Validation of Math Model Using Porous Media for Determining Alveolar co2 in Ventilated Patients.

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO2), area under the CO2 curve, and PaCO2 of 0.918, 0.954, and 0.995. Determination coefficients (R2) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education.

Assessment of the Activity of Nitroisoxazole Derivatives against Trypanosoma cruzi.

The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 ± 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.

MicroRNA-512-3p mediates Trypanosoma cruzi-induced apoptosis during ex vivo infection of human placental explants.

INTRODUCTION: Upon infection, Trypanosoma cruzi, a protozoan parasite, crosses the placental barrier and causes congenital Chagas disease. Ex vivo infection of human placental explants (HPEs) with the parasite induces apoptotic cell death. This cellular process involves changes in gene expression, which are partially regulated by miRNAs. In this study, we investigated the role of miR-512-3p, a highly expressed miRNA in the placenta, in parasite-induced apoptosis. METHODS: HPE cells were transfected with antagomirs or mimics of miR-512-3p and subsequently challenged with the parasite. The expression levels of miR-512-3p, caspase 3, caspase 8, and Livin were measured using RT-qPCR, and apoptotic cell death was analyzed based on caspase activity and DNA fragmentation assays. RESULTS: Targeted inhibition of miR-512-3p effectively prevented parasite-induced expression and enzymatic activity of caspase 3 and caspase 8. However, it did not completely prevent DNA fragmentation, indicating the involvement of other factors in this process. Furthermore, the findings suggest that Livin may be regulated by miR-512-3p. DISCUSSION: Our findings suggest that miR-512-3p modulates parasite-induced apoptosis in the trophoblast. By understanding the mechanisms involved in this process, we can gain insights into the pathogenesis of congenital Chagas disease and develop targeted therapeutic strategies.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review / Uso de estatinas y aspirina en infecciones parasitarias como potencial estrategia terapéutica: Una revisión narrativa

Resumen Las infecciones, incluyendo las zoonosis, constituyen una amenaza a la salud humana debido a la diseminación de patógenos resistentes. Estas enfermedades generan una respuesta inflamatoria controlada por un mecanismo de resolución, en el que participan moléculas especializadas derivadas de lípidos de membrana llamadas lipoxinas, resolvinas, maresinasios o que puede prevenir la derivación hacia cursos crónicos, dañinos para el hospedero. En esta revisión se presenta una puesta al día sobre el uso de estatinas o aspirina para el manejo experimental de infecciones parasitarias, como enfermedad de Chagas, leishmaniasis, toxo-plasmosis y malaria. Se hizo una revisión narrativa, buscando artículos originales de los últimos siete anos, se encontraron 38 que cumplieron con los criterios de inclusión. De acuerdo con las publicaciones consultadas, la resolución de la inflamación modulada mediante estatinas podría ser un adyuvante en la terapia de enfermedades parasitarias. Por otro lado, no se observó una evidencia experimental fuerte con respecto al uso de aspirina, por lo que se recomiendan más estudios para evaluar su rol en el proceso de resolución de la inflamación en enfermedades infecciosas.

Unusual presentation of antisynthetase syndrome: a case series and review of the literature.

BACKGROUND: Antisynthetase syndrome is an inflammatory myopathy that is characterized by the presence of anti-aminoacyl-tRNA synthetase antibodies. Only 30% of those who suffer from the disease can be identified. We present three Hispanic cases of antisynthetase syndrome with unusual clinical pictures were extended myositis panel results enable disease diagnosis and treatment. CASE PRESENTATION: A 57-year-old Hispanic/Latino female with an erythematous scaly plaque, unresolved fever and non-immune haemolytic anaemia in whom inpatient work-up for fever of unknown origin was positive for anti-PL12 positive myositis extended panel. A 72-year-old Hispanic/Latino male with amyopathic weakness syndrome and mechanic hands in whom impatient work-up was relevant for proximal muscle uptake and anti-PM75 and AntiPL-12 myositis extended panel. And a 67-year-old Hispanic/Latino male with progressive interstitial lung disease and unresolved fever ended in myositis extended panel positive for antiPL-7. After systemic immunosuppressor treatment, patients had favourable clinical and paraclinical responses during outpatient follow-up. CONCLUSIONS: The high variability of the antisynthetase syndrome in these cases demonstrates the importance of identification through an expanded panel and highlights the probability that this is a variable disease and that we need to include emerging molecular tests to promote the timely treatment of patients.

SGK1 is necessary to FoxO3a negative regulation, oxidative stress and cardiac fibroblast activation induced by TGF-ß1.

Cardiac fibroblasts (CFs) activation is a common response to most pathological conditions affecting the heart, characterized by increased cellular secretory capacity and increased expression of fibrotic markers, such as collagen I and smooth muscle actin type alpha (α-SMA). Fibrotic activation of CFs induces the increase in tissue protein content, with the consequent tissue stiffness, diastolic dysfunction, and heart failure. Therefore, the search for new mechanisms of CFs activation is important to find novel treatments for cardiac diseases characterized by fibrosis. In this regard, TGF-ß1, a cytokine with proinflammatory and fibrotic properties, is crucial in the CFs activation and the development of fibrotic diseases, whereas its molecular targets are not completely known. Serum and glucocorticoid-regulated kinase (SGK1) is a protein involved in various pathophysiological phenomena, especially cardiac and renal diseases that curse with fibrosis. Additionally, SGK1 phosphorylates and regulates the activity and expression of several targets, highlighting FoxO3a for its role in the regulation of oxidative stress and CFs activation induced by TGF-ß1. However, the regulation of SGK1 by TGF-ß1 and its role in CFs activation have not been studied. In this work, we evaluate the role of SGK1 in CFs isolated from neonatal Sprague-Dawley rats. The participation of SGK1 in the fibrotic activation of CFs induced by TGF-ß1 was analyzed, using an inhibitor or siRNA of SGK1. In addition, the role of SGK1 on the regulation of FoxO3a and oxidative stress induced by TGF-ß1 was analyzed. Our results indicate that TGF-ß1 increased both the activity and expression of SGK1 in CFs, requiring the activation of MAPKs, ERK1/2, p38 and JNK, while inhibition and silencing of SGK1 prevented TGF-ß1-induced fibrotic activation of CFs. In addition, SGK1 inhibition prevented FoxO3a inactivation and expression reduction, catalase and SOD2 expression decrease, and the increase of oxidative stress induced by TGF-ß1. Taken together, our results position SGK1 as an important regulator of CFs activation driven by TGF-ß1, at least in part, through the regulation of FoxO3a and oxidative stress.

Release of phenolic compounds from fermented cocoa powder during fast heating in a novel hot plate reactor.

This article studies the release of phenolic compounds during cocoa heating under vacuum, N2, and air atmospheres, and proposes fast heating (60 °C • s-1) as a methodology that allows the release of polyphenols from fermented cocoa powder. We aim to demonstrate that gas phase transport is not the only mechanism to extract compounds of interest and that convective-type mechanisms can facilitate the process by reducing their degradation. The oxidation and transport phenomena were evaluated both in the extracted fluid and in the solid sample during the heating process. Polyphenols transport phenomena were assessed based on the fluid (chemical condensate compounds) that was collected cold with an organic solvent (methanol) in a hot plate reactor. Out of all the polyphenolic compounds present in cocoa powder, we assessed specifically the release of catechin and epicatechin. We found that high heating rates combined with vacuum or N2 favor the ejection of liquids; then, it is possible to extract compounds such as catechin-which is dissolved/entrained and transported in the ejected liquids-and avoid degradation phenomena.

Statin and aspirin use in parasitic infections as a potential therapeutic strategy: A narrative review.

Infections, including zoonoses, constitute a threat to human health due to the spread of resistant pathogens. These diseases generate an inflammatory response controlled by a resolving mechanism involving specialized membrane lipid-derived molecules called lipoxins, resolvins, maresins, and protectins. The production of some of these molecules can be triggered by aspirin or statins. Thus, it is proposed that modulation of the host response could be a useful therapeutic strategy, contributing to the management of resistance to antiparasitic agents or preventing drift to chronic, host-damaging courses. Therefore, the present work presents the state of the art on the use of statins or aspirin for the experimental management of parasitic infections such as Chagas disease, leishmaniasis, toxoplasmosis or malaria. The methodology used was a narrative review covering original articles from the last seven years, 38 of which met the inclusion criteria. Based on the publications consulted, modulation of the resolution of inflammation using statins may be feasible as an adjuvant in the therapy of parasitic diseases. However, there was no strong experimental evidence on the use of aspirin; therefore, further studies are needed to evaluate its role inflammation resolution process in infectious diseases.

Ibuprofen: Toxicology and Biodegradation of an Emerging Contaminant.

The anti-inflammatory drug ibuprofen is considered to be an emerging contaminant because of its presence in different environments (from water bodies to soils) at concentrations with adverse effects on aquatic organisms due to cytotoxic and genotoxic damage, high oxidative cell stress, and detrimental effects on growth, reproduction, and behavior. Because of its high human consumption rate and low environmental degradation rate, ibuprofen represents an emerging environmental problem. Ibuprofen enters the environment from different sources and accumulates in natural environmental matrices. The problem of drugs, particularly ibuprofen, as contaminants is complicated because few strategies consider them or apply successful technologies to remove them in a controlled and efficient manner. In several countries, ibuprofen's entry into the environment is an unattended contamination problem. It is a concern for our environmental health system that requires more attention. Due to its physicochemical characteristics, ibuprofen degradation is difficult in the environment or by microorganisms. There are experimental studies that are currently focused on the problem of drugs as potential environmental contaminants. However, these studies are insufficient to address this ecological issue worldwide. This review focuses on deepening and updating the information concerning ibuprofen as a potential emerging environmental contaminant and the potential for using bacteria for its biodegradation as an alternative technology.

Lipoxin A4 prevents high glucose-induced inflammatory response in cardiac fibroblast through FOXO1 inhibition.

Cardiac cells respond to various pathophysiological stimuli, synthesizing inflammatory molecules that allow tissue repair and proper functioning of the heart; however, perpetuation of the inflammatory response can lead to cardiac fibrosis and heart dysfunction. High concentration of glucose (HG) induces an inflammatory and fibrotic response in the heart. Cardiac fibroblasts (CFs) are resident cells of the heart that respond to deleterious stimuli, increasing the synthesis and secretion of both fibrotic and proinflammatory molecules. The molecular mechanisms that regulate inflammation in CFs are unknown, thus, it is important to find new targets that allow improving treatments for HG-induced cardiac dysfunction. NFκB is the master regulator of inflammation, while FoxO1 is a new participant in the inflammatory response, including inflammation induced by HG; however, its role in the inflammatory response of CFs is unknown. The inflammation resolution is essential for an effective tissue repair and recovery of the organ function. Lipoxin A4 (LXA4) is an anti-inflammatory agent with cytoprotective effects, while its cardioprotective effects have not been fully studied. Thus, in this study, we analyze the role of p65/NFκB, and FoxO1 in CFs inflammation induced by HG, evaluating the anti-inflammatory properties of LXA4. Our results demonstrated that HG induces the inflammatory response in CFs, using an in vitro and ex vivo model, while FoxO1 inhibition and silencing prevented HG effects. Additionally, LXA4 inhibited the activation of FoxO1 and p65/NFκB, and inflammation of CFs induced by HG. Therefore, our results suggest that FoxO1 and LXA4 could be novel drug targets for the treatment of HG-induced inflammatory and fibrotic disorders in the heart.

Effect of statins on inflammation and cardiac function in patients with chronic Chagas disease: A protocol for pathophysiological studies in a multicenter, placebo-controlled, proof-of-concept phase II trial.

BACKGROUND: Cardiac complications, including heart failure and arrhythmias, are the leading causes of disability and death in Chagas disease (CD). CD, caused by the Trypanosoma cruzi parasite, afflicts 7 million people in Latin America, and its incidence is increasing in non-endemic countries due to migration. The cardiac involvement is explained by parasite-dependent, immune-mediated myocardial injury, microvascular abnormalities, and ischemia. Current treatment of early CD includes the administration of nifurtimox and benznidazole. However, their efficacy is low in the chronic phase and may induce severe adverse events, forcing therapy to halt. Therefore, finding innovative approaches to treat this life-threatening tropical disease is of utmost importance. Thus, improving the efficacy of the current antichagasic drugs by modifying the inflammatory response would render the current treatment more effective. It has been reported that, in mice, simvastatin decreases cardiac inflammation and endothelial activation, and improves cardiac function, effects that require clinical confirmation. OBJECTIVE: The study aims to analyze whether two doses of Atorvastatin, administered after CD treatment is completed, are safe and more efficacious than the antiparasitic drugs alone in reducing general inflammation and improving endothelial and cardiac functions in a proof-of-concept, placebo-controlled phase II trial. METHODS: 300 subjects will be recruited from four Chilean hospitals with an active Program for the Control of Chagas Disease. 40 or 80 mg/day of atorvastatin or placebo will be administered after completion of the antichagasic therapy. The patients will be followed up for 12 months. Efficacy will be determined by measuring changes in plasma levels of anti-inflammatory and pro-inflammatory cytokines, soluble cell adhesion molecules, BNP, and cTnT. Also, the resting 12-lead ECG and a 2D-echocardiogram will be obtained to evaluate cardiac function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04984616.

Factores socioeconómicos, clínicos y quirúrgicos relacionados al manejo de trauma abdominal penetrante en un hospital de alto nivel de complejidad del caribe colombiano: experiencia de 3 años / Socio-economic, clinical, and surgical factors related to the management of penetrating abdominal trauma in a high-complexity institution in the Colombian Caribbean: 3-year experience

Resumen Introducción: El trauma es una importante causa de mortalidad a nivel mundial y la cuarta causa de muerte en Colombia. Esta condición genera morbilidad y discapacidad, impactando sustancialmente sobre los años de vida potencialmente perdidos, sobre todo, en las edades más tempranas donde es más prevalente. Objetivo: Caracterizar epidemiológica y clínicamente pacientes con trauma abdominal penetrante manejados quirúrgicamente. Materiales y métodos: Estudio observacional de corte transversal y linealidad retrospectiva de pacientes con trauma abdominal penetrante, manejados quirúrgicamente en un hospital de alto nivel de complejidad entre 2016 y 2018, que incluye variables sociodemográficas y clínicas relacionadas con el trauma, el tipo de intervención quirúrgica y complicaciones asociadas. Resultados: Se identificaron 115 pacientes, el 94,8% de sexo masculino. El mecanismo de lesión predominante fue por arma corto-punzante con 67,8%. Se encontró consumo de drogas y sustancias embriagantes relacionado en el 43,7% de los casos. Los principales órganos lesionados fueron el intestino delgado 39.1%, pequeños vasos con 20% e hígado con 16.5%. Los tipos de reparo realizados más frecuentemente fueron la rafia de intestino delgado (22,6 %), y la anastomosis de intestino delgado (20,9%). El Penetrating Abdominal Trauma Index >25 mostró mayor hiperlactatemia (80%) y sepsis (50%). La mortalidad fue del 3.4%, asociado a reintervención y sepsis. Conclusión: La mortalidad por trauma abdominal penetrante en la costa del caribe colombiano es baja. 9 de cada 10 casos son hombres, casi la mitad de los casos se relaciona a consumo de sustancias psicoactivas y las principales complicaciones son la hiperlactatemia y sepsis.

Abstract Introduction: Trauma is an important cause of mortality worldwide and the fourth cause of death in Colombia. This condition generates morbidity and disability, having a substantial impact on the years of life potentially lost, especially in the younger ages where it is more prevalent. Objective: To characterize epidemiologically and clinically patients with penetrating abdominal trauma managed surgically. Materials and methods: Observational cross-sectional retrospective study of patients with penetrating abdominal trauma, surgically managed in a high complexity level hospital between 2016 and 2018, including sociodemographic and clinical variables related to trauma, type of surgical intervention and associated complications. Results: A total of 115 patients were identified, 94.8% of whom were male. The predominant mechanism of injury was a short stabbing weapon (67.8%). Drug and intoxicant use were found in 43.7% of the cases. The main organs injured were the small intestine (39.1%), small vessels (20%) and liver (16.5%). The most frequent types of repair performed were small bowel raffia (22.6%) and small bowel anastomosis (20.9%). The Penetrating Abdominal Trauma Index >25 showed higher hyperlactatemia (80%) and sepsis (50%). Mortality was 3.4%, associated with reoperation and sepsis. Conclusion: Mortality due to penetrating abdominal trauma in the Colombian Caribbean coast is low. Nine out of ten cases are men, almost half of the cases are related to the consumption of psychoactive substances and the main complications are hyperlactatemia and sepsis.

Differential microRNAs expression during ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii.

Trypanosoma cruzi and Toxoplasma gondii are two zoonotic parasites that constitute significant human and animal health threats, causing a significant economic burden worldwide. Both parasites can be transmitted congenitally, but transmission rates for T. gondii are high, contrary to what has been observed for T. cruzi. The probability of congenital transmission depends on complex interactions between the pathogen and the host, including the modulation of host cell gene expression by miRNAs. During ex vivo infection of canine and ovine placental explants, we evaluated the expression of 3 miRNAs (miR-30e-3p, miR-3074-5p, and miR-127-3p) previously associated with parasitic and placental diseases and modulated by both parasites. In addition, we identified the possible target genes of the miRNAs by using computational prediction tools and performed GO and KEGG enrichment analyses to identify the biological functions and associated pathologies. The three miRNAs are differentially expressed in the canine and ovine placenta in response to T. cruzi and T. gondii. We conclude that the observed differential expression and associated functions might explain, at least partially, the differences in transmission rates and susceptibility to parasite infection in different species.

MicroRNAs: master regulators in host-parasitic protist interactions.

MicroRNAs (miRNAs) are a group of small non-coding RNAs present in a wide diversity of organisms. MiRNAs regulate gene expression at a post-transcriptional level through their interaction with the 3' untranslated regions of target mRNAs, inducing translational inhibition or mRNA destabilization and degradation. Thus, miRNAs regulate key biological processes, such as cell death, signal transduction, development, cellular proliferation and differentiation. The dysregulation of miRNAs biogenesis and function is related to the pathogenesis of diseases, including parasite infection. Moreover, during host-parasite interactions, parasites and host miRNAs determine the probability of infection and progression of the disease. The present review is focused on the possible role of miRNAs in the pathogenesis of diseases of clinical interest caused by parasitic protists. In addition, the potential role of miRNAs as targets for the design of drugs and diagnostic and prognostic markers of parasitic diseases is also discussed.

Trypanocidal effect of alcoholic extract of Castanedia santamartensis (Asteraceae) leaves is based on altered mitochondrial function.

The deficit of effective treatments for Chagas disease has led to searching for new substances with therapeutic potential. Natural products possess a wide variety of chemical structural motifs and are thus a valuable source of diverse lead compounds for the development of new drugs. Castanedia santamartensis is endemic to Colombia, and local indigenous communities often use it to treat skin sores from leishmaniasis; however, its mechanism of action against the infective form of Trypanosoma cruzi has not been determined. Thus, we performed chemical and biological studies of two alcoholic leaf extracts of C. santamartensis to identify their active fractions and relate them to a trypanocidal effect and evaluate their mechanism of action. Alcoholic extracts were obtained through cold maceration at room temperature and fractionated using classical column chromatography. Both ethanolic and methanolic extracts displayed activity against T. cruzi. Chemical studies revealed that kaurenoic acid was the major component of one fraction of the methanolic extract and two fractions of the ethanolic extract of C. santamartensis leaves. Moreover, caryophyllene oxide, kaurenol, taraxasterol acetate, pentadecanone, and methyl and ethyl esters of palmitate, as well as a group of phenolic compounds, including ferulic acid, caffeic acid, chlorogenic acid, myricetin, quercitrin, and cryptochlorogenic acid were identified in the most active fractions. Kaurenoic acid and the most active fractions CS400 and CS402 collapsed the mitochondrial membrane potential in trypomastigotes, demonstrating for the first time the likely mechanism against T. cruzi, probably due to interactions with other components of the fractions.

Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation.

Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.

Determination of the metabolic pathways for degradation of naphthalene and pyrene in Amycolatopsis sp. Poz14.

Polycyclic aromatic hydrocarbons (PAHs) constitute important soil contaminants derived from petroleum. Poz14 strain can degrade pyrene and naphthalene. Its genome presented 9333 genes, among them those required for PAHs degradation. By phylogenomic analysis, the strain might be assigned to Amycolatopsis nivea. The strain was grown in glucose, pyrene, and naphthalene to compare their proteomes; 180 proteins were detected in total, and 90 of them were exclusives for xenobiotic conditions. Functions enriched with the xenobiotics belonged to transcription, translation, modification of proteins and transport of inorganic ions. Enriched pathways were pentose phosphate, proteasome and RNA degradation; in contrast, in glucose were glycolysis/gluconeogenesis and glyoxylate cycle. Proteins proposed to participate in the upper PAHs degradation were multicomponent oxygenase complexes, Rieske oxygenases, and dioxygenases; in the lower pathways were ortho-cleavage of catechol, phenylacetate, phenylpropionate, benzoate, and anthranilate. The catechol dioxygenase activity was measured and found increased when the strain was grown in naphthalene. Amycolatopsis sp. Poz14 genome and proteome revealed the PAHs degradation pathways and functions helping to contend the effects of such process.

Three-Dimensional Additive Manufacturing of Artificial Oil Reservoir Rock Core Plugs for Core Flooding Experimental Tests.

Laboratory tests in which a fluid or combination of fluids that are injected into a core rock are designed to determine oil reservoir rock petrophysical properties, understand the mobility of fluid flow in the porous samples, and calibrate porous media fluid flow models. The core material is extracted from the oil reservoir. However, the manufacture of core plugs is challenging because of the complexity of extracting natural rocks from the reservoir and their morphological and atypical heterogeneity. In addition, core flooding tests are essentially destructive, making it impossible to achieve experimental repeatability by using identical cores. The use of 3D printing in digital rock physics has permitted the production and replication of synthetic rock samples with the morphological characteristics of natural rocks for core analysis and core flooding tests. This study proposes the 3D manufacture of artificial core plugs from microcomputed tomography of Berea sandstone. The digital samples were constructed using a digital particle packing approach by systematically manipulating rock textural parameters, such as the grain size and shape, cementation pattern, and sorting grain, making it possible to obtain a core plug that fulfills experimental requirements. Before the 3D printing of the sample, the flow distribution through the porous media structure was numerically simulated using the Lattice Boltzmann method to obtain the core plug samples' permeability and porosity. The core plug was digitally embedded within a core holder to generate a stereolithography file for 3D printing of the core flooding setup, which can be used directly in conventional experiments. The permeabilities of the 3D printed plugs were experimentally determined to permit a direct comparison to the numerical results and evaluate the utility of printed plugs for displacement experiments.

microRNAs: Critical Players during Helminth Infections.

microRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally through their interaction with the 3' untranslated regions (3' UTR) of target mRNAs, affecting their stability and/or translation. Therefore, miRNAs regulate biological processes such as signal transduction, cell death, autophagy, metabolism, development, cellular proliferation, and differentiation. Dysregulated expression of microRNAs is associated with infectious diseases, where miRNAs modulate important aspects of the parasite-host interaction. Helminths are parasitic worms that cause various neglected tropical diseases affecting millions worldwide. These parasites have sophisticated mechanisms that give them a surprising immunomodulatory capacity favoring parasite persistence and establishment of infection. In this review, we analyze miRNAs in infections caused by helminths, emphasizing their role in immune regulation and its implication in diagnosis, prognosis, and the development of therapeutic strategies.

Statins change the cytokine profile in Trypanosoma cruzi-infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition.

Introduction: Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1ß, IL-6, and TNF-α to control parasitemia. Although this response contains parasite infection, it causes damage to the heart tissue. Thus, the use of immunomodulators is a rational alternative to CCC. Rho-associated kinase (ROCK) 1 and 2 are RhoA-activated serine/threonine kinases that regulate the actomyosin cytoskeleton. Both ROCKs have been implicated in the polarization of macrophages towards an M1 (pro-inflammatory) phenotype. Statins are FDA-approved lipid-lowering drugs that reduce RhoA signaling by inhibiting geranylgeranyl pyrophosphate (GGPP) synthesis. This work aims to identify the effect of statins on U937 macrophage polarization and cardiac tissue inflammation and its relationship with ROCK activity during T. cruzi infection. Methods: PMA-induced, wild-type, GFP-, CA-ROCK1- and CA-ROCK2-expressing U937 macrophages were incubated with atorvastatin, or the inhibitors Y-27632, JSH-23, TAK-242, or C3 exoenzyme incubated with or without T. cruzi trypomastigotes for 30 min to evaluate the activity of ROCK and the M1 and M2 cytokine expression and secretion profiling. Also, ROCK activity was determined in T. cruzi-infected, BALB/c mice hearts. Results: In this study, we demonstrate for the first time in macrophages that incubation with T. cruzi leads to ROCK activation via the TLR4 pathway, which triggers NF-κB activation. Inhibition of ROCKs by Y-27632 prevents NF-κB activation and the expression and secretion of M1 markers, as does treatment with atorvastatin. Furthermore, we show that the effect of atorvastatin on the NF-kB pathway and cytokine secretion is mediated by ROCK. Finally, statin treatment decreased ROCK activation and expression, and the pro-inflammatory cytokine production, promoting anti-inflammatory cytokine expression in chronic chagasic mice hearts. Conclusion: These results suggest that the statin modulation of the inflammatory response due to ROCK inhibition is a potential pharmacological strategy to prevent cardiac inflammation in CCC.