Peptide PaDBS1R6 has potent antibacterial activity on clinical bacterial isolates and integrates an immunomodulatory peptide fragment within its sequence.

BACKGROUND: Resistant infectious diseases caused by gram-negative bacteria are among the most serious worldwide health problems. Antimicrobial peptides (AMPs) have been explored as promising antibacterial, antibiofilm, and anti-infective candidates to address these health challenges. MAJOR CONCLUSIONS: Here we report the potent antibacterial effect of the peptide PaDBS1R6 on clinical bacterial isolates and identify an immunomodulatory peptide fragment incorporated within it. PaDBS1R6 was evaluated against Acinetobacter baumannii and Escherichia coli clinical isolates and had minimal inhibitory concentration (MIC) values from 8 to 32 µmol L-1. It had a rapid bactericidal effect, with eradication showing within 3 min of incubation, depending on the bacterial strain tested. In addition, PaDBS1R6 inhibited biofilm formation for A. baumannii and E. coli and was non-toxic toward healthy mammalian cells. These findings are explained by the preference of PaDBS1R6 for anionic membranes over neutral membranes, as assessed by surface plasmon resonance assays and molecular dynamics simulations. Considering its potent antibacterial activity, PaDBS1R6 was used as a template for sliding-window fr agmentation studies (window size = 10 residues). Among the sliding-window fragments, PaDBS1R6F8, PaDBS1R6F9, and PaDBS1R6F10 were ineffective against any of the bacterial strains tested. Additional biological assays were conducted, including nitric oxide (NO) modulation and wound scratch assays, and the R6F8 peptide fragment was found to be active in modulating NO levels, as well as having strong wound healing properties. GENERAL SIGNIFICANCE: This study proposes a new concept whereby peptides with different biological properties can be derived by the screening of fragments from within potent AMPs.

Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.

This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 × 105. Moreover, the cells were placed in a 10 µL solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.

Hematoimmunological responses of juvenile Nile tilapia (Oreochromis niloticus) receiving the dietary supplementation of immunomodulators and different levels of vitamins after challenge with physical stress.

In this study, we analyzed the hematoimmunological effects of dietary supplementation with immunomodulators (ß-glucans + nucleotides) and different levels of vitamins on Nile tilapia (Oreochromis niloticus) after exposure to physical stress. The following four diet treatments were used: diets with indicated vitamin levels (Vitind), diets with Vitind + immunomodulator (Vitind + Immune), diets with high vitamin content (Vithigh), and those with Vithigh + immunomodulator (Vithigh + Immune). The experiment included 560 fish in 28 tanks (20 fish tank-1), with seven replicates per treatment. After 60 days of supplementation, the water temperature was set at 20 °C, and complete biometrics were performed. The animals were then subjected to physical stress with temperature oscillations of 20 ºC to 30 ºC/30 ºC to 20 ºC/20 ºC to 30 ºC. Hematoimmunological data from 140 animals were collected post-stress. Antimicrobial titer and total plasma protein levels were significantly higher in fish not receiving immunomodulator-supplemented diets (2.88 ± 0.43 log2 and 26.81 ± 4.01 mg∙mL-1, respectively) than in those that did. Conversely, the agglutination titer increased in fish fed with lower vitamin levels (3.33 ± 0.66 log2) compared to those with higher vitamin levels. Increased immunoglobulin levels were observed in fish fed diets co-supplemented with vitamins and immunomodulators, revealing an interaction between immunomodulators and dietary vitamin levels. In summary, the inclusion of immunomodulators in the diet enhanced the animals' resistance to physical stress and improved hematoimmunological parameters. Additionally, a high vitamin content in the diet did not modulate the immune responses in the animals.

Neste estudo analisamos os efeitos hematoimunológicos da suplementação dietética com imunomoduladores (ß-glucanos+nucleotídeos) e diferentes níveis de vitaminas na tilápia do Nilo (Oreochromis niloticus) após exposição ao estresse físico. Foram utilizados quatro tratamentos: dietas com níveis indicados de vitaminas (Vitind), dietas com Vitind + imunomodulador (Vitind+Immune), dietas com alto teor de vitaminas (Vithigh) e dietas com Vithigh + imunomodulador (Vithigh+Immune). O experimento incluiu 560 peixes em 28 tanques (20 peixes tanques-1), com sete repetições por tratamento. Após 60 dias de suplementação, a temperatura da água foi fixada em 20 °C e realizada biometria completa. Os animais foram submetidos a estresse físico com oscilações de temperatura de 20 ºC a 30 ºC/30 ºC a 20 ºC/20 ºC a 30 ºC. Dados hematoimunológicos de 140 animais foram coletados pós-estresse. O título antimicrobiano e os níveis de proteína plasmática total foram significativamente maiores em peixes que não receberam dietas com imunomodulador (2,88±0,43 log2 e 26,81±4,01 mg∙mL−1) do que naqueles que receberam. Por outro lado, o título de aglutinação aumentou em peixes alimentados com níveis mais baixos de vitaminas (3,33±0,66 log2) comparado àqueles com níveis mais elevados. Níveis aumentados de imunoglobulinas foram observados em peixes alimentados com dietas co-suplementadas com vitaminas e imunomoduladores, revelando interação entre imunomoduladores e níveis de vitaminas na dieta. Em resumo, a inclusão de imunomoduladores na dieta aumentou a resistência dos animais ao estresse físico e melhorou os parâmetros hematoimunológicos. Além disso, o alto teor de vitaminas na dieta não modulou as respostas imunológicas dos animais.

(-)-Fenchone Prevents Cysteamine-Induced Duodenal Ulcers and Accelerates Healing Promoting Re-Epithelialization of Gastric Ulcers in Rats via Antioxidant and Immunomodulatory Mechanisms.

BACKGROUND: (-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. METHODS: The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. RESULTS: In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-ß). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. CONCLUSION: (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.

In vitro anti-tumoral and immunomodulatory effects of acidic polysaccharides isolated from the fungus Gloeosoma mirabile.

Polysaccharides from wood-rooting fungi have attracted attention due to their broad pharmacological properties. Herein, we report the antitumor and immunomodulatory activities of acid polysaccharides isolated from fungi Gloeosoma mirabile. The polysaccharide extracts displayed significant antiproliferative activity against cancer cell lines (MCF-7, HCT-116, U-937) in a dose-dependent manner and induction of IL-6 in macrophage RAW 264.7. Furthermore, flow cytometry analysis showed that high polysaccharide concentrations induced apoptosis by 83% in HL-60 cells. Based on gas chromatography-mass spectrometry (GC-MS) and Fourier transform infra-red (FT-IR) spectroscopy studies, acidic polysaccharides from G. mirabile were mainly composed of arabinose, α-D-galactopyranose and methyl ß-D-galactopyranoside.

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).

Monomeric ubiquitin (Ub) is a 76-amino-acid highly conserved protein found in eukaryotes. The biological activity of Ub first described in the 1970s was extracellular, but it quickly gained relevance due to its intracellular role, i.e., post-translational modification of intracellular proteins (ubiquitination) that regulate numerous eukaryotic cellular processes. In the following years, the extracellular role of Ub was relegated to the background, until a correlation between higher survival rate and increased serum Ub concentrations in patients with sepsis and burns was observed. Although the mechanism of action (MoA) of extracellular ubiquitin (eUb) is not yet well understood, further studies have shown that it may ameliorate the inflammatory response in tissue injury and multiple sclerosis diseases. These observations, compounded with the high stability and low immunogenicity of eUb due to its high conservation in eukaryotes, have made this small protein a relevant candidate for biotherapeutic development. Here, we review the in vitro and in vivo effects of eUb on immunologic, cardiovascular, and nervous systems, and discuss the potential MoAs of eUb as an anti-inflammatory, antimicrobial, and cardio- and brain-protective agent.

Activation of murine macrophages by membrane proteins from Tritrichomonas foetus grown on iron- and calcium-rich conditions.

Tritrichomonas foetus is a protozoan parasite that causes a venereal disease in cattle limiting reproduction by abortions and sterility. The immune response against this parasite is poorly understood. Since the iron and calcium ions are important regulators of the microenvironment of the urogenital tract in cattle, we decided to evaluate the role of these divalent cations on the antigenicity of membrane proteins of T. foetus on macrophage activation as one of the first inflammatory responses towards this pathogen. Colorimetric methods and ELISA were used to detect the nitric oxide and oxygen peroxide production and expression of cytokines in culture supernatant from macrophage incubated with membrane proteins from T. foetus cultured in iron- and calcium-rich conditions. qRT-PCR assays were used to evaluate the transcript expression of genes involved in the inflammatory response on the macrophages. The membrane proteins used for in vitro stimulation caused the up-regulation of the iNOS and NOX-2 genes as well as the generation of NO and H2 O2 in murine macrophages on a dependent way of the metal concentrations. Additionally, after stimulation, macrophages showed a considerable rise in pro-inflammatory cytokines and a downregulation of anti-inflammatory cytokines, as well as up-regulation in the transcription of the TLR4 and MyD88 genes. These data suggest that membrane proteins of T. foetus induced by iron and calcium can activate an inflammatory specific macrophage response via TLR4/MyD88 signalling pathway.

Isolation, characterization, and immunomodulatory activity evaluation of probiotic strains from colostrum and canine milk.

Background: This study aimed to characterize potential probiotic strains for use in dogs to prevent infectious enteropathies. Lactic acid bacteria (LAB) isolated from canine milk and colostrum were characterized according to their functional properties, including their resistance to gastrointestinal conditions, inhibitory effect against pathogens, and intestinal adhesion. Methods: The immunomodulatory effects of the strains were also analyzed in in vitro and in vivo studies. Among the strains evaluated, two LAB strains (TUCO-16 and TUCO-17) showed remarkable resistance to pH 3.0, bile salts, and pancreatin, as well as inhibitory effects against pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Results: The TUCO-16 and TUCO-17 strains induced a significant increase in the expression of TNF-α, IL-8, and TLR2 in canine macrophages. The oral administration of TUCO-16 and TUCO-17 strains to mice significantly augmented their resistance to pathogenic E. coli or Salmonella intestinal infections. Both canine strains reduced intestinal damage and pathogen counts in the liver and spleen and avoided their dissemination into the bloodstream. These protective effects were related to the ability of TUCO-16 and TUCO-17 strains to differentially modulate the production of IFN-γ, IFN-ß, TNF-α, IL-6, KC, MCP-1, and IL-10 in the intestinal mucosa. Conclusion: Both strains, TUCO-16 and TUCO-17, are potential probiotic candidates for improving intestinal health in dogs, particularly for their ability to inhibit the growth of Gram-negative pathogens common in gastrointestinal infections and modulate the animal's immune response. Further studies are required to effectively demonstrate the beneficial effects of TUCO-16 and TUCO-17 strains in dogs.

Platelet transfusion in patients with liver cirrhosis crosstalk with neutrophil: Prospective study

ABSTRACT Introduction: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. Methods: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. Results: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CDllb among cirrhotic patients. Conclusions: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CDllb on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

Impact of Breaking up of Sitting Time on Anti-inflammatory Response Induced by Extracellular Vesicles.

Physical inactivity and sedentary behaviors (SB) have promoted a dramatic increase in the incidence of a host of chronic disorders over the last century. The breaking up of sitting time (i.e., sitting to standing up transition) has been proposed as a promising solution in several epidemiological and clinical studies. In parallel to the large interest it initially created, there is a growing body of evidence indicating that breaking up prolonged sedentary time (i.e., > 7 h in sitting time) could reduce overall mortality risks by normalizing the inflammatory profile and cardiometabolic functions. Recent advances suggest that the latter health benefits, may be mediated through the immunomodulatory properties of extracellular vesicles. Primarily composed of miRNA, lipids, mRNA and proteins, these vesicles would influence metabolism and immune system functions by promoting M1 to M2 macrophage polarization (i.e., from a pro-inflammatory to anti-inflammatory phenotype) and improving endothelial function. The outcomes of interrupting prolonged sitting time may be attributed to molecular mechanisms induced by circulating angiogenic cells. Functionally, circulating angiogenic cells contribute to repair and remodel the vasculature. This effect is proposed to be mediated through the secretion of paracrine factors. The present review article intends to clarify the beneficial contributions of breaking up sitting time on extracellular vesicles formation and macrophage polarization (M1 and M2 phenotypes). Hence, it will highlight key mechanistic information regarding how breaking up sitting time protocols improves endothelial health by promoting antioxidant and anti-inflammatory responses in human organs and tissues.

Larrea divaricata a native Argentine plant with potential activity against SARS-CoV-2? / ¿Larrea divaricata una planta nativa argentina con actividad potencial sobre SARS-CoV-2?

Larrea divaricata Cav. is an autochthonous South American plant popularly used in inflammatory and infectious diseases with reported anti - inflammatory, immunomodulatory, antimicrobial and antioxidant activities. Covid - 19 is an infection ca used by the severe acute respiratory syndrome coronavirus 2 (SARS - CoV - 2). This virus can cause pneumonia and even death in about 5% of the cases. The objective of the article was to demonstrate, through a literature review, that L. divaricata has sufficie nt attributes to be assayed against SARS - CoV - 2. For this, the chemical composition, reported activities and docking studies were taken into account. This review demonstrated that the plant extracts are capable of inhibiting the proliferation of fungi, bact eria and viruses and that they exert anti - inflammatory and immunomodulatory actions in different " in vitro " and " in vivo " models. These results suggest that the plant is a good candidate to be studied for the prevention and/or treatment of SARS - CoV - 2.

Larrea divaricata Cav. es una planta autóctona Sudamericana, utilizada popularmente en enfermedades inflamatorias e infecciosas, con activida d anti - inflamatoria, inmunomoduladora, antimicrobiana y antioxidante reportada. El Covid - 19 es una infección causada por una cepa de coronavirus, SARS - CoV - 2 (coronavirus tipo 2 causante del síndrome respiratorio agudo severo). Este virus puede originar neu monía e incluso la muerte en alrededor del 5% de los casos. Nuestro objetivo fue demostrar, a través de una revisión bibliográfica, que esta planta tiene atributos suficientes para ser ensayada en estudios contra SARS - CoV - 2. Se tuvo en cuenta la composici ón química, los antecedentes científicos y los estudios de acoplamiento molecular. Esta revisión permitió demostrar que extractos de la planta son capaces de inhibir la proliferación de hongos, bacterias y virus y que presentan acción anti - inflamatoria en diferentes modelos " in vitro " e " in vivo ", lo que los hace candidatos a ser estudiados en la prevención y/o tratamiento de la infección contra SARS - CoV - 2.

Origanum vulgare: peroxidase-, superoxide dismutase- and immunomodulatory activities on macrophages activated with Helicobacter pylori derivatives.

Helicobacter pylori, invades the gastric mucosa and is one of the causative agents of stomach cancer and peptic ulcers. Origanum vulgare, is a flavouring herb used worldwide. But little is known about the effects of extracts prepared by maceration in cold PBS. This study was aimed at determining the superoxide dismutase (SOD)- and peroxidase (Px)-like antioxidant activities as well as the immunomodulatory activity (anti-inflammatory/pro-inflammatory) of an aqueous extract of O. vulgare by evaluating the production of nitric oxide (NO) in macrophages stimulated with H. pylori derivatives. The cold extract presented SOD-like and Px-like activities with effective concentration 50 (EC50) values of Px = 489.7 ± 48 µg/ml and SOD= 384.7 ± 30 µg/ml. The extract was also capable of modulating the production of NO in macrophages stimulated by H. pylori derivatives by exerting a pro-inflammatory activity at high concentrations and an anti-inflammatory activity at low concentrations.

Crotoxin Modulates Macrophage Phenotypic Reprogramming.

Macrophage plasticity is a fundamental feature of the immune response since it favors the rapid and adequate change of the functional phenotype in response to the pathogen or the microenvironment. Several studies have shown that Crotoxin (CTX), the major toxin of the Crotalus durissus terrificus snake venom, has a long-lasting antitumor effect both in experimental models and in clinical trials. In this study, we show the CTX effect on the phenotypic reprogramming of macrophages in the mesenchymal tumor microenvironment or those obtained from the peritoneal cavity of healthy animals. CTX (0.9 or 5 µg/animal subcutaneously) administered concomitantly with intraperitoneal inoculation of tumor cells (1 × 107/0.5 mL, injected intraperitoneally) of Ehrlich Ascitic Tumor (EAT) modulated the macrophages phenotype (M1), accompanied by increased NO• production by cells from ascites, and was evaluated after 13 days. On the other hand, in healthy animals, the phenotypic profile of macrophages was modulated in a dose-dependent way at 0.9 µg/animal: M1 and at 5.0 µg/animal: M2; this was accompanied by increased NO• production by peritoneal macrophages only for the dose of 0.9 µg/animal of CTX. This study shows that a single administration of CTX interferes with the phenotypic reprogramming of macrophages, as well as with the secretory state of cells from ascites, influencing events involved with mesenchymal tumor progression. These findings may favor the selection of new therapeutic targets to correct compromised immunity in different systems.

Spray-Dried Animal Plasma as a Multifaceted Ingredient in Pet Food.

Plasma is a co-product from pork and beef obtained during the processing of animals for human consumption. The spray-drying process maintains the solubility of spray-dried animal plasma (SDAP) and its nutritional and functional properties, making this ingredient multifunctional in human and animal nutrition. In pet food, SDAP has been used in the production of wet foods (pates and chunks in gravy) as an emulsifying and binding agent, with the potential to replace hydrocolloids partially or totally, which have some negative implications for digestibility, fecal quality, and intestinal inflammation. From a nutritional point of view, SDAP has high digestibility and an amino acid profile compatible with high-quality ingredients, such as powdered eggs. Studies in companion animals, especially in cats, have shown that SDAP is an ingredient with high palatability. Despite the immunomodulatory, anti-inflammatory, prebiotic, and neuroprotective properties demonstrated in some animal models, there are still few publications demonstrating these effects in dogs and cats, which limits its use as a functional ingredient for these species. In this review, the potential use of SDAP in pet food, aspects related to the sustainability of this ingredient, and opportunities for studies in companion animals are discussed.

Antibacterial and immunological properties of piperine evidenced by preclinical studies: a systematic review.

Aim: To review in vitro, in vivo, and in silico studies examining the antibacterial and immunomodulatory properties of piperine (PPN). Methods: This systematic review followed PRISMA guidelines, and five databases were searched. Results: A total of 40 articles were included in this study. Six aspects of PPN activity were identified, including antibacterial spectrum, association with antibiotics, efflux pump inhibition, biofilm effects, protein target binding, and modulation of immune functions/virulence factors. Most studies focused on Mycobacterium spp. and Staphylococcus aureus. Cell lineages and in vivo models were employed to study PPN antibacterial effects. Conclusion: We highlight PPN as a potential adjuvant in the treatment of bacterial infections. PPN possesses several antibacterial properties that need further exploration to determine the mechanisms behind its pharmacological activity.

Immunonutrients and intestinal microbiota: a gap in the literature.

The human intestinal microbiota is composed of a wide variety of microorganisms that play an important role in intestinal permeability, digestion, and especially, in the maturation of host's immune system. At the same time, effectiveness of immunomodulatory nutrients is known, especially in situations of stress and in strengthening body's defenses. However, the influence of the use of immunonutrients on microbiota's composition and variability is still poorly investigated. Studies indicate that the use of immunomodulators such as omega 3, glutamine, and arginine, can play a role in its modulation, through the immunological enhancement of the hosts. Therefore, this article sought to concentrate the latest evidence on the influence of the use of the main immunonutrients used in clinical practice on human gut microbiota, and their potential benefits.

Papel inmunomodulador de la vitamina D y los ácidos grasos poliinsaturados omega-3 en trastornos autoinmunes: Revisión de la Literatura / Immunomodulatory role of vitamin D and omega-3 polyunsaturated fatty acids in autoinmune disorders: Literature Review

Los trastornos autoinmunes representan una familia de al menos 80 condiciones diferentes que surgen de una respuesta aberrante del sistema inmunológico resultando finalmente en la destrucción de tejidos y órganos específicos del cuerpo. Es importante destacar que durante las últimas tres décadas los estudios epidemiológicos han proporcionado evidencia de un aumento constante en la incidencia y prevalencia de trastornos autoinmunes. En los últimos años, varios estudios han demostrado que la vitamina D y los ácidos grasos poliinsaturados (AGPs) omega-3 ejercen propiedades inmunomoduladoras y antiinflamatorias sinérgicas que pueden aprovecharse positivamente para la prevención y el tratamiento de trastornos autoinmunes. En este sentido, el reciente ensayo clínico denominado VITAL (ensayo de vitamina D y omega 3); un estudio a gran escala, aleatorizado, doble ciego, controlado con placebo encontró que la suplementación conjunta de vitamina D y AGPs omega-3 (VIDOM) puede reducir la incidencia de enfermedades autoinmunes. En esta revisión de la literatura, resumimos los mecanismos moleculares detrás de las propiedades inmunomoduladoras y antiinflamatorias de la vitamina D y los AGPs omega-3, así como la posible interacción bidireccional entre el metabolismo de la vitamina D y el metabolismo de los AGPs omega-3 que justifica la co- suplementación VIDOM en trastornos autoinmunes(AU)

Autoimmune disorders represent a family of at least 80 different conditions that arise from an aberrant immune system response, which ultimately results in the destruction of specific body tissues and organs. It is important to highlight that during the last three decades epidemiological studies have provided evidence of a steady increase in the incidence and prevalence of autoimmune disorders. In recent years, several studies have shown that vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) exert synergistic immunomodulatory and anti-inflammatory properties that can be positively harnessed for the prevention and treatment of autoimmune disorders. In this sense, the recent clinical trial called VITAL (Vitamin D and Omega 3 trial) - a large, randomized, double-blind, placebo- controlled study - found that co-supplementation of vitamin D and omega-3 PUFAs (VIDOM) can reduce the incidence of autoimmune diseases. In this literature review, we summarize the molecular mechanisms behind the immunomodulatory and anti-inflammatory properties of vitamin D and omega-3 PUFAs, as well as the possible bidirectional interaction between vitamin D metabolism and omega-3 PUFA metabolism that justifies VIDOM co- supplementation in autoimmune disorders(AU)

Immunomodulatory and Antioxidant Effects of Spray-Dried Encapsulated Kale Sprouts after In Vitro Gastrointestinal Digestion.

The health-related compounds present in kale are vulnerable to the digestive process or storage conditions. Encapsulation has become an alternative for their protection and takes advantage of their biological activity. In this study, 7-day-old Red Russian kale sprouts grown in the presence of selenium (Se) and sulfur (S) were spray-dried with maltodextrin to assess their capacity to protect kale sprout phytochemicals from degradation during the digestion process. Analyses were conducted on the encapsulation efficiency, particle morphology, and storage stability. Mouse macrophages (Raw 264.7) and human intestinal cells (Caco-2) were used to assess the effect of the intestinal-digested fraction of the encapsulated kale sprout extracts on the cellular antioxidant capacity, the production of nitric oxide (NOx), and the concentrations of different cytokines as indicators of the immunological response. The highest encapsulation efficiency was observed in capsules with a 50:50 proportion of the hydroalcoholic extract of kale and maltodextrin. Gastrointestinal digestion affected compounds' content in encapsulated and non-encapsulated kale sprouts. Spray-dried encapsulation reduced the phytochemicals' degradation during storage, and the kale sprouts germinated with S and Se showed less degradation of lutein (35.6%, 28.2%), glucosinolates (15.4%, 18.9%), and phenolic compounds (20.3%, 25.7%), compared to non-encapsulated ones, respectively. S-encapsulates exerted the highest cellular antioxidant activity (94.2%) and immunomodulatory activity by stimulating IL-10 production (88.9%) and COX-2 (84.1%) and NOx (92.2%) inhibition. Thus, encapsulation is an effective method to improve kale sprout phytochemicals' stability and bioactivity during storage and metabolism.

Extracellular Vesicles from Candida haemulonii var. vulnera Modulate Macrophage Oxidative Burst.

Members of the Candida haemulonii species complex are multidrug-resistant emergent yeast pathogens able to cause superficial and invasive infections in risk populations. Fungal extracellular vesicles (EVs) play a critical role in the pathogenicity and virulence of several species and may perform essential functions during infections, such as carrying virulence factors that behave in two-way communications with the host, affecting survival and fungal resistance. Our study aimed to describe EV production from Candida haemulonii var. vulnera and evaluate whether murine macrophage RAW 264.7 cells respond to their stimuli by generating an oxidative response after 24 h. For this purpose, reactive oxygen species detection assays demonstrated that high concentrations of yeast and EVs (1010 particles/mL) of Candida haemulonii did not change macrophage viability. However, the macrophages recognized these EVs and triggered an oxidative response through the classical NOX-2 pathway, increasing O2•- and H2O2 levels. However, this stress did not cause lipid peroxidation in the RAW 264.7 cells and neither lead to the activation of the COX-2-PGE2 pathway. Thus, our data suggest that low concentrations of C. haemulonii EVs are not recognized by the classical pathway of the oxidative burst generated by macrophages, which might be an advantage allowing the transport of virulence factors via EVs, not identified by the host immune system that could work as fine tube regulators during infections caused by C. haemulonii. In contrast, C. haemulonii var. vulnera and high EV concentrations activated microbicidal actions in macrophages. Therefore, we propose that EVs could participate in the virulence of the species and that these particles could be a source of antigens to be exploited as new therapeutic targets.