Effects of a Yeast Product and Psyllium Husk on Colonic Gene Expression and Histopathology, Mesenteric Lymph Node Immune Cells, and Disease Activity Index of Colitis Mice

Abstract Objectives The beneficial effects of supplementing yeast products in terms of promoting gut health have been demonstrated in several animal species. These benefits include promoting gut integrity, modulating gut microbiota, and positively affecting immune responses. With these benefits, yeast products may be a strategy to relieve clinical signs associated with colitis. The objective of this study was to investigate the effects of a yeast product (YP) on colonic gene expression and histopathology, mesenteric lymph node (MLN) immune cells, and disease activity index (DAI) in a dextran sulfate sodium (DSS)-induced colitis model. Psyllium husk (PH), which has been shown to be protective in this model, also was included. Methods Fifty-four 6-week-old male C57BL/6J mice were assigned to: 1) AIN93G diet (control); 2) control diet + 5% YP; or 3) control diet + 5% PH. After 2 wk (d1–14) of diet adaptation, mice were provided with water or water + 3% (wt: vol) DSS for 5 d (d15–19). Body weight, food intake, water intake, and DAI data were recorded daily during the water/DSS treatment period. Mice were euthanized on d 20, followed by tissue collection. Data were analyzed using the Mixed Models procedure of SAS 9.4. Results MLN immune cell populations and colonic histopathology were not affected (P > 0.05) by diet. PH mice had greater (P < 0.05) gene expression of Cldn2, Cldn3, Cldn8, and Ocln compared to control mice. DAI, immune cell numbers, colonic histopathology, and colonic gene expression were not affected (P > 0.05) by YP in DSS mice. DSS mice consuming PH had lower (P < 0.05) DAI compared to control or YP mice. Conclusions Results suggest that YP at the dose tested failed to attenuate clinical signs or inflammation associated with colitis. PH, on the other hand, showed protective effects on DSS-induced colitis as reported previously. Funding Sources This research was funded internally.

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Endothelial Cell-Immune Cell Interaction in IBD

Digestive Diseases ◽

10.1159/000442925 ◽

2016 ◽

Vol 34 (1-2) ◽

pp. 43-50 ◽

Cited By ~ 8

Author(s):

Silvio Danese ◽

Claudio Fiocchi

Keyword(s):

Endothelial Cells ◽

Immune Cells ◽

Bowel Wall ◽

Regulatory Mechanism ◽

Immune Cell ◽

Cell Interaction ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph ◽

Inflammatory Bowel ◽

Lymphatic Fluid

The proper delivery of immune cells throughout the host's various tissues and organs is essential to health, and abnormalities in the type and quantity of leukocyte distribution is usually associated with disease. Because of its size and presence of a very large amount of immunocytes in the mucosa and mesenteric lymph nodes, the gut is the recipient of a constant influx of leukocytes, a process tightly regulated by multiple factors. These include cell adhesion molecules on the leukocytes and their counter-receptors on the microvascular endothelial cells in the bowel wall, a number of chemokines and cytokines that help attracting immune cells, platelets, bacterial products, danger signals, the size of the vascular and lymphatic beds and the process of leukocyte exit and circulation in the blood and lymphatic fluid. The disruption of any of the above regulatory mechanism can lead to inflammation, as is the case for inflammatory bowel disease. Learning how leukocyte and endothelial cells mutually function in health and what goes wrong in inflammation offers the opportunity to intervene therapeutically and re-establish the normal crosstalk between leukocytes and endothelial cells.

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The Toolbox for Untangling Chromosome Architecture in Immune Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.670884 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shuai Liu ◽

Keji Zhao

Keyword(s):

Gene Expression ◽

Immune Cells ◽

Spatial Organization ◽

Chromosome Structure ◽

Immune Cell ◽

Genome Structure ◽

Chromosome Architecture ◽

The Past ◽

Important Player ◽

The Way

The code of life is not only encrypted in the sequence of DNA but also in the way it is organized into chromosomes. Chromosome architecture is gradually being recognized as an important player in regulating cell activities (e.g., controlling spatiotemporal gene expression). In the past decade, the toolbox for elucidating genome structure has been expanding, providing an opportunity to explore this under charted territory. In this review, we will introduce the recent advancements in approaches for mapping spatial organization of the genome, emphasizing applications of these techniques to immune cells, and trying to bridge chromosome structure with immune cell activities.

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l-Isoleucine Administration Alleviates DSS-Induced Colitis by Regulating TLR4/MyD88/NF-κB Pathway in Rats

Frontiers in Immunology ◽

10.3389/fimmu.2021.817583 ◽

2022 ◽

Vol 12 ◽

Author(s):

Xiangbing Mao ◽

Rui Sun ◽

Qingxiang Wang ◽

Daiwen Chen ◽

Bing Yu ◽

...

Keyword(s):

Mrna Expression ◽

Activity Index ◽

Control Diet ◽

Average Daily Gain ◽

Disease Activity Index ◽

Inflammatory Cells ◽

Feed Conversion ◽

Enterocyte Apoptosis

Inflammatory bowel disease (namely, colitis) severely impairs human health. Isoleucine is reported to regulate immune function (such as the production of immunoreactive substances). The aim of this study was to investigate whether l-isoleucine administration might alleviate dextran sulfate sodium (DSS)-induced colitis in rats. In the in vitro trial, IEC-18 cells were treated by 4 mmol/L l-isoleucine for 12 h, which relieved the decrease of cell viability that was induced by TNF-α (10 ng/ml) challenge for 24 h (P <0.05). Then, in the in vivo experiment, a total of 44 Wistar rats were allotted into 2 groups that were fed l-isoleucine-supplemented diet and control diet for 35 d. From 15 to 35 d, half of the rats in the 2 groups drank the 4% DSS-adding water. Average daily gain, average daily feed intake and feed conversion of rats were impaired by DSS challenge (P <0.05). Drinking the DSS-supplementing water also increased disease activity index (DAI) and serum urea nitrogen level (P <0.05), shortened colonic length (P <0.05), impaired colonic enterocyte apoptosis, cell cycle, and the ZO-1 mRNA expression (P <0.05), increased the ratio of CD11c-, CD64-, and CD169-positive cells in colon (P <0.05), and induced extensive ulcer, infiltration of inflammatory cells, and collagenous fiber hyperplasia in colon. However, dietary l-isoleucine supplementation attenuated the negative effect of DSS challenge on growth performance (P <0.05), DAI (P <0.05), colonic length and enterocyte apoptosis (P <0.05), and dysfunction of colonic histology, and downregulated the ratio of CD11c-, CD64-, and CD169-positive cells, pro-inflammation cytokines and the mRNA expression of TLR4, MyD88, and NF-κB in the colon of rats (P <0.05). These results suggest that supplementing l-isoleucine in diet improved the DSS-induced growth stunting and colonic damage in rats, which could be associated with the downregulation of inflammation via regulating TLR4/MyD88/NF-κB pathway in colon.

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GJA1 Expression and Its Prognostic Value in Cervical Cancer

BioMed Research International ◽

10.1155/2020/8827920 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Silu Meng ◽

Xinran Fan ◽

Jianwei Zhang ◽

Ran An ◽

Shuang Li

Keyword(s):

Gene Expression ◽

Cervical Cancer ◽

Logistic Regression ◽

Gap Junction ◽

Signaling Pathway ◽

Immune Cells ◽

Immune Cell ◽

Normal Tissues ◽

Kaplan Meier ◽

Chi Squared

Gap Junction Protein Alpha 1 (GJA1) belongs to the gap junction family and has been widely studied in cancers. We evaluated the role of GJA1 in cervical cancer (CC) using public data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. The difference of GJA1 expression level between CC and normal tissues was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA), six GEO datasets, and the Human Protein Atlas (HPA). The relationship between clinicopathological features and GJA1 expression was analyzed by the chi-squared test and the logistic regression. Kaplan–Meier survival analysis and Cox proportional hazard regression analysis were used to assessing the effect of GJA1 expression on survival. Gene set enrichment analysis (GSEA) was used to screen the signaling pathways regulated by GJA1. Immune Cell Abundance Identifier (ImmuCellAI) was chosen to analyze the immune cells affected by GJA1. The expression of GJA1 in CC was significantly lower than that in normal tissues based on the GEPIA, GEO datasets, and HPA. Both the chi-squared test and the logistic regression showed that high-GJA1 expression was significantly correlated with keratinization, hormone use, tumor size, and FIGO stage. The Kaplan–Meier curves suggested that high-GJA1 expression could indicate poor prognosis ( p = 0.0058 ). Multivariate analysis showed that high-GJA1 expression was an independent predictor of poor overall survival (HR, 4.084; 95% CI, 1.354-12.320; p = 0.013 ). GSEA showed many cancer-related pathways, such as the p53 signaling pathway and the Wnt signaling pathway, were enriched in the high-GJA1-expression group. Immune cell abundance analysis revealed that the abundance of CD8 naive, DC, and neutrophil was significantly increased in the high-GJA1-expression group. In conclusion, GJA1 can be regarded as a potential prognostic marker of poor survival and therapeutic target in CC. Moreover, many cancer-related pathways may be the critical pathways regulated by GJA1. Furthermore, GJA1 can affect the abundance of immune cells.

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Aerobic training reduces immune cell recruitment and cytokine levels in adipose tissue in obese mice

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2018-0523 ◽

2019 ◽

Vol 44 (5) ◽

pp. 512-520 ◽

Cited By ~ 4

Author(s):

Débora Romualdo Lacerda ◽

Michele Macedo Moraes ◽

Albená Nunes-Silva ◽

Kátia Anunciação Costa ◽

Débora Fernandes Rodrigues ◽

...

Keyword(s):

Adipose Tissue ◽

Immune Cells ◽

Aerobic Training ◽

Immune Cell ◽

Control Diet ◽

Moderate Intensity ◽

Low Grade ◽

Carbohydrate Diet ◽

Cytokine Levels ◽

Low Grade Inflammation

Obesity is associated with an energy imbalance that results from excessive energy intake, low diet quality, and a sedentary lifestyle. The increased consumption of a high-refined carbohydrate (HC) diet is strongly related to higher adiposity and low-grade inflammation. Aerobic training is a well-known nonpharmacological intervention to treat obesity and metabolic disturbances. However, the mechanisms through which aerobic training ameliorates the low-grade inflammation induced by an HC diet should be further investigated. Our hypothesis herein was that aerobic training would decrease the recruitment of leukocytes in adipose tissue, thereby reducing the levels of cytokines and improving metabolism in mice fed an HC diet. Male Balb/c mice were assigned to the following groups: control diet/nontrained (C-NT), control diet/trained (C-T), high-refined carbohydrate diet/nontrained (HC-NT), and high-refined carbohydrate diet/trained (HC-T). Mice were submitted to moderate-intensity training sessions that consisted of running 60 min per day for 8 weeks. An intravital microscopy technique was performed in vivo in anesthetized mice to visualize the microvasculature of the adipose tissue. The HC diet induced obesity and increased the influx of immune cells into the adipose tissue. In contrast, HC-T mice presented a lower adiposity and adipocyte area. Furthermore, relative to HC-NT mice, HC-T mice showed increased resting energy expenditure, decreased recruitment of immune cells in the adipose tissue, reduced cytokine levels, and ameliorated hyperglycemia and fatty liver deposition. Collectively, our data enhance understanding about the anti-inflammatory effect of aerobic training and shed light on the adipose tissue-mediated mechanisms by which training promotes a healthier metabolic profile.

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Grape Pomace Inhibits Colon Carcinogenesis by Suppressing Cell Proliferation and Inducing Epigenetic Modifications in an AOM/DSS Mouse Model

Current Developments in Nutrition ◽

10.1093/cdn/nzaa044_057 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 358-358

Author(s):

Qiyu Tian ◽

Xhixin Xu ◽

Xiaofei Sun ◽

Jeanene Deavila ◽

Min Du ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Activity Index ◽

Control Diet ◽

Disease Activity Index ◽

Experimental Period ◽

Dna Demethylation ◽

Grape Pomace ◽

Protective Effects

Abstract Objectives Grape pomace (GP), a by-product of the wine and juice industry, is rich in bioflavonoids and dietary fibers. We hypothesized that grape pomace has protective effects against colitis-associated colorectal cancer (CRC). Methods Nine-week-old female mice were fed a control diet (CON) or CON with 5% grape pomace (GP) for 2 weeks, when mice were subjected to azoxymethane (AOM)/dextran sulfate sodium (DSS) for colorectal cancer (CRC) induction. All animals were received 1% DSS in drinking water for 7 days followed by a 21-day recovery in a 3-cycle experimental period, while receiving their respective diet. Results GP supplementation ameliorated the disease activity index (DAI) score, reduced tumor number, tumor size and pathological scores in AOM/DSS treated mice. Furthermore, dietary GP suppressed colonic expression of inflammatory cytokines, IL-1β and TNF-α, and inhibited NF-κB inflammatory signaling. Colorectal inflammation is known to enhance Wnt signaling and cell proliferation. In agreement, the content of β-catenin, a key downstream mediator of Wnt signaling, was reduced so for the expression of Cyclin D1 phosphorylation and content of p53 and PCNA level in GP-fed mice. In addition, GP reduced the expression of ALDH1, a marker of cell stemness, and increased the expression of Cdx2, a key transcription factor initiating epithelial cell differentiation. Consistently, DNA methylation of the promoter region of Cdx2 gene and hypermethylation of GpG island methylator phenotype (CIMP), which commonly occurs during CRC carcinogenesis, was alleviated in GP group. Conclusions GP supplementation suppressed colitis-associated CRC carcinogenesis associated with the suppression of inflammation and cell proliferation and the enhancement of DNA demethylation in Cdx2 and CIMP genes in the colon. Funding Sources USDA-NIFA 2018–67,017-27,517.

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MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

BioMed Research International ◽

10.1155/2013/279505 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 15

Author(s):

G. K. Chimal-Ramírez ◽

N. A. Espinoza-Sánchez ◽

D. Utrera-Barillas ◽

L. Benítez-Bribiesca ◽

J. R. Velázquez ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Immune Cells ◽

Immune Cell ◽

Morphological Changes ◽

Tumor Stroma ◽

Collagen Degradation ◽

Tumor Aggressiveness ◽

Soluble Factors ◽

Immune Effector

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

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Calculation of immune cell proportion from batch tumor gene expression profile based on support vector regression

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720020500304 ◽

2020 ◽

Vol 18 (05) ◽

pp. 2050030

Author(s):

Dongmei Ai ◽

Gang Liu ◽

Xiaoxin Li ◽

Yuduo Wang ◽

Man Guo

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Support Vector Regression ◽

Gene Expression Profile ◽

Immune Cells ◽

Immune Cell ◽

Relative Proportion ◽

Support Vector ◽

Cancer Tissues ◽

Cell Proportion

In addition to tumor cells, a large number of immune cells are found in the tumor microenvironment (TME) of cancer patients. Tumor-infiltrating immune cells play an important role in tumor progression and patient outcome. We improved the relative proportion estimation algorithm of immune cells based on RNA-seq gene expression profiling and solved the multiple linear regression model by support vector regression ([Formula: see text]-SVR). These steps resulted in increased robustness of the algorithm and more accurate calculation of the relative proportion of different immune cells in cancer tissues. This method was applied to the analysis of infiltrating immune cells based on 41 pairs of colorectal cancer tissues and normal solid tissues. Specifically, we compared the relative fractions of six types of immune cells in colorectal cancer tissues to those found in normal solid tissue samples. We found that tumor tissues contained a higher proportion of CD8 T cells and neutrophils, while B cells and monocytes were relatively low. Our pipeline for calculating immune cell proportion using gene expression profile data can be freely accessed from GitHub at https://github.com/gutmicrobes/EICS.git.

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ImmuSort, a database on gene plasticity and electronic sorting for immune cells

Scientific Reports ◽

10.1038/srep10370 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 19

Author(s):

Pingzhang Wang ◽

Yehong Yang ◽

Wenling Han ◽

Dalong Ma

Keyword(s):

Gene Expression ◽

Immune Cells ◽

Immune Cell ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Experimental Conditions ◽

Evaluation Scores ◽

Cell Groups ◽

Differential Gene ◽

Disease Associated Genes

Abstract Gene expression is highly dynamic and plastic. We present a new immunological database, ImmuSort. Unlike other gene expression databases, ImmuSort provides a convenient way to view global differential gene expression data across thousands of experimental conditions in immune cells. It enables electronic sorting, which is a bioinformatics process to retrieve cell states associated with specific experimental conditions that are mainly based on gene expression intensity. A comparison of gene expression profiles reveals other applications, such as the evaluation of immune cell biomarkers and cell subsets, identification of cell specific and/or disease-associated genes or transcripts, comparison of gene expression in different transcript variants and probe set quality evaluation. A plasticity score is introduced to measure gene plasticity. Average rank and marker evaluation scores are used to evaluate biomarkers. The current version includes 31 human and 17 mouse immune cell groups, comprising 10,422 and 3,929 microarrays derived from public databases, respectively. A total of 20,283 human and 20,963 mouse genes are available to query in the database. Examples show the distinct advantages of the database. The database URL is http://immusort.bjmu.edu.cn/.

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Novel Prognostic Biomarkers in Gastric Cancer: CGB5, MKNK2, and PAPPA2

Frontiers in Oncology ◽

10.3389/fonc.2021.683582 ◽

2021 ◽

Vol 11 ◽

Author(s):

Min Qin ◽

Zhihai Liang ◽

Heping Qin ◽

Yifang Huo ◽

Qing Wu ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Regression Analysis ◽

Immune Cells ◽

Prognostic Model ◽

Prognostic Markers ◽

Immune Cell ◽

Risk Group ◽

P Value ◽

Expression Data

IntroductionGastric cancer is one of the most common malignant tumors of the digestive tract. However, there are no adequate prognostic markers available for this disease. The present study used bioinformatics to identify prognostic markers for gastric cancer that would guide the clinical diagnosis and treatment of this disease.Materials and MethodsGene expression data and clinical information of gastric cancer patients along with the gene expression data of 30 healthy samples were downloaded from the TCGA database. The initial screening was performed using the WGCNA method combined with the analysis of differentially expressed genes, which was followed by univariate analysis, multivariate COX regression analysis, and Lasso regression analysis for screening the candidate genes and constructing a prognostic model for gastric cancer. Subsequently, immune cell typing was performed using CIBERSORT to analyze the expression of immune cells in each sample. Finally, we performed laboratory validation of the results of our analyses using immunohistochemical analysis.ResultsAfter five screenings, it was revealed that only three genes fulfilled all the screening requirements. The survival curves generated by the prognostic model revealed that the survival rate of the patients in the high-risk group was significantly lower compared to the patients in the low-risk group (P-value < 0.001). The immune cell component analysis revealed that the three genes were differentially associated with the corresponding immune cells (P-value < 0.05). The results of immunohistochemistry also support our analysis.ConclusionCGB5, MKNK2, and PAPPA2 may be used as novel prognostic biomarkers for gastric cancer.

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