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1.
Aging (Albany NY) ; 13(10): 13474-13495, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34091442

RESUMO

The medicinal fungus Ganoderma lucidum is used as a dietary supplement and health tonic, but whether it affects longevity remains unclear. We show here that a water extract of G. lucidum mycelium extends lifespan of the nematode Caenorhabditis elegans. The G. lucidum extract reduces the level of fibrillarin (FIB-1), a nucleolar protein that correlates inversely with longevity in various organisms. Furthermore, G. lucidum treatment increases expression of the autophagosomal protein marker LGG-1, and lifespan extension is abrogated in mutant C. elegans strains that lack atg-18, daf-16, or sir-2.1, indicating that autophagy and stress resistance pathways are required to extend lifespan. In cultured human cells, G. lucidum increases concentrations of the LGG-1 ortholog LC3 and reduces levels of phosphorylated mTOR, a known inhibitor of autophagy. Notably, low molecular weight compounds (<10 kDa) isolated from the G. lucidum water extract prolong lifespan of C. elegans and the same compounds induce autophagy in human cells. These results suggest that G. lucidum can increase longevity by inducing autophagy and stress resistance.


Assuntos
Autofagia , Caenorhabditis elegans/citologia , Caenorhabditis elegans/fisiologia , Longevidade/fisiologia , Reishi/química , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
2.
Ageing Res Rev ; 66: 101240, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33347992

RESUMO

Caloric restriction (CR) mimetics are molecules that produce beneficial effects on health and longevity in model organisms and humans, without the challenges of maintaining a CR diet. Conventional CR mimetics such as metformin, rapamycin and spermidine activate autophagy, leading to recycling of cellular components and improvement of physiological function. We review here novel CR mimetics and anti-aging compounds, such as 4,4'-dimethoxychalcone, fungal polysaccharides, inorganic nitrate, and trientine, highlighting their possible molecular targets and mechanisms of action. The activity of these compounds can be understood within the context of hormesis, a biphasic dose response that involves beneficial effects at low or moderate doses and toxic effects at high doses. The concept of hormesis has widespread implications for the identification of CR mimetics in experimental assays, testing in clinical trials, and use in healthy humans. We also discuss the promises and limitations of CR mimetics and anti-aging molecules for delaying aging and treating chronic diseases.


Assuntos
Envelhecimento , Restrição Calórica , Autofagia , Hormese , Humanos , Longevidade
3.
Microb Cell ; 7(10): 255-269, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-33015140

RESUMO

The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of C. elegans, and explore the possibility that these natural substances may produce health benefits in humans.

4.
Med Res Rev ; 40(6): 2114-2131, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32578904

RESUMO

Senescence is a state of cell cycle arrest that plays an important role in embryogenesis, wound healing and protection against cancer. Senescent cells also accumulate during aging and contribute to the development of age-related disorders and chronic diseases, such as atherosclerosis, type 2 diabetes, osteoarthritis, idiopathic pulmonary fibrosis, and liver disease. Molecules that induce apoptosis of senescent cells, such as dasatinib, quercetin, and fisetin, produce health benefits and extend lifespan in animal models. We describe here the mechanism of action of senolytics and senomorphics, many of which are derived from plants and fungi. We also discuss the possibility of using such compounds to delay aging and treat chronic diseases in humans.

5.
Sci Rep ; 10(1): 8545, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444654

RESUMO

Vascular calcification occurs in various diseases including atherosclerosis, chronic kidney disease and type 2 diabetes but the mechanism underlying mineral deposition remains incompletely understood. Here we examined lower limb arteries of type 2 diabetes subjects for the presence of ectopic calcification and mineral particles using histology, electron microscopy and spectroscopy analyses. While arteries of healthy controls showed no calcification following von Kossa staining, arteries from 83% of diabetic individuals examined (19/23) revealed microscopic mineral deposits, mainly within the tunica media. Mineralo-organic particles containing calcium phosphate and proteins such as albumin, fetuin-A and apolipoprotein-A1 were detected in calcified arteries. Ectopic calcification and mineralo-organic particles were observed in a majority of diabetic patients and predominantly in arteries showing hyperplasia. While a low number of subjects was examined and information about disease severity and patient characteristics is lacking, these calcifications and mineralo-organic particles may represent signs of tissue dysfunction.


Assuntos
Artérias/patologia , Arteriosclerose/patologia , Calcinose/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Minerais/metabolismo , Compostos Orgânicos/metabolismo , Artérias/metabolismo , Arteriosclerose/metabolismo , Calcinose/metabolismo , Fosfatos de Cálcio/metabolismo , Estudos de Casos e Controles , Humanos , Minerais/química , Compostos Orgânicos/química
6.
Trends Biochem Sci ; 45(6): 462-471, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32413323

RESUMO

Phytochemicals in fruits and vegetables produce health benefits, but questions remain regarding their bioavailability, molecular targets, and mechanism of action. Here, we address these issues by considering the prebiotic and biological properties of phytochemicals. A fraction of phytochemicals consumed orally passes through the gut lumen, where it modulates the composition of the gut microbiota and maintains intestinal integrity. Phytochemicals and microbiota-derived metabolites that are absorbed by the organism comprise compounds that, at low doses, induce stress resistance mechanisms, including autophagy, DNA repair, and expression of detoxifying and antioxidant enzymes. We propose that these mechanisms improve cellular and organ function and can account for the promiscuous bioactivities of phytochemicals, despite their limited bioavailability and extremely varied chemical structures.


Assuntos
Compostos Fitoquímicos/farmacologia , Prebióticos , Estresse Fisiológico/efeitos dos fármacos , Disponibilidade Biológica , Microbioma Gastrointestinal , Humanos , Compostos Fitoquímicos/farmacocinética
7.
Microbes Infect ; 22(4-5): 168-171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32387333

RESUMO

The nasal cavity and turbinates play important physiological functions by filtering, warming and humidifying inhaled air. Paranasal sinuses continually produce nitric oxide (NO), a reactive oxygen species that diffuses to the bronchi and lungs to produce bronchodilatory and vasodilatory effects. Studies indicate that NO may also help to reduce respiratory tract infection by inactivating viruses and inhibiting their replication in epithelial cells. In view of the pandemic caused by the novel coronavirus (SARS-CoV-2), clinical trials have been designed to examine the effects of inhaled nitric oxide in COVID-19 subjects. We discuss here additional lifestyle factors such as mouth breathing which may affect the antiviral response against SARS-CoV-2 by bypassing the filtering effect of the nose and by decreasing NO levels in the airways. Simple devices that promote nasal breathing during sleep may help prevent the common cold, suggesting potential benefits against coronavirus infection. In the absence of effective treatments against COVID-19, the alternative strategies proposed here should be considered and studied in more detail.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Administração Intranasal , Betacoronavirus/efeitos dos fármacos , COVID-19 , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Carga Viral/efeitos dos fármacos
8.
Artigo em Inglês | MEDLINE | ID: mdl-31300373

RESUMO

OBJECTIVES: This study aimed to evaluate the clinical and histopathologic features of gingival lesions containing foreign material (GLFMs). In parallel, the composition of the foreign material and its effects in primary human gingival fibroblasts (HGFs) were investigated. STUDY DESIGN: Eighty-six GLFMs were retrieved from an oral pathology biopsy service. Clinical and microscopic data were analyzed, and the composition of the particles was identified by using energy-dispersive X-ray spectroscopy (EDX). Furthermore, HGFs were stimulated with silica (SiO2) microparticles to investigate the production of collagen type 1 (COL-1), matrix metalloproteinase 2 (MMP2), and inflammatory cytokines. RESULTS: GLFMs were most commonly found in women (60.5%) and most frequently described as white plaques. Histopathologic examination identified verrucous hyperplasia in 59% and epithelial dysplasia in 28% of the cases. EDX microanalysis revealed that Si (94%) was the most frequently detected foreign element. SiO2 microparticles induced higher COL-1 expression; higher levels of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-8, and transforming growth factor-ß, and increased MMP-2 activity in HGFs. CONCLUSIONS: There was a strong association between the presence of foreign material in the gingiva and white verrucous clinical lesions. In addition, the most common element in the foreign material was Si, and our in vitro findings demonstrate the importance of silica-mediated effects on gingival fibroblasts.


Assuntos
Gengiva , Células Cultivadas , Feminino , Fibroblastos , Humanos , Interleucina-6 , Masculino , Metaloproteinase 2 da Matriz , Dióxido de Silício
9.
Trends Endocrinol Metab ; 30(6): 335-346, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060881

RESUMO

Caloric restriction, intermittent fasting, and exercise activate defensive cellular responses such as autophagy, DNA repair, and the induction of antioxidant enzymes. These processes improve health and longevity by protecting cells and organs against damage, mutations, and reactive oxygen species. Consuming a diet rich in vegetables, fruits, and mushrooms can also improve health and longevity. Phytochemicals such as alkaloids, polyphenols, and terpenoids found in plants and fungi activate the same cellular processes as caloric restriction, fasting, and exercise. Many of the beneficial effects of fruits and vegetables may thus be due to activation of stress resistance pathways by phytochemicals. A better understanding of the mechanisms of action of phytochemicals may provide important insights to delay aging and prevent chronic diseases.


Assuntos
Compostos Fitoquímicos , Envelhecimento/fisiologia , Restrição Calórica , Suplementos Nutricionais , Hormese/fisiologia , Humanos , Longevidade/fisiologia
10.
Sci Rep ; 9(1): 5145, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30914735

RESUMO

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antrodia/química , Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Proteínas de Neoplasias/metabolismo , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células A549 , Animais , Antineoplásicos Fitogênicos/química , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Extratos Vegetais/química , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Med Res Rev ; 39(5): 1515-1552, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30648267

RESUMO

Aging is influenced by many lifestyle choices that are under human control, including nutrition and exercise. The most effective known antiaging intervention consists of calorie restriction (CR), which increases lifespan in yeasts, worms, fruit flies, mice, and nonhuman primates. CR also improves healthspan by preventing the development of various aging-related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration. Many compounds isolated from plants and fungi prolong lifespan and prevent age-related diseases in model organisms. These plant and fungal compounds modulate the same cellular and physiological pathways as CR, including those involving insulin and insulin-like growth factor-1, mammalian target of rapamycin, and sirtuins. Modulation of these aging-related pathways results in the activation of various cellular processes such as autophagy, DNA repair, and neutralization of reactive oxygen species. Together, these cellular processes are believed to delay aging and prevent chronic diseases by improving bodily functions and stress resistance. We review here the mechanisms of action of plant and fungal molecules possessing antiaging properties and discuss the possibilities and challenges associated with the development of antiaging compounds isolated from natural products.


Assuntos
Envelhecimento/efeitos dos fármacos , Produtos Biológicos/farmacologia , Fungos/química , Plantas/química , Animais , Autofagia , Produtos Biológicos/isolamento & purificação , Restrição Calórica , Humanos , Longevidade , Serina-Treonina Quinases TOR/fisiologia
12.
Gut ; 68(2): 248-262, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30007918

RESUMO

OBJECTIVE: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota. DESIGN: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis. RESULTS: Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance. CONCLUSIONS: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.


Assuntos
Ascomicetos , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/fisiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Polissacarídeos Fúngicos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/prevenção & controle , Animais , Dieta Hiperlipídica , Transplante de Microbiota Fecal , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peso Molecular , Prebióticos , Simbiose
13.
J Immunol ; 201(5): 1478-1490, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30061197

RESUMO

In developed countries, pulmonary nontuberculous mycobacteria (NTM) infections are more prevalent than Mycobacterium tuberculosis infections. Given the differences in the pathogenesis of NTM and M. tuberculosis infections, separate studies are needed to investigate the pathological effects of NTM pathogens. Our previous study showed that anti-IFN-γ autoantibodies are detected in NTM-infected patients. However, the role of NK cells and especially NK cell-derived IFN-γ in this context has not been studied in detail. In the current study, we show that NK1.1 cell depletion increases bacterial load and mortality in a mouse model of pulmonary NTM infection. NK1.1 cell depletion exacerbates NTM-induced pathogenesis by reducing macrophage phagocytosis, dendritic cell development, cytokine production, and lung granuloma formation. Similar pathological phenomena are observed in IFN-γ-deficient (IFN-γ-/-) mice following NTM infection, and adoptive transfer of wild-type NK cells into IFN-γ-/- mice considerably reduces NTM pathogenesis. Injection of rIFN-γ also prevents NTM-induced pathogenesis in IFN-γ-/- mice. We observed that NK cells represent the main producers of IFN-γ in the lungs and production starts as soon as 1 d postinfection. Accordingly, injection of rIFN-γ into IFN-γ-/- mice 1 d (but not 2 wk) postinfection significantly improves immunity against NTM infection. NK cells also stimulate mycobacterial killing and IL-12 production by macrophages. Our results therefore indicate that IFN-γ production by NK cells plays an important role in activating and enhancing innate and adaptive immune responses at early stages of pulmonary NTM infection.


Assuntos
Imunidade Inata , Interferon gama/imunologia , Células Matadoras Naturais/imunologia , Pulmão/imunologia , Infecções por Mycobacterium não Tuberculosas/imunologia , Mycobacterium/imunologia , Pneumonia Bacteriana/imunologia , Imunidade Adaptativa/genética , Animais , Interferon gama/deficiência , Interleucina-12/genética , Interleucina-12/imunologia , Células Matadoras Naturais/patologia , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Infecções por Mycobacterium não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/patologia , Pneumonia Bacteriana/patologia
14.
Sci Rep ; 8(1): 11310, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-30054526

RESUMO

Mineral nanoparticles form in physiological and pathological processes occurring in the human body. The calcium phosphate mineral phase of the particles has affinity for proteins and lipids, but the complete profiling of the organic molecules that bind to the particles has not been described in detail. We report here a comprehensive analysis of organic components found in mineralo-organic particles derived from body fluids. Based on biological staining, fluorescent tagging, proteomics and metabolomics, our results indicate that the mineral particles bind to proteins, amino acids, carbohydrates, polysaccharides, phospholipids, fatty acids, DNA and low molecular weight metabolites. These results can be used to study the formation and effects of mineralo-organic particles in biological fluids.


Assuntos
DNA/metabolismo , Minerais/química , Nanopartículas/química , Proteínas/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Fosfatos de Cálcio/química , Fosfatos de Cálcio/isolamento & purificação , Carboidratos/química , DNA/química , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Humanos , Lipídeos/química , Metabolômica , Minerais/isolamento & purificação , Nanopartículas/metabolismo , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Proteínas/química , Proteômica
15.
Nanomedicine (Lond) ; 13(14): 1787-1793, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29786466

RESUMO

We observed earlier that mineralo-organic nanoparticles form in human body fluids when the concentrations of calcium, carbonate and phosphate exceed saturation. The particles have been shown to represent mineral precursors in developing bones and teeth as well as in ectopic calcification and kidney stones. Recent studies suggest that the mineral particles may also be involved in other physiological processes, including immune tolerance against the gut microbiota and food antigens. We review here the involvement of mineralo-organic nanoparticles in physiological and pathological processes and discuss recent findings that reveal novel and unexpected roles for these particles in the human body.

16.
J Ethnopharmacol ; 220: 239-249, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29609012

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal mushroom Antrodia cinnamomea has been used to treat cancer but its anti-angiogenic effects have not been studied in detail. AIM OF THE STUDY: The main objective of this study was to determine the molecular mechanism of activity underlying the anti-angiogenic effects of A. cinnamomea. MATERIALS AND METHODS: The effects of an A. cinnamomea ethanol extract (ACEE) on cell migration and microvessel formation were investigated in endothelial cells in vitro and Matrigel plugs implanted into mice in vivo. Activation of intracellular signaling pathways was examined using Western blotting. Protein expression was assessed using immunohistochemistry in a mouse model of lung metastasis. RESULTS: We show that treatment with ACEE inhibits cell migration and tube formation in human umbilical vein endothelial cells (HUVECs). ACEE suppresses phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and expression of pro-angiogenic kinases in vascular endothelial growth factor (VEGF)-treated HUVECs, in addition to reducing expression of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription 3 (STAT3). ACEE treatment inhibits VEGF-induced microvessel formation in Matrigel plugs in vivo. In addition, ACEE significantly reduces VEGFR2 expression in Lewis lung carcinoma cells and downregulates the expression of cluster of differentiation 31 (CD31) and VEGFR2 in murine lung metastases. CONCLUSION: These results indicate that A. cinnamomea produces anti-angiogenic effects by inhibiting the VEGFR2 signaling pathway.


Assuntos
Inibidores da Angiogênese/farmacologia , Antrodia/química , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/isolamento & purificação , Animais , Carcinoma Pulmonar de Lewis/irrigação sanguínea , Movimento Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Brain Behav Immun ; 69: 1-8, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28888668

RESUMO

Depression is a mental disorder associated with environmental, genetic and psychological factors. Recent studies indicate that chronic neuro-inflammation may affect brain physiology and alter mood and behavior. Consumption of a high-fat diet leads to obesity and chronic systemic inflammation. The gut microbiota mediates many effects of a high-fat diet on human physiology and may also influence the mood and behavior of the host. We review here recent studies suggesting the existence of a link between obesity, the gut microbiota and depression, focusing on the mechanisms underlying the effects of a high-fat diet on chronic inflammation and brain physiology. This body of research suggests that modulating the composition of the gut microbiota using prebiotics and probiotics may produce beneficial effects on anxiety and depression.


Assuntos
Depressão/psicologia , Microbioma Gastrointestinal/fisiologia , Inflamação/psicologia , Obesidade/psicologia , Barreira Hematoencefálica , Depressão/microbiologia , Dieta Hiperlipídica , Humanos , Inflamação/microbiologia , Obesidade/microbiologia
18.
Sci Rep ; 7(1): 16628, 2017 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29192209

RESUMO

Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1ß by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs.


Assuntos
Armadilhas Extracelulares/imunologia , Proteína HMGB1/metabolismo , Imunidade Inata , Imunomodulação , Minerais/imunologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Animais , Linhagem Celular , Feminino , Proteína HMGB1/genética , Humanos , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Modelos Moleculares , Fator 88 de Diferenciação Mieloide/metabolismo , Espécies Reativas de Oxigênio , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
19.
Trends Biotechnol ; 35(11): 1017-1021, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29055355

RESUMO

The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a dietary supplement for various health conditions, including fatigue, chronic inflammation, and male impotence. Here, we propose strategies to address the existing challenges related to the study and commercial production of this mysterious fungus.


Assuntos
Ascomicetos/química , Suplementos Nutricionais , Disfunção Erétil/terapia , Fadiga/terapia , Doença Crônica , Feminino , Humanos , Masculino
20.
Trends Pharmacol Sci ; 38(11): 967-981, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28863984

RESUMO

Plants and mushrooms are used for medicinal purposes and the screening of molecules possessing biological activities. A single plant or mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on experimental conditions, but the reason behind this dichotomy remains obscure. We present here a large body of experimental data showing that water extracts of plants and mushrooms usually activate immune cells, whereas ethanol extracts inhibit immune cells. The mode of extraction of plants and mushrooms may thus determine the effects produced on immune cells, possibly due to differential solubility and potency of stimulatory and inhibitory compounds. We also examine the possibility of using such plant and mushroom extracts to treat immune system disorders.


Assuntos
Agaricales/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/farmacologia , Plantas/química , Agaricales/imunologia , Animais , Humanos , Fatores Imunológicos/isolamento & purificação , Extratos Vegetais/imunologia , Plantas/imunologia
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