Remodelado del ventrículo izquierdo postinfarto: una mirada desde la perfusión miocárdica gated-SPECT / Left Ventricular Remodeling After Myocardial Infarction: A Perspective from Gated-SPECT Myocardial Perfusion Imaging

RESUMEN Introducción: El estudio gatillado de perfusión miocárdica con tomografía computarizada por emisión de fotón único, o gated-SPECT (por su denominación en inglés) es un método apropiado para cuantificar la magnitud de la escara necrótica y establecer su territorio. El análisis de pacientes con infartos de pequeña y mediana extensión que evolucionan con deterioro de la fracción de eyección ventricular izquierda (FEVI), podría arrojar luz acerca de los factores que influyen en la presencia de remodelado adverso y la consiguiente evolución a disfunción ventricular. Objetivos: a) evaluar la prevalencia de FEVI disminuida y factores asociados en una población de pacientes derivados para estudios de gated-SPECT, y b) definir la prevalencia de remodelado adverso y factores asociados en el subgrupo de pacientes con carga necrótica intermedia a baja. Material y métodos: Realizamos un análisis retrospectivo de pacientes consecutivos que se realizaron gated-SPECT durante el año 2017. Se excluyeron los pacientes con enfermedad valvular significativa o arritmias que produjeran alteración del gatillado. Se consideró remodelado adverso a la conjunción de FEVI disminuida (FEVI < 50%) y porcentaje de miocardio necrótico menor que 20 %. Resultados: Se incluyeron 1902 pacientes. La prevalencia de FEVI disminuida fue del 8 % (n =148). En el análisis multivariado, las variables independientes asociadas a disfunción ventricular fueron el género masculino (OR 2,50; IC 95% 1,30-4,90, p = 0,005), la diabetes (OR 1,83; IC 95% 1,12-3, p = 0,01), y compromiso necrótico mayor que 6,6 % (OR 39 IC 95% 25-61,28, p = 0,00001). En el subgrupo de pacientes con carga necrótica menor que 20% (n =197), la prevalencia de remodelado adverso fue del 25% (n =50). El análisis multivariado arrojó que la diabetes (OR 2,83; IC 95% 1,31 - 6,10 p = 0,007) y el género masculino (OR 5; IC 95% 1,10 - 22,9 p = 0,007) presentaron asociación independiente con el remodelado adverso. Conclusión: La gated-SPECT podría utilizarse en la valoración del remodelado adverso y factores asociados. Dicha valoración surge de la combinación de variables que no requieren un software adicional y se usan en la práctica diaria.

ABSTRACT Background: Gated single-photon emission computed tomography (gated-SPECT) myocardial perfusion imaging is a suitable technique for measuring the infarct scar size and defining its territory. Analyzing patients with small and medium myocardial infarctions that develop reduced left ventricular ejection fraction (LVEF) could provide additional information of the factors that contribute to adverse remodeling and its outcome. Objectives: a) To evaluate the prevalence of reduced LVEF and associated factors in a population of patients referred for gated-SPECT imaging, and b) to define the prevalence of adverse remodeling and associated factors in the subgroup of patients with intermediate to low necrotic burden. Methods: We conducted a retrospective analysis of consecutive patients undergoing gated-SPECT imaging during 2017. Patients with significant valvular heart disease or arrhythmias that could difficult adequate ECG gating were excluded from the study. Adverse remodeling was considered as the combination of reduced LVEF (LVEF < 50%) with percent myocardium scar < 20%. Results: A total of 1902 patients were included. The prevalence of reduced LVEF was 8% (n = 148). On multivariate analysis, the variables with independent association with ventricular dysfunction were male sex (OR 2.50; 95% CI 1.30-4.90, p = 0.005), diabetes (OR 1.83; 95% CI 1.12-3, p = 0.01), and percent myocardium scar > 6.6 % (OR 39; 95% CI 25-61.28, p = 0.00001). In the subgroup of patients with scar burden < 20 % (n = 197), the prevalence of adverse remodeling was 25 % (n = 50). On multivariate analysis, diabetes (OR 2.83; 95% CI 1.31 - 6.1 p = 0.007) and male sex (OR 5; 95% CI 1.1 - 22.9, p = 0.007) showed an independent association with adverse remodeling. Conclusion: Gated-SPECT could be used to assess adverse remodeling and its associated factors. This assessment is the result of combining variables used in daily practice which do not require any additional software.

Remodelado vascular excéntrico: su relación con trastornos metabólicos y el incremento de la masa corporal / Eccentric Vascular Remodeling: Its Relationship with Metabolic Disorders and Increased Body Mass

RESUMEN Introducción: Existe evidencia reciente que establecería a la hipoperfusión muscular como causa primaria de trastornos metabólicos en respuesta a la sobrealimentación. Esta concepción centrípeta del desarrollo de trastornos metabólicos podría implicar no solo alteraciones en la microvasculatura, sino también afectación en las arterias de conductancia. Objetivos: 1) Determinar la asociación entre diámetro basal de la arteria humeral (D-Hum) y la vasodilatación mediada por flujo (VDMF) 2) Analizar la asociación de ambos parámetros conforme aumenta de la masa corporal 3) Evaluar asociaciones entre el D-Hum/VDMF con componentes del síndrome metabólico (SM) 4) Evaluar la asociación independiente de ambas variables con el SM. Material y métodos: Se evaluaron 3493 pacientes. Se excluyeron pacientes < 18 y >80 años, con patología cardiovascular previa, insuficiencia renal crónica (IRC), colagenopatías, y tratados con estatinas. Se determinó presión arterial (PA), parámetros antropométricos y perfil metabólico, y se clasificó a los sujetos de acuerdo con la presencia de SM según AHA/NHLBI 2019. Se midieron D-Hum en mm y VDMF en %. Se analizó la asociación lineal entre D-Hum y VDMF y se analizaron ambas variables según decilos de índice de masa corporal (IMC). Se evaluaron asociaciones entre D-Hum/VDMF con la PA, glucemia (Glu), triglicéridos (TG) y colesterol de alta densidad (HDLc). Se realizaron dos regresiones logísticas con SM como variable dependiente y D-Hum o VDMF más edad, sexo, IMC y factores de riesgo coronario (FRC) como independientes. Resultados: Ingresaron 1995 pacientes (48,2 ± 11 años, 56 % hombres). El D-Hum y la VDMF presentaron una asociación inversa (r= -0,42; p < 0,0001). El D-Hum aumentó según decilos del IMC (p < 0,000001); la VDMF mostró relación inversa con los decilos crecientes de IMC (p < 0,000001). El D-Hum presentó correlación directa con PA, Glu y TG; e inversa con HDLc (p < 0,05 en todos los casos). La VDMF mostró correlación inversa con PA, Glu y TG; y directa con HDLc (p < 0,05 en todos los casos). El D-Hum se asoció en forma independiente con el SM ajustado por edad, sexo, IMC y FRC (OR 1,42, p = 0,0019), mientras que la VDMF no (OR 0,98, p = 0,217). Conclusión: El remodelado vascular excéntrico se asoció con un compromiso en la adaptación vascular ante aumentos en la demanda de flujo sanguíneo y con alteraciones metabólicas a lo largo del incremento de la masa corporal. Así, el compromiso dinámico de la vasculatura podría tener un rol determinante en el desarrollo de alteraciones metabólicas en forma sincrónica con la ganancia de peso.

ABSTRACT Background: Recent evidence would establish muscle hypoperfusion as the primary cause of metabolic disorders in response to overfeeding. This centripetal concept on the development of metabolic disorders could involve not only alterations in the microvasculature, but also affect the conductance arteries. Objectives: The aim of this study was 1) to determine the association between baseline brachial artery diameter (BAD) and flow-mediated vasodilation (FMVD), 2) To analyze the association of both parameters throughout the increase in body mass, 3) To evaluate associations between BAD/FMVD with components of the metabolic syndrome (MS) and 4) To evaluate the independent association of both variables with MS. Methods: A total of 3493 patients were evaluated. Patients <18 and >80 years old, those with previous cardiovascular disease, chronic kidney disease (CKD), collagenopathies, or treated with statins were excluded from the study. Blood pressure (BP), anthropometric parameters and metabolic profile were determined, and the subjects were classified according to the presence of MS conforming AHA/NHLBI 2019 criteria. BAD was measured in mm and FMVD as percentage. The linear association between BAD and FMVD was assessed, and both variables were analyzed according to deciles of body mass index (BMI). Associations between BAD/FMVD with BP, glucose (Glu), triglycerides (TG) and high-density cholesterol (HDL-C) levels were evaluated. Two logistic regression analyses were performed with MS as dependent variable and BAD or FMVD plus age, gender, BMI, and coronary risk factors (CRF) as independent variables. Results: A total of 1995 patients (48.2 ± 11 years, 56% men) were admitted in the study. An inverse correlation was found between BAD and FMVD (r= -0.42; p < 0.0001). BAD increased according to deciles of BMI (p < 0.000001), while FMVD showed an inverse relationship with increasing deciles of BMI (p < 0.000001). BAD exhibited a direct correlation with BP, Glu and TG; and an inverse relationship with HDL-C (p < 0.05 in all cases). FMVD presented an inverse correlation with BP, Glu and TG; and a direct correlation with HDL-C (p < 0.05 in all cases). BAD was independently associated with MS adjusted for age, gender, BMI and CRF (OR 1.42, p=0.0019), while FMVD was not (OR 0.98, p = 0.217). Conclusion: Eccentric vascular remodeling was associated with vascular adaptation to increased blood flow demand and with metabolic alterations throughout the increase in body mass. Thus, the dynamic compromise of vasculature could play a decisive role in the development of metabolic alterations occurring synchronously with weight gain.

La administración de N-acetilcisteína atenúa el remodelado post infarto de miocardio / Administration of N-acetylcysteine Attenuates Post-Myocardial Infarction Remodeling

RESUMEN Introducción: La cardiopatía isquémica es la principal causa de muerte en la República Argentina. La forma de presentación que prevalece es el infarto de miocardio (IM), caracterizado por insuficiente perfusión sanguínea, muerte celular y pérdida de masa contráctil. La evolución del remodelado ventricular provoca dilatación ventricular, deterioro hemodinámico, insuficiencia cardíaca y disminución de la sobrevida. Durante este proceso existe un estrés oxidativo miocárdico que podría ser atenuado mediante la administración de N-acetil cisteína (NAC), a través de un aumento de los niveles de glutatión. Objetivos: Evaluar el efecto de la NAC sobre el remodelado post IM. Material y métodos: Se estudiaron durante 28 días conejos neozelandeses en tres grupos experimentales: Control, IM e IM+NAC. Bajo anestesia general se realizó una toracotomía izquierda y, en los grupos con IM, ligadura de una rama de la coronaria izquierda. Al finalizar el período de seguimiento posterior al infarto, se realizaron estudios ecocardiográficos, hemodinámicos y morfológicos del ventrículo izquierdo (VI). Resultados: En los grupos IM e IM+NAC los infartos estaban ubicados en la pared libre del VI y tuvieron tamaños similares. La administración de NAC evitó el adelgazamiento de la zona no infartada y disminuyó la dilatación provocada por el infarto. También pudo observarse que preservó las funciones sistólica y diastólica del VI, con atenuación del deterioro que las mismas sufrieron como consecuencia del infarto. Conclusión: Estos resultados sugieren que la administración de NAC es una terapéutica promisoria para mitigar los efectos desfavorables del remodelado post IM.

ABSTRACT Background: Ischemic heart disease is the main cause of death in Argentina. The prevailing form of presentation is myocardial infarction (MI), characterized by insufficient blood perfusion, cell death and loss of contractile mass. The evolution of ventricular remodeling causes ventricular dilation, hemodynamic impairment, heart failure, and decreased survival. The oxidative stress occurring during this process could be attenuated by the administration of N-acetyl cysteine (NAC) through increased glutathione levels. Objectives: The aim of this study was to evaluate the effect of NAC administration on post-MI remodeling. Methods: New Zealand rabbits were divided into three experimental groups: Control, MI and MI+NAC. A left thoracotomy was performed under general anesthesia, and in the MI groups a branch of the left coronary artery was ligated. Echocardiographic, hemodynamic and morphological studies of the left ventricle were performed at the end of the 28-day post infarction follow-up period. Results: In the MI and MI+NAC groups, the infarcts were located in the left ventricular free wall and had similar sizes. The administration of NAC prevented non-infarcted area thinning and decreased the dilation caused by the infarction. It also preserved left ventricular systolic and diastolic functions, attenuating the impairment that they suffered as a consequence of the infarction. Conclusion: These results suggest that NAC administration is a promising therapy to mitigate the unfavorable effects of post-MI remodeling.

Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism / 中国药理学通报

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

Advances in the effect of ocular hypertension on ocular refraction / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular hypertension(OH)can cause a variety of ocular structural and functional damage, among which the effect on ocular refraction has long been recognized in the clinic. The effect of OH on ocular refraction is related to the transparency and shape of refractive media, as well as the changes of the axial length. Due to the different speed and degree of intraocular pressure(IOP)elevation, the changes of refraction are reversible or irreversible. Irreversible changes in refraction are often accompanied by visual transmission impairment, and have a certain reference value for the evaluation of the latter condition. IOP changes lead to changes in the axial length, which are related to scleral remodeling and choroidal perfusion changes, and have a certain impact on the development of myopia and refractive error after cataract surgery. In this paper, the research progress of the changes of refractive media and axial length caused by OH, as well as the characteristics of the effects on ocular refraction are summarized, hoping to deepen the understanding of the effect of OH on ocular refraction, and provide reference for preventing irreversible ocular refractive changes, guiding the assessment of visual transmission damage and preventing or controlling the development of axial myopia.

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling / 中国天然药物

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.

Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin / 中国实验方剂学杂志

Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels， electrical activity disorders， myocardial fibrosis， inflammation， dysfunctional mitochondrial biogenesis， mitochondrial calcium overload， out-of-balance energy metabolism， oxidative stress， sympathetic hyperactivity， and other pathological cardiac remodeling， and they are the main causes of sudden cardiac death. In traditional Chinese medicine， arrhythmias are considered to be palpitations， which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach， resulting in malfunction of the Qi mechanism， followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin， consisting of Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. In recent years， clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article， the mechanisms of the active ingredients of Shengmaisan in the electrophysiology， biochemistry， structure， autonomic nervous system， and subcellular fraction of the heart are reviewed， and the multi-target， multi-system， and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition， energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria， as the center of myocardial energy metabolism， play a paramount role in cardiac remodeling， indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria， so as to provide a theoretical basis for the clinical treatment of these arrhythmias.

Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Estado inflamatorio en el infarto agudo de miocardio, su impacto en el remodelado ventricular y nuevas dianas terapéuticas / Inflammation in acute myocardial infarction, impact on ventricular remodeling, and new therapeutic targets

RESUMEN La cardiopatía isquémica es la causa más frecuente de insuficiencia cardíaca, con una alta incidencia de esta a pesar de la revascularización precoz y la modulación neurohormonal. En el contexto del infarto agudo de miocardio los cardiomiocitos necrosados inducen la activación del sistema inmune innato, con aumento de la concentración de células inflamatorias que ayudan a eliminar las células muertas, e iniciar una respuesta correctiva que permite la formación adecuada de tejido cicatrizal.La prolongación o expansión de la respuesta inflamatoria posterior al infarto contribuye al remodelado adverso ventricular y al desarrollo de insuficiencia cardíaca.Entender los mecanismos inflamatorios que se desarrollan producto del infarto, y su impacto en el remodelado adverso que aumenta el número de eventos cardiovasculares mayores, permite comprender a la inflamación como un objetivo terapéutico.

ABSTRACT Ischemic heart disease is the most common cause of heart failure, with a high incidence of heart failure despite early revascularization and neurohormonal modulation.In the acute myocardial infarction setting, necrotized cardiomyocytes induce activation of the innate immune system, increasing the levels of inflammatory cells to help remove dead cells and initiate a corrective response, which allows for proper scar tissue formation.A prolonged or expanded inflammatory response after infarction contributes to adverse ventricular remodeling and development of heart failure.Understanding the inflammatory mechanisms that emerge as a result of myocardial infarction and their impact on adverse remodeling that leads to an increased.

Effects of Chemical inhibition of histone deacetylase proteins in the growth and virulence of Macrophomina phaseolina (Tassi) Goid / Efectos de la inhibición química de las proteínas desacetilasas de histonas en el crecimiento y la virulencia de Macrophomina phaseolina (Tassi) Goid

Abstract Chromatin remodeling enzymes are important "writers'', "readers'' and "erasers'' of the epigenetic code. These proteins are responsible for the placement, recognition, and removal of molecular marks in histone tails that trigger structural and functional changes in chromatin. This is also the case for histone deacetylases (HDACs), i.e., enzymes that remove acetyl groups from histone tails, signaling heterochromatin formation. Chromatin remodeling is necessary for cell differentiation processes in eukaryotes, and fungal pathogenesis in plants includes many adaptations to cause disease. Macrophomina phaseolina (Tassi) Goid. is a nonspe-cific, necrotrophic ascomycete phytopathogen that causes charcoal root disease. M. phaseolina is a frequent and highly destructive pathogen in crops such as common beans (Phaseolus vulgaris L.), particularly under both water and high temperature stresses. Here, we evaluated the effects of the classical HDAC inhibitor trichostatin A (TSA) on M. phaseolina in vitro growth and virulence. During inhibition assays, the growth of M. phaseolina in solid media, as well as the size of the microsclerotia, were reduced (p <0.05), and the colony morphology was remark-ably affected. Under greenhouse experiments, treatment with TSA reduced (p <0.05) fungal virulence in common bean cv. BAT 477. Tests of LIPK, MAC1 and PMK1 gene expression during the interaction of fungi with BAT 477 revealed noticeable deregulation. Our results provide additional evidence about the role of HATs and HDACs in important biological processes of M. phaseolina.

Resumen Las enzimas remodeladoras de la cromatina son «escritores¼, «lectores¼ y «borradores¼ importantes del código epigenético. Estas proteínas son responsables de la localización, el reconocimiento y la remoción de las marcas moleculares sobre las terminaciones de las histonas que desencadenan cambios funcionales y estructurales en la cromatina. Es el caso de las desacetilasas de histonas (HDAC), enzimas que remueven grupos acetilo de las «colas¼ de las histonas, señalizando la formación de heterocromatina. La anterior es una actividad necesaria en los procesos de diferenciación celular de los eucariotas, y se conoce que la patogénesis fúngica en las plantas requiere de adaptaciones diversas para ocasionar enfermedad. Macrophomina phaseolina (Tassi) Goid. es un ascomiceto fitopatógeno, necrótrofo e inespecífico, causante de la pudrición carbonosa. Este es un hongo frecuente y altamente destructivo en cultivos como fríjol común (Phaseolus vulgaris L.), particularmente bajo estrés hídrico y térmico. En este trabajo evaluamos los efectos del inhibidor de HDAC clásicas tricostatina A (TSA) sobre el crecimiento in vitro y la virulencia de M. phaseolina. El TSA redujo el crecimiento de M. phaseolina en medio sólido y el tamano de los microesclerocios (p < 0,05), lo que afectó la morfología colonial. En invernadero, el tratamiento con TSA disminuyó (p<0,05) la gravedad de la infección en la variedad de frijol BAT 477. La expresión de los genes de patogenicidad LIPK, MAC1 y PMK1 durante la interacción del hongo con la planta reveló una desregulación importante. Estos resultados proporcionan evidencia adicional del papel que cumplen las HDAC en la regulación de procesos biológicos fundamentales de M. phaseolina. © 2023 Asociación Argentina de Microbiología. Publicado por Elsevier Espana, S.L.U.

The development of nasal polyps involves early middle meatus mucous remodeling via TGF-β1 mediated PAI-1 reduction

Abstract Objective Our study aimed to elucidate the effect of PAI-1 (Plasminogen Activator Inhibitor-1) and t-PA (Tissue-type Plasminogen Activator) in tissue remodeling in nasal polyps patients. Methods Samples were streamed as early Nasal Polyps (eNP, n = 10) and inferior tissue from the same patient, mature Nasal Polyps (mNP, n = 14), and Control group (n = 15), respectively. Immunohistochemistry and immunofluorescence were applied to detect localization. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blot were used to measure different levels among three groups. The mNP tissue was cultured in vitro and treated with TGF-β1 (Transforming Growth Factor-beta 1) activator, TGF-β1 inhibitor (SB431542), and PAI-1 inhibitor (TM5275); then Western blot, qRT-PCR, and ELISA were used to assess changes. Results The immunohistochemistry and immunofluorescence showed that PAI-1 expression decreased in eNP and mNP, mainly in epithelium and glands. The transcriptional expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 were lower in eNP than IT while mNP group demonstrated lower mRNA expression and protein level of TGF-β1/t-PA/PAI-1/Collagen1 than Control group. In mNP tissue culture in vitro, TGF-β1 activator elevated t-PA, PAI-1, and Collagen1 with higher release of PAI-1 and Collagen1 in supernatant, whereas SB431542 suppressed above reactions; TM5275 lowered transcriptional and protein level of Collagen1 in supernatant. Conclusion Early Nasal polyps' formation in middle meatus mucous is related with fibrillation system PAI-1/t-PA and tissue remodeling; moreover, nasal polyps' development is regulated by TGF-β1-mediated PAI-1 reduction. Level of evidence 3b.

Mecanismos de adaptação do coração em atletas de elite do sexo feminino: comparação com indivíduos sadios e tempo de treinamento / Heart adaptation mechanisms in elite female athletes: comparison with healthy individuals and time of training

Fundamento: O exercício intenso e continuado em atletas provoca fenótipos de remodelamento adaptativo, cujos parâmetros podem ser avaliados pela ecocardiografia convencional, e de deformação miocárdica. Assim, foi comparado o remodelamento miocárdico em atletas do sexo feminino (grupo atletas) com mulheres sedentárias da mesma faixa etária (grupo-controle) e entre atletas com maior e menor tempo de treinamento. Métodos: Foram selecionadas 57 futebolistas femininas (grupo atletas) e 25 mulheres sadias sedentárias (grupocontrole). As atletas foram divididas em dois grupos: grupo principal, com 32 atletas, e grupo sub-17, com 25 atletas. Foram determinadas, através de ecocardiografia, as dimensões, a função sistólica e diastólica das câmaras cardíacas e a deformação miocárdica (strain longitudinal, circunferencial, radial e mecânica rotacional), utilizando a estatística Z com significância de p < 0,05. Resultados: A idade dos grupos atletas, controle, principal e sub-17 foi de 22,1±6,3; 21,2±5,0; 26,5±5,1; e 16,5±0,6, respectivamente. O peso, o índice de massa corporal e a frequência cardíaca foram menores no grupo atletas. A espessura das paredes, o índice de massa do ventrículo esquerdo (VE), o volume do átrio esquerdo (AE), a fração de ejeção e as dimensões do ventrículo direito (VD) foram maiores no grupo atletas, mas dentro de valores normais. A deformação miocárdica mostrou diminuição do strain radial, da rotação basal, da rotação apical e do twist, sugerindo mecanismo de reserva contrátil. Esses parâmetros foram menores no grupo principal, que também apresentava maior espessura das paredes, maior volume do AE e maior tamanho do VD, sugerindo que o aumento da reserva contrátil se relaciona com maior tempo de treinamento. Conclusões: As atletas do sexo feminino com treinamento intenso de longa duração apresentam remodelamento adaptativo das câmaras cardíacas e aumento da reserva contrátil observada em repouso, com esses parâmetros mais acentuados nas atletas com maior tempo de treinamento.(AU)

Background: Intense continuous exercise provokes adaptive remodeling phenotypes in athletes, the parameters of which can be evaluated through conventional echocardiography and myocardial deformation. We compared myocardial remodeling in female athletes (athlete group) with sedentary women of the same age range (control group) and between older and younger athletes. Methods: A total of 57 female soccer players and 25 healthy sedentary women were selected. The athlete group was subdivided into a main group and those under 17 years of age (< 17 group). The dimensions and systolic and diastolic function of the cardiac chambers and myocardial deformation (longitudinal and circumferential, as well as radial strain and rotational mechanics) was determined through echocardiography, using the Z statistic with a significance level of p< 0.05. Results: The mean age of the athlete, control, main, and < 17 groups was 22.1 (SD, 6.3); 21.2 (SD, 5.0); 26.5 (SD, 5.1); 16.5 (SD, 0.6) years, respectively. Weight, body mass index and heart rate were lower in the athlete group. Wall thickness, left ventricular mass index, left atrial (LA) volume, ejection fraction, and right ventricular dimensions were higher in athlete group, but remained within normal ranges. Regarding myocardial deformation, there was decreased radial strain, basal rotation, apical rotation, and twisting in the athlete group, suggesting a contractile reserve mechanism. These parameters were lesser in the main athlete group, who also had greater wall thickness, greater volume in the left atrium (LA) and larger size in the right ventricle (RV), suggesting that increased contractile reserve is related to longer time spent in the sport. Conclusions: In female athletes who had undergone intense long-term training, we observed adaptive remodeling of the cardiac chambers and increased contractile reserve (at rest), and these changes were more pronounced in those with longer involvement in the sport.(AU)

Remodelado eléctrico reverso en pacientes tratados con terapia de resincronización cardíaca / Reverse electrical remodeling in patients under cardiac resynchronization therapy

RESUMEN Introducción : La terapia de resincronización cardíaca (TRC) se indica en pacientes que habitualmente presentan remodelado cardíaco generado por dilatación y disincronía contráctil. La TRC contribuye al remodelado reverso, relacionado con menor mortalidad y hospitalizaciones por insuficiencia cardíaca (IC). Se han observado además mejoras en la conducción intraventricular, con reducción del tiempo de activación. La cuantificación del remodelado eléctrico reverso se ha subutilizado como parámetro de respuesta, con escasos reportes sobre su asociación con la respuesta clínica-estructural. Objetivo : Analizar el remodelado eléctrico reverso intraventricular como parámetro de respuesta a la TRC. Métodos: Se incluyeron pacientes con más de 6 meses de implante. Se obtuvo un ECG con estimulación desactivada (QRS intrínseco, QRSi, post TRC), y por ecocardiograma transtorácico se definió la fracción de eyección ventricular izquierda (FEVI), el diámetro de fin de diástole del ventrículo izquierdo (DFDVI) y la presencia de insuficiencia mitral. Se clasificó a los pacientes según la respuesta clínica-estructural. El remodelado eléctrico se caracterizó con la comparación de la duración del QRS pre y post TRC y la valoración de los cambios del QRS (ΔQRSi) entre grupos. Resultados : Se incluyeron 23 pacientes. Un 39% presentó disminución >10 mseg del QRSi. Observamos un QRSi de -9,3 ± 20,7 mseg en respondedores, y 11,25 ± 18,9 mseg en no respondedores (p = 0,027), más acentuada en los hiper respondedores (ΔQRSi: -14,44 ± 17,40 mseg, p = 0,026). Las mujeres con QRS ≥150 mseg pre TRC exhibieron disminución significativa del QRSi (p = 0,0195). Conclusiones : El remodelado eléctrico reverso se comprobó en 39% de los pacientes que recibieron TRC. Observamos una relación significativa del QRSi con la respuesta clínica-estructural, mayor en hiper respondedores. Mujeres con QRS ancho pre-TRC exhiben remodelado eléctrico reverso más acentuado. Este es un parámetro de fácil acceso e interpretación durante los controles ambulatorios.

ABSTRACT Introduction : Cardiac resynchronization therapy (CRT) is indicated in patients who often present cardiac remodeling due to dilatation and contractile dyssynchrony. CRT contributes to reverse remodeling which is associated with reduced mortality and heart failure (HF) hospitalizations. Improvements in intraventricular conduction with decreased ventricular activation time have also been observed. The quantification of reverse electrical remodeling has been underused as a parameter of response, and there are few reports on its association with the clinical-structural response. Objective : To analyze intraventricular reverse electrical remodeling as a parameter of response to CRT in living individuals. Methods : We included patients implanted at least 6 months ago. A deactivated stimulation ECG (post-CRT intrinsic QRS) was obtained, and by means of transthoracic echocardiography (TTE), the left ventricular ejection fraction (LVEF), the left ventricular end-diastolic diameter (LVEDD) and the presence of mitral regurgitation were defined. Patients were classified according to their clinical-structural response. Electrical remodeling was characterized by comparing pre- and post-CRT QRS duration and assessing QRS changes (ΔiQRS) between groups. Results : A total of 23 patients were included, 39% of which showed a >10 ms decrease in iQRS. We observed a iQRS of -9.3±20.7 ms in responders, and of 11.25±18.9 ms in non-responders (p=0.027), more marked in hyper-responders (ΔiQRS: -14.44±17.40 ms, p=0.026). Women with pre-CRT QRS ≥150 ms showed a significant decrease in iQRS (p=0.0195). Conclusion : Reverse electrical remodeling was found in 39% of the patients under CRT. We noted a significant relationship between iQRS and clinical-structural response, higher in hyper-responders. Women with wider pre-CRT QRS showed more marked reverse electrical remodeling. This parameter is accessible and easy to read in outpatient visits.

Synovium and blood capillaries at the femoral attachment of anterior cruciate ligament are significantly abundant than those at the tibial attachment / Sinovial y capilares sanguíneos en la inserción femoral del ligamento cruzado anterior son significativamente más abundantes que los de la inserción tibial

SUMMARY: The anterior cruciate ligament (ACL) is a ligament that mainly controls the anterior and rotational mobility of the knee joint, and its surface is covered by a synovial membrane with large number of blood vessels. In general, nutritional supply to the ligament is from many capillaries in the adjacent synovium. However, statistical studies of the capillaries distributed to the ACL are insufficient. In this study, we examined cross-sectional histological images of the femoral attachment (femoral level), middle level of the tendon (middle level), and tibial attachment (tibial level) of the ACL and statistically analyzed blood capillary distribution among the three levels. The ACLs of 10 cadavers were divided into 5 equal sections, and 4mm-thick paraffin sections were made at the femoral level, middle level, and tibial level, and then hematoxylin-eosin (HE) staining were performed. The area of each transverse section was measured using Image-J 1.51n (U. S. National Institutes of Health, Bethesda, MD, USA). Fiber bundles of the ACL were relatively small and sparse in cross-sectional area at the femoral level and became larger and denser toward the tibial level. Many blood levels. The synovium at the attachment of ACL covered the surface of the fiber bundle and also penetrated deeply between the fiber bundles. In particular, the blood capillaries were densely distributed in the synovium at the femoral attachment rather than another two levels. Indeed, the number of capillaries were also most abundant in the femoral level. The cross-sectional ACL area at the femoral level is significantly small, however, the blood capillaries were most abundant. Therefore, when the ACL is injured, its reconstruction with preservation of the femoral ligamentous remnant may be clinically useful for remodeling of the grafted tendon.

El ligamento cruzado anterior (LCA) es un ligamento que controla principalmente la movilidad anterior y rotacional de la articulación de la rodilla, y su superficie está cubierta por una membrana sinovial con gran cantidad de vasos sanguíneos. En general, el suministro de nutrientes al ligamento proviene de muchos capilares en la sinovial adyacente. Sin embargo, los estudios estadísticos de los capilares distribuidos en el LCA son insuficientes. En este estudio, examinamos imágenes histológicas trans- versales de la inserción femoral (nivel femoral), el nivel medio del tendón (nivel medio) y la inserción tibial (nivel tibial) del LCA y analizamos estadísticamente la distribución de los capilares sanguíneos entre los tres niveles. Los LCA de 10 cadáveres se dividieron en 5 secciones iguales y se realizaron cortes en parafina de 4 µm de espesor a nivel femoral, medio y tibial, y luego se realizó tinción con hematoxilina-eosina (HE). El área de cada sección transversal se midió utilizando Image-J 1.51n (Institutos Nacionales de Salud de EE. UU., Bethesda, MD, EE. UU.). Los haces de fibras del LCA eran relativamente pequeños y escasos en el área de la sección transversal a nivel femoral y se hicieron más grandes y más densos hacia el nivel tibial. La membrana sinovial en la unión del LCA cubría la superficie del haz de fibras y también penetraba profundamente entre entre los haces de fibras. En particular, los capilares sanguíneos estaban densamente distribuidos en la unión femoral de la sinovial respecto a los otros dos niveles. De hecho, el número de capilares también fue más abundante a nivel femoral. El área transversal del LCA a nivel femoral era significativamente pequeña, sin embargo, los capilares sanguíneos fueron los más abundantes. Por lo tanto, cuando hay una lesión del LCA su reconstrucción con preservación del ligamento femoral remanente puede ser clínicamente útil para remodelar el tendón injertado.

Como eu faço no Coração de Atleta: avaliação dos diferentes tipos de adaptação ao exercício / My approach to "Athlete'S Heart": evaluation of the different types of adaptation to exercise

A prática regular de esportes pode induzir adaptações no coração, sendo essa condição comumente chamada de "coração de atleta". As alterações observadas incluem dilatação das câmaras cardíacas, aumento da espessura miocárdica, melhora do enchimento ventricular, aumento da trabeculação do ventrículo esquerdo (VE), dilatação da veia cava inferior, entre outras. Essas alterações também podem ser observadas em algumas doenças cardíacas, como cardiomiopatia (CMP) dilatada, hipertrófica e outras. Dessa forma, os exames de imagem cardíaca são fundamentais na identificação dessas alterações e na diferenciação entre o "coração de atleta" e uma possível cardiopatia.(AU)

Exercise-induced adaptation may occur in amateur and professional athletes. This condition is commonly named "athlete's heart". The alterations observed include dilation of the heart chambers, increased myocardial thickness, improved ventricular filling, increased left ventricular trabeculation, dilation of the inferior vena cava, among others. These changes can also be observed in some heart diseases, such as dilated, hypertrophic and other cardiomyopathies (CMP). Thus, cardiac imaging tests are fundamental in identifying these alterations and in differentiating between "athlete's heart" and possible heart disease. (AU)

Efectos de la microvibración y estrógeno en la remodelación ósea: revisión sistemática / Effects of micro-vibration and estrogen on bone: a systematic review

Introducción: la pérdida de hueso es un suceso que afecta a la totalidad del esqueleto. Así, las alteraciones musculoesqueléticas afectan a millones de personas en todo el mundo y están entre las causas más comunes de dolor crónico. Objetivo: conocer los efectos de la microvibración y estrógeno en el remodelado óseo. Material y métodos: se realizó una revisión sistemática, se buscó en siete bases de datos, se incluyeron estudios clínicos controlados realizados con ratas o ratones en el periodo de publicación del 2004 al 2022. La calidad de la evidencia sintetizada se evaluó con la escala de Jadad. Resultados: se identificaron quince artículos como estudios primarios. La microvibración reportó cambios in vivo/in vitro totalmente dependientes del estímulo que conlleva incremento de la cortical externa. A su vez, con la administración de estrógeno se reportaron efectos, específicamente, en el hueso trabecular y en el periostio, así como colágeno inmaduro que indican un recambio óseo. Conclusión: tanto la microvibración como la administración de estrógeno coadyuvan a la remodelación del tejido óseo y son aprovechables como tratamiento en el momento que exista un problema de pérdida ósea (AU)

Introduction: Bone loss is an event that affects the entire skeleton. Thus, musculoskeletal disorders affect millions of people worldwide and are among the most common causes of chronic pain. Objective: to know the effects of micro-vibration and estrogen on bone remodelling. Material and methods: a systematic review was carried out; seven databases were searched; Controlled clinical studies conducted with rats or mice in the publication period from 2004 to 2022 were included. The quality of the synthesized evidence was assessed using the Jadad scale. Results: fifteen articles were identified as primary studies. Micro vibration reported in vivo/in vitro changes dependent on the stimulus that entails an increase in the outer cortex. In turn, with the administration of estrogen, effects were reported, specifically in the trabecular bone and in the periosteum, as well as immature collagen that indicates bone turnover. Conclusion: both micro-vibration and the administration of estrogen contribute to the remodelling of bone tissue and are usable as a treatment for bone loss (AU)

Differences in Cardiovascular Remodeling in Kidney Transplant Recipients and Peritoneal Dialysis Patients

Aims: Cardiovascular disease (CVD) is the leading cause of death in dialysis patients as well as in kidney transplant recipients (KTx). Left ventricular hypertrophy (LVH) starts early during the course of chronic kidney disease and is a strong predictor of CVD. We hypothesised that kidney transplant is significantly associated with improvement in cardiovascular reserve. We conducted a prospective study to compare changes in CV before and after kidney transplantation in patients with ESRD who received KTx to control individuals who received PD but did not receive a KTx. Study Design: A Case-Control Study. Place and Duration of Study: Clinic for nephrology Clinical Center University of Sarajevo, Bosnia and Herzegovina. Methodology: In this case-control study, we included 50 KTx from the Kidney Transplant Outpatient Clinic for nephrology Clinical Center. For each 50 KTx, PD outpatients matched for gender and age were recruited. All patients underwent transthoracic echocardiography, and LV (left ventricular) mass (LVM), LV mass index (LVMi), and indices of cardiac function were measured. In the small subgroup of 18 KTx, we retrospectively assessed and compared the LVMI measurements, during dialysis and the post-transplant period. Results: The prevalence of LVH was 24% in KTx patients and 72% in PD patients (NS). KTx had significantly lower LVM, LVMi levels, E/A ratio, FS, and LA diameter compared with the PD group, while the EF and other echocardiographic parameters did not differ. In the subgroup of 18 KTx, LVMi levels after transplantation were significantly lower than dialysis LVMi levels. Conclusion: LVH is the most frequent cardiac abnormality at the time of kidney transplantation. After KTx, the reduction of LVH and diastolic dysfunction was significant. CV remodelling after successful KTx is related to better kidney function, and can explain better outcomes for patients with kidney transplants over patients on long-term dialysis.