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1.
Microorganisms ; 10(12)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36557570

RESUMO

Polyethylene glycol (PEG) is one of the most commonly used bowel cleansing methods. Although the safety of PEG for bowel cleansing has been proven, its impact on intestinal microbiota has not been clearly explained, especially in terms of the dynamic changes in intestinal microbiota after PEG bowel cleansing, and there are no consistent results. In this study, stool samples were collected from 12 participants at six time points before and after bowel cleansing. We obtained data on the microbiota of these samples using 16S rRNA gene sequencing and analysis. The data revealed that the structure and composition of the microbiota changed greatly approximately 7 d after intestinal cleansing. The analysis of the dynamic changes in the microbiota showed that the change was most significant at day 3, but the internal structure of the microbiota was similar to that before bowel cleansing. A comparison of the most significantly changed microbiota at different time points before and after bowel cleansing revealed four bacteria: Bacteroides, Roseburia, Eubacterium, and Bifidobacterium. We also established a humanized mouse model to simulate human bowel cleansing using PEG. The results showed that the mouse model achieved similar effects to human bowel cleansing, but its recovery speed was one stage earlier than that of humans. These findings suggest that the intestinal microbiota after bowel cleansing initially underwent a short-term change and then actively returned to its initial status. The results on key bacteria and establishment of mouse models can provide a reference for subsequent research on bowel cleansing.

2.
Front Nutr ; 9: 1046833, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386919

RESUMO

Although excessive salt consumption appears to hasten intestinal aging and increases susceptibility to cardiovascular disease, the molecular mechanism is unknown. In this study, mutual validation of high salt (HS) and aging fecal microbiota transplantation (FMT) in C56BL/6 mice was used to clarify the molecular mechanism by which excessive salt consumption causes intestinal aging. Firstly, we observed HS causes vascular endothelial damage and can accelerate intestinal aging associated with decreased colon and serum expression of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and increased malondialdehyde (MDA); after transplantation with HS fecal microbiota in mice, vascular endothelial damage and intestinal aging can also occur. Secondly, we also found intestinal aging and vascular endothelial damage in older mice aged 14 months; and after transplantation of the older mice fecal microbiota, the same effect was observed in mice aged 6-8 weeks. Meanwhile, HS and aging significantly changed gut microbial diversity and composition, which was transferable by FMT. Eventually, based on the core genera both in HS and the aging gut microbiota network, a machine learning model was constructed which could predict HS susceptibility to intestinal aging. Further investigation revealed that the process of HS-related intestinal aging was highly linked to the signal transduction mediated by various bacteria. In conclusion, the present study provides an experimental basis of potential microbial evidence in the process of HS related intestinal aging. Even, avoiding excessive salt consumption and actively intervening in gut microbiota alteration may assist to delay the aging state that drives HS-related intestinal aging in clinical practice.

3.
Foods ; 11(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36230211

RESUMO

Limosilactobacillus fermentum is ubiquitous in traditional fermented vegetables, meat products, and the human gut. It is regarded as a "generally recognized as safe" organism by the US Food and Drug Administration. So far, the genetic features and evolutionary strategies of L. fermentum from the human gut and food remain unknown. In this study, comparative genomic analysis of 224 L. fermentum strains isolated from food and human gut (164 L. fermentum strains isolated from human gut was sequenced in our lab) was performed to access genetic diversity and explore genomic features associated with environment. A total of 20,505 gene families were contained by 224 L. fermentum strains and these strains separated mainly into six clades in phylogenetic tree connected with their origin. Food source L. fermentum strains carried more carbohydrate active enzyme genes (belonging to glycosyltransferase family 2, glycoside hydrolase family 43_11, and glycoside hydrolase family 68) compared with that of human gut and L. fermentum derived from food showed higher ability to degrade xylulose and ribose. Moreover, the number of genes encoding otr(A), tetA(46), lmrB, poxtA, and efrB were more abundant in food source L. fermentum, which was consistent with the number of CRISPR spacers and prophages in L. fermentum of food source. This study provides new insight into the adaption of L. fermentum to the food and intestinal tract of humans, suggesting that the genomic evolution of L. fermentum was to some extent driven by environmental stress.

4.
J Cancer ; 12(18): 5622-5632, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34405022

RESUMO

Background: Although we previously revealed that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and important for gemcitabine resistance, the role of DNA-PKcs in the progression and metastasis of PDAC remain unclear. To date, the upstream signaling events stimulating DNA-PKcs overexpression in PDAC are still not well characterized. Methods: Expression of DNA-PKcs was measured by western blot. The levels of miRNA-101 and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) were detected by real-time PCR. Cell viability was determined by CCK-8. Cell migration and cell invasion were measured by transwell assay. The regulatory relationship between NEAT1 and miR-101 was determined by a luciferase assay. Results: DNA-PKcs expression was significantly elevated in human PDAC tissues and cells. DNA-PKcs overexpression was correlated with TNM stage and lymph node metastasis. Higher expression of DNA-PKcs was closely correlated with patients of worse overall survival (OS). DNA-PKcs knockdown suppresses malignant behaviors of PDAC cells. Further study showed that miRNA-101 level was decreased in PDAC tissues and cells, which could be responsible for DNA-PKcs overexpression and DNA-PKcs mediated oncogenic actions in PDAC cells. Moreover, NEAT1 functions as an oncogene influencing cell proliferation, migration and invasion in part by serving as a competing endogenous RNA (ceRNAs) modulating miR-101 expression, leading to up-regulation of DNA-PKcs. Conclusion: These findings suggest that NEAT1/miR-101-dependent up-regulation of DNA-PKcs promotes the malignant behaviors of PDAC cells. The NEAT1/miR-101/DNA-PKcs axis may serve as a viable prognostic marker and therapeutic target for PDAC.

5.
Aging (Albany NY) ; 13(14): 18924-18945, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314382

RESUMO

MicroRNAs (miRNAs) are known to be involved in the development and progression of pancreatic cancer (PAC). The expression levels and roles of miR-1252-5p in PAC remain unclear. Quantitative real-time PCR and in situ hybridization were used to detect miR-1252-5p expression in PAC cells and human tissues. We studied the gain and loss of function of miR-1252-5p in the PAC cell lines in vitro and in vivo. The direct targets of miR-1252-5p were analyzed using public databases and a dual-luciferase reporter assay. Expression levels of miR-1252-5p are downregulated in PAC cell lines and tissue samples, and its expression is negatively associated with adverse clinical features and poor prognosis. In vitro and in vivo experiments show that miR-1252-5p overexpression inhibits the proliferation, migration, invasion, and epithelial-mesenchymal transition of PAC cells, and miR-1252-5p knockdown enhances these biological behaviors. MiR-1252-5p negatively regulates neural precursor cell expressed, developmentally downregulated 9 (NEDD9) by directly binding its 3'- untranslated region. Further mechanism research revealed that the SRC/STAT3 pathway is involved in miR-1252-5p/NEDD9 mediation of PAC's biological behaviors. We also verified that Myb inhibited miR-1252-5p by directly binding at its promoter. MiR-1252-5p may act as a tumor-suppressing miRNA in PAC and may be a potential therapeutic target for PAC patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose/genética , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Med Food ; 24(3): 319-330, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33739885

RESUMO

Diabetes mellitus is a global health problem, and its prevalence continues to increase. Dietary supplements, including probiotics, prebiotics, and plant extracts, have been shown to alleviate diabetes. In this study, the synergistic effects of two types of dietary supplements were investigated in a mouse model of type 2 diabetes mellitus (T2DM). Sixty mice were divided into the following six groups: control, model (induced by a high-fat diet and intraperitoneal injection of streptozotocin), drug (metformin), probiotic (Lactobacillus spp.), formula A (probiotics, plant extracts, and soybean peptide), and formula B (probiotics, prebiotics, and soybean peptide). All three dietary interventions (probiotic, formula A, and formula B groups) significantly reduced the blood glucose level and oral glucose tolerance level and effectively improved some biochemical parameters (e.g., chronic inflammation, oxidative stress, and blood lipid level) and regulated gut microbiota. Notably, formula B exhibited a better ability on reducing the blood glucose level, regulating the gut microbiota, and increasing the short-chain fatty acid levels compared with the probiotics alone and formula A. Thus, formula B may exert synergistic protective effects against T2DM through a mechanism involving probiotics and prebiotics of gut microbiota regulation. This study provides a theoretical basis for the application of probiotic dietary supplements to the treatment of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Probióticos , Animais , Suplementos Nutricionais , Camundongos , Prebióticos
7.
Ann Palliat Med ; 9(6): 3785-3792, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302648

RESUMO

BACKGROUND: Constipation is a common gastrointestinal complication during pregnancy. The prevalence of constipation is higher in pregnant women compared to the general population owing to the physiological changes that occur throughout pregnancy. Lactulose and polyethylene glycol belong to a class of medications known as osmotic laxatives. The purpose of this study is to compare the safety and efficacy of polyethylene glycol and lactulose in pregnant women with constipation. METHODS: In this study, we selected 113 pregnant women with constipation who attended the Department of Gastroenterology, Affiliated Hospital of Jiangnan University from May 1, 2017 to April 30, 2020. The included patients were randomly divided into two groups. The observation group used polyethylene glycol 4000 (manufactured by Beau four Ipsen Industry, France, National Medicine Standard: H20130145), 10 g, twice daily. The control group used lactulose (manufactured by Abbott Biologicals BV, Netherlands, National Medicine Standard: H20120387) 15 mL, twice daily. Both groups were given a 3-week course of treatment, and were observed for any adverse drug reactions. The clinical effects were compared every week during the 3-week treatment. RESULTS: Treatment was found to be effective in both the observation and control groups, as measured by a significant difference in the Wexner constipation scores of patients before and after treatment (P<0.05). Although no significant differences in the final effect of treatment were observed between the two groups (P>0.05), analysis of the Wexner scores at the first and second week of treatment indicated that polyethylene glycol had a faster therapeutic effect than lactulose (P=0.06, P=0.029). CONCLUSIONS: Compared with lactulose, Polyethylene glycol 4000 can significantly shorten the treatment course for constipation during pregnancy.


Assuntos
Lactulose , Gestantes , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Feminino , França , Humanos , Lactulose/uso terapêutico , Polietilenoglicóis/uso terapêutico , Gravidez , Resultado do Tratamento
8.
Cancer Cell Int ; 20: 513, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093811

RESUMO

BACKGROUND: CD137 is a target for tumor immunotherapy. However, the role of CD137 in gastric cancer (GC), especially in inducing GC cell apoptosis, has not been studied. METHODS: Foxp3+ and CD8+ T cells in GCs were investigated using immunohistochemistry (IHC). CD137 expression in GCs was detected using flow cytometry, IHC and immunofluorescence (IF). Peripheral blood mononuclear cells (PBMCs) and CD8+ T cells isolated from peripheral blood were stimulated with a CD137 agonist in vitro. CD8+ T cell proliferation and p65 expression was examined using flow cytometry. P65 nuclear translocation was analyzed using IF. IL-10, TGF-ß, IFN-γ, perforin and granzyme B were detected using real-time quantitative PCR (real-time PCR). PBMCs and primary GC cells were cocultured and stimulated with a CD137 agonist in vitro. Apoptosis of primary GC cells was detected using flow cytometry. RESULTS: Our data demonstrated that GC tumors showed characteristics of an immunosuppressive microenvironment. CD137 was predominantly expressed in CD8+ T cells in GCs and had a positive correlation with tumor cell differentiation. The CD137 agonist promoted CD8+ T cell proliferation and increased the secretion of IFN-γ, perforin and granzyme B, which induced primary GC cell apoptosis. Mechanistically, this study found that the CD137 agonist induced NF-κB nuclear translocation in CD8+ T cells. CONCLUSION: Our results demonstrated that a CD137 agonist induced primary GC cell apoptosis by enhancing CD8+ T cells via activation of NF-κB signaling.

9.
Cancer Manag Res ; 12: 7363-7373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903925

RESUMO

PURPOSE: The expression of microRNA-125b (miR-125b) is low in a variety of cancers, including gastric, lung, bladder, thyroid, and esophageal cancers. However, its specific mechanism in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study is aimed to explore the role of miR-125b in PDAC. METHODS: PDAC tissues and adjacent tissues were collected for miR-125b analysis by qRT-PCR. Different PDAC cell lines were cultured for miR-125b detection by qRT-PCR, and CAPAN1 cells were selected for the downstream experiments. Cell proliferation was characterized by methyl thiazolyl tetrazolium (MTT) and 5-bromo-2-deoxyUridine (BrdU) staining. Flow cytometry was utilized for apoptosis and cell cycle changes. Cell invasion was determined by the Transwell assay and the dual-luciferase assay was utilized for validating the target gene. Western blotting was used to detect apoptosis related and PI3K/AKT signaling proteins. RESULTS: miR-125b was significantly down-regulated in human PDAC tissues and cell lines (P < 0.05). miR-125b inhibited the growth and invasion of CAPAN1 cells, facilitated apoptosis, and blocked the cell cycle at the G0/G1 phase. Furthermore, miR-125 directly targeted NEDD9. The high expression of NEDD9 impaired the anti-proliferative and anti-apoptotic activity of miR-125b. miR-125b also inhibited apoptosis-related proteins and PI3K/AKT signaling pathways via NEDD9. CONCLUSION: miR-125b decreased cell growth and invasion, and facilitated apoptosis in CAPAN1 cells through PI3K/AKT inhibition via targeting NEDD9.

10.
Ann Palliat Med ; 9(4): 1944-1952, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692218

RESUMO

BACKGROUND: The imbalance of Treg/Thl7 cells and inflammatory injury are believed to be involved in the development of ulcerative colitis (UC). Meanwhile, 6-gingerol has been reported to alleviate intestinal inflammatory damage in mice models, but the underlying mechanism remains elusive. METHODS: In this study, dextran sulfate sodium (DSS)-induced colitis mice models were established to examine the effects of 6-gingerol on IL-17 and IL-10 secretion, and the activation of NF-κB signaling was evaluated using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry. RESULTS: 6-gingerol could significantly reduce the weight loss caused by DSS in mice models (P<0.05), which is similar to the therapeutic drug, mesalazine. Immunohistochemistry showed that 6-gingerol can repair the damaged glandular structure gradually caused by DSS, significantly decrease the IL-17 level, and increase IL-10 level in bowel tissue. ELISA revealed that 6-gingerol could significantly decrease the IL17 level and increase IL-10 level in both serum and bowel tissue, and the differences were all statistically significant (P<0.05). In addition, 6-gingerol could suppress the phosphorylation level of IκBα and p65, which was up-regulated by DSS. Further analysis with immunohistochemistry indicated p-p65 staining was mainly in the nucleus with some in the cytoplasm after DSS treatment, and the treatment with 6-gingerol could significantly weaken the density of p-p65 both in the cytoplasm and nucleus. CONCLUSIONS: Our study suggests that 6-gingerol may alleviate inflammatory injury in UC mice by regulating NF-κB signaling pathway.


Assuntos
Catecóis , Colite Ulcerativa , Álcoois Graxos , NF-kappa B , Transdução de Sinais , Animais , Catecóis/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana , Álcoois Graxos/farmacologia , Camundongos , NF-kappa B/metabolismo
11.
Ann Transl Med ; 8(7): 442, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32395486

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a non-specific chronic intestinal inflammatory disease with unclear etiology. Previous studies have suggested that the imbalance of Treg/Thl7 cells may be involved in the development of UC. It was found that 6-gingerol can alleviate the intestinal inflammatory damage and improve the weight loss of colitis mice. However, whether 6-gingerol can regulate the balance of Th17/Treg cells and inhibit the intestinal inflammatory response remains to be clarified. METHODS: In this study, a dextran sulfate sodium (DSS)-induced colitis mouse model was established, and the effects of 6-gingerol on cytokines and the balance of Th17/Treg cells were observed usingserial assays, including enzyme-linked immunosorbent assay (ELISA), quantitative real time-polymerase chain reaction (qPCR), and Western blotting. RESULTS: DSS caused the damage of bowel tissue and a 100% weight loss rate in colitis mice. The treatment of 6-gingerol can significantly relieve bowel damage and reduce incidence of weight loss to 16.7% at a low or high dose (P<0.05), which was similar to the therapeutic effect of mesalazine. It was found that DSS can up-regulate the mRNA levels of IL-6 and IL-17 in serum (by qPCR), and the serum and bowel levels of IL-6 and IL-17 (by ELISA); these levels were significantly different from those of the blank group (P<0.05). Furthermore, 6-gingerol was found to inhibit the increase of mRNA levels and serum and bowel levels of IL-6 and IL-17 induced by DSS, which is similar with mesalazine. It was also found that DSS can down-regulate the mRNA level of IL-10 in serum, along with the serum and bowel level of IL-10, with this being significantly different from the levels of the blank group (P<0.05). 6-gingerol could also inhibit the decrease of mRNA levels and serum and bowel levels of IL-10 induced by DSS, which is also similar to mesalazine. In addition, DSS could increase Th17 cell count and decrease Treg cell count in blood, with significant difference from that of the blank group (P<0.05). 6-gingerol could significantly (P<0.05) inhibit the increase of Th17 cells and the decrease of Treg cells induced by DSS, which is similar to the effect of mesalazine. The detection of expression levels of transcription factors RORγT for Th17 and FOXP3 for Treg at both mRNA and protein levels showed that DSS can up-regulate the mRNA and protein levels of RORγT, and down-regulate the mRNA and protein levels of FOXP3. Furthermore, 6-gingerol could significantly (P<0.05) inhibit the up-regulation of RORγT mRNA and protein, and the down-regulation of FOXP3 mRNA and protein induced by DSS, which is similar to the effect of mesalazine. CONCLUSIONS: 6-gingerol showed efficacy in the treatment of DSS-induced UC in mice, by regulating the cell balance of Th17/Treg, and by relieving inflammatory responses both systematically and locally.

12.
Food Funct ; 11(1): 221-235, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31915776

RESUMO

Lactobacillus salivarius is a species of lactic acid bacteria with probiotic potency. Compared to such well-known probiotics as L. rhamnosus and L. casei, the genomic characteristics and health-beneficial effects of L. salivarius are inadequately researched. For this study, a medium with enhanced selectivity for the isolation of L. salivarius was developed by optimizing the carbon source and antibiotics in the medium. Seventy-three L. salivarius strains were isolated from 472 fecal samples from Chinese populations, and their pan-genomic and phylogenetic characterizations were analyzed. Three strains (L. salivarius HN26-4, NT4-8, and FXJCJ7-2) that were clearly categorized in different sub-phylotypes of the phylogenetic tree were randomly selected for further studies. Compared to the other two tested strains, L. salivarius FXJCJ7-2 showed higher tolerance to simulated gastrointestinal tract conditions and more significant anti-inflammatory effects in lipopolysaccharides (LPS)-treated RAW264.7 murine macrophages. This strain was also more effective in reversing LPS-induced alterations in gut barrier function, colonic histopathology, Treg/Th-17 balance, immunomodulatory indicators, nuclear factor kappa B pathway activation, and the intestinal microenvironment of the mice than the other two tested strains. Comparative genomic analysis indicated that these protective effects may be related to the specific genes of L. salivarius FXJCJ7-2 that were involved in the tolerance to the gastrointestinal environment, short-chain fatty acid production, and host-bacterium interaction.


Assuntos
Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Inflamação/metabolismo , /isolamento & purificação , Animais , China , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Linfócitos T Reguladores/citologia , Células Th17/citologia
13.
Food Funct ; 11(2): 1279-1291, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-31984399

RESUMO

Lactobacillus plantarum is a probiotic that is widely used to prevent ulcerative colitis (UC). However, the effects of this species are strain-specific. We believe that the physiological characteristics of L. plantarum strains may affect their UC-alleviating function. Therefore, this study investigated the relationship between the alleviating effect of L. plantarum strains on UC and their physiological characteristics in vitro. The physiological characteristics of 14 L. plantarum strains were assayed in vitro, including gastrointestinal transit tolerance, oligosaccharide fermentation, HT-29 cell adhesion, generation time, exopolysaccharide production, acetic acid production, and conjugated linoleic acid (CLA) synthesis. To create animal models, colitis was established in C57BL/6 mice by adding 3.5% dextran sulfate sodium to drinking water for 7 days. L. plantarum strains with significantly different physiological characteristics were orally administered to the mice at a dose of 3 × 109 CFU. The results indicated that among the tested L. plantarum strains, L. plantarum N13 and L. plantarum CCFM8610 significantly alleviated colitis in the mice, as observed from the restoration of the body weight and disease activity index (DAI) score, recovery of the gut microbiota composition, reduced expression of pro-inflammatory cytokines, and significantly inhibited expression of p65. Correlation analysis indicated that four of the measured physiological characteristics (gastrointestinal transit tolerance, HT-29 cell adhesion, generation time, and CLA synthesis) were related to the UC-alleviating effects to different degrees. The strongest correlation was observed between the CLA synthesis ability and UC-alleviating effects (with Pearson correlation coefficients for IL-1ß, IL-6, IL-17F, TNF-α, myeloperoxidase, and the DAI all below -0.95). The ability to synthesize CLA may be the key physiological characteristic of L. plantarum in UC alleviation. Our findings may contribute to the rapid screening of lactic acid bacterial strains with UC-alleviating effects.


Assuntos
Colite Ulcerativa , Lactobacillus plantarum , Probióticos/farmacologia , Animais , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Colo/química , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Células HT29 , Humanos , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Microbiol Res ; 233: 126409, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927503

RESUMO

Insomnia is a common health problem in modern societies. GABA, an inhibitory neurotransmitter, can promote relaxation and reduce anxiety. In this study, milk was fermented with Lactobacillus brevis DL1-11, a strain with high GABA-producing capacity. The potential beneficial effects of this fermented milk on anxiety and sleep quality were evaluated in animal experiments. Sixty mice were divided into control, non-GABA fermented milk (NGFM), low-dose GABA fermented milk (LGFM, 8.83 mg/kg.bw), medium-dose GABA fermented milk (MGFM, 16.67 mg/kg.bw), high-dose GABA fermented milk (HGFM, 33.33 mg/kg.bw) and diazepam groups. The results of open field test and elevated plus-maze test indicated decreases in anxiety behavior after oral HGFM administration. Moreover, mice in the HGFM group exhibited a significantly prolonged sleep time after an intraperitoneal injection of sodium pentobarbital and a shortened sleep latency after an intraperitoneal injection of sodium barbital. These results indicate a beneficial effect of HGFM on sleep. Additionally, significant increases in the relative abundances of Ruminococcus, Adlercreutzia and Allobaculum and the levels of some short-chain fatty acids (SCFAs), such as butyric acid, were observed in the HGFM group. The results suggest that GABA-fermented milk may improve sleep and the protective pathways may involve in regulation of gut microbiota and increase of SCFAs level.


Assuntos
Produtos Fermentados do Leite , Microbioma Gastrointestinal , Distúrbios do Início e da Manutenção do Sono/terapia , Ácido gama-Aminobutírico/química , Animais , Ácidos Graxos Voláteis/análise , Masculino , Camundongos , Camundongos Endogâmicos ICR
15.
J Gastrointest Oncol ; 11(6): 1253-1260, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33456998

RESUMO

BACKGROUND: To investigate the correlation between Claudin-18 expression and the clinicopathological features and prognosis of gastric cancer. METHODS: A total of 63 patients who underwent gastric cancer surgery from December 2012 to June 2013 were recruited as the research participants. The clinicopathological data and prognostic information of the participants were collected, and expression levels of Claudin-18 in gastric cancer and adjacent tissues were detected by immunohistochemical (IHC) staining. The correlation between Claudin-18 expression and clinicopathological features of gastric cancer patients was analyzed. The Cox regression model was used to analyze the risk factors associated with the prognosis of gastric cancer patients. RESULTS: The expression of Claudin-18 was positive in 35 (55.6%) of the participants' gastric cancer tissues, which was significantly lower than that in the adjacent tissues (51 tissues/81.0%), and the difference was statistically significant (P=0.002). In addition, the IHC staining score of Claudin-18 expression in gastric cancer tissues (1.49±1.69), was significantly lower than that in the adjacent tissues (4.61±1.81), and the difference was statistically significant (P=0.016), The incidence of nerve invasion in patients with low expression of Claudin-18 was significantly higher than that in patients with high expression of Claudin-18 (P=0.038). In addition, univariate Cox regression analysis showed that nerve invasion, Claudin-18 staining score, tumor size, and positive count of lymph nodes were risk factors associated with the survival of gastric cancer patients. Multivariate Cox regression analysis showed that Claudin-18 staining score and tumor size were independent risk factors associated with the survival of gastric cancer patients. The overall survival (OS) of patients with low Claudin-18 staining score or larger tumor size was significantly reduced. CONCLUSIONS: The low expression of Claudin-18 was closely related to nerve invasion in gastric cancer, which indicated the poor clinical prognosis of gastric cancer patients.

16.
Ann Palliat Med ; 8(4): 483-489, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31431023

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory colonic disease strongly associated with intestinal epithelial cell (IEC) death. Necroptosis is characterized by a newly programmed cell death through a caspase-independent pathway. Receptor interacting protein 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) are very important in the pathway of necroptosis. However, their expression in UC remains unelucidated. This study aimed to investigate the expression of RIP3 and MLKL in patients with UC, along with its correlation with disease activity. METHODS: Colonic tissue samples were taken from 22 UC patients and 19 healthy controls. RIP3 and MLKL expression levels were evaluated by immunohistochemical staining and western blotting. RESULTS: RIP3 and MLKL were upregulated in inflamed tissues of UC (P<0.01). No variations were observed in healthy control subjects and non-inflamed colons (P>0.05). RIP3 and MLKL were positively correlated with UC disease activity (P<0.01). CONCLUSIONS: Our results suggest that necroptosis is strongly associated with intestinal inflammation in patients with UC. Further studies of necroptosis may be helpful in future treatments of UC.


Assuntos
Colite Ulcerativa/metabolismo , Necroptose/fisiologia , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Humanos , MAP Quinase Quinase Quinases/metabolismo , Masculino , Pessoa de Meia-Idade , Regulação para Cima/fisiologia , Adulto Jovem
17.
Transl Cancer Res ; 8(5): 1873-1881, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35116938

RESUMO

BACKGROUND: Neural precursor cell-expressed, developmentally downregulated protein 9 (NEDD9) is an invasion and metastasis-related gene. It has been proven to be highly expressed and closely associated with tumor proliferation and invasion in several types of human cancers including pancreatic adenocarcinoma. The present study was aimed to investigate and characterize the efficacy of silencing NEDD9 by lentivirus-delivered shRNA in pancreatic cancer (PC) BxPC-3 cells in vivo and in vitro. METHODS: Five kinds of PC cell lines were used to determine the cell line which expressed NEDD9 the most with qRT-PCR and western blotting. Then, we transduced the lentivirus-delivered NEDD9 shRNA into the human PC BxPC-3 cells to obtain a stable cell line expressing shRNA targeting NEDD9. NEDD9 mRNA and protein expression were measured by qRT-PCR and western blotting, respectively. Cell proliferation, migration, and invasion were assessed by cell colony formation, scratch wound healing, and Transwell assays, respectively. Mouse tumor xenografts were established by injecting tumor cells into the right flank of BALB/c nude mice. The effects of silencing NEDD9 on the growth of BxPC-3 cells in vivo were also examined. RESULTS: Among 5 kinds of PC cell lines, BxPC-3 cells were selected as the most suitab to carry out the following experiment. Transduction of lentivirus-delivered NEDD9 shRNA efficiently reduced NEDD9 expression in pancreatic adenocarcinoma BxPC-3 cells. Silencing NEDD9 by RNAi inhibited proliferation, migration, and invasion of BxPC-3 cells in cell culture. Importantly, it significantly reduced the growth of BxPC-3 cells in mouse xenografts. CONCLUSIONS: Silencing NEDD9 by lentivirus-delivered shRNA efficiently inhibited the growth of PC BxPC-3 cells both in vitro and in vivo, and may prove to be a potential new therapeutic agent for human PC.

18.
Int J Clin Exp Pathol ; 10(8): 8640-8646, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-31966721

RESUMO

The epithelial-to-mesenchymal transition (EMT) is a critical step in tumor metastasis. NEDD9 has been shown to be an oncogene in colorectal cancer. However, little is known about the relationship between NEDD9 and EMT in colorectal cancer metastasis. A total of 63 pairs of freshly frozen colorectal cancer tissues and adjacent noncancerous tissues were evaluated for NEDD9 gene expression using quantitative real-time PCR. The expression of NEDD9 and three epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, ß-catenin and vimentin) was examined in 122 colorectal cancers by immunohistochemistry. The expression of NEDD9 was markedly increased in colorectal cancer tissues compared with adjacent noncancerous tissues. The expression level of NEDD9 was positively correlated and TNM stage but not with other clinicopathological features of colorectal tumors. Furthermore, the expression of NEDD9 was strongly associated with the loss of epithelial marker E-cadherin and acquired expression of the mesenchymal markers nuclear ß-catenin and vimentin. These findings suggested that NEDD9 might promote EMT and the progression of colorectal cancer, and thus may be a potential therapeutic target of colorectal cancers.

19.
Hum Immunol ; 75(2): 176-81, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24269697

RESUMO

Helicobacter pylori infection is a risk factor for gastric cancer. In addition, toll-like receptor 4 (TLR4) plays a fundamental role in pathogen recognition and activation of innate immunity. This study investigated the association of TLR4 polymorphisms with a risk of intestinal metaplasia (IM) and intraepithelial neoplasia (IN) in a Chinese Han population. This study analyzed TLR4 gene polymorphisms in 333 patients (IM, 193 cases; IN, 140 cases) and 312 atypia-free controls in a Chinese Han population using a Taqman allelic discrimination assay. The TLR4 single nucleotide polymorphisms +896A/G and +1196C/T were not associated with the risk of IM or IN. However, the single-locus analysis showed that the C allele of TLR4+2856T/C had significantly reduced risk of IM and IN [adjusted odds ratio (OR)=0.42; 95%CI=0.29-0.62 and OR=0.62; 95%CI=0.41-0.93, respectively] compared with the wild-type homozygote (TT). The frequencies of TLR4+2856T/C TC and T carrier were significantly lower in patients with Sydney's slight IM and low grade IN (P<0.01 and P=0.01, respectively), while the TC genotype showed a lower risk of moderate IM compared to healthy controls (P=0.045). In addition, the data revealed that H. pylori infection, heavy alcohol consumption and high salt uptake were associated with a higher susceptibility for developing this neoplasm. TLR4 rs10759932 TC and C carriers were associated with a lower risk in developing precancerous lesions in the stomach in a Chinese Han population.


Assuntos
Infecções por Helicobacter/imunologia , Helicobacter pylori/fisiologia , Mucosa Intestinal/fisiologia , Intestinos/patologia , Neoplasias Gástricas/imunologia , Receptor 4 Toll-Like/genética , Adulto , Idoso , Estudos de Casos e Controles , China , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Humanos , Imunidade Inata/genética , Masculino , Pessoa de Meia-Idade , Neoplasias , Polimorfismo de Nucleotídeo Único , Risco , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética , Adulto Jovem
20.
Tumour Biol ; 34(5): 2857-61, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23681804

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of PDA; however, the molecular mechanisms that lead to pancreatic carcinogenesis are still not clearly understood. The aims of this study were to investigate the relationship between DLC-1 methylation status and clinicopathological characteristics of PDA patients and evaluate the role of DLC-1 methylation status in PDA. The expression of DLC-1 mRNA in PDA tissues was analyzed by real-time PCR. The methylation status of DLC-1 was analyzed by methylation-specific polymerase chain reaction (MSP). Furthermore, we determined the prognostic importance of DLC-1 methylation status in PDA patients. Our results showed that the expression level of DLC-1 mRNA in PDA tissues was lower than that in non-cancerous tissues. The rate of DLC-1 promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (p < 0.001). Downregulation of DLC-1 was strongly correlated with promoter methylation (P = 0.003). The presence of DLC-1 methylation in PDA tissue samples was significantly correlated with clinical stage (P = 0.005), histological differentiation (P = 0.05), and lymph node metastasis (P = 0.006). Kaplan-Meier survival analysis showed that DLC-1 methylation status was inversely correlated with overall survival of the PDA patients. Further, Cox multivariate analysis indicated that DLC-1 methylation status was an independent prognostic factor for the overall survival rate of PDA patients. In conclusion, our data suggest that downregulation of DLC-1 may be explained by DNA methylation; DLC-1 may be a biomarker for PDA.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Proteínas Ativadoras de GTPase/genética , Neoplasias Pancreáticas/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Metilação de DNA , Regulação para Baixo , Feminino , Proteínas Ativadoras de GTPase/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Regiões Promotoras Genéticas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Supressoras de Tumor/metabolismo
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