First evidence of a serine arginine protein kinase (SRPK) in leishmania braziliensis and its potential as therapeutic target.

Leishmaniasis is a parasitic disease found in tropical and subtropical regions around the world, caused by parasites of the genus Leishmania. The disease is a public health concern and presents clinical manifestations that can cause death, disability, and mutilation. The parasite has promastigote (vector) and amastigote (vertebrate host) forms and kinase enzymes are involved in this differentiation process.

Depletion of Na/H Exchanger Isoform 1 Increases the Host Cell Resistance to Invasion.

Na/H exchanger isoform 1 (NHE1), a member of a large family of integral membrane proteins, plays a role in regulating the cortical actin cytoskeleton. , the agent of Chagas disease, depends on F-actin rearrangement and lysosome mobilization to invade host cells. To determine the involvement of NHE1 in metacyclic trypomastigote (MT) internalization, the effect of treatment in cells with NHE1 inhibitor amiloride or of NHE1 depletion was examined in human epithelial cells.

Gp35/50 mucin molecules of Trypanosoma cruzi metacyclic forms that mediate host cell invasion interact with annexin A2.

Host cell invasion is a critical step for infection by Trypanosoma cruzi, the agent of Chagas disease. In natural infection, T. cruzi metacyclic trypomastigote (MT) forms establish the first interaction with host cells.

Ablation of the Gene of Provides Evidence of P21 as a Mediator in the Control of Epimastigote and Intracellular Amastigote Replication.

P21 is an immunomodulatory protein expressed throughout the life cycle of , the etiologic agent of Chagas disease. and studies have shown that P21 plays an important role in the invasion of mammalian host cells and establishment of infection in a murine model. P21 functions as a signal transducer, triggering intracellular cascades in host cells and resulting in the remodeling of the actin cytoskeleton and parasite internalization.

Annatto Oil Loaded Nanostructured Lipid Carriers: A Potential New Treatment for Cutaneous Leishmaniasis.

Annatto ( L.) is extensively used as food pigment worldwide. Recently, several studies have found it to have healing and antioxidant properties, as well as effective action against leishmaniasis.

Shedding of Surface Molecules That Regulate Host Cell Invasion Involves Phospholipase C and Increases Upon Sterol Depletion.

Metacyclic trypomastigote (MT) forms of have been shown to release into medium gp82 and gp90, the stage-specific surface molecules that regulate host cell invasion, either in vesicles or in soluble form. Here, we found that during interaction of poorly invasive G strain with the host cell, gp82 and gp90 were released in vesicle-like forms, whereas no such release by highly invasive CL strain was observed. Shedding of vesicles of varying sizes by CL and G strains was visualized by scanning electron microscopy, and the protein profile of conditioned medium (CM) of the two strains was similar, but the content of gp82 and gp90 differed, with both molecules being detected in G strain as bands of high intensity in Western blotting, whereas in CL strain, they were barely detectable.

Interaction of Gp82 With Host Cell LAMP2 Induces Protein Kinase C Activation and Promotes Invasion.

The surface molecule gp82 of metacyclic trypomastigote (MT) forms of , the protozoan parasite that causes Chagas disease, mediates the host cell invasion, a process critical for the establishment of infection. Gp82 is known to bind to the target cell in a receptor-dependent manner, triggering Ca signal, actin cytoskeleton rearrangement and lysosome spreading. The host cell receptor for gp82 was recently identified as LAMP2, the major lysosome membrane-associated protein.

Synthesis of cinnamic acid derivatives and leishmanicidal activity against Leishmania braziliensis.

Leishmania braziliensis is one of the pathogenic agents of cutaneous and mucocutanoeous leishmaniasis. There are no validated vaccines to prevent the infection and the treatment relies on drugs that often present severe side effects, which justify the efforts to find new potential antileishmanial drugs. An alternative to promote the discovery of new drugs would be the association of different chemical groups of bioactive compounds.

Carbohydrate-independent antibiofilm effect of Bothrops jararacussu lectin BJcuL on Staphylococcus aureus.

The antivirulence approach to fighting biofilm-based infections caused by Staphylococcus aureus is a promising therapy that has been studied extensively. Here, we compare the antibiofilm activity of a purified lectin from Bothrops jararacussu venom (BJcuL) and commercial lectins obtained from Triticum vulgaris (Wheat Germ Agglutinin, WGA), Bandeiraea simplicifolia BS-II, and Maclura pomifera. Only WGA had antibiofilm activity, although no effect was seen on pre-formed biofilms.

Depletion of Host Cell Focal Adhesion Kinase Increases the Susceptibility to Invasion by Metacyclic Forms.

Focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase (PTK), is implicated in diverse cellular processes, including the regulation of F-actin dynamics. Host cell F-actin rearrangement is critical for invasion of , the protozoan parasite that causes Chagas disease. It is unknown whether FAK is involved in the internalization process of metacyclic trypomastigote (MT), the parasite form that is important for vectorial transmission.

Trifluoromethyl arylamides with antileukemia effect and intracellular inhibitory activity over serine/arginine-rich protein kinases (SRPKs).

The serine/arginine-rich protein kinases (SRPKs) have frequently been found with altered activity in a number of cancers, suggesting they could serve as potential therapeutic targets in oncology. Here we describe the synthesis of a series of twenty-two trifluoromethyl arylamides based on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and the evaluation of their antileukemia effects. Some derivatives presented superior cytotoxic effects against myeloid and lymphoid leukemia cell lines compared to SRPIN340.

Achievement of constitutive fluorescent pLEXSY-egfp Leishmania braziliensis and its application as an alternative method for drug screening in vitro.

Background: Gene reporter-fluorescent cells have emerged as alternative method for drug screening.

Objective: Achievement of constitutive expression of fluorescent protein GFP by Leishmania braziliensis as alternative method for drug screening.

Methods: L.

A porcine circovirus-2 mutant isolated in Brazil contains low-frequency substitutions in regions of immunoprotective epitopes in the capsid protein.

Porcine circovirus-2 (PCV2) is the etiologic agent of several diseases in pigs, including multi-systemic wasting syndrome (PMWS). In this work, a new mutant PCV2b was isolated from PMWS-affected pigs on a Brazilian farm. Its genome showed high sequence similarity (>99% identity) to those from a group of emerging mutants isolated from cases of PMWS outbreaks in vaccinated pigs in China, the USA and South Korea.

Identification of an Emergent Porcine Circovirus-2 in Vaccinated Pigs from a Brazilian Farm during a Postweaning Multisystemic Wasting Syndrome Outbreak.

Three porcine circovirus-2 strains were isolated from pigs on a Brazilian farm during an outbreak, indicating a vaccine failure. They present identical genomic sequences, with high identities to other isolates that were also related to vaccination failures, supporting the recent theory about an antigen drift being associated with vaccine failures throughout the world.

Verification of natural infection of peridomestic rodents by PCV2 on commercial swine farms.

The porcine circovirus-2 (PCV2) is the main agent responsible for porcine circovirus associated diseases (PCVAD). Few studies have been done regarding PCV2 infection in other species. The purpose of this study was to investigate the occurrence of PCV2 infection in the peridomestic rodent species Mus musculus and Rattus rattus on commercial pig farms in Brazil.