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1.
Nature ; 611(7937): 794-800, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36323785

RESUMEN

Protective immunity relies on the interplay of innate and adaptive immune cells with complementary and redundant functions. Innate lymphoid cells (ILCs) have recently emerged as tissue-resident, innate mirror images of the T cell system, with which they share lineage-specifying transcription factors and effector machinery1. Located at barrier surfaces, ILCs are among the first responders against invading pathogens and thus could potentially determine the outcome of the immune response2. However, so far it has not been possible to dissect the unique contributions of ILCs to protective immunity owing to limitations in specific targeting of ILC subsets. Thus, all of the available data have been generated either in mice lacking the adaptive immune system or with tools that also affect other immune cell subsets. In addition, it has been proposed that ILCs might be dispensable for a proper immune response because other immune cells could compensate for their absence3-7. Here we report the generation of a mouse model based on the neuromedin U receptor 1 (Nmur1) promoter as a driver for simultaneous expression of Cre recombinase and green fluorescent protein, which enables gene targeting in group 2 ILCs (ILC2s) without affecting other innate and adaptive immune cells. Using Cre-mediated gene deletion of Id2 and Gata3 in Nmur1-expressing cells, we generated mice with a selective and specific deficiency in ILC2s. ILC2-deficient mice have decreased eosinophil counts at steady state and are unable to recruit eosinophils to the airways in models of allergic asthma. Further, ILC2-deficient mice do not mount an appropriate immune and epithelial type 2 response, resulting in a profound defect in worm expulsion and a non-protective type 3 immune response. In total, our data establish non-redundant functions for ILC2s in the presence of adaptive immune cells at steady state and during disease and argue for a multilayered organization of the immune system on the basis of a spatiotemporal division of labour.


Asunto(s)
Sistema Inmunológico , Inmunidad Innata , Linfocitos , Animales , Ratones , Asma/genética , Asma/inmunología , Asma/patología , Modelos Animales de Enfermedad , Eosinófilos/patología , Inmunidad Innata/inmunología , Linfocitos/clasificación , Linfocitos/inmunología , Proteínas Fluorescentes Verdes , Sistema Inmunológico/citología , Sistema Inmunológico/inmunología , Sistema Inmunológico/patología
2.
Nucleic Acids Res ; 51(18): 9672-9689, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37638761

RESUMEN

Enhancer activation by the MLR family of H3K4 mono-methyltransferases requires proper recognition of histones for the deposition of the mono-methyl mark. MLR proteins contain two clusters of PHD zinc finger domains implicated in chromatin regulation. The second cluster is the most highly conserved, preserved as an ancient three finger functional unit throughout evolution. Studies of the isolated 3rd PHD finger within this cluster suggested specificity for the H4 [aa16-20] tail region. We determined the histone binding properties of the full three PHD finger cluster b module (PHDb) from the Drosophila Cmi protein which revealed unexpected recognition of an extended region of H3. Importantly, the zinc finger spacer separating the first two PHDb fingers from the third is critical for proper alignment and coordination among fingers for maximal histone engagement. Human homologs, MLL3 and MLL4, also show conservation of H3 binding, expanding current views of histone recognition for this class of proteins. We further implicate chromatin remodeling by the SWI/SNF complex as a possible mechanism for the accessibility of PHDb to globular regions of histone H3 beyond the tail region. Our results suggest a two-tail histone recognition mechanism by the conserved PHDb domain involving a flexible hinge to promote interdomain coordination.

3.
Surg Endosc ; 37(9): 6885-6894, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37311892

RESUMEN

BACKGROUND: Prophylactic intra-abdominal onlay mesh (IPOM) implantation has been shown to reduce the rate of fascial dehiscence and incisional hernia. However, surgical site infection (SSI) in presence of an IPOM remains a concern. The aim of this study was to assess predictors for SSI following IPOM placement in hernia and non-hernia abdominal surgery in clean and contaminated surgical fields. METHODS: Observational study including patients undergoing IPOM placement at a Swiss tertiary care hospital 2007-2016. IPOM implantation was performed in hernia and non-hernia elective and emergency abdominal surgery, including contaminated and infected surgical fields. The incidence of SSI was prospectively assessed by Swissnoso according to CDC criteria. The effect of disease- and procedure-related factors on SSI was assessed in multivariable regression analysis, adjusting for patient-related factors. RESULTS: A total of 1072 IPOM implantations were performed. Laparoscopy was performed in 415 patients (38.7%), laparotomy in 657 patients (61.3%). SSI occurred in 172 patients (16.0%). Superficial, deep, and organ space SSI were found in 77 (7.2%), 26 (2.4%), and 69 (6.4%) patients, respectively. Multivariable analysis revealed emergency hospitalization (OR 1.787, p = 0.006), previous laparotomy (1.745, p = 0.029), duration of operation (OR 1.193, p < 0.001), laparotomy (OR 6.167, p < 0.001), bariatric (OR 4.641, p < 0.001), colorectal (OR 1.941, p = 0.001), and emergency (OR 2.510, p < 0.001) surgery, wound class ≥ 3 (OR 3.878, p < 0.001), and non-polypropylene mesh (OR 1.818, p = 0.003) as independent predictors for SSI. Hernia surgery was independently associated with a lower risk for SSI (OR 0.165, p < 0.001). CONCLUSION: This study revealed emergency hospitalization, previous laparotomy, duration of operation, laparotomy, as well as bariatric, colorectal, and emergency surgery, abdominal contamination or infection, and usage of non-polypropylene mesh as independent predictors for SSI. In contrast, hernia surgery was associated with a lower risk for SSI. The knowledge of these predictors will help to balance benefits of IPOM implantation against the risk for SSI.


Asunto(s)
Cavidad Abdominal , Neoplasias Colorrectales , Hernia Ventral , Hernia Incisional , Laparoscopía , Humanos , Cavidad Abdominal/cirugía , Neoplasias Colorrectales/cirugía , Hernia Ventral/prevención & control , Hernia Ventral/cirugía , Hernia Ventral/etiología , Herniorrafia/efectos adversos , Hernia Incisional/etiología , Hernia Incisional/prevención & control , Hernia Incisional/cirugía , Laparoscopía/efectos adversos , Mallas Quirúrgicas/efectos adversos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control
4.
Entropy (Basel) ; 25(12)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38136508

RESUMEN

The complexity measure for the distribution in space-time of a finite-velocity diffusion process is calculated. Numerical results are presented for the calculation of Fisher's information, Shannon's entropy, and the Cramér-Rao inequality, all of which are associated with a positively normalized solution to the telegrapher's equation. In the framework of hyperbolic diffusion, the non-local Fisher's information with the x-parameter is related to the local Fisher's information with the t-parameter. A perturbation theory is presented to calculate Shannon's entropy of the telegrapher's equation at long times, as well as a toy model to describe the system as an attenuated wave in the ballistic regime (short times).

5.
Gac Med Mex ; 159(1): 24-31, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36930551

RESUMEN

INTRODUCTION: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. OBJECTIVE: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. METHODS: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. RESULTS: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. CONCLUSIONS: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.


INTRODUCCIÓN: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. OBJETIVO: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. MÉTODOS: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. RESULTADOS: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. CONCLUSIONES: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.


Asunto(s)
Fibrilación Atrial , Insuficiencia Cardíaca , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Anticoagulantes/efectos adversos , Fibrinolíticos/efectos adversos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/epidemiología , Factores de Riesgo Cardiometabólico , Volumen Sistólico , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control
6.
Am J Physiol Gastrointest Liver Physiol ; 323(4): G348-G361, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36044679

RESUMEN

Impaired oxygen utilization has been proposed to play a significant role in sepsis-induced liver dysfunction, but its magnitude and temporal course during prolonged resuscitation is controversial. The aim of this study is to evaluate the capability of the liver to increase oxygen extraction in sepsis during repeated acute portal vein blood flow reduction. Twenty anesthetized and mechanically ventilated pigs with hepatic hemodynamic monitoring were randomized to fecal peritonitis or controls (n = 10, each). After 8-h untreated sepsis, the animals were resuscitated for three days. The ability to increase hepatic O2 extraction was evaluated by repeated, acute decreases in hepatic oxygen delivery (Do2) via reduction of portal flow. Blood samples for liver function and liver biopsies were obtained repeatedly. Although liver function tests, ATP content, and Do2 remained unaltered, there were signs of liver injury in blood samples and overt liver cell necrosis in biopsies. With acute portal vein occlusion, hepatic Do2 decreased more in septic animals compared with controls [max. decrease: 1.66 ± 0.68 mL/min/kg in sepsis vs. 1.19 ± 0.42 mL/min/kg in controls; portal venous flow (Qpv) reduction-sepsis interaction: P = 0.028]. Hepatic arterial buffer response (HABR) was impaired but recovered after 3-day resuscitation, whereas hepatic oxygen extraction increased similarly during the procedures in both groups (max. increase: 0.27 ± 0.13 in sepsis vs. 0.18 ± 0.09 in controls; all P > 0.05). Our data indicate maintained capacity of the liver to acutely increase O2 extraction, whereas blood flow regulation is transiently impaired with the potential to contribute to liver injury in sepsis.NEW & NOTEWORTHY The capacity to acutely increase hepatic O2 extraction with portal flow reduction is maintained in sepsis with accompanying liver injury, but hepatic blood flow regulation is impaired.


Asunto(s)
Hemodinámica , Sepsis , Adenosina Trifosfato , Animales , Arteria Hepática , Circulación Hepática/fisiología , Oxígeno , Porcinos
7.
Int J Mol Sci ; 23(11)2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35682696

RESUMEN

Identification of alternative attenuation targets of Mycobacterium tuberculosis (Mtb) is pivotal for designing new candidates for live attenuated anti-tuberculosis (TB) vaccines. In this context, the CtpF P-type ATPase of Mtb is an interesting target; specifically, this plasma membrane enzyme is involved in calcium transporting and response to oxidative stress. We found that a mutant of MtbH37Rv lacking ctpF expression (MtbΔctpF) displayed impaired proliferation in mouse alveolar macrophages (MH-S) during in vitro infection. Further, the levels of tumor necrosis factor and interferon-gamma in MH-S cells infected with MtbΔctpF were similar to those of cells infected with the parental strain, suggesting preservation of the immunogenic capacity. In addition, BALB/c mice infected with Mtb∆ctpF showed median survival times of 84 days, while mice infected with MtbH37Rv survived 59 days, suggesting reduced virulence of the mutant strain. Interestingly, the expression levels of ctpF in a mouse model of latent TB were significantly higher than in a mouse model of progressive TB, indicating that ctpF is involved in Mtb persistence in the dormancy state. Finally, the possibility of complementary mechanisms that counteract deficiencies in Ca2+ transport mediated by P-type ATPases is suggested. Altogether, our results demonstrate that CtpF could be a potential target for Mtb attenuation.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Animales , Calcio , ATPasas Transportadoras de Calcio , Membrana Celular/patología , Ratones , Tuberculosis/microbiología , Virulencia/genética
8.
Int J Mol Sci ; 23(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35216083

RESUMEN

Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.


Asunto(s)
Antiinflamatorios/farmacología , Antituberculosos/farmacología , Encéfalo/microbiología , Curcumina/farmacología , Pulmón/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis/tratamiento farmacológico , Animales , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/metabolismo , Tuberculosis Pulmonar/metabolismo
9.
Am J Orthod Dentofacial Orthop ; 161(5): 638-651.e1, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35016812

RESUMEN

INTRODUCTION: This study aimed to assess sagittal and vertical skeletal and dentoalveolar changes through the use of 3-dimensional imaging in prepubertal Class II malocclusion patients treated with a cantilever Herbst appliance (HA). Condyle-glenoid fossa positional changes were also quantified. METHODS: This retrospective cohort study assessed 22 children (11.2 years ± 1.2) consecutively treated with a cantilever HA for 12 months and 11 untreated children (aged 9.3 ± 0.30 years) that served as controls. Cone-beam computed tomography was performed at baseline (T1) and at the end of the observation period (T2). Movements in the regions of interest were measured as linear displacements from cone-beam computed tomography images through algebraic calculations. A Student t test for independent samples was used for group equivalence testing at T1, and the treatment differences between T2 and T1 were evaluated by 2 analyses of covariance, one considering the expected growth unit as a covariate and the other with an annualized factor. RESULTS: The largest dental movement was a mesial movement of mandibular molars (3.70 mm), whereas the largest skeletal changes consisted of a larger relative length of the mandible (difference of 1.2 mm) in the HA group than in the control group. CONCLUSIONS: Within the study limitations (retrospective cohort, historical control group, and sample size), 3-dimensional imaging suggests that HA corrected Class II malocclusion in a predominantly prepubertal sample through more dental than skeletal changes. The changes were more significant in the sagittal than in the vertical direction. In addition, relative stability in the condyle-fossa relationship was noted.


Asunto(s)
Maloclusión Clase II de Angle , Aparatos Ortodóncicos Funcionales , Cefalometría , Niño , Humanos , Maloclusión Clase II de Angle/diagnóstico por imagen , Maloclusión Clase II de Angle/terapia , Mandíbula , Estudios Retrospectivos
10.
An Acad Bras Cienc ; 93(suppl 4): e20201821, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34730620

RESUMEN

The objective of the study was to compare the richness and diversity of ant assemblages in an agroecological system under peach orchard, conventional system under peach orchard cultivation and native vegetation in rural properties located in a Pampa Biome. The study was conducted in four samplings in 2017: 1st and 09th March (summer); 24th and 31st July (winter); and four samplings in 2018: 23rd and 30th January (summer); 31st July and 07th August (winter). Pitfall traps were used. The assemblages were characterized and compared using richness, number of occurrences of ants, Shannon diversity (H'), equitability, rarefaction analysis and Chao 1. The association of the species with the samples was evaluated by a Principal Component Analysis (PCA). The agroecological system had the highest number of occurrences, while the conventional orchard the lowest number. Richness and abundance were greatest during the summer. The conventional peach orchard obtained the lowest H' for both seasons when compared to the agroecological orchard and native vegetation. The PCA explained 77.40% of the occurrence of ants in the environments and in the seasons. The results found demonstrated that conservationist systems tend to harbor greater wealth and diversity of ant assemblages, as well as occurring in native áreas.


Asunto(s)
Hormigas , Animales , Biodiversidad , Productos Agrícolas , Ecosistema , Estaciones del Año
11.
Molecules ; 26(7)2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33917541

RESUMEN

This work aimed to evaluate the physical, chemical and antioxidant properties of Ceiba aesculifolia subsp. parvifolia (CAP) tuber and determinate rheological, thermal, physicochemical and morphological properties of the starch extracted. The CAP tuber weight was 3.66 kg; the edible yield was 82.20%. The tuber presented a high hardness value (249 N). The content of carbohydrates (68.27%), crude fiber (15.61%) and ash (9.27%) from the isolated starch, reported in dry weight, were high. Phenolic compounds and flavonoid content of CAP tuber peel were almost 3-fold higher concerning the pulp. CAP tuber starch exhibited a pseudoplastic behavior and low viscosity at concentrations of 5-15%. Purity percentage and color parameters describe the isolated starch as high purity. Thermal characteristics indicated a higher degree of intermolecular association within the granule. Pasting properties describes starch with greater resistance to heat and shear. CAP tuber starch has X-ray diffraction patterns type A. The starch granules were observed as oval and diameters ranging from 5 to 30 µm. CAP tuber could be a good source of fiber and minerals, while its peel could be used for extracting bioactive compounds. Additionally, the starch separated from this tuber could be employed as a thickening agent in food systems requiring a low viscosity and subjected to high temperatures.


Asunto(s)
Ceiba/química , Tubérculos de la Planta/química , Reología , Almidón/química , Antioxidantes/análisis , Rastreo Diferencial de Calorimetría , Color , Elasticidad , Flavonoides/análisis , Polifenoles/análisis , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Almidón/ultraestructura , Temperatura , Viscosidad , Difracción de Rayos X
12.
J Sci Food Agric ; 101(8): 3298-3307, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33222200

RESUMEN

BACKGROUND: External preference mapping is a powerful tool to explain consumer preference or rejection. Combining the technique for order of preference by similarity to ideal solution (TOPSIS) multicriteria analysis with rapid descriptive techniques can improve preference map (PREFMAP) results. This study was conducted to compare the PREFMAPs generated with rapid descriptive flash profile (FP), check-all-that-apply (CATA), and Napping® versus PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS. RESULTS: Only 38.46%, 63.66%, and 42% of sensory attributes initially generated by FP, CATA, and Napping techniques respectively were considered for the determination of their weight W and allocation as positive or negative in the TOPSIS technique. The PREFMAPs constructed with FP-TOPSIS, CATA-TOPSIS, and Napping-TOPSIS presented a better explanation of the preference and rejection than the PREFMAPs directly generated with rapid sensory techniques. The results of the multiple factor analysis and coefficient Rv indicated similarities in the sensory vocabularies used after the TOPSIS technique. CONCLUSION: The combination of the TOPSIS technique with rapid sensory techniques is a reliable alternative for the construction of PREFMAPs in order to identify the sensory attributes responsible for preference and rejection of food products. © 2020 Society of Chemical Industry.


Asunto(s)
Comportamiento del Consumidor , Gusto , Coffea/química , Coffea/metabolismo , Café/química , Café/metabolismo , Humanos , Proyectos de Investigación , Semillas/química , Semillas/metabolismo
13.
Mol Cell ; 48(5): 681-91, 2012 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-23103253

RESUMEN

The mammalian target of rapamycin (mTOR) pathway, which is essential for cell proliferation, is repressed in certain cell types in hypoxia. However, hypoxia-inducible factor 2α (HIF2α) can act as a proliferation-promoting factor in some biological settings. This paradoxical situation led us to study whether HIF2α has a specific effect on mTORC1 regulation. Here we show that activation of the HIF2α pathway increases mTORC1 activity by upregulating expression of the amino acid carrier SLC7A5. At the molecular level we also show that HIF2α binds to the Slc7a5 proximal promoter. Our findings identify a link between the oxygen-sensing HIF2α pathway and mTORC1 regulation, revealing the molecular basis of the tumor-promoting properties of HIF2α in von Hippel-Lindau-deficient cells. We also describe relevant physiological scenarios, including those that occur in liver and lung tissue, wherein HIF2α or low-oxygen tension drive mTORC1 activity and SLC7A5 expression.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/metabolismo , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Proteínas/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Sitios de Unión , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Hipoxia de la Célula , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Transportador de Aminoácidos Neutros Grandes 1/genética , Hígado/metabolismo , Pulmón/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Ratones Noqueados , Ratones SCID , Complejos Multiproteicos , Trasplante de Neoplasias , Regiones Promotoras Genéticas , Proteínas/genética , Interferencia de ARN , Transducción de Señal , Serina-Treonina Quinasas TOR , Factores de Tiempo , Transfección , Carga Tumoral , Regulación hacia Arriba , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo
14.
Int J Mol Sci ; 21(24)2020 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-33322180

RESUMEN

Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogenic substrate of such manifestations have remained unknown. Here, using a mouse model of progressive pulmonary TB, we report that, even in the absence of brain infection, TB is associated with marked increased synthesis of both inflammatory and anti-inflammatory cytokines in discrete brain areas such as the hypothalamus, the hippocampal formation and cerebellum accompanied by substantial changes in the synthesis of neurotransmitters. Moreover, histopathological findings of neurodegeneration and neuronal death were found as infection progressed with activation of p38, JNK and reduction in the BDNF levels. Finally, we perform behavioural analysis in infected mice throughout the infection, and our data show that the cytokine and neurochemical changes were associated with a marked onset of cognitive impairment as well as depressive- and anxiety-like behaviour. Altogether, our results suggest that besides pulmonary damage, TB is accompanied by an extensive neuroinflammatory and neurodegenerative state which explains some of the behavioural abnormalities found in TB patients.


Asunto(s)
Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Citocinas/metabolismo , Inflamación/metabolismo , Mycobacterium tuberculosis/metabolismo , Neuronas/patología , Tuberculosis Pulmonar/metabolismo , Animales , Ansiedad/metabolismo , Ansiedad/microbiología , Síntomas Conductuales/microbiología , Barrera Hematoencefálica/citología , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/patología , Encéfalo/citología , Encéfalo/enzimología , Encéfalo/patología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Cromatografía Líquida de Alta Presión , Disfunción Cognitiva/microbiología , Depresión/metabolismo , Depresión/microbiología , Modelos Animales de Enfermedad , Regulación hacia Abajo , Hipocampo/citología , Hipocampo/inmunología , Hipocampo/metabolismo , Hipocampo/patología , Quinasas Janus/metabolismo , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones Endogámicos BALB C , Mycobacterium tuberculosis/patogenicidad , Neuronas/citología , Neurotransmisores/metabolismo , Tuberculosis Pulmonar/enzimología , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/psicología , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
BMC Oral Health ; 20(1): 153, 2020 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-32460733

RESUMEN

BACKGROUND: With the aid of implants, Björk identified two-dimensional mandibular stable structures in cephalograms during facial growth. However, we do not know what the three-dimensional stable structures are with certainty. The purpose of this study was to identify the most stable mandibular landmarks in growing patients using three-dimensional images. METHODS: The sample was comprised of two cone-beam computed tomography (CBCT) scans taken about 4.6 years apart in 20 growing patients between the ages of 12.5 (T1) and 17.1 years (T2). After head orientation, landmarks were located on the chin (Pog), internal symphysis (Points C, D and E), and mandibular canals, which included the mental foramina (MF and MFA) and mandibular foramina (MdF). The linear distance change between Point C and these landmarks was measured on each CBCT to test stability through time. The reliability of the suggested stable landmarks was also evaluated. RESULTS: The total distance changes between Point C and points D, E, Pog, MF, and MFA were all less than 1.0 mm from T1 to T2. The reliability measures of these landmarks, which were measured by the Cronbach alpha, were above 0.94 in all three dimensions for each landmark. From T1 to T2, the distance changes from Point C to the right and left mandibular foramina were 3.39 ± 3.29 mm and 3.03 ± 2.83 mm, respectively. CONCLUSIONS: During a growth period that averaged 4.6 years, ranging from 11.2 to 19.8 years old, the structures that appeared relatively stable and could be used in mandibular regional superimpositions included Pog, landmarks on the inferior part of the internal symphysis, and the mental foramen. The centers of the mandibular foramina and the starting points of the mandibular canal underwent significant changes in the transverse and sagittal dimensions.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Mandíbula , Adolescente , Adulto , Puntos Anatómicos de Referencia/diagnóstico por imagen , Niño , Humanos , Imagenología Tridimensional , Mandíbula/diagnóstico por imagen , Reproducibilidad de los Resultados , Adulto Joven
16.
J Hepatol ; 71(6): 1126-1140, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31295531

RESUMEN

BACKGROUND & AIMS: Pathological bacterial translocation (PBT) in cirrhosis is the hallmark of spontaneous bacterial infections, increasing mortality several-fold. Increased intestinal permeability is known to contribute to PBT in cirrhosis, although the role of the mucus layer has not been addressed in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined, but we hypothesize that the recently described gut-vascular barrier (GVB) is impaired in experimental portal hypertension, leading to increased accessibility of the vascular compartment for translocating bacteria. MATERIALS: Cirrhosis was induced in mouse models using bile-duct ligation (BDL) and CCl4. Pre-hepatic portal-hypertension was induced by partial portal vein ligation (PPVL). Intestinal permeability was compared in these mice after GFP-Escherichia coli or different sized FITC-dextrans were injected into the intestine. RESULTS: Healthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-E. coli from the small intestine to the liver, whereas BDL and CCl4-induced cirrhotic mice demonstrate pathological translocation, which is not altered by prior thoracic-duct ligation. The mucus layer is reduced in thickness, with loss of goblet cells and Muc2-staining and expression in cirrhotic but not PPVL mice. These changes are associated with bacterial overgrowth in the inner mucus layer and pathological translocation of GFP-E. coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran, but only slightly altered in PPVL mice. This pathological endothelial permeability and accessibility in cirrhotic mice is associated with augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB, whereas both FXR-agonists ameliorate gut to liver translocation of GFP-E. coli. CONCLUSIONS: Cirrhosis, but not portal hypertension per se, grossly impairs the endothelial and muco-epithelial barriers, promoting PBT to the portal-venous circulation. Both barriers appear to be FXR-modulated, with FXR-agonists reducing PBT via the portal-venous route. LAY SUMMARY: For intestinal bacteria to enter the systemic circulation, they must cross the mucus and epithelial layer, as well as the gut-vascular barrier. Cirrhosis disrupts all 3 of these barriers, giving bacteria access to the portal-venous circulation and thus, the gut-liver axis. Diminished luminal bile acid availability, cirrhosis and the associated reduction in farnesoid x receptor (FXR) signaling seem, at least partly, to mediate these changes, as FXR-agonists reduce bacterial translocation via the portal-venous route to the liver in cirrhosis.


Asunto(s)
Traslocación Bacteriana/efectos de los fármacos , Permeabilidad Capilar , Dextranos/farmacocinética , Escherichia coli , Microbioma Gastrointestinal/fisiología , Mucosa Intestinal , Cirrosis Hepática Experimental , Receptores Citoplasmáticos y Nucleares , Animales , Ácidos y Sales Biliares/metabolismo , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/fisiología , Modelos Animales de Enfermedad , Escherichia coli/aislamiento & purificación , Escherichia coli/fisiología , Hipertensión Portal/metabolismo , Hipertensión Portal/fisiopatología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Cirrosis Hepática Experimental/metabolismo , Cirrosis Hepática Experimental/microbiología , Cirrosis Hepática Experimental/fisiopatología , Ratones , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores Citoplasmáticos y Nucleares/metabolismo
17.
Lasers Med Sci ; 34(8): 1705-1715, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31154599

RESUMEN

The aim of this study was to evaluate the effect of photobiomodulation (PBM) on the stability and displacement of orthodontic mini-implants (MIs) submitted to loading. Forty-eight and 35 mini-implants (1.5 × 8 × 1 mm) were assessed for stability and displacement, respectively (19 patients). MIs were allocated according to the intervention in 1-PBM + immediate loading (IL), 2-PBM + delayed loading (DL) (four weeks after implantation), 3-IL only, and 4-DL only. PBM (Therapy XT, DCM) was implemented using a red emission (660 nm, 4 J/cm2, 0.1 W, 20 s) immediately after implantation (day 0) and infrared emissions (808 nm; 8 J/cm2, 0.1 W, 40 s) in the following appointments every 48-72 h during two weeks (days 2, 4, 7, 9, 11, and 14). Loading of 150 gF was applied during three months for all MIs. The stability was assessed by resonance frequency analysis (Osstell ISQ), and images from Cone beam computed tomography were evaluated to determine the amount of the displacement of the MI's head. MIs from the PBM groups presented lower loss of stability (P = 0.0372). When the analysis considered the loading protocol as an additional variable, group two showed the lowest loss of stability, being significantly different from groups that did not receive PBM (P = 0.0161). There was no difference between groups two and four during the period without loading (P > 0.05). DL groups presented lower loss when the effective period of loading was assessed, independently of the application of PBM (P < 0.0001). All groups showed displacement of the MIs head without significant differences (P > 0.05). DL potentiated the effect of PBM, decreasing the loss of stability.


Asunto(s)
Implantes Dentales , Terapia por Luz de Baja Intensidad , Ortodoncia , Adolescente , Puntos Anatómicos de Referencia , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Adulto Joven
18.
Cleft Palate Craniofac J ; 56(3): 408-414, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-29906221

RESUMEN

In this article, we demonstrate an effective, cheap, and fast way to shape the nasal alar cartilage in patients with unilateral cleft lip and palate. This technique straightens the vomer and brings the philtrum, columella, premaxilla, and the maxillary frenum to the midsagittal plane, while the alveolar ridges are shaped and positioned. This reduces the lip and palatal cleft to zero even in a 4-week period.


Asunto(s)
Labio Leporino , Fisura del Paladar , Proceso Alveolar , Humanos , Lactante , Labio , Cuidados Preoperatorios
19.
Am J Orthod Dentofacial Orthop ; 155(2): 198-206, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30712691

RESUMEN

INTRODUCTION: Rapid maxillary expansion (RME) might cause buccal displacement of anchor teeth. Dislocation of teeth outside their alveolar process can damage the periodontium; for this reason, maxillary expansion using deciduous teeth as anchorage in the mixed dentition might be suggested. The aim of this study was to compare changes of buccal bone plate thickness on the maxillary permanent first molars after RME in the mixed and permanent dentitions with different types of anchorage. METHODS: Two groups of patients were evaluated with cone-beam computed tomography before and after RME. Group E (21 patients) underwent RME using deciduous teeth as anchorage; group 6 (16 patients) underwent RME using permanent teeth as anchorage. The Wilcoxon test was used to compare changes between the time points in the same groups, and the Mann-Whitney U test was used to compare differences between the groups. RESULTS: In group E, generally, no statistically significant reduction was found in buccal bone plate thickness between the time points. In group 6, most measurements showed significant reductions in buccal bone plate thickness (P <0.05) between the time points, with a maximum decrease of 1.25 mm. CONCLUSIONS: RME in the mixed dentition with the appliance anchored to deciduous teeth did not reduce the buccal bone plate thickness of the maxillary permanent first molars, except for the mesial roots on both sides. RME in the permanent dentition caused a reduction of the buccal bone plate thickness of the maxillary permanent first molars when they were used as anchorage in the permanent dentition.


Asunto(s)
Dentición Mixta , Dentición Permanente , Maxilar/anatomía & histología , Técnica de Expansión Palatina , Adolescente , Niño , Femenino , Humanos , Masculino , Tamaño de los Órganos , Estudios Retrospectivos , Factores de Tiempo
20.
Minerva Pediatr ; 71(4): 380-389, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30511557

RESUMEN

INTRODUCTION: Growth retardation was frequently observed in obstructive sleep apnea (OSA) patients but the complex mechanisms causing this condition are still unclear. Several findings suggested growth catch-up after surgical treatment but other studies did not confirm the results, showing no improvement in OSA patients after tonsillectomy and adenoidectomy (T&A). The aim of the present study was to systematically review scientific literature of the relationships between OSA and metabolic changes involving growth hormone (GH) axis before and after treatment in patients. EVIDENCE ACQUISITION: Different databases were searched without limitations up to August 2017. Additionally, the bibliographies of the finally selected articles were hand searched to identify any relevant publications that were not previously identified. EVIDENCE SYNTHESIS: From the 37 studies collected from all the databases based on their title and abstract, only 12 studies actually fulfilled the selection criteria. From the twelve finally selected articles, eight focused on growth mediators, two evaluated endothelial mediators, one focused on neurocognitive function and mediators and one focused on local inflammation. CONCLUSIONS: OSA children present lower levels of growth mediators (IGF-I and IGFBP-3) thus indicating growth retardation, significantly higher cardiovascular disease risk and decreased cognitive functions when compared to controls. T&A seems to improve all the above mentioned functions with great impact on general health.


Asunto(s)
Trastornos del Crecimiento/etiología , Hormona de Crecimiento Humana/metabolismo , Apnea Obstructiva del Sueño/complicaciones , Adenoidectomía/métodos , Niño , Trastornos del Crecimiento/epidemiología , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Apnea Obstructiva del Sueño/cirugía , Tonsilectomía/métodos
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