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1.
Front Immunol ; 12: 650176, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512619

RESUMO

Diabetes-related cognitive dysfunction (DRCD) is a serious complication induced by diabetes. However, there are currently no specific remedies for DRCD. Here, we show that streptozotocin-induced DRCD can be prevented without causing side effects through oral administration of lipopolysaccharide (LPS) derived from Pantoea agglomerans. Oral administration of LPS (OAL) prevented the cerebral cortex atrophy and tau phosphorylation induced by DRCD. Moreover, we observed that neuroprotective transformation of microglia (brain tissue-resident macrophages) is important for preventing DRCD through OAL. These findings are contrary to the general recognition of LPS as an inflammatory agent when injected systemically. Furthermore, our results strongly suggest that OAL promotes membrane-bound colony stimulating factor 1 (CSF1) expression on peripheral leukocytes, which activates the CSF1 receptor on microglia, leading to their transformation to the neuroprotective phenotype. Taken together, the present study indicates that controlling innate immune modulation through the simple and safe strategy of OAL can be an innovative prophylaxis for intractable neurological diseases such as DRCD. In a sense, for modern people living in an LPS-depleted environment, OAL is like a time machine that returns microglia to the good old LPS-abundant era.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Complicações do Diabetes/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Pantoea/química , Administração Oral , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Células Cultivadas , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Transdução de Sinais
2.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34328201

RESUMO

Diabetes­associated neuronal dysfunction (DAND) is one of the serious complications of diabetes, but there is currently no remedy for it. Streptozotocin [2­deoxy­2­(3­methy1­3­nitrosoureido) D­glucopyranose; STZ] is one of the most well­established diabetes inducers and has been used in vivo and in vitro DAND models. The aim of the present study was to demonstrate that C8­B4 microglia transformed by the stimulus of repetitive low­dose lipopolysaccharide (LPSx3­microglia) prevent STZ­induced Neuro­2a neuronal cell death in vitro. The ELISA results showed that neurotrophin­4/5 (NT­4/5) secretion was promoted in LPSx3­microglia and the cell viability assay with trypan blue staining revealed that the culture supernatant of LPSx3­microglia prevented STZ­induced neuronal cell death. In addition, reverse transcription­quantitative PCR showed that neurons treated with the culture supernatant of LPSx3­microglia promoted the gene expression of B­cell lymphoma­extra large and glucose­dependent insulinotropic polypeptide receptor. Furthermore, the inhibition of tyrosine kinase receptor B, a receptor of NT­4/5, suppressed the neuroprotective effect of LPSx3­microglia. Taken together, the present study demonstrated that LPSx3­microglia prevent STZ­induced neuronal death and that NT­4/5 may be involved in the neuroprotective mechanism of LPSx3­microglia.


Assuntos
Morte Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Neurônios/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Glicoproteínas de Membrana/antagonistas & inibidores , Camundongos , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Receptores dos Hormônios Gastrointestinais/genética , Estreptozocina/farmacologia , Proteína bcl-X/genética
3.
Anticancer Res ; 41(8): 4053-4059, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281874

RESUMO

BACKGROUND/AIM: Diabetes is a risk factor for dementia. However, no radical preventive method for diabetes-associated dementia has yet been developed. Our previous study revealed that oral administration of lipopolysaccharide (LPS) prevents high-fat diet-induced cognitive impairment. Therefore, we investigated here whether oral administration of LPS (OAL) could also prevent diabetes-associated dementia. MATERIALS AND METHODS: Diabetic mice were produced by intraperitoneal administration of streptozotocin (STZ), and then mice were orally administered LPS. Cognitive ability was evaluated using the Morris water maze, and gene expression was analyzed in isolated microglia. RESULTS: OAL prevented STZ-induced diabetic cognitive impairment, but did not affect blood glucose levels. Moreover, OAL promoted the expression of neuroprotective genes in microglia, such as heat shock protein family 40 (HSP40) and chemokine CCL7. CONCLUSION: OAL prevents diabetes-associated dementia, potentially via promotion of HSP40 and CCL7 expression in microglia.


Assuntos
Disfunção Cognitiva/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Administração Oral , Animais , Glicemia/efeitos dos fármacos , Quimiocina CCL7/genética , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/genética , Proteínas de Choque Térmico HSP40/genética , Lipopolissacarídeos/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia
4.
Anticancer Res ; 41(8): 4071-4076, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281876

RESUMO

BACKGROUND/AIM: Increased expression of inflammatory cytokine genes through cell interactions in tissues may cause chronic inflammation, leading to the development of lifestyle-related diseases. Since the activation of inflammatory cytokine genes in monocytes/macrophages by co-culturing with cancer cells or adipocytes was suppressed by pre-treatment with low-dose lipopolysaccharide (LPS), we hypothesized that low-dose LPS-activated macrophages may regulate the expression of immune response-related genes in other cells. MATERIALS AND METHODS: Phorbol myristate acetate-treated human monocytes (THP-1) were activated by LPS. The conditioned medium of LPS-activated THP-1 cells was added to human adipocytes. After 5 days, the expression of genes encoding interleukin (IL)-6 (IL6), IL-8 (IL8), monocyte chemotactic protein (MCP)-1 (CCL2), adiponectin (ADIPOQ), and plasminogen activator inhibitor (PAI)-1 (SERPINE1) was analyzed using quantitative real-time PCR. RESULTS: The increased expression of inflammation-related genes and SERPINE1 in adipocytes was suppressed by the conditioned medium of THP-1 cells activated by low-dose LPS, whereas the expression of ADIPOQ was significantly increased. CONCLUSION: Low-dose LPS-activated macrophages convert adipocytes to anti-inflammatory phenotypes.


Assuntos
Adipócitos/metabolismo , Adiponectina/genética , Citocinas/genética , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/genética , Linhagem Celular , Humanos , Ativação de Macrófagos
5.
Anticancer Res ; 41(8): 4093-4100, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281880

RESUMO

BACKGROUND/AIM: We investigated the effect of Kumaizasa leaf extract (KLE) on innate immunity using the HEK293 and RAW 264.7 cell lines. MATERIALS AND METHODS: KLE, lipopolysaccharides (LPS), or KLE with LPS were added to RAW 264.7 cells. The TNF-α and IL-1ß mRNA expression was then quantified. The expression of MAPKs, NFĸB, TNF-α and IL-1ß proteins was also quantified. In addition, KLE was added to HEK293 cells and the IL-8 concentration was measured. RESULTS: In RAW 264.7 cells, KLE increased the levels of TNF-α and IL-1ß mRNA. By contrast, when KLE and LPS were added to RAW 264.7 cells, the increase in TNF-α and IL-1ß mRNA was ameliorated. Similarly, the expression of JNK and ERK proteins was reduced. The addition of KLE to HEK293 cells induced IL-8 production. CONCLUSION: Based on these results, a KLE-mediated mechanism may regulate immunity by suppressing the expression of JNK and ERK, which are involved in inflammatory signal transduction.


Assuntos
Imunidade Inata/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sasa , Animais , Citocinas/genética , Citocinas/imunologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Células HEK293 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Folhas de Planta , Células RAW 264.7
6.
Anticancer Res ; 40(8): 4457-4464, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727775

RESUMO

BACKGROUND/AIM: Our previous studies suggested that oral administration of lipopolysaccharide (LPS) regulates the progression of various diseases via transformation of tissue-resident macrophages (MΦ). Recently, we characterized microglia transformed by repetitive low-dose LPS treatment (REPELL-microglia) in vitro, and this response was similar to that observed in response to oral administration of LPS in vivo. Here, we examined the characteristics of peritoneal tissue-resident MΦ (pMΦ) transformed by repetitive low-dose LPS treatment (REPELL-pMΦ). MATERIALS AND METHODS: Primary pMΦ were treated with low-dose LPS (1 ng/ml) three times; subsequently, phagocytic activity and gene expression were evaluated. RESULTS: REPELL-pMΦ exhibited high phagocytic activity and elevated expression of Arg1, Gipr, Gdnf, and Fpr2. The gene expression profiles observed in REPELL-pMΦ were distinct from those of REPELL-microglia. CONCLUSION: REPELL-pMΦ have the potential to promote clearance of xenobiotics and to suppress inflammation. The present study also demonstrates the diversity of tissue-resident MΦ transformation that reflect their tissue origin.


Assuntos
Arginase/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Lipopolissacarídeos/efeitos adversos , Macrófagos Peritoneais/fisiologia , Receptores de Formil Peptídeo/genética , Receptores dos Hormônios Gastrointestinais/genética , Administração Oral , Animais , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Especificidade de Órgãos , Fagocitose/efeitos dos fármacos , Fenótipo , Cultura Primária de Células , Regulação para Cima
7.
Anticancer Res ; 40(8): 4681-4685, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727792

RESUMO

BACKGROUND/AIM: The functions of macrophages change in response to environmental factors such as lipopolysaccharide (LPS). LPS derived from Pantoea agglomerans (LPSp) is involved in macrophage activation and tissue repair when administered dermally. LPSp-activated macrophages may be useful for restoring and maintaining homeostasis of the skin. MATERIALS AND METHODS: Phorbol myristate acetate-treated human monocytes (THP-1 cells) were activated with LPSp. The medium of LPSp-activated THP-1 cells was added to normal human dermal fibroblasts (NHDF cells). After 24 h, the expression of hyaluronan (HA) synthase (HAS)2, hyaluronidase (HYAL)1, and tropoelastin in NHDF cells was analyzed using quantitative real-time PCR. RESULTS: The expression of HAS2 and tropoelastin was significantly increased, but that of HYAL1 was significantly decreased. It was demonstrated that the abilities of HA and elastin synthesis in NHDF cells increased through LPSp-activated THP-1 cells. CONCLUSION: LPSp-activated macrophages may be useful for enhancing the abilities of HA and elastin synthesis in fibroblasts, subsequently improving dysfunction and reducing various age-related disorders.


Assuntos
Elastina/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ácido Hialurônico/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Linhagem Celular , Humanos , Ativação de Macrófagos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pantoea/metabolismo , Fagocitose/efeitos dos fármacos , Células Th1
8.
Anticancer Res ; 40(8): 4711-4717, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727797

RESUMO

BACKGROUND: Continuous oral administration of lipopolysaccharide (LPS) enhances the phagocytic ability of macrophages, which is useful for preventing various diseases. Here, we attempted to create an in vitro model of continuous administration of LPS. MATERIALS AND METHODS: RAW264.7 cells were stimulated with LPS three times every 24 h (repeated stimulation), and phagocytic ability and inflammatory cytokine [interleukin-6 (IL6) and tumor necrosis factor-α (TNFα)] production were measured. RESULTS: The phagocytic ability was increased by a single stimulation with LPS and was maintained by repeated stimulation. IL6 production increased with a single stimulation with LPS; however, IL6 production by repeated stimulation with LPS was comparable to that of non-stimulation with LPS. On the other hand, the amount of TNFα was significantly increased by single and repeated stimulation with LPS. CONCLUSION: Repeated stimulation with LPS in RAW264.7 cells triggered a phenotype that was similar to that of macrophages after continuous oral administration of LPS. This suggests that this study model may reproduce the enhancement of macrophage phagocytosis, an effect afforded by continuous oral administration of LPS.


Assuntos
Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Animais , Linhagem Celular , Citocinas/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
9.
Anticancer Res ; 40(8): 4719-4727, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727798

RESUMO

BACKGROUND/AIM: We investigated whether mastication affects microglia, whose activity is thought to be associated with cognition and brain tumor progression. MATERIALS AND METHODS: We kept mice by feeding either a hard or soft diet for 2, 4 or 8 months. After each period, we removed the whole brains and isolated microglia. The total RNA extracted from each brain's microglia was subjected to DNA microarray analysis. RESULTS: Many genes were found to be significantly differentially expressed between hard- and soft-diet-fed mice in each group of the same feeding period. The expression of several genes involved in the regulation of actin cytoskeleton was down-regulated in the soft-diet-fed mice. CONCLUSION: Mastication may affect microglia's roles in cognition as well as their neuroimmune activity through their activity of patrolling the brain.


Assuntos
Mastigação/fisiologia , Microglia/fisiologia , Transcriptoma/fisiologia , Animais , Encéfalo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C3H
10.
Anticancer Res ; 40(8): 4755-4762, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727802

RESUMO

BACKGROUND: Developmental disorders are associated with microglial dysfunction. Oral administration of lipopolysaccharide derived from Pantoea agglomerans bacteria (LPSp) leads to normalization of phagocytic activity of microglia and suppression of inflammation in mice. In this article, we report on a successful trial in which we achieved a significant improvement of symptoms in patients with developmental disorders. PATIENTS AND METHODS: Five pediatric patients diagnosed with autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD) who visited our clinic received either 0.75 or 1 mg/day LPSp for 6 months or more, in addition to our usual therapy regimens (detoxification therapy, nutritional therapy, and vibration therapy). A survey questionnaire was completed by the patients' parents and evaluated using the Numerical Rating Scale. RESULTS: Behavior, verbal ability, and communication disabilities associated with ASD/ADHD improved in all patients. CONCLUSION: Oral administration of LPSp may represent a new treatment option in the area of developmental disorders where there is currently no treatment available.


Assuntos
Deficiências do Desenvolvimento/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Criança , Pré-Escolar , Citocinas/metabolismo , Deficiências do Desenvolvimento/metabolismo , Feminino , Humanos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fagocitose/efeitos dos fármacos
11.
Sci Rep ; 10(1): 8945, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488176

RESUMO

Although lipopolysaccharide (LPS) is regarded as an inducer of inflammation, previous studies have suggested that repetitive low-dose LPS has neuroprotective effects via immunomodulation of microglia, resident macrophages of brain. However, microglia transformed by the stimulus of repetitive low-dose LPS (REPELL-microglia) are not well characterized, whereas microglia transformed by repetitive high-dose LPS are well studied as an endotoxin tolerance model in which the induction of pro-inflammatory molecules is suppressed. In this study, to characterize REPELL-microglia, the gene expression and phagocytic activity of REPELL-microglia were analyzed with the murine C8-B4 microglia cell line. The REPELL-microglia were characterized by a high expression of pro-inflammatory molecules (Nos2, Ccl1, IL-12B, and CD86), anti-inflammatory molecules (IL-10, Arg1, Il13ra2, and Mrc1), and neuroprotective molecules (Ntf5, Ccl7, and Gipr). In addition, the phagocytic activity of REPELL-microglia was promoted as high as that of microglia transformed by single low-dose LPS. These results suggest the potential of REPELL-microglia for inflammatory regulation, neuroprotection, and phagocytic clearance. Moreover, this study revealed that gene expression of REPELL-microglia was distinct from that of microglia transformed by repetitive high-dose LPS treatment, suggesting the diversity of microglia transformation by different doses of LPS.


Assuntos
Lipopolissacarídeos/farmacologia , Microglia/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fenótipo , Transdução de Sinais/efeitos dos fármacos
12.
Food Sci Nutr ; 7(11): 3520-3526, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763002

RESUMO

Compared with regular brown rice, dewaxed brown rice (DBR), prepared by excluding only the wax layer in the outermost layer of brown rice using a new rice milling technique, has improved water absorbency, digestibility, and taste. Dewaxed brown rice has a nutritional value close to that of brown rice and contains a large amount of lipopolysaccharides (LPS), which are known to improve the cognitive function of mice. In this study, we examined the effect of continuous DBR ingestion on the cognitive function of elderly people. A crossover comparison test was performed, in which elderly people who moved into an elderly welfare facility were divided into two groups and ingested DBR or polished white rice for three meals a day for 6 months, followed by a change in test meals for the next 6 months. Cognitive function was assessed using Revised Hasegawa's Dementia Scale (HDS-R) before starting the test and 6 months after ingesting each test meal. No subjects withdrew or discontinued DBR intake during the study period, and all subjects continued the test for 6 months. In subjects with low cognitive function (defined as subjects with HDS-R total score of ≥1 but <10 at the start of the study), there was a significant association between continuous DBR ingestion and cognitive function improvement (increase in total HDS-R score). Our findings suggest that the long-term DBR ingestion as a staple food could be useful for preventing cognitive decline in elderly; it offers an easily implemented option as a daily diet for preventing cognitive decline.

13.
J Nutr Sci Vitaminol (Tokyo) ; 65(Supplement): S122-S124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31619610

RESUMO

Dewaxed brown rice (DBR), which is prepared by removing only the outermost wax layer of brown rice using a new rice milling technique, has improved water absorbency, digestibility, and taste compared to regular brown rice. DBR has a nutritional value close to that of brown rice, including a rich amount of lipopolysaccharides that are known to improve cognitive function in mice. This study thus aimed to verify the influence of continuous DBR ingestion on cognitive function among elderly individuals. The present study employed a crossover comparison design using the Revised Hasegawa Dementia Scale to assess cognitive function. Our findings confirmed that long-term DBR ingestion contributed to the prevention and reduction of overall cognitive decline, especially among elderly individuals with low cognitive function. Thus, DBR has the potential to be a useful staple food that maintains brain homeostasis among elderly individuals.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/prevenção & controle , Dieta/métodos , Ingestão de Alimentos/fisiologia , Oryza/química , Idoso , Feminino , Humanos , Masculino , Valor Nutritivo
14.
Anticancer Res ; 39(8): 4475-4478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366547

RESUMO

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 ß, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.


Assuntos
Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Quimiocina CCL2/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Interleucina-1beta/genética , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Neoplasias/genética , Obesidade/patologia , Fator de Necrose Tumoral alfa/genética
15.
Anticancer Res ; 39(8): 4503-4509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366552

RESUMO

BACKGROUND/AIM: Oral administration of Pantoea agglomerans-derived lipopolysaccharide (LPSp) has been reported to have a preventive effect against various lifestyle-related diseases. Therefore, we examined the preventive effect on high blood pressure, which is a kind of reserve arm for lifestyle-related diseases. MATERIALS AND METHODS: Spontaneous hypertensive rat (SHR) and WKY rat were bred from 6 to 16 weeks of age. SHR were orally administered 100 µg/kg LPSp and 0.1% NaCl, and blood pressure was measured at 6, 10, 13 and 16 weeks. Furthermore, at 16 weeks of age, blood biochemical markers were measured and microbial community composition was analyzed. RESULTS: SHRs developed hypertension with age, which was exacerbated by salt loading. Although there was almost no reduction in blood pressure in SHRs that received LPSp. It was suppressed at 13-16 weeks of age in those with salt loading. CONCLUSION: Oral administration of LPSp showed a preventive effect on salt-loaded hypertension.


Assuntos
Citocinas/genética , Hipertensão/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipertensão/genética , Hipertensão/patologia , Lipopolissacarídeos/química , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Sais/toxicidade
16.
Anticancer Res ; 39(8): 4511-4516, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366553

RESUMO

BACKGROUND/AIM: Gluconacetobacter hansenii (G. hansenii) is an acetic acid bacterium of vinegar production. Its anti-allergic effect on mice upon oral administration was examined. MATERIALS AND METHODS: The amount of LPS was measured by the Limulus reaction. Mice were sensitized by peritoneal and intranasal administration of cedar pollen and alum followed by oral administration of 30 or 150 mg/kg of heated G. hansenii cells. Pollen was administered intranasally to evaluate nasal symptoms, and at 8 weeks, IgE and IL-10 levels in blood were measured by ELISA. RESULTS: The amount of LPS in dried bacterial cells was 10.4±3.3 mg/g. In the cedar pollinosis model of mice, a significant reduction was observed in nose scratching of both groups administered with the bacterial cells (30, 150 mg/kg). CONCLUSION: G. hansenii contains LPS, and its oral administration showed an anti-allergic effect by a significant mitigation of the symptoms in a pollen allergy mouse model.


Assuntos
Antialérgicos/administração & dosagem , Gluconacetobacter/imunologia , Pólen/efeitos adversos , Rinite Alérgica Sazonal/prevenção & controle , Ácido Acético/química , Administração Oral , Alérgenos/efeitos adversos , Animais , Antialérgicos/imunologia , Modelos Animais de Doenças , Humanos , Imunoglobulina E/imunologia , Camundongos , Rinite Alérgica Sazonal/microbiologia , Rinite Alérgica Sazonal/patologia
17.
Anticancer Res ; 38(7): 4289-4294, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970563

RESUMO

BACKGROUND/AIM: A system is being developed that can be used to easily evaluate the health condition of an individual with the help of trace amounts of a blood sample by focusing on xenobiotics. The system is called "Multimodal homeostasis evaluation system" (measurement of neutrophil activity, phagocytic activity of phagocytes and quantification of oxidized LDL (OxLDL)). To elucidate the possibility of using this system as an evaluation system for the health condition of an individual, clearly explaining the changes in various diseases is essential. In this study, evaluations were carried out using hypertensive model animals. MATERIALS AND METHODS: Spontaneously hypertensive model rats SHR/NCrlCrlj and control rats WKY/NCrlCrlj were raised for 10 weeks from 6 to 16 weeks of age and their blood pressure was measured over time. Blood neutrophil activity (superoxide anion (O2•-) generation and myeloperoxidase (MPO) activity) and phagocytic activity of phagocytes was measured by our developed apparatus (a simple prototype device under development). OxLDL was measured by an ELISA kit, and biochemical markers were measured using the blood sample. RESULTS: Compared to WKY rats of the control group, systolic blood pressure, diastolic blood pressure, and mean blood pressure of SHR rats increased significantly with age. In SHR rats, there was a significant elevation in O2•- generation and MPO activity of neutrophils, alanine aminotransferase and triglycerides of blood, while phagocytic activity, OxLDL, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol and total-bilirubin decreased. CONCLUSION: In the hypertensive model, biochemical markers were found to have a relationship with O2•- generation, MPO activity, phagocytic activity of phagocytes, and OxLDL. This system is expected to be useful for clinical monitoring of hypertension diseases.


Assuntos
Biomarcadores/sangue , Hipertensão/sangue , Lipoproteínas LDL/análise , Neutrófilos , Animais , Modelos Animais de Doenças , Masculino , Fagocitose , Ratos , Ratos Endogâmicos SHR
18.
Anticancer Res ; 38(7): 4339-4345, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970571

RESUMO

BACKGROUND/AIM: Dewaxed brown rice has macrophage activation ability via TLR4 and contains a high amount of lipopolysaccharides (LPS). It is expected that dewaxed brown rice can help prevent lifestyle diseases. In this study, the anti-obesity effect of dewaxed brown rice was investigated using obese and diabetic model mice. MATERIALS AND METHODS: Dewaxed brown rice and white rice were polished and powdered by Toyo Rice Co. Diet pellets were prepared (AIN-93) with 50% dewaxed brown rice or white rice powder and fed to type II diabetic model KK-Ay mice for 10 weeks. Weight and fasting blood glucose were measured every week, and whole blood and liver was collected on the final day for the evaluation of biochemical data. RESULTS: A 20% reduction in body weight was found in the dewaxed brown rice feed and white rice feed groups compared to the normal feed group. Fasting blood glucose increased in the normal-diet group, but on the other hand, the blood glucose in the white rice and the dewaxed brown rice feed group was almost constant. Dewaxed brown rice feed group of plasma ALT and AST, liver TG and T-CHO were significantly lower than that of the control and the white rice feed group. CONCLUSION: Dewaxed brown rice feed has an anti-obesity effect to suppress increasing body weight, fasting blood glucose, and an effect of suppressing fatty liver.


Assuntos
Diabetes Mellitus Tipo 2 , Fígado Gorduroso , Obesidade , Oryza , Animais , Dieta , Modelos Animais de Doenças , Feminino , Manipulação de Alimentos/métodos , Camundongos , Oryza/química
19.
Anticancer Res ; 38(7): 4375-4379, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970576

RESUMO

BACKGROUND/AIM: The wound-healing effect of lipopolysaccharide (LPS) reportedly results from its ability to induce the removal of foreign bodies, anti-inflammatory function, and tissue-repair function. We reported the improvement of patients with protracted wound healing after the dermal administration of topical cream containing LPS derived from Pantoea agglomerans, which is a symbiotic bacterium present in wheat and confirmed as safe. PATIENTS AND METHODS: Topical cream with LPS was applied on four patients who showed protracted wound healing, after their informed consent. The wound was evaluated on the basis of the change in the approximate wound volume calculated from the width, length, and depth of the wound. RESULTS: Case 1: A 76-year-old man developed infection at the puncture site after endovascular laser treatment of the right lower extremity varicose veins and suffered protracted wound healing. The wound was treated with gentamicin application containing LPS, and shrank in two weeks. Case 2: A 72-year-old man developed a wound infection and had purulent drainage one week after endovascular laser treatment of the left lower extremity varicose veins. The wound was closed in one month using gentamicin application containing LPS. Case 3: A 67-year-old woman with protracted wound healing developed infection in the right inguinal region after the surgical treatment of acute aortic dissection and experienced complete wound dehiscence. The wound shrank one week after gauze packing with LPS and was temporarily sutured. The wound was completely closed in two weeks with gentamicin application containing LPS. Case 4: An 86-year-old woman with protracted wound healing became bedridden after cerebral infarction and developed pressure ulcers in the sacral area. The ulcer disappeared in four months with LPS-containing sugar and povidone-iodine application twice a day. There were no adverse effects from LPS application in any of these patients. CONCLUSION: In diabetes, one cause of protracted wound healing is the low innate immune function, such as the phagocytic activity of macrophages. LPS is expected to promote healing by improving innate immunity, and its beneficial effect of promoting wound healing was clearly demonstrated in the present cases. The topical application of LPS is clinically effective for wound healing and is considered a potentially novel treatment method.


Assuntos
Lipopolissacarídeos/administração & dosagem , Pantoea , Cicatrização/efeitos dos fármacos , Administração Tópica , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
20.
PLoS One ; 13(6): e0198493, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29856882

RESUMO

The pathogenesis of Alzheimer's disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-ß (Aß) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aß clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aß clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aß phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aß burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aß phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.


Assuntos
Doença de Alzheimer/patologia , Dieta Hiperlipídica , Lipopolissacarídeos/uso terapêutico , Transtornos da Memória/prevenção & controle , Doenças Metabólicas/prevenção & controle , Pantoea/metabolismo , Administração Oral , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Glucose/metabolismo , Hemoglobina A Glicada/análise , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Doenças Metabólicas/patologia , Camundongos , Microglia/citologia , Microglia/metabolismo , Fagocitose
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