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1.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540695

RESUMO

Lipidomics is a lipid-targeted metabolomics approach that aims to the comprehensive analysis of lipids in biological systems in order to highlight the specific functions of lipid species in health and disease. Lipids play pivotal roles as they are major structural components of the cellular membranes and energy storage molecules but also, as most recently shown, they act as functional and regulatory components of intra- and intercellular signaling. Herein, emphasis is given to the recently highlighted roles of specific bioactive lipids species, as polyunsaturated fatty acids (PUFA)-derived mediators (generally known as eicosanoids), endocannabinoids (eCBs), and lysophospholipids (LPLs), and their involvement in the mesenchymal stem cells (MSCs)-related inflammatory scenario. Indeed, MSCs are a heterogenous population of multipotent cells that have attracted much attention for their potential in regulating inflammation, immunomodulatory capabilities, and reparative roles. The lipidomics of the inflammatory disease osteoarthritis (OA) and the influence of MSCs-derived lipids have also been addressed.


Assuntos
Inflamação/metabolismo , Lipídeos/fisiologia , Células-Tronco Mesenquimais/metabolismo , Imunidade Adaptativa , Animais , Diferenciação Celular , Eicosanoides/fisiologia , Endocanabinoides/fisiologia , Vesículas Extracelulares , Ácidos Graxos Insaturados/farmacologia , Humanos , Imunidade Inata , Inflamação/imunologia , Lipídeos/classificação , Lisofosfolipídeos/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoartrite/metabolismo , Osteoartrite/terapia
2.
Molecules ; 26(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33573088

RESUMO

SARS-CoV-2 infects host cells by interacting its spike protein with surface angiotensin-converting enzyme 2 (ACE2) receptors, expressed in lung and other cell types. Although several risk factors could explain why some countries have lower incidence and fatality rates than others, environmental factors such as diet should be considered. It has been described that countries with high polyunsaturated fatty acid (PUFA) intake have a lower number of COVID-19 victims and a higher rate of recovery from the disease. Moreover, it was found that linoleic acid, an omega-6 PUFA, could stabilize the spike protein in a closed conformation, blocking its interaction with ACE2. These facts prompted us to perform in silico simulations to determine if other PUFA could also stabilize the closed conformation of spike protein and potentially lead to a reduction in SARS-CoV-2 infection. We found that: (a) countries whose source of omega-3 is from marine origin have lower fatality rates; and (b) like linoleic acid, omega-3 PUFA could also bind to the closed conformation of spike protein and therefore, could help reduce COVID-19 complications by reducing viral entrance to cells, in addition to their known anti-inflammatory effects.


Assuntos
/epidemiologia , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Simulação por Computador , Ingestão de Alimentos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Alimentos Marinhos , Internalização do Vírus/efeitos dos fármacos
3.
Nutrients ; 13(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375042

RESUMO

Gut microbiota changes correlate with health status. Literature data on gut microbiota show that all dietary changes can induce the alteration of gut microbiota composition. Mediterranean diet (MD) is associated with a reduction of all-cause mortality and in this review, we analyzed its interactions with human microbiota. In particular, we explored the modulation of the human microbiota, in response to MD adherence, focusing the attention on polyphenols, polyunsaturated fatty acids (PUFA) ω-3 and fiber. Evidences suggest that MD is able to modulate the gut microbiota, increasing its diversity. In fact, a Mediterranean-type dietary pattern is associated with specific gut microbiota characteristics. The available evidence, suggests that gut microbiota of subjects that follow a MD is significantly different from subjects that follow a Western diet model. In fact, the latter show an increased gut permeability, which is responsible for metabolic endotoxemia. For this reason, we can speculate that the gut microbiota of the subjects following a MD is able to prevent the onset of chronic non-communicable degenerative diseases, such as cardiovascular diseases and some types of cancer. However, in order to understand these correlations with dietary patterns, controlled intervention studies on the gut microbiota composition and activity are needed.


Assuntos
Dieta Mediterrânea , Microbioma Gastrointestinal/efeitos dos fármacos , Doenças Cardiovasculares , Bases de Dados Factuais , Dieta , Fibras na Dieta , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Insaturados/farmacologia , Humanos , Azeite de Oliva , Polifenóis/farmacologia
4.
Int J Exp Pathol ; 101(1-2): 55-64, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32459025

RESUMO

Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-term consequences; novel targeted biologics and small-molecule inhibitors are promising options. In this study, we investigated whether purified omega unsaturated fatty acids (ω-UFAs) and dialysable leukocyte extracts (DLEs) prevented the development of arthritis in a model of collagen-induced arthritis (CIA) in mice. We also investigated whether the transcription factor NF-κB and the NLRP3 inflammasome were involved in the process and whether their activity was modulated by treatment. The development of arthritis was evaluated for 84 days following treatment with nothing, dexamethasone, DLEs, docosahexaenoic acid, arachidonic acid, and oleic acid. Progression of CIA was monitored by evaluating clinical manifestations, inflammatory changes, and histological alterations in the pads' articular tissues. Both DLEs and ω-UFAs led to an almost complete inhibition of the inflammatory histopathology of CIA and this was concomitant with the inhibition of NF-kB and the inhibition of the activation of NLRP3. These data suggest that ω-UFAs and DLEs might have NF-κB as a common target and that they might be used as ancillary medicines in the treatment of arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Artrite Experimental/prevenção & controle , Cartilagem Articular/efeitos dos fármacos , Extratos Celulares/farmacologia , Ácidos Graxos Insaturados/farmacologia , Leucócitos , Animais , Ácido Araquidônico/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Colágeno Tipo II , Diálise , Ácidos Docosa-Hexaenoicos/farmacologia , Feminino , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Oleico/farmacologia
5.
PLoS One ; 15(4): e0232224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343717

RESUMO

The Amazon region is rich in genetic resources such as oilseeds which have potentially important local commercial exploitation. Despite its high concentration of bioactive compounds, cacay (Caryodendron orinocense Karst.) oil is poorly investigated and explored. Thus, this study focuses on the physicochemical characterization (moisture, density, and saponification, iodine, and acidity values), fatty acid composition as determined by gas chromatograph mass spectrometry (GC/MS), total phenolic content (TPC), and antioxidant activity (DPPH and ABTS radical scavenging assay) of cacay oil, coconut oil and a coconut/cacay oil blend, also known as cacay butter. The antibacterial activity of cacay oil was additionally evaluated. Our study demonstrated that cacay oil presents a high amount of polyunsaturated fatty acid (PUFA) (58.3%) with an emphasis on linoleic acid and a lower acidity value (2.67 ± 0.01 cg I2/g) than butter and coconut oil, indicating a low concentration of free fatty acids. In contrast, cacay butter and coconut oil presented higher saturated fatty acid percentages (69.1% and 78.4%, respectively) and higher saponification values (242.78 and 252.22 mg KOH/g, respectively). The samples showed low moisture and relative density between 912 and 916 kg/m3. The hydrophilic fraction of cacay oil was highlighted in the quantification of TPC (326.27 ± 6.79 mg GAE/kg) and antioxidant capacity in vitro by DPPH radical scavenging assay (156.57 ± 2.25 µmol TE/g). Cacay oil inhibited the growth of Bacillus cereus (44.99 ± 7.68%), Enterococcus faecalis (27.76 ± 0.00%), and Staphylococcus aureus (11.81 ± 3.75%). At long last, this is the first study reporting the physicochemical characterization and bioactive properties of cacay butter. Coconut oil and cacay butter showed great oxidative stability potential due to higher contents of saturated fatty acids. Moreover, cacay oil presents as an alternative source of raw materials for cosmetic and biotechnology industries due to its high concentration of PUFA and for being a rich source of phenolic compounds.


Assuntos
Óleo de Coco/química , Euphorbiaceae/química , Óleos Vegetais/química , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Fenômenos Químicos , Óleo de Coco/farmacologia , Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Óleos Vegetais/farmacologia
6.
Arch Med Res ; 51(3): 282-286, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32229155

RESUMO

SARS-CoV-2, SARS and MERS are all enveloped viruses that can cause acute respiratory syndrome. Arachidonic acid (AA) and other unsaturated fatty acids (especially eicosapentaenoic acd, EPA and docosahexaenoic acid DHA) are known to inactivate enveloped viruses and inhibit proliferation of various microbial organisms. The pro-inflammatory metabolites of AA and EPA such as prostaglandins, leukotrienes and thromboxanes induce inflammation whereas lipoxins, resolvins, protectins and maresins derived from AA, EPA and DHA not only suppress inflammation but also enhance would healing and augment phagocytosis of macrophages and other immunocytes and decrease microbial load. In view of these actions, it is suggested that AA and other unsaturated fatty acids and their metabolites may serve as endogenous anti-viral compounds and their deficiency may render humans susceptible to SARS-CoV-2, SARS and MERS and other similar viruses' infections. Hence, oral or intravenous administration of AA and other unsaturated fatty acids may aid in enhancing resistance and recovery from SARS-CoV-2, SARS and MERS infections.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Ácidos Graxos Insaturados/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Inativação de Vírus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Ácidos Graxos Insaturados/farmacologia , Humanos , Modelos Moleculares , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia
8.
Sci Rep ; 10(1): 2902, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076010

RESUMO

The experimental approach for the study of cardiometabolic disorders requires the use of animal models fed with commercial diets whose composition differs notably, even between diets used for control groups. While chow diets are usually made of agricultural by-products, purified low-fat diets (LF) contain a higher percentage of easy metabolizable carbohydrates, together with a reduced amount of polyunsaturated fatty acids, micronutrients and fiber, all associated with metabolic and vascular dysfunction. We hypothesize that the LF diet, commonly used in control animals, could promote adverse vascular and metabolic outcomes. To address this issue, 5-week-old male C57BL6J mice were fed with a standard (Chow) or a LF diet for 6 weeks. Changes in body weight, adiposity, biochemical parameters, systemic and aortic insulin sensitivity and endothelial function were recorded. LF diet did not modify body weight but significantly impaired systemic glucose tolerance and increased triglycerides and cholesterol levels. Endothelial function and aortic insulin sensitivity were significantly impaired in the LF group, due to a reduction of NO availability. These findings highlight the importance of selecting the proper control diet in metabolic studies. It may also suggest that some cardiometabolic alterations obtained in experimental studies using LF as a control diet may be underestimated.


Assuntos
Aorta Torácica/fisiologia , Dieta , Glucose/metabolismo , Homeostase , Acetilcolina/farmacologia , Adiposidade/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Disponibilidade Biológica , Peso Corporal/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Colesterol/metabolismo , Dieta com Restrição de Gorduras , Fibras na Dieta/farmacologia , Ácidos Graxos Insaturados/farmacologia , Glucose/administração & dosagem , Insulina/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Fenilefrina/metabolismo , Solubilidade , Gordura Subcutânea/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
9.
Sci Rep ; 10(1): 2630, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060341

RESUMO

G Protein-Coupled receptors represent the main communicating pathway for signals from the outside to the inside of most of eukaryotic cells. They define the largest family of integral membrane receptors at the surface of the cells and constitute the main target of the current drugs on the market. The low affinity leukotriene receptor BLT2 is a receptor involved in pro- and anti-inflammatory pathways and can be activated by various unsaturated fatty acid compounds. We present here the NMR structure of the agonist 12-HHT in its BLT2-bound state and a model of interaction of the ligand with the receptor based on a conformational homology modeling associated with docking simulations. Put into perspective with the data obtained with leukotriene B4, our results illuminate the ligand selectivity of BLT2 and may help define new molecules to modulate the activity of this receptor.


Assuntos
Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/farmacologia , Receptores do Leucotrieno B4/agonistas , Receptores do Leucotrieno B4/metabolismo , Humanos , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Receptores do Leucotrieno B4/química
10.
Lipids Health Dis ; 19(1): 4, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915015

RESUMO

BACKGROUND: Menopause predisposes individuals to affective disorders, such as depression, which is tightly related to neuroinflammation. While the neuroinflammatory condition has been demonstrated in ovariectomized (OVX) rodents, there is limited evidence concerning microglial polarization, a key process in brain immune activation, in menopause-related brain. METHODS: Therefore, the present study aims to evaluate the polarized microglia in long-term OVX rats and we further explored whether supplementation of ω-3 polyunsaturated fatty acids (PUFA), the pleiotropic bioactive nutrient, is effective in the neurobehavioral changes caused by OVX. RESULTS: Our data showed that OVX-induced anxiety and depression-like behaviors in rats, accompanied with increased neural apoptosis and microglial activation in the hippocampus. Additionally, OVX enhanced proinflammatory cytokines expression and suppressed the expression of anti-inflammatory cytokine, IL-10. Correspondingly, OVX reinforced NFκB signaling and shifted the microglia from immunoregulatory M2 phenotype to proinflammatory M1 phenotype. Meanwhile, daily supplementation with PUFA suppressed microglial M1 polarization and potentiated M2 polarization in OVX rats. In parallel, PUFA also exerted antidepressant and neuroprotective activities, accompanied with neuroimmune-modulating actions. CONCLUSION: Collectively, the present study firstly demonstrated the disturbed microglial polarization in the OVX brain and provide novel evidence showing the association between the antidepressant actions of PUFA and the restraint neuroinflammatory progression.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Interleucina-10/genética , Animais , Depressão/genética , Depressão/patologia , Modelos Animais de Doenças , Ácidos Graxos Insaturados/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Masculino , Microglia/efeitos dos fármacos , Microglia/patologia , NF-kappa B/genética , Ratos , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979341

RESUMO

Estrogen (E2) and polyunsaturated fatty acids (n-3PUFA) supplements independently support general wellbeing and enhance muscle regeneration in-vivo and myotube formation in-vitro. However, the combined effect of E2 and n-3PUFA on myoblast differentiation is not known. The purpose of the study was to identify whether E2 and n-3PUFA possess a synergistic effect on in-vitro myogenesis. Mouse C2C12 myoblasts, a reliable model to reiterate myogenic events in-vitro, were treated with 10nM E2 and 50µM eicosapentaenoic acid (EPA) independently or combined, for 0-24 h or 0-120 h during differentiation. Immunofluorescence, targeted qPCR and next generation sequencing (NGS) were used to characterize morphological changes and differential expression of key genes involved in the regulation of myogenesis and muscle function pathways. E2 increased estrogen receptor α (Erα) and the expression of the mitogen-activated protein kinase 11 (Mapk11) within 1 h of treatment and improved myoblast differentiation and myotube formation. A significant reduction (p < 0.001) in myotube formation and in the expression of myogenic regulatory factors Mrfs (MyoD, Myog and Myh1) and the myoblast fusion related gene, Tmem8c, was observed in the presence of EPA and the combined E2/EPA treatment. Additionally, EPA treatment at 48 h of differentiation inhibited the majority of genes associated with the myogenic and striated muscle contraction pathways. In conclusion, EPA and E2 had no synergistic effect on myotube formation in-vitro. Independently, EPA inhibited myoblast differentiation and overrides the stimulatory effect of E2 when used in combination with E2.


Assuntos
Ácido Eicosapentaenoico/farmacologia , Estrogênios/farmacologia , Desenvolvimento Muscular/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Mioblastos/metabolismo , Animais , Linhagem Celular , DNA Glicosilases/metabolismo , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Ácidos Graxos Insaturados/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Membrana/metabolismo , Camundongos , Proteína Quinase 11 Ativada por Mitógeno/metabolismo , Desenvolvimento Muscular/genética , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , Proteína MyoD/metabolismo , Mioblastos/citologia , Miogenina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética
12.
Am J Physiol Endocrinol Metab ; 318(4): E514-E524, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990576

RESUMO

We examined the methionine aminopeptidase 2 inhibitor fumagillin in dogs consuming a high-fat and -fructose diet (HFFD). In pilot studies (3 dogs that had consumed HFFD for 3 yr), 8 wk of daily treatment with fumagillin reduced food intake 29%, weight 6%, and the glycemic excursion during an oral glucose tolerance test (OGTT) 44%. A second group of dogs consumed the HFFD for 17 wk: pretreatment (weeks 0-4), treatment with fumagillin (FUM; n = 6), or no drug (Control, n = 8) (weeks 4-12), washout period (weeks 12-16), and fumagillin or no drug for 1 wk (week 17). OGTTs were performed at 0, 4, 11, and 16 wk. A hyperinsulinemic hyperglycemic clamp was performed in week 12; 4 chow-fed dogs underwent identical clamps. Kilocalories per day intake during the treatment period was 2,067 ± 50 (Control) versus 1,824 ± 202 (FUM). Body weights (kg) increased 1.9 ± 0.3 vs. 2.7 ± 0.8 (0-4 wk) and 1.2 ± 0.2 vs. -0.02 ± 0.9 (4-12 wk) in Control versus fumagillin. The OGTT glycemic response was 30% greater in Control versus fumagillin at 11 wk. Net hepatic glucose uptake (NHGU; mg·kg-1·min-1) in the Chow, Control, and fumagillin dogs was ~1.5 ± 0.6, -0.1 ± 0.1, and 0.3 ± 0.4 (with no portal glucose infusion) and 3.1 ± 0.6, 0.5 ± 0.3, and 1.5 ± 0.5 (portal glucose infusion at 4 mg·kg-1·min-1), respectively. Fumagillin improved glucose tolerance and NHGU in HFFD dogs, suggesting methionine aminopeptidase 2 (MetAP2) inhibitors have the potential for improving glycemic control in prediabetes and diabetes.


Assuntos
Aminopeptidases/antagonistas & inibidores , Cicloexanos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Insaturados/farmacologia , Frutose/efeitos adversos , Glucose/metabolismo , Glucose/farmacologia , Metaloendopeptidases/antagonistas & inibidores , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Dieta , Cães , Ingestão de Alimentos/efeitos dos fármacos , Técnica Clamp de Glucose , Teste de Tolerância a Glucose , Resistência à Insulina , Masculino , Sesquiterpenos/farmacologia
13.
J Vet Sci ; 21(1): e15, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31940694

RESUMO

The present study evaluated the anti-inflammatory effect of horse oil in 2, 4-dinitrochlorobenzene (DNCB)-treated BALB/c mice. After the application of DNCB, the mice showed atopic dermatitis symptoms, including severe erythema, hemorrhage, and erosion, whereas those symptoms were alleviated by treatment with horse oil. To explain the anti-dermatitis effect of horse oil, the gene expression levels in the healing process in dorsal skin were observed using a cDNA microarray. The cDNA microarray analysis revealed that the expression levels of 30 genes related to the inflammation, including Ccr1, Ccr2, Ccl20, Anxa1, and Hc genes, were up-regulated (higher than 2.0-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. In contrast, the gene expression levels of 28 genes related to inflammation, including chemokine genes Ccl5, Ccl7, Ccl8, Cxcl10, and Cxcl13 genes, were down-regulated (lower than 0.5-fold) in the DNCB group compared to the levels in the control group, whereas the levels were restored to the control level in the DNCB + horse oil-treated group. Overall, the results show that horse oil restores the expression levels of genes related to inflammation that were perturbed by DNCB treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/farmacologia , Expressão Gênica/imunologia , Irritantes/farmacologia , Sebo , Administração Tópica , Animais , Dermatite Atópica/induzido quimicamente , Ácidos Graxos Insaturados/administração & dosagem , Ácidos Graxos Insaturados/farmacologia , Cavalos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
14.
PLoS One ; 15(1): e0227484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31923212

RESUMO

Nosema ceranae is a microsporidian parasite that causes nosemosis in the honey bee (Apis mellifera). As alternatives to the antibiotic fumagillin, ten nutraceuticals (oregano oil, thymol, carvacrol, trans-cinnmaldehyde, tetrahydrocurcumin, sulforaphane, naringenin, embelin, allyl sulfide, hydroxytyrosol) and two immuno-stimulatory compounds (chitosan, poly I:C) were examined for controlling N. ceranae infections. Caged bees were inoculated with N. ceranae spores, and treatments were administered in sugar syrup. Only two compounds did not significantly reduce N. ceranae spore counts compared to the infected positive control, but the most effective were sulforaphane from cruciferous vegetables, carvacrol from oregano oil, and naringenin from citrus fruit. When tested at several concentrations, the highest sulforaphane concentration reduced spore counts by 100%, but also caused 100% bee mortality. For carvacrol, the maximum reduction in spore counts was 57% with an intermediate concentration and the maximum bee mortality was 23% with the highest concentration. For naringenin, the maximum reduction in spore counts was 64% with the highest concentration, and the maximum bee mortality was only 15% with an intermediate concentration. In the longevity experiment, naringenin-fed bees lived as long as Nosema-free control bees, both of which lived significantly longer than infected positive control bees. While its antimicrobial properties may be promising, reducing sulforaphane toxicity to bees is necessary before it can be considered as a candidate for controlling N. ceranae. Although further work on formulation is needed with naringenin, its effect on extending longevity in infected bees may give it an additional value as a potential additive for bee feed in honey bee colonies.


Assuntos
Abelhas/microbiologia , Suplementos Nutricionais/análise , Nosema/fisiologia , Animais , Abelhas/efeitos dos fármacos , Abelhas/metabolismo , Cicloexanos/farmacologia , Cimenos/farmacologia , Ácidos Graxos Insaturados/farmacologia , Flavanonas/farmacologia , Isotiocianatos/farmacologia , Longevidade/efeitos dos fármacos , Nosema/efeitos dos fármacos , Sesquiterpenos/farmacologia , Esporos Fúngicos/fisiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-31816410

RESUMO

Juvenile hormone binding proteins (JHBPs) serve as the carriers that transport juvenile hormone (JH) to target tissues to activate JH signals. In this study, seven JHBPs from mud crab Scylla paramamosain were obtained. All Sp-JHBPs contained one JHBP domain, and Sp-JHBP4, 5, 6 also contained one Grp7_allergen domain. The predicted secondary and 3D structures are conserved among the seven Sp-JHBP domains, but the complete 3D structure of Sp-JHBP4, 5, 6 were more similar to lipopolysaccharide binding protein. Additionally, the potential ligands for Sp-JHBP1, 2, 3, 7 were ubiquinone 8 (UQ8) and JH II or JH III, and the predicted binding location and sites for JHs were similar to the structured known BmJHBP, suggesting that MF is a potential ligand for these Sp-JHBPs. Furthermore, the expression analysis showed that Sp-JHBP1 expression is relatively low in the 14 detected tissues, and Sp-JHBP2 has the highest expression in the ovary, while the other five JHBPs are highly expressed in the hepatopancreas. During larval development, Sp-JHBP2 is highly expressed during the Z1, M and C1 stages, which are three post-metamorphosis stages, while Sp-JHBP3 and 4 expression levels were significantly lower during the Z5 and M stages, which are two pre-metamorphosis stages. Moreover, the in vivo and in vitro study revealed that Sp-JHBP2 expression was reduced by MF, while the in vitro studies showed that Sp-JHBP3, 6, 7 are induced by MF in a concentration-independent manner. Taken together, we hypothesized Sp-JHBP1, 2, 3, 7 has the potential to bind MF and Sp-JHBP2, 3, 7 play a more important roles in MF signal, while Sp-JHBP4, 5, 6 were more likely to participate in immune response.


Assuntos
Braquiúros/metabolismo , Proteínas de Transporte/biossíntese , Ácidos Graxos Insaturados/farmacologia , Proteínas de Insetos/biossíntese , Sequência de Aminoácidos , Animais , Braquiúros/efeitos dos fármacos , Braquiúros/genética , Braquiúros/crescimento & desenvolvimento , Proteínas de Transporte/genética , Clonagem Molecular , Feminino , Proteínas de Insetos/genética , Conformação Proteica , Isoformas de Proteínas , Homologia de Sequência de Aminoácidos
16.
Histochem Cell Biol ; 153(3): 165-175, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31858211

RESUMO

In diabetic nephropathy (DN), intercellular communication is disrupted. Connexins (Cx) have a crucial role in that process. Dietary ratios and supplementation with polyunsaturated fatty acids (PUFAs) can alleviate diabetic complications and cause alterations in Cx levels. Although pannexins (Panx) share similarities with members of the Cx family, their function in diabetic nephropathy has still not been fully determined. We studied the influence of PUFA supplementation on the immunoexpression of Px1 and Cx family members in diabetic kidneys of rats. Four groups of rats in experimental DM1 model were supplemented with different dietary n-6/n-3 ratios; ≈7 in control (C) and diabetic groups (STZ), ≈ 60 in the STZ + N6 group and ≈ 1 (containing 16% EPA and 19% DHA) in the STZ + N3 group. Immunoexpression of Cx40, Cx43, Cx45 and Panx1 was evaluated in the renal tissue of diabetic rats using immunohistochemistry. Diabetes significantly decreased the protein expression of Cx40 and Cx43 and increased Panx1 protein expression in the renal cortex (p < 0.05-p < 0.01). There was a significant impact of diet on Cx and Panx1 immunoexpression. Dietary supplementation with a high n-6/n-3 ratio downregulated the protein expression of Cx45 and Panx1 in diabetic rats (p < 0.05-p < 0.01), while Cx43 immunoexpression was increased in diabetic rats fed with high and low n-6/n-3 ratios (p < 0.01-p < 0.001). Hyperglycaemic conditions in DN interfere with cell-to-cell communication and disturb the connection between cells and their immediate environment due to variations in connexin and pannexin immunoexpression. These variations can be regulated by PUFA dietary intake, suggesting their beneficial effect and possible therapeutic option.


Assuntos
Conexinas/antagonistas & inibidores , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Ácidos Graxos Insaturados/farmacologia , Rim/efeitos dos fármacos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Animais , Conexinas/análise , Conexinas/biossíntese , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Suplementos Nutricionais , Ácidos Graxos Insaturados/administração & dosagem , Rim/metabolismo , Rim/patologia , Masculino , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/biossíntese , Ratos , Ratos Wistar , Estreptozocina
17.
Biochem Biophys Res Commun ; 522(1): 68-73, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31740001

RESUMO

We examined whether the acetylenic fatty acids 6-octadecynoic acid (6-ODA) and 9-octadecynoic acid (9-ODA) perform as ligands for free fatty acid receptors of medium- and long-chain fatty acids FFAR1 and FFAR4, previously called GPR40 and GPR120, respectively. Phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 was increased through FFAR1 but not through FFAR4 expressed in HEK 293 cells, suggesting that 6-ODA and 9-ODA function as an FFAR1 ligand, but not as an FFAR4 ligand. Activation of ERK in FFAR1-expressing HEK293 cells by 6-ODA and 9-ODA peaked at 10 min after stimulation followed by a slow decrease, similar to ERK activation by rosiglitazone, which peaked at 10 min after stimulation and lasted longer. Glucose-dependent production of insulin from MIN6 insulinoma cells was induced by 6-ODA and 9-ODA in an FFAR1-dependent manner. In this process, 6-ODA and 9-ODA stimulated the production of insulin not in the first phase that occurred within 10 min after stimulation but in the second phase. F-actin-remodeling that reflects insulin granule recruiting to the plasma membrane in the second phase of insulin secretion by 6-ODA and 9-ODA suggested that they have an FFAR1-dependent function in insulin secretion from MIN6 cells.


Assuntos
Ácidos Graxos/metabolismo , Insulina/metabolismo , Insulinoma/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Actinas/metabolismo , Alquinos/farmacologia , Animais , Linhagem Celular Tumoral , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/farmacologia , Glucose/metabolismo , Células HEK293 , Humanos , Camundongos
18.
Biosci Biotechnol Biochem ; 84(2): 290-296, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31619134

RESUMO

Chromosome region maintenance 1 (CRM1) plays a critical role in tumorigenesis and progression through modulating nuclear export of several proteins. However, the precise effects of CRM1 inhibitor on gastric carcinoma have not yet been illustrated. Here, we investigated the potential anti-cancer activities of leptomycin B, the most potent CRM1 antagonist, on cultured gastric carcinoma cells. Our findings demonstrate that CRM1 was highly expressed in four gastric carcinoma cell lines. Leptomycin B inhibited the viability of HGC-27 and AGS cells in a dose- and time-dependent pattern. Leptomycin B at the dose of 10 nM or 100 nM suppressed the migration and invasion of HGC-27 and AGS cells. Leptomycin B elevated the expressions of autophagy-related protein LC3-II and autophagy substrate p62. Moreover, leptomycin B enhanced the LC3-positive puncta formation in cells. Our data suggest that leptomycin B may exert an anti-cancer activity possibly through interfering autophagy function in gastric carcinoma cells.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Invasividade Neoplásica/prevenção & controle , Neoplasias Gástricas/patologia , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ácidos Graxos Insaturados/farmacologia , Humanos , Carioferinas/antagonistas & inibidores , Carioferinas/metabolismo , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo
19.
J Sci Food Agric ; 100(4): 1418-1425, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31667852

RESUMO

BACKGROUND: Silkworm pupa oil polyunsaturated fatty acid (SPO PUFA) has been confirmed to have a cholesterol-lowering function. METHODS AND RESULTS: The effect of SPO PUFA and its main component, α-linolenic acid (ALA), on the metabolism of cholesterol and its regulation was investigated. The model of lipid denatured cells were constructed to carry out lipid accumulation, cholesterol metabolism and transformation. Real-time PCR and western blots were also used to analyze the expression levels of related genes and proteins to investigate the cholesterol efflux regulation mechanism. The data indicated that SPO PUFA and ALA dose-dependently decreased intracellular total cholesterol (TC) and enhanced total bile acid (TBA). They could also promote cholesterol removal by enhancing bile acid secretion and by upregulating genes LXRα, PPARγ, ABCA1, ABCG1, and CYP7A1, which were regulated by LXRα/PPARγ-ABCA1/ABCG1-CYP7A1 nuclear receptor signal pathways. CONCLUSIONS: This study is of great significance in maintaining the balance of cholesterol and lipid metabolism, and in reducing the risk of steatohepatitis. © 2019 Society of Chemical Industry.


Assuntos
Bombyx/química , Colesterol/metabolismo , Ácidos Graxos Insaturados/farmacologia , Hepatócitos/metabolismo , Pupa/química , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Biomed Chromatogr ; 34(3): e4743, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31715013

RESUMO

Lipotoxicity is defined as deposition of excess fat associated with an inflammatory response. Metabolomic analysis of fatty acids (FAs) can be a marker of silent inflammation. ω3-Enriched diet, celecoxib, and safranal may have a protective anti-inflammatory role. In this work, total FAs extracted from red blood cells and arachidonic acid-to-eicosapentaenoic acid (AA-to-EPA) ratios were assessed using GC-MS assay in single-ion monitoring mode. The study was conducted on 64 male rats divided into eight groups: I, controls; II, rats received high-fat diet (HFD), III, rats received ω-6-enriched HFD; IV, rats received ω-3-enriched HFD; V, rats received celecoxib with HFD; VI, rats received safranal with HFD; VII and VIII, rats received celecoxib and safranal with ω-3 HFD, respectively. GC-MS Gas chromatography Mass spectrometry was performed for analysis of fatty acid methyl ester. Enzyme-linked immunosorbent assay was used to analyze serum interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-ß1) concentrations. A statistically significant decrease of AA-to-EPA ratio was observed in group VII when compared with the groups receiving HFDs. This group also showed the lowest serum IL-6 level and highest TGF-ß1 level. In conclusion, ω3-enriched diet along with drugs (e.g. celecoxib) and herbal medications (e.g. safranal) may have an anti-inflammatory effect in lipotoxicity. GC-MS with single-ion monitoring is valid for the analysis of FAs.


Assuntos
Anti-Inflamatórios/farmacologia , Dieta Hiperlipídica , Ácidos Graxos Insaturados , Inflamação/metabolismo , Obesidade/metabolismo , Animais , Celecoxib/farmacologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Ratos
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