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1.
J Genet Genomics ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36356718

RESUMO

The immune regulatory effects of probiotics have been widely recognized to be strain-specific. However it is unknown if there is a species- or genus-dependent manner. In this study, we use an in vitro mesenteric lymph node (MLN) model to systematically evaluate the immunostimulatory effects of gut-derived potential probiotics. The results exhibite an obvious species or genus consensus immune response pattern. RNA-seq shows that T cell-dependent B cell activation and antibody responses may be inherent to this model. Of the five tested genera, Akkermansia spp. and Clostridium butyrium directly activate the immune response in vitro, as indicated by the secretion of interleukin-10. Bifidobacterium spp. and Bacteroides spp. activate immune response with the help of stimuli (anti-CD3 and anti-CD28 antibodies). Lactobacillus spp. blunt the immune response with or without stimuli. Further investigations show that the cell surface protein of A. muciniphila AH39, which may serve as a T cell receptor cognate antigen, might evoke an in vitro immune activation. In vivo, oral administration of A. muciniphila AH39 influences the proportion of T regulatory cells (Tregs) in MLNs and the spleen under homeostasis in both specific pathogen-free and germ-free mice. All these findings indicate the distinct effects of different genera or species of potential gut-derived probiotics on intestinal and systemic immunity.

2.
Nutrients ; 14(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364939

RESUMO

There is mounting evidence that the microbiota-gut-brain axis (MGBA) is critical in the pathogenesis and progression of Parkinson's disease (PD), suggesting that probiotic therapy restoring gut microecology may slow down disease progression. In this study, we examined the disease-alleviating effects of Bifidobacterium breve CCFM1067, orally administered for 5 weeks in a PD mouse model. Our study shows that supplementation with the probiotic B. breve CCFM1067 protected dopaminergic neurons and suppressed glial cell hyperactivation and neuroinflammation in PD mice. In addition, the antioxidant capacity of the central nervous system was enhanced and oxidative stress was alleviated. Moreover, B. breve CCFM1067 protected the blood-brain and intestinal barriers from damage in the MPTP-induced mouse model. The results of fecal microbiota analysis showed that B. breve CCFM1067 intervention could act on the MPTP-induced microecological imbalance in the intestinal microbiota, suppressing the number of pathogenic bacteria (Escherichia-Shigella) while increasing the number of beneficial bacteria (Bifidobacterium and Akkermansia) in PD mice. In addition, the increase in short chain fatty acids (acetic and butyric acids) may explain the anti-inflammatory action of B. breve CCFM1067 in the gut or brain of the MPTP-induced PD mouse model. In conclusion, we demonstrated that the probiotic B. breve CCFM1067, which can prevent or treat PD by modulating the gut-brain axis, can be utilized as a possible new oral supplement for PD therapy.


Assuntos
Bifidobacterium breve , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/etiologia , Doença de Parkinson/prevenção & controle , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Bifidobacterium , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
Nutrients ; 13(6)2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34070274

RESUMO

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Isoflavonas/farmacologia , Menopausa/metabolismo , Obesidade/dietoterapia , Probióticos/farmacologia , Animais , Bifidobacterium longum/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Feminino , Humanos , Lactobacillus plantarum/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças Metabólicas/dietoterapia , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia/métodos
4.
J Cell Mol Med ; 24(14): 8045-8056, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32469149

RESUMO

Plastic polarization of macrophage is involved in tumorigenesis. M1-polarized macrophage mediates rapid inflammation, entity clearance and may also cause inflammation-induced mutagenesis. M2-polarized macrophage inhibits rapid inflammation but can promote tumour aggravation. ω-3 long-chain polyunsaturated fatty acid (PUFA)-derived metabolites show a strong anti-inflammatory effect because they can skew macrophage polarization from M1 to M2. However, their role in tumour promotive M2 macrophage is still unknown. Resolvin D1 and D2 (RvD1 and RvD2) are docosahexaenoic acid (DHA)-derived docosanoids converted by 15-lipoxygenase then 5-lipoxygenase successively. We found that although dietary DHA can inhibit prostate cancer in vivo, neither DHA (10 µmol/L) nor RvD (100 nmol/L) can directly inhibit the proliferation of prostate cancer cells in vitro. Unexpectedly, in a cancer cell-macrophage co-culture system, both DHA and RvD significantly inhibited cancer cell proliferation. RvD1 and RvD2 inhibited tumour-associated macrophage (TAM or M2d) polarization. Meanwhile, RvD1 and RvD2 also exhibited anti-inflammatory effects by inhibiting LPS-interferon (IFN)-γ-induced M1 polarization as well as promoting interleukin-4 (IL-4)-mediated M2a polarization. These differential polarization processes were mediated, at least in part, by protein kinase A. These results suggest that regulation of macrophage polarization using RvDs may be a potential therapeutic approach in the management of prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
5.
Stem Cells Int ; 2019: 5010184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885611

RESUMO

This is a study on the relationship between the protective effect of ginsenoside Rg1 on senescent neural stem cells and Wnt-ß/catenin signaling pathway. Background. Recent studies have shown that overactivation of the Wnt/ß-catenin signaling pathway is closely related to stem cell senescence. Whether Rg1 delays the senescence of NSCs is related to the regulation of this signaling pathway. Methods. The whole brain of Nestin-GFP transgenic newborn rat was extracted, and NSCs were extracted and cultured to P3 generation. The following indicators were detected: (1) NSC culture identification, (2) the effect of LiCl on the proliferation and survival rate of NSCs, (3) the effect of ginsenoside Rg1 on the proliferation and survival of NSCs, (4) the growth of NSCs in each group observed by an optical microscope, (5) the cell cycle of each group detected by flow cytometry, (6) the proliferative ability of each group detected by BrdU, (7) the fluorescence intensity of Nestin and Sox2 of NSCs in each group observed by a fluorescence microscope, (8) the positive rate of senescence staining analyzed by SA-ß-Gal staining, (9) the localization of ß-catenin in NSCs observed by laser confocal microscopy, and (10) the changes of the Wnt/ß-catenin pathway-related proteins in each group detected by Western blotting. Results. LiCl activates the Wnt/ß-catenin pathway and promotes mouse neural stem cell senescence. Ginsenoside Rg1 promotes proliferation of neural stem cells and inhibits Wnt/ß-catenin pathway activation. Conclusions. LiCl can activate the Wnt/ß-catenin signaling pathway of NSCs, and ginsenoside Rg1 can antagonize the senescence of NSCs caused by activation of the Wnt/ß-catenin signaling pathway and delay brain aging.

6.
Neurochem Int ; 122: 149-156, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30196146

RESUMO

The incidence of neurodegenerative diseases is severely increasing with the aging. It has been proposed that NSCs (neural stem cells) help to control aging, but the mechanisms responsible remain unclear. Angelica polysaccharide is an active ingredient of Angelica sinensis in traditional Chinese medicine, which possesses versatile pharmacological activities including anti-oxidative and anti-aging effects. In this study, D-gal (D-galactose) was used to construct an aging model of Nestin-GFP transgenic mice brain tissues and NSCs. Mouse model was subcutaneously injected with D-gal, as we observed that mice consistently displayed acceleration of aging-like behavior change, energy metabolism decreased, the expression of aging-related genes was up-regulated. Conversely, aging retardation was achieved in Nestin-GFP mice Induced by D-gal that was locally injected with ASP (Angelica polysaccharide). Mechanistically, we isolated and cultured NSCs in vitro. ASP protected NSCs by increasing the cell proliferation; decreasing the number of SA-ß-gal stained neurons; increasing the activity of SOD(superoxide dismutase) and T-AOC(total antioxidant capacity), decreasing the content of MDA(malondialdehyde); decreasing the levels of IL-1b,IL-6,TNF-a and ROS; and down-regulated the expression of cellular senescence associated genes p53, p21 in the aging NSCs. In conclusion, ASP can delay aging speed by protecting NSCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity, up-regulation of p53/p21 signaling pathway. As to provide theoretical basis for treatment for brain aging related diseases, add new scientific connotation for "qi and blood theory" and "supplement blood and delay aging" of Traditional Chinese Medicine.


Assuntos
Encéfalo/efeitos dos fármacos , Galactose/farmacologia , Nestina/metabolismo , Polissacarídeos/farmacologia , Angelica sinensis/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Masculino , Malondialdeído/metabolismo , Camundongos Transgênicos , Células-Tronco Neurais/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
7.
Cell Physiol Biochem ; 48(6): 2318-2336, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30114709

RESUMO

BACKGROUND/AIMS: Rapamycin (Rp), the main mammalian target of rapamycin complex inhibitor, is a promising therapeutic agent for breast cancer. However, metabolic disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and experimental studies have demonstrated that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) significantly reduce the incidence and mortality of breast cancer and improve metabolic disorders. METHODS: Three breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Rp plus ω-3 PUFA treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics, seahorse experiments, and western blot analysis. RESULTS: We found that ω-3 PUFAs and Rp synergistically induced cell cycle arrest and apoptosis in vitro and in vivo, accompanied by autophagy blockage. In addition, Rp-induced hypertriglyceridemia and hypercholesterolemia were completely abolished by ω-3 PUFA supplementation. Moreover, the combined treatment of ω-3 PUFA and Rp significantly inhibited glycolysis and glutamine metabolism. The anti-tumor effects of this combination treatment were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. CONCLUSION: Our study revealed that ω-3 PUFA enhanced the anti-tumor activity of Rp while minimizing its side effects in vitro and in vivo. These results provide novel insights into the mechanisms underlying the potential beneficial effects of Rp combined with ω-3 PUFAs on the prevention of breast cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Sirolimo/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Ácido Láctico/metabolismo , Células MCF-7 , Malondialdeído/metabolismo , Metabolômica , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sirolimo/uso terapêutico
8.
Lipids Health Dis ; 16(1): 136, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28697730

RESUMO

BACKGROUND: α-linolenic acid (ALA) is an n-3 polyunsaturated fatty acid (PUFA) and the substrate for long-chain n-3 PUFAs. The beneficial effects of ALA on chronic diseases are still in dispute, unlike those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). METHODS: The primary objective of this investigation was to evaluate the efficiency of ALA uptake from a vegetable oil source and its subsequent conversion to n-3 long-chain PUFAs (LCPUFAs) in the tissues of growing mice, and to investigate its protective role in a prostate cancer animal model. We carried out the investigation in prostate-specific Pten-knockout mice with specified low-ALA (L-ALA, 2.5%) and high-ALA (H-ALA, 7.5%) diets. Total fatty acids in blood, liver, epididymal fat pad, prostate were detected and prostate weight were adjusted for body weight (mg/25 g). RESULTS: We found that dietary ALA triggered significant increases in ALA, EPA, docosapentaenoic acid (DPA) and DHA levels and a significant decrease in arachidonic acid levels during the mice's growth stage. A dose-dependent effect was observed for ALA, EPA and DPA, but not DHA. Furthermore, the average prostate weights in the L-ALA and H-ALA groups were lower than those in the control and n-6 groups, and similar to those in the EPA and n-3 groups. CONCLUSIONS: Our data suggest that dietary supplementation with ALA is an efficient means of improving n-3 LCPUFAs in vivo, and it has a biologically effective role to play in prostate cancer, similar to that of fish oils.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/metabolismo , Ácido alfa-Linolênico/sangue , Ácido alfa-Linolênico/metabolismo , Animais , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/sangue , Ácido Eicosapentaenoico/metabolismo , Masculino , Camundongos , Camundongos Knockout
9.
Food Funct ; 8(8): 2847-2856, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28726934

RESUMO

Numerous medicinal plants have been reported to prevent various chronic diseases. In this study, we screened a new FASN inhibitor-alcohol extract of clove (AEC) using a fast microplate method developed in our laboratory. The major components of AEC were: eugenol (42.27%), acetyl eugenol (29.12%), caryophyllene (15.40%), and humulene (3.22%). Fatty acid synthase (FASN) is a key enzyme for de novo lipogenesis, and it has been suggested as a potential therapeutic target in cancer and obesity. We have tested the ability of AEC to inhibit FASN in mammalian cells and tissues. Furthermore, we found that AEC as a FASN inhibitor could inhibit the S-phase DNA replication of HepG2 cells and adipocyte differentiation of OP9 cells. AEC also limited the development of high fat diet (HFD) induced obesity. AEC supplementation significantly reduced body weight and abdominal adipose tissue weight, lowered lipid accumulation in the liver and epididymal adipose tissue compared with the HFD control group. The serum lipid profiles showed that AEC could regulate the content of total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C). Collectively, our data suggest that FASN inhibitor AEC is a potential therapeutic agent for obesity.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Ácido Graxo Sintases/antagonistas & inibidores , Obesidade/prevenção & controle , Extratos Vegetais/administração & dosagem , Syzygium/química , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/enzimologia , Tecido Adiposo/metabolismo , Animais , Modelos Animais de Doenças , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/biossíntese , Humanos , Lipoproteínas LDL/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Triglicerídeos/metabolismo
10.
Lipids Health Dis ; 16(1): 10, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28095863

RESUMO

BACKGROUND: Dietary polyunsaturated fatty acids (PUFAs), especially n-3 PUFAs, are important for human health. The intestinal tract, a location that is heavily colonized by microorganisms, is the main organ for absorbing fatty acids. METHODS: The purpose of this study was to analyze the effects of dietary n-3 and n-6 PUFAs on the distribution of different types of fatty acids and their bioavailability along the gut. Mice were fed for a week with experimental diets containing high n-3 or high n-6 fatty acid levels. Blood was collected at different time points, and after 7 days the mice were euthanized and their digestive tract was divided into 17 segments for fatty acids analyses. RESULTS: We found that supplementing n-3 fatty acids significantly changed the ratio of n-6/n-3 PUFAs, increased the bioavailability of n-3 PUFAs, and altered fatty acid distribution. In addition, in the n-3 diet group, the absorption of saturated fatty acids (SFAs) along the gut was found to be inhibited, which was confirmed by feeding the mice with a diet containing deuterium-labeled palmitic acid and stearic acid. CONCLUSION: These results show that a diet rich in n-3 PUFAs can significantly modify the distribution and bioavailability of fatty acids, and particularly, may block the absorption of SFAs in the mouse gastrointestinal (GI) tract.


Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3 , Ácidos Graxos/metabolismo , Trato Gastrointestinal/metabolismo , Animais , Disponibilidade Biológica , Masculino , Camundongos
11.
ACS Chem Biol ; 9(1): 156-63, 2014 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-24147816

RESUMO

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) and is characterized by the destruction of myelin and axons leading to progressive disability. Peptide epitopes from CNS proteins, such as myelin oligodendrocyte glycoprotein (MOG), possess promising immunoregulatory potential for treating MS; however, their instability and poor bioavailability is a major impediment for their use clinically. To overcome this problem, we used molecular grafting to incorporate peptide sequences from the MOG35-55 epitope onto a cyclotide, which is a macrocyclic peptide scaffold that has been shown to be intrinsically stable. Using this approach, we designed novel cyclic peptides that retained the structure and stability of the parent scaffold. One of the grafted peptides, MOG3, displayed potent ability to prevent disease development in a mouse model of MS. These results demonstrate the potential of bioengineered cyclic peptides for the treatment of MS.


Assuntos
Esclerose Múltipla/prevenção & controle , Glicoproteína Mielina-Oligodendrócito/química , Glicoproteína Mielina-Oligodendrócito/uso terapêutico , Peptídeos Cíclicos/química , Peptídeos Cíclicos/uso terapêutico , Sequência de Aminoácidos , Animais , Encefalomielite Autoimune Experimental/prevenção & controle , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Dados de Sequência Molecular , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Peptídeos Cíclicos/imunologia
12.
Zhongguo Zhong Yao Za Zhi ; 39(22): 4442-7, 2014 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-25850282

RESUMO

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.


Assuntos
Envelhecimento/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ginsenosídeos/farmacologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley
13.
J Am Coll Cardiol ; 61(21): 2185-92, 2013 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-23541964

RESUMO

OBJECTIVES: This study investigated the feasibility of noninvasive renal sympathetic denervation (RSD) by using the novel approach of extracorporeal high-intensity focused ultrasound (HIFU). BACKGROUND: Catheter-based RSD has achieved promising clinical outcomes. METHODS: Under the guidance of Doppler flow imaging, therapeutic ablations (250 W × 2 s) were performed by using extracorporeal HIFU on the bilateral renal nerves (36.3 ± 2.8 HIFU emissions in each animal) in a mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar procedures without acoustic energy treatment were conducted in 5 canines of the sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma noradrenaline (NA) level, and renal function were determined on days 0, 6, and 28. Pathological examinations were performed on all retrieved samples. RESULTS: All of the animals survived the treatment. After ablation, BP and NA significantly decreased compared with the baseline values (BP changed -15.9/-13.6 mmHg, NA changed -55.4% [p < 0.001] 28 days after ablation]) and compared with the sham group on days 6 and 28. Ablation lesions around the renal artery adventitia were observed on day 6. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation on day 28. No procedure-related complications were observed. CONCLUSIONS: Effective RSD was successfully achieved by using the extracorporeal HIFU method in canines. Thus, noninvasive HIFU may be further explored as an important and novel strategy for RSD.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Hipertensão/cirurgia , Rim/inervação , Simpatectomia/métodos , Animais , Pressão Sanguínea , Cateterismo , Modelos Animais de Doenças , Cães , Estudos de Viabilidade , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Fluxo Sanguíneo Regional , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia , Circulação Renal , Ultrassonografia Doppler
14.
J Immunol ; 181(11): 7571-80, 2008 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19017946

RESUMO

Autoimmune diseases are incurable. We have hypothesized that these diseases can be cured by the transplantation of bone marrow (BM) stem cells that have been genetically engineered to express self-Ag. Here we have tested this hypothesis in experimental autoimmune encephalomyelitis (EAE) induced by the self-Ag myelin oligodendrocyte glycoprotein (MOG). We show that, in mice, transplantation of BM genetically modified to express MOG prevented the induction and progression of EAE, and combined with antecedent corticosteroid treatment, induced long-term remission of established disease. Mice remained resistant to EAE development upon subsequent rechallenge with MOG. Transfer of BM from these mice rendered recipients resistant to EAE. Splenocytes from these mice failed to proliferate or produce IL-17, IFN-gamma, and GM-CSF in response to MOG(35-55) peptide stimulation and they failed to produce MOG autoantibody. Mechanistically, we demonstrated in vivo reduction in development of CD4(+) MOG(35-55)-specific thymocytes, indicative of clonal deletion with no evidence for selection of Ag-specific regulatory T cells. These findings validate our hypothesis that transplantation of genetically modified BM expressing disease-causative self-Ag provides a curative approach by clonal deletion of disease-causative self-reactive T cells.


Assuntos
Autoantígenos/imunologia , Transplante de Medula Óssea , Deleção Clonal/imunologia , Encefalomielite Autoimune Experimental/imunologia , Glicoproteínas/imunologia , Tolerância Imunológica/imunologia , Fragmentos de Peptídeos/imunologia , Linfócitos T Reguladores/imunologia , Corticosteroides/farmacologia , Animais , Autoanticorpos/genética , Autoanticorpos/imunologia , Autoantígenos/genética , Deleção Clonal/efeitos dos fármacos , Deleção Clonal/genética , Citocinas/genética , Citocinas/imunologia , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/terapia , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Glicoproteínas/genética , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/genética , Imunidade Inata/genética , Imunidade Inata/imunologia , Camundongos , Camundongos Transgênicos , Glicoproteína Mielina-Oligodendrócito , Fragmentos de Peptídeos/genética , Timo/imunologia , Transdução Genética
15.
Autoimmunity ; 41(5): 405-13, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18568646

RESUMO

Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis (MS). EAE, induced by immunisation with myelin-associated autoantigens, is characterised by an inflammatory infiltrate in the central nervous system (CNS) associated with axonal degeneration, demyelination and damage. We have recently shown in an experimental mouse model of autoimmune gastritis that methylprednisolone treatment induces a reversible remission of gastritis with regeneration of the gastric mucosa. Here, we examined the effect of oral methylprednisolone on the mouse EAE model of human MS induced by immunisation with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)). We examined the clinical scores, CNS pathology and lymphocyte reactivity to MOG(35-55) following treatment and withdrawal of the steroid. Methylprednisolone remitted the clinical signs of EAE and the inflammatory infiltrate in the CNS, accompanied by loss of lymphocyte reactivity to MOG(35-55) peptide. Methylprednisolone withdrawal initiated relapse of the clinical features, a return of the CNS inflammatory infiltrate and lymphocyte reactivity to MOG(35-55) peptide. This is the first study to show that methylprednisolone induced a reversible remission in the clinical and pathological features of EAE in mice accompanied by loss of lymphocyte reactivity to the encephalitogen. This model will be useful for studies directed at a better understanding of mechanisms associated with steroid-induced disease remission, relapse and remyelination and also as an essential adjunct to an overall curative strategy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Metilprednisolona/uso terapêutico , Animais , Encéfalo/patologia , Proliferação de Células , Células Cultivadas , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/patologia , Feminino , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Proteínas da Mielina , Glicoproteína Associada a Mielina/imunologia , Glicoproteína Mielina-Oligodendrócito , Indução de Remissão , Medula Espinal/patologia
16.
Huan Jing Ke Xue ; 29(11): 3124-7, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19186814

RESUMO

Aerobic granules were cultivated with synthetic wastewater and were added in the course of aerobic starvation. Results showed that EPS produced by aerobic granules was composed of 40% biodegradable and 60% nonbiodegradable EPS. Among these, only biodegradable EPS could be utilized by their producers, while nonbiodegradable EPS contributed to maintain the spatial structures of aerobic granules. EPS extracted from fresh aerobic granules was fed as the sole carbon source to their own producers and activated sludge and was utilized by them. The average biodegradation rate of activated sludge in terms of EPS was 1.5 times faster than that of aerobic granules. When EPS extracted from starved aerobic granules was fed as the sole carbon source to their own producers and activated sludge, it could not be utilized and could not be energy source.


Assuntos
Biopolímeros/metabolismo , Reatores Biológicos , Matriz Extracelular/metabolismo , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Aerobiose , Biodegradação Ambiental , Biopolímeros/química , Matriz Extracelular/química
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