Exploring the biofilm inhibitory potential of Candida sp. UFSJ7A glycolipid on siliconized latex catheters.

Biosurfactants, sustainable alternatives to petrochemical surfactants, are gaining attention for their potential in medical applications. This study focuses on producing, purifying, and characterizing a glycolipid biosurfactant from Candida sp. UFSJ7A, particularly for its application in biofilm prevention on siliconized latex catheter surfaces. The glycolipid was extracted and characterized, revealing a critical micellar concentration (CMC) of 0.98 mg/mL, indicating its efficiency at low concentrations. Its composition, confirmed through Fourier transform infrared spectroscopy (FT-IR) and thin layer chromatography (TLC), identified it as an anionic biosurfactant with a significant ionic charge of -14.8 mV. This anionic nature contributes to its biofilm prevention capabilities. The glycolipid showed a high emulsification index (E24) for toluene, gasoline, and soy oil and maintained stability under various pH and temperature conditions. Notably, its anti-adhesion activity against biofilms formed by Escherichia coli, Enterococcus faecalis, and Candida albicans was substantial. When siliconized latex catheter surfaces were preconditioned with 2 mg/mL of the glycolipid, biofilm formation was reduced by up to 97% for E. coli and C. albicans and 57% for E. faecalis. These results are particularly significant when compared to the efficacy of conventional surfactants like SDS, especially for E. coli and C. albicans. This study highlights glycolipids' potential as a biotechnological tool in reducing biofilm-associated infections on medical devices, demonstrating their promising applicability in healthcare settings.

Identification of Hypoglycemic Glycolipids from Ipomoea murucoides by Affinity-Directed Fractionation, In Vitro, In Silico and Dynamic Light Scattering Analysis.

In the pursuit of identifying the novel resin glycoside modulators glucose-6-phosphatase and α-glucosidase enzymes, associated with blood sugar regulation, methanol-soluble extracts from the flowers of Ipomoea murucoides (cazahuate, Nahuatl), renowned for its abundance of glycolipids, were employed. The methanol-soluble extracts were fractionated by applying the affinity-directed method with glucose-6-phosphatase enzymes from a rat's liver and α-glucosidase enzymes from its intestines. Mass spectrometry and nuclear magnetic resonance were employed to identify the high-affinity compound as a free ligand following the release from the enzymatic complex. Gel permeation through a spin size-exclusion column allowed the separated high-affinity molecules to bind to glucose-6-phosphatase and α-glucosidase enzymes in solution, which led to the identification of some previously reported resin glycosides in the flowers of cazahuate, where a glycolipid mainly structurally related to murucoidin XIV was observed. In vitro studies demonstrated the modulating properties of resin glycosides on the glucose-6-phosphatase enzyme. Dynamic light scattering revealed conformational variations induced by resin glycosides on α-glucosidase enzyme, causing them to become more compact, akin to observations with the positive control, acarbose. These findings suggest that resin glycosides may serve as a potential source for phytotherapeutic agents with antihyperglycemic properties.

Inhibition of multidrug-resistant MCF-7 breast cancer cells with combinations of clinical drugs and resin glycosides from Operculina hamiltonii.

The jalap roots, Operculina hamiltonii D.F. Austin & Staples (Convolvulaceae), are extensively commercialized as a depurative and laxative remedy in traditional medicine of the north and northeast regions of Brazil. The purification by recycling HPLC and structure elucidation of three new acyl sugars or resin glycosides are described here from a commercial product made of powdered roots. Three macrocyclic structures of a tetrasaccharide of (11S)-hydroxyhexadecanoic acid, operculinic acid C (1), the undescribed hamiltonins II and III (3 and 4), in addition to the known batatinoside III (5), presented a diastereoisomeric relationship as one residue of n-dodecanoic acid esterified the oligosaccharide core on a different position in each compound. Furthermore, hamiltonin IV (6) was characterized as an ester-type homodimer of acylated operculinic acid C with the same substitution pattern identified in hamiltonins II (3) and III (4) for each of the dimer subunits. All the isolated resin glycosides did not display any intrinsic cytotoxicity (IC50 > 25 µM). However, a combination of the individual isolated compounds 3-6 (1-50 µM) demonstrated an enhancement of cytotoxic effects with sublethal doses of vinblastine and podophyllotoxin (0.003 µM) in multidrug-resistant breast carcinoma epithelial cells (MCF-7/Vin).

Glycolipids from Sargassum filipendula, a Natural Alternative for Overcoming ABC Transporter-Mediated MDR in Cancer.

Chemotherapy is a widely used strategy to treat cancer, a disease that causes millions of deaths each year. However, its efficacy is reduced by the overexpression of ABC transporters, which are proteins that expel the drugs used in chemotherapy and involved in the multidrug resistance (MDR). Glycolipids have been identified as potential inhibitors of ABC transporters. Algae of the genus Sargassum contain high levels of glycolipids, making them a promising therapeutic alternative against the MDR phenotype. Sargassum filipendula glycolipids were obtained by exhaustive maceration with chloroform/methanol, purified by column and thin layer chromatography, and then characterized by FTIR, NMR, and LC-MS. Cell viability by PI labeling and inhibition of ABC transporters were analyzed by flow cytometry. Assessment of resistance reversal was determined by MTT assay. Ten sulfoquinovosylglycerol-type compounds were found, and six of them are reported for the first time. In particular, moiety 4 (GL-4) showed strong and moderate inhibitory activity against ABCC1 and ABCB1 transporters respectively. Treatment of GL-4 in combination with the antineoplastic drug vincristine sensitized Lucena-1 cell model to drug and reversed the MDR phenotype. This is the first report of glycolipids isolated from S. filipendula capable of inhibiting ABC transporters and thus overcoming acquired drug resistance.

Gangliosides in nervous system development, regeneration, and pathologies.

Gangliosides, sialic acid-containing sphingolipids, are major constituents of neuronal membranes. According to the number of sialic acids and the structure of the oligosaccharide chain, gangliosides can be classified as simple or complex and grouped in different ganglio-series. Hundreds of gangliosides have been identified in vertebrate cells, with different expression patterns during development and related to several physiological processes, especially in the nervous system. While GD3 and its O-acetylated form, 9acGD3, are highly expressed in early developmental stages, GM1, GD1a, GD1b, and GT1b are the most abundant ganglioside species in the mature nervous system. Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species, a condition termed gangliosidosis and usually marked by severe neurological impairment. Changes in ganglioside levels have also been described in several neurodegenerative diseases, such as Alzheimer's and Parkinson's. In this review, we summarized recent information about the roles of GD3, 9acGD3, GM1, GD1a, GD1b, GT1b, and other ganglioside species in nervous system development and regeneration, as well as clinical trials evaluating possible therapeutic applications of these molecules.

Biosurfactant Production by Bacillus amyloliquefaciens C11 and Streptomyces lavendulae C27 Isolated from a Biopurification System for Environmental Applications.

Biosurfactant-producing bacteria can be found in contaminated environments such as biopurification systems (BPS) for pesticide treatments. A total of 18 isolates were screened to determine their ability to produce extracellular biosurfactants, using olive oil as the main carbon source. Out of the eighteen isolates, two strains (C11 and C27) were selected for biosurfactant production. The emulsification activities of the C11 and C27 strains using sunflower oil was 58.4 and 53.7%, respectively, and 46.6 and 48.0% using olive oil. Using molecular techniques and MALDI-TOF, the strains were identified as Bacillus amyloliquefaciens (C11) and Streptomyces lavendulae (C27). The submerged cultivation of the two selected strains was carried out in a 1 L stirred-tank bioreactor. The maximum biosurfactant production, indicated by the lowest surface tension measurement, was similar (46 and 45 mN/m) for both strains, independent of the fact that the biomass of the B. amyloliquefaciens C11 strain was 50% lower than the biomass of the S. lavendulae C27 strain. The partially purified biosurfactants produced by B. amyloliquefaciens C11 and S. lavendulae C27 were characterized as a lipopeptide and a glycolipid, respectively. These outcomes highlight the potential of the selected biosurfactant-producing microorganisms for improving pesticides' bioavailability and therefore the degradational efficacy of BPS.

Golgi Phosphoprotein 3 Regulates the Physical Association of Glycolipid Glycosyltransferases.

Glycolipid glycosylation is an intricate process that mainly takes place in the Golgi by the complex interplay between glycosyltransferases. Several features such as the organization, stoichiometry and composition of these complexes may modify their sorting properties, sub-Golgi localization, enzymatic activity and in consequence, the pattern of glycosylation at the plasma membrane. In spite of the advance in our comprehension about physiological and pathological cellular states of glycosylation, the molecular basis underlying the metabolism of glycolipids and the players involved in this process remain not fully understood. In the present work, using biochemical and fluorescence microscopy approaches, we demonstrate the existence of a physical association between two ganglioside glycosyltransferases, namely, ST3Gal-II (GD1a synthase) and ß3GalT-IV (GM1 synthase) with Golgi phosphoprotein 3 (GOLPH3) in mammalian cultured cells. After GOLPH3 knockdown, the localization of both enzymes was not affected, but the fomation of ST3Gal-II/ß3GalT-IV complex was compromised and glycolipid expression pattern changed. Our results suggest a novel control mechanism of glycolipid expression through the regulation of the physical association between glycolipid glycosyltransferases mediated by GOLPH3.

Pigment and Fatty Acid Heterogeneity in the Sea Slug Elysia crispata Is Not Shaped by Habitat Depth.

Long-term retention of functional chloroplasts in animal cells occurs only in sacoglossan sea slugs. Analysis of molecules related to the maintenance of these organelles can provide valuable information on this trait (kleptoplasty). The goal of our research was to characterize the pigment and fatty acid (FA) composition of the sea slug Elysia crispata and their associated chloroplasts that are kept functional for a long time, and to quantify total lipid, glycolipid and phospholipid contents, identifying differences between habitats: shallow (0-4 m) and deeper (8-12 m) waters. Specimens were sampled and analyzed after a month of food deprivation, through HPLC, GC-MS and colorimetric methods, to ensure an assessment of long-term kleptoplasty in relation to depth. Pigment signatures indicate that individuals retain chloroplasts from different macroalgal sources. FA classes, phospholipid and glycolipid contents displayed dissimilarities between depths. However, heterogeneities in pigment and FA profiles, as well as total lipid, glycolipid and phospholipid amounts in E. crispata were not related to habitat depth. The high content of chloroplast origin molecules, such as Chl a and glycolipids after a month of starvation, confirms that E. crispata retains chloroplasts in good biochemical condition. This characterization fills a knowledge gap of an animal model commonly employed to study kleptoplasty.

Effects of exercise on glucose and lipid metabolism in elderly patients / Os efeitos do exercício no metabolismo de glicose e lipídios em pacientes idosos / Los efectos del ejercicio en el metabolismo de glucosas y lípidos en pacientes ancianos

ABSTRACT Introduction: Metabolic syndrome is a condition in which multiple cardiovascular metabolic risk factors gather in the body. Objective: To explore the effects of exercise prescription on glucose and lipid metabolism in elderly patients with metabolic syndrome. Methods: A total of 85 elderly people were selected from a pension community. The influencing factors of physical activity were analyzed by the Pearson correlation analysis method, Mann-Whitneyu test and Kruskal-Wallish test. Finally, we quantitatively analyzed the influence and path of each factor on the physical activity of the elderly. Results: Among the 85 elderly people in nursing homes, 2 cases (1.1%) had a high level of physical activity, 70 cases (38.9%) had a medium level of physical activity, and 51 cases (60.0%) had a low level of physical activity. Conclusions: The improvement of glucose and lipid metabolism and healthy body fitness with the prescription of exercises of high oxygen + low resistance and that of exercises of high resistance + low oxygen is better than that with the prescription of exercises of full oxygen and full resistance. The improvement of sleep quality with the prescription of exercise with high oxygen and low resistance was better than that of exercise with complete oxygen, complete resistance and high resistance and low oxygen. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A síndrome metabólica é uma condição em que múltiplos fatores de risco metabólicos cardiovasculares se juntam no corpo. Objetivo: Explorar os efeitos da prescrição de exercícios no metabolismo de glicose e lipídios em pacientes idosos com síndrome metabólica. Métodos: Um total de 85 idosos foram selecionados de uma comunidade de pensionistas. Os fatores que influenciam a atividade física foram analisados pelo método de análise de correlação de Pearson, o teste Mann-Whitneyu e o teste Kruskal-Wallish. No final, analisamos quantitativamente a influência e o curso de cada fator na atividade física dos idosos. Resultados: entre os 85 idosos em casas de repouso, 2 casos (1,1%) apresentavam alto nível de atividade física, 70 casos (38,9%) apresentavam nível médio de atividade física, e 51 casos (60,0%) apresentavam baixo nível de atividade física. Conclusões: A melhora no metabolismo de glicose e lipídios e preparo físico saudável com a prescrição de exercícios de oxigênio alto + resistência baixa e aquela de exercícios de resistência alta + oxigênio baixo é mais eficaz do que a de prescrição de exercícios de oxigênio pleno e resistência plena. A melhora na qualidade do sono com a prescrição de exercícios de oxigênio alto e resistência baixa foi maior do que aquela de exercícios com oxigênio pleno, resistência completa e resistência alta e oxigênio baixo. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

RESUMEN Introducción: El síndrome metabólico es una condición en que múltiples factores de riesgo metabólicos cardiovasculares se juntan en el cuerpo. Objetivo: Explorar los efectos de la prescripción de ejercicios en el metabolismo de glucosa y lípidos en paciente ancianos con síndrome metabólico. Métodos: Se seleccionó un total de 85 ancianos de una comunidad de pensionistas. Los factores que influenciaron la actividad física fueron analizados por el método de análisis de correlación de Pearson, la prueba Mann-Whitneyu y la prueba Kruskal-Wallish. Al final, analizamos cuantitativamente la influencia y el curso de cada factor en la actividad física de los ancianos. Resultados: Entre los 85 ancianos en casas de reposo, 2 casos (1,1%) presentaban alto nivel de actividad física, 70 casos (38,9%) presentaban nivel medio de actividad física y 51 casos (60,0%) presentaban bajo nivel de actividad física. Conclusiones: La mejoría en el metabolismo de glucosa y lípidos y preparo físico saludable con la prescripción de ejercicios de oxígeno alto + resistencia baja y la de ejercicios de resistencia alta + oxígeno bajo es más eficaz que a prescripción de ejercicios de oxígeno pleno y resistencia plena. La mejoría en la calidad del sueño con la prescripción de ejercicios de oxígeno alto y resistencia baja fue mayor que la de ejercicios con oxígeno pleno, resistencia completa y resistencia alta y oxígeno bajo. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Biosurfactant inducers for enhanced production of surfactin and rhamnolipids: an overview.

Biosurfactants can be widely used in industries as pharmaceutical agents, for microbial enhanced oil recovery, crop biostimulation, among others. Surfactin and rhamnolipids are well-known biosurfactants. These compounds have several advantages over chemical surfactants, however they are not economically competitive, since their production cost is up to 12 times higher than chemical surfactants. In this sense, an interesting approach is to replace synthetic culture medium, which represents ≈ 30% of the production cost by agro-industrial wastes. In addition, biosurfactant productivity can be easily enhanced by inductor supplementation into culture medium that triggers biosurfactant metabolism. Biosurfactant inducers are mainly a pool of hydrophobic molecules (e.g. olive oil-saturated and unsaturated fatty acids, proteins and vitamins). Nevertheless, there is little information on inducer effects of specific molecules (e.g. oleic acid). In general, hydrophobic inducers lead to higher fatty acid chain lengths (biosurfactant chemical structure). Therefore, the aim of this review was to critically discuss the current state of the art and future trends on biosurfactant production, in particular biosurfactant inducers. Taking into account the last 10 years, there is a clear lack of information on correlation between "inducers" or "hydrophobic inducers" AND "biosurfactants", since only 13 documents were found (Scopus database). Thus, it is essential to deeply investigate all inducer effects on biosurfactant production, mainly yield and chemical structure.

Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases.

The immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State.

The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomycolate antigens stained TRAV1-2+ GEM T cells or TRBV4-1+ LDN5-like T cells in the majority of subjects tested, at rates ~10-fold lower than NKT cells. Thus, GEM T cells and LDN5-like T cells are a normal part of the human immune system. Unlike prior studies measuring MHC- or CD1b-mediated activation, this large-scale tetramer study found no significant differences in rates of CD1b tetramer-mycobacterial lipid staining of T cells among subjects with Mtb exposure, latent Mtb infection or active tuberculosis (TB) disease. In all subjects, including "uninfected" subjects, CD1b tetramer+ T cells expressed memory markers at high levels. However, among controls with lower mycobacterial antigen exposure in Boston, we found significantly lower frequencies of T cells staining with CD1b tetramers loaded with mycobacterial lipids. These data link CD1b-specific T cell detection to mycobacterial exposure, but not TB disease status, which potentially explains differences in outcomes among CD1-based clinical studies, which used control subjects with low Mtb exposure.

Exploiting the internalization feature of an antibody against the glycosphingolipid SSEA-4 to deliver immunotoxins in breast cancer cells.

The stage-specific embryonic antigen-4 (SSEA-4) is a cell surface glycosphingolipid antigen expressed in early stages of human development. This surface marker is downregulated during the differentiation process but is found re-expressed in several types of tumors, including breast cancer. This feature makes SSEA-4 an attractive target for the development of therapeutic antibodies against tumors. In this work, we first studied the binding and intracellular fate of the monoclonal antibody MC-813-70 directed against SSEA-4. MC-813-70 was found to be rapidly internalized into triple-negative breast cancer cells following binding to its target at the plasma membrane, and to accumulate in acidic organelles, most likely lysosomes. Given the internalization feature of MC-813-70, we next tested whether the antibody was able to selectively deliver the saporin toxin inside SSEA-4-expressing cells. Results show that the immunotoxin complex was properly endocytosed and able to reduce cell viability of breast cancer cells in vitro, either alone or in combination with chemotherapeutic drugs. Our findings indicate that the MC-813-70 antibody has the potential to be developed as an alternative targeted therapeutic agent for cancer cells expressing the SSEA-4 glycolipid.

Cryptococcus neoformans Glucuronoxylomannan and Sterylglucoside Are Required for Host Protection in an Animal Vaccination Model.

Cryptococcus neoformans is an encapsulated fungal pathogen that causes meningoencephalitis. There are no prophylactic tools for cryptococcosis. Previously, our group showed that a C. neoformans mutant lacking the gene encoding sterylglucosidase (Δsgl1) induced protection in both immunocompetent and immunocompromised murine models of cryptococcosis. Since sterylglucosidase catalyzes degradation of sterylglucosides (SGs), accumulation of this glycolipid could be responsible for protective immunity. In this study, we analyzed whether the activity of SGs is sufficient for the protective effect induced by the Δsgl1 strain. We observed that the accumulation of SGs impacted several properties of the main polysaccharide that composes the fungal capsule, glucuronoxylomannan (GXM). We therefore used genetic manipulation to delete the SGL1 gene in the acapsular mutant Δcap59 to generate a double mutant (strain Δcap59/Δsgl1) that was shown to be nonpathogenic and cleared from the lung of mice within 7 days post-intranasal infection. The inflammatory immune response triggered by the Δcap59/Δsgl1 mutant in the lung differed from the response seen with the other strains. The double mutant did not induce protection in a vaccination model, suggesting that SG-related protection requires the main capsular polysaccharide. Finally, GXM-containing extracellular vesicles (EVs) enriched in SGs delayed the acute lethality of Galleria mellonella against C. neoformans infection. These studies highlighted a key role for GXM and SGs in inducing protection against a secondary cryptococcal infection, and, since EVs notoriously contain GXM, these results suggest the potential use of Δsgl1 EVs as a vaccination strategy for cryptococcosis.IMPORTANCE The number of deaths from cryptococcal meningitis is around 180,000 per year. The disease is the second leading cause of mortality among individuals with AIDS. Antifungal treatment is costly and associated with adverse effects and resistance, evidencing the urgency of development of both therapeutic and prophylactic tools. Here we demonstrate the key roles of polysaccharide- and glycolipid-containing structures in a vaccination model to prevent cryptococcosis.

Current status in biotechnological production and applications of glycolipid biosurfactants.

Biosurfactants are natural compounds with surface activity and emulsifying properties produced by several types of microorganisms and have been considered an interesting alternative to synthetic surfactants. Glycolipids are promising biosurfactants, due to low toxicity, biodegradability, and chemical stability in different conditions and also because they have many biological activities, allowing wide applications in different fields. In this review, we addressed general information about families of glycolipids, rhamnolipids, sophorolipids, mannosylerythritol lipids, and trehalose lipids, describing their chemical and surface characteristics, recent studies using alternative substrates, and new strategies to improve of production, beyond their specificities. We focus in providing recent developments and trends in biotechnological process and medical and industrial applications.

Integrative literature review of the reported uses of serological tests in leprosy management

Abstract: An integrative literature review was conducted to synthesize available publications regarding the potential use of serological tests in leprosy programs. We searched the databases Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol em Ciências da Saúde, Acervo da Biblioteca da Organização Pan-Americana da Saúde, Medical Literature Analysis and Retrieval System Online, Hanseníase, National Library of Medicine, Scopus, Ovid, Cinahl, and Web of Science for articles investigating the use of serological tests for antibodies against phenolic glycolipid-I (PGL-I), ML0405, ML2331, leprosy IDRI diagnostic-1 (LID-1), and natural disaccharide octyl-leprosy IDRI diagnostic-1 (NDO-LID). From an initial pool of 3.514 articles, 40 full-length articles fulfilled our inclusion criteria. Based on these papers, we concluded that these antibodies can be used to assist in diagnosing leprosy, detecting neuritis, monitoring therapeutic efficacy, and monitoring household contacts or at-risk populations in leprosy-endemic areas. Thus, available data suggest that serological tests could contribute substantially to leprosy management.

Mecanismos de activación de las células T asesinas naturales invariantes (iNKT) / Mecanismos de ativação das células T assassinas naturais invariantes (iNKT) / Activation mechanisms of invariant natural killer T cells (iNKTs)

Aunque se ha logrado un conocimiento amplio acerca de las células T asesinas naturales (iNKT), aún no existe consenso sobre sus mecanismos de activación. Dichas células reconocen diferentes antígenos glicolipídicos presentados por medio de la molécula CD1d, los cuales pueden ser endógenos, exógenos derivados de organismos como bacterias y sintéticos desarrollados para aplicaciones clínicas. Existe mucho interés en entender cómo estas distintas variantes glicolipídicas inducen diferentes tipos de polarización, pero ha sido muy difícil llegar a un consenso, debido a que la respuesta depende de varios factores como la naturaleza, la internalización y el procesamiento de los glicolípidos. Además, la activación de las células iNKT la determinan el tipo y estado de activación de la célula presentadora de antígeno, las moléculas coestimuladoras, los mecanismos de transactivación y la localización de los complejos CD1d-glicolípido en distintas microrregiones de la membrana plasmática, como las balsas lipídicas. Esta revisión explora la evidencia sobre los factores que afectan la activación de las células iNKT con el fin de entender su potencial inmunomodulador.

A great amount of knowledge on natural killer T cells (iNKTs) is now available, but a consensus about their activation mechanisms has not been reached. These cells recognize different glycolipid antigens through the CD1d molecule. Such antigens may be endogenous, derived from bacteria (foreign) and synthetic, the latter have been developed for clinical applications. There exists much interest in understanding how these different glycolipid compounds induce different types of polarization, but it has been difficult to reach a consensus due to the fact that responses depend on different factors such as: the nature of the molecule, the internalization process and the presentation of the glycolipids. Moreover, activation of iNKT cells is determined by the type and state of the antigen presenting cell, the co-stimulatory molecules, the transactivation mechanisms and the location of the glycolipid-CD1d complexes on the plasma membrane, such as the lipid rafts. This review explores the evidence about the factors that affect activation of iNKT cells in order to understand their immune-modulatory potential.

Ainda que se conseguiu um conhecimento amplo a respeito das células T assassinas naturais (iNKT), ainda não existe consenso sobre seus mecanismos de ativação. Ditas células reconhecem diferentes antígenos glicolipídicos apresentados por meio da molécula CD1d, os quais pode ser: endógenos, exógenos derivados de organismos como bactérias e sintéticos desenvolvidos para aplicações clínicas. Existe muito interesse em entender como estas diferentes variantes glicolipídicas induzem diferentes tipos de polarização, mas foi muito difícil chegar a um consenso, devido a que a resposta depende de vários fatores como a natureza, a internalização e o processamento dos glicolípidos. Ademais, a ativação das células iNKT a determinam o tipo e estado de ativação da célula apresentadora de antígeno, as moléculas co-estimuladoras, os mecanismos de transativação e a localização dos complexos CD1d-glicolípido em diferentes microrregiões da membrana plasmática, como as balsas lipídicas. Esta revisão explora a evidência sobre os fatores que afetam a ativação das células iNKT com o fim de entender seu potencial imunomodulador.

Resin glycosides from Ipomoea wolcottiana as modulators of the multidrug resistance phenotype in vitro.

Recycling liquid chromatography was used for the isolation and purification of resin glycosides from the CHCl3-soluble extracts prepared using flowers of Ipomoea wolcottiana Rose var. wolcottiana. Bioassay-guided fractionation, using modulation of both antibiotic activity against multidrug-resistant strains of Gram-negative bacteria and vinblastine susceptibility in breast carcinoma cells, was used to isolate the active glycolipids as modulators of the multidrug resistance phenotype. An ester-type dimer, wolcottine I, one tetra- and three pentasaccharides, wolcottinosides I-IV, in addition to the known intrapilosin VII, were characterized by NMR spectroscopy and mass spectrometry. In vitro assays established that none of these metabolites displayed antibacterial activity (MIC>512 µg/mL) against multidrug-resistant strains of Escherichia coli, and two nosocomial pathogens: Salmonella enterica serovar Typhi and Shigella flexneri; however, when tested (25 µg/mL) in combination with tetracycline, kanamycin or chloramphenicol, they exerted a potentiation effect of the antibiotic susceptibility up to eightfold (64 µg/mL from 512 µg/mL). It was also determined that these non-cytotoxic (CI50>8.68 µM) agents modulated vinblastine susceptibility at 25 µg/mL in MFC-7/Vin(+) cells with a reversal factor (RFMCF-7/Vin(+)) of 2-130 fold.

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents.

Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation, and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets.