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1.
Chemosphere ; 287(Pt 1): 131902, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34438209

RESUMO

Understanding the lethal effects of pesticides nano formulations on the targeted organisms (pathogens) and the non-targeted organisms (fish, earthworms, etc) is essential in assessing the probable impact of new technologies on agriculture and environment. Here we evaluated the bioactivity and the biotoxicity of new type of fungicide smart-delivery formulation based on conjugating carboxymethylated-ß-glucans on the mesoporous silica nanoparticles (MSNs) surface after loading chlorothalonil (CHT) fungicide in the MSNs pores. The obtained formulation has been characterized with FE-SEM, and HR-TEM. The CHT loading efficiency has been measured with TGA. The bioactivity of the obtained formulation (CHT@MSNs-ß-glucans) has been tested against four pathogens, fusarium head blight (Fusarium graminearum), sheath rot (Sarocladium oryzae), rice sheath blight (Rhizoctonia solani), and soyabean anthracnose (Colletotrichum truncatum) compared with CHT WP 75% commercial formulation (CHT-WP) and technical CHT. The environmental biotoxicity of CHT@MSNs-ß-glucans compared with CHT-WP has been tested toward earthworm (Eisenia fetida) and zebra fish (Danio rerio). The results showed that CHT@MSNs-ß-glucans has an excellent bioactivity against the subjected pathogens with better inhabiting effects than CHT-WP. CHT@MSNs-ß-glucans toxicity to Eisenia fetida was found 2.25 times lower than CHT-WP toxicity. The LC50 of CHT@MSNs-ß-glucans to zebra fish after the first 24h was 2.93 times higher than CHT-WP. After 96h of treatment, the LC50 of CHT@MSNs-ß-glucans was 2.66 times higher than CHT-WP. This work highlighted the necessity to increase the mandatory bioassays of nano formulations with the major non-target organisms in the environmental risk assessment of new pesticide formulations.


Assuntos
Fungicidas Industriais , Nanopartículas , beta-Glucanas , Animais , Colletotrichum , Portadores de Fármacos , Fungicidas Industriais/toxicidade , Fusarium , Hypocreales , Nanopartículas/toxicidade , Nitrilas , Porosidade , Rhizoctonia , Dióxido de Silício/toxicidade , beta-Glucanas/toxicidade
2.
Oncol Rep ; 47(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34779494

RESUMO

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side­effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier ß­glucan [ß­glucan vaccine adjuvant approach to treating cancer via immune enhancement (B­VACCIEN)] and its beneficial effects, including vaccine­adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long­term prophylaxis in immunocompromised individuals or genetically prone to cancer.


Assuntos
/administração & dosagem , Hospedeiro Imunocomprometido/imunologia , Neoplasias/imunologia , Neoplasias/prevenção & controle , beta-Glucanas/imunologia , Animais , Humanos
3.
J Agric Food Chem ; 70(1): 21-33, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34936332

RESUMO

Termitomyces are well-known wild edible and medicinal basidiomycete mushrooms. The frequent consumption of Termitomyces stimulated studies on their health-promoting properties. Numerous health benefits of Termitomyces are associated with the main categories of components in Termitomyces, polysaccharides. Although the homopolysaccharides ß-glucans are believed to be the major bioactive polysaccharides of Termitomyces, other heteropolysaccharides also possess biological activities. In this review, the extraction methods, chemical structures, and biological activities of polysaccharides from Termitomyces were thoroughly reviewed. The polysaccharides from different species of Termitomyces differ in molecular weight, monosaccharide composition, and linkages of constituent sugars. The health-promoting effects, including antioxidation, ulcer-healing and analgesic properties, immunomodulation, hypolipidemic and hepatoprotective effects, and antidiabetic properties of Termitomyces polysaccharides were summarized and discussed. Further studies were needed for a better understanding of the relationship between the fine chemical structure and health-promoting properties. This review provides a theoretical overview for future studies and utilization of Termitomyces polysaccharides.


Assuntos
Agaricales , Basidiomycota , Termitomyces , beta-Glucanas , Polissacarídeos
4.
Appl Microbiol Biotechnol ; 106(2): 563-578, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34939133

RESUMO

ß-1,3-Glucans are well-known biological and health-promoting compounds in edible fungi. Our previous results characterized a glucan synthase gene (GFGLS) of Grifola frondosa for the first time to understand its role in mycelial growth and glucan biosynthesis. In the present study, we identified and functionally reannotated another glucan synthase gene, GFGLS2, based on our previous results. GFGLS2 had a full sequence of 5944 bp including 11 introns and 12 exons and a coding information for 1713 amino acids of a lower molecular weight (195.2 kDa) protein with different conserved domain sites than GFGLS (5927 bp with also 11 introns and a coding information for 1781 aa). Three dual-promoter RNA-silencing vectors, pAN7-iGFGLS-dual, pAN7-iGFGLS2-dual, and pAN7-CiGFGLS-dual, were constructed to downregulate GFGLS, GFGLS2, and GFGLS/GFGLS2 expression by targeting their unique exon sequence or conserved functional sequences. Silencing GFGLS2 resulted in higher downregulation efficiency than silencing GFGLS. Cosilencing GFGLS and GFGLS2 had a synergistic downregulation effect, with slower mycelial growth and glucan production by G. frondosa. These findings indicated that GFGLS2 plays major roles in mycelial growth and polysaccharide synthesis and provides a reference to understand the biosynthesis pathway of mushroom polysaccharides. KEY POINTS: • The 5944-bp glucan synthase gene GFGLS2 of G. frondosa was cloned and reannotated • GFGLS2 showed identity and significant differences with the previously identified GFGLS • GFGLS2 played a major role in fermentation and glucan biosynthesis.


Assuntos
Grifola , beta-Glucanas , Glucosiltransferases , Grifola/genética , Polissacarídeos
5.
Methods Mol Biol ; 2412: 269-280, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34918250

RESUMO

Beta-glucans are a group of polysaccharides with intrinsic immunostimulatory properties which makes the design of new particulate vaccine adjuvants based on ß-glucans very promising. The size of the particles and the antigen loading method, encapsulated into particles or adsorbed on its surface, will influence the toxicological and adjuvanticity properties of the particulate adjuvant. Herein we describe the production of glucan nanoparticles (NPs) with three different sizes, approximately 150 nm, 350 nm, and microparticles as shells (GPs) with approximately 3 µm. The association of the antigen to the particulate adjuvant is described using model protein antigens. The method can be easily adapted for real protein antigens.


Assuntos
Nanopartículas , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos , Antígenos , Glucanos , beta-Glucanas
6.
Food Chem ; 367: 130708, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352692

RESUMO

In this study, we explored structural differences of five commercial samples of yeast ß-glucan. Samples were assayed for their ß-glucan content and the yeast storage carbohydrate, glycogen. The ß-glucan content ranged from 74% to 86%, the glycogen content varied from 0 to 20%. The linkage pattern of each sample was measured by the partially methylated alditol acetate method. This method showed that the samples varied from 1.9% to 9.2% branching. The side chain length distribution for each sample was analyzed by an alkaline degradation assay followed by ion chromatography. The side length distributions of the samples were shown to be similar. The samples were also analyzed by FT-IR and 1HNMR spectroscopy but it was difficult to derive quantitative differences in the samples by these methods. Our findings confirm that each proprietary source of yeast ß-glucan has a unique purity profile, branching, and linkage patterns that determine the chemical structure and composition.


Assuntos
Saccharomyces cerevisiae , beta-Glucanas , Parede Celular , Glucanos , Saccharomyces cerevisiae/genética , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Food Chem ; 372: 131291, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638062

RESUMO

White wheat salted noodles containing oats have a slower digestion rate those without oats, with potential health benefits. Oat ß-glucan may play an important role in this. Effects of sheeting and shearing during noodle-making and subsequent cooking on ß-glucan concentration, solubility, molecular size and starch digestibility were investigated. The levels of ß-glucan were reduced by 16% after cooking, due to the loss of ß-glucan into the cooking water. Both the noodle-making process and cooking increased the solubility of ß-glucan but did not change its average molecular size. Digestion profiles show that ß-glucan in wholemeal oat flour did not change starch digestion rates compared with isolated starch, but reduced the starch digestion rate of oat-fortified wheat noodles compared to the control (wheat noodles). Confocal laser scanning microscopy suggests that interaction between ß-glucan and protein contributes to the starch-protein matrix and changes noodle microstructure, and thus alters their digestibility.


Assuntos
Amido , beta-Glucanas , Avena , Culinária , Farinha/análise , Solubilidade
8.
Nutrients ; 13(12)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34959802

RESUMO

Dietary fiber supplementation has been studied as a promising strategy in the treatment of obesity and its comorbidities. A systematic review and meta-analysis were performed to verify whether the consumption of yeast beta-glucan (BG) favors weight loss in obese and non-obese rodents. The PICO strategy was employed, investigating rodents (Population), subjected to the oral administration of yeast BG (Intervention) compared to animals receiving placebo (Comparison), evaluating body weight changes (Outcome), and based on preclinical studies (Study design). Two reviewers searched six databases and the grey literature. We followed the PRISMA 2020 guidelines, and the protocol was registered on PROSPERO (CRD42021267788). The search returned 2467 articles. Thirty articles were selected for full-text evaluation, and seven studies remained based on the eligibility criteria. The effects of BG intake on body weight were analyzed based on obese (n = 4 studies) and non-obese animals (n = 4 studies). Even though most studies on obese rodents (75%) indicated a reduction in body weight (qualitative analysis), the meta-analysis showed this was not significant (mean difference -1.35 g-95% CI -5.14:2.45). No effects were also observed for non-obese animals. We concluded that the ingestion of yeast BG barely affects the body weight of obese and non-obese animals.


Assuntos
Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Obesidade/metabolismo , Saccharomyces cerevisiae , beta-Glucanas/farmacologia , Animais , Camundongos , Ratos , Perda de Peso/efeitos dos fármacos
9.
Nutrients ; 13(12)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34959898

RESUMO

A single-center, randomized, double-blind, placebo-controlled study was conducted in 72 volunteers who received a synergistic combination of yeast-based ingredients with a unique ß-1,3/1,6-glucan complex and a consortium of heat-treated probiotic Saccharomyces cerevisiae rich in selenium and zinc (ABB C1®) or placebo on the next day after getting vaccinated against influenza (Chiromas®) (n = 34) or the COVID-19 (Comirnaty®) (n = 38). The duration of treatment was 30 and 35 days for the influenza and COVID-19 vaccine groups, respectively. Mean levels of CD4+T cells increased from 910.7 at baseline to 1000.2 cells/µL after the second dose of the COVID-19 vaccine in the ABB C1® group, whereas there was a decrease from 1055.1 to 929.8 cells/µL in the placebo group. Changes of CD3+T and CD8+T lymphocytes showed a similar trend. In the COVID-19 cohort, the increases in both IgG and IgM were higher in the ABB C1® supplement than in the placebo group. Serum levels of selenium and zinc showed a higher increase in subjects treated with the active product than in those receiving placebo. No serious adverse events related to ABB C1® or tolerance issues were reported. The study findings validate the capacity of the ABB C1® product to stimulate trained immunity.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Suplementos Nutricionais , Vacinas contra Influenza/administração & dosagem , Saccharomyces cerevisiae , Selênio/administração & dosagem , Zinco/administração & dosagem , beta-Glucanas/administração & dosagem , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas contra COVID-19/imunologia , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Vacinas contra Influenza/imunologia , Masculino , Pessoa de Meia-Idade , Selênio/imunologia , Zinco/imunologia , beta-Glucanas/imunologia
10.
J Immunol ; 207(11): 2785-2798, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34740960

RESUMO

Bacterial infections are a common and deadly threat to vulnerable patients. Alternative strategies to fight infection are needed. ß-Glucan, an immunomodulator derived from the fungal cell wall, provokes resistance to infection by inducing trained immunity, a phenomenon that persists for weeks to months. Given the durability of trained immunity, it is unclear which leukocyte populations sustain this effect. Macrophages have a life span that surpasses the duration of trained immunity. Thus, we sought to define the contribution of differentiated macrophages to trained immunity. Our results show that ß-glucan protects mice from Pseudomonas aeruginosa infection by augmenting recruitment of innate leukocytes to the site of infection and facilitating local clearance of bacteria, an effect that persists for more than 7 d. Adoptive transfer of macrophages, trained using ß-glucan, into naive mice conferred a comparable level of protection. Trained mouse bone marrow-derived macrophages assumed an antimicrobial phenotype characterized by enhanced phagocytosis and reactive oxygen species production in parallel with sustained enhancements in glycolytic and oxidative metabolism, increased mitochondrial mass, and membrane potential. ß-Glucan induced broad transcriptomic changes in macrophages consistent with early activation of the inflammatory response, followed by sustained alterations in transcripts associated with metabolism, cellular differentiation, and antimicrobial function. Trained macrophages constitutively secreted CCL chemokines and robustly produced proinflammatory cytokines and chemokines in response to LPS challenge. Induction of the trained phenotype was independent of the classic ß-glucan receptors Dectin-1 and TLR-2. These findings provide evidence that ß-glucan induces enhanced protection from infection by driving trained immunity in macrophages.


Assuntos
Memória Imunológica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , beta-Glucanas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Feminino , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Memória Imunológica/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
11.
Poult Sci ; 100(12): 101483, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700101

RESUMO

The study was conducted to evaluate the effects of the combination of mannan-oligosaccharides (MOS) and ß-glucan on growth performance, intestinal morphology, and immune gene expression in broiler chickens. A total of 640, one-day-old male Cobb 500 broilers were randomly allocated into 32 pens with 8 replicates and 20 birds per pen. Thirty-two pens were divided into 4 treatments, including control, 0.04% MOS, 0.002% ß-glucan, and a combination of MOS and ß-glucan. Growth performance was measured on d14, 28, and 35. The ileum and cecal tonsils were collected from one bird per pen at 21 and 35 d of age for further analyses of immune gene expression. Duodenum, jejunum, and ileum were collected for intestinal morphology on d 35. Results indicated that both MOS and ß-glucan improved growth performance during starter phase (P < 0.05). In addition, ß-glucan further increased body weight gain of birds from d 0 to 28 (P < 0.05). Furthermore, the combination of MOS and ß-glucan presented higher villi height in the jejunum on d 35 (P < 0.05). There were no significant differences for gene expressions of immune responses on d 21 and 35. In conclusion, the application of prebiotic combination of MOS and ß-glucan might perform multiple pathways, improving growth performance in broiler chickens.


Assuntos
Galinhas , beta-Glucanas , Ração Animal/análise , Animais , Galinhas/genética , Dieta , Suplementos Nutricionais , Expressão Gênica , Masculino , Mananas , Oligossacarídeos/farmacologia , beta-Glucanas/farmacologia
12.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638753

RESUMO

A novel fluorapatite/glucan composite ("FAP/glucan") was developed for the treatment of bone defects. Due to the presence of polysaccharide polymer (ß-1,3-glucan), the composite is highly flexible and thus very convenient for surgery. Its physicochemical and microstructural properties were evaluated using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), mercury intrusion, mechanical testing and compared with the reference material, which was a hydroxyapatite/glucan composite ("HAP/glucan") with hydroxyapatite granules (HAP) instead of FAP. It was found that FAP/glucan has a higher density and lower porosity than the reference material. The correlation between the Young's modulus and the compressive strength between the materials is different in a dry and wet state. Bioactivity assessment showed a lower ability to form apatite and lower uptake of apatite-forming ions from the simulated body fluid by FAP/glucan material in comparison to the reference material. Moreover, FAP/glucan was determined to be of optimal fluoride release capacity for osteoblasts growth requirements. The results of cell culture experiments showed that fluoride-containing biomaterial was non-toxic, enhanced the synthesis of osteocalcin and stimulated the adhesion of osteogenic cells.


Assuntos
Apatitas , Regeneração Óssea/efeitos dos fármacos , Osso e Ossos/metabolismo , Osteoblastos/metabolismo , beta-Glucanas , Apatitas/química , Apatitas/farmacologia , Linhagem Celular , Humanos , Porosidade , beta-Glucanas/química , beta-Glucanas/farmacologia
14.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639025

RESUMO

The concept of trained immunity has become one of the most interesting and potentially commercially and clinically relevant ideas of current immunology. Trained immunity is realized by the epigenetic reprogramming of non-immunocompetent cells, primarily monocytes/macrophages and natural killer (NK) cells, and is less specific than adaptive immunity; therefore, it may cross-protect against other infectious agents. It remains possible, however, that some of the observed changes are simply caused by increased levels of immune reactions resulting from supplementation with immunomodulators, such as glucan. In addition, the question of whether we can talk about trained immunity in cells with a life span of only few days is still unresolved.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Animais , Suscetibilidade a Doenças , Homeostase/imunologia , Humanos , Imunidade Celular , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , beta-Glucanas/metabolismo
15.
Molecules ; 26(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34641356

RESUMO

Inflammatory bowel disease (IBD), which significantly affects human health, has two primary presentations: Crohn's disease and ulcerative colitis (UC). Highland barley is the most common food crop for Tibetans and contains much more ß-glucan than any other crop. Highland barley ß-glucan (HBBG) can relieve the gastrointestinal dysfunction and promote intestines health. This study aimed to evaluate whether HBBG can relieve UC in mice. A mouse model of UC was established by adding 2% dextran sulfate sodium (DSS) to drinking water for 1 week. UC was alleviated after the introduction of the HBBG diet, as indicated by reductions in the disease activity index (DAI) score, histopathological damage, and the concentration of colonic myeloperoxidase (MPO), along with an improvement in colonic atrophy. Furthermore, we found that HBBG can increase the relative transcriptional levels of genes encoding ZO-1, claudin-1, occludin, and mucin2 (MUC2), thereby reducing intestinal permeability. Additionally, HBBG maintained the balance of proinflammatory and anti-inflammatory cytokines and modulated the structure of the intestinal flora.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Hordeum/química , Extratos Vegetais/farmacologia , beta-Glucanas/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Citocinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , beta-Glucanas/isolamento & purificação
16.
Molecules ; 26(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500837

RESUMO

We previously described the biosynthesis, isolation, and immunosuppressive activity of the selenium-containing polysaccharide fraction isolated from the mycelial culture of Lentinula edodes. Structural studies have shown that the fraction was a protein-containing mixture of high molar mass polysaccharides α- and ß-glucans. However, which of the components of the complex fraction is responsible for the immunosuppressive activity non-typical for polysaccharides of fungal origin has not been explained. In the current study, we defined four-polysaccharide components of the Se-containing polysaccharide fraction determined their primary structure and examined the effect on T- and B-cell proliferation. The isolated Se-polysaccharides, α-1,4-glucan (Mw 2.25 × 106 g/mol), unbranched ß-1,6-d-glucan, unbranched ß-1,3-d-glucan and ß-1,3-branched ß-1,6-d-glucan (Mw 1.10 × 105 g/mol), are not typical as components of the cell wall of L. edodes. All are biologically active, but the inhibitory effect of the isolated polysaccharides on lymphocyte proliferation was weaker, though more selective than that of the crude fraction.


Assuntos
Proliferação de Células/efeitos dos fármacos , Imunossupressores/química , Polissacarídeos/química , Selênio/química , Linfócitos B , Ativação Linfocitária , Peso Molecular , Cogumelos Shiitake/metabolismo , Linfócitos T , beta-Glucanas/metabolismo
17.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34502174

RESUMO

Invasive fungal infections (IFIs) are serious infections that develop in conjunction with neutropenia after chemotherapy for acute leukemia or with hematopoietic stem cell transplantation. Conventionally, empirical antifungal therapy was recommended to treat IFIs for patient safety despite a lack of evidence of fungal infections. However, many studies have indicated that antifungals were not necessary for over half of patients, and several detriments of empirical therapy were noted, e.g., antifungals caused adverse reactions, an increase in drug-resistant fungi was a possibility, and medical costs soared. ß-D-glucan (BDG) is a component of clinically important fungi such as Aspergillus and Candida. The G-test was developed in Japan as a way to measure BDG in serum using a coagulation factor from the blood of the horseshoe crab. Pre-emptive antifungal therapy based upon serodiagnosis with a BDG or galactomannan assay and CT imaging has been introduced. With pre-emptive antifungal therapy, the prognosis is equivalent to that with empirical therapy, and the dose of the antifungal has been successfully reduced. Measurement of BDG has been adopted widely as a method of diagnosing IFIs and is listed in the key guidelines for fungal infections and febrile neutropenia.


Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , beta-Glucanas/análise , Aspergillus/metabolismo , Biomarcadores/análise , Candida/metabolismo , Humanos , Infecções Fúngicas Invasivas/diagnóstico
18.
PLoS One ; 16(9): e0258069, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591937

RESUMO

ß-glucans has been reported to be associated with many health-promoting and improvements in animal performance, however, information about their effects on the bacterial community remains unknown. This study aimed to investigate how the addition of ß-glucans can affect the fecal bacterial community with possible consequences on animal growth and health. For this, newborn Holstein calves (n = 14) were individually housed in tropical shelters and blocked according to sex, date, and weight at birth and randomly assigned to one of the following treatments: (1) Control: milk replacer (14% solids, 24% CP, 18.5% fat); (2) ß-glucans: milk replacer supplemented with ß-glucans (2 g/d). All calves were bucket fed 6 L/d of milk replacer and received water and starter concentrate ad libitum starting on d 2. To evaluate the bacteriome, fecal samples were collected at weeks 1, 2, 4, and 8. The bacterial community was assessed through sequencing of the V3-V4 region of the 16S rRNA gene on the Illumina MiSeq platform and analyzed using the DADA2 pipeline. No differences for Shannon and Chao1 indexes were observed for treatments, but both indexes increased with age (P < 0.001). There were dissimilarities in the structure of the bacterial community during the pre-weaning period (P = 0.01). In a deeper taxonomic level, Collinsella (Actinobacteriota), Prevotella (Bacteroidota), and Lactobacillus (Firmicutes) were the most abundant genera (9.84, 9.54, and 8.82% of the sequences, respectively). ß-glucans promoted a higher abundance of Alloprevotella and Holdemanella, which may indicate a beneficial effect of supplementation on dairy calves. The bacterial community was highly correlated with the fecal score at weeks 1 and 2 and with starter concentrate intake at week 8. In conclusion, algae ß-glucan supplementation could be beneficial to fecal bacteriome and consequently to the health and performance of dairy calves.


Assuntos
Ração Animal/análise , Fezes/microbiologia , beta-Glucanas/análise , Animais , Bovinos , Dieta/veterinária , Microbiota
19.
Nat Commun ; 12(1): 5373, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508078

RESUMO

Ankylosing spondylitis (AS) is a type of rheumatic disease characterized by chronic inflammation and pathological osteogenesis in the entheses. Previously, we demonstrated that enhanced osteogenic differentiation of MSC from AS patients (AS-MSC) resulted in pathological osteogenesis, and that during the enhanced osteogenic differentiation course, AS-MSC induced TNF-α-mediated local inflammation. However, whether TNF-α in turn affects AS-MSC remains unknown. Herein, we further demonstrate that a high-concentration TNF-α treatment triggers enhanced directional migration of AS-MSC in vitro and in vivo, which enforces AS pathogenesis. Mechanistically, TNF-α leads to increased expression of ELMO1 in AS-MSC, which is mediated by a METTL14 dependent m6A modification in ELMO1 3'UTR. Higher ELMO1 expression of AS-MSC is found in vivo in AS patients, and inhibiting ELMO1 in SKG mice produces therapeutic effects in this spondyloarthritis model. This study may provide insight into not only the pathogenesis but also clinical therapy for AS.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Células-Tronco Mesenquimais/patologia , Osteogênese/genética , Espondilite Anquilosante/patologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Biópsia , Medula Óssea/patologia , Estudos de Casos e Controles , Diferenciação Celular/genética , Movimento Celular/genética , Metilação de DNA , Modelos Animais de Doenças , Epigênese Genética , Feminino , Células HEK293 , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Cultura Primária de Células , Espondilite Anquilosante/induzido quimicamente , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genética , Microtomografia por Raio-X , beta-Glucanas/administração & dosagem , beta-Glucanas/efeitos adversos
20.
J Control Release ; 338: 792-803, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34530053

RESUMO

Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune cells is here described. In this approach, a macromolecular complex of oligonucleotides and the ß-1,3-glucan schizophyllan (SPG) is selectively delivered to cells expressing a lectin receptor, Dectin-1, via SPG-Dectin-1 interaction. Detailed investigation of Dectin-1-expressing cells revealed that Dectin-1 is expressed in all subsets of monocytes as well as dendritic cell (DC) populations, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), in humans. The expression patterns in mice and humans are comparable, except for the expression in pDCs. The results indicate that Dectin-1 is expressed on cells capable of professional antigen presentation, except for B cells. We chose CD40 as a target gene for small interfering RNA (siRNA) as CD40 expression in antigen-presenting cells (APCs), particularly in DCs, plays critical roles in regulating immune responses. Dose-dependent cellular uptake of siCD40-SPG complexes was confirmed in cells expressing Dectin-1. Gene silencing activity was confirmed in vitro by the reduction of CD40 mRNA and by the site-specific cleavage of CD40 mRNA as determined by the 5' RNA ligase-mediated rapid amplification of cDNA ends (5'RLM-RACE) technique. In vivo activity of siCD40-SPG complexes was demonstrated as the reduced CD40 protein expression in monocytes and DCs in mice. Furthermore, the in vivo activity of siCD40-SPG targeting human CD40 was confirmed in cynomolgus monkeys by the 5'RLM-RACE technique. In conclusion, we have demonstrated the receptor-ligand binding-mediated delivery of siRNA targeting immune-regulating monocytes and DCs via the interaction of SPG and its receptor, Dectin-1. As monocytes and DCs play central roles in inducing and controlling immune responses, Dectin-1-targeted delivery of nucleic acids should provide a useful tool for developing drugs to treat a wide range of diseases, including autoimmune diseases, allergy, and cancer, as well as transplantation.


Assuntos
Sizofirano , beta-Glucanas , Animais , Células Dendríticas , Lectinas Tipo C/genética , Camundongos , Oligonucleotídeos , RNA Interferente Pequeno
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