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BACKGROUND The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. METHODS To identify a microRNA specific for myocarditis, we performed microRNA micro-array analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Thl7) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. RESULTS We confirmed that Thl7 cells, which are characterized by the production of inter-leukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Thl7 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:%, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. CONCLUSIONS After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.) [ABSTRACT FROM AUTHOR]

To gain a better understanding of the molecular mechanisms controlling microspore embryogenesis (ME) in triticale (× Triticosecale Wittm.), the expression patterns of 13 genes, previously identified in bread wheat to be associated with microspore-derived embryo development, were analysed. Four triticale doubled haploid (DH) lines, significantly different with respect to embryogenic potential, were studied. The gene expression profile was dissected at different points of the ME induction procedure up to the 8th day of in vitro culture (dc). RT-PCR revealed that these 13 genes were expressed during triticale ME. Variations in gene expression profiles were observed between the studied DH lines. DH28 (highly embryogenic) was the only one in which all analysed genes ( Ta.TPD1- like, TAA1b, GSTF2, GSTA2, CHI3, Tad1, XIP- R1, TaAGL14, TaNF- YA7, SERK2, SERK1, TaEXPB4, TaME1) were up-regulated during the first 8dc. In the less embryogenic DH31, TAA1b, GSTA2 and TaEXPB4 were already induced on 4dc. In DH25, ME was initiated quite efficiently but soon inhibited, which coincided with the lack of gene expression ( TaEXPB4, TaME1) or down-regulation ( Tad1, XIP- R1, TaAGL14, TaNF- YA, SERK2, SERK1) on 8dc. In the recalcitrant DH50 line, the majority of genes were expressed at a lower level or not at all, indicating disturbances in ME initiation. In this study, the molecular mechanisms involved in triticale ME induction were analysed for the first time, laying the foundation for further characterisation of specific genes controlling microspore-derived embryo development. [ABSTRACT FROM AUTHOR]

Introducción: Esta prueba consiste en recorrer 120 kilómetros entre Tuy y Santiago en un máximo de 34 horas y 40 minutos incluyendo recorrido topográfico, tiro, pista de aplicación, rápel, natación, lanzamiento de granadas y recorrido cronometrado. Objetivos: Valorar la utilidad de la preparación psicológica para maximizar el rendimiento en la Tuy-Santiago. Material y Método: La intervención se ha realizado con los dos equipos del Regimiento Príncipe n.º 3 que compitieron en 2017. Ambos participaron en dos sesiones sobre introducción a la psicología deportiva con evaluación de necesidades y otra, de nivel de activación. En el caso del San Quintín se hicieron con diez miembros en mayo, en la quincena previa a la competición. Mientras el Toledo, con trece, las repartió desde el inicio del entrenamiento en enero y febrero, lo que permitió dos más en marzo y abril, basadas en la motivación y la concentración. Terminada la competición colaboraron con una encuesta de satisfacción. Resultados: El San Quintín, que obtuvo el sexto puesto, valoró mejor el entrenamiento psicológico con un 6,75 de media, considerando positivamente los ejercicios de relajación y el establecimiento de objetivos. El Toledo quedó noveno, y tuvo opiniones muy dispares con un 5,2, desde valorar el control de la respiración, establecer metas a corto plazo y rutinas, la información sobre la evaluación, hasta no encontrar nada aplicable a su caso. En general, para futuras ocasiones, recomendaron fomentar la cohesión y mejorar la logística. Conclusiones: La preparación psicológica fue satisfactoria para la mayoría de los participantes pero se podría optimizar su efectividad con una mejor organización que le proporcionara continuidad. Parece obvia la necesidad de entrenar habilidades psicológicas para afrontar una competición tan exigente. Además, muchas de estas estrategias se pueden aplicar en la instrucción diaria complementando la formación integral del militar. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) has long been considered an immune-privileged site, with minimal interaction between immune cells, particularly of the adaptive immune system. Previously, the presence of immune cells in this organ was primarily linked to events involving disruption of the blood-brain barrier (BBB) or inflammation. However, current research has shown that immune cells are found patrolling CNS under homeostatic conditions. Specifically, T cells of the adaptive immune system are able to cross the BBB and are associated with ageing and cognitive impairment. In addition, T-cell infiltration has been observed in pathological conditions, where inflammation correlates with poor prognosis. Despite ongoing research, the role of this population in the ageing brain under both physiological and pathological conditions is not yet fully understood. In this review, we provide an overview of the interactions between T cells and other immune and CNS parenchymal cells, and examine the molecular mechanisms by which these interactions may contribute to normal brain function and the scenarios in which disruption of these connections lead to cognitive impairment. A comprehensive understanding of the role of T cells in the ageing brain and the underlying molecular pathways under normal conditions could pave the way for new research to better understand brain disorders. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc., (© 2023 British Pharmacological Society.)

Early fire detection is an efficient method to mitigate disastrous fire loss. However, developing smart low-temperature fire-warning sensors that better diminish fire hazards, especially those caused by household appliances, is still challenging. Herein, a salts-modified chitosan (salts-modified CS) based sensor with integrated fire-warning and humidity-monitoring capability is proposed using an easy assembling method. This sensor can respond to temperatures as low as 50 °C and a flame within 2 s quickly and detect relative humidity (RH) range above 50 % at 50 °C and 75 °C sensitively. This system can be reusable for multiple ignitions and works in high-humidity environments (>50 %). Furthermore, the comparison between different salts-modified CS films is carried out to elucidate the mechanism of the formation of electric current under the joint driven by temperature and humidity. Moreover, real-time temperature and RH monitoring can be achieved with a wireless transmission section. This design shows a promising approach for multifunctional CS-based sensors and paves a path to developing a new generation of smart fire-warning detectors., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: This work aimed to isolate bacterial strains with antagonist activity against Vibrio parahaemolyticus, the causative agent of acute hepatopancreatic necrosis disease (VP AHPND ) that was isolated from outbreaks in Mexico. Here, we report the draft genome sequences of two antagonistic strains, isolated from saline sediment in Sonora, Mexico., Methods: Cross-streak and well diffusion tests were employed to find the bacterial strains with higher inhibitory activity against VP AHPND . The whole genomes of B. pumilus 36R ATNSAL and B. safensis 13L LOBSAL were sequenced using Ion Torrent TM (PGM) and Illumina Miseq TM platforms, respectively. Annotation was performed using the RAST server, and the genes involved in the biosynthesis of bacterial secondary metabolites were predicted using antiSMASH., Results: Two bacterial isolates, B. safensis 13L LOBSAL and B. pumilus 36R ATNSAL, were chosen based on their strong antagonistic profiles. The genome of 36R ATNSAL was 3.94 Mbp in length and contained 3824 genes and a total of 4116 coding sequences (CDSs); the genome of 13L LOBSAL was 3.68 Mbp and contained 3619 genes and 3688 CDSs. Twenty-eight and 32 biosynthetic gene clusters responsible for putative antimicrobial metabolite production were identified in 36R ATNSAL and 13L LOBSAL, respectively., Conclusions: The two strains 13L LOBSAL and 36R ATNSAL showed excellent probiotic profiles in vitro. The genome sequences will help with the mining and reconstruction of metabolic pathways in Bacillus strains. Genome sequence-guided strain improvement could augment the probiotic potential of Bacillus strains for applications in shrimp aquaculture., Competing Interests: Competing interests None declared., (Copyright © 2022. Published by Elsevier Ltd.)

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69-/- mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

In the last decade, approaches based on T cells and their immunomodulatory receptors have emerged as a solid improvement in treatments for various types of cancer. However, the roles of these molecules in the therapeutic context of autoimmune and cardiovascular diseases are still relatively unexplored. Here, we review the best known and most commonly used immunomodulatory T cell receptors in clinical practice (PD-1 and CTLA-4), along with the rest of the receptors with known functions in animal models, which have great potential as modulators in human pathologies in the medium term. Among these other receptors is the receptor CD69, which has recently been described to be expressed in mouse and human T cells in autoimmune and cardiovascular diseases and cancer. However, inhibition of these receptors individually or in combination by drugs or monoclonal antibodies generates a loss of immunological tolerance and can trigger multiple autoimmune disorders in different organs and immune-related adverse effects. In the coming decades, knowledge on the functions of different immunomodulatory receptors will be pivotal for the development of new and better therapies with less harmful side effects. In this review, we discuss the roles of these receptors in the control of immunity from a perspective focused on therapeutic potential in not only cancer but also autoimmune diseases, such as systemic lupus erythematosus, autoimmune diabetes and rheumatoid arthritis, and cardiovascular diseases, such as atherosclerosis, acute myocardial infarction, and myocarditis.

Objectives: This study reports the draft genome sequence of Pseudoalteromonas piscicida strain 36Y_RITHPW, a marine Gammaproteobacteria that synthesises bioactive compounds with antagonistic activity against Vibrio parahaemolyticus, a multidrug-resistant strain that is the causative agent of acute hepatopancreatic necrosis disease (AHPND), reported in shrimp farm outbreaks from Asia to Mexico with mortality rates of 80-100%., Methods: The genome of P. piscicida 36Y_RITHPW was sequenced with an Ion Torrent™ Personal Genome Machine™ (PGM) platform. A total of 606805 reads were constructed for a 308.48Mbp and 33.5×coverage. A high-quality draft assembly and ordering of contigs was obtained with Mauve. The annotation was obtained with RAST and antiSMASH., Results: The genome size consists of 5.15Mbp, with a total of 4548 genes, 4217 protein-coding sequences and a GC content of 43.3%. Several resistance genes as well as other genes involved in the production of bacteriocins and ribosomally synthesised antibacterial peptides are also present., Conclusions: Mining of this draft genome provides valuable information to explain the antagonistic capacity of P. piscicida 36Y_RITHPW, a useful strain as a potential probiotic in shrimp aquaculture against pathogenic V. parahaemolyticus., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Background: Although the role of Th17 and regulatory T cells in the progression of atherosclerosis has been highlighted in recent years, their molecular mediators remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/regulatory T cell immunity, and atherosclerosis development in animal models and in patients with subclinical disease., Methods: Low-density lipoprotein receptor-deficient chimeric mice expressing or not expressing CD69 on either myeloid or lymphoid cells were subjected to a high fat diet. In vitro functional assays with human T cells were performed to decipher the mechanism of the observed phenotypes. Expression of CD69 and NR4A nuclear receptors was evaluated by reverse transcription-polymerase chain reaction in 305 male participants of the PESA study (Progression of Early Subclinical Atherosclerosis) with extensive (n=128) or focal (n=55) subclinical atherosclerosis and without disease (n=122)., Results: After a high fat diet, mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/regulatory T cell ratio in blood. Oxidized low-density lipoprotein was shown to bind specifically and functionally to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% CI, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the expression of NR4A1, the level of oxidized low-density lipoprotein, and the counts of different leucocyte subsets., Conclusions: CD69 depletion from the lymphoid compartment promotes a Th17/regulatory T cell imbalance and exacerbates the development of atherosclerosis. CD69 binding to oxidized low-density lipoprotein on T cells induces the expression of anti-inflammatory transcription factors. Data from a cohort of the PESA study with subclinical atherosclerosis indicate that CD69 expression in PBLs inversely correlates with the presence of disease. The expression of CD69 remained an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.

Thymus-derived regulatory T (tTreg) cells are key to preventing autoimmune diseases, but the mechanisms involved in their development remain unsolved. Here, we show that the C-type lectin receptor CD69 controls tTreg cell development and peripheral Treg cell homeostasis through the regulation of BIC/microRNA 155 (miR-155) and its target, suppressor of cytokine signaling 1 (SOCS-1). Using Foxp3-mRFP/ cd69 +/ - or Foxp3-mRFP/ cd69 -/- reporter mice and short hairpin RNA (shRNA)-mediated silencing and miR-155 transfection approaches, we found that CD69 deficiency impaired the signal transducer and activator of transcription 5 (STAT5) pathway in Foxp3 + cells. This results in BIC/miR-155 inhibition, increased SOCS-1 expression, and severely impaired tTreg cell development in embryos, adults, and Rag2 -/- γc -/- hematopoietic chimeras reconstituted with cd69 -/- stem cells. Accordingly, mirn155 - / - mice have an impaired development of CD69 + tTreg cells and overexpression of the miR-155-induced CD69 pathway, suggesting that both molecules might be concomitantly activated in a positive-feedback loop. Moreover, in vitro -inducible CD25 + Treg (iTreg) cell development is inhibited in Il2r γ - / - / cd69 - / - mice. Our data highlight the contribution of CD69 as a nonredundant key regulator of BIC/miR-155-dependent Treg cell development and homeostasis., (Copyright © 2017 American Society for Microbiology.)

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69 -/- mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody-mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69 -/- mice. Finally, IL-17 blockade in cd69 -/- mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69 -/- and Rag2 -/- γ c -/- mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69 -/- mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation., Competing Interests: The authors declare no conflict of interests., (Copyright © 2016 by the American Society of Nephrology.)

The activation marker CD69 is expressed by skin γδ T cells. Here we found that CD69 controlled the aryl hydrocarbon receptor (AhR)-dependent secretion of interleukin 22 (IL-22) by γδ T cells, which contributed to the development of psoriasis induced by IL-23. CD69 associated with the aromatic-amino-acid-transporter complex LAT1-CD98 and regulated its surface expression and uptake of L-tryptophan (L-Trp) and the intracellular quantity of L-Trp-derived activators of AhR. In vivo administration of L-Trp, an inhibitor of AhR or IL-22 abrogated the differences between CD69-deficient mice and wild-type mice in skin inflammation. We also observed LAT1-mediated regulation of AhR activation and IL-22 secretion in circulating Vγ9(+) γδ T cells of psoriatic patients. Thus, CD69 serves as a key mediator of the pathogenesis of psoriasis by controlling LAT1-CD98-mediated metabolic cues., Competing Interests: Authors declare no competing financial interest.

Although FoxP3(+) regulatory T cells are key players in the maintenance of immune tolerance and autoimmunity, the lack of specific markers constitute an obstacle to their use for immunotherapy protocols. In this study, we have investigated the role of the C-type lectin receptor CD69 in the suppressor function of Tregs and maintenance of immune tolerance towards harmless inhaled antigens. We identified a novel FoxP3(+)CD69(+) Treg subset capable to maintain immune tolerance and protect to developing inflammation. Although CD69(+) and CD69(-)FoxP3(+) Tregs exist in homeostasis, only CD69-expressing Tregs express high levels of CTLA-4, ICOS, CD38 and GITR suppression-associated markers, secrete high amounts of TGFβ and have potent suppressor activity. This activity is regulated by STAT5 and ERK signaling pathways and is impaired by antibody-mediated down-regulation of CD69 expression. Moreover, immunotherapy with FoxP3(+)CD69(+) Tregs restores the homeostasis in Cd69(-/-) mice, that fail to induce tolerance, and is also highly proficient in the prevention of inflammation. The identification of the FoxP3(+)CD69(+) Treg subset paves the way toward the development of new therapeutic strategies to control immune homeostasis and autoimmunity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study evaluated the relationship between the physicochemical properties, membrane permeability and in vitro giardicidal activity of twenty nine benzimidazole derivatives (1-7n). The retention time data from reverse phase high performance chromatography (RP-HPLC) were used to estimate aqueous solubility and lipophilicity of these compounds. The apparent permeability was determined using Caco-2 cell monolayer. The calculation of some descriptors, such as Clog P, PSA, was performed using ACD labs software. For benzimidazole derivatives with NHCOOCH(3), CH(3), NH(2), SH and SCH(3) groups at the 2-position, a quadratic type of regression model was obtained with giardicidal activity and aqueous solubility or lipophilicity. On the other hand, giardicidal activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives was influenced by lipophilicity, hydrogen bond donors and molecular volume but it was not determined by their apparent permeability in Caco-2 cell line., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)