Modifying Membranotropic Action of Antimicrobial Peptide Gramicidin S by Star-like Polyacrylamide and Lipid Composition of Nanocontainers.

Gramicidin S (GS), one of the first discovered antimicrobial peptides, still shows strong antibiotic activity after decades of clinical use, with no evidence of resistance. The relatively high hemolytic activity and narrow therapeutic window of GS limit its use in topical applications. Encapsulation and targeted delivery may be the way to develop the internal administration of this drug.

Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.

Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis.

The role of P450 enzymes in malaria and other vector-borne infectious diseases.

Vector-borne infectious diseases are still an important global health problem. Malaria is the most important among them, mainly pediatric, life-threatening disease. Malaria and other vector-borne disorders caused by parasites, bacteria, and viruses have a strong impact on public health and significant economic costs.

Micromolar Dihydroartemisinin Concentrations Elicit Lipoperoxidation in -Infected Erythrocytes.

Malaria is still the most important parasitic infectious disease. Numerous substances are known to have antimalarial activity; among them, artemisinin is the most widely used one, and artemisinin-based combination therapy (ACT) is recommended for the treatment of malaria. Antitumor, immunomodulatory, and other therapeutic applications of artemisinin are under extensive study.

Posttranslational Modification of Human Cytochrome CYP4F11 by 4-Hydroxynonenal Impairs ω-Hydroxylation in Malaria Pigment Hemozoin-Fed Monocytes: The Role in Malaria Immunosuppression.

Malaria is a frequent parasitic infection becomes life threatening due to the disequilibrated immune responses of the host. Avid phagocytosis of malarial pigment hemozoin (HZ) and HZ-containing Plasmodium parasites incapacitates monocyte functions by bioactive lipoperoxidation products 4-hydroxynonenal (4-HNE) and hydroxyeicosatetraenoic acids (HETEs). CYP4F conjugation with 4-HNE is hypothesised to inhibit ω-hydroxylation of 15-HETE, leading to sustained monocyte dysfunction caused by 15-HETE accumulation.

Oligonucleotide Insecticides for Green Agriculture: Regulatory Role of Contact DNA in Plant-Insect Interactions.

Insects vastly outnumber us in terms of species and total biomass, and are among the most efficient and voracious consumers of plants on the planet. As a result, to preserve crops, one of the primary tasks in agriculture has always been the need to control and reduce the number of insect pests. The current use of chemical insecticides leads to the accumulation of xenobiotics in ecosystems and a decreased number of species in those ecosystems, including insects.

An Optimized Dihydrodibenzothiazepine Lead Compound (SBI-0797750) as a Potent and Selective Inhibitor of Plasmodium falciparum and P. vivax Glucose 6-Phosphate Dehydrogenase 6-Phosphogluconolactonase.

In , the first two and rate-limiting enzymes of the pentose phosphate pathway, glucose 6-phosphate dehydrogenase (G6PD) and the 6-phosphogluconolactonase, are bifunctionally fused to a unique enzyme named GluPho, differing structurally and mechanistically from the respective human orthologs. Consistent with the enzyme's essentiality for malaria parasite proliferation and propagation, human G6PD deficiency has immense impact on protection against severe malaria, making GluPho an attractive antimalarial drug target. Herein we report on the optimized lead compound -(((2R,4S)-1-cyclobutyl-4-hydroxypyrrolidin-2-yl)methyl)-6-fluoro-4-methyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide (SBI-0797750), a potent and fully selective GluPho inhibitor with robust nanomolar activity against recombinant GluPho, G6PD, and P.

Malaria Pigment Hemozoin Impairs GM-CSF Receptor Expression and Function by 4-Hydroxynonenal.

Malarial pigment hemozoin (HZ) generates the lipoperoxidation product 4-hydroxynonenal (4-HNE), which is known to cause dysregulation of the immune response in malaria. The inhibition of granulocyte macrophage colony-stimulating factor (GM-CSF)-dependent differentiation of dendritic cells (DC) by HZ and 4-HNE was previously described in vitro, and the GM-CSF receptor (GM-CSF R) was hypothesised to be a primary target of 4-HNE in monocytes. In this study, we show the functional impact of HZ on GM-CSF R in monocytes and monocyte-derived DC by (i) impairing GM-CSF binding by 50 ± 9% and 65 ± 14%, respectively ( = 3 for both cell types); (ii) decreasing the expression of GM-CSF R functional subunit (CD116) on monocyte's surface by 36 ± 11% ( = 6) and in cell lysate by 58 ± 16% ( = 3); and (iii) binding of 4-HNE to distinct amino acid residues on CD116.

Oxidative Stress, Lipid Peroxidation, and Loss of Hyaluronic Acid in the Human Vitreous Affected by Synchysis Scintillans.

The aim of this study was to assess the oxidative stress status in eyes affected by synchysis scintillans and to compare it to vitreoretinal disorders without synchysis scintillans. Human aqueous and vitreous humors were obtained during vitrectomy from thirty-seven otherwise healthy patients that were randomly chosen among patients that had to undergo a 25-gauge vitrectomy from the central vitreous cavity, for either synchysis scintillans ( = 16) or vitreoretinal disorders without synchysis scintillans ( = 21), such as idiopathic epimacular membrane ( = 12), macular hole ( = 5), or rhegmatogenous retinal detachment ( = 4). The redox parameters thiobarbituric acid reactive substances (TBARS), a measurement of lipid peroxidation, nitrite concentration, an estimate of nitric oxide (NO) production, 4-hydroxynonenal (4-HNE)-protein conjugates, a structural protein modification by lipid peroxidation product 4-HNE, and the antioxidative activities of Cu,Zn-superoxide dismutase (SOD), and catalase were measured in aqueous and vitreous humors and compared between synchysis scintillans affected and not-affected patients.

Induction of oxidative stress in human aqueous and vitreous humors by Nd:YAG laser posterior capsulotomy.

Aim: To evaluate whether the Q-switched Nd:YAG laser treatment applied in routine capsulotomy elicits oxidative stress in aqueous and vitreous humors.

Methods: Thirty-six patients who had to undergo a 25 gauge pars plana vitrectomy due to vitreoretinal disorders were enrolled, 15 of them underwent a Q-switched Nd:YAG laser capsulotomy 7d before vitrectomy due to posterior capsule opacification (PCO) (Nd:YAG laser group) while the remaining 21 patients were not laser treated before vitrectomy (no Nd:YAG laser group). Samples of the aqueous and vitreous humors were collected during vitrectomy from all patients for the assessment of oxidative parameters which were compared between the Nd:YAG laser group and no Nd:YAG laser group.

Molecular Alliance of Lymantria dispar Multiple Nucleopolyhedrovirus and a Short Unmodified Antisense Oligonucleotide of Its Anti-Apoptotic IAP-3 Gene: A Novel Approach for Gypsy Moth Control.

Baculovirus IAP (inhibitor-of-apoptosis) genes originated by capture of host genes. Unmodified short antisense DNA oligonucleotides (oligoDNAs) from baculovirus IAP genes can down-regulate specific gene expression profiles in both baculovirus-free and baculovirus-infected insects. In this study, gypsy moth () larvae infected with multiple nucleopolyhedrovirus (LdMNPV), and LdMNPV-free larvae, were treated with oligoDNA antisense to the RING (really interesting new gene) domain of the LdMNPV gene.

Oocyte polarized light microscopy, assay of specific follicular fluid metabolites, and gene expression in cumulus cells as different approaches to predict fertilization efficiency after ICSI.

Background: The complex relationship between oocyte morphology, specific follicular fluid metabolites, gene expression in cumulus granulosa cells, and oocyte competence toward fertilization and embryo development still needs further clarification.

Methods: Forty-six oocytes retrieved from the largest pre-ovulatory follicle of patients undergoing intra-cytoplasmic sperm injection (ICSI) were considered assessing: (a) oocyte morphological characteristics at polarized light microscopy (PLM), (b) specific follicular fluid (FF) metabolites previously suggested to influence oocyte competence (AMH, markers of redox status and of cytotoxicity), (c) transcription of AMH and AMH type II receptor genes in cumulus cells. Data were analyzed using mono-parametric tests and multivariable logistic analysis in order to correlate morphological and biochemical data with fertilization.

Syk inhibitors interfere with erythrocyte membrane modification during growth and suppress parasite egress.

Band 3 (also known as the anion exchanger, SLCA1, AE1) constitutes the major attachment site of the spectrin-based cytoskeleton to the erythrocyte's lipid bilayer and thereby contributes critically to the stability of the red cell membrane. During the intraerythrocytic stage of 's lifecycle, band 3 becomes tyrosine phosphorylated in response to oxidative stress, leading to a decrease in its affinity for the spectrin/actin cytoskeleton and causing global membrane destabilization. Because this membrane weakening is hypothesized to facilitate parasite egress and the consequent dissemination of released merozoites throughout the bloodstream, we decided to explore which tyrosine kinase inhibitors might block the kinase-induced membrane destabilization.

The RING for gypsy moth control: Topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide.

Numerous studies suggest a cellular origin for the Lymantria dispar multicapsid nuclear polyhedrosis virus (LdMNPV) anti-apoptosis genes IAPs, thus opening a possibility to use the fragments of these genes for modulation of host metabolism. We report here the strong insecticidal and metabolic effect of single-stranded antisense DNA fragment from RING (really interesting new gene) domain of gypsy moth LdMNPV IAP-3 gene: specifically, on reduction of biomass (by 35%) and survival of L. dispar caterpillars.

Data for increase of Lymantria dispar male survival after topical application of single-stranded RING domain fragment of IAP-3 gene of its nuclear polyhedrosis virus.

This data article is related to the research article entitled "The RING for gypsy moth control: topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide" [1]. This article reports on significantly higher survival of gypsy moth Lymantria dispar male individuals in response to topical application of single-stranded DNA, based on RING (really interesting new gene) domain fragment of LdMNPV (L. dispar multicapsid nuclear polyhedrosis virus) IAP-3 (inhibitor of apoptosis) gene and acted as DNA insecticide.

Preferential binding of 4-hydroxynonenal to lysine residues in specific parasite proteins in plakortin-treated Plasmodium falciparum-parasitized red blood cells.

The data show the frequencies by which the amino acid residues lysine, histidine and cysteine of six proteins of the malaria parasite Plasmodium falciparum are post-translationally modified by the lipoperoxydation endproduct 4-hydroxynonenal after challenging the parasitized red blood cell with plakortin. Plakortin is an antimalarial endoperoxide whose molecular anti-parasitic effect is described in Skorokhod et al. (2015) [1].

Oxidative stress-mediated antimalarial activity of plakortin, a natural endoperoxide from the tropical sponge Plakortis simplex.

Plakortin, a polyketide endoperoxide from the sponge Plakortis simplex has antiparasitic activity against P. falciparum. Similar to artemisinin, its activity depends on the peroxide functionality.

Malaria-derived hemozoin exerts early modulatory effects on the phenotype and maturation of human dendritic cells.

Plasmodium falciparum (P. falciparum)-induced effects on the phenotype of human dendritic cells (DC) could contribute to poor induction of long-lasting protective immunity against malaria. DC ability to present antigens to naïve T cells, thus initiating adaptive immune responses depends on complex switches in chemokine receptors, production of soluble mediators and expression of molecules enabling antigen-presentation and maturation.

Role of the lipoperoxidation product 4-hydroxynonenal in the pathogenesis of severe malaria anemia and malaria immunodepression.

Oxidative stress plays an important role in the pathogenesis of falciparum malaria, a disease still claiming close to 1 million deaths and 200 million new cases per year. Most frequent complications are severe anemia, cerebral malaria, and immunodepression, the latter being constantly present in all forms of malaria. Complications are associated with oxidative stress and lipoperoxidation.

Single-stranded DNA fragments of insect-specific nuclear polyhedrosis virus act as selective DNA insecticides for gypsy moth control.

This paper focuses on the DNA insecticides as a novel preparation against gypsy moth (Lymantria dispar) based on DNA fragments of the anti-apoptotic gene of its nuclear polyhedrosis virus. It was found that the external application of a solution with two single-stranded DNA fragments from BIR and RING domains of LdMNPV (L.dispar multicapsid nuclear polyhedrosis virus) IAP-3 (inhibitor of apoptosis) gene induces a significantly higher mortality of gypsy moth caterpillars in comparison with the application of the control solutions.

Malarial pigment hemozoin impairs chemotactic motility and transendothelial migration of monocytes via 4-hydroxynonenal.

Natural hemozoin, nHZ, is avidly phagocytosed in vivo and in vitro by human monocytes. The persistence of the undigested β-hematin core of nHZ in the phagocyte lysosome for long periods of time modifies several cellular immune functions. Here we show that nHZ phagocytosis by human primary monocytes severely impaired their chemotactic motility toward MCP-1, TNF, and FMLP, by approximately 80% each, and their diapedesis across a confluent human umbilical vein endothelial cell layer toward MCP-1 by 45±5%.

Plasma advanced oxidative protein products are associated with anti-oxidative stress pathway genes and malaria in a longitudinal cohort.

Background: Advanced oxidation protein products (AOPP) are newly identified efficient oxidative stress biomarkers. In a longitudinal birth cohort the effects were investigated of genetic polymorphisms in five oxidative pathway genes on AOPP levels.

Methods: This study is part of a three-arm randomized, double-blind, placebo-controlled trial.

Blood oxidative stress markers and Plasmodium falciparum malaria in non-immune African children.

Converging in vitro evidence and clinical data indicate that oxidative stress may play important roles in Plasmodium falciparum malaria, notably in the pathogenesis of severe anaemia. However, oxidative modifications of the red blood cell (RBC)-membrane by 4-hydroxynonenal (4-HNE) and haemoglobin-binding, previously hypothesized to contribute mechanistically to the pathogenesis of clinical malaria, have not yet been tested for clinical significance. In 349 non-immune Mozambican newborns recruited in a double-blind placebo-controlled chemoprophylaxis trial, oxidative markers including 4-HNE-conjugates and membrane-bound haemoglobin were longitudinally assessed from 2·5 to 24 months of age, at first acute malaria episode and in convalescence.