Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid ...Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.展开更多
Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA infl...Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression.We quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell lines.Assessments were made of cell viability,apoptosis,and autophagy-related protein expression following PA administration.Interaction analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell lines.The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models.MiR-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control group.PA treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of DNMT3A.The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 methylation.Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis.In vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis.Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.展开更多
Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumu...Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumulation in NIT-1 pancreatic 13 cells. Methods： Cells were incubated in culture medium containing PA （0.25 mmol/L） for 24 h. Then treatments with BBR （10 μmol/L）, CA （100 μmol/L） and the combination of BBR and CA （BBR＋CA） were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase （AMPK） protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase （FAS）, acetyl-coA carboxylase （ACC）, phosphorylation acetyl-coA carboxylase （pACC）, carnitine acyl transferase 1 （CPT-1） and sterol regulating element binding protein lc （SREBP-lc） were determined by Western blot or real time polymerase chain reaction. Results： PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-I. Meanwhile, AMPK downstream lipogenic genes including SREBP-lc mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR＋CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic 13 cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. Conclusion： It can be concluded that in vitro, BBR and BBR＋CA could inhibit PA-induced lipid accumulation by decreasing lipoqenesis and increasin.cl lipid oxidation in NIT-1 pancreatic B cells.展开更多
Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[N...Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[Ni]^(−1)h^(−1))of palmitic acid and 100%selectivity of hydrocarbons with the outstanding stability during recycling application,compared to the impregnated Ni/HZSM-5 catalyst(14.0 g[palmitic acid]g[Ni]^(−1)h^(−1)).展开更多
Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Method...Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.展开更多
This study evaluated the effects of different proportions of palmitic(C16:0)and oleic(cis-9 C18:1)acids in fat supplements on rumen fermentation,glucose(GLU)and lipid metabolism,antioxidant function,and visceral fat f...This study evaluated the effects of different proportions of palmitic(C16:0)and oleic(cis-9 C18:1)acids in fat supplements on rumen fermentation,glucose(GLU)and lipid metabolism,antioxidant function,and visceral fat fatty acid(FA)composition in Angus bulls.The design of the experiment was a randomized block design with 3 treatments of 10 animals each.A total of 30 finishing Angus bulls(21±0.5 months)with an initial body weight of 626±69 kg were blocked by weight into 10 blocks,with 3 bulls per block.The bulls in each block were randomly assigned to one of three experimental diets:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic calcium salt(PA;90%C16:0),(3)CON+2.5%mixed FA calcium salts(MA;60%C16:0+30%cis-9 C18:1).Both fat supplements increased C18:0 and cis-9 C18:1 in visceral fat(P<0.05)and up-regulated the expression of liver FA transport protein 5(FATP5;P<0.001).PA increased the insulin concentration(P<0.001)and aspartate aminotransferase activity(AST;P=0.030)in bull's blood while reducing the GLU concentration(P=0.009).PA increased the content of triglycerides(TG;P=0.014)in the liver,the content of the C16:0 in visceral fat(P=0.004),and weight gain(P=0.032),and up-regulated the expression of liver diacylglycerol acyltransferase 2(DGAT2;P<0.001)and stearoyl-CoA desaturase 1(SCD1;P<0.05).MA increased plasma superoxide dismutase activity(SOD;P=0.011),reduced the concentration of acetate and total volatile FA(VFA)in rumen fluid(P<0.05),and tended to increase plasma non-esterified FA(NEFA;P=0.069)concentrations.Generally,high C16:0 fat supplementation increased weight gain in Angus bulls and triggered the risk of fatty liver,insulin resistance,and reduced antioxidant function.These adverse effects were alleviated by partially replacing C16:0 with cis-9 C18:1.展开更多
Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the s...Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.展开更多
Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H...Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H（δD） values and salinity. In this study we collected suspended particles along a salinity gradient from the Changjiang River Estuary（CRE）, and measured δD values in fatty acids in these particles. The results indicated that δD values of water were correlated highly with salinity from the CRE, in agreement with the results from other estuaries. δD values in palmitic acid and stearic acid had a positive correlation with δD values of water from the CRE. Nevertheless, in the CRE, hydrogen isotope fractionation in fatty acids relative to water increased as salinity increased, opposite the trend in hydrogen isotope fractionation with salinity found in microalgal culture and field studies. We attribute the increase in hydrogen isotope fractionation as salinity increased to light availability, which was likely lower in the particle rich mixing zone at the end of the estuary, and potentially as well to multiple sources of fatty acids in the CRE.展开更多
In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was elimin...In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.展开更多
The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-...The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-C bond cleavages in the hydrodeoxygenation of palmitic acid over Ni-Mo_(2)C catalyst.The catalytic activity on Ni doped Mo_(2)C with TOF of 6.9×10^(3)h^(-1)is much superior to intrinsic Mo_(2)C catalyst,which is also higher than most noble metal catalysts.Structurally,the doped Ni raises the active particle dispersion and the coordination numbers of Mo species(Mo-C and Mo-O),improves the graphitization degree to promote the electron transfer,and increases the amount of Lewis and Br?nsted acid,which are responsible for the excellent hydrodeoxygenation performance.The Ni promotes simultaneously C-O and C-C bonds cleavage to produce pentadecane and hexadecane owing to the increase of electron-rich Mo sites after Ni doping.These findings contribute to the understanding of the nature of Ni-doped Mo_(2)C on the roles as catalytic active sites for C-O and C-C bonds cleavage.展开更多
The aim of this study was</span><span style="font-family:Verdana;"> to investigate the effects of different modified fats on the body weight, biochemical profile, and biomarkers of hepatic oxidat...The aim of this study was</span><span style="font-family:Verdana;"> to investigate the effects of different modified fats on the body weight, biochemical profile, and biomarkers of hepatic oxidative status in Balb-</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">c</span></i><i><span style="font-family:Verdana;"></i></span></i><i><span style="font-family:""> </span></i><span style="font-family:""><span style="font-family:Verdana;">mice. The animals were divided into four groups and fed for 75 days with a </span><span style="font-family:Verdana;">normolipidic</span><span style="font-family:Verdana;"> (Control Group</span></span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;"> CG) or </span><span style="font-family:Verdana;">hiperlipidic</span><span style="font-family:Verdana;"> diets (40% kcal) containing a commercial interesterified fat (IFG) rich in palmitic acid (39%);a blend of non-interesterified fat (NIFG), with 2-fold less saturated fatty acids at the </span></span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">sn</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:""><span style="font-family:Verdana;">-2 position of triacylglycerols;or </span><span style="font-family:Verdana;">a partially</span><span style="font-family:Verdana;"> hydrogenated vegetable oil (</span><span style="font-family:Verdana;">PHFG), source of trans fatty acid (20%) and of linolenic acid (6%). The mice of the IFG and NIFG presented similar results in all evaluated parameters. The serum biochemical profile and hepatic oxidative stress markers in mice of the PHFG were similar to CG, except for total cholesterol (TC) which was significantly higher (p < 0.05) for the mice of th</span><span style="font-family:Verdana;">e PHFG. The mice feed with interesterified fat (IFG) showed serum TC (p < 0.01), non-HDL-C (p < 0.05), glucose (p < 0.05) and hepatic reduced glutathione values (2.7 fold, p < 0.05) and glutathione reductase activity (2.4 fold, p < 0.001) significantly higher when compared to the mice </span><span style="font-family:Verdana;">fed</span><span style="font-family:Verdana;"> with partially hydrogenated vegetable oil (PHFG). The hydrogenated fat source of trans fatty acid (20%) had less important metabolic effects than fats containing </span><span style="font-family:Verdana;">amount</span></span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> of palmitic acid (interesterified or non-interesterified). Our results suggest that the replacement of hydrogenated fats by interesterified fats may not be such a simple solution to reduce or eliminate </span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">trans</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:Verdana;"> fatty acids in foods.展开更多
This study presents the volatile constituents from leaves of Trifolium alexandrinum from Pakistan.The dried leaves were subjected to hydrodistillation for extraction and extracted volatile oil was subsequently charact...This study presents the volatile constituents from leaves of Trifolium alexandrinum from Pakistan.The dried leaves were subjected to hydrodistillation for extraction and extracted volatile oil was subsequently characterized by gas chromatography-mass spectrometry technique.A total of 22 compounds were identified where the most dominant constituents were:phytol(46.00%),palmitic acid(9.26%),phytol acetate(6.44%),and linolenic acid(3.47%).Most of these are well-known constituents to exhibit antibacterial,antioxidant,antitumor,and anti-inflammatory activities.展开更多
Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incub...Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.展开更多
Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and ery...Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.展开更多
Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we...Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.展开更多
Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagi...Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagic acid.The present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic conditions.Rat NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1βsecretion.Ellagic acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin A.Urolithin A did not statistically stimulate insulin secretion and did not inhibit IL-1β.展开更多
s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs ...s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs展开更多
Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expre...Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms.Calf hepatocytes were obtained from 5 healthy calves(1 d old;30to 40 kg)and exposed to 0-,1-,2.5-,or 5-mM sodium propionate(NaP),which is known to promote the expression of genes involved in the gluconeogenesis pathway,including fructose 1,6-bisphosphatase,phosphoenolpyruvate carboxykinase,and glucose-6-phosphatase.With regard to the underlying mechanism,propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha,hepatocyte nuclear factor 4,and forkhead box O1(transcription factors that regulate the expression of hepatic gluconeogenic genes)by promoting mammalian target of rapamycin complex 1(mTORC1),but inhibiting mTORC2 activity(P<0.01).We also established a model of palmitic acid(PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes,inhibiting m TORC1,and promoting the activity of m TORC2(P<0.01).In contrast,NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes(P<0.05).Collectively,these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity.Thus,in addition to improving the glucose production potential,propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows.展开更多
Kojic dipalmitate（KDP） was synthesized by the way of esterification ofpalmitic and kojic acids in organic solvent, with double-lipase as the biocatalyst. Four commercially available lipases（Amano PS, Novozym 435, L...Kojic dipalmitate（KDP） was synthesized by the way of esterification ofpalmitic and kojic acids in organic solvent, with double-lipase as the biocatalyst. Four commercially available lipases（Amano PS, Novozym 435, Lipozyme TL IM and Lipozyme RM IM） were used to group six double-lipase combinations. These combinations were studied and Amano PS-Novozym 435 was found to have the best efficiency and was selected for optimizing the reaction conditions. The optimal reaction conditions were as follows. The mass ratio ofAmano PS to Novozyme 435 was 1：1.5, with stirring speed of 500 r/min, substrates molar ratio of 1：2, 50 ℃, 5%（mass fraction） catalyst dosage of kojic acid quantity and using acetone as co-solvent. Under these conditions, the diesterification of C5 and C7 hydroxyl groups of kojic acid molecule could be well catalyzed by double-lipase and realize a high KDP yield of 85%.展开更多
基金supported by the National Natural Science Foundation of China,No.U1304815a grant from Key Project of Science and Technology Research of Henan Province of China,No.132102310097
文摘Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.
基金supported by Henan Province Science and Technology Research and Development in 2023(Guiding Project Approval):Study on the role and mechanism of Xiakucao extract in regulating autophagy therapy for diffuse large B-cell lymphoma through the PI3K/AKT signaling pathway(No.232102310451)Henan Province Traditional Chinese Medicine Top Talents Project:Study on the effect and mechanism of Xiakucao extract on diffuse large B-cell lymphoma(No.2022ZYBJ18).
文摘Diffuse large B-cell lymphoma(DLBCL)is characterized by significant treatment resistance.Palmitic acid(PA)has shown promising antitumor properties.This study aims to elucidate the molecular mechanisms by which PA influences DLBCL progression.We quantified the expression levels of microRNAs(miRNAs),Forkhead box protein O1(FOXO1),and DNA methyltransferase 3A(DNMT3A)in both untreated and PA-treated DLBCL tumors and cell lines.Assessments were made of cell viability,apoptosis,and autophagy-related protein expression following PA administration.Interaction analyses among miR-429,DNMT3A,and FOXO1 were conducted using luciferase reporter assays and methylation-specific(MSP)Polymerase chain reaction(PCR).After transfecting the miR-429 inhibitor,negative control(NC)inhibitor,shRNA against DNMT3A(sh-DNMT3A),shRNA negative control(sh-NC),over-expression vector for DNMT3A(oe-DNMT3A),or overexpression negative control(oe-NC),we evaluated the effects of miR-429 and DNMT3A on cell viability,mortality,and autophagy-related protein expression in PA-treated DLBCL cell lines.The efficacy of PA was also tested in vivo using DLBCL tumor-bearing mouse models.MiR-429 and FOXO1 expression levels were downregulated,whereas DNMT3A was upregulated in DLBCL compared to the control group.PA treatment was associated with enhanced autophagy,mediated by the upregulation of miR-429 and downregulation of DNMT3A.The luciferase reporter assay and MSP confirmed that miR-429 directly inhibits DNMT3A,thereby reducing FOXO1 methylation.Subsequent experiments demonstrated that PA promotes autophagy and inhibits DLBCL progression by upregulating miR-429 and modulating the DNMT3A/FOXO1 axis.In vivo PA signific-antly reduced the growth of xenografted tumors through its regulatory impact on the miR-429/DNMT3A/FOXO1 axis.Palmitic acid may modulate autophagy and inhibit DLBCL progression by targeting the miR-429/DNMT3A/FOXO1 signaling pathway,suggesting a novel therapeutic target for DLBCL management.
基金Supported by the National Natural Science Foundation of China(No.81373871 and 81273683)
文摘Objective： To investigate the effects of berberine （BBR） and cinnamic acid （CA）, the main active components in Jiaotai Pill （交泰丸, JTP）, on palmitic acid （PA）-induced intracellular tdglyceride （TG） accumulation in NIT-1 pancreatic 13 cells. Methods： Cells were incubated in culture medium containing PA （0.25 mmol/L） for 24 h. Then treatments with BBR （10 μmol/L）, CA （100 μmol/L） and the combination of BBR and CA （BBR＋CA） were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase （AMPK） protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase （FAS）, acetyl-coA carboxylase （ACC）, phosphorylation acetyl-coA carboxylase （pACC）, carnitine acyl transferase 1 （CPT-1） and sterol regulating element binding protein lc （SREBP-lc） were determined by Western blot or real time polymerase chain reaction. Results： PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-I. Meanwhile, AMPK downstream lipogenic genes including SREBP-lc mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR＋CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic 13 cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study. Conclusion： It can be concluded that in vitro, BBR and BBR＋CA could inhibit PA-induced lipid accumulation by decreasing lipoqenesis and increasin.cl lipid oxidation in NIT-1 pancreatic B cells.
基金financial supports from the Natural Science Foundation of China (No.21908225)the National Key Research and Development Program (No.2018YFC1801501)。
文摘Meso-Ni@HZSM-5 bi-functional catalysts were successfully post-encapsulated with about 3-7 nm Ni nanoparticles within HZSM-5 crystals,which exhibited significantly efficient conversion activity(67.4 g[palmitic acid]g[Ni]^(−1)h^(−1))of palmitic acid and 100%selectivity of hydrocarbons with the outstanding stability during recycling application,compared to the impregnated Ni/HZSM-5 catalyst(14.0 g[palmitic acid]g[Ni]^(−1)h^(−1)).
基金supported by a grant from Department of Animal Biology and Research Center for Bioscience and Biotechnology(RCBB),University of Tabriz(6906).
文摘Objective DUF538(domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function. Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques. Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability. Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.
基金supported by the earmarked fund for CARS36,the Natural Science Foundation of Heilongjiang Province,China (YQ2023C011)the"Academic Backbone"Project of Northeast Agricultural University.China (22XG35).
文摘This study evaluated the effects of different proportions of palmitic(C16:0)and oleic(cis-9 C18:1)acids in fat supplements on rumen fermentation,glucose(GLU)and lipid metabolism,antioxidant function,and visceral fat fatty acid(FA)composition in Angus bulls.The design of the experiment was a randomized block design with 3 treatments of 10 animals each.A total of 30 finishing Angus bulls(21±0.5 months)with an initial body weight of 626±69 kg were blocked by weight into 10 blocks,with 3 bulls per block.The bulls in each block were randomly assigned to one of three experimental diets:(1)control diet without additional fat(CON),(2)CON+2.5%palmitic calcium salt(PA;90%C16:0),(3)CON+2.5%mixed FA calcium salts(MA;60%C16:0+30%cis-9 C18:1).Both fat supplements increased C18:0 and cis-9 C18:1 in visceral fat(P<0.05)and up-regulated the expression of liver FA transport protein 5(FATP5;P<0.001).PA increased the insulin concentration(P<0.001)and aspartate aminotransferase activity(AST;P=0.030)in bull's blood while reducing the GLU concentration(P=0.009).PA increased the content of triglycerides(TG;P=0.014)in the liver,the content of the C16:0 in visceral fat(P=0.004),and weight gain(P=0.032),and up-regulated the expression of liver diacylglycerol acyltransferase 2(DGAT2;P<0.001)and stearoyl-CoA desaturase 1(SCD1;P<0.05).MA increased plasma superoxide dismutase activity(SOD;P=0.011),reduced the concentration of acetate and total volatile FA(VFA)in rumen fluid(P<0.05),and tended to increase plasma non-esterified FA(NEFA;P=0.069)concentrations.Generally,high C16:0 fat supplementation increased weight gain in Angus bulls and triggered the risk of fatty liver,insulin resistance,and reduced antioxidant function.These adverse effects were alleviated by partially replacing C16:0 with cis-9 C18:1.
基金supported by a National Natural Science Foundation of China grant(31701558)the Young Elite Scientists Sponsorship Program by CAST(2017QNRC001)+1 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B90719028)the national first-class discipline program of Food Science and Technology(JUFSTR20180202).
文摘Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41476058 & 41221004)the Program for New Century Excellent Talents in University (Grant No. NCET-13-0535)
文摘Hydrogen isotopes in lipid biomarkers can trace past changes in the hydrologic cycle. Recent studies have revealed the potential of hydrogen isotopes in microalgal lipids for quantitatively reconstructing water δ~2H（δD） values and salinity. In this study we collected suspended particles along a salinity gradient from the Changjiang River Estuary（CRE）, and measured δD values in fatty acids in these particles. The results indicated that δD values of water were correlated highly with salinity from the CRE, in agreement with the results from other estuaries. δD values in palmitic acid and stearic acid had a positive correlation with δD values of water from the CRE. Nevertheless, in the CRE, hydrogen isotope fractionation in fatty acids relative to water increased as salinity increased, opposite the trend in hydrogen isotope fractionation with salinity found in microalgal culture and field studies. We attribute the increase in hydrogen isotope fractionation as salinity increased to light availability, which was likely lower in the particle rich mixing zone at the end of the estuary, and potentially as well to multiple sources of fatty acids in the CRE.
文摘In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.
基金financially supported by the National Natural Science Foundation of China(21972099)the Application Foundation Program of Sichuan Province(2021YJ0305)+1 种基金the 111 project(B17030).Shanghai Synchrotron Radiation Facility(SSRF)for XAS experiments and the support by the project from NPL of CAEP(2019BB08)。
文摘The selective cleavage of C-O and C-C is facing a challenge in the field of catalysis.In the present work,we studied the influence of doped Ni on the structure and electronic properties,as well as the selective C-O/C-C bond cleavages in the hydrodeoxygenation of palmitic acid over Ni-Mo_(2)C catalyst.The catalytic activity on Ni doped Mo_(2)C with TOF of 6.9×10^(3)h^(-1)is much superior to intrinsic Mo_(2)C catalyst,which is also higher than most noble metal catalysts.Structurally,the doped Ni raises the active particle dispersion and the coordination numbers of Mo species(Mo-C and Mo-O),improves the graphitization degree to promote the electron transfer,and increases the amount of Lewis and Br?nsted acid,which are responsible for the excellent hydrodeoxygenation performance.The Ni promotes simultaneously C-O and C-C bonds cleavage to produce pentadecane and hexadecane owing to the increase of electron-rich Mo sites after Ni doping.These findings contribute to the understanding of the nature of Ni-doped Mo_(2)C on the roles as catalytic active sites for C-O and C-C bonds cleavage.
文摘The aim of this study was</span><span style="font-family:Verdana;"> to investigate the effects of different modified fats on the body weight, biochemical profile, and biomarkers of hepatic oxidative status in Balb-</span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">c</span></i><i><span style="font-family:Verdana;"></i></span></i><i><span style="font-family:""> </span></i><span style="font-family:""><span style="font-family:Verdana;">mice. The animals were divided into four groups and fed for 75 days with a </span><span style="font-family:Verdana;">normolipidic</span><span style="font-family:Verdana;"> (Control Group</span></span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;"> CG) or </span><span style="font-family:Verdana;">hiperlipidic</span><span style="font-family:Verdana;"> diets (40% kcal) containing a commercial interesterified fat (IFG) rich in palmitic acid (39%);a blend of non-interesterified fat (NIFG), with 2-fold less saturated fatty acids at the </span></span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">sn</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:""><span style="font-family:Verdana;">-2 position of triacylglycerols;or </span><span style="font-family:Verdana;">a partially</span><span style="font-family:Verdana;"> hydrogenated vegetable oil (</span><span style="font-family:Verdana;">PHFG), source of trans fatty acid (20%) and of linolenic acid (6%). The mice of the IFG and NIFG presented similar results in all evaluated parameters. The serum biochemical profile and hepatic oxidative stress markers in mice of the PHFG were similar to CG, except for total cholesterol (TC) which was significantly higher (p < 0.05) for the mice of th</span><span style="font-family:Verdana;">e PHFG. The mice feed with interesterified fat (IFG) showed serum TC (p < 0.01), non-HDL-C (p < 0.05), glucose (p < 0.05) and hepatic reduced glutathione values (2.7 fold, p < 0.05) and glutathione reductase activity (2.4 fold, p < 0.001) significantly higher when compared to the mice </span><span style="font-family:Verdana;">fed</span><span style="font-family:Verdana;"> with partially hydrogenated vegetable oil (PHFG). The hydrogenated fat source of trans fatty acid (20%) had less important metabolic effects than fats containing </span><span style="font-family:Verdana;">amount</span></span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> of palmitic acid (interesterified or non-interesterified). Our results suggest that the replacement of hydrogenated fats by interesterified fats may not be such a simple solution to reduce or eliminate </span><span style="font-family:Verdana;"><i></span><i><span style="font-family:Verdana;">trans</span></i><i><span style="font-family:Verdana;"></i></span></i><span style="font-family:Verdana;"> fatty acids in foods.
文摘This study presents the volatile constituents from leaves of Trifolium alexandrinum from Pakistan.The dried leaves were subjected to hydrodistillation for extraction and extracted volatile oil was subsequently characterized by gas chromatography-mass spectrometry technique.A total of 22 compounds were identified where the most dominant constituents were:phytol(46.00%),palmitic acid(9.26%),phytol acetate(6.44%),and linolenic acid(3.47%).Most of these are well-known constituents to exhibit antibacterial,antioxidant,antitumor,and anti-inflammatory activities.
基金supported by Nantong Science and Technology Project(MS12018020,MS12018041)Jiangsu Government Scholarship for Overseas Studies(JS-2017-200)+1 种基金the Doctoral Scientific Research Foundation of Nantong University(135420505015)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(11KJB180010).
文摘Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.
文摘Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among others.With this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its toxicity.Methods:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro experiments.IR-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of doses.Cell counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ferroptosis.Results:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 cells.Celastrol downregulated glutathione peroxidase 4(GPX4)m RNA.Molecular docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by celastrol.Importantly,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 cells.Conclusion:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis inhibitors.These findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.
基金supported by National Natural Science Foundation of China(Nos.81273569,81001465)Natural Science Foundation of Jiangsu Province,China(No.BK2012726)the Ph.D. Programs Foundation of Ministry of Education of China(No.20100091120028)
文摘Serum palmitic acid(PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes.Ethanol(Et OH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of Et OH on PA-induced lipotoxicity in the liver. Our results indicated that Et OH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. Et OH intensified PA-caused endoplasmic reticulum(ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. Et OH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP–/– mice treated with Et OH and high fat diet(HFD), Et OH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of Et OH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing Et OH and saturated fatty acid-induced metabolic complications.
文摘Glucolipotocixity induces IL-1βsecretion which impairs pancreaticβ-cell insulin secretion.Ellagic acid and urolithin A have strong anti-inflammatory effect on cells.Muscadine and amla are very good sources of ellagic acid.The present study examined the effect of ellagic acid,ellagic acid-rich muscadine or amla extract,or urolothin A on inflammation inβcells under glucolipotoxic conditions.Rat NIT-1βcells were incubated in glucolipotoxic conditions(33.3 mM glucose,250μM palmitic acid or 33.3 mM glucose+250μM palmitic acid with or without ellagic acid,ellagic acid-rich muscadine or amla extracts standardized to its ellagic acid content,or urolithin A).Inflammatory status was evidenced by ELISA analysis of insulin and IL-1βsecretion.Ellagic acid-rich muscadine or amla extracts dose-dependently stimulated insulin secretion and down-regulated IL-1βbetter than pure ellagic acid,or urolithin A.Urolithin A did not statistically stimulate insulin secretion and did not inhibit IL-1β.
文摘s To investigate the effects of glucose and free fatty acids (FFAs) on the proliferation and cell cycle of human vascular endothelial cells in vitro , and to examine whether the combined presence of elevated FFAs and glucose may cross amplify their individual injurious effects Methods Cultured human vascular endothelial cells (ECV304) were incubated with various concentrations of glucose and/or FFAs (palmitate and/or oleate) for 24-96 h Morphologic alterations were observed using a phase contrast microscope and an electron microscope Inhibition of proliferation was measured by a colorimetric 3 [4, 5 dimethyl thiazol 2 yl] 2, 5 diphenyltetrazolium bromide (MTT) assay Cell viability was determined using trypan blue exclusion Distribution of cells along phases of the cell cycle was analyzed by flow cytometry Results Glucose 15 or 30 mmol/L, palmitate (PA) 0 25 or 0 5 mmol/L, and oleate (OA) 0 5 mmol/L inhibited proliferation and accelerated death of endothelial cells in a dose and time dependent manner After treatment with elevated glucose and/or FFAs, the G 0/G 1 phase cells increased, whereas S phase cells decreased, suggesting that high glucose and/or FFAs mainly arrested endothelial cells at G 0/G 1 phase The inhibitive rates of proliferation and population of dead cells in endothelial cells incubated with glucose plus FFAs (glucose 30 mmol/L+PA 0 25 mmol/L, glucose 30 mmol/L+OA 0 5 mmol/L, glucose 30 mmol/L+PA 0 25 mmol/L+OA 0 5 mmol/L) increased more markedly than those treated with high glucose or FFAs (PA and/or OA) alone Conclusion Both high ambient glucose and FFAs can inhibit proliferation and accelerate death of endothelial cells in vitro These changes were cross amplified in the combined presence of high levels of glucose and FFAs
基金supported by the National Natural Science Foundation of China(grant numbers 32070782,32072761,32100578)the Guangdong Basic and Applied Basic Research Foundation(grant number 2021A1515220036).
文摘Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows.This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms.Calf hepatocytes were obtained from 5 healthy calves(1 d old;30to 40 kg)and exposed to 0-,1-,2.5-,or 5-mM sodium propionate(NaP),which is known to promote the expression of genes involved in the gluconeogenesis pathway,including fructose 1,6-bisphosphatase,phosphoenolpyruvate carboxykinase,and glucose-6-phosphatase.With regard to the underlying mechanism,propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha,hepatocyte nuclear factor 4,and forkhead box O1(transcription factors that regulate the expression of hepatic gluconeogenic genes)by promoting mammalian target of rapamycin complex 1(mTORC1),but inhibiting mTORC2 activity(P<0.01).We also established a model of palmitic acid(PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes,inhibiting m TORC1,and promoting the activity of m TORC2(P<0.01).In contrast,NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes(P<0.05).Collectively,these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity.Thus,in addition to improving the glucose production potential,propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows.
文摘Kojic dipalmitate（KDP） was synthesized by the way of esterification ofpalmitic and kojic acids in organic solvent, with double-lipase as the biocatalyst. Four commercially available lipases（Amano PS, Novozym 435, Lipozyme TL IM and Lipozyme RM IM） were used to group six double-lipase combinations. These combinations were studied and Amano PS-Novozym 435 was found to have the best efficiency and was selected for optimizing the reaction conditions. The optimal reaction conditions were as follows. The mass ratio ofAmano PS to Novozyme 435 was 1：1.5, with stirring speed of 500 r/min, substrates molar ratio of 1：2, 50 ℃, 5%（mass fraction） catalyst dosage of kojic acid quantity and using acetone as co-solvent. Under these conditions, the diesterification of C5 and C7 hydroxyl groups of kojic acid molecule could be well catalyzed by double-lipase and realize a high KDP yield of 85%.
