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1.
Nature ; 574(7776): 45-56, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578484

RESUMO

New therapies that promote antitumour immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy. Given the crucial role of innate immune responses in immunity, harnessing these responses opens up new possibilities for long-lasting, multilayered tumour control.


Assuntos
Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos , Neoplasias/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
2.
Chemosphere ; 226: 915-923, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31509921

RESUMO

Fine particulate matter ≤2.5 µm (PM2.5) is a prominent global public health risk factor that can cause respiratory infection by downregulating the amounts of antimicrobial proteins and peptides (AMPs). Both salivary agglutinin (SAG) and surfactant protein D (SPD) are important AMPs in respiratory mucosal fluid, providing protection against airway pathogen invasion and infection by inducing microbial aggregation and enhancing pathogen clearance. However, the relationship between PM2.5 and these AMPs is unclear. To better understand the relationship between PM2.5 and airway innate immune defenses, we review the respiratory antimicrobial activities of SAG and SPD, as well as the adverse effects of PM2.5 on airway innate antimicrobial defense. We speculate there exists a dual effect between PM2.5 and respiratory antimicrobial activity, which means that PM2.5 suppresses respiratory antimicrobial activity through downregulating airway AMPs, while airway AMPs accelerate PM2.5 clearance by inducing PM2.5 microbial aggregation. We propose further research on the relationship between PM2.5 and these AMPs.


Assuntos
Aglutininas/farmacologia , Antibacterianos/farmacologia , Imunidade Inata/efeitos dos fármacos , Material Particulado/efeitos adversos , Proteína D Associada a Surfactante Pulmonar/farmacologia , Sistema Respiratório/efeitos dos fármacos , Infecções Respiratórias/tratamento farmacológico , Peptídeos Catiônicos Antimicrobianos/farmacologia , Humanos , Infecções Respiratórias/induzido quimicamente
3.
Fish Shellfish Immunol ; 92: 621-628, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31260736

RESUMO

Intestine in fish is a complex multifunctional organ, not only plays roles in digestion and absorption of nutrient, but also has critical role in immunity. The present study evaluated the effects of different levels of dietary sodium butyrate [Butirex® C4 (Butirex)] on intestinal immune-,antioxidant-and tight junction-related gene expression injuvenile rainbow trout(Oncorhynchusmykiss). 240 healthy rainbow trout were dispensed in 12 fiberglass tanks appointed to four treatments [0 (control), 1.5 (B1.5), 2.5 (B2.5) and 5 (B5)g Butirex per kg diet]. After a 45-day feeding trial, the fish fed with the Butirex-supplemented diets showed higher intestinal lysozyme (LYZ), complement(ACH50) and bactericidal activities; the elevations in ACH50 and bactericidal activities depended on Butirex levels (P < 0.05). The Butirex-supplemented groups, particularly the B2.5 group, had significantly higher LYZ gene expression compared to the control group (P < 0.05). Butirex at 2.5 and 5 g/kg levels led to significantly higher IL-1ß gene expression. B2.5 and B5 had significantly lower and higher TNF-α gene expression compared to the control group (P < 0.05). The B2.5 group had significantly higher TGF-B, and significantly lower IL-8 compared to the control group (P < 0.05). The B1.5 and B2.5 group had significantly higher IL-10 gene expression compared to the control group (P < 0.05). The B2.5 and B5 groups had significantly higher SOD gene expression compared to the other groups; the highest expression was related to the B2.5 group (P < 0.05). Dietary Butirex supplementation significantly up-regulated CAT and GPx genes expression compared to the control group; the highest expression as related to the B2.5 and B5 groups (P < 0.05). The B2.5 group had significantly lower CLD12 gene expression compared to the control group (P < 0.05). The B2.5 and B5 groups had significantly higher CLD3, OCLD and ZO-1 gene expression compared to the control. The highest CLD3, ZO-1 gene expressions was related to the B2.5, and B5 groups respectively (P < 0.05). After challenge with Streptococcus iniae, B2.5 and B5 had significantly higher survival compared to the control group (55.6 ±â€¯7.70 and 68.9 ±â€¯10.2 vs. 33.3 ±â€¯6.67). In conclusion, Butirex is efficient immune stimulant and health booster in rainbow trout, which augments the fish resistance to disease. Modulation of immune components, cytokines, antioxidant system and intestinal integrity might involve in improving disease resistance in Butirex-treated fish. Although most of the examined genes were modulated by 2.5 g/kg Butirex under normal conditions, 5 g/kg level is recommended under pathogenic state to mitigate mortality.


Assuntos
Ácido Butírico/metabolismo , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , Oncorhynchus mykiss/imunologia , Transcriptoma/efeitos dos fármacos , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Ácido Butírico/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Proteínas de Peixes/metabolismo , Intestinos/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Distribuição Aleatória , Sódio na Dieta/administração & dosagem , Infecções Estreptocócicas/imunologia , Streptococcus iniae/fisiologia , Proteínas de Junções Íntimas/metabolismo , Transcriptoma/imunologia
4.
Fish Shellfish Immunol ; 92: 719-727, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271838

RESUMO

The aim of this study was to investigate the effects of intestinal microbial manipulation by dietary probiotic supplementation on digestive enzyme activity, immune-related gene transcription, intestinal structure alteration, and viability against pathogenic challenge in olive flounder. Similar-sized flounders (14.92 ±â€¯0.21 g) were divided into three groups and supplemented with a control (without probiotic) or 1 × 108 CFU/g diet of each of Bacillus sp. SJ-10 (ProB) and Lactobacillus plantarum (ProL) for eight weeks. At the end of the feeding trial, the estimated intestinal microbial richness (Chao1) and diversity (Shannon) demonstrated a significant (P < 0.05) abundance in the ProB group (484.80 ±â€¯88.75, 5.08 ±â€¯0.17) compared to the ProL (285.32 ±â€¯17.78, 4.54 ±â€¯0.09) and control groups (263.23 ±â€¯20.20, 4.30 ±â€¯0.20). A similar alteration phenomenon was also found at the phylum level, with a higher abundance of Proteobacteria, Actinobacteria, and Acidobacteria. Trypsin and lipase activities were elevated in both the ProB and ProL groups compared to the control, but amylase was only higher in the ProB group. The expression levels of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were significantly higher in the ProB group than in the other two groups. There was a significant increase in transcription of IL-10 in both the ProB and ProL groups compared to the control. The length of villi and microvilli of probiotic-fed olive flounder was increased but was not significantly different from the control group. In an in vivo challenge experiment with Streptococcus iniae (1 × 108 CFU/mL), the survival rates of the ProB and ProL groups were 29.17% and 12.50%, respectively, when control mortality reached 100%. Therefore, intestinal microbiota manipulation by probiotic supplementation increased the richness of the bacterial population, digestive enzyme activity, intestinal immune gene transcription, and infectious disease protection in olive flounder.


Assuntos
Digestão/efeitos dos fármacos , Linguados/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Proteínas de Vegetais Comestíveis/administração & dosagem , Probióticos/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Linguados/anatomia & histologia , Linguados/microbiologia , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Intestinos/enzimologia , Intestinos/microbiologia , Probióticos/administração & dosagem
5.
Fish Shellfish Immunol ; 92: 913-924, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306761

RESUMO

A feeding trial was performed to compare the effects of five ethanol herbal extracts (bhumi amla, Phyllanthus amarus Schum and Thonn [Pa]; guava, Psidium guajava L. [Pg]; sensitive plant, Mimosa pudica L. [Mp]; neem, Azadirachta indica A. Juss [Ai] and asthma plant, Euphorbia hirta L. [Eh]) on the immune response and disease resistance against Edwardsiella ictaluri infection of striped catfish (Pangasianodon hypophthalmus). Fish were fed diets supplemented with two doses of each plant extract (0% [basal diet], 0.4% Eh [Eh0.4], 2.0% Eh [Eh2.0], 0.2% Pa [Pa0.2], 1.0% Pa [Pa1.0], 0.2% Pg [Pg0.2], 1.0% Pg [Pg1.0], 0.4% Mp [Mp0.4], 2.0% Mp [Mp2.0], 0.4% Ai [Ai0.4], 2.0% Ai [Ai2.0]) for 8 weeks. Results showed that hematological parameters (total red blood cells, white blood cells, lymphocytes, monocytes, and neutrophils) of fish fed extract-based diets were significantly higher than in those fed the control diet (p < 0.05) after 4 and 8 weeks. Plasma lysozyme activity increased in fish whose diets contained both doses of Eh (p < 0.05) in week 4 (W4), whereas lysozyme activity increased in fish fed 0.2% Pa and Pg, and 2.0% Ai and Eh (p < 0.05) in week 8 (W8). The lysozyme levels in skin mucus did not significantly differ between treatments (p > 0.05) in W4 and after the bacterial challenge test. At the end of the feeding trial, levels of ACH50 significantly increased in most of extract groups compared to the control group (p < 0.05). Total immunoglobulin increased considerably in both the plasma and skin mucus of fish fed extract-supplemented diets after 8 weeks. In addition, dietary supplementation with Pg, Mp, Pa0.2, Eh2.0, and Ai0.4 for 8 weeks considerably reduced the cumulative mortality against E. ictaluri infection in striped catfish. The results suggest that plant extracts possibly modulate the striped catfish immune response in a time and dose dependent manner. Specifically, diets enriched with extracts of P. guajava at 0.2 and 1.0%, or M. pudica at 2.0% for 8 weeks, have great potential for improving striped catfish health by enhancing the immune system and reducing mortality against bacterial challenges.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Peixes-Gato/imunologia , Resistência à Doença/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Extratos Vegetais/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Edwardsiella ictaluri/fisiologia , Infecções por Enterobacteriaceae/imunologia , Doenças dos Peixes/imunologia , Extratos Vegetais/administração & dosagem , Distribuição Aleatória
6.
Aquat Toxicol ; 214: 105243, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31319294

RESUMO

Glyphosate is one of the most widely used pesticides in the world and can be transported easily by surface runoff, air, and rivers, potentially affecting aquaculture. In this study, the survival rate, intestinal and hepatopancreatic immune and digestive functions, and the intestinal microbial diversity of Chinese mitten crab (Eriocheir sinensis) were evaluated after 7 days of exposure to glyphosate (48.945 mg/L from 1/2 96-h LC50 value). The results showed that glyphosate significantly reduced the survival rate of E. sinensis. After exposure to glyphosate, the totoal antioxidant capacity (T-AOC) in the midgut and hindgut of E. sinensis was significantly decreased, and malondialdehyde (MDA) content in the midgut was significantly increased (P < 0.05). After glyphosate exposure, the activities of digestive enzymes (including lipase and amylase) in the intestinal tract were significantly decreased and trypsin was significantly increased, while three enzymes in the hepatopancreas were significantly increased (P < 0.05). Using high-throughput sequencing analysis of the gut microbiota, the results showed that glyphosate significantly decreased the diversity of E. sinensis gut microbiota, while significantly increasing the taxonomic richness of Bacteroidetes and Proteobacteria (P < 0.05). This study suggested that these bacteria may be involved in glyphosate effects on survival by regulation of immune and digestive function.


Assuntos
Braquiúros/imunologia , Braquiúros/microbiologia , Digestão/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Imunidade Inata/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Sequência de Bases , Biodiversidade , Braquiúros/efeitos dos fármacos , Braquiúros/enzimologia , Análise Discriminante , Glicina/toxicidade , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/enzimologia , Hepatopâncreas/microbiologia , Intestinos/efeitos dos fármacos , Intestinos/enzimologia , Intestinos/microbiologia , Análise dos Mínimos Quadrados , Filogenia , Análise de Componente Principal , Poluentes Químicos da Água/toxicidade
7.
Arch Anim Nutr ; 73(1): 44-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31274343

RESUMO

The study evaluated the effects of different doses of 25-hydroxyvitamin D3 (25(OH)D3) on growth performance, immune function and antioxidative capacity in piglets. In a 21-d trial, 35 weaned pigs were divided into five groups and diets were supplemented with 5.5 (control), 43.0, 80.5, 118.0 and 155.5 µg 25(OH)D3/kg, respectively. No treatment effects were observed for average daily gain, average daily feed intake and feed to gain ratio. Increasing dietary 25(OH)D3 levels increased serum 25(OH)D3 concentrations linearly (p < 0.01), decreased the frequency of CD3+CD4+ and CD3+CD8+ T cells (p < 0.01), and the serum level of complement component 3 (p < 0.05). Supplementation of 80.5 and 118.0 µg 25(OH)D3/kg enhanced the activity of serum glutathione peroxidase (p < 0.05) and addition of 43.0 µg 25(OH)D3/kg increased the malondialdehyde concentration (p < 0.05). Overall, feeding high-dose 25(OH)D3 to weaned pigs partly improved immune functions and the antioxidative capacity.


Assuntos
Antioxidantes/metabolismo , Calcifediol/metabolismo , Imunidade Inata/imunologia , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata/efeitos dos fármacos , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/imunologia , Vitaminas/administração & dosagem , Desmame
8.
Res Vet Sci ; 125: 333-344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31352282

RESUMO

Minthostachys verticillata essential oil (EO) is a natural product that reports immunomodulatory effects on human T cells as well as anti-inflammatory activity. Bovine mastitis is a worldwide disease, mainly caused by bacteria, affecting milk quality and yield, leading to high economic losses. Environmental pathogens, as Enterococcus faecium, are implicated in the disease. Antibiotic therapy is adequate, although it can leave residues in milk, causing problems in human health. The search of immunomodulatory substances for bovine mastitis treatment is a promising alternative strategy. The aim of this study was to characterize the effect of M. verticillata EO on macrophage phagocytosis and evaluate its immunomodulatory and protective effects in mice challenged with E. faecium. The results showed that EO activated macrophage phagocytosis mechanisms inducing reactive oxygen species production. Moreover, EO modulated the innate immune response in mammary glands of female Balb/c mice challenged with E. faecium decreasing the infiltration of polymorphonuclear neutrophils and IL-1ß and TNF-α mRNA expression. In addition, EO increased the expression of IL-10 in the last hours of infection. Treatment with EO did not increase the number of activated CD4+ or CD8+ T cells or the production of specific antibodies. These results suggest that EO play an important role in helping to resolve the infection in the first hours without activating adaptive immunity. In addition, a marked decrease of the bacterial count in the glands of mice treated with EO was observed. A natural product such as M. verticillata EO could have a potential use to control bovine mastitis.


Assuntos
Enterococcus faecium/fisiologia , Imunidade Inata/efeitos dos fármacos , Lamiaceae/química , Macrófagos/efeitos dos fármacos , Mastite Bovina/tratamento farmacológico , Óleos Voláteis/farmacologia , Fagocitose/efeitos dos fármacos , Animais , Bovinos , Feminino , Fatores Imunológicos/farmacologia , Macrófagos/imunologia , Mastite Bovina/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Óleos Voláteis/química , Substâncias Protetoras/farmacologia
9.
AAPS PharmSciTech ; 20(6): 241, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31250260

RESUMO

Particulate drug delivery systems (PDDS) have been broadly explored as platforms for delivery of drugs, enzymes, cells, and vaccines for pharmaceutical applications. Studies suggest that microspheres (MS) can stimulate innate immune cells even without a drug payload; however, less is known regarding how they impact host cells in dealing with the bacillary infection. We examined the role of drug-free inhalable alginate microspheres (A-MS) on phagocytosis efficiency and subsequent immune cell activation in Escherichia coli-infected THP-1-derived macrophages. Alginate particles have been widely investigated as carriers for prolonged delivery of bioactive (i.e., drugs, diagnostics, and vaccines). A-MS were fabricated by industry scalable spray-congealing process using divalent cation-induced gelification. E. coli-infected macrophages (multiplicity of infection (MOI 1:10) were treated with drug-free A-MS, where we found a consistent moderate reduction in bacillary viability. Particles were more efficiently and rapidly phagocytized by infected macrophages as compared with normal macrophage cells. Subsequently, A-MS induced markers of M1 macrophage responses and stimulated the processing and secretion of pro-inflammatory cytokines (IL-6, IL-12). It also notably augmented the generation of reactive oxygen species (ROS) and nitric oxide (NO) in infected cells. Results illustrate that, the blank A-MS (without a drug payload) able to moderately check the growth of intracellular E. coli (without significant cytotoxicity) by modulating the M1 inflammatory response by host cells. This "added value" can be utilized in the design and development of therapeutic system with the additional advantage of immune-modulatory activity, in addition to serving as a drug carrier.


Assuntos
Alginatos/farmacologia , Escherichia coli/imunologia , Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Microesferas , Alginatos/química , Animais , Citocinas/metabolismo , Humanos , Macrófagos/imunologia , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos
10.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180062

RESUMO

The human microbiota plays a crucial role in educating the immune system and influencing host health right since birth. Various maternal factors along with the vertical microbial transfer from the mother, as well as the horizontal environmental transmission and internal factors relating to the infant, play a crucial role in modulating the gut microbiota. The early life microflora is highly unstable and undergoes dynamic changes during the first few years, converging towards a more stabilized adult microbiota by co-evolving with the host by the age of 3-4 years. Microbiota studies have underlined the role of dysbiosis in developing several metabolic disorders like obesity, diabetes and immune-related disorders like asthma, to name a few. Thus, understanding early life microbial composition and various factors affecting the microbial community will provide a platform for developing strategies/techniques to maintain host health by restoring gut microbial flora. This review focuses on the factors that affect the microbial composition of the foetus in utero, during birth, infancy through childhood.


Assuntos
Asma/microbiologia , Diabetes Mellitus/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal/imunologia , Obesidade/microbiologia , Adulto , Antibacterianos/efeitos adversos , Asma/imunologia , Criança , Pré-Escolar , Diabetes Mellitus/imunologia , Dieta/métodos , Disbiose/imunologia , Feminino , Feto , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Lactente , Masculino , Obesidade/imunologia , Gravidez , Fatores de Risco
11.
Sci Total Environ ; 685: 836-846, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247433

RESUMO

The effects of microplastic exposure on the non-specific immune responses and intestinal microflora remain unclear. In this study, juveniles of the Chinese mitten crab (Eriocheir sinensis) were exposed to different concentrations of microplastics (0, 0.04, 0.4, 4, and 40 mg/L) for 7, 14, and 21 days to explore their effects. Under microplastic-induced stress, the contents or activities of most immune-related factors [haemocyanin (Hc), alkaline phosphatase (AKP), phenoloxidase (PO), lysozyme (LSZ), and acid phosphatase (ACP)] decreased after an initial increase in the low-dose or short exposure times in the haemolymph and hepatopancreas. The trends in Hc and LSZ gene expression were consistent with the corresponding changes in enzyme activities. Moreover, the haemocyte expression of caspase and MyD88 in the groups with microplastic-induced stress was higher than that in the control group, whereas the expression levels in the hepatopancreas were first increased and then decreased. Furthermore, the relative abundance of Firmicutes and Bacteroidetes decreased following exposure to 40 mg/L microplastics, whereas that of Fusobacteria and Proteobacteria increased. These results indicate that microplastics affect immune enzyme activity and immune-related gene expression and change the diversity and composition of the intestinal microflora in E. sinensis.


Assuntos
Braquiúros/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Plásticos/toxicidade , Poluentes da Água/toxicidade , Animais , Braquiúros/microbiologia
12.
Vet Res Commun ; 43(3): 179-186, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31187404

RESUMO

Endometrial epithelial cells play a key defensive role as part of the innate immune response of cow uterus. An association between risk of acquiring infectious diseases and increased levels of free fatty acids postpartum has been suggested, and the use of omega-3 fatty acids such as docosahexaenoic acid (DHA) has been proposed as a beneficial strategy to improve immunity and fertility. The goal of our study was to demonstrate the presence of free fatty acid (FFA)-1 and 4 receptors in endometrial cells and to investigate their role on DHA interference in lipopolysaccharide (LPS)-induced inflammatory endometrial activation. We demonstrated that the bovine endometrial (BEND) cells line and bovine endometrium express both FFA1 and FFA4 receptors. FFA1 and FFA4 receptors were localized in the epithelium lining the endometrial cavity and in endometrial glands whereas in BEND cells a characteristic cell membrane localization of both receptors was observed. DHA, a FFA4 natural agonist, increased intracellular calcium mobilization in BEND cells, but the FFA1 agonists oleic and linoleic acids did not increase this response. DHA-induced intracellular calcium mobilization was inhibited by the FFA4 and FFA1 antagonists AH7614 and GW1100, respectively. DHA significantly reduced LPS-induced prostaglandin E2 (PGE2) production, but none of the antagonists reduced the effect produced by DHA. On the contrary, linoleic acid increased LPS-induced PGE2 production. In conclusion, endometrial cells express FFA4 and FFA1 receptors, and DHA induces intracellular calcium release via FFA4 and FFA1 receptors. DHA reduces PGE2, but this response was not mediated by FFA4 or FFA1 receptors.


Assuntos
Endométrio/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia , Animais , Bovinos , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Receptores Acoplados a Proteínas-G/metabolismo
13.
Int J Mol Sci ; 20(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174254

RESUMO

Mycotoxins, which are widely found in feed ingredients and human food, can exert harmful effects on animals and pose a serious threat to human health. As the first barrier against external pollutants, the intestinal mucosa is protected by a mechanical barrier, chemical barrier, immune barrier, and biological barrier. Firstly, mycotoxins can disrupt the mechanical barrier function of the intestinal mucosa, by destroying the morphology and tissue integrity of the intestinal epithelium. Secondly, mycotoxins can cause changes in the composition of mucin monosaccharides and the expression of intestinal mucin, which in turn affects mucin function. Thirdly, mycotoxins can cause damage to the intestinal mucosal immune barrier function. Finally, the microbiotas of animals closely interact with ingested mycotoxins. Based on existing research, this article reviews the effects of mycotoxins on the intestinal mucosal barrier and its mechanisms.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Micotoxinas/toxicidade , Animais , Humanos , Imunidade Inata/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucinas/genética , Mucinas/metabolismo , Micotoxinas/farmacologia
14.
Expert Opin Drug Metab Toxicol ; 15(7): 565-575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31211608

RESUMO

Introduction: There are concerns that opioids may be associated with an increased risk of infection. This safety issue is alarming given the widespread use of opioids in pain management. Areas covered: In this review, we summarize the pharmacologic aspects of opioids related to the immune system and to the assumed pathophysiology of opioid-related infections. We also synthesize and critically appraise the available clinical evidence on the potential association between the use of opioids and the risk of infection. PubMed was searched from inception to 1 February 2019 for all articles published in English with terms corresponding to 'opioids' and 'infections'. Expert opinion: Morphine appears to suppress the immune system via affecting cells of the innate and the adaptive immunity as well as via modulating the hypothalamic-pituitary-adrenal axis. However, knowledge gaps exist regarding the immune-related pharmacology of non-morphine opioids. Observational studies have suggested an increased risk of infections associated with the use of opioids. However, methodological limitations such as confounding by indication due to the choice of non-use as comparator render the interpretation of most of these studies difficult. Thus, further efforts in preclinical research and well-conducted observational studies are needed to provide more robust evidence in this regard.


Assuntos
Analgésicos Opioides/efeitos adversos , Sistema Imunitário/efeitos dos fármacos , Infecção/etiologia , Imunidade Adaptativa/efeitos dos fármacos , Analgésicos Opioides/administração & dosagem , Animais , Humanos , Imunidade Inata/efeitos dos fármacos , Infecção/epidemiologia , Infecção/imunologia , Morfina/administração & dosagem , Morfina/efeitos adversos , Dor/tratamento farmacológico , Risco
15.
Nat Commun ; 10(1): 2730, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227691

RESUMO

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.


Assuntos
Antibacterianos/farmacologia , Imunidade Inata/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tiazolidinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Peptídeos/imunologia , Peptídeos Cíclicos/uso terapêutico , Cultura Primária de Células , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Tiazolidinas/uso terapêutico
16.
Fish Shellfish Immunol ; 91: 122-129, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31055018

RESUMO

Selenium (Se) is a micronutrient that becomes toxic when present at higher concentrations in fish tissues. Allium mongolicum Regel flavonoids (AMRF) have been documented to possess antioxidant, immunoenhancement and anti-inflammation properties. The aim of this study was to investigate the protective effects and potential mechanisms of dietary supplementation of AMRF and Se exposure on oxidative stress, immune responses and immune-related genes expression in Channa argus. A total of 480 C. argus were randomly divided into eight groups housed in twenty-four 200 L glass aquarium (3 tanks per group, 20 fish per tank). The fish were exposed for 56 days to waterborne Se at 0, 50, 100 and 200 µg/L and/or dietary AMRF at 40 mg/kg. The result indicated that AMRF exerted significant protective effects by preventing alterations in the levels of bioaccumulation, malondialdehyde, lysozyme, complement C3 and immunoglobulin M. AMRF also assists in the elevation of catalase and glutathione peroxidase in the liver and spleen while regulating the expression of immune-related genes including NF-κB p65, IκB-α, TNF-α, IL-1ß, IL-8, HSP70, HSP90, and glucocorticoid receptor after 56 days of Se exposure. Our results suggest that administration of AMRF (40 mg/kg) has the potential to combat Se toxicity in C. argus.


Assuntos
Allium/química , Peixes/imunologia , Flavonoides/farmacologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/imunologia , Estresse Oxidativo , Selênio/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Distribuição Aleatória , Testes de Toxicidade Subcrônica
17.
Fish Shellfish Immunol ; 90: 264-273, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054356

RESUMO

We investigated the effects of icariin (ICA) on growth performance, antioxidant capacity and non-specific immunity in Chinese mitten crab (Eriocheir sinensis). A total of 200 healthy crabs (average weight: 33.58 ±â€¯0.05 g) were randomly assigned to four treatments with five replicates, each with ten individuals per pool. There were four dietary treatments: the control group (fed with the basal diet), the ICA 50 group, the ICA100 group, and the ICA 200 group (fed with the basal diet supplemented with 50, 100, and 200 mg/kg ICA, respectively). These diets were provided for 8 weeks. Results indicated that ICA100 crabs had higher weight gain (WG), specific growth rate (SGR) and survival rate (SR) than the controls. Protein carbonyl content (PCC) and malondialdehyde (MDA) concentrations in the haemolymph and hepatopancreas of ICA100 crabs were significantly lower than in the control group, while the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly higher. The activities of PO, LZM, ACP and AKP were significantly enhanced with ICA supplementation at 50 and 100 mg/kg, yet decreased subsequently at 200 mg/kg. Furthermore, supplementation of 100 mg/kg ICA up-regulated the mRNA expression of prophenoloxidase (proPO), catalase (CAT), mitochondrial manganese superoxide dismutase (mtMnSOD), thioredoxin-1 (Trx1) and peroxiredoxin 6 (Prx6), while the mRNA expression of toll like receptors (TLRs), NF-κB-like transcription factor Relish and lipopolysaccharide-induced TNF-α factor (LITAF) were down-regulated in the hepatopancreas (P < 0.05). These findings indicate that dietary ICA supplementation at an optimum dose of 100 mg/kg may be effective in improving growth performance, antioxidant capability and non-specific immunity of Chinese mitten crab.


Assuntos
Adjuvantes Imunológicos/metabolismo , Braquiúros/imunologia , Flavonoides/metabolismo , Imunidade Inata/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Antioxidantes , Braquiúros/genética , Braquiúros/crescimento & desenvolvimento , Braquiúros/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Distribuição Aleatória
18.
Fish Shellfish Immunol ; 90: 456-465, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075403

RESUMO

This study was conducted to elucidate the effects of dietary mixed probiotics on growth, non-specific immunity, intestinal morphology and microbiota of juvenile pacific white shrimp, Litopenaeus vannamei. Juvenile shrimp (initial body weight 1.21 ±â€¯0.01 g) were fed diets containing graded probiotics (F1: 0 mg/kg probiotics; F2: 1000 mg/kg probiotics; F3: 2000 mg/kg probiotics; F4: 4000 mg/kg compound probiotics; F5: 6000 mg/kg probiotics; F6: 8000 mg/kg probiotics) for 8 weeks. The result of this trial showed that the growth performance (SGR, WG, FBW) of shrimp fed diets containing probiotics (F2∼F6) were significantly higher than that of shrimp fed diet without supplemental probiotics (F1) (P < 0.05), and the highest values of the growth performance (SGR, WG, FBW) and lowest FCR were found in shrimp fed the diet containing 2000 mg/kg probiotics. Total antioxidant capacity of shrimp fed diet F2 and F3 were significantly higher than that of shrimp fed the basal diets (P < 0.05). Superoxide dismutase in F4 treatment was significantly higher than that of basal treatment (P < 0.05). Catalase of shrimp in all probiotics supplemented (F2∼F6) treatments were significantly higher than that of the control one (F1) (P < 0.05). Malondialdehyde in F5 groups was significantly lower than that of F1 groups (P < 0.05). Alkline phosphatase and acid phosphatase in F3 treatments were significantly higher than those of the basal one (P < 0.05). Lysozyme of shrimp fed F2∼F6 were significantly higher than that of shrimp fed F1 diet (P < 0.05). The lipase and amylase activities in 2000 mg/kg probiotics groups showed the highest activities and were significantly higher than that of control one (P < 0.05). Intestinal villi height in F3∼F6 treatments were significantly higher than that of control one (P < 0.05). Alpha diversity indices including observed species, chao1, ACE and shannon indices showed that F2 and F3 groups had higher microbial diversity in their intestines, both richness and evenness. PCA plot showed that there was a clear shift of F2 and F3 groups from the control groups in microbial community structure. The dominant phyla in pacific white shrimp are proteobacteria, bacteroidetes and actinobacteria, the dominant genus were algoriphagus and vibrio. As the probiotics increased, the gemmatimonadetes, acidobacteria, deltaproteobacteria and xanthomonadales firstly increased and then decreased, with the highest content in F2 group, which was no significant difference to F3 group (P > 0.05) while significantly higher than other groups (P < 0.05). In conclusion, the supplement of mixed species probiotics can promote growth performance, enhance the non-specific immunity, influence the microbiota of the pacific white shrimps and the recommended optimum dosage in diet of Litopenaeus vannamei was 2000 mg/kg.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Penaeidae/imunologia , Probióticos/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Relação Dose-Resposta a Droga , Intestinos/anatomia & histologia , Intestinos/microbiologia , Penaeidae/anatomia & histologia , Penaeidae/crescimento & desenvolvimento , Penaeidae/microbiologia , Probióticos/administração & dosagem , Distribuição Aleatória
19.
Int J Mol Sci ; 20(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100828

RESUMO

In spite of therapeutic improvements in the treatment of different hematologic malignancies, the prognosis of acute myeloid leukemia (AML) treated solely with conventional induction and consolidation chemotherapy remains poor, especially in association with high risk chromosomal or molecular aberrations. Recent discoveries describe the complex interaction of immune effector cells, as well as the role of the bone marrow microenvironment in the development, maintenance and progression of AML. Lipids, and in particular omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) have been shown to play a vital role as signaling molecules of immune processes in numerous benign and malignant conditions. While the majority of research in cancer has been focused on the role of lipid mediators in solid tumors, some data are showing their involvement also in hematologic malignancies. There is a considerable amount of evidence that AML cells are targetable by innate and adaptive immune mechanisms, paving the way for immune therapy approaches in AML. In this article we review the current data showing the lipid mediator and lipidome patterns in AML and their potential links to immune mechanisms.


Assuntos
Leucemia Mieloide Aguda/tratamento farmacológico , Lipídeos/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , Medula Óssea , Progressão da Doença , Ácidos Graxos Ômega-3/imunologia , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/imunologia , Ácidos Graxos Ômega-6/uso terapêutico , Ácidos Graxos Insaturados , Neoplasias Hematológicas/tratamento farmacológico , Hematopoese , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia , Inflamação , Leucemia Mieloide Aguda/imunologia , Lipídeos/imunologia , Neoplasias/tratamento farmacológico , Prognóstico , Microambiente Tumoral
20.
Fish Shellfish Immunol ; 91: 284-292, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125664

RESUMO

Selenium (Se) is a necessity in multiple species of fish. Se plays an important role in immunoregulation, inflammation, and antioxidant systems in fish and other animals. The head kidney is the major immune organ in adult carp, and it produces white blood cells and destroys old red blood cells. The present study aimed to explore the effects and regulatory molecular mechanisms of Se on ROS and micRNA-146a as part of the inflammatory response in fancy carp. Adult fancy carp were fed different concentrations of Se in their diets. The Se content of the head kidney changed in a pattern consistent with the dietary content of Se. Se deficiency induced a significant increase in ROS, restrained the activities of GPx, SOD and CAT and increased MDA content. qPCR analysis showed a reduction in micRNA-146a with Se deficiency. The Se content, miRNA-146a expression and ROS levels were correlated. H2O2 cell stimulation assays found that ROS could activate the MAPK pathway, and ELISA results showed p38, JNK and ERK phosphorylation significantly increased with H2O2 stimulation. TNF-α, IL-1ß, and IL-6 were appreciably increased. At same time, miRNA-146a, which should have increased to regulate the inflammatory response, was reduced with Se deficiency. Therefore, with Se deficiency, the head kidney was inflamed. All these results indicated that Se deficiency inhibits micRNA-146a to promote ROS-induced inflammation via regulating the MAPK pathway in the head kidney of carp. The present study revealed that supplementing the diet of carp with selenium is beneficial for growth and disease prevention.


Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , MicroRNAs/genética , Selênio/deficiência , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças dos Peixes/induzido quimicamente , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/veterinária , Sistema de Sinalização das MAP Quinases/imunologia , MicroRNAs/metabolismo , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo , Selênio/administração & dosagem
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