Immunogenic potential and neutralizing ability of a heterologous version of the most abundant three-finger toxin from the coral snake .

is a coral snake of public health concern in Colombia. Its venom is mainly composed of three-finger toxins (3FTxs), Mipartoxin-1 being the most abundant protein partially responsible for its lethal effect. In this work, we present the production of Mipartoxin-1 in a recombinant form and evaluate its immunogenic potential.

In Vitro Cytotoxicity of Fluorinated Quaternary Ammonium Salts in Colorectal Cancer Cells and In Silico Pharmacology.

Colorectal cancer (CRC) is a multifactorial disease driven by genetic and epigenetic alterations that modulate specific metabolic pathways. Despite the availability of effective treatments like 5-fluorouracil (5-FU), pharmacological therapy for CRC still faces significant challenges, including drug resistance, toxicity, and limited specificity. Therefore, discovering new compounds remains critical to overcoming these barriers and expanding treatment options.

The membrane-binding bacterial toxin long direct repeat D inhibits protein translation.

Bacterial plasmids and chromosomes widely contain toxin-antitoxin (TA) loci, which are implicated in stress response, growth regulation and even tolerance to antibiotics and environmental stress. Type I TA systems consist of a stable toxin-expressing mRNA, which is counteracted by an unstable RNA antitoxin. The Long Direct Repeat (LDR-) D locus, a type I TA system of Escherichia Coli (E.

Heterologous Expression and Immunogenic Potential of the Most Abundant Phospholipase A from Coral Snake to Develop Antivenoms.

is a coral snake of clinic interest in Colombia. Its venom is mainly composed of phospholipases A being MdumPLA the most abundant protein. Nevertheless, species produce a low quantity of venom, which makes it difficult to produce anticoral antivenoms.

Effect of the variation in the extracellular concentration of l-arginine in the physiology of Leishmania (Viannia) braziliensis and its susceptibility to some antileishmanial drugs.

The knowledge about amino acid metabolism in trypanosomatids is a valuable source of new therapeutic targets. l-arginine is an essential amino acid for Leishmania parasites, and it participates in the synthesis of polyamines, a group of essential nutrients used for nucleic acids, proteins biosynthesis, and redox modulation necessary for proliferation. In the present study, we evaluated the effect of changes in the availability of this amino acid on promastigotes and intracellular amastigotes on U937 macrophages and showed that the absence of l-arginine in culture medium negatively influences the growth and infectivity of Leishmania (Viannia) braziliensis, causing a decrease in the percentage of the infected cells and parasite load tested through light microscopy.

Structural and DNA-binding properties of the cytoplasmic domain of Vibrio cholerae transcription factor ToxR.

ToxR represents an essential transcription factor of Vibrio cholerae, which is involved in the regulation of multiple, mainly virulence associated genes. Its versatile functionality as activator, repressor or coactivator suggests a complex regulatory mechanism, whose clarification is essential for a better understanding of the virulence expression system of V. cholerae.

Effect of Early Weight Bearing on Outcomes After Open Reduction and Internal Fixation of Trimalleolar Ankle Fractures.

Current practice allows early weight bearing of unstable ankle fractures after fixation. This study offers a unique comparison of early weight bearing (EWB) vs late weight bearing (LWB) in operatively stabilized trimalleolar ankle fractures. The goal of this study was to evaluate union rates, clinical outcomes, and complications for patients who were managed with EWB vs LWB.

Studies in vitro on infectivity and sensitivity to antileishmanial drugs in New World Leishmania species transfected with the green fluorescent protein [pIR3(-)-eGFP].

Current chemotherapeutic agents for leishmaniasis have several disadvantages interfering with the effective treatment and therefore more and better antileishmanial drugs are needed. Discovery of candidates for leishmaniasis treatment requires not only accurate and precise methodologies but also well-known biological system to measure infectivity of parasites and antileishmanial activity of the new compounds. Significant variation in the in vitro and in vivo infectivity and sensitivity to established and experimental drugs in Leishmania strains are reported.

Insights into the phosphatidylcholine and phosphatidylethanolamine biosynthetic pathways in Leishmania parasites and characterization of a choline kinase from Leishmania infantum.

The protozoan parasite Leishmania infantum is a causative agent of the disease visceral leishmaniasis, which can be fatal if not properly treated. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis pathways are attractive targets for new antileishmanial compounds since these Leishmania cell membrane phospholipids are important for parasite morphology and physiology. In this work we observed Leishmania synthesize PC and PE from extracellular choline and ethanolamine, respectively, suggesting the presence of CDP-choline and CDP-ethanolamine pathways.

Is There Still a Role for Irrigation and Debridement With Liner Exchange in Acute Periprosthetic Total Knee Infection?

Background: Periprosthetic joint infection (PJI) is an important cause of failure in total knee arthroplasty. Irrigation and debridement including liner exchange (I&D/L) success rates have varied for acute PJI. The purpose of this study is to present results of a specific protocol for I&D/L with retention of total knee arthroplasty components.

PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.

Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake.

A non-commercial approach for the generation of transgenic Leishmania tarentolae and its application in antileishmanial drug discovery.

Leishmaniasis is a parasitic infection caused by several species of the genus Leishmania that is considered as a neglected disease. Drug development process requires a robust and updated high-throughput technology to the evaluation of candidate compounds that imply the manipulation of the pathogenic species of the parasite in the laboratory. Therefore, it is restricted to trained personal and level II biosafety environments.

Structural and functional implications of the interaction between macrolide antibiotics and bile acids.

Macrolide antibiotics, such as azithromycin and erythromycin, are in widespread use for the treatment of bacterial infections. Macrolides are taken up and excreted mainly by bile. Additionally, they have been implicated in biliary system diseases and to modify the excretion of other drugs through bile.

Collapse of the native structure caused by a single amino acid exchange in human NAD(P)H:quinone oxidoreductase(1.).

Unlabelled: Human

Nad(p)h: quinone oxidoreductase 1 (NQO1) is essential for the antioxidant defense system, stabilization of tumor suppressors (e.g. p53, p33, and p73), and activation of quinone-based chemotherapeutics.

Improvement of the green fluorescent protein reporter system in Leishmania spp. for the in vitro and in vivo screening of antileishmanial drugs.

Development of new therapeutic approaches for leishmaniasis treatment requires new high throughput screening methodologies for the antileishmanial activity of the new compounds both in vitro and in vivo. Reporter genes as the GFP have become one of the most promissory and widely used tools for drug screening in several models, since it offers live imaging, high sensibility, specificity and flexibility; additionally, the use of GFP as a reporter gene in screening assays eliminates all the drawbacks presented in conventional assays and also those technical problems found using other reporter genes. The utility of the GFP as a reporter gene in drug screening assays with Leishmania parasites depends on the homogeneity and stability of the GFP transfected strains.

Cs6Nb4Se22 and K12Nb6Se35.3: two new compounds containing the M4Q22 building block.

The title compounds, namely hexacaesium tetraniobium docosaselenide and dodecapotassium hexaniobium pentatriacontaselenide, were formed from their respective alkali chalcogenide reactive flux and niobium metal. Both compounds fall into the larger family of solid-state compounds that contain the M(2)Q(11) building block (M = Nb, Ta; Q = Se, S), where the metal chalcogenide forms dimers of face-shared pentagonal bipyramids. Cs(6)Nb(4)Se(22) contains two Nb(2)Se(11) building blocks linked by an Se-Se bond to form isolated Nb(4)Se(22) tetrameric building blocks surrounded by caesium ions.