Effects of Palm Oil Deodorizer Distillate on the Ruminal Environment of Sheep.

This study aimed to assess the impact of palm oil deodorizer distillate (POD) on the ruminal environment, including (i) microbial community, (ii) ruminal degradability, and (iii) apparent digestibility in sheep. The data used were derived from twenty rumen-cannulated sheep fed five isoproteic and isofiber diets based on elephant grass (Pennisetum purpureum Schum. cv. Roxo) silage supplemented with 0, 25, 50, 75, or 100 g kg-1 POD on a dry matter (DM) basis. Rumen fluid samples were collected three hours after feeding directly from the ventral sac of the rumen via a cannula and then subjected to DNA extraction, which was subsequently used for 16S rDNA amplification, followed by sequencing and diversity analysis. In this study, the microbial diversity was dominated by Bacteroidetes and Firmicutes, followed by Euryarchaetoa, Actinobacteria, and Tenericutes, in the ruminal environment, and was slightly modified when supplemented with the POD up to 100 g/kg (10%), leading to only a slight decrease in the diversity index. The ruminal degradability, ruminal fermentation parameters, and apparent digestibility were slightly compromised by the inclusion of up to 25 g of POD per kg of DM, and larger inclusions interfered with the ruminal degradability of fibrous fractions and the apparent digestibility of dry matter. This lipid supplement showed good results for feeding sheep and is an inexpensive and abundant alternative in the regional market.

Exploring the role non-coding RNAs during myocardial cell fate.

Myocardial cell fate specification takes place during the early stages of heart development as the precardiac mesoderm is configured into two symmetrical sets of bilateral precursor cells. Molecular cues of the surrounding tissues specify and subsequently determine the early cardiomyocytes, that finally matured as the heart is completed at early postnatal stages. Over the last decade, we have greatly enhanced our understanding of the transcriptional regulation of cardiac development and thus of myocardial cell fate. The recent discovery of a novel layer of gene regulation by non-coding RNAs has flourished their implication in epigenetic, transcriptional and post-transcriptional regulation of cardiac development. In this review, we revised the current state-of-the-art knowledge on the functional role of non-coding RNAs during myocardial cell fate.

STEERING THE MICROBIOTA-GUT-BRAIN AXIS BY ANTIBIOTICS TO MODEL NEURO-IMMUNE-ENDOCRINE DISORDERS.

BACKGROUND: Over the last century, animal models have been employed to study the gut-brain axis and its relationship with physiological processes, including those necessary for survival, such as food intake regulation and thermoregulation; those involved in diseases, ranging from inflammation to obesity; and those concerned to the development of neurodegenerative diseases and neuropsychiatric disorders, such as Alzheimer's disease and autism spectrum disorder, respectively. SUMMARY: The gut microbiota has been recognized in the last decade as an essential functional component of this axis. Many reports demonstrate that the gut microbiota influences the development of a vast array of physiological processes. Experiments that use animal models to assess the effect of the gut microbiota on the brain and behavior may involve the acute or chronic administration of wide-spectrum antibiotics. KEY MESSAGES: This narrative review summarizes the beneficial or detrimental effects of antibiotics administered prenatally or postnatally to rodents during acute or chronic periods in a wide range of protocols. These include animal models of disease and behavioral paradigms of learning and memory, anxiety, obsessive-compulsive disorder, and autism spectrum disorder. Biomarkers and behavioral assays associated with antibiotic exposure are also included in this review.

Lp(a) Levels in Relatives of Patients with Acute Coronary Syndrome and Elevated Lp(a): HER(a) Study.

Background: Lipoprotein(a) [Lp(a)] is a proatherogenic particle associated with increased cardiovascular risk. It is mainly genetically determined; so, the aim of our study is to evaluate the levels of Lp(a) in the relatives of a prospective cohort of patients who have suffered from an acute coronary syndrome (ACS) with Lp(a) ≥ 50 mg/dL. Methods: We conducted a multicenter prospective study, in which consecutive patients who had suffered from an ACS and presented Lp(a) ≥ 50 mg/dL and their first-degree relatives were included. Results: We included 413 subjects, of which 56.4% were relatives of the patients. Family history of early ischemic heart disease was present in 57.5%, and only 20.6% were receiving statin treatment. The family cohort was younger (37.5 vs. 59.1 years; p < 0.001), and 4% had ischemic heart disease and fewer cardiovascular risk factors. Mean Lp(a) levels were 64.9 mg/dL, 59.4% had levels ≥ 50 mg/dL, and 16.1% had levels ≥ 100 mg/dL. When comparing the patients with respect to their relatives, the mean level of Lp(a) was lower but without significant differences regarding the levels of LDLc, ApoB, and non-HDL. However, relatives with Lp(a) ≥ 50 mg/dL, had values similar to the group of patients with ACS (96.8 vs. 103.8 mg/dL; p = 0.18). No differences were found in Lp(a) levels in relatives based on the other lipid parameters. Conclusions: Overall, 59.4% of the first-degree relatives of patients who suffered from an ACS with Lp(a) ≥ 50 mg/dL also had elevated levels. Relatives with elevated Lp(a) had similar levels as patients.

High-resolution X-Ray imaging of small animal samples based on Commercial-Off-The-Shelf CMOS image sensors.

 An automated system for acquiring microscopic-resolution radiographic images of biological samples was developed. Mass-produced, low-cost, and easily automated components were used, such as Commercial-Off-The-Self CMOS image sensors (CIS), stepper motors, and control boards based on Arduino and RaspberryPi. System configuration, imaging protocols, and Image processing (filtering and stitching) were defined to obtain high-resolution images and for successful computational image reconstruction. Radiographic images were obtained for animal samples including the widely used animal models zebrafish (Danio rerio) and the fruit-fly (Drosophila melanogaster), as well as other small animal samples. The use of phosphotungstic acid (PTA) as a contrast agent was also studied. Radiographic images with resolutions of up to (7±0.6)µm were obtained, making this system comparable to commercial ones. This work constitutes a starting point for the development of more complex systems such as X-ray attenuation micro-tomography systems based on low-cost off-the-shelf technology. It will also bring the possibility to expand the studies that can be carried out with small animal models at many institutions (mostly those working on tight budgets), particularly those on the effects of ionizing radiation and absorption of heavy metal contaminants in animal tissues.

SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice.

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis.

Unraveling the Signaling Dynamics of Small Extracellular Vesicles in Cardiac Diseases.

Effective intercellular communication is essential for cellular and tissue balance maintenance and response to challenges. Cellular communication methods involve direct cell contact or the release of biological molecules to cover short and long distances. However, a recent discovery in this communication network is the involvement of extracellular vesicles that host biological contents such as proteins, nucleic acids, and lipids, influencing neighboring cells. These extracellular vesicles are found in body fluids; thus, they are considered as potential disease biomarkers. Cardiovascular diseases are significant contributors to global morbidity and mortality, encompassing conditions such as ischemic heart disease, cardiomyopathies, electrical heart diseases, and heart failure. Recent studies reveal the release of extracellular vesicles by cardiovascular cells, influencing normal cardiac function and structure. However, under pathological conditions, extracellular vesicles composition changes, contributing to the development of cardiovascular diseases. Investigating the loading of molecular cargo in these extracellular vesicles is essential for understanding their role in disease development. This review consolidates the latest insights into the role of extracellular vesicles in diagnosis and prognosis of cardiovascular diseases, exploring the potential applications of extracellular vesicles in personalized therapies, shedding light on the evolving landscape of cardiovascular medicine.

miRNAs in Heart Development and Disease.

Cardiovascular diseases (CVD) are a group of disorders that affect the heart and blood vessels. They include conditions such as myocardial infarction, coronary artery disease, heart failure, arrhythmia, and congenital heart defects. CVDs are the leading cause of death worldwide. Therefore, new medical interventions that aim to prevent, treat, or manage CVDs are of prime importance. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level and play important roles in various biological processes, including cardiac development, function, and disease. Moreover, miRNAs can also act as biomarkers and therapeutic targets. In order to identify and characterize miRNAs and their target genes, scientists take advantage of computational tools such as bioinformatic algorithms, which can also assist in analyzing miRNA expression profiles, functions, and interactions in different cardiac conditions. Indeed, the combination of miRNA research and bioinformatic algorithms has opened new avenues for understanding and treating CVDs. In this review, we summarize the current knowledge on the roles of miRNAs in cardiac development and CVDs, discuss the challenges and opportunities, and provide some examples of recent bioinformatics for miRNA research in cardiovascular biology and medicine.

[Correlation of left ventricular contractile function with the presence of collateral coronary circulation in non-reperfused acute myocardial infarction]. / Correlación de la función contráctil del ventrículo izquierdo con la presencia de circulación coronaria colateral en infarto agudo de miocardio no reperfundido.

Objective: To assess the association between coronary collateral circulation and ventricular contractile function in patients with non-reperfused acute myocardial infarction. Method: A retrospective and descriptive clinical study was conducted on patients with ST-elevation myocardial infarction (STEMI) at a reference cardiovascular center, from January 2006 to December 2022. Coronary angiographies and echocardiograms were reviewed to evaluate coronary collateral circulation and ventricular function, respectively. Patients were divided into groups based on the presence of collateral circulation. Both groups were compared and mortality during the index hospitalization was analyzed. Results: Out of a total of 14,985 patients with acute coronary syndrome, 8134 (54.3%) had the diagnosis of STEMI. We excluded 12,880, leaving a total of 2105 non-reperfused STEMI patients who underwent coronary angiography, revealing lesions. There were more patients without collateral circulation: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Patients without collateral circulation had a higher left ventricular ejection fraction (median of 47% vs. 42%; p < 0.001). Mortality in patients with collateral circulation was higher compared to those without it (11.6% vs. 9.8%; p = 0.225), but statistical significance was not reached. Conclusions: Non-reperfused STEMI patients did not show protection from collateral circulation when assessing left ventricular systolic function. We did not find a difference in mortality compared to the population without development of collateral circulation.

Objetivo: Evaluar la asociación entre la circulación coronaria colateral y la función contráctil ventricular en pacientes con infarto agudo de miocardio no reperfundido. Método: Estudio observacional descriptivo y retrospectivo en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en un centro cardiovascular de referencia, de enero de 2006 a diciembre de 2022. Se analizaron las coronariografías y los ecocardiogramas para evaluar la circulación coronaria colateral y la función ventricular, respectivamente. Se dividieron en grupos de acuerdo con la presencia de circulación colateral. Se compararon ambos grupos y se analizó la mortalidad durante la hospitalización del evento índice. Resultados: De 14,985 pacientes con síndrome coronario agudo, 8134 (54.3%) presentaron IAMCEST. Se excluyeron 12,880, quedando así 2105 pacientes con IAMCEST no reperfundidos y sometidos a coronariografía, revelando lesiones. Hubo más pacientes sin circulación colateral: 1547 (73.5%) vs. 558 (26.5%) (p = 0.025). Los pacientes sin circulación colateral presentaron una mayor fracción de eyección ventricular izquierda (mediana del 47% vs. 42%; p < 0.001). La mortalidad en los pacientes con circulación colateral fue mayor que en los pacientes sin ella (11.6% vs. 9.8%; p = 0.225), pero no se alcanzó significancia estadística. Conclusiones: Los pacientes con IAMCEST no reperfundidos no presentaron protección por la circulación colateral al evaluar la función sistólica ventricular izquierda. No se encontró diferencia en la mortalidad en comparación con la población sin desarrollo de circulación colateral.

miR-195b is required for proper cellular homeostasis in the elderly.

Over the last decade we have witnessed an increasing number of studies revealing the functional role of non-coding RNAs in a multitude of biological processes, including cellular homeostasis, proliferation and differentiation. Impaired expression of non-coding RNAs can cause distinct pathological conditions, including herein those affecting the gastrointestinal and cardiorespiratory systems, respectively. miR-15/miR-16/miR-195 family members have been broadly implicated in multiple biological processes, including regulation of cell proliferation, apoptosis and metabolism within distinct tissues, such as heart, liver and lungs. While the functional contribution of miR-195a has been reported in multiple biological contexts, the role of miR-195b remains unexplored. In this study we dissected the functional role of miR-195b by generating CRISPR-Cas9 gene edited miR-195b deficient mice. Our results demonstrate that miR-195b is dispensable for embryonic development. miR-195b-/- mice are fertile and displayed no gross anatomical and/or morphological defects. Mechanistically, cell cycle regulation, metabolism and oxidative stress markers are distinctly impaired in the heart, liver and lungs of aged mice, a condition that is not overtly observed at midlife. The lack of overt functional disarray during embryonic development and early adulthood might be due to temporal and tissue-specific compensatory mechanisms driven by selective upregulation miR-15/miR-16/miR-195 family members. Overall, our data demonstrated that miR-195b is dispensable for embryonic development and adulthood but is required for cellular homeostasis in the elderly.

Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Metagenomic and genomic analysis of heavy metal-tolerant and -resistant bacteria in resource islands in a semi-arid zone of the Colombian Caribbean.

Bacteria from resource islands can adapt to different extreme conditions in semi-arid regions. We aimed to determine the potential resistance and tolerance to heavy metals from the bacterial community under the canopy of three resource islands in a semi-arid zone of the Colombian Caribbean. Total DNA was extracted from soil and through a metagenomics approach, we identified genes related to heavy metal tolerance and resistance under the influence of drought and humidity conditions, as well as the presence or absence of vegetation. We characterized the genomes of bacterial isolates cultivated in the presence of four heavy metals. The abundances of genes related to heavy metal resistance and tolerance were favored by soil moisture and the presence of vegetation. We observed a high abundance of resistance genes (60.4%) for Cu, Zn, and Ni, while 39.6% represented tolerance. These genes positively correlated with clay and silt content, and negatively correlated with sand content. Resistance and tolerance were associated with detoxification mechanisms involving oxidoreductase enzymes, metalloproteases, and hydrolases, as well as transmembrane proteins involved in metal transport such as efflux pumps and ion transmembrane transporters. The Bacillus velezensis C3-3 and Cytobacillus gottheilii T106 isolates showed resistance to 5 mM of Cd, Co, Mn, and Ni through detoxification genes associated with ABC pumps, metal transport proteins, ion antiporter proteins, and import systems, among others. Overall, these findings highlight the potential of bacteria from resource islands in bioremediation processes of soils contaminated with heavy metals.

Novel Insights into the Molecular Mechanisms Governing Embryonic Epicardium Formation.

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of an epithelial-mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.

Insights into Antarctic microbiomes: diversity patterns for terrestrial and marine habitats.

Microorganisms in Antarctica are recognized for having crucial roles in ecosystems functioning and biogeochemical cycles. To explore the diversity and composition of microbial communities through different terrestrial and marine Antarctic habitats, we analyze 16S rRNA sequence datasets from fumarole and marine sediments, soil, snow and seawater environments. We obtained measures of alpha- and beta-diversities, as well as we have identified the core microbiome and the indicator microbial taxa of a particular habitat. Our results showed a unique microbial community structure according to each habitat, including specific taxa composing each microbiome. Marine sediments harbored the highest microbial diversity among the analyzed habitats. In the fumarole sediments, the core microbiome was composed mainly of thermophiles and hyperthermophilic Archaea, while in the majority of soil samples Archaea was absent. In the seawater samples, the core microbiome was mainly composed by cultured and uncultured orders usually identified on Antarctic pelagic ecosystems. Snow samples exhibited common taxa previously described for habitats of the Antarctic Peninsula, which suggests long-distance dispersal processes occurring from the Peninsula to the Continent. This study contributes as a baseline for further efforts on evaluating the microbial responses to environmental conditions and future changes.

Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart-Part II: Molecular Mechanisms of Cardiac Regeneration.

Cardiovascular diseases are the leading cause of death worldwide, among which ischemic heart disease is the most representative. Myocardial infarction results from occlusion of a coronary artery, which leads to an insufficient blood supply to the myocardium. As it is well known, the massive loss of cardiomyocytes cannot be solved due the limited regenerative ability of the adult mammalian hearts. In contrast, some lower vertebrate species can regenerate the heart after an injury; their study has disclosed some of the involved cell types, molecular mechanisms and signaling pathways during the regenerative process. In this 'two parts' review, we discuss the current state-of-the-art of the main response to achieve heart regeneration, where several processes are involved and essential for cardiac regeneration.

Understanding Epicardial Cell Heterogeneity during Cardiogenesis and Heart Regeneration.

The outermost layer of the heart, the epicardium, is an essential cell population that contributes, through epithelial-to-mesenchymal transition (EMT), to the formation of different cell types and provides paracrine signals to the developing heart. Despite its quiescent state during adulthood, the adult epicardium reactivates and recapitulates many aspects of embryonic cardiogenesis in response to cardiac injury, thereby supporting cardiac tissue remodeling. Thus, the epicardium has been considered a crucial source of cell progenitors that offers an important contribution to cardiac development and injured hearts. Although several studies have provided evidence regarding cell fate determination in the epicardium, to date, it is unclear whether epicardium-derived cells (EPDCs) come from specific, and predetermined, epicardial cell subpopulations or if they are derived from a common progenitor. In recent years, different approaches have been used to study cell heterogeneity within the epicardial layer using different experimental models. However, the data generated are still insufficient with respect to revealing the complexity of this epithelial layer. In this review, we summarize the previous works documenting the cellular composition, molecular signatures, and diversity within the developing and adult epicardium.