Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Mapping and identification of QTLs for seed fatty acids in soybean(Glycine max L.)

Soybean is one of the most important sources of vegetable oil.The oil content and fatty acid ratio have attracted significant attention due to their impacts on the shelf-life of soybean oil products and consumer health.In this study,a high-density genetic map derived from Guizao 1 and Brazil 13 was used to analyze the quantitative trait loci of palmitic acid(PA),stearic acid(SA),oleic acid(OA),linoleic acid(LA),linolenic acid(LNA),and oil content(OC).A total of 54 stable QTLs were detected in the genetic map linkage analysis,which shared six bin intervals.Among them,the bin interval on chromosome 13(bin106-bin118 and bin123-bin125)was found to include stable QTLs in multiple environments that were linked to OA,LA,and LNA.Eight differentially expressed genes(DEGs)within these QTL intervals were determined as candidate genes according to the combination of parental resequencing,bioinformatics and RNA sequencing data.All these results are conducive to breeding soybean with the ideal fatty acid ratio for food,and provide the genetic basis for mining genes related to the fatty acid and oil content traits in soybean.

Effects of light spectra on growth and compositions of biomass,fatty acids,and pigments in three typical microalgae from different phyla

The growth and nutrients of photosynthetic organisms are significantly influenced by light spectra,yet this relationship is not well-understood in microalgae.Herein,we studied three microalgae species—Chaetoceros sp.,Isochrysis galbana,and Tetraselmis helgolandica—distinguished by their pigments.We exposed them to seven light spectra,including white(control),red,orange,green,blue,violet,and full spectrum.The results showed distinct responses in the three microalgae to varying light spectra.Optimal growth occurred under blue,violet,and white lights for Chaetoceros sp.,Ⅰ.galbana,and T.helgolandica,respectively,while orange,red,and green lights inhibited growth.Notably,green light significantly increased the protein content in all three microalgae.Carbohydrate and lipid content exhibited species-specific responses:the highest carbohydrate accumulation was achieved for Chaetoceros sp.under red light(73.27±1.45 mg/g),Ⅰ.galbana under orange light(122.89±12.28 mg/g),and T.helgolandica under blue light(43.62±2.79 mg/g).Meanwhile,the highest lipid content was obtained under violet light for Chaetoceros sp.andⅠ.galbana(250.80±7.27 and 320.23±5.75 mg/g,respectively),and under green light for T.helgolandica(255.12±31.19 mg/g).Furthermore,violet light greatly promoted the accumulation of polyunsaturated fatty acids in all three microalgae.Specific pigment compositions also responded to variations in light spectra.For instance,the diadinoxanthin content in Chaetoceros sp.increased significantly under orange light(194.77±13.78μg/g),while chlorophyll-a content inⅠ.galbana increased significantly under violet and blue lights((88.84±33.46)-(141.38±1.64)μg/g),and in T.helgolandica under red,green,and blue lights((1485.04±190.46)-(1886.60±387.42)μg/g).Additionally,Ⅰ.galbana exhibited the highest fucoxanthin,diadinoxanthin,andβ-carotene contents under white light.In conclusion,our results highlight the species-specific impact of light spectra on microalgae growth and nutrients,providing valuable guidance for flexible application of light spectra in microalgal production to enhance yields and target specific nutrients.

Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

Background The placenta plays a crucial role in supporting and influencing fetal development.We compared the effects of prepartum supplementation with omega-3(n-3)fatty acid(FA)sources,flaxseed oil(FLX)and fish oil(FO),on the expression of genes and proteins related to lipid metabolism,inflammation,oxidative stress,and the endocannabinoid system(ECS)in the expelled placenta,as well as on FA profile and inflammatory response of neonates.Late-pregnant Holstein dairy cows were supplemented with saturated fat(CTL),FLX,or FO.Placental cotyledons(n=5)were collected immediately after expulsion,and extracted RNA and proteins were analyzed by RTPCR and proteomic analysis.Neonatal blood was assessed for FA composition and concentrations of inflammatory markers.Results FO increased the gene expression of fatty acid binding protein 4(FABP4),interleukin 10(IL-10),catalase(CAT),cannabinoid receptor 1(CNR1),and cannabinoid receptor 2(CNR2)compared with CTL placenta.Gene expression of ECS-enzyme FA-amide hydrolase(FAAH)was lower in FLX and FO than in CTL.Proteomic analysis identified 3,974 proteins;of these,51–59 were differentially abundant between treatments(P≤0.05,|fold change|≥1.5).Top canonical pathways enriched in FLX vs.CTL and in FO vs.CTL were triglyceride metabolism and inflammatory processes.Both n-3 FA increased the placental abundance of FA binding proteins(FABPs)3 and 7.The abundance of CNR1 cannabinoid-receptor-interacting-protein-1(CNRIP1)was reduced in FO vs.FLX.In silico modeling affirmed that bovine FABPs bind to endocannabinoids.The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1,whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs.CTL placenta.Maternal FO enriched neonatal plasma with n-3 FAs,and both FLX and FO reduced interleukin-6 concentrations compared with CTL.Conclusion Maternal n-3 FA from FLX and FO differentially affected the bovine placenta;both enhanced lipid metabolism and modulated oxidative stress,however,FO increased some transcriptional ECS components,possibly related to the increased FABPs.Maternal FO induced a unique balance of pro-and anti-inflammatory components in the placenta.Taken together,different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes,which may affect the neonatal immune system.

Role of short-chain fatty acids in host physiology

Short-chain fatty acids(SCFAs)are major metabolites produced by the gut microbiota through the fermentation of dietary fiber,and they have garnered significant attention due to their close association with host health.As important mediators between the gut microbiota and the host,SCFAs serve as energy substrates for intestinal epithelial cells and maintain homeostasis in host immune and energy metabolism by influencing host epigenetics,activating G protein-coupled receptors,and inhibiting pathogenic microbial infections.This review provides a comprehensive summary of SCFAs synthesis and metabolism and offering an overview of the latest research progress on their roles in protecting gut health,enhancing energy metabolism,mitigating diseases such as cancer,obesity,and diabetes,modulating the gut-brain axis and gut-l ung axis,and promoting bone health.

Effects of forsythin extract in Forsythia leaves on intestinal microbiota and short-chain fatty acids in rats fed a high-fat diet

Forsythia suspensa,belonging to the deciduous shrubs of the Luteaceae family,a traditional Chinese medicine,has effects of alleviating swelling,clearing heat,detoxification and promoting blood circulation.The leaves of F.suspensa contain multiple chemical components and have a long history of use in folk medicines and health foods.The purpose of this study was to explore the effects of forsythin extract from F.suspensa leaves on intestinal microbiota and short-chain fatty acid(SCFA)content in rats with obesity induced by a high-fat diet.Forsythin extract in F.suspensa leaves increased the abundance of the intestinal microbiota,ameliorated intestinal microbiota disorders and inhibited the increase in total SCFA content in the intestinal tract in rats with obesity induced by a high-fat diet.These results suggested that forsythin extract in F.suspensa leaves may slow the development of obesity induced by a high-fat diet;thus,its active components and efficacy are worthy of further study.

Electrolyte dependence for the electrochemical decarboxylation of medium-chain fatty acids (n-octanoic acid) into fuel on Pt electrode

The deoxygenation of organic acids, important biomass feedstocks and derivatives, to synthesize hydrocarbon products under mild electrochemical conditions, holds significant importance for the production of carbon-neutral biofuels. There is still limited research on the influential factors of the electrochemical decarboxylation reaction of medium-chain fatty acids. In this study, n-octanoic acid (OA) was chosen as the research subject to investigate the electrochemical decarboxylation behavior of OA on a platinum electrode, focusing on the influence of different alkali metal cations (Li^(+), Na^(+), K^(+)), common anions (SO^(4)^(2−), Cl^(−)), and electrolyte pH. It was found that KOH as an electrolyte exhibited the best performance for OA. Possibly, the larger size of K^(+) increased the alkalinity of the electrode surface, facilitating OA deprotonation. LiOH electrolyte reduced the solubility of OA, thereby inhibiting the decarboxylation reaction. SO^(4)^(2−) exhibited a weak promoting effect on the decarboxylation reaction of OA, while Cl^(−) showed no adverse effect although Cl^(−) may adsorb on the electrode surface. Furthermore, unlike short-chain fatty acids, medium-chain OA can only achieve efficient decarboxylation under alkaline conditions due to its solubility properties. This study provides references and foundations for future efforts to enhance the efficiency of electrochemical decarboxylation synthesis of hydrocarbon biofuels from medium-chain fatty acids.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats

BACKGROUND Hepatorenal syndrome(HRS)is the most prevalent form of acute kidney injury in cirrhotic patients.It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease.Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients.Regular omega-3 supplementation has significantly reduced the risk of liver disease.This supplementation could represent an additional therapy for individuals with HRS.AIM To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats.METHODS Secondary biliary cirrhosis was induced in rats by biliary duct ligation(BDL)for 28 d.We used 24 male Wistar rats divided into the following groups:I(control);II(treated with omega-3,1 g/kg of body weight);III(BDL treated with omega-3,1 g/kg of body weight);and IV(BDL without treatment).The animals were killed by overdose of anesthetic;the kidneys were dissected,removed,frozen in liquid nitrogen,and stored in a freezer at-80℃for later analysis.We evaluated oxidative stress,nitric oxide(NO)metabolites,DNA damage by the comet assay,cell viability test,and apoptosis in the kidneys.Data were analyzed by one-way analysis of variance,and means were compared using the Tukey test,with P≤0.05.RESULTS Omega-3 significantly decreased the production of reactive oxygen species(P<0.001)and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3(P<0.001).The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group(P<0.01).NO production,DNA damage,and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group.There was an increase in mitochondrial electrochemical potential(P<0.001)in BDL treated with omega-3 compared to BDL.No changes in the cell survival index in HRS with omega-3 compared to the control group(P>0.05)were observed.CONCLUSION The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes,inhibiting the formation of free radicals,and reducing apoptosis.

A Review on Tibetan Swine(a)——Carcass,Meat Quality,Basic Nutrition Component,Amino Acids,Fatty Acids,Inosine Monophosphate and Muscle Fiber

In this review, the carcass, meat quality, internal organs, basic nutrition component, amino acids （AAs）, fatty acids, inosine monophosphate （IMP） and mus- cle fiber of Tibetan swine were summarized for the first time. The formation mecha- nism of excellent features was analyzed from the aspects of physiological traits, ge- ographical environments and constraint reasons. Thereby, the outstanding features of Tibetan swine could be extended continuously, and the poor characteristics should be improved in the future.

Preliminary Studies on High-performance Liquid Chro-matography Chemiluminescence Determination of theSaturated Fatty Acids(C_(16) C_(18))in Human Serum

The peroxyoxalate chemiluminescence(CL)detection of fatty acids in human se- rum combined with high-performance liquid chromatography (HPLC)is described.Some fatty acids in serum were extracted with a 1 :1(v/v)mixture of chloroform-n-heptane.2-(4-Hydrazinocarbonyl- phenyl)-4,5-diphenylimidazole (HCPI) was used as a fluorescent labelling reagent of the fatty acids. The labelling reaction was carried out at 30℃ for 1 h at pH 6.5 and the resulting reaction mixture was sudjected to HPLC. The labelled fatty acid C_(17)(P-C_(17))was used as the internal standard. The la- belled fatty acids C_(16) and C_(18) were separated within 18 min on an ODS-8OTM column (150 mm× 6 mm ID,5μm,Tosoh Japan).The calibrlation curves of fatty acids from the spiked control serum were Y_1=-0.003 7 + 0.0028X_1,r=0.994 for FA C_( 16) and Y_2=0.00 1 2 + 0.00098X_2,r=0.999 for FA C_( 18),respectively.The average recoveries of facids from the spiked contrl serum were 107.2%(n=8,RSD=4.3%)for FA C_(16) and 97.35%(n=8, RSD=4.0%)for FA C_(18),respectively.The lower detection limits of fatty acids after reaction were 12μmol per 20μl injection for FA C_(16) and 18 μmol per 20μl injection for FA C_(18),respectively(signal to noise ratio, S/N=2).The HPLC/CL method was applied to the determination of FA C_(16) and FA C_(18) in normal human serum and the results showed that the concentrations of fatty acids in normal human serum were 0.134 ± 0.009 μ mol/ml serum(n=5) for FA C_(16) and 0.052±0.028 μmol/ml serum(n=5)for FA C_(18),respectively.

Distinctive roles of unsaturated and saturated fatty acids in hyperlipidemic pancreatitis

AIM: To investigate how the saturated and unsaturated fatty acid composition influences the susceptibility of developing acute pancreatitis. METHODS: Primary pancreatic acinar cells were treated with low and high concentrations of different saturated and unsaturated fatty acids, and changes in the cytosolic Ca2+ signal and the expression of protein kinase C(PKC) were measured after treatment. RESULTS: Unsaturated fatty acids at high concentrations, including oleic acid, linoleic acid, palmitoleic acid, docosahexaenoic acid, and arachidonic acid, induced a persistent rise in cytosolic Ca2+ concentrations in acinar cells. Unsaturated fatty acids at low concentrations and saturated fatty acids, including palmitic acid, stearic acid, and triglycerides, at low and high concentrations were unable to induce a rise in Ca2+ concentrations in acinar cells. Unsaturated fatty acids at high concentrations but not saturated fatty acids induced intra-acinar cell trypsin activation and cell damage and increased PKC expression.CONCLUSION: At sufficiently high concentrations, unsaturated fatty acids were able to induce acinar cells injury and promote the development of pancreatitis. Unsaturated fatty acids may play a distinctive role in the pathogenesis of pancreatitis through the activation of PKC family members.

Role of free fatty acids in proliferation of rat hepatic stellate cells(Ⅱ)

AIM To study the role of free fatty acids (arachidonic acid and linoleic acid) in proliferation of rat hepatic stellate cells (HSC). METHODS HSC were isolated and cultured from liver of Wistar rats by in situ perfusion with pronase and collagenase, and density gradient centrifugation with Nycodenz. MTT colorimetric assay was detected for HSC proliferation. RESULTS Arachidonic acid and linoleic acid had an effect on proliferation of HSC. Arachidonic acid of 25mg/L promoted HSC proliferation ( P <0 01), but 50 and 100mg/L had an inhibitory effect on HSC ( P <0 01), and showed cytotoxity on HSC under inverted microscope; 6 25, 12 5 and 25mg/L of linoleic acid had no effect on HSC proliferation ( P >0 05), but with concentration increasing, 50 and 100mg/L of linoleic acid might promote HSC proliferation ( P <0 05 or 0 01). CONCLUSION Arachidonic acid and linoleic acid may promote HSC proliferation, but increased concentration can have cytotoxity on HSC. Arachidonic acid and linoleic acid might be associated with fatty liver and hepatic fibrogenesis by lipid peroxidation.

Kinetic analysis of waste activated sludge hydrolysis and short-chain fatty acids production at pH 10

The accumulation of short-chain fatty acids （SCFAs）, a preferred carbon source for enhanced biological phosphorus removal microbes, was significantly improved when waste activated sludge （WAS） was fermented at pH 10. The kinetics of WAS hydrolysis and SCFAs production at pH 10 was investigated. It was observed that during WAS anaerobic fermentation the accumulation of SCFAs was limited by the hydrolysis process, and both the hydrolysis of WAS particulate COD and the accumulation of SCFAs followed first-order kinetics. The hydrolysis and SCFAs accumulation rate constants increased with increasing temperature from 10 to 35℃, which could be described by the Arrhenius equation. The kinetic data further indicated that SCFAs production at pH 10 was a biological process. Compared with the experiment of pH uncontrolled （blank test）, both the rate constants of WAS hydrolysis and SCFAs accumulation at 20℃ were improved significantly when WAS was fermented at pH 10.

Expression profile of polyunsaturated fatty acids in colorectal cancer

AIM:To investigate the relationship between the metabolism of polyunsaturated fatty acids(PUFAs)andtumor-associated factors for predicting the outcome of colorectal carcinoma(CRC)in Chinese patients.METHODS:Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography.The levels of vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2),prostaglandin E2 and platelet-derived growth factor(PDGF)were measured by enzyme-linked immunosorbent assay,and the levels of VEGF,p53 and Ki-67 were measured by immunohistochemistry.RESULTS:In malignant tissue,compared with normal tissue,the levels of totalω-6 PUFAs(24.64%±3.41%vs 26.77%±3.37%,P=0.00)and linoleic acid(LA)(15.46%±3.51%vs 18.30%±2.83%,P<0.01)were lower,whereas the levels of totalω-3 PUFAs(1.58%±0.74%vs 1.35%±0.60%,P<0.01)and dihomo-gamma-linolenic acid(DGLA)(1.32%±0.69%vs 0.85%±0.29%,P<0.01)were significantly higher.The ratios of arachidonic acid(AA)/LA(0.53±0.22 vs0.42±0.19,P<0.01)and AA/totalω-6 PUFAs(0.31±0.09 vs 0.27±0.10,P<0.01)were also significantly higher in malignant tissue.The levels of PDGF(353.10±148.85 pg/m L vs 286.09±104.91 pg/m L,P<0.01),COX-2(125.21±70.29 ng/m L vs 67.06±42.22 ng/m L,P<0.01)and VEGF(357.11±128.76 pg/m L vs211.38±99.47 pg/m L,P<0.01)were also higher in malignant tissue compared to normal tissue.COX-2was inversely correlated with LA(R=-0.3244,P<0.05)and positively correlated with AA/totalω-6 PUFAs(R=0.3083,P<0.05)and AA/LA(R=0.3001,P<0.05).The tissue level of LA was highest in poorly differentiated tumors(19.9%±6.3%,P<0.05),while the ratio of AA/ω-3 PUFAs was lowest in these tumors(10.8±2.6,P<0.05).In VEGF-positive tumors,the level of LA was higher(16.2%±3.7%vs 13.9%±2.7%,P<0.01),while the AA/ω-3PUFA,AA/ω-6 PUFA,and AA/LA ratios were lower than in VEGF-negativetumors(5.0±1.8 vs 6.7±3.3,0.30±0.09 vs 0.34±0.09,0.50±0.21 vs 0.61±0.21,P<0.01).CONCLUSION:The metabolism of PUFAs may playan important role in the evolution of inflammationdriven tumorigenesis in CRC and may be considered apotential marker for prognosis.

Evaluation and comparison of short chain fatty acids composition in gut diseases

BACKGROUND An altered (dysbiosis) and unhealthy status of the gut microbiota is usually responsible for a reduction of short chain fatty acids (SCFAs) concentration. SCFAs obtained from the carbohydrate fermentation processes are crucial in maintaining gut homeostasis and their determination in stool samples could provide a faster, reliable and cheaper method to highlight the presence of an intestinal dysbiosis and a biomarker for various gut diseases. We hypothesize that different intestinal diseases, such as celiac disease (CD), adenomatous polyposis (AP) and colorectal cancer (CRC) could display a particular fecal SCFAs’ signature. AIM To compare the fecal SCFAs’ profiles of CD, AP, CRC patients and healthy controls, using the same analytical method. METHODS In this cross-sectional study, we defined and compared the SCFAs’ concentration in fecal samples of 9 AP, 16 CD, 19 CRC patients and 16 healthy controls (HC). The SCFAs’ analysis were performed using a gas-chromatography coupled with mass spectrometry method. Data analysis was carried out using Wilcoxon ranksum test to assess pairwise differences of SCFAs’ profiles, partial least squaresdiscriminate analysis (PLS-DA) to determine the status membership based on distinct SCFAs’ profiles, and Dirichlet regression to determine factors influencing concentration levels of SCFAs. RESULTS We have not observed any difference in the SCFAs’ amount and composition between CD and healthy control. On the contrary, the total amount of SCFAs was significantly lower in CRC patients compared to HC (P = 0.044) and CD (P = 0.005). Moreover, the SCFAs’ percentage composition was different in CRC and AP compared to HC. In detail, HC displayed higher percentage of acetic acid (P value = 1.3 × 10-6) and a lower amount of butyric (P value = 0.02192), isobutyric (P value = 7.4 × 10-5), isovaleric (P value = 0.00012) and valeric (P value = 0.00014) acids compared to CRC patients. AP showed a lower abundance of acetic acid (P value = 0.00062) and higher percentages of propionic (P value = 0.00433) and isovaleric (P value = 0.00433) acids compared to HC. Moreover, AP showed higher levels of propionic acid (P value = 0.03251) and a lower level of isobutyric acid (P value = 0.00427) in comparison to CRC. The PLS-DA model demonstrated a significant separation of CRC and AP groups from HC, although some degree of overlap was observed between CRC and AP. CONCLUSION Analysis of fecal SCFAs shows the potential to provide a non-invasive means of diagnosis to detect patients with CRC and AP, while CD patients cannot be discriminated from healthy subjects.

Anti-inflammatory properties of the short-chain fatty acids acetate and propionate:A study with relevance to inflammatory bowel disease

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.

A randomized controlled trial of omega-3 fatty acids in dry eye syndrome

AIM:To evaluate the role of dietary supplementation of omega-3 fatty acids in dry eye syndrome.METHODS:A prospective,interventional,placebo controlled,double blind randomized trial was done at two referral eye centers.Two hundred and sixty-four eyes of patients with dry eye were randomized to receive one capsule(500mg)two times a day containing 325mg EPA and 175mg DHA for 3 months(omega-3 group).The omega-3 group was compared to a group of patients(n=254)who received a placebo(placebo group).There were 4 patient visits(at baseline,1 month,2 months and3 months).On each visit,recording of corrected distance visual acuity(CDVA),slit lamp examination and questionnaire based symptom evaluation and scoring was done.A symptomatic score of 0-6 was mild,6.1-12moderate and 12.1-18 severe dry eye.Response to intervention was monitored by routine tear function tests like Schirmer I test,tear film break-up time(TBUT),Rose Bengal staining and most notably,conjunctival impression cytology.RESULTS:Sixty-five percent of patients in the omega-3group and 33%of patients in placebo group had significant improvement in symptoms at 3 months(P=0.005).There was a significant change in both Schirmer’s test value and TBUT values in the omega-3group(P【0.001),both comparisons.However,there was a larger drift in TBUT values in omega-3 than the placebo group,in comparison to Schirmer’s test values.The mean TBUT score was 2.54±2.34 in the omega-3group and 0.13±0.16 in placebo group,respectively.The mean reduction in symptom score in omega-3 group was 2.02±0.96 as compared to 0.48±0.22 in placebogroup(P【0.001).Despite a slight increase mean score,the Schirmer scores did not correlate well with symptomatic improvement.CONCLUSION:Omega-3 fatty acids have a definite role for dry eye syndrome.The benefit seems to be more marked in conditions such as blepharitis and meibomian gland disease.The role of omega fatty acids in tear production and secretion needs further evaluation.

Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids

BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (P<0.05). The elevation of plasma free fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (P<0.01). Sodium salicylate treatment decreased HGP, elevated GU (P<0.05), reduced MDA content by 60% (P<0.01), and increased the GSH-PX activity by 35% (P<0.05). CONCLUSIONS: Short-term elevation of fatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic links to oxidative stress.