Hydrogen peroxide (H2O2) is a compound involved in some mammalian reactions and processes. It modulates and signals the redox metabolism of cells by acting as a messenger together with hydrogen ...sulfide (H2S) and the nitric oxide radical (•NO), activating specific oxidations that determine the metabolic response. The reaction triggered determines cell survival or apoptosis, depending on which downstream metabolic pathways are activated. There are several ways to produce H2O2 in cells, and cellular systems tightly control its concentration. At the cellular level, the accumulation of hydrogen peroxide can trigger inflammation and even apoptosis, and when its concentration in the blood reaches toxic levels, it can lead to bioenergetic failure. This review summarizes existing research from a chemical perspective on the role of H2O2 in various enzymatic pathways and how this biochemistry leads to physiological or pathological responses.
Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be ...highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.
Myeloid-derived suppressor cells MDSCs are a heterogeneous population of cells that expand beyond their physiological regulation during pathologies such as cancer, inflammation, bacterial, and viral ...infections. Their key feature is their remarkable ability to suppress T cell and natural killer NK cell responses. Certain risk factors for severe COVID-19 disease, such as obesity and diabetes, are associated with oxidative stress. The resulting inflammation and oxidative stress can negatively impact the host. Similarly, cancer cells exhibit a sustained increase in intrinsic ROS generation that maintains the oncogenic phenotype and drives tumor progression. By disrupting endoplasmic reticulum calcium channels, intracellular ROS accumulation can disrupt protein folding and ultimately lead to proteostasis failure. In cancer and COVID-19, MDSCs consist of the same two subtypes (PMN-MSDC and M-MDSC). While the main role of polymorphonuclear MDSCs is to dampen the response of T cells and NK killer cells, they also produce reactive oxygen species ROS and reactive nitrogen species RNS. We here review the origin of MDSCs, their expansion mechanisms, and their suppressive functions in the context of cancer and COVID-19 associated with the presence of superoxide anion
O
and reactive oxygen species ROS.
IP3-dependent Ca2+ signaling controls a myriad of cellular processes in higher eukaryotes and similar signaling pathways are evolutionarily conserved in Plasmodium, the intracellular parasite that ...causes malaria. We have reported that isolated, permeabilized Plasmodium chabaudi, releases Ca2+ upon addition of exogenous IP3. In the present study, we investigated whether the IP3 signaling pathway operates in intact Plasmodium falciparum, the major disease-causing human malaria parasite. P. falciparum-infected red blood cells (RBCs) in the trophozoite stage were simultaneously loaded with the Ca2+ indicator Fluo-4/AM and caged-IP3. Photolytic release of IP3 elicited a transient Ca2+ increase in the cytosol of the intact parasite within the RBC. The intracellular Ca2+ pools of the parasite were selectively discharged, using thapsigargin to deplete endoplasmic reticulum (ER) Ca2+ and the antimalarial chloroquine to deplete Ca2+ from acidocalcisomes. These data show that the ER is the major IP3-sensitive Ca2+ store. Previous work has shown that the human host hormone melatonin regulates P. falciparum cell cycle via a Ca2+-dependent pathway. In the present study, we demonstrate that melatonin increases inositol-polyphosphate production in intact intraerythrocytic parasite. Moreover, the Ca2+ responses to melatonin and uncaging of IP3 were mutually exclusive in infected RBCs. Taken together these data provide evidence that melatonin activates PLC to generate IP3 and open ER-localized IP3-sensitive Ca2+ channels in P. falciparum. This receptor signaling pathway is likely to be involved in the regulation and synchronization of parasite cell cycle progression.
Hydrogen sulfide (H
S) was recognized as a gaseous signaling molecule, similar to nitric oxide (-NO) and carbon monoxide (CO). The aim of this review is to provide an overview of the formation of ...hydrogen sulfide (H
S) in the human body. H
S is synthesized by enzymatic processes involving cysteine and several enzymes, including cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), cysteine aminotransferase (CAT), 3-mercaptopyruvate sulfurtransferase (3MST) and D-amino acid oxidase (DAO). The physiological and pathological effects of hydrogen sulfide (H
S) on various systems in the human body have led to extensive research efforts to develop appropriate methods to deliver H
S under conditions that mimic physiological settings and respond to various stimuli. These functions span a wide spectrum, ranging from effects on the endocrine system and cellular lifespan to protection of liver and kidney function. The exact physiological and hazardous thresholds of hydrogen sulfide (H
S) in the human body are currently not well understood and need to be researched in depth. This article provides an overview of the physiological significance of H
S in the human body. It highlights the various sources of H
S production in different situations and examines existing techniques for detecting this gas.
Ageing entails changes in complex cognitive functions that lead to a decrease in autonomy and quality of life. Everyday cognition is the ability to solve cognitively complex problems in the everyday ...world, enabling instrumental activities of life. Benefits have been found in studies using everyday cognition-based assessment and intervention, as the results predict improvements in everyday performance, not just in specific cognitive functions. A study protocol is presented based on assessment and training in everyday cognition versus traditional cognitive stimulation for the improvement of functionality, emotional state, frailty and cognitive function.
A parallel randomised controlled clinical trial with two arms will be conducted. It will be carried out by the University of Salamanca (Spain) in eleven centres and associations for the elderly of the City Council of Salamanca. People aged 60 years or older without cognitive impairment will be recruited. Participants will be randomly distributed into two groups: the experimental group will undergo a training programme in everyday cognition and the control group a programme of traditional cognitive stimulation, completing 25 sessions over 7 months. All participants will be assessed at the beginning and at the end of the intervention, where socio-demographic data and the following scales will be collected: The Medical Outcomes Study (MOS), Questionnaire ARMS-e, Everyday Cognition Test (PECC), Scale Yesavage, Test Montreal Cognitive Assessment (MoCA), The Functional Independence Measure (FIM), Fragility Index and Lawton y Brody Scale.
The present study aims to improve conventional clinical practice on cognitive function training by proposing a specific assessment and intervention of everyday cognition based on the importance of actual cognitive functioning during the resolution of complex tasks of daily life, giving priority to the improvement of autonomy.
ClinicalTrials.gov; ID: NCT05688163. Registered on: January 18, 2023.
La alfabetización en salud es el proceso centrado en la obtención del conocimiento, la motivación y las competencias individuales para entender y acceder a información, expresar opiniones y tomar ...decisiones relacionadas con la promoción y el mantenimiento de la salud, lo que es aplicable en diferentes contextos, entornos y a lo largo de toda la vida. Esta perspectiva conceptual es muy necesaria ante la emergencia del virus SARS-CoV-2 que produce la enfermedad Covid-19, la cual ha producido una pandemia con efectos devastadores, no sólo desde el punto de vista de la salud, sino también, de manera muy importante, desde el económico, político y social. En este ensayo se tratan de establecer los elementos basados en la evidencia científica que orientan las políticas públicas de prevención y control, entre los que destacan: a) la inteligencia epidemiológica, la cual incluye no sólo la estrategia de vigilancia poblacional sino, ante la imposibilidad real de identificación de todos los casos positivos, la puesta en práctica de estrategias de vigilancia centinela y la vigilancia basada en eventos; b) las medidas de mitigación de la propagación de la epidemia, tales como distanciamiento social e higiene, lavado de manos, cuarentena, restricción de movimiento y utilización de cubrebocas, entre otras; c) medidas de supresión de la transmisión cuando el número de casos es muy elevado, como el endurecimiento de medidas drásticas de encierro en casa; d) fortalecimiento de la capacidad de atención médica en los sistemas de salud e incremento de la capacidad de prevención de la transmisión en los servicios de salud, incluyendo la utilidad de las pruebas diagnósticas; y e) el desarrollo de vacunas profilácticas contra Covid-19, así como la generación de agentes terapéuticos. Todas estas acciones no sólo deben implementarse rápidamente desde la perspectiva multidisciplinaria y multisectorial de la salud pública para contener, prevenir y controlar la epidemia, sino que necesitan obligatoriamente del concurso de la comunidad como responsabilidad compartida. Debido a todo esto, es necesaria la alfabetización en salud pública.
The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one ...potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.
Phytochemicals from plant extracts are becoming increasingly popular in the world of food science and technology because they have positive effects on human health. In particular, several bioactive ...foods and dietary supplements are being investigated as potential treatments for chronic COVID. Hydroxytyrosol (HXT) is a natural antioxidant, found in olive oil, with antioxidant anti-inflammatory properties that has been consumed by humans for centuries without reported adverse effects. Its use was approved by the European Food Safety Authority as a protective agent for the cardiovascular system. Similarly, arginine is a natural amino acid with anti-inflammatory properties that can modulate the activity of immune cells, reducing the production of pro-inflammatory cytokines such as IL-6 and TNF-α. The properties of both substances may be particularly beneficial in the context of COVID-19 and long COVID, which are characterised by inflammation and oxidative stress. While l-arginine promotes the formation of
NO, HXT prevents oxidative stress and inflammation in infected cells. This combination could prevent the formation of harmful peroxynitrite, a potent pro-inflammatory substance implicated in pneumonia and COVID-19-associated organ dysfunction, as well as reduce inflammation, improve immune function, protect against free radical damage and prevent blood vessel injury. Further research is needed to fully understand the potential benefits of HXT and arginine in the context of COVID-19.
Everyday cognition is the application of basic cognitive skills and knowledge of the specific cognitive domain for the resolution of problems that are integrated within the instrumental domains of ...functioning. The main objective is to evaluate the effectiveness of a Training Programme in Everyday Cognition in order to improve the levels of everyday cognition and global cognitive performance in older adults.
A randomised controlled trial of two groups. The sample was composed of healthy older adults. The intervention of the experimental group consisted of an Everyday Cognition Training Programme, and the intervention of the control group consisted of a Conventional Cognitive Training Programme. The Rapid Assessment of Cognitive Functions test (ERFC) and the Everyday Cognition Battery test (ECB) were used to assess the intervention.
Total sample (n = 237) composed of 44 men and 223 women, with a mean age of 73.45 years. Statistically significant differences (p < 0.001) were evidenced between the control group and the experimental group in both the ECB and ERFC; in the final evaluation of the study and in the follow-up.
The use of a Daily Cognition Training Programme presents greater benefits in terms of both global cognitive performance and everyday cognition than the use of a Conventional Cognitive Training Programme in elderly adults.
ClinicalTrials.gov : NCT04041999 . Retrospectively registered. Date of trial registration: 8th July 2019.
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