PMID: 

Sci Rep. 2019 Dec 5 ;9(1):18418. Epub 2019 Dec 5. PMID: 31804534

Abstract Title: 

Seven-day Green Tea Supplementation Revamps Gut Microbiome and Caecum/Skin Metabolome in Mice from Stress.

Abstract: 

Green tea supplementation has beneficial health effects. However, its underlying mechanisms, such as effects on modulating the intestinal microbiome and endogenous metabolome, particularly following short-term supplementation, are largely unclear. We conducted an integrative metabolomics study to evaluate the effects of short-term (7-day) supplementation of green tea extract (GTE) or its components, epigallocatechin gallate, caffeine, and theanine, on the caecum microbiota and caecum/skin metabolome in mice. Further, we established an integrative metabolome-microbiome model for correlating gut and skin findings. The effects of short-term supplementation with dietary compounds were evaluated with respect to UV stress response, with GTE showing the most remarkable effects. Biplot analysis revealed that Bifidobacteria and Lactobacillus spp. were considerably influenced by short-term GTE supplementation, while Clostridium butyricum was significantly increased by UV stress without supplementation. GTE supplementation helped the skin metabolome defend against UV stress. Interestingly, a significant positive correlation was observed between caecum bacteria (Bifidobacteria, Lactobacillus spp.) and metabolites including skin barrier function-related skin metabolites, caecal fatty acids, and caecal amino acids. Overall, 7-day GTE supplementation was sufficient to alter the gut microbiota and endogenous caecum/skin metabolome, with positive effects on UV stress response, providing insight into the mechanism of the prebiotic effects of GTE supplementation.

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PMID: 

Biomed Pharmacother. 2019 Nov 28 ;122:109689. Epub 2019 Nov 28. PMID: 31786467

Abstract Title: 

Ficus carica leaves extract inhibited pancreaticβ-cell apoptosis by inhibiting AMPK/JNK/caspase-3 signaling pathway and antioxidation.

Abstract: 

The aim of this study was to explore the inhibitory effects of Ficus carica leaves (FCL) extract on AMPK/JNK/caspase3 signaling pathway and antioxidation in pancreaticβ-cells. H&E staining, insulin immunohistochemistry, and TUNEL methods were used to investigate the effects of FCL on pancreatic histopathology in type 1 diabetic mice. The expression levels of caspase-3, AMPK, and JNK protein in the pancreatic tissue and MIN6 cells [induced by palmitic acid (PA) and hydrogen peroxide] were determined. Flow cytometry was used to detect the effects of FCL on apoptosis and ROS production of MIN6 cells. FCL (2 g/kg, continuous gavage for 6 weeks) significantly improved the pancreatic tissue injury in type 1 diabetic mice and reduced the expression levels of apoptosis-related proteins such as FasL, caspase8, Bax/Bcl-2, Cyt-C, caspase-3, p-AMPK, and p-JNK. FCL inhibited cell apoptosis induced by PA and the protein expression levels of caspase-3, p-AMPK, and p-JNK. The AMPK agonist AICAR could reverse the protective effects of FCL on MIN6 cells. The AMPK inhibitor compound C had a similar effect on MIN6 cells as that of FCL. FCL could inhibit cell apoptosis induced by hydrogen peroxide and reduced the production of ROS. In conclusion, FCL could inhibit pancreatic β-cell apoptosis by inhibiting the AMPK/JNK/caspase-3 signaling pathway and by antioxidation properties.

PMID: 

J Bioequivalence Bioavailab. 2019 ;11(2):19-28. Epub 2019 Apr 1. PMID: 31814674

Abstract Title: 

Crude Edible Fig () Leaf Extract Prevents Diethylstilbestrol (DES)-Induced DNA Strand Breaks in Single-Cell Gel Electrophoresis (SCGE)/Comet Assay: Literature Review and Pilot Study.

Abstract: 

Fig () trees are among the oldest plants on earth. The chemopreventive properties of constituent polyphenols and fiber that implicate figs in having a functional role in averting cancer have not been fully elucidated. We therefore hypothesized that fig leaf extract would inhibit (or attenuate) DES-induced DNA single-strand breakage in MCF10A human breast epithelial cells. To test this hypothesis, MCF10A cells were treated with DES (1, 10, 100μM), crude fig leaf extract (5, 10, 15 μL), or concomitant doses of DES (100 μM)/fig leaf extract (5, 10, 15 μL). The cells were analyzed for DNA strand breakage using the SCGE/COMET assay with mean olive tail moment as a marker of DNA damage. DES induced DNA strand breaks at all treatment levels compared to DMSO and non-treatment controls. DES at concentrations of 1, 10, and 100 μM produced mean olive tail moments of 1.2082 (177.6%), 1.2702 (186.7%), and 1.1275 (165.7%), respectively, which were statistically significantly (p

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PMID: 

Br J Pharmacol. 2019 Nov 25. Epub 2019 Nov 25. PMID: 31769014

Abstract Title: 

Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice.

Abstract: 

BACKGROUND AND PURPOSE: The gut microbial metabolite butyrate is closely linked to the modulation of metabolic disease. However, the efficacy and molecular mechanism of butyrate involved in atherosclerosis remain to be identified. Here, the pharmacological benefits and mechanism of butyrate were investigated in high-fat diet-fed ApoEmice after 16 weeks' administration.EXPERIMENTAL APPROACH: Gut microbiota composition was analysed via 16S rRNA gene sequencing of caecal contents. The pharmacological effects of butyrate on atherosclerosis were evaluated in vivo using the ApoEmice model. Serum samples were analysed for physiological parameters, whereas differentially expressed genes in liver samples were identified by hepatic transcriptome profiling. The proteins involved in reverse cholesterol transport were quantified by Western blot and immunohistochemical staining. Finally, the up-regulatory effects of butyrate on ABCA1 were further evaluated in RAW 264.7 cells, and the potential involvement of Sp1 was evaluated by Sp1 inhibition and silencing.KEY RESULTS: Oral gavage of butyrate altered microbiota composition and enhanced gut microbial diversity that decreased by HFD. Butyrate treatment significantly inhibited the HFD-induced atherosclerosis as well as hepatic steatosis without changing body weight gain in ApoEmice. Butyrate showed the metabolic effects in the liver through regulation of gene expression involved in lipid/glucose metabolism. Furthermore, ABCA1 was significantly induced by butyrate in vivo, ex vivo and in vitro, and Sp1 pathway was identified as a potential mechanism.CONCLUSIONS AND IMPLICATIONS: Our results demonstrated that butyrate ameliorates HFD-induced atherosclerosis in ApoEmice via ABCA1-mediated cholesterol efflux in macrophages, which suggesting a promising therapeutic strategy for protecting against atherosclerosis.

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PMID: 

J Mol Endocrinol. 2019 Nov 1. Epub 2019 Nov 1. PMID: 31770101

Abstract Title: 

Butyrate Modulates Diabetes-Linked Gut Dysbiosis: Epigenetic and Mechanistic Modifications.

Abstract: 

Diabetic dysbiosis has been described as a novel key player in diabetes and diabetic complications. However, the cellular/molecular alteration associated with dysbiosis remain poorly characterized. For that, control, non-obese type 2 diabetic MKR mice and MKR mice treated with butyrate were used to delineate the epigenetic, cellular and molecular mechanisms by which dysbiosis associated with diabetes induces colon shortening, inflammation attesting to gastrointestinal disturbance. Our results show that dysbiosis is associated with T2DM and characterized by reduced Bacteroid fragilis population and butyrate-forming bacteria. The reduction of butyrate-forming bacteria and inadequate butyrate secretion result in alleviating HDAC3 inhibition and alter colon permeability. The observed changes are also associated with increased ROS production, a rise in NOX4 proteins, and a shift in the inflammatory markers, where IL-1 is increased and IL-10 and IL-17 are reduced. Treatment with butyrate restores the homeostatic levels of NOX4 and IL-1. In summary, our data suggest that in T2DM, dysbiosis associates with a reduction in butyrate content leading to increased HDAC3 activity. Butyrate treatment restores thehomeostatic levels of the inflammatory markers and reduces ROS production known to mediate diabetes-induced colon disturbance. Taken together our results suggest that butyrate could be a potential treatment to attenuate diabetic complications.

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PMID: 

Int Immunopharmacol. 2019 Nov 25:106004. Epub 2019 Nov 25. PMID: 31780370

Abstract Title: 

Butyrate alleviates inflammatory response and NF-κB activation in human degenerated intervertebral disc tissues.

Abstract: 

Butyrate has multiple protective effects in inflammation-related intestinal diseases. Previous studies have found that butyrate could inhibit inflammation in rheumatoid arthritis. Inflammation is a pivotal inducement in the degeneration progress of the intervertebral disc. The anti-inflammatory treatment has an apparent curative effect in the symptomatic treatment of spine-related disease. Herein we investigated whether butyrate plays a protective role in degenerated intervertebral disc model. To mimic the lumbar disc local inflammatory environment, human primary nucleus pulposus cells were cultured with interleukin-1β (IL-1β, 10 ng/ml) to build a nucleus pulposus cell inflammation model. Butyrate was added to the cell culture medium to test the effect of butyrate on disc inflammation. Furthermore, a cultured nucleus pulposus tissue model was treated with butyrate (1 mM) to simulate the local treatment ofintervertebral disc disease. Herein, we found that butyrate could downregulate the production of the inflammatory mediator caused by IL-1β stimulation in the cell culture model. Additionally, butyrate inhibits the secretion of pro-inflammatory cytokines or graded enzymes in disc tissues from lumbardisc herniation patients. Furthermore, the anti-inflammatory function of butyrate in lumbar disc degenerated model may be caused by inhibiting the activation of the nuclear factor kappa B (NF-κB) signal pathway. This study presents butyrate as a candidate therapeutic method to treat lumbar disc degenerative disease.

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PMID: 

Toxicology. 2019 Nov 27 ;429:152338. Epub 2019 Nov 27. PMID: 31785310

Abstract Title: 

Kaempferol alleviates acute alcoholic liver injury in mice by regulating intestinal tight junction proteins and butyrate receptors and transporters.

Abstract: 

An impaired gut-liver axis is a potential factor that contributes to alcoholic liver disease. Specifically, ethanol decreases intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is negatively altered following acute ethanol exposure. This study aimed to determine whether kaempferol could protect against alcoholic liver injury (AALI) in mice by regulating tight junction (TJ) proteins and butyrate receptors and transporters in intestines. Male Institute of Cancer Research (ICR) mice were randomly divided into five treatment groups: control, ethanol administered (5 g/kg), and the low-, medium- and high-dosage kaempferol (25, 50, 100 mg/kg) treatments. Intestinal expression was evaluated for the TJ proteins ZO-1 and occludin and the butyrate receptor GPR109A and butyrate transporter SLC58A proteins, in addition to plasma ALT and AST levels and pathomorphological changes in liver and intestinal tissues. The expression of the TJ proteins ZO-1 and occludin, butyrate receptors, and butyrate transporters in the ileum and proximal colon decreased in AALI mice, while plasma ALT and AST levels markedly increased. Kaempferol supplementation reversed these effects. These results suggest that kaempferol could serve as a prophylactic treatment against AALI in mice by increasing the expression of butyrate receptors, transporters, and TJ proteins in the intestinal mucosa.

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PMID: 

Eur J Nutr. 2019 Dec 10. Epub 2019 Dec 10. PMID: 31822987

Abstract Title: 

Associations between tea and coffee beverage consumption and the risk of lung cancer in the Singaporean Chinese population.

Abstract: 

BACKGROUND: Tea and coffee are widely consumed beverages. Tea flavonoids have been shown to inhibit lung tumorigenesis using in vitro and in vivo models. Conversely, coffee contains complex mixtures of biochemically active compounds, some of which may have genotoxic and mutagenic properties. However, previous epidemiologic studies have shown inconsistent results on tea and coffee in relation to lung cancer risk.METHODS: The Singapore Chinese Health Study is a population-based prospective cohort of 63,257 Singaporean Chinese men and women, with an average of 17.7 years of follow-up. Information on tea and coffee consumption and other lifestyle factors was collected through in-person interviews at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders.RESULTS: There were 1486 incident lung cancer cases. Compared to non-daily coffee drinkers, HRs (95% CIs) of lung cancer risk for those consuming one, two, and three or more cups of coffee per day were 1.18 (1.02-1.36), 1.21 (1.05-1.40), and 1.32 (1.08-1.62) respectively (P for trend = 0.0034). The highest category of black tea consumption (at least 2 cups per day) was inversely associated with risk of lung cancer [HR (95% CI) = 0.73 (0.53-0.99)], particularly among men [HR (95% CI) = 0.67 (0.47-0.95)], compared to less-than-weekly black tea drinkers, although the interaction by sex was not statistically significant.CONCLUSIONS: Coffee beverage consumption was associated with higher risk of developing lung cancer. On the other hand, black tea intake was associated with lower risk of lung cancer among men in our cohort, and further studies are needed to confirm this association.

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PMID: 

Neurochem Int. 2016 10 ;99:110-132. Epub 2016 Jun 23. PMID: 27346602

Abstract Title: 

The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis?

Abstract: 

Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and d-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitorof histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neurological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication.

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PMID: 

Pneumologie. 2009 Sep ;63(9):508-11. Epub 2009 Aug 25. PMID: 19708009

Abstract Title: 

[Allergic alveolitis after influenza vaccination].

Abstract: 

Allergic alveolitis as a side effect of vaccination is very rare. We report a life-threatening complication in a female patient after influenza vaccination. The causative antigen was the influenza virus itself. Our Patient has suffered from exogen-allergic alveolitis for 12 years. Because of the guidelines of regular administration of influenza vaccination in patients with chronic pulmonary disease further research in patients with known exogen-allergic alveolitis is vitally important for the pharmaceutical drug safety.

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