Dietary sodium acetate and sodium butyrate improve high-carbohydrate diet utilization by regulating gut microbiota, liver lipid metabolism, oxidative stress, and inflammation in largemouth bass(Micropterus salmoides)

Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.

Alginate oligosaccharide-mediated butyrate-HIF-1a axis improves skin aging in mice

The“gut-skin”axis has been proved and is considered as a novel therapy for the prevention of skin aging.The antioxidant efficacy of oligomannonic acid(MAOS)makes it an intriguing target for use to improve skin aging.The present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in mice.The data indicated the skin aging phenotypes,oxidative stress,skin mitochondrial dysfunction,and intestinal dysbiosis(especially the butyrate and HIF-1a levels decreased)in aging mice.Similarly,fecal microbiota transplantation(FMT)from aging mice rebuild the aging-like phenotypes.Further,we demonstrated MAOS-mediated colonic butyrate-HIF-1a axis homeostasis promoted the entry of butyrate into the skin,upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1a/mitophagy loop in skin of mice.Overall,our study offered a better insights of the effectiveness of alginate oligosaccharides(AOS),promised to become a personalized targeted therapeutic agents,on gut-skin axis disorder inducing skin aging.

Coated sodium butyrate ameliorates high‑energy and low‑protein diet induced hepatic dysfunction via modulating mitochondrial dynamics, autophagy and apoptosis in laying hens

Background Fatty liver hemorrhagic syndrome(FLHS),a fatty liver disease in laying hens,poses a grave threat to the layer industry,stemming from its ability to trigger an alarming plummet in egg production and usher in acute mortality among laying hens.Increasing evidence suggests that the onset and progression of fatty liver was closely related to mitochondria dysfunction.Sodium butyrate was demonstrated to modulate hepatic lipid metabolism,alle-viate oxidative stress and improve mitochondrial dysfunction in vitro and mice models.Nevertheless,there is limited existing research on coated sodium butyrate(CSB)to prevent FLHS in laying hens,and whether and how CSB exerts the anti-FLHS effect still needs to be explored.In this experiment,the FLHS model was induced by administering a high-energy low-protein(HELP)diet in laying hens.The objective was to investigate the effects of CSB on alleviating FLHS with a focus on the role of CSB in modulating mitochondrial function.Methods A total of 288 healthy 28-week-old Huafeng laying hens were arbitrarily allocated into 4 groups with 6 replicates each,namely,the CON group(normal diet),HELP group(HELP diet),CH500 group(500 mg/kg CSB added to HELP diet)and CH750 group(750 mg/kg CSB added to HELP diet).The duration of the trial encompassed a period of 10 weeks.Results The result revealed that CSB ameliorated the HELP-induced FLHS by improving hepatic steatosis and patho-logical damage,reducing the gene levels of fatty acid synthesis,and promoting the mRNA levels of key enzymes of fatty acid catabolism.CSB reduced oxidative stress induced by the HELP diet,upregulated the activity of GSH-Px and SOD,and decreased the content of MDA and ROS.CSB also mitigated the HELP diet-induced inflammatory response by blocking TNF-α,IL-1β,and F4/80.In addition,dietary CSB supplementation attenuated HELP-induced activation of the mitochondrial unfolded protein response(UPRmt),mitochondrial damage,and decline of ATPase activity.HELP diet decreased the autophagosome formation,and downregulated LC3B but upregulated p62 protein expression,which CSB administration reversed.CSB reduced HELP-induced apoptosis,as indicated by decreases in the Bax/Bcl-2,Caspase-9,Caspase-3,and Cyt C expression levels.Conclusions Dietary CSB could ameliorate HELP diet-induced hepatic dysfunction via modulating mitochondrial dynamics,autophagy,and apoptosis in laying hens.Consequently,CSB,as a feed additive,exhibited the capacity to prevent FLHS by modulating autophagy and lipid metabolism.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Sodium butyrate alleviates fructose-induced non-alcoholic fatty liver disease by remodeling gut microbiota to promoteγ-amino butyric acid production

Sodium butyrate(NaB)can regulate lipid metabolism and inhibit hepatic steatosis.This study aimed to investigate whether NaB can alleviate fructose-induced hepat ic steatosis via remodeling the gut microbiota and evaluate the anti-fatty liver mechanisms.The results showed that NaB and NaB-remodeled gut microbiota significantly alleviated fructose-induced hepatic steatosis and increased plasma uric acid and fructose levels.Furthermore,both NaB and NaB-remodeled gut microbiota increased the abundance of Lactobacillus and altered the levels of plasma amino acids(upregulating gamma-amino butyric acid(GABA)and downregulating L-glutamic acid and L-arginine)in fructose-exposed mice.The correlation analysis showed that GABA levels positively correlated with Lactobacillus abundance,and increased GABA levels might promote the reduction of the hepatic triglyceride content.Further studies confirmed that GABA significantly reduced lipid deposition in mouse hepatocytes induced via fructose pretreatment in vitro.These findings suggested that NaB could ameliorate fructose-induced hepatic steatosis by regulating gut microbiota.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.

Preparation of Cellulose Acetate Butyrate Porous Micro/Nanofibrous Membranes and Their Properties

Cellulose acetate butyrate(CAB)is a cellulose ester that is commonly used in applications such as coatings and leather brighteners.However,its appearance in a fibrous form is rarely reported.CAB porous micro/nanofibrous membranes with a large number of nanopores on the fiber surface were successfully prepared by electrospinning with dichloromethane(DCM)/acetone(AC)as the mixed solvent.Apparent morphology,porosity,moisture permeability,air permeability,static water contact angles,and thermal conductivity of the fibrous membranes were investigated at different spinning voltages.The results showed that with the increase of the spinning voltage,the average fiber diameter of the CAB porous micro/nanofibrous membranes gradually decreased and the fiber diameter distribution was more uniform.When the spinning voltage reached 40 kV,the porosity reached 91.38%,the moisture permeability was up to 7430 g/(m^(2)·d),the air permeability was up to 36.289 mm/s,the static water contact angle was up to 145.0°,while the thermal conductivity of the fibrous membranes reached 0.030 W/(m·K).The material can be applied as thermal-insulation,waterproof and moisture-permeable membranes.

Chain Dynamics Heterogeneity in Plasticized Poly(vinyl butyral)(PVB) as Elucidated by Solid-State NMR

The chain dynamics heterogeneity of the poly(vinyl butyral)(PVB) plasticized by triethylene glycol bis(2-ethylhexa noate)(TEG-EH) was investigated by various solid-state NMR techniques.The plasticized PVB shows two domains in distinct molecular dynamics differences,namely,rigid and soft domains,where the latter is the plasticizer-rich domain.The time domain low field NMR was first used to investigate the dynamics heterogeneity of the plasticized PVB,and the results show the decreasing activated energy of components in the soft domain of plasticized PVB(E_a=20.2 kJ/mol) as compared with that of the pristine one(E_a=24.3 kJ/mol).Detailed dynamics heterogeneity was obtained by high-field NMR with site-specific features.The quadrupole-echo ~2H-NMR was adopted to elucidate the dynamics heterogeneity of the vinyl alcohol(VA) units,where only the hydroxyl group of VA is deuterated.The ~1H-^(13)C WISE NMR spectra show that there is not much difference in the mobility of the VB unit in PVB with and without plasticizer,whereas the glass transition temperature differed by approximately 53℃.This is further supported by Torchia's T_1 relaxation measurements.The origin of such an unusual phenomenon is attributed to the critical role of the remaining VA(~22%) in the soft domain,where the VA units locally aggregate through hydrogen bonding.Also,the existence of a mobility gradient in the VB unit has been demonstrated.Moreover,the mobility difference for VB with different stereo-geometry(meso or racemic conformation) is observed for the first time.This indicates the importance of modulating the ratio of meso over racemic VB for controlling the macroscopic perfo rmance of PVB.

Xylanase improves the intestinal barrier function of Nile tilapia(Oreochromis niloticus)fed with soybean(Glycine max)meal

Background Soybean(Glycine max)meal is one of the important protein sources for fish,but the non-starch polysaccharides(NSP)in soybean meal impair the intestinal barrier function.Here we aimed to investigate whether xylanase can alleviate the adverse effects on the gut barrier induced by soybean meal in Nile tilapia and to explore the possible mechanism.Results Nile tilapia(Oreochromis niloticus)(4.09±0.02 g)were fed with two diets including SM(soybean meal)and SMC(soybean meal+3,000 U/kg xylanase)for 8 weeks.We characterized the effects of xylanase on the gut barrier,and the transcriptome analysis was performed to investigate the underlying mechanism.Dietary xylanase improved intestinal morphology and decreased the concentration of lipopolysaccharide(LPS)in serum.The results of transcriptome and Western blotting showed that dietary xylanase up-regulated the expression level of mucin2(MUC2)which may be related to the inhibition of protein kinase RNA-like endoplasmic reticulum kinase(perk)/activating transcription factor 4(atf4)signaling pathways.Microbiome analysis showed that addition of xylanase in soybean meal altered the intestinal microbiota composition and increased the concentration of butyric acid in the gut.Notably,dietary sodium butyrate was supplemented into the soybean meal diet to feed Nile tilapia,and the data verified that sodium butyrate mirrored the beneficial effects of xylanase.Conclusions Collectively,supplementation of xylanase in soybean meal altered the intestinal microbiota composition and increased the content of butyric acid which can repress the perk/atf4 signaling pathway and increase the expression of muc2 to enhance the gut barrier function of Nile tilapia.The present study reveals the mechanism by which xylanase improves the intestinal barrier,and it also provides a theoretical basis for the application of xylanase in aquaculture.

Sodium butyrate alleviates deoxynivalenol-induced hepatic cholesterol metabolic dysfunction via RORγ-mediated histone acetylation modification in weaning piglets

Background:Cholesterol is an essential component of lipid rafts in cell plasma membrane,which exerts a hepatoprotective role against mycotoxin exposure in pigs,and cholesterol metabolism is vulnerable to epigenetic histone acetylation.Therefore,our present study aimed to investigate whether a histone deacetylase inhibitor(sodium butyrate [NaBu]) could protect the porcine liver from deoxynivalenol(DON) exposure by modulating cholesterol metabolism.Herein,we randomly divided 28 pigs into four groups,which were fed an uncontaminated basal diet,contaminated diet(4 mg DON/kg),uncontaminated diet supplemented with 0.2% NaBu or 4 mg/kg DON contaminated diet(4 mg DON/kg) supplemented with 0.2% NaBu for 28 d.Results:We found that the serum alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP) were all increased in pigs exposed to DON,indicative of significant liver injury.Furthermore,the cholesterol content in the serum of DON-exposed pigs was significantly reduced,compared to the healthy Vehicle group.Transcriptome analysis of porcine liver tissues revealed that the cholesterol homeostasis pathway was highly enriched due to DON exposure.In which we validated by qRT-PCR and western blotting that the cholesterol program was markedly activated.Importantly,NaBu effectively restored parameters associated with liver injury,along with the cholesterol content and the expression of key genes involved in the cholesterol biosynthesis pathway.Mechanistically,we performed a ChIP-seq analysis of H3K27ac and showed that NaBu strongly diminished DON-increased H3K27ac genome-wide enrichment.We further validated that the elevated H3K27ac and H3K9ac occupancies on cholesterol biosynthesis genes were both decreased by NaBu,as determined by ChIP-qPCR analysis.Notably,nuclear receptor RORγ,a novel regulator of cholesterol biosynthesis,was found in the hyperacetylated regions.Again,a remarkable increase of RORγ at both mRNA and protein levels in DON-exposed porcine livers was drastically reduced by NaBu.Consistent with RORγ expression,NaBu also hindered RORγ transcriptional binding enrichments on these activated cholesterol biosynthesis genes like HMGCR,SQLE,and DHCR24.Furthermore,we conducted an in vitro luciferase reporter assay to verify that porcine RORγ directly bonds to the promoters of the above target genes.Conclusions:Collectively,our results demonstrate the utility of the natural product Na Bu as a potential anti-mycotoxin nutritional strategy for regulating cholesterol metabolism via RORγ-mediated histone acetylation modification.

The specificity of ten non-digestible carbohydrates to enhance butyrate-producing bacteria and butyrate production in vitro fermentation

Butyrate and butyrate-producing bacteria are important indicators of gut microbial metabolism in human health.Ten non-digestible carbohydrates(NDCs),including inulin,fructooligosaccharide(FOS),oatsβ-glucans(OGS),oatsβ-glucan oligosaccharides(OGOS),Astragalus polysaccharides(APS),Astragalus oligosaccharides(AOS),xanthan gum oligosaccharides(XGOS),gellan gum oligosaccharides(GGOS),curdlan oligosaccharides(COS),and pullulan oligosaccharides(POS)were used to investigate NDC specifi city in modulating butyrate-producing bacteria and butyrate production in 48 h in vitro fermentation studies in combination with fecal inocula from 7 healthy donors and 11 patients with type 2 diabetes(T2D).We observed that the amount of these ten NDCs utilized depended on NDC structure and inter-individual gut microbial differences.XGOS and GGOS fermentations signifi cantly increased butyrate-producing bacteria(especially f_Lachnospiraceae)and butyric acid production.Furthermore,XGOS and GGOS fermentations showed a better ability to consistently modulate gut microbiota composition and metabolic properties between individuals of healthy donors or T2D patients when compared to inulin,FOS,APS,AOS,OGS,OGOS,COS and POS fermentation.This research indicated that xanthan gum and gellan gum oligosaccharides have strong specifi city to enhance butyrate-producing bacteria and butyrate production.

Short communication Catalytic synthesis of butyric esters with TiSiW_(12)O_(40)/TiO_2

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.

Supplementation with sodium butyrate improves growth and antioxidant function in dairy calves before weaning

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.

New-found link between microbiota and obesity

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.

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

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.

CREB-binding protein, p300, butyrate, and Wnt signaling in colorectal cancer

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.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.METHODS: Rats were divided into seven groups. Fourgroups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha(TNF-α) and interlukin-1β(IL-1β), myeloperoxidase(MPO), thiobarbituric acid reactive substances(TBARS), and ferric reduced ability of plasma(FRAP) were determined in the colon.RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α(114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β(24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS(0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO(15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP(23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.

Experimental study on model establishment，mechanism of production，and reverse therapy of gastric mucosal precancerous lesions

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Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2

Objective To investigate the role of extracellular signal-regulated kinase （ERK） in apoptosis of human colon cancer （HCT116） cells. Methods After the HCT116 cells were pretreated with specific ERK inhibitor （U0126） or specific siRNA and exposed to 10 mmol/L sodium butyrate （NaBT） for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. Results The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the UO126-blocked export of SphK2. Conclusion ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.

Sodium butyrate protects against toxin-induced acute liver failure in rats

BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.