Integration of proteomics and metabolomics reveals promotion of proliferation by exposure of bisphenol S in human breast epithelial MCF-10A cells.

PMID: 

Sci Total Environ. 2020 Jan 7 ;712:136453. Epub 2020 Jan 7. PMID: 31945527

Abstract Title: 

Integration of proteomics and metabolomics reveals promotion of proliferation by exposure of bisphenol S in human breast epithelial MCF-10A cells.

Abstract: 

Bisphenol S (BPS) has been reported to have similar estrogenic effects as bisphenol A (BPA). Considering the endocrine disrupting effects of BPS, in this study, we investigated the effects of BPS exposure on normal human breast epithelial cell line MCF-10A by using mass spectrometry (MS)-based metabolomics and quantitative proteomics. We found that exposure to BPS for 24 h altered the proliferation of MCF-10A cells in a hormetic manner with the highest proliferation rate at the dosage of 1 μM. A total of 200 proteins were identified to be significantly changed by 1 μM of BPS exposure. The upregulation of epidermal growth factor receptor (EGFR) and Ras/mTOR-related proteins implied that EGFR-mediated pathways were involved in BPS-induced proliferation of MCF-10A cells. In addition, several proliferation-related protein markers were found to be elevated, such as MKI67 and CDH1, further indicating the promotion of proliferation by low dose of BPS exposure.Besides, 35 endogenous metabolites were found to be significantly changed. The joint pathway analysis of the altered metabolites and proteins suggested changes in pathways of tricarboxylic acid (TCA) cycle, purine metabolism, pyruvate metabolism and lipid metabolism, which were involved in sustaining cell proliferation and cellular signal transduction. Taken together, this study provides insights into the effects and the potential mechanisms of BPS on estrogen receptor α-negative normal breast cell line MCF-10A, broadening our knowledge about the risk of using BPS as the alternative of BPA.

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Exposure to proton pump inhibitors and risk of pancreatic cancer.

PMID: 

Expert Opin Drug Saf. 2020 Jan 11. Epub 2020 Jan 11. PMID: 31928106

Abstract Title: 

Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis.

Abstract: 

: To estimate the pooled pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. An overall association between PPI exposure and pancreatic cancer risk was observed (OR=1.75, 95%CI=1.12-2.72, I=99%). This was confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose (DDD) of PPI exposure. In addition to the class effect for PPIs, rabeprazole had a singular significant association with pancreatic cancer (OR=5.40, 95%CI=1.98-14.703, I=87.9%).: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses, but was independent of duration, and Defined Daily Dose.

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The use of proton pump inhibitors may increase symptoms of muscle function loss in patients with chronic illnesses.

PMID: 

Int J Mol Sci. 2020 Jan 3 ;21(1). Epub 2020 Jan 3. PMID: 31947724

Abstract Title: 

The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses.

Abstract: 

Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota's composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.

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Lactobacillus reuteri improves gut barrier function and affects diurnal variation of the gut microbiota in mice fed a high-fat diet.

PMID: 

Food Funct. 2019 Aug 1 ;10(8):4705-4715. Epub 2019 Jul 15. PMID: 31304501

Abstract Title: 

Lactobacillus reuteri improves gut barrier function and affects diurnal variation of the gut microbiota in mice fed a high-fat diet.

Abstract: 

Lactobacillus reuteri FN041 is a secretory IgA-targeted Lactobacillus strain from human breast milk that has probiotic potential. The aim of this study was to test whether FN041 can alleviate dyslipidaemia and mucosal-barrier damage caused by a high-fat diet (HFD) and whether it can affect diurnal variation of the intestinal microbiota. C57BL/6 mice were fed either a normal chow diet or high-fat diet (HFD) for 7 weeks and were treated with either PBS as a control or L. reuteri FN041 for 4 weeks. Our results showed that FN041 treatment significantly attenuated HFD-induced weight gain (P

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Lactobacillus reuteri V3401 reduces inflammatory biomarkers and modifies the gastrointestinal microbiome in adults with metabolic syndrome.

PMID: 

Nutrients. 2019 Jul 31 ;11(8). Epub 2019 Jul 31. PMID: 31370223

Abstract Title: 

V3401 Reduces Inflammatory Biomarkers and Modifies the Gastrointestinal Microbiome in Adults with Metabolic Syndrome: The PROSIR Study.

Abstract: 

: Previous studies have reported that probiotics may improve clinical and inflammatory parameters in patients with obesity and metabolic syndrome (MetS).V3401 has shown promising results on the components of MetS in animal studies. We aimed to evaluate the effects ofV3401 together with healthy lifestyle recommendations on adult patients with MetS.METHODS: We carried out a randomized, crossover, placebo-controlled, single-center trial in which we included 53 adult patients newly diagnosed with MetS. Patients were block randomly allocated by body mass index (BMI) and sex to receive a capsule containing either the probioticV3401 (5× 10colony-forming units) or a placebo once daily for 12 weeks. Anthropometric variables, biochemical and inflammatory biomarkers, as well as the gastrointestinal microbiome composition were determined.RESULTS: There were no differences between groups in the clinical characteristics of MetS. However, we found that interleukin-6 (IL-6) and soluble vascular cell adhesion molecule 1 (sVCAM-1) diminished by effect of the treatment withV3401. Analysis of the gastrointestinal microbiome revealed a rise in the proportion of.CONCLUSIONS: Consumption ofV3401 improved selected inflammatory parameters and modified the gastrointestinal microbiome. Further studies are needed to ascertain additional beneficial effects of other probiotic strains in MetS as well as the mechanisms by which such effects are exerted.

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Lactobacillus reuteri extracts promoted wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway

PMID: 

Stem Cell Res Ther. 2019 Aug 7 ;10(1):243. Epub 2019 Aug 7. PMID: 31391121

Abstract Title: 

Lactobacillus reuteri extracts promoted wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway.

Abstract: 

BACKGROUND: The balance of oral microbiomes is crucial to maintain oral health. Microecological imbalance can impair the function of mesenchymal stem cells (MSCs) and lead to delay wound healing. Probiotics is a promising prevention approach for the treatment of oral inflammatory diseases caused by a bacterial infection. However, the effect of probiotics on oral MSCs and wound healing is unclear. In the present study, we used one type of probiotics Lactobacillus reuteri extracts to determine whether bacterial extracts could regulate the functions of gingiva MSCs (GMSCs) and promote wound healing.METHODS: Lactobacillus reuteri was prepared with bacterial extracts using ultrasonic crushing apparatus. The effects of Lactobacillus reuteri extracts on GMSCs were tested using the cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of Lactobacillus reuteri extracts in the wound in mice, the wound position of bilateral mesial gingival of the maxillary first molar was established, the wound area with a size of 1 mm × 2 mm and the full thickness gingiva was removed. Mice with wound were randomly distributed to two groups: injection of 0.9% NaCl (NS group) or injection of 50 μg/ml bacterial extracts.RESULTS: We discovered that 50 μg/ml Lactobacillus reuteri extracts increased the capacities of migration, expression of stem cell markers, osteogenic differentiation, and proliferation of GMSCs. In addition, local injection of 50 μg/ml bacterial extracts could promote wound-healing process in mice models. Mechanistically,we found that Lactobacillus reuteri extracts accelerated the process of wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway.CONCLUSIONS: These data showed that Lactobacillus reuteri extracts could activate the potentials of GMSCs, thus promote wound healing. Our discovery provided the insight of the underlying mechanism activating functions of MSCs and identified Lactobacillus reuteri extracts as a potential therapeutic strategy for accelerating oral wound and potential application in the future dental clinic.

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The application of Lactobacillus reuteri CCM 8617 and flaxseed positively improved the health of mice challenged with enterotoxigenic E. coli O149:F4.

PMID: 

Probiotics Antimicrob Proteins. 2019 Aug 13. Epub 2019 Aug 13. PMID: 31410766

Abstract Title: 

The Application of Lactobacillus reuteri CCM 8617 and Flaxseed Positively Improved the Health of Mice Challenged with Enterotoxigenic E. coli O149:F4.

Abstract: 

The aim of our study was to monitor the effects of dietary synbiotics on experimentally infected mice. Sixty mice were divided into the following three groups: negative control group C1, positive control group C2 (mice infected with enterotoxigenic Escherichia coli O149:F4), and experimental group LF (Lactobacillus reuteri CCM 8617 + 10% flaxseed + E. coli O149:F4). Supplements were administered for 42 days. Microbiological, hematological, and biochemical analyses, electrophoretic analysis of lactate dehydrogenase (LDH) isoenzymes, and analysis of fatty acids using gas chromatography and isotachophoresis were performed. We recorded higher numbers of jejunal and ileal lactic acid bacteria, lowerEnterobacteriaceae counts in the feces of the animals, and an increased production of organic acids in the synbiotic-fed group. The supplements applied favored n-3 polyunsaturated fatty acid (PUFA) metabolism and inhibited n-6 PUFA metabolism; thus, they influenced the n-6 to n-3 and eicosapentaenoic to arachidonic acid ratios. Additionally, the incorporation of n-3 PUFAs to the cell membrane decreased the activity of LDH, transaminases, and alkaline phosphatase. Results obtained in our study indicate the positive effect of continuous supplementation of combination of probiotic cheese enrichedwith L. reuteri CCM 8617and crushed flaxseed on composition of intestinal microflora and alleviation of the course of infection induced by pathogenic bacterium E. coli O149:F4.

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Lactobacillus reuteri protects mice against Salmonella typhimurium challenge by activating macrophages to produce nitric oxide.

PMID: 

Microb Pathog. 2019 Dec ;137:103754. Epub 2019 Sep 17. PMID: 31539587

Abstract Title: 

Lactobacillus reuteri protects mice against Salmonella typhimurium challenge by activating macrophages to produce nitric oxide.

Abstract: 

Lactobacillus reuteri, a typical intestinal symbiotic bacterium, plays an important role in maintaining intestinal flora stability and host health. However, the effect of Lactobacillus reuteri on peritoneal macrophages has not been thoroughly studied. Our study indicated that Lactobacillus reuteri could activate macrophages and that macrophages treated with Lactobacillus reuteri have an enhanced ability to phagocytose and to kill intracellular Salmonella typhimurium. Lactobacillus reuteri may reduce the inflammatory response caused by Salmonella typhimurium by regulating NO, thus effectively protecting mice against Salmonella typhimurium invasion and dissemination to the liver and spleen. Taken together, these data demonstrated the protective effect of Lactobacillus reuteri on macrophages and mice challenged with Salmonella typhimurium through in vitro and in vivo experiments.

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Systematic seview with meta-analysis: Lactobacillus reuteri DSM 17938 for treating acute gastroenteritis in children.

PMID: 

Nutrients. 2019 Nov 14 ;11(11). Epub 2019 Nov 14. PMID: 31739457

Abstract Title: 

Systematic Review with Meta-Analysis:DSM 17938 for Treating Acute Gastroenteritis in Children. An Update.

Abstract: 

The effectiveness ofDSM 17938 () for the management of acute gastroenteritis (AGE) has been recently questioned. We performed a systematic review to update evidence onfor treating AGE in children. We searched MEDLINE, EMBASE, the Cochrane Library databases, and additional data sources from January 2016 (end of search for our 2016 systematic review) to August 2019. The primary outcomes were stool volume and duration of diarrhea. Four RCTs were included. None of them evaluated stool volume. Compared with placebo or no treatment,reduced diarrhea duration (four RCTs,= 347, mean difference, MD -0.87 days, 95% CI [-1.43, -0.31]).use was also associated with a reduced duration of hospitalization (three RCTs,= 284, MD -0.54 days, 95% CI [-1.09, 0.0]). The small effect sizes of limited clinical relevance and methodological limitations of the included trials should be noted when interpreting these findings.

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L. reuteri is a good alternative for patients with chronic dyspepsia for the eradication of H. pylori infection.

PMID: 

Med Pharm Rep. 2019 Oct ;92(4):352-355. Epub 2019 Oct 25. PMID: 31750434

Abstract Title: 

versus triple therapy for the eradication ofin functional dyspepsia.

Abstract: 

Background and aim: The eradication ofinfection using PPI associated with different combinations of two or three antibiotics entails high risks of side effects and non- adherence. Therefore probiotics have been proposed foreradication.We tested the efficacy ofplus Pantoprazole compared to a triple regimen based on Pantoprazole plus Amoxicillin plus Clarithromycin in patients withinfection and functional dyspepsia.Methods: In a prospective design, 46 patients (M: 13, F: 33, mean age 48.80± 13.82 years) fulfilled the following inclusion criteria: age at least 18, documented informed consent, positivefinding by histology, no morphological changes of the gastric mucosa at upper gastrointestinal endoscopy and complaints of functional dyspepsia according to the Rome III criteria. Exclusion criteria were: presence of any other chronic organic diseases that required drug treatment, use of antibiotics, PPIs or H2 antagonists in the previous 3 months; pregnancy or lactation. Patients were randomly divided into two equal groups (23 patients each group). One group received the standard therapy in our area: Pantoprazole 40 mg bid for 30 days associated with Amoxicillin 2×1000 mg/day and Clarithromycin 500 mg bid for 14 days. The other group received Pantoprazole 40 mg/day plusDSMZ 17648 twice a day for 8 weeks. Post-treatment eradication was tested byantigen stool assay at 30 days after therapy.Results: The group onplus Pantoprazole presented 65.22% eradication rate compared to 73.91% cure rate in the group that received the Pantoprazole and Amoxicillin and Clarithromycin therapy, with no statistically significant difference in eradication rate between the two groups (p=0.75). The total adherence was good and eradication ofwas associated with improvement of dyspeptic symptoms for both eradication regimens.Conclusion: is a good alternative for patients with chronic dyspepsia for the eradication ofinfection. Its efficacy is similar to the triple therapy.

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