PMID: 

Biomed Res Int. 2020 ;2020:3617514. Epub 2020 Mar 16. PMID: 32258115

Abstract Title: 

Berberine Inhibits MDA-MB-231 Cells by Attenuating Their Inflammatory Responses.

Abstract: 

Breast cancer initiation is closely associated with cytokines that can change the inflammatory tumor microenvironment. Compounds extracted from plants have been explored for the possibility of cancer treatment in the recent decades. Berberine is an isoquinoline plant alkaloid with remarkable antioxidant and anti-inflammation roles, which is used in ethnic medicines, including traditional Chinese and North American medicine. In the present study, we investigated the effects of berberine on the malignant tumor cell behaviors in a breast cell line, MDA-MB-231. We found that berberine could not influence the cell viability in normal condition but was able to decrease the cancer cell migration capability in a scratch wound model and accordingly prolong the wound healing time. Furthermore, our results demonstrated that berberine inhibited the increased phosphorylation of c-Jun and c-Fos in these scratched cancer cells. With the cotreatment with LPS, which could boost the expression of cytokines in these cancer cells, berberine significantly reduced the increased expression of TNF-and IL-6. Meanwhile, we found that berberine inhibited the activation of NF-B by preventing the degradation of IB.

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PMID: 

J BUON. 2020 Jan-Feb;25(1):314-318. PMID: 32277648

Abstract Title: 

Berberine inhibits human gastric cancer cell growth via deactivation of p38/JNK pathway, induction of mitochondrial-mediated apoptosis, caspase activation and NF-κB inhibition.

Abstract: 

PURPOSE: Gastric cancer accounts for considerable mortality across the globe. In this study the anticancer effects of a natural compound Berberine were investigated in vitro. Effects of berberine on cell migration, cellular apoptosis, Nf-kB and JNK/p38 signalling pathways were also studied.METHODS: The cell viability of SNU-1 gastric cancer cells after berberine treatment was evaluated by CCK-8 assay, while the effects on cell migration were checked by wound healing assay. Effects on cellular apoptosis were evaluated by fluorescence microscopy using DAPI staining, as well as using flow cytometry with annexin V/propidium iodide (PI) staining. Effects on apoptosis-related protein expressions were checked by western blot method.RESULTS: The results showed that Berberine decreased the viability of the gastric cancer SNU-1 cells and exhibited an IC50 of 30µM. The cytoxicity of Berberine was also investigated on the normal GES-1 gastric cells and it was found that Berberine exerted very low toxic effects on these cells and exhibited an IC50 of 120 µM. Berberine also caused remarkable changes in the morphology of the SNU-1 cells. PI and DAPI stainingrevealed that Berberine prompted apoptosis of the SNU-1 cells in a dose-dependent manner. The apoptotic cells increased from 2.2% in control to around 35% at 30 µM concentration. Berberine also suppressed the migration and invasion of the gastric cancer cells via blocking of the JNK/p38 signallingpathway.CONCLUSIONS: Berberine may act as a promising drug candidate for gastric cancer as demonstrated from the current study.

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Studies reveal that ginger can be used to help alleviate rheumatoid arthritis’ persistent symptoms

PMID: 

Curr Microbiol. 2019 Jan ;76(1):29-36. Epub 2018 Oct 9. PMID: 30302554

Abstract Title: 

Adhesion-Related Immunomodulatory Activity of the Screened Lactobacillus plantarum from Sichuan Pickle.

Abstract: 

Lactic acid bacteria are the majority fermentation starter in the traditional fermented foods. In this research, a promising Lactobacillus plantarum was isolated from Sichuan pickle and its adhesion properties were analyzed in simulated gastrointestinal fluid with different methods. Meanwhile, the immunomodulatory effect of this strain was also evaluated in the Caco-2 cells. Results found that adhesion-related mub genes and other genes like lsp and tuf were upregulated in different culture times. Furthermore, L. plantarum cultured at alkaline environment revealed some anti-inflammation activity through inhibited expression of cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in Caco-2 cells. The texture of yogurt after fermented by this kind of isolated strain was also investigated, which provides the foundation for the further development and application of this kind of strain in food production. More investigations need to be carried out to determine whether this probiotic contributes to regulation of intestinal flora and prevention of gut inflammation.

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PMID: 

J Dairy Sci. 2019 Jan ;102(1):37-53. Epub 2018 Oct 19. PMID: 30343915

Abstract Title: 

Yogurt starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus ameliorate symptoms and modulate the immune response in a mouse model of dextran sulfate sodium-induced colitis.

Abstract: 

We investigated the yogurt starter cultures of Lactobacillus bulgaricus 151 and Streptococcus thermophilus MK-10 for their effect on the severity of experimental colitis, lymphocyte profile, and regulatory T-cell response. Colitis was induced in BALB/c mice via the administration of 3.5% dextran sulfate sodium salt (DSS) in drinking water for 6 d. Next, the mice were gavaged intragastrically with an active yogurt cultures (YC) mixture (∼5 × 10cfu/mouse per day) or saline (vehicle) for 8 d. Mice receiving DSS or saline alone served as positive and negative controls, respectively. The length of the colon, disease activity index, histological scores, myeloperoxidase activity, epithelium-associated microbes, short-chain fatty acid profile, total IgA antibody-forming cells, CD3CD8, CD3CD4, CD3CD4CD25, CD3CD4CD25Foxp3T-cell subsets, and cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and tumor necrosis factor) were examined after termination of the mice. Feeding mice with YC mixture reduced disease symptoms and modified intestinal microbiota and host inflammatory responsiveness to DSS. We observed limited weight loss and a decreased disease activity index score, lowered myeloperoxidase activity, and somewhat reduced damage of the intestine. The YC mixture upregulated the colon length, increased the amount and diversity of mucosa-associated microbes (enterobacteria, enterococci, and yeast), and decreased the concentration of putrefactive short-chain fatty acids in the cecal contents. It downregulated the input of cytotoxic CD3CD8T cells and CD3CD4CD25FoxP3regulatory T cells in Peyer's patches and enhanced CD3CD4CD25T cells in spleens and CD3CD4CD25FoxP3cells in peripheral blood mononuclear cells. Simultaneously, IgA antibody-forming cells were downregulated in mesenteric lymph nodes (MLN) and enhanced in spleens (SPL). The cultures mostly enhanced the production of cytokines tested in MLN and SPL, except for IL-6, which was downregulated in MLN. Interleukin-2 and IL-4 were the most upregulated in MLN, whereas IL-10, IL-4, IL-2, IFN-γ, and tumor necrosis factor were most upregulated in SPL. In serum, the YC mixture downregulated IFN-γ and clearly increased IL-2. Based on these results, we recognize the high anti-inflammatory and immunomodulatory potential of the L. bulgaricus 151 and S. thermophilus MK-10 set. The strains possess the ability to modulate the intestinal mucosal and systemic immune system toward both IgA production and induction of regulatory T cells, shifting Th1/Th2 balance.

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PMID: 

Microbiol Immunol. 2014 Oct ;58(10):559-69. PMID: 25130071

Abstract Title: 

Isolation of Enterococcus faecium NM113, Enterococcus faecium NM213 and Lactobacillus casei NM512 as novel probiotics with immunomodulatory properties.

Abstract: 

Probiotics, defined as living bacteria that are beneficial for human health, mainly function through their immunomodulatory abilities. Hence, these microorganisms have proven successful for treating diseases resulting from immune deregulation. The aim of this study was to find novel candidates to improve on and complement current probiotic treatment strategies. Of 60 lactic acid bacterial strains that were isolated from fecal samples of healthy, full-term, breast-fed infants, three were chosen because of their ability to activate human immune cells. These candidates were then tested with regard to immunomodulatory properties, antimicrobial effects on pathogens, required pharmacological properties and their safety profiles. To identify the immunomodulatory structures of the selected isolates, activation of specific innate immune receptors was studied. The three candidates for probiotic treatment were assigned Enterococcus faecium NM113, Enterococcus faecium NM213 and Lactobacillus casei NM512. Compared with the established allergy-protective strain Lactococcus lactis G121, these isolates induced release of similar amounts of IL-12, a potent inducer of T helper 1 cells. In addition, all three neonatal isolates had antimicrobial activity against pathogens. Analysis of pharmacological suitability showed high tolerance of low pH, bile salts and pancreatic enzymes. In terms of safe application in humans, the isolates were sensitive to three antibiotics (chloramphenicol, tetracycline and erythromycin). In addition, the Enterococcus isolates were free from the four major virulence genes (cylA, agg, efaAfs and ccf). Moreover, the isolates strongly activated Toll-like receptor 2, which suggests lipopeptides as their active immunomodulatory structure. Thus,three novel bacterial strains with great potential as probiotic candidates and promising immunomodulatory properties have here been identified and characterized.

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PMID: 

Genome Announc. 2015 Feb 12 ;3(1). Epub 2015 Feb 12. PMID: 25676767

Abstract Title: 

A17, the First Sequenced Strain of Lactococcus lactis subsp. cremoris with Potential Immunomodulatory Functions.

Abstract: 

Lactococcus lactis subsp. cremoris A17, isolated from Taiwan fermented cabbage, is the first sequenced strain of L. lactis subsp. cremoris with immunomodulatory activity and antiallergic functions. The resulting A17 draft genome contains 2,679,936 bp and indicates that A17 is a potential exopolysaccharide-producing strain without any known virulence gene.

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PMID: 

J Dairy Sci. 2016 Mar ;99(3):2288-2296. Epub 2016 Jan 13. PMID: 26774727

Abstract Title: 

Antibacterial activity and immunomodulatory effects on a bovine mammary epithelial cell line exerted by nisin A-producing Lactococcus lactis strains.

Abstract: 

Twenty-nine strains of mastitis pathogens were used to study the antibacterial activity of the cell-free supernatants (CFS) of 25 strains of Lactococcus lactis ssp. lactis. Out of the tested strains, only the CFS of L. lactis LL11 and SL153 were active, inhibiting and killing most of the pathogens. By means of ultra-performance liquid chromatography/high resolution mass spectrometry, they were shown to produce nisin A, a class I bacteriocin. A variable sensitivity to nisin A-containing CFS was observed among Streptococcus uberis and Enterococcus faecalis strains. Nonetheless, Streptococcus agalactiae, Strep. uberis, and E. faecalis displayed high minimum inhibitory concentration values, reaching 384 arbitrary units/mL. Interestingly, the minimum inhibitory values and the bactericidal concentrations were almost identical among them for each of the 2 stains, LL11 and SL153. Staphylococci were, on average, less sensitive than streptococci, but the 2 CFS inhibited and killed, at different dilutions, strains of methicillin-resistant Staphylococcus aureus. The immune response to nisin A-containing CFS was tested using the bovine mammary epithelial cell line BME-UV1. Application of CFS did not damage epithelial integrity, as demonstrated by the higher activity of N-acetyl-β-d-glucosaminidase (NAGase) and lysozyme inside the cells, in both treated and control samples. On the other hand, the increase of released NAGase after 15 to 24h of treatment with LL11 or SL153 live cultures demonstrated an inflammatory response of epithelial cells. Similarly, a significantly higher lysozyme activity was detected in the cells treated with LL11 live culture confirming the stimulation of lysosomal activity. The treatment of epithelial cells with SL153 live culture induced a significant tumor necrosis factor-α downregulation in the cells, but did not influence IL-8 expression. The control of tumor necrosis factor-α release could be an interesting approach to reduce the symptoms linked to clinical intramammary infections. Due to their antibacterial activity and to the stimulation of lysosomal activity of mammary epithelial cells, the L. lactis strains SL153 and LL11 could be of interest for the development of alternative intramammary treatments to control cow mastitis.

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PMID: 

Nutrients. 2020 Mar 14 ;12(3). Epub 2020 Mar 14. PMID: 32183266

Abstract Title: 

Effect of the11/19-B1 Strain on Atopic Dermatitis in a Clinical Test and Mouse Model.

Abstract: 

Some lactic acid bacteria (LAB) are known to improve atopic dermatitis (AD) through the regulation and stimulation of the host immune system. In this study, we found that ingestion of yogurt containing11/19-B1 strain (11/19-B1) daily for 8 weeks significantly improved the severity scoring of atopic dermatitis (SCORAD) system score from 38.8± 14.4 to 24.2 ± 12.0 in children suffering from AD. We tried to identify which LAB species among the five species contained in the test yogurt contributed to the improvement in AD pathology using an AD mouse model induced by repeated application of 1-fluoro-2, 4-dinitrobenzene (DNFB). AD-like skin lesions on the dorsal skin and ear were most improved by11/19-B1 intake among the five LAB species. In addition, analysis of CD4+ T cell subsets in Peyer's patches (PPs) and cervical lymph nodes (CLNs) indicated that the intake of11/19-B1 generally suppressed all subsets related to inflammation, i.e., Th1, Th2 and Th17, instead of activating the suppressive system, Treg, in the AD mouse model. Histological observations showed ingestion of11/19-B1 significantly suppressed severe inflammatory findings, such as inflammatory cell filtration, epidermal erosion and eosinophil infiltration. These results suggest that the immunomodulatory effects of11/19-B1 contribute to improvements in AD pathology.

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PMID: 

J Dairy Sci. 2019 Aug ;102(8):6802-6819. Epub 2019 Jun 13. PMID: 31202650

Abstract Title: 

Effect of fermented milk from Lactococcus lactis ssp. cremoris strain JFR1 on Salmonella invasion of intestinal epithelial cells.

Abstract: 

The process of fermentation contributes to the organoleptic properties, preservation, and nutritional benefits of food. Fermented food may interfere with pathogen infections through a variety of mechanisms, including competitive exclusion or improving intestinal barrier integrity. In this study, the effect of milk fermented with Lactococcus lactis ssp. cremoris JFR1 on Salmonella invasion of intestinal epithelial cell cultures was investigated. Epithelial cells (HT29-MTX, Caco-2, and cocultures of the 2) were treated for 1 h with Lactococcus lactis ssp. cremoris JFR1 fermented milk before infection with Salmonella enterica ssp. enterica Typhimurium. Treatment with fermented milk resulted in increased transepithelial electrical resistance, which remained constant for the duration of infection (up to 3 h), illustrating a protective effect. After gentamicin treatment to remove adhered bacterial cells, enumeration revealed a reduction in numbers of intracellular Salmonella. Quantitative reverse-transcription PCR data indicated a downregulation of Salmonella virulence genes hilA, invA, and sopD after treatment with fermented milk. Fermented milk treatment of epithelial cells also exhibited an immunomodulatory effect reducing the production of proinflammatory IL-8. In contrast, chemically acidified milk (glucono delta-lactone) failed to show the same effect on monolayer integrity, Salmonella Typhimurium invasion, and gene expression as well as immune modulation. Furthermore, an oppA knockout mutant of Salmonella Typhimurium infecting treated epithelial cells did not show suppressed virulence gene expression. Collectively, these results suggest that milk fermented with Lactococcus lactis ssp. cremoris JFR1 is effective in vitro in the reduction of Salmonella invasion into intestinal epithelial cells. A functional OppA permease in Salmonella is required to obtain the antivirulence effect of fermented milk.

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