Morphological differentiation of peritumoral brain zone microglia.

The Peritumoral Brain Zone (PBZ) contributes to Glioblastoma (GBM) relapse months after the resection of the original tumor, which is influenced by a variety of pathological factors. Among those, microglia are recognized as one of the main regulators of GBM progression and probably relapse. Although microglial morphology has been analyzed inside GBM and its immediate surroundings, it has not been objectively characterized throughout the PBZ. Thus, we aimed to perform a thorough characterization of microglial morphology in the PBZ and its likely differentiation not just from the tumor-associated microglia but from control tissue microglia. For this purpose, Sprague Dawley rats were intrastriatally implanted with C6 cells to induce a GBM formation. Gadolinium-based magnetic resonance imaging (MRI) was performed to locate the tumor and to define the PBZ (2 mm beyond the tumor border), thus delimitating the different regions of interest (ROIs: core tumoral zone and immediate interface; contralateral striatum as control). Brain slices were obtained and immunolabeled with the microglia marker Iba-1. Sixteen morphological parameters were measured for each cell, significative differences were found in all parameters when comparing the four ROIs. To determine if PBZ microglia could be morphologically differentiated from microglia in other ROIs, hierarchical clustering analysis was performed, revealing that microglia can be separated into four morphologically differentiated clusters, each of them mostly integrated by cells sampled in each ROI. Furthermore, a classifier based on linear discriminant analysis, including only three morphological parameters, categorized microglial cells across the studied ROIs and showed a gradual transition between them. The robustness of this classification was assessed through principal component analysis with the remaining 13 morphological parameters, corroborating the obtained results. Thus, in this study we provided objective and quantitative evidence that PBZ microglia represent a differentiable microglial morphotype that could contribute to the recurrence of GBM in this area.

Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification.

Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.

Liver cancer: A geometric approach to fractals and scaling analysis.

In the study of liver cancer, invasive techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) are used. In the present work, an in vivo 3D study will be carried out using MRI and CT images, using scaling dynamics, that is, calculating critical exponents of local roughness and fractal dimension. The results obtained for stages IA, IIA, and IIIA in liver cancer correspond to what was proposed by F. Family and T. Vicsek (1991).

Deleterious and protective effects of epothilone-D alone and in the context of amyloid ß- and tau-induced alterations.

Amyloid-ß (Aß) and hyperphosphorylated tau (P-tau) are Alzheimer's disease (AD) biomarkers that interact in a complex manner to induce most of the cognitive and brain alterations observed in this disease. Since the neuronal cytoskeleton is a common downstream pathological target of tau and Aß, which mostly lead to augmented microtubule instability, the administration of microtubule stabilizing agents (MSAs) can protect against their pathological actions. However, the effectiveness of MSAs is still uncertain due to their state-dependent negative effects; thus, evaluating their specific actions in different pathological or physiological conditions is required. We evaluated whether epothilone-D (Epo-D), a clinically used MSA, rescues from the functional and behavioral alterations produced by intracerebroventricular injection of Aß, the presence of P-tau, or their combination in rTg4510 mice. We also explored the side effects of Epo-D. To do so, we evaluated hippocampal-dependent spatial memory with the Hebb-Williams maze, hippocampal CA1 integrity and the intrinsic and synaptic properties of CA1 pyramidal neurons with the patch-clamp technique. Aß and P-tau mildly impaired memory retrieval, but produced contrasting effects on intrinsic excitability. When Aß and P-tau were combined, the alterations in excitability and spatial reversal learning (i.e., cognitive flexibility) were exacerbated. Interestingly, Epo-D prevented most of the impairments induced Aß and P-tau alone and combined. However, Epo-D also exhibited some side effects depending on the prevailing pathological or physiological condition, which should be considered in future preclinical and translational studies. Although we did not perform extensive histopathological evaluations or measured microtubule stability, our findings show that MSAs can rescue the consequences of AD-like conditions but otherwise be harmful if administered at a prodromal stage of the disease.

Multi-sensorial perceptions of risk: the aesthetics behind (muco)cutaneous leishmaniasis-related stigma in Ecuador.

Previous research on the stigma associated with cutaneous leishmaniasis, a vector-transmitted parasitic disease, focuses on aesthetic appearance affectation as the leading cause of stigmatisation. However, Indigenous populations in the hinterland of Amazonian Ecuador trigger stigma expressions by recognising (muco)cutaneous leishmaniasis, primarily through atypical smell, followed by the odd voice sound, appearance and taste. This empirical way of recognising symptoms relies on embodied forms of identifying a disease, contrasting the Western supremacy of visuality and demanding to be understood via multi-sensorial anthropology. Through ethnographic research and data retrieved from eighty-three semistructured interviews and fifteen focus groups in seven Ecuadorian ethnic groups - including six Indigenous groups in the Amazon region - this paper analyses how the sensorium is a health thermometer. Findings reveal that differentiated cultural responses to a sense of peril, contagion and social (self)rejection, understood as stigma expressions, are linked to the holistic approach to health (or well-being) shared by Indigenous populations. In forest societies, well-being is explained through successful (non-)human relationships, and disease permeates through bodies that lack balanced relations.

Selective Photooxidation of Valencene and Thymol with Nano-TiO2 and O2 as Oxidant.

The selective photocatalytic oxidation with O2 as oxidant of valencene and thymol was evaluated using nanostructured TiO2 under UV-Vis radiation at atmospheric conditions. The effect of the morphology and optical properties of TiO2 nanotubes and aminate nanoparticles was studied. Different scavengers were used to detect the presence of positive holes (h+), electrons (e-), hydroxyl radicals (•OH), and the superoxide radical anion (O2-) during the photooxidation reaction. Superoxide anion radical is the main oxidizing specie formed, which is responsible for the selective formation of nootkatone and thymoquinone using aminated TiO2 nanoparticles under 400 nm radiation.

Sociodemographic Variables and Body Mass Index Associated with the Risk of Eating Disorders in Spanish University Students.

BACKGROUND: The passage through university is a complex experience that can heighten personal susceptibility to eating disorders. The objective of this research is to determine how gender, age, course, educational faculty, and body mass index (BMI) can influence the risk of eating disorders among university students. METHOD: A transversal and descriptive study is conducted with a sample of 516 Spanish students (57.2% female, 42.8% male; Mage = 21.7, SDage = 4.1) following 26 university degrees. The Inventory Eating Disorder-Reference criterion (EDI-3-RF) was administered to the students. Contingency tables were used between categorical variables with the chi-squared statistic, at a significance level of p < 0.05. The Student t-test was used for two independent samples and a one-way ANOVA test with the post hoc Bonferroni test for more than two groups. Pearson's correlation and a simple linear regression analysis were used to analyze the relationship between the variables in its quantitative version. RESULTS: It was found that the female students enrolled in the second year presented a greater obsession with thinness and body dissatisfaction (p = 0.029; d = 0.338); the male students practiced more physical exercise to control their weight (p = 0.003); and that students under the age of twenty (p < 0.010; d = 0.584) and students from both the Health (p = 0.0.13) and Law (p = 0.021) educational faculties showed greater bulimic behavior (d = 0.070). More females are underweight (z = 2.8), and more men are overweight (z = 2.4). Normal-weight students scored significantly higher in thinness obsession (p = 0.033). Overweight students scored significantly higher on thinness obsession (p < 0.001) and body dissatisfaction (p < 0.001). Obese students scored significantly higher on body dissatisfaction (p = 0.04). CONCLUSIONS: The data obtained in this study, reinforce the hypothesis that the female gender, at an age within the limits of early adolescence, in the first year of the degree courses, with specific university qualifications, and a high BMI constituted factors that could provoke an eating disorder. Consequently, it is necessary to implement preventive measures adapted to the circumstances of each university student.

Hallazgos en tomografía de tórax en el seguimiento a 4, 8 y 12 meses después de una neumonía grave por COVID-19 / Chest Tomography Findings in Follow-Up at 4, 8 and 12 Months after Severe COVID-19 Pneumonia

Introducción: el SARS-CoV-2 causa daño multiorgánico, con predilección al epitelio respiratorio. Los estudios de imagen en tórax han sido determinantes en muchas patologías y, durante la reciente pandemia, no fue excepción. En el seguimiento con tomografía de tórax post COVID-19 en varias series, se ha observado persistencia de lesiones al egreso y a lo largo de varios meses. El objetivo del trabajo fue describir los hallazgos tomográficos en pacientes con seguimiento hasta un año post egreso hospitalario por COVID-19 moderado-grave. Material y métodos: estudio retrospectivo, observacional, de pacientes hospitalizados por COVID-19 moderado-grave de marzo 2020 a marzo 2022 en el hospital del ISSSTE, Chiapas-México; con prueba RT-PCR SARS-CoV-2 positiva, TC de hospitalización y de seguimiento posterior al egreso (0-4 meses; 4-8 meses; 8-12 meses). Se utilizó la terminología de la sociedad Fleischner. Además, se evaluó la extensión por lóbulo afectado (>75%, 75-50%, 50-25%, <25%). Resultados: Se estudiaron 27 pacientes, 74% hombres, edad promedio 56 años. El patrón tomográfico predominante al ingreso fue el mixto con 56% y extensión pulmonar >75%; vidrio despulido 30% y 11% consolidación. Al cuarto y octavo mes el patrón mixto fue el más frecuente, al doceavo mes persistía en el 33% de los pacientes y en el 30% de los casos la tomografía fue normal. Conforme pasaron los meses, la extensión del daño fue limitándose. Conclusión: el seguimiento con tomografía en COVID-19 moderado-grave es indiscutible. Permite identificar con precisión el patrón tomográfico en los diferentes momentos de la enfermedad, optimizar el tratamiento y disminuir las secuelas.

Arbuscular mycorrhizal fungi enhance monoterpene production in red clover (Trifolium pratense L.): a potential tool for pest control.

The possibility of modifying terpene production in plants is a defensive strategy that has been studied in conjunction with their biosynthetic pathways. A biotic factor such as Arbuscular Mycorrhizal Fungi (AMF) could modify terpene production in Trifolium pratense L. In this work, the enzymatic production of monoterpenes in Superqueli INIA cultivar with two AMF was evaluated via HeadSpace-Gas Chromatography (HS-GC). A significant increase of (S)-limonene was found in plants inoculated with Claroideoglomus claroideum as well as with the AMF mix (genera Scutellospora, Acaulospora and Glomus). Moreover, significant increases in other monoterpenes such as (-)-ß-pinene, myrcene, linalool, were observed. Results showed higher monoterpene production capacities in the Superqueli-INIA cultivar, suggesting the participation of monoterpene synthases (MTS). The significant rise of (S)-limonene in red clover plants inoculated with AMF suggests this strategy could be implemented in an agronomical manage for controlling the H. obscurus, the primary pest.

Conclusiones de las XI Jornadas del Grupo Avilés sobre Medicina del Deporte 3 y 4 de Octubre de 2022 (Barcelona) / Conclusões da XI Conferência do Grupo Aviles de Medicina Esportiva, 3 e 4 de outubro de 2022 (Barcelona) / Conclusions of the XI Conference of the Aviles Group on Sports Medicine, October 3 and 4, 2022 (Barcelona)

El Grupo de Trabajo Avilés fue impulsado por el Consejo Superior de Deportes en 2009 y está formado por representantes de los Centros de Medicina dela Educación Física y el Deporte de todas las comunidades autónomas que cuentan con estas infraestructuras y representantes de centros de medicinadel deporte de centros de tecnificación, centros municipales de medicina del deporte y la Agencia Española de Protección de la Salud en el Deporte. Comoobjetivos de este grupo de trabajo figuran la coordinación entre estas estructuras autonómicas de la medicina del deporte, el planteamiento de solucionescomunes a las diferentes problemáticas que sufren cada uno de los centros y el ser un grupo de asesoramiento, en los diferentes ámbitos de la medicinade la educación física y el deporte, para el Consejo Superior de Deportes.Este grupo de trabajo se reúne periódicamente; en su última reunión, celebrada en Barcelona el 3 y 4 de octubre de 2022, se acordaron una serie deconclusiones, en relación a la muerte súbita y las arritmias en el deporte, el SARS Cov-2, la prevención, la salud mental, la diversidad sexual y laespecialidad MIR.(AU)

The Avilés Working Group was promoted by the National Sports Council in 2009 and is made up of representatives of Physical Education and SportsMedicine Centers of all the autonomous communities that have these infrastructures, Sports Technification Centers, municipal Sports Medicine Centersand the Spanish Agency for Health Protection in Sport. The objectives of this working group include the coordination between these autonomousstructures of Sports Medicine, the proposal of common solutions to the different problems suffered by each of the centers and to be an advisory group inthe different areas of the Physical Education and Sports Medicine, for the National Sports Council.This working group meets periodically; at its last online meeting, held in Barcelona on October 3-4, 2022, a series of conclusions were agreed in relationto sudden death and arrytmias in sport, SARS Cov-2, prevention, mental health, sexual diversity and the MIR specialty.(AU)

O grupo de Trabalho Avilés foi incentivado pelo Conselho Superior de Esportes em 2009. É composto por representantes dos Centros de Medicina daEducação Física e Esporte de todas as comunidades autônomas que contam com estas infraestruturas, bem como representantes dos centros de medicinado esporte de centros técnicos, centros municipais de medicina do esporte e da Agencia Espanhola de Proteção da saúde no Esporte. Como objetivos detrabalho desde grupo, figuram a coordenação entre estas estruturas autonômicas da medicina do esporte, a criação de soluções comuns as diferentesproblemáticas que sofrem cada um dos centros, além de ser um grupo de assessoramento, nos diferentes âmbitos da medicina da educação física e doesporte, para o Conselho Superior de Esportes.Este grupo de trabalho se reúne periodicamente; Em sua última reunião, realizada em Barcelona de 3 e 4 de outubro de 2022, foi acordada uma série deconclusões em relação à morte súbita e arritmias no esporte, SARS Cov-2, prevenção, saúde mental, diversidade sexual e especialidade MIR.(AU)

Amyloid Beta Alters Prefrontal-dependent Functions Along with its Excitability and Synaptic Plasticity in Male Rats.

Prefrontal cortex (PFC)-related functions, such as working memory (WM) and cognitive flexibility (CF), are among the first to be altered at early stages of Alzheimer's disease (AD). Likewise, transgenic AD models carrying different AD-related mutations, mostly linked to the overproduction of amyloid beta (Aß) and other peptides, show premature behavioral and functional symptoms associated with PFC alterations. However, little is known about the effects of intracerebral or intra-PFC Aß infusion on WM and CF, as well as on pyramidal cell excitability and plasticity. Thus, here we evaluated the effects of a single Aß injection, directly into the PFC, or its intracerebroventricular (icv) application, on PFC-dependent behaviors and on the intrinsic and synaptic properties of layer V pyramidal neurons in PFC slices. We found that a single icv Aß infusion reduced learning and performance of a delayed non-matching-to-sample WM task and prevented reversal learning in a matching-to-sample version of the task, several weeks after its infusion. The inhibition of WM performance was reproduced more potently by a single PFC Aß infusion and was associated with Aß accumulation. This behavioral disruption was related to increased layer V pyramidal cell firing, larger sag membrane potential, increased fast after-hyperpolarization and a failure to sustain synaptic long-term potentiation, even leading to long-term depression, at both the hippocampal-PFC pathway and intracortical synapses. These findings show that Aß can affect PFC excitability and synaptic plasticity balance, damaging PFC-dependent functions, which could constitute the foundations of the early alterations in executive functions in AD patients.

Abnormal innate and learned behavior induced by neuron-microglia miscommunication is related to CA3 reconfiguration.

Neuron-microglia communication through the Cx3cr1-Cx3cl1 axis is essential for the development and refinement of neural circuits, which determine their function into adulthood. In the present work we set out to extend the behavioral characterization of Cx3cr1-/- mice evaluating innate behaviors and spatial navigation, both dependent on hippocampal function. Our results show that Cx3cr1-deficient mice, which show some changes in microglial and synaptic terminals morphology and density, exhibit alterations in activities of daily living and in the rapid encoding of novel spatial information that, nonetheless, improves with training. A neural substrate for these cognitive deficiencies was found in the form of synaptic dysfunction in the CA3 region of the hippocampus, with a marked impact on the mossy fiber (MF) pathway. A network analysis of the CA3 microcircuit reveals the effect of these synaptic alterations on the functional connectivity among CA3 neurons with diminished strength and topological reorganization in Cx3cr1-deficient mice. Neonatal population activity of the CA3 region in Cx3cr1-deficient mice shows a marked reorganization around the giant depolarizing potentials, the first form of network-driven activity of the hippocampus, suggesting that alterations found in adult subjects arise early on in postnatal development, a critical period of microglia-dependent neural circuit refinement. Our results show that interruption of the Cx3cr1-Cx3cl1/neuron-microglia axis leads to changes in CA3 configuration that affect innate and learned behaviors.

Microtubules as Regulators of Neural Network Shape and Function: Focus on Excitability, Plasticity and Memory.

Neuronal microtubules (MTs) are complex cytoskeletal protein arrays that undergo activity-dependent changes in their structure and function as a response to physiological demands throughout the lifespan of neurons. Many factors shape the allostatic dynamics of MTs and tubulin dimers in the cytosolic microenvironment, such as protein-protein interactions and activity-dependent shifts in these interactions that are responsible for their plastic capabilities. Recently, several findings have reinforced the role of MTs in behavioral and cognitive processes in normal and pathological conditions. In this review, we summarize the bidirectional relationships between MTs dynamics, neuronal processes, and brain and behavioral states. The outcomes of manipulating the dynamicity of MTs by genetic or pharmacological approaches on neuronal morphology, intrinsic and synaptic excitability, the state of the network, and behaviors are heterogeneous. We discuss the critical position of MTs as responders and adaptative elements of basic neuronal function whose impact on brain function is not fully understood, and we highlight the dilemma of artificially modulating MT dynamics for therapeutic purposes.

Hyperphosphorylated Tau Relates to Improved Cognitive Performance and Reduced Hippocampal Excitability in the Young rTg4510 Mouse Model of Tauopathy.

BACKGROUND: Tau hyperphosphorylation at several sites, including those close to its microtubule domain (MD), is considered a key pathogenic event in the development of tauopathies. Nevertheless, we recently demonstrated that at the very early disease stage, tau phosphorylation (pTau) at MD sites promotes neuroprotection by preventing seizure-like activity. OBJECTIVE: To further support the notion that very early pTau is not detrimental, the present work evaluated the young rTg4510 mouse model of tauopathy as a case study. Thus, in mice at one month of age (PN30-35), we studied the increase of pTau within the hippocampal area as well as hippocampal and locomotor function. METHODS: We used immunohistochemistry, T-maze, nesting test, novel object recognition test, open field arena, and electrophysiology. RESULTS: Our results showed that the very young rTg4510 mouse model has no detectable changes in hippocampal dependent tasks, such as spontaneous alternation and nesting, or in locomotor activity. However, at this very early stage the hippocampal neurons from PN30-35 rTg4510 mice accumulate pTau protein and exhibit changes in hippocampal oscillatory activity. Moreover, we found a significant reduction in the somatic area of pTau positive pyramidal and granule neurons in the young rTg4510 mice. Despite this, improved memory and increased number of dendrites per cell in granule neurons was found. CONCLUSION: Altogether, this study provides new insights into the early pathogenesis of tauopathies and provides further evidence that pTau remodels hippocampal function and morphology.

Immune responses to mRNA vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory rheumatic diseases.

BACKGROUND: Patients with immune-mediated rheumatic diseases (IMRDs) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-CoV-2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-CoV-2 mRNA vaccines. AIMS: To fully characterise B-cell and T-cell immune responses elicited by mRNA SARS-CoV-2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine's immunogenicity. METHODS: Humoral, CD4 and CD8 immune responses were investigated in 100 naïve patients with SARS-CoV-2 with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-CoV-2 mRNA vaccine. Responses were compared with age, gender and disease-matched patients with IMRD not receiving immunosuppressors and with healthy controls. RESULTS: Patients with IMRD showed decreased seroconversion rates (80% vs 100%, p=0.03) and cellular immune responses (75% vs 100%, p=0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titres were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines. CONCLUSIONS: Patients with IMRD exhibit impaired SARS-CoV-2 vaccine immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine's immunogenicity.

Main olfactory bulb reconfiguration by prolonged passive olfactory experience correlates with increased brain-derived neurotrophic factor and improved innate olfaction.

The main olfactory bulb (MOB) is highly plastic and constantly reconfiguring its function and structure depending on sensory experience. Despite the extensive evidence of anatomical, functional and behavioural changes in the olfactory system induced by highly variable olfactory experiences, it is still unknown whether prolonged passive odour experience could reconfigure the MOB at its input and network activity levels and whether these changes impact innate olfaction. Here, by measuring odour-induced glomerular activation, MOB network activity and innate olfactory behaviours, we described a profound MOB reconfiguration induced by prolonged passive olfactory experience in adult animals that impacts MOB input integration at the glomerular layer including an increase in the activated glomerular area and signal intensity, which is combined with a refinement in the number of activated glomeruli and less-overlapped glomerular maps. We also found that prolonged passive olfactory experience dramatically changes MOB population activity in the presence and absence of odours, which is reflected as a decrease in slow oscillations (<12 Hz) and an increase in fast oscillations (>12 Hz). All these functional changes in awake and anaesthetized mice correlate with an increase in brain-derived neurotrophic factor (BDNF) and with improved innate olfactory responses such as habituation/dishabituation and innate preference/avoidance. Our study shows that prolonged passive olfactory experience in adult animals produces a dramatic reconfiguration of the MOB network, possibly driven by BDNF, that improves innate olfactory responses.

Optimization of enzymatic parameters for the production of formononetin from red clover (Trifolium pratense L.) through a response surface methodology.

Trifolium pratense, is a forage found worldwide, but it is negatively impacted by the clover root borer, Hylastinus obscurus. Methanolic extraction has been reported for isolating formononetin from vegetal tissues, with an antifeeding effect on H. obscurus. However, this methodology is time-consuming and also extracts other secondary metabolites, whereas enzymatic assays can provide higher specificity. Hence, the objective of this work was to determine the optimal conditions in pH, temperature, and incubation time for the activity of isoflavone synthase via a response surface model. Once these parameters were optimized, the concentration of formononetin in cultivars and experimental lines of T. pratense was evaluated enzymatically. The results showed that the best condition for developing the enzymatic assay was pH 9.1 with an incubation at 34.5 °C for 155 min. The formononetin content fluctuated between 0.74 and 1.96 mg/g of fresh weight, where Precoz-3, Precoz-1, and Superqueli-INIA presented the highest production.

Perinatal inflammation and gestational intermittent hypoxia disturbs respiratory rhythm generation and long-term facilitation in vitro: Partial protection by acute minocycline.

Perinatal inflammation triggers breathing disturbances early in life and affects the respiratory adaptations to challenging conditions, including the generation of amplitude long-term facilitation (LTF) by acute intermittent hypoxia (AIH). Some of these effects can be avoided by anti-inflammatory treatments like minocycline. Since little is known about the effects of perinatal inflammation on the inspiratory rhythm generator, located in the preBötzinger complex (preBötC), we tested the impact of acute lipopolysaccharide (LPS) systemic administration (sLPS), as well as gestational LPS (gLPS) and gestational chronic IH (gCIH), on respiratory rhythm generation and its long-term response to AIH in a brainstem slice preparation from neonatal mice. We also evaluated whether acute minocycline administration could influence these effects. We found that perinatal inflammation induced by sLPS or gLPS, as well as gCIH, modulate the frequency, signal-to-noise ratio and/or amplitude (and their regularity) of the respiratory rhythm recorded from the preBötC in the brainstem slice. Moreover, all these perinatal conditions inhibited frequency LTF and amplitude long-term depression (LTD); gCIH even induced frequency LTD of the respiratory rhythm after AIH. Some of these alterations were not observed in slices pre-treated in vitro with minocycline, when compared with slices obtained from naïve pups, suggesting that ongoing inflammatory conditions affect respiratory rhythm generation and its plasticity. Thus, it is likely that alterations in the inspiratory rhythm generator and its adaptive responses could contribute to the respiratory disturbances observed in neonates that suffered from perinatal inflammatory challenges.

Laser photo-thermal therapy of epithelial carcinoma using pterin-6-carboxylic acid conjugated gold nanoparticles.

Gold nanoparticles functionalized with folic acid toward the internalization into cancer cells have received considerable attention recently. Folic acid is recognized by folate receptors, which are overexpressed in several cancer cells; it is limited in normal cells. In this work, pterin-6-carboxylic acid is proposed as an agonist of folic acid since the pterin-6-carboxylic acid structure has a pterin moiety, the same as folic acid that is recognized by the folate receptor. Here a simple photochemical synthesis of gold nanoparticles functionalized with pterin-6-carboxylic acid is studied. These conjugates were used to cause photothermal damage of HeLa cells irradiating with a diode laser of 808 nm. Pterin-6-carboxylic acid-conjugated gold nanoparticles caused the death of the cell after near-infrared irradiation, dose-dependently. These results indicate a possible internalization of AuNPs via folate receptor-mediated endocytosis due to the recognition or interaction between the folate receptors of HeLa cells and pterin, P6CA.