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1.
Front Immunol ; 12: 755481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603341

RESUMO

The beneficial effect of short-chain fatty acids (SCFAs) on host health has been well recognized based on the booming knowledge from gut microbiome research. The role of SCFA in influencing psychological function is highlighted in recent years but has not been fully elucidated. In this study, the SCFA-acylated starches were used to accomplish a sizeable intestine-targeted release of the SCFAs, and the neurobehavioral, immunological, and microbial effects were further investigated. Acetylated-, butylated-, and isobutylated-starch could attenuate the depression-like behaviors and excessive corticosterone production in chronically stressed mice. Butylated- starch significantly reduced the colonic permeability via increasing the tight junction proteins (including ZO-1, Claudin, and Occludin) gene expression and reduced the level of the inflammatory cytokines (including IL-1ß and IL-6). The butylated starch's neurological and immunological benefits may be derived from the gut microbiome modifications, including normalizing the abundance of certain beneficial microbes (Odoribacter and Oscillibacter) and metabolomic pathways (Tryptophan synthesis and Inositol degradation). The present findings further validate the brain-beneficial effect of butyrate and offer novel guidance for developing novel food or dietary supplements for improving mental health.

2.
Food Funct ; 12(22): 11241-11249, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34704999

RESUMO

The discovery of psychobiotics has improved the therapeutic choices available for clinical mental disorders and shows promise for regulating mental health in people by combining the properties of food and medicine. A Pediococcus acidilactici strain CCFM6432 was previously isolated and its mood-regulating effect was investigated in this study. Viable bacteria were given to chronically stressed mice for five weeks, and then the behavioral, neurobiological, and gut microbial changes were determined. CCFM6432 significantly reduced stress-induced anxiety-like behaviors, mitigated hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and reversed the abnormal expression of hippocampal phosphorylated CREB and the c-Fos protein. In particular, CCFM6432 improved the gut microbial composition by inhibiting the over-proliferated pathogenic bacteria (e.g., Escherichia-shigella) and promoting beneficial bacteria growth (e.g., Bifidobacterium). Lactic acid, rather than bacteriocin, was further confirmed as the key compound that determined the antimicrobial activity of CCFM6432. Collectively, these results first proved the psychobiotic potential of the Pediococcus acidilactici strain. Ingestion of CCFM6432, or fermented food containing it, may facilitate mental health management in daily life, especially during the COVID-19 pandemic.

3.
PeerJ ; 9: e11103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986978

RESUMO

Researches on gut microbiota in autism have mostly focused on children, but the dynamic changes of gut microbiota from weaning to adulthood were still not clear because of the difficulty of diagnosing autism. In this study, autistic-like rats indued by valproate (VPA) were tracked from weaning (end of breastfeeding; four weeks old) to sexual maturation (food; eight weeks old). Autistic-like rats were found to show obvious developmental disorders. During weaning, autistic-like rats only exhibited obvious repetitive stereotyped behaviors, but the autistic-like behaviors were fully apparent upon sexual maturation. Significant differences were observed between the gut microbiota of autistic-like and healthy rats across both age groups. The correlation analysis results revealed that the correlation between behaviors and some microbiota, especially Helicobacter, did not vary with age or diet. The total amount of short-chain fatty acids (SCFAs) decreased, butyric acid metabolism decreased, and propionic acid metabolism increased in the feces of autistic-like rats. The correlation between autistic-like behaviors and the butyric acid and propionic acid levels did not vary with diet or age. Inositol phosphate metabolism, amino acid metabolism, and lipopolysaccharide biosynthesis were significantly associated with autistic-like behaviors. Our results showed that although the microbiota and SCFAs related to autism were affected by age and diet, some remained consistent irrespective of age and diet, and they could be considered two of the factors related to autistic-like behaviors development.

4.
Mol Nutr Food Res ; 65(8): e2000704, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33594816

RESUMO

SCOPE: The antidepressant-like effect of psychobiotics has been observed in both pre-clinical and clinical studies, but the molecular mechanisms of action are largely unclear. To address this, the psychobiotic strain Bifidobacterium breve CCFM1025 is investigated for its genomic features, metabolic features, and gut microbial and metabolic modulation effect. METHODS AND RESULTS: Unlike B. breve FHLJDQ3M5, CCFM1025 significantly decreases the chronically stressed mice's depressive-like behaviors and neurological abnormalities. CCFM1025 has more genes encoding glycoside hydrolases (GHs) when comparing to FHLJDQ3M5's genome, which means CCFM1025 has a superior carbohydrate utilization capacity and living adaptivity in the gut. CCFM1025 also produces higher levels of neuromodulatory metabolites, including hypoxanthine, tryptophan, and nicotinate. The administration of CCFM1025 reshapes the gut microbiome of chronically stressed mice. It results in higher cecal xanthine, tryptophan, short-chain fatty acid levels, and enhances fatty acid and tryptophan biosynthesis capability in the gut-brain interaction (identified by in silico analyses) than FHLJDQ3M5-treated mice. CONCLUSIONS: Genomic and metabolic features involving GHs and neuromodulatory metabolites may determine the antidepressant-like effect of B. breve CCFM1025. Psychobiotics' characterization in this manner may provide guidelines for developing novel psychopharmacological agents in the future.


Assuntos
Bifidobacterium breve , Microbioma Gastrointestinal/fisiologia , Estresse Psicológico/microbiologia , Estresse Psicológico/terapia , Animais , Antidepressivos/farmacologia , Bifidobacterium breve/enzimologia , Bifidobacterium breve/genética , Bifidobacterium breve/metabolismo , Metabolismo dos Carboidratos , Fezes/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo , Probióticos
5.
Food Funct ; 12(6): 2591-2604, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33629689

RESUMO

Probiotic therapy targeting gut-brain axis has been proven to be effective in treating autistic patients. The present study aimed to assess the ability of three Lactobacillus strains (L. helveticus CCFM1076, L. acidophilus La28, and L. acidophilus JCM 1132) to alleviate autistic-like behavioral symptoms in VPA-treated rats from weaning to sexual maturation. For the first time, we assessed the synthesis of 5-hydroxytryptamine (5HT) and the metabolic capacity of the 5HT system in the peripheral and central nervous systems (PNS and CNS, respectively) based on tryptophan metabolism based on VPA-induced autism model. We also assessed gut microbiota, and short-chain fatty acids (SCFAs) at the end of week 8. While improving autistic-like behavioral symptoms, we found L. helveticus CCFM1076 was more beneficial in regulating 5HT anabolism and catabolism, balancing excitatory and inhibitory neurotransmitter release in the PNS and CNS, and increasing oxytocin (OT) synthesis in the hypothalamus. A significant correlation was noted between 5HT levels and the release of GABA, glutamate (Glu), and OT, suggesting that 5HT plays a vital role in the neuroendocrine network. Analyses of the gut microbiota and SCFA levels revealed greater Turicibacter abundance and lower butyric acid levels in VPA-treated rats, which have been reported to be associated with 5HT levels. L. helveticus CCFM1076 helped reduce Turicibacter abundance and up-regulate butyric acid levels, while L. acidophilus La28 and L. acidophilus JCM 1132 did not. L. helveticus CCFM1076 restored neurotransmitter homeostasis by improving the balance of the 5HT system in the PNS and CNS, thereby ameliorating autistic-like behaviors. This finding will help in the development of bioproducts for treating autism and in the establishment of a treatment model mimicking the intestinal environment of autistic patients.


Assuntos
Transtorno Autístico/fisiopatologia , Lactobacillus , Probióticos , Serotonina/metabolismo , Animais , Transtorno Autístico/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Ácido Butírico/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Probióticos/farmacologia , Ratos , Maturidade Sexual , Triptofano/metabolismo , Ácido Valproico/efeitos adversos , Desmame
6.
Food Funct ; 12(2): 646-655, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33404580

RESUMO

Certain probiotics can regulate the host's neurobehavioral function through the microbiota-gut-brain axis. However, screening these probiotics is mainly carried out in animal models, and is costly and inefficient. Herein, a putative enterochromaffin cell line (RIN14B) was used as an in vitro pre-screening model; 30 bacterial strains were tested for bacteria-stimulated tryptophan hydroxylase 1 gene (Tph1) expression and 5-hydroxytryptophan/5-hydroxytryptamine secretion. All strains were further validated for their neurobehavioral effects in chronic stress-induced depressive mice. Using partial least squares (PLS) modeling of in vitro and in vivo datasets, we found that the level of Tph1 mRNA in RIN14B significantly correlated with the performance of a forced swim test and sucrose preference test, and serum corticosterone level in chronically stressed mice. Four strains were identified as the best candidates among 30 strains using principal component analysis on all in vivo measures, and unsurprisingly, three of them could enhance Tph1 expression in RIN14B, which further proved that the RIN14B-based screening method (especially the detection of bacteria-stimulated Tph1 mRNA) has good predictive validity and screening efficiency for the strain's antidepressant-like capacity. Collectively, this study provides a novel in vitro method for screening probiotics (or other related bioproducts) with antidepressant-like potential.


Assuntos
Antidepressivos/farmacologia , Células Enterocromafins/efeitos dos fármacos , Probióticos/farmacologia , Triptofano Hidroxilase/metabolismo , Animais , Bactérias , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Componente Principal , Serotonina/metabolismo , Estresse Fisiológico , Natação , Triptofano Hidroxilase/genética
7.
Food Funct ; 11(7): 5898-5914, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32572400

RESUMO

The prevalence of diabetes mellitus is increasing worldwide. Lactic acid bacteria have shown efficacy in alleviating diabetes. We studied the remission effect of nine strains of lactic acid bacteria on the symptoms of high-fat diet- and streptozotocin-induced type 2 diabetes and its mechanism in mice. The oral administration of Bifidobacterium adolescentis, B. bifidum or Lactobacillus rhamnosus to mice every day for more than 12 weeks showed that the individual strains could reduce the fasting and postprandial blood sugar levels, improve glucose tolerance and prevent pancreatic damage. However, L. rhamnosus strains showed greater efficacy than Bifidobacterium strains in the regulation of blood lipid levels. The effects of lactic acid bacteria on the recovery of glycolipid metabolism disorder and gut microbiota dysbiosis showed inter- and intraspecific differences. In addition, the strains that exhibited hypoglycaemic effects played a beneficial role in reducing insulin resistance by contributing to the production of short-chain fatty acids and alleviation of inflammation. The ability of lactic acid bacteria to reduce inflammation was found to be closely related to their ability to alleviate diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Disbiose/tratamento farmacológico , Microbioma Gastrointestinal , Inflamação/tratamento farmacológico , Lactobacillus rhamnosus , Probióticos/uso terapêutico , Animais , Bifidobacterium , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Dieta Hiperlipídica , Ácidos Graxos Voláteis/metabolismo , Resistência à Insulina , Lactobacillales , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL
8.
Front Microbiol ; 11: 1088, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528454

RESUMO

Diverse CRISPR-Cas systems constitute an indispensable part of the bacterial adaptive immune system against viral infections. However, to escape from this immune system, bacteriophages have also evolved corresponding anti-defense measures. We investigated the diversity of CRISPR-Cas systems and the presence of prophages in the genomes of 66 Bifidobacterium pseudocatenulatum strains. Our findings revealed a high occurrence of complete CRISPR-Cas systems (62%, 41/66) in the B. pseudocatenulatum genomes. Subtypes I-C, I-U and II-A, were found to be widespread in this species. No significant association was found between the number of bacterial CRISPR spacers and its host's age. This study on prophages within B. pseudocatenulatum genomes revealed that prophage genes related to distinct functional modules became degraded at different levels, indicating that these prophages were not likely to enter lytic cycle spontaneously. Further, the evolutionary analysis of prophages in this study revealed that they might be derived from different phage ancestors. Notably, self-targeting phenomenon within B. pseudocatenulatum and Anti-CRISPR (Acr) coding genes in prophages was observed. Overall, our results indicate that the competition between B. pseudocatenulatum and phages is a major driving factor for the genomic diversity of both partners.

9.
Neurobiol Stress ; 12: 100216, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32258258

RESUMO

Background: Accumulating evidence points to an association between gut microbial abnormalities and depression disorder. The microbiota-gut-brain axis is an emerging target for treating depression using nutritional strategies, considering the numerous limitations of current pharmacological approaches. Here we studied the effect and probable mechanisms of psychobiotic treatment on depression. Methods: Chronically stressed C57BL/6J male mice were administered viable Bifidobacterium breve CCFM1025 for 5 weeks prior to behavioral testing. Brain neurological alterations, serum corticosterone, cytokines levels, fecal microbial composition, and short-chain fatty acid (SCFA) content were measured. In addition, the effect of SCFA on 5-hydroxytryptophan (5-HTP) biosynthesis was investigated in an in vitro model of enterochromaffin cells (RIN14B). Results: CCFM1025 treatment significantly reduced depression- and anxiety-like behaviors. The hyperactive hypothalamic-pituitary-adrenal response, as well as inflammation, were also alleviated, possibly via regulating the expression of glucocorticoid receptors (Nr3c1). Moreover, CCFM1025 also down-regulated the pCREB-c-Fos pathway but increased the expression of brain-derived neurotrophic factor (BDNF). Meanwhile, chronic stress-induced gut microbial abnormalities were restored, accompanied by increased SCFA and 5-HTP levels. The intestinal 5-HTP biosynthesis positively correlated with fecal SCFA and Bifidobacterium breve levels. Conclusions: In summary, Bifidobacterium breve CCFM1025 showed considerable antidepressant-like and microbiota-regulating effects, which opens avenues for novel therapeutic strategies towards treating depression.

10.
Environ Pollut ; 261: 114164, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32088434

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer, which can enter the body through a variety of ways and exerted multiple harmful effects, including liver toxicity, reproductive toxicity and even glucose metabolism disorder. Many studies have suggested that changes of gut microbiota are closely related to the occurrence of various diseases, but the effects of DEHP exposure on gut microbiota are still unclear. It was found in this study that the damage to different tissues by DEHP on two strains each from two different species of male rodents before puberty was dose and time of exposure dependent, and also depending on the strain and species of rodent. Sprague-Dawley (SD) rats showed highest sensitivity to DEHP exposure, with most severe organ damage, highest Th1 inflammatory response and most significant body weight gain. Correspondingly, the gut microbiota of SD rats showed most significant changes after DEHP exposure. Only SD rats, but not Wistar rats, BALB/c and C57BL/6J mice showed an increase in Firmicutes/Bacteroidetes ratio and Proteobacteria abundance in the fecal samples, which are known to associate with obesity and diabetes. This is consistent with the increasing body weight gain which was only found in SD rats. In addition, the decrease in the level of butyrate, increase in the abundance of potential pathogens and microbial genes linked to colorectal cancer, Parkinson's disease, and type 2 diabetes in the SD rats were associated with issue and functional damages and Th1 inflammatory response caused by DEHP exposure. We postulate that the differential effects of DEHP on gut microbiota may be an important cause of the differences in the toxicity on different strains and species of rodents to DEHP.


Assuntos
Diabetes Mellitus Tipo 2 , Dietilexilftalato , Microbioma Gastrointestinal , Animais , Disbiose , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ácidos Ftálicos , Ratos , Ratos Sprague-Dawley , Roedores
11.
Microorganisms ; 8(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881756

RESUMO

The production of bacteriocin is considered to be a probiotic trait of lactic acid bacteria (LAB). However, not all strains of LAB harbour bacteriocin genes, even within the same species. Moreover, the effects of bacteriocins on the host gut microbiota and on host physiological indicators are rarely studied. This study evaluated the effects of the bacteriocin-producing Lactobacillus acidophilus strain JCM1132 and its non-producing spontaneous mutant, L. acidophilus CCFM720, on the physiological statuses and gut microbiota of healthy mice. Mice that received the bacteriocin-producing strain JCM1132 exhibited reduced water and food intake. Furthermore, the administration of these strains induced significant changes in the compositional abundance of faecal microbiota at the phylum and genus levels, and some of these changes were more pronounced after one week of withdrawal. The effects of CCFM720 treatment on the gut microbiota seemed to favour the prevention of metabolic diseases to some extent. However, individuals that received JCM1132 treatment exhibited weaker inflammatory responses than those that received CCFM720 treatment. Our results indicate that treatment with bacteriocin-producing or non-producing strains can have different effects on the host. Accordingly, this trait should be considered in the applications of LAB.

12.
Food Funct ; 10(11): 7588-7598, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31687714

RESUMO

Increasing evidence points to the effect of the gut microbiota on central nervous system functions. Supplementation of certain microbial strains has been demonstrated to alleviate depressive behaviors and neurological abnormalities. This study took the approach to screen for an anti-depressive Bifidobacterium longum strain from fourteen candidates and systematically verified its effect in a chronic stress-induced depression mice model. B. longum subsp. infantis strain CCFM687 could significantly enhance the biosynthesis of 5-hydroxytryptamine (5-HTP) in vitro in RIN14B cells through up-regulation of the Tph1 gene expression. Administration of CCFM687 in mice significantly improved the scores in behavioral tests and increased the level of 5-HTP and serotonin (5-HT) in the prefrontal cortex (PFC) of the brain. The brain-derived neurotrophic factor (BDNF) in the PFC was also increased, possibly through the 5-HT1A-CREB-BDNF pathway. In addition, CCFM687 alleviated the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis response and accordingly reversed the peripheral inflammation status. Moreover, the stress-induced structural and functional dysbiosis of the gut microbiome was improved by CCFM687, through increased alpha diversity and abundance of butyrate-producing bacteria, in conjunction with inhibition of pathogenic gene expression. In summary, these results indicate that supplementation of B. longum subsp. infantis strain CCFM687 may prevent the onset of depression from chronic stress, and RIN14B could serve as an efficient cell model for rapid screening of anti-depressive probiotics.


Assuntos
Bifidobacterium longum subspecies infantis/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/terapia , Microbioma Gastrointestinal/fisiologia , Estresse Fisiológico/fisiologia , Animais , Depressão/etiologia , Fluoxetina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Probióticos , Serotonina/metabolismo
13.
J Nutr Biochem ; 66: 43-51, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30743155

RESUMO

Depression disorder is rapidly advancing worldwide, and therapeutic strategy through gut-brain axis has been proven to be effective in the treatment. Here we studied the effect of lactic acid bacteria (LAB) treatment on depression. C57BL/6J mice were administered with LAB during a 5-week chronic unpredictable mild stress. Bifidobacterium longum subsp. infantis E41 and Bifidobacterium breve M2CF22M7, which improved the expression of Tph1 and secretion of 5-hydroxytryptophan (5-HTP) in RIN14B cells, significantly reduced depressive behaviors of mice in the forced swim test, sucrose preference test and step-down test, as well as increased the level of 5-hydroxytryptamine and brain-derived neurotrophic factor concentration in brain. Besides, M2CF22M7 reduced the serum corticosterone level. E41 increased cecal butyrate level, which significantly and positively correlated with some depression-related indexes. Using 16S rRNA-amplicon sequencing of faces, E41 and M2CF22M7 were found to improve the chronic-stress-induced microbial dysbiosis. They also normalized the host's pathways involving metabolism and gene information processing. These results indicate that Bifidobacterium E41 and M2CF22M7 have an antidepressant effect in mice partly in a 5-HTP dependent and microbiota-regulating manner. Nurturing the gut microbiota with these strains may become an emerging therapeutic way for mood disorder.


Assuntos
5-Hidroxitriptofano/biossíntese , Bifidobacterium , Depressão/terapia , Disbiose/terapia , Microbioma Gastrointestinal , Probióticos/farmacologia , Animais , Comportamento Animal , Butiratos/metabolismo , Depressão/microbiologia , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Hipocampo/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Ratos , Estresse Psicológico/terapia , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo
14.
Eur J Pediatr ; 176(8): 1035-1045, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28593405

RESUMO

Henoch-Schönlein purpura (HSP) is the most common form of systemic small-vessel vasculitis in children, and HSP nephritis (HSPN) is a major complication of HSP and is the primary cause of morbidity and mortality. Previous studies have suggested that inducible nitric oxide synthase (iNOS) may play an important role in the pathogenesis of HSP. In this study, we performed a detailed analysis to investigate the potential association between iNOS polymorphisms and the risk of HSP and the tendency for children with HSP to develop HSPN in a Chinese Han population. A promoter pentanucleotide repeat (CCTTT)n and 10 functional single-nucleotide polymorphisms (SNPs) from 532 healthy controls and 513 children with HSP were genotyped using the MassARRAY system and GeneScan. The results suggested that the allelic and genotypic frequencies of the rs3729508 polymorphism were nominally associated with susceptibility to HSP. In addition, there was a significant difference in the allelic distribution of the (CCTTT)12 repeats and rs2297518 between the HSP children with and without nephritis; the HSP children with nephritis exhibited a significantly higher frequency of the (CCTTT)12 repeats and A allele of rs2297518 than the HSP children without nephritis (P FDR = 0.033, OR = 1.624, 95% CI = 1.177-2.241 and P FDR = 0.030, OR = 1.660, 95% CI = 1.187-2.321, respectively). CONCLUSION: Our results support that iNOS polymorphisms are associated with the risk of HSP and may strongly contribute to the genetic basis of individual differences in the progression to nephritis among children with HSP in the Chinese Han population. What is Known: • The etiology of HSP is unknown, but the genetic factors may play an important role in the pathogenesis of HSP. • iNOS could contribute to the development and clinical manifestations of HSP, and this has not been studied extensively so far. What is New: • Our results support that iNOS polymorphisms not only are associated with HSP risk but also strongly contribute to the genetic basis of individual differences in the progression of HSP to nephritis among Chinese Han children.


Assuntos
Nefrite/etiologia , Óxido Nítrico Sintase Tipo II/genética , Polimorfismo de Nucleotídeo Único , Púrpura de Schoenlein-Henoch/complicações , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Criança , China , Feminino , Seguimentos , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Nefrite/etnologia , Púrpura de Schoenlein-Henoch/etnologia , Púrpura de Schoenlein-Henoch/genética , Fatores de Risco
15.
Med Sci Monit ; 22: 5116-5123, 2016 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-28013316

RESUMO

BACKGROUND This study was aimed to reveal the role of miR-149-5p in acute myeloid leukemia (AML) cells apoptosis and the possible mechanism involved. MATERIAL AND METHODS The expression of miR-149-5p in leukemia cell lines, as well as the blood and bone marrow (BM) samples from leukemia patients, were monitored by reverse-transcription polymerase chain reaction (RT-PCR). AML cell line THP-1 was transfected with miR-149-5p mimic or inhibitor, and then cell apoptosis was determined using the APO Percentage assay kit. The target of miR-149-5p was predicted by using the microRNA.org database, and verified by RT-PCR, Western blot, and Dual-Luciferase reporter assays. Further, small interfering RNA (siRNA) against the target gene was co-transfected with miR-149-5p inhibitor, and then the cell apoptosis and the expression of apoptosis-related proteins were assessed. RESULTS MiR-149-5p was significantly up-regulated in leukemia cell lines and samples from leukemia patients (P<0.01 or P<0.001), especially in THP-1 cells and samples from AML patients. Cell apoptosis was significantly decreased by miR-149-5p overexpression (P<0.01) and increased by miR-149-5p suppression (P<0.05). Fas Ligand (FASLG) was a direct target of miR-149-5p, and was negatively regulated by miR-149-5p. More importantly, the inductive effects of miR-149-5p suppression on cell apoptosis were abrogated by si-FASLG (P<0.01). Furthermore, the up-regulative effects of miR-149-5p suppression on the phosphorylated form of Fas-associated via death domain (p-FADD), caspase-8, caspase-2, caspase-3, and the cleaved forms of these caspases were abrogated by si-FASLG. CONCLUSIONS Inhibition of miR-149-5p can induce apoptosis in THP-1 cells. These inductive effects might be via targeting FASLG and activating FADD and caspases.


Assuntos
Apoptose/genética , Proteína Ligante Fas/genética , Leucemia Mieloide Aguda/genética , MicroRNAs/genética , Adulto , Idoso , Sequência de Bases , Caspases/metabolismo , Linhagem Celular Tumoral , Proteína Ligante Fas/metabolismo , Proteína de Domínio de Morte Associada a Fas/metabolismo , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genética , Adulto Jovem
16.
Food Funct ; 7(9): 3789-3797, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27713957

RESUMO

The antidiabetic effects of Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 in high fat diet and streptozotocin-induced type 2 diabetic (T2D) rats were evaluated in this study. The strains were separated from Chinese traditional fermented dairy food. Administration of G15 and Q14 for 6 weeks significantly improved the glucose tolerance and reduced the HbA1c levels in T2D rats. The probiotic treatment reduced the intestinal mucosal permeability and improved the epithelial barrier function through modification of the gut microbiota, which in turn lowered circulating LPS and inflammation cytokines, including IL-1ß and IL-8, and eventually alleviated the inflammatory status and islet ß-cell dysfunction. Combination of Q14 and metformin reversed the thymic atrophy and both G15 and Q14 lowered the circulating IL-6 level, indicating the immune-modulating potential of the strains. Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 provide an insight into the biotherapy application of traditional fermented foods and their functional ingredients in the treatment of diabetes.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/terapia , Microbioma Gastrointestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Lactobacillus casei/fisiologia , Lactobacillus paracasei/fisiologia , Animais , Produtos Fermentados do Leite/microbiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Intolerância à Glucose/terapia , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Inflamação/microbiologia , Inflamação/terapia , Interleucina-1beta/sangue , Interleucina-8/sangue , Lactobacillus casei/isolamento & purificação , Lactobacillus paracasei/isolamento & purificação , Lipopolissacarídeos/sangue , Masculino , Permeabilidade , Ratos , Ratos Wistar
17.
Int J Mol Sci ; 16(8): 20033-49, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26305246

RESUMO

L. paracasei subp. paracasei X12 was previously isolated from a Chinese traditional fermented cheese with anticancer activities and probiotic potential. Herein, the integral peptidoglycan (X12-PG) was extracted by a modified trichloroacetic acid (TCA) method. X12-PG contained the four representative amino acids Asp, Glu, Ala and Lys, and displayed the similar lysozyme sensitivity, UV-visible scanning spectrum and molecular weight as the peptidoglycan standard. X12-PG could induce the production of apoptotic bodies observed by transmission electron microscopy (TEM). X12-PG could significantly induced the translocation of calreticulin (CRT) and the release of high mobility group box 1 protein (HMGB1), the two notable hallmarks of immunogenic cell death (ICD), with the endoplastic reticulum (ER) damaged and subsequently intracellular [Ca(2+)] elevated. Our findings implied that X12-PG could induce the ICD of HT-29 cells through targeting at the ER. The present results may enlighten the prospect of probiotics in the prevention of colon cancer.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Lactobacillus/química , Peptidoglicano/isolamento & purificação , Peptidoglicano/farmacologia , Apoptose , Cálcio/metabolismo , Calreticulina/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/metabolismo , Células HT29 , Humanos
18.
Tumour Biol ; 36(12): 9789-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26159850

RESUMO

Midkine overexpression has been shown to be a tumor biomarker in several types of human cancer, but little is known about the clinical significance of midkine in breast cancer patients. The aim of this study was to analyze the expression of midkine in breast cancer and its correlation with clinicopathological characteristics, including breast cancer patient's survival. The expression status of midkine in breast cancer from Gene Expression Omnibus (GEO accession number: GDS3853) was observed initially. Furthermore, the expression of midkine messenger RNA (mRNA) and protein was examined in breast cancer and normal mammary tissues through real-time PCR and immunohistochemistry. Moreover, the relationship of midkine protein expression with clinical characteristics of 170 breast cancer patients was analyzed by immunohistochemistry. In our results, midkine was up-expressed in breast cancer tissues compared with normal mammary tissues in microarray data (GDS3853). Midkine mRNA and protein expression was significantly increased in breast cancer tissues than in normal mammary tissues. By immunohistochemistry, high levels of midkine protein were positively associated with the status of clinical stage, T classification, N classification, and M classification in breast cancer patients. Furthermore, midkine overexpression was an independent poor prognostic indicator for the survival of patients with breast cancer. In conclusion, overexpression of midkine protein serves as an unfavorable prognostic biomarker in breast cancer patients.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Citocinas/biossíntese , Prognóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Citocinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Midkina , Estadiamento de Neoplasias
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