Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the colon.Over the years,butyrate has att...Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the colon.Over the years,butyrate has attracted significant attention due to its diverse roles within cells.展开更多
Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide...Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide(LPS)-induced intestinal injury from the perspective of macrophage-intestinal epithelial cell interactions.Lactobacillus intervention improved the histopathological score;elevated ZO-1 and Occludin protein production;reduced CD16^(+)cell numbers;diminished IL-1β,IL-6,and TNF-αlevels;decreased inducible nitric oxide synthase(iNOS)expression;increased CD163^(+)cell numbers;elevated IL-10 concentration;and increased arginase-1(Arg1)expression in LPS-challenged piglets.Lactobacillus pretreatment also altered the colonic microbiota,thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets.Compared with those in the LPS group,sodium butyrate(SB)pretreatment decreased IL-1β,IL-6 and TNF-αsecretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages.The SB-pretreated macrophages reduced the protein expression of TLR4,MyD88,and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells.Moreover,GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells.This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.展开更多
Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify...Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.展开更多
Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force t...Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.展开更多
Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,hav...Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule ...Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.展开更多
[Objective] This study was to understand the effects of β-Amino butyric acid(abbreviated as BABA) induced rice blast resistance on reactive oxygen metabolism. [Method] Using the cultivar Chaochan 2 that is highly sus...[Objective] This study was to understand the effects of β-Amino butyric acid(abbreviated as BABA) induced rice blast resistance on reactive oxygen metabolism. [Method] Using the cultivar Chaochan 2 that is highly susceptible to disease as experimental material, the changes of catalase(CAT), and superoxide dismutase(SOD) and MDA activities in rice treated by BABA were investigated. [Result] In rice plants treated by BABA, the activities of CAT and SOD increased, meanwhile the MDA content also rose to some extent, resulting in the disease resistance to rice blast. [Conclusion] By influencing reactive oxygen metabolism, BABA endows rice plants with resistance to rice blast. BABA is safe to environment and has highly resistance-inducing capacity, it could be generalized in production.展开更多
Copolymer of maleic acid and acrylic acid （PMA-100）, combining with polyvinyl butyral （PVB） ultrafiltration membrane was used for the removal of Mn（II） from waste water by complexation-ultrafiltration. The carbo...Copolymer of maleic acid and acrylic acid （PMA-100）, combining with polyvinyl butyral （PVB） ultrafiltration membrane was used for the removal of Mn（II） from waste water by complexation-ultrafiltration. The carboxylic group content of PMA-100 and the rate of complexation reaction were measured. Effects of the mass ratio of PMA-100 to Mn（II） （n）, pH, background electrolyte, etc on the rejection rate （R） and permeate flux （J） were investigated. The results show that carboxylic group content of PMA-100 is 9.5 mmol/g. The complexation of Mn（II） with PMA-100 is rapid and completed within 5 min at pH 6.0. Both R and J increase with pH increasing in the range of 2.5-7.0, and R increases with the increase of n at pH 6.0 while J is little affected. The background electrolyte leads to the decrease of R, and CaCl2 has much greater effect on R than NaCl at the same ionic strength.展开更多
AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine rel...AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.展开更多
AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice we...AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.展开更多
The catalytic activities of TiSiW_(12)O_(40)/TiO_(2)in synthesizing ethylester;propyl ester,n-butyl ester;and amyl ester were reported.It was demonstrated thatTiSiW_(12)O_(40)/TiO_(2)is an excellent catalyst.Various f...The catalytic activities of TiSiW_(12)O_(40)/TiO_(2)in synthesizing ethylester;propyl ester,n-butyl ester;and amyl ester were reported.It was demonstrated thatTiSiW_(12)O_(40)/TiO_(2)is an excellent catalyst.Various factors concerned with esterification wereinvestigated.The optimum conditions were found:the mole ratio of alcohol to acid is 1.3:1,themass ratio of catalyst to reactants is 1.5 percent,and the reaction time is 1.0 h.Under theoptimum conditions,the yields are 88.0 percent for ethyl ester,94.5 percent for propyl ester,98.6percent for n-butyl ester,99.1 percent for n-amyl ester,and 96.7 percent for iso-amyl ester,respectively.展开更多
AIM： To investigate the effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. METHODS： Effects of tachyplesin and n-sodium butyrate on p...AIM： To investigate the effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. METHODS： Effects of tachyplesin and n-sodium butyrate on proliferation of BGC-823 cells were determined with trypan blue dye exclusion test and HE staining. Effects of tachyplesin and n-sodium butyrate on cell cycle were detected by flow cytometry. Protein levels of c-erbB-2, c-myc, p53 and p16 were examined by immunocytochemistry. RESULTS： The inhibiting effects were similar after 2.0 mg/L tachyplesin and 2.0 mmol/L n-sodium butyrate treatment, the inhibitory rate of cellular growth was 62.66% and 60.19% respectively, and the respective maximum mitotic index was decreased by 49.35% and 51.69% respectively. Tachyplesin and n-sodium buD/rate treatment could markedly increase the proportion of cells at G0/G1 phase and decrease the proportion at S phase. The expression levels of oncogene c-erbB-2, c-myc, and mtp53 proteins were down-regulated while the expression level of tumor suppressor gene p16 protein was up-regulated after the treatment with tachyplesin or n-sodium buD/rate. The effects of 1.0 mg/L tachyplesin in combination with 1.0 mmol/L n-sodium butyrate were obviously superior to their individual treatment in changing cell cycle distribution and expression of c-erbB-2, c-myc, mtp53 and p16 protein. The inhibitory rate of cellular growth of BGC-823 cells after combination treatment was 62.29% and the maximum mitotic index wasdecreased by 51.95%. CONCLUSION： Tachyplesin as a differentiation inducer of tumor cells has similar effects as n-sodium butyrate on proliferation of tumor cells, expression of correlative oncogene and tumor suppressor gene. It also has a synergistic effect on differentiation of tumor cells.展开更多
Background: There is increasing research interest in using short-chain fatty acids(SCFAs) including butyrate as potential alternatives to antibiotic growth promoters in animal production. This study was conducted to e...Background: There is increasing research interest in using short-chain fatty acids(SCFAs) including butyrate as potential alternatives to antibiotic growth promoters in animal production. This study was conducted to evaluate the effects of supplementation of sodium butyrate(SB) in liquid feeds(milk, milk replacer, and the mixture of both)on the growth performance, rumen fermentation, and serum antioxidant capacity and immunoglobins in dairy calves before weaning. Forty healthy female Holstein calves(4-day-old, 40 ± 5 kg of body weight) were housed in individual hutches and randomly allocated to 1 of 4 treatment groups(n = 10 per group) using the RAND function in Excel. The control group was fed no SB(SB0), while the other three groups were supplemented with 15(SB15),30(SB30), or 45(SB45) g/d of SB mixed into liquid feeds offered. The calves were initially fed milk only(days 2 to 20), then a mixture of milk and milk replacer(days 21 to 23), and finally milk replacer only(days 24 to 60).Results: The SB supplementation enhanced growth and improved feed conversion into body weight gain compared with the SB0 group, and the average daily gain increased quadratically with increasing SB supplementation. No significant effect on rumen pH;concentrations of NH_3-N, individual and total VFAs;or acetate:propionate(A:P) ratio was found during the whole experimental period. Serum glutathione peroxidase activity increased linearly with the increased SB supplementation, while the serum concentration of maleic dialdehyde linearly decreased. Serum concentrations of immunoglobulin A, immunoglobulin G, or immunoglobulin M were not affected by the SB supplementation during the whole experimental period.Conclusions: Under the conditions of this study, SB supplementation improved growth performance and antioxidant function in pre-weaned dairy calves. We recommended 45 g/d as the optimal level of SB supplementation mixed into liquid feeds(milk or milk replacer) to improve the growth and antioxidant function of dairy calves before weaning.展开更多
Due to the grave pathological role of obesity, worldwide research is being continued to find out the causative factors involved in it. Recent advances in this field reveal a possible relationship between the compositi...Due to the grave pathological role of obesity, worldwide research is being continued to find out the causative factors involved in it. Recent advances in this field reveal a possible relationship between the compositional pattern of gut microbiota and genesis of obesity. Several study results have shown that short-chain fatty acids(SCFAs, microbiota-induced fermentation products) and lipopolysaccharides(LPS, an integral component of Gram negative microorganisms) play the key role in linking the two. Though several SCFAs are produced as microbiota-fermentation products, three of them, i.e., butyrate, propionate and acetate have been found to be definitely involved in obesity; though individually they are neither purely obesogenic nor antiobesogenic. Out of these, butyrate and propionate are predominantly antiobesogenic. Butyrate, though a major energy source for colonocytes, has been found to increase mitochondrial activity, prevent metabolic endotoxemia, improve insulin sensitivity, possess antiinflammatory potential, increase intestinal barrier function and protect against diet-induced obesity without causing hypophagia. Propionate has been found to inhibit cholesterol synthesis, thereby antagonizing the cholesterol increasing action of acetate, and to inhibit the expression of resistin in adipocytes. Moreover, both these SCFAs have been found to cause weight regulation through their stimulatory effect on anorexigenic gut hormones and to increase the synthesis of leptin. Unlike butyrate and propionate, acetate, which is substantially absorbed, shows more obesogenic potential, as it acts as a substrate for hepatic and adipocyte lipogenesis. High fat diet increases the absorption of LPS, which, in turn, has been found to be associated with metabolic endotoxemia and to induce inflammation resulting in obesity. Multiple independent and interrelated mechanisms have been found to be involved in such linking processes which are discussed in this review work along with some possible remedial measures for prevention of weight gain and obesity.展开更多
The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morpholog...The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.展开更多
This paper reviews the distinctive roles played by the transcriptional coactivators CREB-binding protein(CBP) and p300 in Wnt/β-catenin signaling and cell physiology in colorectal cancer(CRC). Specifically, we focus ...This paper reviews the distinctive roles played by the transcriptional coactivators CREB-binding protein(CBP) and p300 in Wnt/β-catenin signaling and cell physiology in colorectal cancer(CRC). Specifically, we focus on the effects of CBP- and p300-mediated Wnt activity on(1) neoplastic progression;(2) the activities of butyrate, a breakdown product of dietary fiber, on cell signaling and colonic cell physiology;(3) the development of resistance to histone deacetylase inhibitors(HDACis), including butyrate and synthetic HDACis, in colonic cells; and(4) the physiology and number of cancer stem cells. Mutations of the Wnt/β-catenin signaling pathway initiate the majority of CRC cases, and we have shown that hyperactivation of this pathway by butyrate and other HDACis promotes CRC cell apoptosis. This activity by butyrate may in part explain the preventive action of fiber against CRC. However, individuals with a high-fiber diet may still develop neoplasia; therefore, resistance to the chemopreventive action of butyrate likely contributes to CRC. CBP or p300 may modify the ability of butyrate to influence colonic cell physiology since the two transcriptional coactivators affect Wnt signaling, and likely, its hyperactivation by butyrate. Also, CBP and p300 likely affect colonic tumorigenesis, as well as stem cell pluripotency. Improvement of CRC prevention and therapy requires a better understanding of the alterations in Wnt signaling and gene expression that underlie neoplastic progression, stem cell fate, and the development of resistance to butyrate and clinically relevant HDACis. Detailed knowledge of how CBP- and p300 modulate colonic cell physiology may lead to new approaches for anti-CRC prevention and therapeutics, particularly with respect to combinatorial therapy of CBP/p300 inhibitors with HDACis.展开更多
Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in anim...Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.展开更多
AIM： To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS： One-gram sodium butyrate coate...AIM： To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS： One-gram sodium butyrate coated tablets containing ^13C-butyrate were orally administered to 12 healbhy subjects and 12 Crohn＇s disease patients and the rate of ^13C-butyrate absorption was evaluated by t3CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid （500 rag） was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS： The coated formulation delayed the ^13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn＇s disease patients than in healthy subjects. The variability of the peak ^13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION： Simultaneous evaluation of breath ^13CO2 and tauroursodeoxycholic acid concentrationtime curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn＇s disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.展开更多
Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetyla...Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the Gl-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.展开更多
This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. ...This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.展开更多
基金supported by an NHMRC Project Grant GNT2012895(to ASL)。
文摘Butyrate is a short-chain fatty acid of four carbons in length that is a by-product produced by the microbial fermentation of dietary fiber and undigested carbohydrates within the colon.Over the years,butyrate has attracted significant attention due to its diverse roles within cells.
基金supported by the National Nature Science Foundation of China(32272898)the National Key Research and Development Program(2021YFA0805904)the Fundamental Research Funds for the Central Universities(2662020DKQD004).
文摘Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function.This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide(LPS)-induced intestinal injury from the perspective of macrophage-intestinal epithelial cell interactions.Lactobacillus intervention improved the histopathological score;elevated ZO-1 and Occludin protein production;reduced CD16^(+)cell numbers;diminished IL-1β,IL-6,and TNF-αlevels;decreased inducible nitric oxide synthase(iNOS)expression;increased CD163^(+)cell numbers;elevated IL-10 concentration;and increased arginase-1(Arg1)expression in LPS-challenged piglets.Lactobacillus pretreatment also altered the colonic microbiota,thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets.Compared with those in the LPS group,sodium butyrate(SB)pretreatment decreased IL-1β,IL-6 and TNF-αsecretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages.The SB-pretreated macrophages reduced the protein expression of TLR4,MyD88,and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells.Moreover,GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells.This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.
基金support for the project was provided by Chicken Farmers of Saskatchewan(424357)Canadian Poultry Research Council(424854)+1 种基金Natural Sciences and Engineering Research Council of Canada(424679)Saskatchewan Agriculture Development Fund(426954).
文摘Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.
基金funded in part by Quanta Computer,Inc.,in Tanyuan,Taiwan,under contract number 6950759,as part of the AIR project.
文摘Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.
基金supported by grants from the National Natural Science Foundation of China(81873565 and 81900507).
文摘Background:Metabolic dysfunction-associated steatotic liver disease(MASLD)is one of the leading causes of chronic liver disease worldwide.Recently,short-chain fatty acids(SCFAs),as metabolites of intesti-nal flora,have been found to participate in the progression of MASLD.Sodium butyrate(NaB),one of the most important SCFAs,shows therapeutic potentials in MASLD and its mechanisms have not been fully understood.The present study aimed to investigate the effects of NaB on metabolic dysfunction-associated steatohepatitis(MASH)associated fibrosis as well as the underlying mechanisms.Methods:Male Sprague-Dawley rats were randomly assigned to three groups:(i)control group,stan-dard chow for 24 weeks;(ii)HFD group,high-fat and high-cholesterol diet(HFD)for 24 weeks;and(iii)HFD+NaB group,HFD for 24 weeks and NaB gavage for the last 16 weeks.Body weight,liver index(liver weight/body weight×100%),serum parameters,and liver histology were analyzed to evaluate MASH and fibrosis severity.AML12,RAW264.7 and LX2 cell lines were used for in vitro study.Results:Compared to MASH rats with fibrosis induced by 24-week HFD,NaB intervention alleviated the degree of hepatic steatosis,inflammation,hepatocyte ballooning,and fibrosis.Further mechanistic study showed that NaB supplementation significantly decreased miR-155-5p level in the liver and the serum of MASH rats,and the inhibition effects of miR-155-5p on suppressor of cytokine signaling 1(SOCS1)in both hepatocytes and hepatic stellate cells(HSCs)were blunted when they were treated with NaB.Fur-thermore,NaB also significantly decreased the production of platelet-derived growth factor-BB(PDGF-BB),a pro-fibrotic mediator,in hepatocytes.NaB treatment on AML12 cells markedly impaired the prolifera-tion ability of co-cultured LX2 cells.Moreover,NaB intervention or miR-155-5p mimics also interferes extracellular regulated protein kinases signaling in LX2 cells.Conclusions:NaB intervention inhibited HSCs activation via miR-155-5p/SOCS1/PDGF signaling pathway and consequently relieved fibrosis in MASH rats.NaB might be a potential agent for the treatment of fibrosis in patients with MASH.
基金supported by the Central Government Guidance Local Science and Technology Development Fund Project(2021Szvup119)the Key Research and Development Plan of Shaanxi Province(2023-YBNY-184)+3 种基金the Regional Consolidated Fund-Youth Fund Project in Guangdong Province(2022A1515110717)China Postdoctoral Science Foundation(2022M72261)Guangdong Basic and Applied Basic Research Foundation(2021A1515110813)the 2021-National Center of Technology Innovation for Dairy-5.
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.
基金Supported by National Key Technology R&D Program During the Eleventh Five Year Plan (2006BAD08A04)Innovation Project(20076020)~~
文摘[Objective] This study was to understand the effects of β-Amino butyric acid(abbreviated as BABA) induced rice blast resistance on reactive oxygen metabolism. [Method] Using the cultivar Chaochan 2 that is highly susceptible to disease as experimental material, the changes of catalase(CAT), and superoxide dismutase(SOD) and MDA activities in rice treated by BABA were investigated. [Result] In rice plants treated by BABA, the activities of CAT and SOD increased, meanwhile the MDA content also rose to some extent, resulting in the disease resistance to rice blast. [Conclusion] By influencing reactive oxygen metabolism, BABA endows rice plants with resistance to rice blast. BABA is safe to environment and has highly resistance-inducing capacity, it could be generalized in production.
基金Project (21176264) supported by the National Natural Science Foundation of ChinaProject (11JJ2010) supported by Hunan Provincial Natural Science Foundation of ChinaProject (LC13076) supported by Undergraduate Innovation Foundation of Central South University,China
文摘Copolymer of maleic acid and acrylic acid （PMA-100）, combining with polyvinyl butyral （PVB） ultrafiltration membrane was used for the removal of Mn（II） from waste water by complexation-ultrafiltration. The carboxylic group content of PMA-100 and the rate of complexation reaction were measured. Effects of the mass ratio of PMA-100 to Mn（II） （n）, pH, background electrolyte, etc on the rejection rate （R） and permeate flux （J） were investigated. The results show that carboxylic group content of PMA-100 is 9.5 mmol/g. The complexation of Mn（II） with PMA-100 is rapid and completed within 5 min at pH 6.0. Both R and J increase with pH increasing in the range of 2.5-7.0, and R increases with the increase of n at pH 6.0 while J is little affected. The background electrolyte leads to the decrease of R, and CaCl2 has much greater effect on R than NaCl at the same ionic strength.
文摘AIM： To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation. METHODS： The effect of SCFAs on cytokine release from human neutrophils was studied with EHSA. SCFA- dependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice. RESULTS： Acetate, propionate and butyrate at 30 mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release. All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures. CONCLUSION： In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity, immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.
基金the State Key Development Program for Basic Research of China,No.2012CB517501National Natural Science Foundation of China,No.81070322,No.81270491,No.81470840 and No.31400001100 Talents Program,No.XBR2011007h
文摘AIM To investigate whether gut microbiota metabolite sodium butyrate (NaB) is an effective substance for attenuating non-alcoholic fatty liver disease (NAFLD) and the internal mechanisms. METHODS Male C57BL/6J mice were divided into three groups, normal control were fed standard chow and model group were fed a high-fat diet (HFD) for 16 wk, the intervention group were fed HFD for 16 wk and treated with NaB for 8 wk. Gut microbiota from each group were detected at baseline and at 16 wk, liver histology were evaluated and gastrointestinal barrier indicator such as zonula occluden-1 (ZO-1) were detected by immunohistochemistry and realtime-PCR, further serum or liver endotoxin were determined by ELISA and inflammation-or metabolism-associated genes were quantified by real-time PCR. RESULTS NaB corrected the HFD-induced gut microbiota imbalance in mice, while it considerably elevated the abundances of the beneficial bacteria Christensenellaceae, Blautia and Lactobacillus. These bacteria can produce butyric acid in what seems like a virtuous circle. And butyrate restored HFD induced intestinal mucosa damage, increased the expression of ZO-1 in small intestine, further decreased the levels of gut endotoxin in serum and liver compared with HF group. Endotoxin-associated genes such as TLR4 and Myd88, pro-inflammation genes such as MCP-1, TNF-alpha, IL-1, IL-2, IL-6 and IFN-gamma in liver or epididymal fat were obviously downregulated after NaB intervention. Liver inflammation and fat accumulation were ameliorated, the levels of TG and cholesterol in liver were decreased after NaB intervention, NAS score was significantly decreased, metabolic indices such as FBG and HOMA-IR and liver function indicators ALT and AST were improved compared with HF group. CONCLUSION NaB may restore the dysbiosis of gut microbiota to attenuate steatohepatitis, which is suggested to be a potential gut microbiota modulator and therapeutic substance for NAFLD.
文摘The catalytic activities of TiSiW_(12)O_(40)/TiO_(2)in synthesizing ethylester;propyl ester,n-butyl ester;and amyl ester were reported.It was demonstrated thatTiSiW_(12)O_(40)/TiO_(2)is an excellent catalyst.Various factors concerned with esterification wereinvestigated.The optimum conditions were found:the mole ratio of alcohol to acid is 1.3:1,themass ratio of catalyst to reactants is 1.5 percent,and the reaction time is 1.0 h.Under theoptimum conditions,the yields are 88.0 percent for ethyl ester,94.5 percent for propyl ester,98.6percent for n-butyl ester,99.1 percent for n-amyl ester,and 96.7 percent for iso-amyl ester,respectively.
基金Supported by the National Natural Science Foundation of China, No.30170724
文摘AIM： To investigate the effects of tachyplesin and n-sodium butyrate on proliferation and gene expression of human gastric adenocarcinoma cell line BGC-823. METHODS： Effects of tachyplesin and n-sodium butyrate on proliferation of BGC-823 cells were determined with trypan blue dye exclusion test and HE staining. Effects of tachyplesin and n-sodium butyrate on cell cycle were detected by flow cytometry. Protein levels of c-erbB-2, c-myc, p53 and p16 were examined by immunocytochemistry. RESULTS： The inhibiting effects were similar after 2.0 mg/L tachyplesin and 2.0 mmol/L n-sodium butyrate treatment, the inhibitory rate of cellular growth was 62.66% and 60.19% respectively, and the respective maximum mitotic index was decreased by 49.35% and 51.69% respectively. Tachyplesin and n-sodium buD/rate treatment could markedly increase the proportion of cells at G0/G1 phase and decrease the proportion at S phase. The expression levels of oncogene c-erbB-2, c-myc, and mtp53 proteins were down-regulated while the expression level of tumor suppressor gene p16 protein was up-regulated after the treatment with tachyplesin or n-sodium buD/rate. The effects of 1.0 mg/L tachyplesin in combination with 1.0 mmol/L n-sodium butyrate were obviously superior to their individual treatment in changing cell cycle distribution and expression of c-erbB-2, c-myc, mtp53 and p16 protein. The inhibitory rate of cellular growth of BGC-823 cells after combination treatment was 62.29% and the maximum mitotic index wasdecreased by 51.95%. CONCLUSION： Tachyplesin as a differentiation inducer of tumor cells has similar effects as n-sodium butyrate on proliferation of tumor cells, expression of correlative oncogene and tumor suppressor gene. It also has a synergistic effect on differentiation of tumor cells.
基金partially supported by the National Natural Science Foundation of China (award number:31802092)the National Key Research and Development Program of China (award numbers:2018YFE0101400 and 2017YFD0500502)+1 种基金the Agriculture Science and Technology Innovation Program (award number:ASTIP-IAS07-1)Beijing Dairy Industry Innovation Team (award number:BAIC06–2020)。
文摘Background: There is increasing research interest in using short-chain fatty acids(SCFAs) including butyrate as potential alternatives to antibiotic growth promoters in animal production. This study was conducted to evaluate the effects of supplementation of sodium butyrate(SB) in liquid feeds(milk, milk replacer, and the mixture of both)on the growth performance, rumen fermentation, and serum antioxidant capacity and immunoglobins in dairy calves before weaning. Forty healthy female Holstein calves(4-day-old, 40 ± 5 kg of body weight) were housed in individual hutches and randomly allocated to 1 of 4 treatment groups(n = 10 per group) using the RAND function in Excel. The control group was fed no SB(SB0), while the other three groups were supplemented with 15(SB15),30(SB30), or 45(SB45) g/d of SB mixed into liquid feeds offered. The calves were initially fed milk only(days 2 to 20), then a mixture of milk and milk replacer(days 21 to 23), and finally milk replacer only(days 24 to 60).Results: The SB supplementation enhanced growth and improved feed conversion into body weight gain compared with the SB0 group, and the average daily gain increased quadratically with increasing SB supplementation. No significant effect on rumen pH;concentrations of NH_3-N, individual and total VFAs;or acetate:propionate(A:P) ratio was found during the whole experimental period. Serum glutathione peroxidase activity increased linearly with the increased SB supplementation, while the serum concentration of maleic dialdehyde linearly decreased. Serum concentrations of immunoglobulin A, immunoglobulin G, or immunoglobulin M were not affected by the SB supplementation during the whole experimental period.Conclusions: Under the conditions of this study, SB supplementation improved growth performance and antioxidant function in pre-weaned dairy calves. We recommended 45 g/d as the optimal level of SB supplementation mixed into liquid feeds(milk or milk replacer) to improve the growth and antioxidant function of dairy calves before weaning.
文摘Due to the grave pathological role of obesity, worldwide research is being continued to find out the causative factors involved in it. Recent advances in this field reveal a possible relationship between the compositional pattern of gut microbiota and genesis of obesity. Several study results have shown that short-chain fatty acids(SCFAs, microbiota-induced fermentation products) and lipopolysaccharides(LPS, an integral component of Gram negative microorganisms) play the key role in linking the two. Though several SCFAs are produced as microbiota-fermentation products, three of them, i.e., butyrate, propionate and acetate have been found to be definitely involved in obesity; though individually they are neither purely obesogenic nor antiobesogenic. Out of these, butyrate and propionate are predominantly antiobesogenic. Butyrate, though a major energy source for colonocytes, has been found to increase mitochondrial activity, prevent metabolic endotoxemia, improve insulin sensitivity, possess antiinflammatory potential, increase intestinal barrier function and protect against diet-induced obesity without causing hypophagia. Propionate has been found to inhibit cholesterol synthesis, thereby antagonizing the cholesterol increasing action of acetate, and to inhibit the expression of resistin in adipocytes. Moreover, both these SCFAs have been found to cause weight regulation through their stimulatory effect on anorexigenic gut hormones and to increase the synthesis of leptin. Unlike butyrate and propionate, acetate, which is substantially absorbed, shows more obesogenic potential, as it acts as a substrate for hepatic and adipocyte lipogenesis. High fat diet increases the absorption of LPS, which, in turn, has been found to be associated with metabolic endotoxemia and to induce inflammation resulting in obesity. Multiple independent and interrelated mechanisms have been found to be involved in such linking processes which are discussed in this review work along with some possible remedial measures for prevention of weight gain and obesity.
文摘The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.
基金Supported by National Institutes of Health(Bethesda,MD)National Cancer Institute,No.1R15CA149589-01
文摘This paper reviews the distinctive roles played by the transcriptional coactivators CREB-binding protein(CBP) and p300 in Wnt/β-catenin signaling and cell physiology in colorectal cancer(CRC). Specifically, we focus on the effects of CBP- and p300-mediated Wnt activity on(1) neoplastic progression;(2) the activities of butyrate, a breakdown product of dietary fiber, on cell signaling and colonic cell physiology;(3) the development of resistance to histone deacetylase inhibitors(HDACis), including butyrate and synthetic HDACis, in colonic cells; and(4) the physiology and number of cancer stem cells. Mutations of the Wnt/β-catenin signaling pathway initiate the majority of CRC cases, and we have shown that hyperactivation of this pathway by butyrate and other HDACis promotes CRC cell apoptosis. This activity by butyrate may in part explain the preventive action of fiber against CRC. However, individuals with a high-fiber diet may still develop neoplasia; therefore, resistance to the chemopreventive action of butyrate likely contributes to CRC. CBP or p300 may modify the ability of butyrate to influence colonic cell physiology since the two transcriptional coactivators affect Wnt signaling, and likely, its hyperactivation by butyrate. Also, CBP and p300 likely affect colonic tumorigenesis, as well as stem cell pluripotency. Improvement of CRC prevention and therapy requires a better understanding of the alterations in Wnt signaling and gene expression that underlie neoplastic progression, stem cell fate, and the development of resistance to butyrate and clinically relevant HDACis. Detailed knowledge of how CBP- and p300 modulate colonic cell physiology may lead to new approaches for anti-CRC prevention and therapeutics, particularly with respect to combinatorial therapy of CBP/p300 inhibitors with HDACis.
基金supported by the Nuclear Research and Development Program(NRF-2012M2A2A7012377,NRF-2015M2B2B1068627 and NRF-2015R1C1A2A01053041)of the National Research Foundation of Korea(NRF)funded by the Korean Government Ministry of Science,ICT&Future Planning
文摘Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.
文摘AIM： To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS： One-gram sodium butyrate coated tablets containing ^13C-butyrate were orally administered to 12 healbhy subjects and 12 Crohn＇s disease patients and the rate of ^13C-butyrate absorption was evaluated by t3CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid （500 rag） was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS： The coated formulation delayed the ^13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn＇s disease patients than in healthy subjects. The variability of the peak ^13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION： Simultaneous evaluation of breath ^13CO2 and tauroursodeoxycholic acid concentrationtime curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn＇s disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.
基金supported by the grant from the National High-tech R&D Program(863 Program)(No.2007AA02Z163)the National Natural Science Foundation of China(No. 31000574)the Fundamental Research Fund for the Central Universities(No.78210042)
文摘Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the Gl-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.
文摘This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.
