that can be magnetically guided to the tumor sites and act as agents for a synergistic effect combining magnetic hyperthermia and controlled drug release.
Cancer immunoediting is a dynamic process of crosstalk between tumor cells and the immune system. Herein, we explore the fast zebrafish xenograft model to investigate the innate immune contribution ...to this process. Using multiple breast and colorectal cancer cell lines and zAvatars, we find that some are cleared (regressors) while others engraft (progressors) in zebrafish xenografts. We focus on two human colorectal cancer cells derived from the same patient that show contrasting engraftment/clearance profiles. Using polyclonal xenografts to mimic intra-tumor heterogeneity, we demonstrate that SW620_progressors can block clearance of SW480_regressors. SW480_regressors recruit macrophages and neutrophils more efficiently than SW620_progressors; SW620_progressors however, modulate macrophages towards a pro-tumoral phenotype. Genetic and chemical suppression of myeloid cells indicates that macrophages and neutrophils play a crucial role in clearance. Single-cell-transcriptome analysis shows a fast subclonal selection, with clearance of regressor subclones associated with IFN/Notch signaling and escaper-expanded subclones with enrichment of IL10 pathway. Overall, our work opens the possibility of using zebrafish xenografts as living biomarkers of the tumor microenvironment.
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