-derived exovesicles contribute to parasite infection, tissue damage, and apoptotic cell death during infection of human placental explants.

, the causative agent of Chagas disease, can be congenitally transmitted by crossing the placental barrier. This study investigates the role of -derived exovesicles (TcEVs) in facilitating parasite infection and the consequent tissue damage and apoptotic cell death in human placental explants (HPEs). Our findings demonstrate that TcEVs significantly enhance the parasite load and induce tissue damage in HPEs, both in the presence and absence of the parasite.

Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route.

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC-such as 5-fluorouracil (5FU)-remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential.

First-in-Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986308: A Renal Outer Medullary Potassium Channel Inhibitor.

In patients with heart failure (HF) who respond inadequately to loop diuretic therapy, BMS-986308, an oral, selective, reversible renal outer medullary potassium channel (ROMK) inhibitor may represent an effective diuretic with a novel mechanism of action. We present data from the first-in-human study aimed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) following single ascending doses of BMS-986308 in healthy adult participants. Forty healthy participants, aged from 20 to 55 years, and body mass index (BMI) from 19.

Assessment of the Activity of Nitroisoxazole Derivatives against .

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 , with a 52 ± 4% trypanocidal effect for compound .

Validation of Math Model Using Porous Media for Determining Alveolar CO 2 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.

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.

SGK1 is necessary to FoxO3a negative regulation, oxidative stress and cardiac fibroblast activation induced by TGF-β1.

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.

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, N, and air atmospheres, and proposes fast heating (60 °C • s) 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.

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.

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.

Statins change the cytokine profile in -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-1β, IL-6, and TNF-α to control parasitemia.

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.

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.

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

Congenital Chagas disease, caused by the protozoan parasite , 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.

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.

Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation in a murine model of early chronic Chagas disease.

Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. In 30% of cases, after years of infection and in the absence of treatment, the disease progresses from an acute asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy.

Computational model of trachea-alveoli gas movement during spontaneous breathing.

A computational model of the transport of gases involved in spontaneous breathing, from the trachea inlet to the alveoli was developed for healthy patients. Convective and diffusive transport mechanisms were considered simultaneously, using a diffusion coefficient (D) that has considered the four main species of gases present in the exchange carried out by the human lung, nitrogen (N), oxygen (O), carbon dioxide (CO) and water vapor (HO). A Matlab® script was programmed to simulate the trachea-alveolus gas exchange model under three respiratory frequencies: 12, 24 and 40 breaths per minute (BPM), each with three diaphragmatic movements of 2 cm, 4 cm, and 6 cm.

New benzimidazolequinones as trypanosomicidal agents.

Herein, the design and synthesis of new 2-phenyl(pyridinyl)benzimidazolequinones and their 5-phenoxy derivatives as potential anti-Trypanosoma cruzi agents are described. The compounds were evaluated in vitro against the epimastigotes and trypomastigote forms of Trypanosoma cruzi. The replacing of a benzene moiety in the naphthoquinone system by an imidazole enhanced the trypanosomicidal activity against Trypanosoma cruzi.

Ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii: differential activation of NF kappa B signaling pathways.

Chagas disease and toxoplasmosis, caused by Trypanosoma cruzi and Toxoplasma gondii, respectively, are important zoonotic diseases affecting humans, companion animals, and livestock, responsible for major health and economic burden. Both parasites can be transmitted vertically in different mammalian species through the placenta. Of note, the transmission rate of T.

and Induce a Differential MicroRNA Profile in Human Placental Explants.

and are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for and high for . Infection success or failure depends on complex parasite-host interactions in which parasites can alter host gene expression by modulating non-coding RNAs such as miRNAs.

Immunoglobulin G4 (IgG4)-Related Sialadenitis and Dacryoadenitis With Chronic Rhinosinusitis.

Immunoglobulin G4-related disease (IgG4-RD) is a new disease entity of rare and complex immune-mediated fibroinflammatory conditions that can affect any organ. The concomitance of IgG4 sclerosing sialadenitis and dacryoadenitis with rhinosinusitis is extremely rare. We report a case of IgG4 sclerosing sialadenitis and dacryoadenitis (Mikulicz's disease) diagnosed in a middle-aged African American man with a long-standing history of chronic rhinosinusitis who presented with progressively worsening bilateral salivary and lacrimal glands swelling.

Simvastatin Improves Cardiac Function through Notch 1 Activation in BALB/c Mice with Chronic Chagas Cardiomyopathy.

Chagas disease, caused by the protozoan , endemic in Latin America but distributed worldwide because of migration. Without appropriate treatment, the disease progresses from an acute asymptomatic phase to a chronic, progressive inflammatory cardiomyopathy causing heart failure and death. Despite specific trypanocidal therapy, heart damage progression cannot be stopped or reversed.

Novel benzoate-lipophilic cations selectively induce cell death in human colorectal cancer cell lines.

Introduction: Colorectal cancer (CRC) is a critical health issue worldwide. The high rate of liver and lung metastasis associated with CRC creates a significant barrier to effective and efficient therapy. Tumour cells, including CRC cells, have metabolic alterations, such as high levels of glycolytic activity, increased cell proliferation and invasiveness, and chemo- and radio-resistance.