Challenges and advancements in the development of vaccines and therapies against Chagas disease.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, presents a substantial global health burden, affecting millions of individuals worldwide and posing a continual risk of infection. Despite the high mortality and morbidity rates, effective vaccines to prevent infection by the parasite remain elusive, and the drugs currently available are suboptimal. Understanding the intricate dynamics of parasite-host interactions and the resulting immune responses, which contribute to both protection and pathology, is crucial for the development of effective vaccines and therapies against Chagas disease.

Enzymatic Synthesis of Austroeupatol Esters with Enhanced Antiprotozoal Activity.

Austroeupatol, the principal diterpene isolated from the invasive shrub , holds promise for structural diversification and biological assessment of its derivatives due to its abundant availability and high yield isolation. We propose an efficient enzymatic synthesis of a series of austroeupatol esters derived from aliphatic and heterocyclic carboxylic acids. Systematic optimization of reaction parameters, including enzyme type and quantity, acylating agent amount, solvent, and temperature, was conducted.

Trypanocidal and Anti-Inflammatory Effects of Three -Kaurane Diterpenoids from var. (Asteraceae).

Chagas disease, caused by the protozoan , affects 6-7 million people worldwide. The dichloromethane extract obtained from the aerial parts of var showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: -9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16)--11α-hydroxy-15-oxokauran-19-oic acid and -11α-hydroxy-15-oxo-kaur-16-en-19-oic acid.

Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties.

Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including , , , , , and , along with pure phytochemicals isolated from Asteraceae: mikanolide (), eupatoriopicrin (), eupahakonenin B (), minimolide (), estafietin (), 2-oxo-8-deoxyligustrin (), santhemoidin C (), euparin (), jaceidin (), nepetin (), jaceosidin (), eryodictiol (), eupatorin (), and 5-demethylsinensetin (). Results showed that the dichloromethane extracts of and and the methanolic extracts prepared from and were highly active and selective against DENV-2, affording EC values of 0.

Zika virus NS4B protein targets TANK-binding kinase 1 and inhibits type I interferon production.

Background: During viral infections, nucleic acid sensing by intracellular receptors can trigger type I interferon (IFN-I) production, key mediators in antiviral innate immunity. However, many flaviviruses use non-structural proteins to evade immune sensing favoring their survival. These mechanisms remain poorly characterized.

toxicologic profile and trypanocidal activity of estafietin, a sesquiterpene lactone isolated from Stevia alpina Griseb.

Chagas disease is an infection caused by the protozoan affecting 6-8 million people worldwide. Only two drugs are available for its treatment, having a limited efficacy and adverse side-effects. Estafietin is a sesquiterpene lactone isolated from with activity against and low cytotoxicity against mammalian cells.

Anti- Properties of Sesquiterpene Lactones Isolated from spp.: In Vitro and In Silico Studies.

species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, var. and were studied.

Enzymatic synthesis of amlodipine amides and evaluation of their anti- activity.

Advancing with our project about the development of new antiparasitic agents, we have enzymatically synthesized a series of amides derived from amlodipine, a calcium channel blocker used as an antihypertensive drug. Through lipase-catalyzed acylation with different carboxylic acids, nineteen amlodipine derivatives were obtained, eighteen of which were new compounds. To optimize the reaction conditions, the influence of several reaction parameters was analyzed, finding different requisites for aliphatic carboxylic acids and phenylacetic acids.

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients.

Oxonitrogenated Derivatives of Eremophilans and Eudesmans: Antiproliferative and Anti- Activity.

Cancer is one of the most important causes of death worldwide. Solid tumors represent the vast majority of cancers (>90%), and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpenes are a group of natural compounds that have shown a wide range of biological activities, including cytotoxic and antiparasitic activity, among others.

, , and Studies of Cumanin Diacetate as a Potential Drug against Infection.

The sesquiterpene lactones cumanin, helenalin, and hymenin and their semisynthetic derivatives were evaluated against epimastigotes. The cytotoxicity of the compounds was evaluated on murine splenocytes. Cumanin diacetate was one of the most active and selective compounds [IC = 3.

Characterization of a new type of neuronal 5-HT G- protein coupled receptor in the cestode nervous system.

Cestodes are platyhelminth parasites with a wide range of hosts that cause neglected diseases. Neurotransmitter signaling is of critical importance for these parasites which lack circulatory, respiratory and digestive systems. For example, serotonin (5-HT) and serotonergic G-protein coupled receptors (5-HT GPCRs) play major roles in cestode motility, development and reproduction.

Right Sinus of Valsalva Aneurysm Mimicking Right Coronary Artery Ischemia.

An aneurysm of a single sinus of Valsalva is rare. It is usually asymptomatic and rarely discovered, unless it compresses the adjacent cardiac structures, or it presents in association with other pathology. We herein describe a case of a male, with known ischemic heart disease, collapsing after sudden back pain.

Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against .

Chagas disease caused by the protozoan parasite is endemic in 21 Latin American countries and the southern United States and now is spreading into several other countries due to migration. Despite the efforts to control the vector throughout the Americas, currently, there are almost seven million infected people worldwide, causing ~10,000 deaths per year, and 70 million people at risk to acquire the infection. Chagas disease treatment is restricted only to two parasiticidal drugs, benznidazole and nifurtimox, which are effective during the acute and early infections but have not been found to be as effective in chronic infection.

Heterologous Chimeric Construct Comprising a Modified Bacterial Superantigen and a Cruzipain Domain Confers Protection Against Infection.

Chagas disease is an endemic chronic parasitosis in Latin America affecting more than 7 million people. Around 100 million people are currently at risk of acquiring the infection; however, no effective vaccine has been developed yet. is the etiological agent of this parasitosis and as an intracellular protozoan it can reside within different tissues, mainly muscle cells, evading host immunity and allowing progression towards the chronic stage of the disease.

Trypanocidal Activity of Four Sesquiterpene Lactones Isolated from Asteraceae Species.

The sesquiterpene lactones eupatoriopicrin, estafietin, eupahakonenin B and minimolide have been isolated from Argentinean Astearaceae species and have been found to be active against epimastigotes. The aim of this work was to evaluate the activity of these compounds by analyzing their effect against the stages of the parasites that are infective for the human. Even more interesting, we aimed to determine the effect of the most active and selective compound on an model of infection.

Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against .

There are several unmet needs in modern immunology. Among them, vaccines against parasitic diseases and chronic infections lead. , the causative agent of Chagas disease, is an excellent example of a silent parasitic invasion that affects millions of people worldwide due to its progression into the symptomatic chronic phase of infection.

Chagas disease vaccine design: the search for an efficient Trypanosoma cruzi immune-mediated control.

Chagas disease is currently endemic to 21 Latin-American countries and has also become a global concern because of globalization and mass migration of chronically infected individuals. Prophylactic and therapeutic vaccination might contribute to control the infection and the pathology, as complement of other strategies such as vector control and chemotherapy. Ideal prophylactic vaccine would produce sterilizing immunity; however, a reduction of the parasite burden would prevent progression from Trypanosoma cruzi infection to Chagas disease.

Recombinant Cysteine Proteinase B from Leishmania braziliensis and Its Domains: Promising Antigens for Serodiagnosis of Cutaneous and Visceral Leishmaniasis in Dogs.

Leishmaniasis represents a group of parasitic diseases caused by a protozoan of the genus and is widely distributed in tropical and subtropical regions. Leishmaniasis is one of the major tropical neglected diseases, with 1.5 to 2 million new cases occurring annually.

Activity of Estafietin and Analogues on and .

Sesquiterpene lactones are naturally occurring compounds mainly found in the Asteraceae family. These types of plant metabolites display a wide range of biological activities, including antiprotozoal activity and are considered interesting structures for drug discovery. Four derivatives were synthesized from estafietin (), isolated from (Asteraceae): 11βH,13-dihydroestafietin (), epoxyestafietin ( and ), 11βH,13-methoxyestafietin, () and 11βH,13-cianoestafietin.

Preparation of Sesquiterpene Lactone Derivatives: Cytotoxic Activity and Selectivity of Action.

Cancer is one of the most important causes of death worldwide. Solid tumors represent the great majority of cancers (>90%) and the chemotherapeutic agents used for their treatment are still characterized by variable efficacy and toxicity. Sesquiterpene lactones are a group of naturally occurring compounds that have displayed a diverse range of biological activities including cytotoxic activity.

Endoscopic management of tracheoesophageal fistulas.

Tracheoesophageal fistulas (TEF) are pathologic communications between the trachea and esophagus. TEF can lead to significant respiratory distress that may result in lethal respiratory compromise, often due to recurrent and intractable infections. Through the use of endoscopy, some TEF can be successfully repaired using different approaches depending on the size, location, availability, and experience of the treating endoscopist.

Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine.

Background: Chagas disease, also known as American Trypanosomiasis, is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection. Despite of being endemic on 21 Latin-American countries, Chagas disease has become a global concern due to migratory movements. Unfortunately, available drugs for the treatment have several limitations and they are generally administered during the chronic phase of the infection, when its efficacy is considered controversial.