Nerve growth factor protects against palmitic acid- induced injury in retinal ganglion cells

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.

Eicosane, pentadecane and palmitic acid: The effects in in vitro wound healing studies

Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-microbial activities of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for realtime mRNA genes expression studies of TNF-毩 and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast. Results: None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-毩 and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation. Conclusions: This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.

Cannabidiol (CBD) Prevents Palmitic Acid-Induced Drop in Mitochondrial Membrane Potential

Exposure of macrophages and microglia cells to the saturated palmitic acid (PA) leads to reduction in the mitochondrial membrane potential (), shrinkage of the cells and apoptosis. Here we show that the Cannabis component Cannabidiol (CBD) rescues both macrophages and microglia cells from the detrimental effects of PA. CBD prevents the shrinkage in cell size and the reduction incaused by PA. The protective effect of CBD on the macrophage mitochondria is important for sustaining the macrophage population even under the immunosuppressed conditions caused by this drug. To a similar extent, the antagonistic effect of CBD on PA-mediated microglia cytotoxicity is important for its role in neuroprotection.

Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

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.

Effects of Berberine and Cinnamic Acid on Palmitic Acid-Induced Intracellular Triglyceride Accumulation in NIT-1 Pancreatic β Cells

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.

Hydrogen isotopes in palmitic and stearic acids in suspended particles from the Changjiang River Estuary

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.

Long-Term Impact of Acute Retinoic Acid Supplementation at the Young Age on Testicular Architecture of Wistar Albino Rats

Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, during childhood, impaired spermatogenesis was identified at the adult age with an arrest of spermatogenesis. The reversibility of that lack of differentiation by a return to a normal diet is questionable and would need more investigation.

Ni nanoparticles encapsulated within H-type ZSM-5 crystals for upgrading palmitic acid to diesel-like fuels

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)).

Endoplasmic Reticulum Stress Mediates Palmitic Acid-induced Insulin Resistance in Mouse Skeletal Muscle Cells

Increasing evidence shows that pathological elevation of plasma fatty acids, especially long-chain saturated forms, which ordinarily occurs in obesity patients, increases the risk

Similarity of Binding Potentials Between Plant DUF538 and Animal Lipocalin: Cholesterol Binding Ability of DUF538

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.

Scavenger receptor A-mediated nanoparticles target M1 macrophages for acute liver injury

Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.

旋覆花杀菌活性成分的分离与鉴定

以小麦赤霉病菌(FusariumgraminearumSchw)和小麦白粉病菌(ErysiphegraminisDC)为活性跟踪菌种,从旋覆花(InulabritanicaL.)花中分离得到3种杀菌活性化合物。经波谱分析并与标准图谱比较,鉴定化合物 为倍半萜类化合物1-O-Acetylbritannilactone,化合物 和 分别为三萜类化合物Taraxasterylpalmitate和Taraxasterolacetate。

Lipase-Catalyzed Synthesis of Sn-2 Palmitate: A Review

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.

Lipase-catalyzed regioselective synthesis of palmitolyglucose ester in ionic liquids

Candida antarctica lipase B (CAL-B) was used as a catalyst in the synthesis of palmitolyglucose ester in the ionic liquids, 1-butyl-3-methylimidazolium triflu- oromethanesulfonate ([Bmim][TfO]), with glucose as a substrates and palmitic acid vinyl ester as the acyl donor. The effect of substrate ratio, lipase content, and temperature on the activity and stability of lipase was studied. The reaction conditions in [Bmim][TfO] re- sulting in the highest yield of the sugar ester were a temperature of 50?C, enzyme concentration of 50 mg/ mL, and a molar ratio of glucose/vinyl palmitate of 1:3. The major reaction product was purified and char- acterized by FT-IR, HPLC, MS and NMR, as being 6-O-palmitolyglucose ester. The advantages of ionic liquid vs. organic solvent were noted.

Reaction kinetics of isopropyl palmitate synthesis

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.

Palm oil and the heart:A review

Palm oil consumption and its effects on serum lipid levels and cardiovascular disease in humans is still a subject of debate. Advocacy groups with varying agenda fuel the controversy. This update intends to identify evidence-based evaluations of the influence of palm oil on serum lipid profile and cardiovascular disease. Furthermore, it suggests a direction for future research. The sources of information were based on a Pub Med, Google Scholar, African Journal online and Medline search using key words including: palm oil, palmitic acid, saturated fatty acids and heart disease. Published animal and human experiments on the association of palm oil and its constituents on the serum lipid profile and cardiovascular disease were also explored for relevant information. These papers are reviewed and the available evidence is discussed. Most of the information in mainstream literature is targeted at consumers and food companies with a view to discourage the consumption of palm oil. The main argument against the use of palm oil as an edible oil is the fact that it contains palmitic acid, which is a saturated fatty acid and by extrapolation should give rise to elevated total cholesterol and low-density lipoprotein cholesterol levels. However, there are many scientific studies, both in animals and humans that clearly show that palm oil consumption does not give rise to elevated serum cholesterol levels and that palm oil is not atherogenic. Apart from palmitic acid, palm oil consists of oleic and linoleic acids which are monounsaturated and polyunsaturated respectively. Palm oil also consists of vitamins A and E, which are powerful antioxidants. Palm oil has been scientifically shown to protect the heart and blood vessels from plaques and ischemic injuries. Palm oil consumed as a dietary fat as a part of a healthy balanced diet does not have incremental risk for cardiovascular disease. Little or no additional benefit will be obtained by replacing it with other oils rich in mono or polyunsaturated fatty acids.

Structural and electronic effects boosting Ni-doped Mo_(2)C catalyst toward high-efficiency C-O/C-C bonds cleavage

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.

C₁₆Saturated Fatty Acid Induced Autophagy in A549 Cells through Topoisomerase I Inhibition

C16 saturated fatty acid (Palmitic acid) is one of the most common dietary fatty acids which played an important role in the cellular biological functions. Palmitic acid (PA) was tested for potential inhibition of DNA topoisomerase I (topo I) and it exhibited inhibitory activity in the nanomolar range. Treatment of lung adenocarcinoma cell line A549 with PA resulted in a decrease in cell viability in a concentration-dependent manner, and PA showed cytotoxicity with an IC50 value of 150 μM. DNA fragmentation assay and caspase activity indicated that PA does not induce apoptotic cell death in A549 cells. Finally, we found that PA was able to cause an increase in autophagic flux in a time-dependent manner, evidenced by the accumulation of LC3 through monodansylcadaverine (MDC) staining. More importantly, inhibition of autophagy by blocking autophagosome formation via the inhibition of type III Phosphatidylinositol 3-kinases (PI-3K), by 3-Methyladenine (3-MA) was able to effectively suppress PA-induced autophagy. We showed that inhibition of autophagy sensitized the cells signal to PA-induced apoptosis, suggesting the pro-survival function of autophagy induced by PA. Taken together, results from this study reveal that PA as a topo I inhibitor induced autophagic cell death in A549 cells.

Effect of a Diet Rich in Interesterified, Non-Interesterified and Trans Fats on Biochemical Parameters and Oxidative Status of Balb-c Mice

The aim of this study was to investigate the effects of different modified fats on the body weight, biochemical profile, and biomarkers of hepatic oxidative status in Balb-c mice. The animals were divided into four groups and fed for 75 days with a normolipidic (Control Group, CG) or hiperlipidic 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 sn-2 position of triacylglycerols;or a partially hydrogenated vegetable oil (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 the 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 fed with partially hydrogenated vegetable oil (PHFG). The hydrogenated fat source of trans fatty acid (20%) had less important metabolic effects than fats containing amounts 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 trans fatty acids in foods.