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1.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803858

RESUMO

Beta glucans are known to have immunomodulatory effects that mediated by a variety of mechanisms. In this article, we describe experiments and simulations suggesting that beta-1,3 glucans may promote activation of T cells by a previously unknown mechanism. First, we find that treatment of a T lymphoblast cell line with beta-1,3 oligoglucan significantly increases mRNA levels of T cell activation-associated cytokines, especially in the presence of the agonistic anti-CD3 antibody. This immunostimulatory activity was observed in the absence of dectin-1, a known receptor for beta-1,3 glucans. To clarify the molecular mechanism underlying this activity, we performed a series of molecular dynamics simulations and free-energy calculations to explore the interaction of beta-1,3 oligoglucans with potential immune receptors. While the simulations reveal little association between beta-1,3 oligoglucan and the immune receptor CD3, we find that beta-1,3 oligoglucans bind to CD28 near the region identified as the binding site for its natural ligands CD80 and CD86. Using a rigorous absolute binding free-energy technique, we calculate a dissociation constant in the low millimolar range for binding of 8-mer beta-1,3 oligoglucan to this site on CD28. The simulations show this binding to be specific, as no such association is computed for alpha-1,4 oligoglucan. This study suggests that beta-1,3 glucans bind to CD28 and may stimulate T cell activation collaboratively with T cell receptor activation, thereby stimulating immune function.


Assuntos
Antígenos CD28/metabolismo , Ativação Linfocitária/imunologia , Receptores Imunológicos/metabolismo , Linfócitos T/imunologia , beta-Glucanas/metabolismo , Antígenos CD28/química , Citocinas/metabolismo , Humanos , Células Jurkat , Modelos Moleculares , Ligação Proteica , Receptores Imunológicos/química , Termodinâmica , beta-Glucanas/química
2.
J Perinat Med ; 46(1): 53-57, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28245191

RESUMO

OBJECTIVE: The object of our study was to determine whether serum fibrinogen levels could be used to predict the success rates of balloon tamponade and decrease the use of invasive methods. METHODS: This retrospective study, conducted at Rinku General Medical Center, was aimed to identify factors associated with high success rates in balloon tamponade. Forty-six patients with postpartum hemorrhage (PPH), non-responsive to uterotonics and treated with balloon tamponade between April 2008 and March 2015, were included. RESULTS: Forty-six women were included, of which 34 underwent vaginal delivery and 12 underwent cesarean delivery. There were no complications from balloon tamponade and its success rate was 73.3%. Seven women required additional procedures: One used gauze packing, three used uterine artery embolization, and five underwent peripartum hysterectomy. The cut-off line of serum fibrinogen level was 172.5 mg/dL (P=0.002) with its 77.4% sensitivity and 66.7% specificity. CONCLUSION: We recommend measuring serum fibrinogen level for predicting whether the balloon tamponade can be used successfully or not.


Assuntos
Fibrinogênio/metabolismo , Hemorragia Pós-Parto/sangue , Tamponamento com Balão Uterino , Adulto , Feminino , Humanos , Hemorragia Pós-Parto/terapia , Gravidez , Estudos Retrospectivos , Adulto Jovem
3.
Biochem Biophys Res Commun ; 494(1-2): 379-383, 2017 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-28974421

RESUMO

Euglena gracilis Z is a micro-algae that is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of Euglena gracilis Z has ß-1, 3-glucan structure. Euglena gracilis Z and paramylon are reported to affect the immune system. In this study, we investigated the protective effects of Euglena gracilis Z and paramylon against influenza virus infection in mice. Euglena gracilis Z and paramylon were administered to mice as a 2% dietary mixture ad libitum. At 2 weeks after initiation of dietary administration, mice were infected intranasally with influenza virus A/PR/8/34 (H1N1). Survival rate was monitored 10 days after infection. In addition, we performed virus titer and cytokine profiles in the lung. High survival rates were observed for Euglena gracilis Z and paramylon-treated groups compared to the control group. Significantly lower virus titer in the lung was observed in the Euglena gracilis Z and paramylon-treated groups compared to the control group from day 1 after infection. Higher amount of IL-1ß, IL-6, IL-12 (p70), IFN-γ, and IL-10 was observed in the paramylon groups compared to the control group. Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon which provides protection against influenza virus infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Suplementos Nutricionais , Euglena gracilis/imunologia , Glucanos/administração & dosagem , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/dietoterapia , Administração Oral , Animais , Euglena gracilis/química , Feminino , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H1N1/patogenicidade , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-12/biossíntese , Interleucina-12/imunologia , Interleucina-1beta/biossíntese , Interleucina-1beta/imunologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Pulmão/imunologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/virologia , Análise de Sobrevida
4.
Cells ; 13(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38334622

RESUMO

Neuronal cell death is a key mechanism involved in the development and exacerbation of Parkinson's disease (PD). The excessive production of reactive oxygen species (ROS) is a major cause leading to neuronal death; therefore, compounds that prevent oxidative stress-dependent neuronal death may be promising as a preventive method for PD. Ergothioneine is a natural amino acid with antioxidant properties, and its protective functions in the body are attracting attention. However, there has been no investigation into the protective functions of ergothioneine using in vivo and in vitro PD models. Thus, in this study, we analyzed the efficacy of ergothioneine against 6-hydroxydopamine (6-OHDA)-dependent neuronal cell death using immortalized hypothalamic neurons (GT1-7 cells). First, we found that ergothioneine prevents 6-OHDA-dependent neuronal cell death by suppressing ROS overproduction in GT1-7 cells. The cytoprotective effect of ergothioneine was partially abolished by verapamil, an inhibitor of OCTN1, which is involved in ergothioneine uptake. Furthermore, ergothioneine-rich Rice-koji (Ergo-koji) showed cytoprotective and antioxidant effects similar to those of ergothioneine. Taken together, these results suggest that ergothioneine or foods containing ergothioneine may be an effective method for preventing the development and progression of PD.


Assuntos
Ergotioneína , Ergotioneína/farmacologia , Ergotioneína/metabolismo , Oxidopamina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neurotoxinas/farmacologia , Morte Celular , Antioxidantes/farmacologia , Antioxidantes/metabolismo
5.
Integr Cancer Ther ; 22: 15347354231195323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37646331

RESUMO

Extracts from Euglena gracilis have been shown to prevent cancer growth in mouse models. However, the molecular mechanism of this anti-cancer activity has not been determined nor has the effect of Euglena extracts on tobacco smoke carcinogen-induced carcinogenesis. Here, we investigate the hypothesis that this anti-cancer activity is a result of changes in the intestinal microbiota induced by oral administration of the extract. We found that a Euglena gracilis water extract prevents lung tumorigenesis induced by a tobacco smoke-specific carcinogen (NNK) in mice treated either 2 weeks before or 10 weeks after NNK injection. Both of these treatment regimens are associated with significant increases in 27 microbiota metabolites found in the mouse feces, including large increases in triethanolamine, salicylate, desaminotyrosine, N-acetylserine, glycolate, and aspartate. Increases in the short-chain fatty acids (SCFAs) including acetate, propionate and butyrate are also observed. We also detected a significant attenuation of lung carcinoma cell growth through the induction of cell cycle arrest and apoptosis caused by low levels of SCFAs. This study provides strong evidence of anti-cancer activity in Euglena gracilis extracts against tobacco smoke carcinogen-induced tumorigenesis and demonstrates that this activity is linked to increased production of specific gut microbiota metabolites and the resultant induction of cell cycle arrest and apoptosis of lung carcinoma cells.


Assuntos
Carcinoma , Euglena gracilis , Microbioma Gastrointestinal , Neoplasias Pulmonares , Poluição por Fumaça de Tabaco , Camundongos , Animais , Carcinógenos/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/prevenção & controle , Poluição por Fumaça de Tabaco/efeitos adversos , Carcinogênese/induzido quimicamente
6.
Front Nutr ; 10: 1113118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051126

RESUMO

Paramylon, a ß-1,3-glucan storage polysaccharide derived from Euglena gracilis, has various health benefits, such as anti-obesity effects and modulation of immune function. However, whether paramylon intake affects the circadian clock remains unknown. In this study, we examined the effect of paramylon intake on the circadian clock. The results showed that the paramylon intake regulated peripheral clocks in mice. Furthermore, cecal pH and short-chain fatty acid concentrations after paramylon intake were measured. The correlation between changes in the expression of clock-related genes and alterations in the intestinal environment was confirmed. In addition, peripheral clock entrainment by paramylon intake was not observed in antibiotic-treated mice whose gut microbiota was weakened. These findings suggest that the regulation of the circadian clock by paramylon intake was mediated by changes in gut microbiota. In addition, the entraining effect of paramylon intake was also confirmed in mice bred under conditions mimicking social jetlag, which implies that paramylon intake may contribute to recovery from social jetlag. Thus, the appropriate consumption of paramylon may have a beneficial effect on health from a chrono-nutritional perspective.

7.
Nutrients ; 14(3)2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35277036

RESUMO

The antitumor effects of a partially purified water extract from Euglena gracilis (EWE) and EWE treated by boiling (bEWE) were evaluated using orthotopic lung cancer syngeneic mouse models with Lewis lung carcinoma (LLC) cells. Daily oral administration of either EWE or bEWE started three weeks prior to the inoculation of LLC cells significantly attenuated tumor growth as compared to the phosphate buffered saline (PBS) control, and the attenuation was further enhanced by bEWE. The intestinal microbiota compositions in both extract-treated groups were more diverse than that in the PBS group. Particularly, a decrease in the ratio of Firmicutes to Bacteroidetes and significant increases in Akkermansia and Muribaculum were observed in two types of EWE-treated groups. Fecal microbiota transplantation (FMT) using bEWE-treated mouse feces attenuated tumor growth to an extent equivalent to bEWE treatment, while tumor growth attenuation by bEWE was abolished by treatment with an antibiotic cocktail. These studies strongly suggest that daily oral administration of partially purified water extracts from Euglena gracilis attenuates lung carcinoma growth via the alteration of the intestinal microbiota.


Assuntos
Carcinoma , Euglena gracilis , Microbioma Gastrointestinal , Neoplasias Pulmonares , Administração Oral , Animais , Pulmão , Neoplasias Pulmonares/prevenção & controle , Camundongos , Água/farmacologia
8.
Nutrients ; 14(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36558358

RESUMO

Wild watermelon contains various nutrients, but the effect of its acute ingestion on arterial stiffness is unclear. This study aimed to investigate whether a single bout of acute ingestion of wild watermelon-extracted juice decreased arterial stiffness concomitant with an increase in nitric oxide (NO) production. Twelve healthy young female participants were tested under two conditions in a randomized, double-blind crossover study: (1) a beverage containing 90 g of wild watermelon extract and (2) a control beverage: a placebo. Pulse wave velocity (PWV), an index of arterial stiffness, blood flow, and plasma nitrate/nitrite (NOx) levels were measured in the supine position at 30, 60, and 90 min after the intake of each beverage. The changes in femoral-ankle PWV were significantly reduced after wild watermelon-extracted juice intake compared to those in the placebo group. Additionally, the changes in blood flow in the posterior tibial artery and plasma NOx levels after intake of wild watermelon-extracted juice were significantly increased compared to those in the placebo group. These data show that acute ingestion of wild watermelon-extracted juice reduces peripheral (lower limb) arterial stiffness and increases NO bioavailability. To confirm these associations, more detailed investigations of the nutrients that influence these effects should be conducted.


Assuntos
Citrullus , Rigidez Vascular , Humanos , Feminino , Estudos Cross-Over , Óxido Nítrico/farmacologia , Projetos Piloto , Análise de Onda de Pulso , Suplementos Nutricionais , Ingestão de Alimentos , Pressão Sanguínea
9.
Food Sci Nutr ; 10(3): 926-935, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35282012

RESUMO

We previously demonstrated the anti-influenza activity of Citrullus lanatus var. citroides (wild watermelon, WWM); however, the active ingredient was unknown. Here, we performed metabolomic analysis to evaluate the ingredients of WWM associated with antiviral activity. Many low-molecular weight compounds were identified, with flavonoids accounting for 35% of all the compounds in WWM juice. Prenylated flavonoids accounted for 30% of the flavonoids. Among the measurable components of phytoestrogens in WWM juice, 8-prenylnaringenin showed the highest antiviral activity. We synthesized 8-prenylnaringenin and used liquid chromatography-mass spectrometry to quantitate the active ingredient in WWM. The antiviral activities of 8-prenylnaringenin were observed against H1N1 and H3N2 influenza A subtypes and influenza B viruses. Moreover, 8-prenylnaringenin was found to inhibit virus adsorption and late-stage virus replication, suggesting that the mechanisms of action of 8-prenylnaringenin may differ from those of amantadine and oseltamivir. We confirmed that 8-prenylnaringenin strongly inhibited the viral entry of all the influenza virus strains that were examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. This result indicates that 8-prenylnaringenin may activate the host cell's defense mechanisms, rather than directly acting on the influenza virus. Since 8-prenylnaringenin did not inhibit late-stage virus replication of oseltamivir-resistant strains, 8-prenylnaringenin may interact directly with viral neuraminidase. These results are the first report on the anti-influenza virus activity of 8-prenylnaringenin. Our results highlight the potential of WWM and phytoestrogens to develop effective prophylactic and therapeutic approaches to the influenza virus.

10.
Nutrients ; 14(14)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889858

RESUMO

A water extract derived from the isolated cell walls of Chlorella sorokiniana (C. sorokiniana, Chlorella water extract, CWE) was analyzed for the presence of lipopolysaccharide (LPS)-related material via the Limulus amebocyte lysate (LAL) assay and evaluated for its growth stimulation effect on the bone marrow cells and splenocytes in vitro cell cultures. The extract contained low levels of LPS-related material, and a mass spectrum suggested that the extract contained many components, including a low level of a lipid A precursor, a compound known as lipid X, which is known to elicit a positive response in the LAL assay. Treatment with the CWE dose- and time-dependently stimulated the growth of mouse bone marrow cells (BMCs) and splenocytes (SPLs). Treatment with the CWE also increased specific BMC subpopulations, including antigen-presenting cells (CD19+ B cells, 33D1+ dendritic cells and CD68+ macrophages), and CD4+ and CD8+ T cells, but decreased the number of LY6G+ granulocytes. Treatment with the CWE also increased cytokine mRNA associated with T cell activation, including TNFα, IFNγ, and granzyme B in human lymphoblasts. The present study indicates that the cell wall fraction of C.sorokiniana contains an LPS-like material and suggests a candidate source for the bioactivity that stimulates growth of both innate and adaptive immune cells.


Assuntos
Chlorella , Animais , Células da Medula Óssea , Linfócitos T CD8-Positivos , Parede Celular , Humanos , Lipopolissacarídeos , Camundongos , Baço , Água
11.
Circ Rep ; 4(2): 83-91, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35178484

RESUMO

Background: Patients with heart failure (HF) often experience gastrointestinal problems such as constipation, diarrhea, and disturbances to drug absorption. In HF, hypoperfusion and congestion cause structural and functional changes in the gut, which, in turn, lead to impaired cardiac function. Euglena gracilis Z (hereafter "Euglena"), called Midorimushi in Japanese, is a microalga that is used as a food or nutritional supplement. It is unclear whether Euglena is beneficial for bowel habitus and cardiac function in subjects with HF. Methods and Results: We injected C57BL/6 male mice subcutaneously with isoproterenol (ISO) (20 mg/kg/day) for 7 days to examine bowel movement in HF. Euglena was orally administered to mice on an ad libitum-feeding to a normal chow containing 2% dietary mixture. ISO induced a decrease in bowel movement and an increase in fecal retention in the cecum, as well as a decrease in left ventricular (LV) contraction. Euglena accelerated intestinal transit, relieved fecal retention, and prevented the alterations in gut pathology in ISO-treated mice. Euglena also suppressed ISO-induced decreases in LV contraction, although it had no significant effect on LV hypertrophy. Conclusions: The results suggested that oral administration of Euglena alleviated constipation and cardiac dysfunction in a mouse model of ISO-induced HF, and highlight the potential clinical benefit of Euglena in patients with HF in preventing constipation and contractile deterioration.

12.
Nutrients ; 13(11)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34836165

RESUMO

It is difficult to match annual vaccines against the exact influenza strain that is spreading in any given flu season. Owing to the emergence of drug-resistant viral strains, new approaches for treating influenza are needed. Euglena gracilis (hereinafter Euglena), microalga, used as functional foods and supplements, have been shown to alleviate symptoms of influenza virus infection in mice. However, the mechanism underlying the inhibitory action of microalgae against the influenza virus is unknown. Here, we aimed to study the antiviral activity of Euglena extract against the influenza virus and the underlying action mechanism using Madin-Darby canine kidney (MDCK) cells. Euglena extract strongly inhibited infection by all influenza virus strains examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. A time-of-addition assay revealed that Euglena extract did not affect the cycle of virus replication, and cell pretreatment or prolonged treatment of infected cells reduced the virus titer. Thus, Euglena extract may activate the host cell defense mechanisms, rather than directly acting on the influenza virus. Moreover, various minerals, mainly zinc, in Euglena extract were found to be involved in the antiviral activity of the extract. In conclusion, Euglena extract could be a potent agent for preventing and treating influenza.


Assuntos
Antivirais , Misturas Complexas/farmacologia , Euglena , Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza B/crescimento & desenvolvimento , Animais , Cães , Euglena/química , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza B/efeitos dos fármacos , Células Madin Darby de Rim Canino , Replicação Viral/efeitos dos fármacos , Zinco/análise , Acetato de Zinco/farmacologia
13.
Int Cancer Conf J ; 10(1): 72-77, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33489706

RESUMO

Peritoneal carcinosarcoma is a highly aggressive and uncommon neoplasm that has carcinomatous and sarcomatous components; the malignancy rarely localizes to the omentum. We report a case of a bulky peritoneal carcinosarcoma with tiny high-grade serous carcinoma of the fallopian tube. A 60-year-old female with a huge pelvic mass (12 cm in diameter) underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy for tumor debulking. Pathological findings showed minimally invasive high-grade serous carcinoma of the left fallopian tube and carcinosarcoma of the omentum. Similar p53 diffuse immunostaining in the omental carcinosarcoma and the tubal carcinoma provides evidence for a clonal relationship between the two neoplasias. This case suggests a small serous carcinoma, originating in the tubal mucosa, subsequently became implanted in the omentum and grew preferentially, converting to a carcinosarcoma at a remote site.

14.
Sci Rep ; 11(1): 1074, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441865

RESUMO

The alga Euglena gracilis (E. gracilis) has recently gained attention as a health food, but its effects on human gut microbiota remain unknown. This study aimed to determine the effect of E. gracilis on gut microbiota and defecation due to modulation of microbiota composition in vitro and in vivo. The in vitro model simulating human colonic microbiota revealed that E. gracilis addition stimulated the growth of commensal Faecalibacterium. Further, E. gracilis addition enhanced butyrate production by Faecalibacterium prausnitzii. Paramylon, an insoluble dietary fibre that accumulates in E. gracilis and is the main component of E. gracilis, did not stimulate Faecalibacterium growth in vitro. Daily ingestion of 2 g of E. gracilis for 30 days increased bowel movement frequency as well as stool volume in 28 human participants. Collectively, these findings indicate that E. gracilis components other than paramylon, stimulate the growth of Faecalibacterium to improve digestive health as well as promote defecation by increasing butyrate production.


Assuntos
Defecação , Euglena gracilis/fisiologia , Faecalibacterium/fisiologia , Adulto , Butiratos/metabolismo , Defecação/fisiologia , Faecalibacterium prausnitzii/fisiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
15.
Food Sci Nutr ; 9(1): 544-552, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33473315

RESUMO

Vaccines and various anti-influenza drugs are clinically used to prevent and treat influenza infections. However, with the antigenic mismatch of vaccines and the emergence of drug-resistant viral strains, new approaches for treating influenza are warranted. This study focused on natural foods as potential candidates for the development of new treatment options for influenza infections. The screening of plants from the Cucurbitaceae family revealed that the juice of Citrullus lanatus var. citroides (wild watermelon) had the strongest ability to inhibit the replication of influenza virus in Madin-Darby canine kidney cells. The results of a time-of-addition assay indicated that wild watermelon juice (WWMJ) inhibits the adsorption and late stages of viral replication, suggesting that WWMJ contains multiple constituents with effective anti-influenza activity. A viral adsorption analysis showed that WWMJ reduces the amount of viral RNA in the cells at 37°C but not at 4°C, confirming that WWMJ inhibits viral entry into the host cells at 37°C. These results suggest that a mechanism other than the inhibition of viral attachment is involved in the anti-influenza action of WWMJ, which is perhaps responsible for a reduction in internalization of the virus. Administration of WWMJ into the nasal mucosa of BALB/c mice infected with the A/PR/8/34 mouse-adapted influenza virus was seen to significantly improve the survival rate. The findings of this study, therefore, demonstrate the anti-influenza potential of WWMJ in vitro and in vivo, thereby suggesting the candidature of WWMJ as a functional food product that can be used to develop anti-influenza agents and drugs.

16.
Sci Rep ; 11(1): 13640, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210998

RESUMO

Euglena gracilis is widely utilized as food or supplement to promote human and animal health, as it contains rich nutrients. In this study, we administered spray-dried powder of E. gracilis and paramylon, ß-glucan stored in E. gracilis cells, to A4gnt knockout (KO) mice. A4gnt KO mice are a mutant mouse model that spontaneously develops gastric cancer through hyperplasia-dysplasia-adenocarcinoma sequence in the antrum of the stomach, and we observed the effects of E. gracilis and paramylon on the early involvements of A4gnt KO mice. Male and female 10-week-old A4gnt KO mice and their age-matched wildtype C57BL/6J mice were orally administered with 50 mg of E. gracilis or paramylon suspended in saline or saline as a control. After 3-week administration, animals were euthanatized and the stomach was examined histopathologically and immunohistochemically. Gene expression patterns of the stomach, which have been reported to be altered with A4gnt KO, and IgA concentration in small intestine were also analyzed with real-time PCR and ELISA, respectively. Administration of Euglena significantly reduced the number of stimulated CD3-positive T-lymphocytes in pyloric mucosa of A4gnt KO mice and tend to reduce polymorphonuclear leukocytes infiltration. Euglena administration further downregulated the expression of Il11 and Cxcl1 of A4gnt KO mice. Euglena administration also affected IgA concentration in small intestinal contents of A4gnt KO mice. Paramylon administration reduced the number of CD3-positive lymphocytes in pyloric mucosa of A4gnt KO mice, and downregulated the expressions of Il11 and Ccl2 of A4gnt KO mice. Although we found no significant effects on gross and microscopic signs of gastric dysplasia and cell proliferation, the present study suggests that the administration of Euglena and paramylon may ameliorate the early involvements of A4gnt mice through the effects on inflammatory reactions in the gastric mucosa. The cancer-preventing effects should be studied with long-term experiments until actual gastric cancer formation.


Assuntos
Anticarcinógenos/uso terapêutico , Euglena gracilis , Glucanos/uso terapêutico , N-Acetilglucosaminiltransferases/genética , Neoplasias Gástricas/prevenção & controle , Administração Oral , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/análise , Suplementos Nutricionais/análise , Euglena gracilis/química , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Glucanos/administração & dosagem , Glucanos/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
17.
Front Immunol ; 12: 803647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095889

RESUMO

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a spread of coronavirus disease 2019 (COVID-19) globally. In order to end the COVID-19 pandemic, an effective vaccine against SARS-CoV-2 must be produced at low cost and disseminated worldwide. The spike (S) protein of coronaviruses plays a pivotal role in the infection to host cells. Therefore, targeting the S protein is one of the most rational approaches in developing vaccines and therapeutic agents. In this study, we optimized the expression of secreted trimerized S protein of SARS-CoV-2 using a silkworm-baculovirus expression vector system and evaluated its immunogenicity in mice. The results showed that the S protein forming the trimeric structure was the most stable when the chicken cartilage matrix protein was used as the trimeric motif and could be purified in large amounts from the serum of silkworm larvae. The purified S protein efficiently induced antigen-specific antibodies in mouse serum without adjuvant, but its ability to induce neutralizing antibodies was low. After examining several adjuvants, the use of Alum adjuvant was the most effective in inducing strong neutralizing antibody induction. We also examined the adjuvant effect of paramylon from Euglena gracilis when administered with the S protein. Our results highlight the effectiveness and suitable construct design of the S protein produced in silkworms for the subunit vaccine development against SARS-CoV-2.


Assuntos
Compostos de Alúmen/farmacologia , Hidróxido de Alumínio/farmacologia , Bombyx/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Linhagem Celular , Galinhas/genética , Galinhas/imunologia , Chlorocebus aethiops , Euglena gracilis/imunologia , Infecções por Euglenozoa/imunologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Pandemias/prevenção & controle , SARS-CoV-2/imunologia , Vacinação/métodos , Células Vero
18.
Sci Rep ; 10(1): 2149, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034251

RESUMO

In recent years, it has been reported that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs, act as melanogenesis-regulating molecules in melanocytes. We found that the expression levels of miR-141-3p and miR-200a-3p were decreased significantly by α-melanocyte-stimulating hormone (α-MSH) stimulation in mouse melanocyte B16-4A5 cells, as demonstrated by a miRNA array. Overexpression of miR-141-3p and miR-200a-3p in B16-4A5 cells suppressed melanogenesis and tyrosinase activity. Moreover, both miR-141-3p and miR-200a-3p showed direct targeting of microphthalmia-associated transcription factor using a luciferase reporter assay. Furthermore, topical transfection of miR-141-3p and miR-200a-3p to three-dimensional reconstructed human skin tissue inhibited α-MSH-stimulated melanin biosynthesis. Taken together, our findings indicate that downregulation of miR-141-3p and miR-200a-3p during the α-MSH-stimulated melanogenesis process acts as an important intrinsic signal. This result is expected to lead to the development of miRNA-based whitening therapeutics.


Assuntos
Melaninas/biossíntese , MicroRNAs/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Animais , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Camundongos , MicroRNAs/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , alfa-MSH/farmacologia
19.
Nutrients ; 12(8)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751743

RESUMO

The intestinal tract contains over half of all immune cells and peripheral nerves and manages the beneficial interactions between food compounds and the host. Paramylon is a ß-1,3-glucan storage polysaccharide from Euglena gracilis (Euglena) that exerts immunostimulatory activities by affecting cytokine production. This study investigated the signaling mechanisms that regulate the beneficial interactions between food compounds and the intestinal tract using cell type-specific calcium (Ca2+) imaging in vivo and in vitro. We successfully visualized Euglena- and paramylon-mediated Ca2+ signaling in vivo in intestinal epithelial cells from mice ubiquitously expressing the Yellow Cameleon 3.60 (YC3.60) Ca2+ biosensor. Moreover, in vivo Ca2+ imaging demonstrated that the intraperitoneal injection of both Euglena and paramylon stimulated dendritic cells (DCs) in Peyer's patches, indicating that paramylon is an active component of Euglena that affects the immune system. In addition, in vitro Ca2+ imaging in dorsal root ganglia indicated that Euglena, but not paramylon, triggers Ca2+ signaling in the sensory nervous system innervating the intestine. Thus, this study is the first to successfully visualize the direct effect of ß-1,3-glucan on DCs in vivo and will help elucidate the mechanisms via which Euglena and paramylon exert various effects in the intestinal tract.


Assuntos
Sinalização do Cálcio/fisiologia , Euglena gracilis , Trato Gastrointestinal/citologia , Glucanos/farmacologia , beta-Glucanas , Animais , Citocinas/biossíntese , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Glucanos/química , Sistema Imunitário/metabolismo , Sistema Imunitário/microbiologia , Camundongos
20.
Nutrients ; 12(11)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33113956

RESUMO

While the human body maintains homeostasis by altering the balance in the autonomic nervous, endocrine, and immune systems, a prolonged imbalance in these systems can result in physical and mental symptoms, including a decline in sleep quality and work efficiency. Euglena gracilis (Euglena) is a single-celled microalga with the properties of both plants and animals and contains abundant nutrients, such as vitamins, minerals, amino acids, and fatty acids, which have various beneficial health effects. This study evaluated the effects of Euglena intake on the mood states and stress coping under mental workload tasks, and subjective sleep quality. We assigned men and women aged 20 to 64 years to Euglena and placebo intake groups, and measured indices related to the autonomic nervous system, psychological states, and sleep quality together with the application of workload stress before food intake, and 4, 8, and 12 weeks after commencing intake. Euglena intake regulated the autonomic nervous system under a workload and improved psychological parameters and sleep conditions. These results indicate that the consumption of Euglena may regulate the balance of the autonomic nervous system during stress and may have a favorable effect on psychological status and sleep quality.


Assuntos
Afeto/fisiologia , Sistema Nervoso Autônomo/parasitologia , Euglena gracilis , Sono/fisiologia , Estresse Psicológico/parasitologia , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pós , Adulto Jovem
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