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Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.
Ortega, MA, De Leon-Oliva, D, Gimeno-Longas, MJ, Boaru, DL, Fraile-Martinez, O, García-Montero, C, de Castro, AV, Barrena-Blázquez, S, López-González, L, Amor, S, et al
Biomolecules. 2024;(3)
Abstract
Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.
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Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.
Jimenez-Gómez, N, López-Suárez, A, Haro, S, Fernández-González, P, Monserrat, J, Eraña-Tomás, I, Cuevas-Santos, J, Rodríguez-Luna, A, Ortega, MA, Gómez-Sánchez, MJ, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:115929
Abstract
Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.
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The diversity of salicylic acid biosynthesis and defense signaling in plants: Knowledge gaps and future opportunities.
Ullah, C, Chen, YH, Ortega, MA, Tsai, CJ
Current opinion in plant biology. 2023;:102349
Abstract
The phytohormone salicylic acid (SA) is known to regulate plant immunity against pathogens. Plants synthesize SA via the isochorismate synthase (ICS) pathway or the phenylalanine ammonia-lyase (PAL) pathway. The ICS pathway has been fully characterized using Arabidopsis thaliana, a model plant that exhibits pathogen-inducible SA accumulation. Many species including Populus (poplar) depend instead on the partially understood PAL pathway for constitutive as well as pathogen-stimulated SA synthesis. Diversity of SA-mediated defense is also evident in SA accumulation, redox regulation, and interplay with other hormones like jasmonic acid. This review highlights the contrast between Arabidopsis and poplar, discusses potential drivers of SA diversity in plant defenses, and offers future research directions.
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AIF1: Function and Connection with Inflammatory Diseases.
De Leon-Oliva, D, Garcia-Montero, C, Fraile-Martinez, O, Boaru, DL, García-Puente, L, Rios-Parra, A, Garrido-Gil, MJ, Casanova-Martín, C, García-Honduvilla, N, Bujan, J, et al
Biology. 2023;(5)
Abstract
Macrophages are a type of immune cell distributed throughout all tissues of an organism. Allograft inflammatory factor 1 (AIF1) is a calcium-binding protein linked to the activation of macrophages. AIF1 is a key intracellular signaling molecule that participates in phagocytosis, membrane ruffling and F-actin polymerization. Moreover, it has several cell type-specific functions. AIF1 plays important roles in the development of several diseases: kidney disease, rheumatoid arthritis, cancer, cardiovascular diseases, metabolic diseases and neurological disorders, and in transplants. In this review, we present a comprehensive review of the known structure, functions and role of AIF1 in inflammatory diseases.
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Exploring Perceptions About Paracetamol, Tramadol, and Codeine on Twitter Using Machine Learning: Quantitative and Qualitative Observational Study.
Carabot, F, Donat-Vargas, C, Santoma-Vilaclara, J, Ortega, MA, García-Montero, C, Fraile-Martínez, O, Zaragoza, C, Monserrat, J, Alvarez-Mon, M, Alvarez-Mon, MA
Journal of medical Internet research. 2023;:e45660
Abstract
BACKGROUND Paracetamol, codeine, and tramadol are commonly used to manage mild pain, and their availability without prescription or medical consultation raises concerns about potential opioid addiction. OBJECTIVE This study aims to explore the perceptions and experiences of Twitter users concerning these drugs. METHODS We analyzed the tweets in English or Spanish mentioning paracetamol, tramadol, or codeine posted between January 2019 and December 2020. Out of 152,056 tweets collected, 49,462 were excluded. The content was categorized using a codebook, distinguishing user types (patients, health care professionals, and institutions), and classifying medical content based on efficacy and adverse effects. Scientific accuracy and nonmedical content themes (commercial, economic, solidarity, and trivialization) were also assessed. A total of 1000 tweets for each drug were manually classified to train, test, and validate machine learning classifiers. RESULTS Of classifiable tweets, 42,840 mentioned paracetamol and 42,131 mentioned weak opioids (tramadol or codeine). Patients accounted for 73.10% (60,771/83,129) of the tweets, while health care professionals and institutions received the highest like-tweet and tweet-retweet ratios. Medical content distribution significantly differed for each drug (P<.001). Nonmedical content dominated opioid tweets (23,871/32,307, 73.9%), while paracetamol tweets had a higher prevalence of medical content (33,943/50,822, 66.8%). Among medical content tweets, 80.8% (41,080/50,822) mentioned drug efficacy, with only 6.9% (3501/50,822) describing good or sufficient efficacy. Nonmedical content distribution also varied significantly among the different drugs (P<.001). CONCLUSIONS Patients seeking relief from pain are highly interested in the effectiveness of drugs rather than potential side effects. Alarming trends include a significant number of tweets trivializing drug use and recreational purposes, along with a lack of awareness regarding side effects. Monitoring conversations related to analgesics on social media is essential due to common illegal web-based sales and purchases without prescriptions.
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Assessment of beliefs and attitudes about electroconvulsive therapy posted on Twitter: An observational study.
de Anta, L, Alvarez-Mon, MA, Donat-Vargas, C, Lara-Abelanda, FJ, Pereira-Sanchez, V, Gonzalez Rodriguez, C, Mora, F, Ortega, MA, Quintero, J, Alvarez-Mon, M
European psychiatry : the journal of the Association of European Psychiatrists. 2023;(1):e11
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Abstract
BACKGROUND Electroconvulsive therapy (ECT) is an effective and safe medical procedure that mainly indicated for depression, but is also indicated for patients with other conditions. However, ECT is among the most stigmatized and controversial treatments in medicine. Our objective was to examine social media contents on Twitter related to ECT to identify and evaluate public views on the matter. METHODS We collected Twitter posts in English and Spanish mentioning ECT between January 1, 2019 and October 31, 2020. Identified tweets were subject to a mixed method quantitative-qualitative content and sentiment analysis combining manual and semi-supervised natural language processing machine-learning analyses. Such analyses identified the distribution of tweets, their public interest (retweets and likes per tweet), and sentiment for the observed different categories of Twitter users and contents. RESULTS "Healthcare providers" users produced more tweets (25%) than "people with lived experience" and their "relatives" (including family members and close friends or acquaintances) (10% combined), and were the main publishers of "medical" content (mostly related to ECT's main indications). However, more than half of the total tweets had "joke or trivializing" contents, and such had a higher like and retweet ratio. Among those tweets manifesting personal opinions on ECT, around 75% of them had a negative sentiment. CONCLUSIONS Mixed method analysis of social media contents on Twitter offers a novel perspective to examine public opinion on ECT, and our results show attitudes more negative than those reflected in studies using surveys and other traditional methods.
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The Use of Prebiotics from Pregnancy and Its Complications: Health for Mother and Offspring-A Narrative Review.
García-Montero, C, Fraile-Martinez, O, Rodriguez-Martín, S, Saz, JV, Rodriguez, RA, Moreno, JMP, Labarta, JR, García-Honduvilla, N, Alvarez-Mon, M, Bravo, C, et al
Foods (Basel, Switzerland). 2023;(6)
Abstract
Pregnancy involves a metabolic reprogramming that includes changes in the gut microbiota composition in women. Evidence shows that maternal dysbiosis is linked to neonatal dysbiosis, and this factor can determine health status in adulthood. Although there is little literature available on this topic, high heterogeneity is a limitation when examining nutritional interventions. Information has been gathered to contrast the benefits of prebiotic usage, specifically in pregnancy, in its possible complications and in newborns' gut microbiota development. The objective pursued in this brief narrative review is to provide a clear summary of relevant content when searching with regard to the use of prebiotics in pregnancy, the effects in prenatal and postnatal periods, and to help in clinical decision-making in pregnancy management and lactation. A search has found that the nutritional status of the pregnant mother is key for the earliest microbial colonization in newborns, and thus intervention programs from pregnancy could assure better outcomes in both the mother and offspring. In this sense, prebiotics (administered to mothers who breastfeed or provided in formula milk) are feasible and cost-effective elements that can prevent allergies, colic, and other maladies in newborns.
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Microbiota-gut-brain axis mechanisms in the complex network of bipolar disorders: potential clinical implications and translational opportunities.
Ortega, MA, Álvarez-Mon, MA, García-Montero, C, Fraile-Martínez, Ó, Monserrat, J, Martinez-Rozas, L, Rodríguez-Jiménez, R, Álvarez-Mon, M, Lahera, G
Molecular psychiatry. 2023;(7):2645-2673
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Abstract
Bipolar disorders (BD) represent a severe leading disabling mental condition worldwide characterized by episodic and often progressive mood fluctuations with manic and depressive stages. The biological mechanisms underlying the pathophysiology of BD remain incompletely understood, but it seems that there is a complex picture of genetic and environmental factors implicated. Nowadays, gut microbiota is in the spotlight of new research related to this kind of psychiatric disorder, as it can be consistently related to several pathophysiological events observed in BD. In the context of the so-called microbiota-gut-brain (MGB) axis, it is shown to have a strong influence on host neuromodulation and endocrine functions (i.e., controlling the synthesis of neurotransmitters like serotonin or mediating the activation of the hypothalamic-pituitary-adrenal axis), as well as in modulation of host immune responses, critically regulating intestinal, systemic and brain inflammation (neuroinflammation). The present review aims to elucidate pathophysiological mechanisms derived from the MGB axis disruption and possible therapeutic approaches mainly focusing on gut microbiota in the complex network of BD. Understanding the mechanisms of gut microbiota and its bidirectional communication with the immune and other systems can shed light on the discovery of new therapies for improving the clinical management of these patients. Besides, the effect of psychiatric drugs on gut microbiota currently used in BD patients, together with new therapeutical approaches targeting this ecosystem (dietary patterns, probiotics, prebiotics, and other novelties) will also be contemplated.
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Unfolding the role of placental-derived Extracellular Vesicles in Pregnancy: From homeostasis to pathophysiology.
Ortega, MA, Fraile-Martínez, O, García-Montero, C, Paradela, A, Asunción Sánchez-Gil, M, Rodriguez-Martin, S, De León-Luis, JA, Pereda-Cerquella, C, Bujan, J, Guijarro, LG, et al
Frontiers in cell and developmental biology. 2022;:1060850
Abstract
The human placenta is a critical structure with multiple roles in pregnancy, including fetal nutrition and support, immunological, mechanical and chemical barrier as well as an endocrine activity. Besides, a growing body of evidence highlight the relevance of this organ on the maternofetal wellbeing not only during gestation, but also from birth onwards. Extracellular vesicles (EVs) are complex macromolecular structures of different size and content, acting as carriers of a diverse set of molecules and information from donor to recipient cells. Since its early development, the production and function of placental-derived EVs are essential to ensure an adequate progress of pregnancy. In turn, the fetus receives and produce their own EVs, highlighting the importance of these components in the maternofetal communication. Moreover, several studies have shown the clinical relevance of EVs in different obstetric pathologies such as preeclampsia, infectious diseases or gestational diabetes, among others, suggesting that they could be used as pathophysiological biomarkers of these diseases. Overall, the aim of this article is to present an updated review of the published basic and translational knowledge focusing on the role of placental-derived EVs in normal and pathological pregnancies. We suggest as well future lines of research to take in this novel and promising field.
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Understanding the basis of major depressive disorder in oncological patients: Biological links, clinical management, challenges, and lifestyle medicine.
Fraile-Martinez, O, Alvarez-Mon, MA, Garcia-Montero, C, Pekarek, L, Guijarro, LG, Lahera, G, Saez, MA, Monserrat, J, Motogo, D, Quintero, J, et al
Frontiers in oncology. 2022;:956923
Abstract
In recent years, the incidence of different types of cancer and patient survival have been rising, as well as their prevalence. The increase in survival in recent years exposes the patients to a set of stressful factors such as more rigorous follow-up and more aggressive therapeutic regimens that, added to the diagnosis of the disease itself, cause an increase in the incidence of depressive disorders. These alterations have important consequences for the patients, reducing their average survival and quality of life, and for these reasons, special emphasis has been placed on developing numerous screening tests and early recognition of depressive symptoms. Despite that cancer and major depressive disorder are complex and heterogeneous entities, they also share many critical pathophysiological mechanisms, aiding to explain this complex relationship from a biological perspective. Moreover, a growing body of evidence is supporting the relevant role of lifestyle habits in the prevention and management of both depression and cancer. Therefore, the present study aims to perform a thorough review of the intricate relationship between depression and cancer, with a special focus on its biological links, clinical management, challenges, and the central role of lifestyle medicine as adjunctive and preventive approaches to improve the quality of life of these patients.