Modulación por Passiflora edulis de triglicéridos y colesterol intracelulares en líneas celulares de cáncer colorrectal SW480 y sus derivadas metastásicas (SW620) / Modulation by Passiflora edulis of intracellular triglycerides and cholesterol in SW480 col orectal cancer cell lines and their metastatic derivatives (SW620)

Cancer cells modify lipid metabolism to proliferate, Passiflora edulis ( P. edulis ) fruit juice (ZuFru) has antitumor activity, but whether a mechanism is through modulation of cell lipids is unknown. T o establish if ZuFru modifies cholesterol and triglycerides in SW480 and SW620. ZuFru composition was studied by phytochemical march; antiproliferative activity by sulforhodamine B, cholesterol , and triglycerides by Folch method. Z ufru contains anthocyanins, flavonoids, alkaloids , and tannins. Cell lines showed differences in their growth rate ( p =0.049). At 39.6 µg/m L of ZuFru, cell viability was decreased: SW480 (45.6%) and SW620 (45.1%). In SW480, cholesterol (44.6%) and triglycerides (46.5%) decreased; In SW620, cholesterol decreased 14.8% and triglycerides increased 7%, with significant differences for both lines. A ntiproliferative activity of ZuFru could be associated with the inhibition of intracellular biosynthesis of cholesterol and triglycerides in SW480. Action mechanisms need to be further investigated.

Las células cancerosas modifican el metabolismo lipídico para proliferar; el zumo de fruta (ZuFru) de Passiflora edulis ( P. edulis ) tiene activida d antitumoral, sin embargo, se desconoce si se involucran los lípidos celulares. E stablecer si ZuFru modifica colesterol y triglicéridos en células SW480 y SW620. C omposición del ZuFru, actividad antiproliferativa, colesterol y triglicéridos. Se encontraro n antocianinas, flavonoides, alcaloides y taninos. Las líneas celulares mostraron diferencias en su tasa de crecimiento ( p =0 . 049); ZuFru 39,6 µg/ml se disminuyó la viabilidad celular; SW480 (45,6%) y SW620 (45,1%); en SW480 colesterol (44,6%) y triglicérid os (46,5%) en SW620, colesterol (14,8%) y los triglicéridos aumentaron 7%, con diferencias significativas para ambas líneas. La actividad antiproliferativa del ZuFru podría estar asociada a la inhibición de la biosíntesis intracelular de colesterol y de tr iglicéridos en SW480, pero no en SW620. Estos mecanismos de acción deben ser fuertemente investigados.

Activation of pannexin-1 mediates triglyceride-induced macrophage cell death.

The accumulation of triglycerides (TGs) in macrophages induces cell death, a risk factor in the pathogenesis of atherosclerosis. We had previously reported that TG-induced macrophage death is triggered by caspase-1 and -2, therefore we investigated the mechanism underlying this phenomenon. We found that potassium efflux is increased in TG-treated THP-1 macrophages and that the inhibition of potassium efflux blocks TG-induced cell death as well as caspase-1 and -2 activation. Furthermore, reducing ATP concentration (known to induce potassium efflux), restored cell viability and caspase-1 and -2 activity. The activation of pannexin-1 (a channel that releases ATP), was increased after TG treatment in THP-1 macrophages. Inhibition of pannexin-1 activity using its inhibitor, probenecid, recovered cell viability and blocked the activation of caspase-1 and -2 in TG-treated macrophages. These results suggest that TG-induced THP-1 macrophage cell death is induced via pannexin- 1 activation, which increases extracellular ATP, leading to an increase in potassium efflux. [BMB Reports 2020; 53(11): 588-593].

Using total plasma triacylglycerol to assess hepatic de novo lipogenesis as an alternative to VLDL triacylglycerol.

Background: Hepatic de novo lipogenesis (DNL) is ideally measured in very low-density lipoprotein (VLDL)-triacylglycerol (TAG). In the fasting state, the majority of plasma TAG typically represents VLDL-TAG; however, the merits of measuring DNL in total plasma TAG have not been assessed. This study aimed to assess the performance of DNL measured in VLDL-TAG (DNLVLDL-TAG) compared to that measured in total plasma TAG (DNLPlasma-TAG).Methods: Using deuterated water, newly synthesised palmitate was determined in fasting plasma VLDL-TAG and total TAG in 63 subjects taking part in multiple studies resulting in n = 123 assessments of DNL (%new palmitate of total palmitate). Subjects were split into tertiles to investigate if DNLPlasma-TAG could correctly classify subjects having 'high' (top tertile) and 'low' (bottom tertile) DNL. Repeatability was assessed in a subgroup (n = 16) with repeat visits.Results: DNLVLDL-TAG was 6.8% (IQR 3.6-10.7%) and DNLPlasma-TAG was 7.5% (IQR 4.0%-11.0%), and the correlation between the methods was rs = 0.62 (p < 0.0001). Bland-Altman plots demonstrated similar performance (mean difference 0.81%, p = 0.09); however, the agreement interval was wide (-9.6% to 11.2%). Compared to DNLVLDL-TAG, 54% of subjects with low DNL were correctly classified, whilst 66% of subjects with high DNL were correctly classified using DNLPlasma-TAG. Repeatability was acceptable (i.e. not different) at the group level, but the majority of subjects had an intra-individual variability over 25%.Conclusion: DNL in total plasma TAG performed similarly to DNL in VLDL-TAG at the group level, but there was large variability at the individual level. We suggest that plasma TAG could be useful for comparing DNL between groups.

Triglycerides and residual risk.

PURPOSE OF REVIEW: To review the recent evidence from observational/genetic/interventional studies addressing triglycerides and residual cardiovascular risk (CVRisk). RECENT FINDINGS: Large population-based and secondary prevention studies consistently show an association of higher triglycerides with increased CVRisk. This is compounded by genetic studies demonstrating an independent relationship between triglyceride raising or lowering genetic variants affecting triglyceride-rich lipoproteins (TRL) metabolism and CVRisk. Mendelian randomization analysis suggests the benefit of genetic lowering of triglycerides and LDL-cholesterol is similar per unit change in apolipoprotein-B. Among cholesterol-lowering trials, more intensive statin therapy produced greater CVRisk reductions in patients with higher TRL-cholesterol or triglycerides; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition led to similar triglycerides reduction but greater non-HDL-C or apolipoprotein-B reductions than fibrates or fish oils. Regarding n-3 fatty acids, A Study of Cardiovascular Events in Diabetes (ASCEND) and Vitamin D and Omega-3 Trial (VITAL) primary prevention trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid failed to demonstrate cardiovascular benefits, Conversely, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) using high-dose icosapent-ethyl (purified EPA) in primary (diabetes) and secondary prevention with hypertriglyceridemia showed significant cardiovascular events reductions (greater than expected by the observed triglycerides or apolipoprotein-B reductions, suggesting potential benefits through non-lipid pathways). SUMMARY: Evidence suggests higher triglycerides are a marker of CVRisk and may help identify patients who benefit from intensification of therapy. Moreover, genetic studies support a causal link between TRL/triglycerides and cardiovascular disease. Treatment with high-dose EPA may be of benefit in high-risk patients with hypertriglyceridemia to reduce CVRisk.

Targeting PLIN2/PLIN5-PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets.

SCOPE: The effects of sulforaphane (SFN) on the maturation of lipid droplets (LDs)-the storage units for free fatty acids and sterols as triacylglycerides (TAG) and cholesterol esters (CE)-are far from being understood, despite the fact that SFN is known to be beneficial for ameliorating lipid metabolism disorders. METHODS AND RESULTS: High-fat-intake models are established in both HHL-5 hepatocytes and rodents. The numbers and sizes of LDs are decreased by SFN. The accumulation of lipid core components (TAG & CE) is reduced and the expression of their key synthetases, acyl-coenzyme A: diacylglycerol acyltransferases 2 (DGAT2) and acyl-coenzyme A: cholesterol acyltransferases 1 (ACAT1), is also inhibited. Moreover, SFN decreases LD-associated protein PLIN2 and PLIN5 expression, but not that of PLIN1 and PLIN3, both in vivo and in vitro. Furthermore, over-expression of peroxisome proliferator-activated receptor gamma (PPARγ) induces the accumulation of TAG and the up-regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPARγ may be a target of SFN in lipid metabolism. CONCLUSION: SFN disturbs LD maturation by inhibiting the formation of the neutral lipid core and decreases PLIN2 and PLIN5 via down-regulation of PPARγ.

The impact of lactic acid and medium chain triglyceride on blood glucose, lactate and diurnal motor activity: A re-examination of a treatment of major depression using lactic acid.

While investigating the effect of alternative energy substrates on extracellular brain glucose or lactate, Béland-Millar (2017) noted a reduction of physical activity after intraperitoneal administration of lactate and ketone bodies. These observations were similar to an older study that examined the impact of drinking a sodium lactate/lactic acid solution before sleep in hospitalized patients with major depression. Patients and control participants self-reported drowsiness, early sleep onset and better overall sleep after consumption. Some patients showed improved mood after several days of treatment. We re-evaluated the effects of the solution used (0.59 g/kg) as well as several smaller doses (0.47, 0.35, 0.24 and 0.12 g/kg) on blood lactate and glucose in CD-1 mice and on sleep onset associated activity reduction. Because of adverse effects with the lactate/lactic acid solution, we also examined the effects of a medium chain triglyceride (MCT) solution (10, 5, 2.5, and 1 ml/kg) on blood lactate and glucose. Oral gavage administration of lactic acid/lactate produced adverse effects particularly for the largest doses. However consumption of 10 and 5 ml/kg volumes of MCT oils significantly increased blood lactate concentration to levels comparable to Lowenbach's solution without piloerection indicative of adverse effects. To evaluate pre-sleep activity reduction produced by lactate, mice were intraperitoneally administered diluted sodium lactate (2.0 g/kg, 1.0 g/kg, 0.5 g/kg, 0.25 g/kg, or saline) for 6 days, 120 min before their sleep period and their running activity was measured. Larger lactate doses reduced pre-sleep running each day up to 60 min post injection. Smaller doses reduced running after a single treatment only. These results suggest that the modulation of blood lactate levels may be useful in treating sleep onset problems associated with depression.

Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis.

PURPOSE OF REVIEW: In this review, we intend to show the heterogenicity of the triglyceride group, including the triglyceride-rich lipoproteins and its subparticles, apolipoproteins, and its role in atherogenesis through epidemiological and genetic studies, observing the association of these various components and subclasses with subclinical atherosclerosis and cardiovascular events. Also, we reevaluated the moment of blood collection for the triglyceride measurement and its repercussion in atherosclerosis. Finally, we present the current scenario and new insights about the pharmacologic treatment of hypertriglyceridemia. RECENT FINDINGS: Recent studies have been observed, a correlation between cardiovascular disease and triglyceride components (as apolipoproteins A-V, C-I, C-III) as well as proteins involved in the metabolism pathway, such as the angiopoietin-like proteins. Also, the triglyceride-rich lipoproteins, also known as remnants, were recently associated with atherogenesis. Another important topic addressed is about nonfasting triglyceride level, which has been postulated as a better predictor of cardiovascular events than fasting collection. SUMMARY: Regarding hypertriglyceridemia treatment, the drug therapy was updated, as the omega-3 polyunsaturated fatty acids were tested in primary prevention as eicosapentaenoic acid and docosahexaenoic acid combination resulted in no benefit, whereas the administration of icosapent ethyl in secondary prevention and high-risk patients showed a robust decrease of the cardiovascular outcomes.

A synaptic theory of internal delays.

Neurons in the medial superior olive perform a coincidence analysis between inputs from the two ears, as predicted by Jeffress [J. Comp. Psychol. 41, 35-39 (1948)]. Jeffress also correctly predicted inputs to express a range of internal delays for which he invoked axonal delay lines. These, however, cannot explain that the inputs of many binaural neurons differ by a combination of a time delay and a phase shift. This study proposes an alternative source of internal delay. An interaural asymmetry in the activation threshold of the inner hair cell synapses is shown to reproduce the main features of internal delays of binaural neurons.

The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial triglyceride-rich lipoproteins.

OBJECTIVE: Insulin resistance is associated with impaired receptor dependent hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL) receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by insulin action contributes to the rapid clearance of TRL in the postprandial state. Here, we investigated the hypothesis that the adaptor protein phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1 function, thereby controlling hepatic endocytosis of postprandial lipoproteins. METHODS: Localization and interaction of PID1 and LRP1 in cultured hepatocytes was studied by confocal microscopy of fluorescent tagged proteins, by indirect immunohistochemistry of endogenous proteins, by GST-based pull down and by immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr-deficient (Ldlr-/-) background. Intravital microscopy was used to study LRP1 translocation in the liver. Lipoprotein metabolism was investigated by lipoprotein profiling, gene and protein expression as well as organ-specific uptake of radiolabelled TRL. RESULTS: PID1 co-localized in perinuclear endosomes and was found associated with LRP1 under fasting conditions. We identified the distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the site critical for the interaction with PID1. Insulin-mediated NPxY-phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1 translocation to the plasma membrane. PID1 deletion resulted in higher LRP1 abundance at the cell surface, higher LDLR protein levels and, paradoxically, reduced total LRP1. The latter can be explained by higher receptor shedding, which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1 deficiency alone led to increased LDLR-dependent endocytosis of postprandial lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion on an Ldlr-/- background reduced lipoprotein uptake into liver and caused plasma TRL accumulation. CONCLUSIONS: By acting as an insulin-dependent retention adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of postprandial lipoproteins. PID1 inhibition provides a novel approach to lower plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function of both LRP1 and LDLR in the liver.

Impact of delipidated estrous sheep serum supplementation on in vitro maturation, cryotolerance and endoplasmic reticulum stress gene expression of sheep oocytes.

High lipid content of oocytes and embryos in domestic animals is one of the well-known factors associated with poor cryosurvival. Herein, we wanted to determine whether the use of delipidated estrous sheep serum during in vitro maturation (IVM) of ovine oocytes reduces the cytoplasmic lipid droplets content and improves embryo development and cryotolerance after vitrification. Cumulus oocytes complexes (COCs) were matured in vitro for 24 h in medium supplemented with whole or delipidated estrous sheep serum prior to vitrification. Neutral lipid present in lipid droplets of COCs, cleavage rate, embryo development rate on Day 6 and Day 8, and hatching rate on Day 8, were compared among experimental groups. Endoplasmic reticulum stress genes were evaluated in in vitro matured COCs under different lipid conditions prior to vitrification. The lipid droplets' content (mean fluorescence intensity) of oocytes cultured with IVM media supplemented with delipidated serum was lower than COCs matured with whole serum (7.6 ± 1.7 vs. 22.8 ± 5.0 arbitrary units, respectively; P< 0.05). Despite IVM treatment, oocytes subjected to vitrification showed impaired competence compared with the non-vitrified groups (P<0.05). No significant differences in embryo production were observed in non-vitrified COCs after maturation in delipidated or whole serum (33.4±4.9 vs 31.9 ±4.2). COCs matured in delipidated serum and subjected to vitrification showed increased expression of ATF4, ATF6, GRP78, and CHOP10 genes (ER stress markers). Collectively, our results demonstrate that although supplementation of IVM medium with delipidated estrous sheep serum reduces the presence of cytoplasmic lipid droplets in oocytes after maturation, oocyte cryotolerance is not improved. Notably, the expression of genes associated with the unfolded protein response (UPR) was increased in COCs, with fewer lipid droplets subjected to vitrification, suggesting that oocyte cryopreservation is associated with ER stress and activation of adaptive responses.

Caspase-2 mediates triglyceride (TG)-induced macrophage cell death.

Triglyceride (TG) accumulation causes macrophage cell death, which affects the development of atherosclerosis. Here, we examined whether caspase-2 is implicated in TG-induced macrophage cell death. We found that caspase-2 activity is increased in TG-treated THP-1 macrophages, and that inhibition of caspase-2 activity drastically inhibits TG-induced cell death. We previously reported that TG-induced macrophage cell death is triggered by caspase-1, and thus investigated the relationship between caspase-2 and caspase-1 in TG-induced macrophage cell death. Inhibition of caspase-2 activity decreased caspase-1 activity in TG-treated macrophages. However, caspase-1 inhibition did not affect caspase-2 activity, suggesting that caspase-2 is upstream of caspase-1. Furthermore, we found that TG induces activation of caspase-3, -7, -8, and -9, as well as cleavage of PARP. Inhibition of caspase-2 and -1 decreased TG-induced caspase-3, -7, -8, and -9 activation and PARP cleavage. Taken together, these results suggest that TG-induced macrophage cell death is mediated via the caspase-2/caspase-1/apoptotic caspases/PARP pathways. [BMB Reports 2017; 50(10): 510-515].

[Nutrition management in obese patients with type 2 diabetes mellitus after laparoscopic sleeve gastrectomy].

OBJECTIVE: To explore the value of nutrition management in obese patients with type 2 diabetes mellitus(T2DM) after laparoscopic sleeve gastrectomy(LSG). METHODS: Clinical data of 22 obese T2DM patients undergoing LSG from March 2013 to July 2015 in Fudan University Pudong Medical Center were collected. All the patients strictly followed the specialized instruction by nutritionists: diabetic and low calorie diet 3347.2 to 5020.8 kJ (800 to 1200 kcal) per day before the operation; low calorie liquid diet 2510.4 kJ(600 kcal) per day before operation for promoting gastric emptying; fasting diet before postoperative ventilation; clear liquid diet 1673.6 to 2510.4 kJ (400 to 600 kcal) per day after postoperative ventilation (liquid intake >2000 ml); low fat liquid diet 2928.8 to 3765.6 kJ (700 to 900 kcal) per day (protein 60 g per day at least, 2000 ml liquid) 2 weeks after the operation; semi-liquid diet 1 month after operation and gradually normal diet. All the 22 patients were followed up at 1 week, 1, 3, 6 months after operation on time. Changes of body weight, waist circumference, hip circumference, body mass index(BMI), blood glucose indexes induding fasting blood glucose(FBG), 2-hour postparandial blood glucose(PBG), fasting C-peptide, 2-hour postprandial C-peptide, fasting serum inculin(FINS), 2-hour postprandial inculin(INS), HbAlc, blood pressure and blood lipid indexes were observed and analyzed before and 1 week, 1, 3, 6 months after operation. RESULTS: The average age of 22 patients (10 men and 12 women) was 38.6 years (18 to 66 years). The duration of diabetes varied from 1 month to 15 years. Comorbidity included 12 patients of high blood pressure, 14 of fatty liver, 1 of coronary heart disease, 1 of gout, 1 of chronic thyroiditis and 1 of menstrual disorder. LSG was performed successfully in all the patients and no severe complications and transference to laparotomy occurred. As compared to pre-operation, at 6 months after operation, the average body weight decreased from (103.9±20.2) kg to (80.9±12.6) kg (t=6.294, P=0.000), waist circumference from (118.6±13.8) cm to (96.4±8.0) cm (t=6.331, P=0.000), hip circumference from (116.9±12.6) cm to (104.0±7.7) cm (t=3.854, P=0.000), BMI from (36.2±5.9) kg/m2 to (27.9±3.5) kg/m2 (t=5.630, P=0.000), showing a decreasing trend over time. There was no underweight patient after 6 months follow-up. As compared to pre-operation, at 6 months after operation, the average FBG reduced from (7.4±1.4) mmol/L to (6.0±0.9) mmol/L (t=3.172, P=0.003), 2 h PBG from (14.1±4.9) mmol/L to (7.5±2.2) mmol/L (t=7.026, P=0.000), FINS from (160.0±71.9) mIU/L to (43.8±20.8) mIU/L (t=7.259, P=0.000), 2-hour postprandial INS from (437.6±261.4) mIU/L to (140.5±104.6) mIU/L (t=5.858, P=0.000), fasting C-peptide from (1.1±0.6) µg/L to (0.7±0.3) µg/L (t=3.560, P=0.000), 2-hour postprandial C-peptide from (2.5±0.9) µg/L to (1.5±0.7) µg/L (t=3.865, P=0.000), HbAlc from (8.0±1.6)% to (5.9±0.6)% (t=5.953, P=0.000), showing a decreasing trend over time except FBG, 2h postprandial C-peptide and HbAlc(all P<0.05). FBG and 2-hour PBG of 16 patients returned to normal 3 months after the operation. Blood pressure and trigly ceride decreased obviously 6 months after operation compared to pre-operation with significant difference(P<0.05). At 6 months after operation, blood pressure of 8 comorbidity patients with high blood pressure became normal (8/12, 66.7%) and of 4 patients improved(4/12, 33.3%); B ultrasound examination revealed normal in 11 comorbidity patients with fatty liver(11/14,78.6%) and improvement in 3 patients (3/14,15.4%). Blood uric acid of the gout patient and the menstruation of the menstrual disorder patient returned to normal 3 months and 1 month after the operation respectively. CONCLUSION: As for obese patients with T2DM undergoing LSG, reasonable nutrition management is helpful to decrease body weight, and to obtain an ideal improvement of blood glucose and blood lipid levels.

Survival, physical and physiological changes of Taenia hydatigena eggs under different conditions of water stress.

Taenia hydatigena eggs were investigated for morphological and physiological changes under water stress conditions. Fresh eggs were exposed at 31%, 47% and 89% of relative humidity (RH), and survival, size and ultrastructural changes were accounted up to 365 days of exposition. The article shows how each RH environment affects the vitality of the eggs. Results of this study suggest that T. hydatigena eggs have mechanisms to withstand water stress, indicating that the eggs clustering improves protection against desiccation, and that endogenous metabolism using triacylglycerols play an important role in the maintenance of embryo vitality under low, medium and high relative humidity conditions. This contributes to understanding the water stress resistance mechanism in eggs belonging to Taeniidae family. The findings shown herein have provided a basis to better comprehend basic biology and epidemiology of the cysticercosis caused by T. hydatigena.

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

SCOPE: Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. METHODS AND RESULTS: Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe-/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1ß mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. CONCLUSION: Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs.

[Correlations between lipid ratio/oxidative stress status in COPD patients and pulmonary hypertension as well as prognosis].

OBJECTIVE: To investigate the correlations between lipid ratio/oxidative stress status in chronic obstructive pulmonary disease (COPD) patients and pulmonary hypertension as well as the prognosis.
 Methods: A total of 120 patients with COPD were randomly selected and served as the COPD group and 30 healthy persons were selected as the control group. The ratios of low density lipoprotein (LDL)/high-density lipoprotein (HDL), triglyceride (TG)/HDL and total cholesterol (TC)/HDL were measured. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) level in the control group and COPD patients were detected. Pulmonary hypertension incidence and 3-year survival rate for COPD patients were statistically analyzed. Spearman rank correlation method was used to analyze relationship between lipid ratio /oxidative stress status and pulmonary hypertension.
 Results: Compared with control group, the ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA level in the COPD group were increased, while the serum SOD and T-AOC level in the COPD group were decreased; compared with stable period, lipid ratios and MDA levels in the acute period were elevated, while serum SOD and T-AOC levels were reduced (P<0.05). Pulmonary hypertension incidence and 3-year survival rates in the COPD group were 56.67% and 81.67% respectively; the lipid ratios and serum MDA levels in COPD patients with pulmonary hypertension were elevated compared with that in COPD patients without pulmonary hypertension; the serum SOD and T-AOC levels in COPD patients with pulmonary hypertension were reduced compared with that in patients without pulmonary hypertension (P<0.05). Spearman rank correlation analysis showed that ratios of LDL/HDL, TG/HDL and TC/HDL, and the serum MDA levels in COPD patients were positively correlated with 3-years pulmonary hypertension incidence (r=0.752, 0.748, 0.752, 0.748; P<0.05), and negatively correlated with 3-years survival rate (r=-0.722, -0.751, -0.736, -0.748; P<0.05); serum SOD and T-AOC levels in COPD patients were negatively correlated with 3-years pulmonary hypertension (r=-0.711, -0.734; P<0.05), and positively correlated with 3-year survival rate (r=0.726, 0.733; P<0.05). 
 Conclusion: Blood lipid ratio and oxidative stress levels in COPD patients are elevated while antioxidant abilities were attenuated. The lipid ratio and oxidative stress status in COPD patients is closely related to the prognosis of pulmonary hypertension. Therefore, blood lipid ratio and oxidative stress status may be used in evaluation of pulmonary hypertension and prognosis for COPD patients.

Comportamiento de los lípidos durante la gestación y su relación con acontecimientos obstétricos desfavorables / Relationship between lipid alterations during pregnancy and adverse pregnancy outcomes

Los lípidos juegan un importante papel durante la gestación, y en este periodo tienen lugar cambios importantes en el metabolismo lipoproteico. Durante el tercer trimestre del embarazo los niveles plasmáticos de colesterol y triglicéridos se ven sustancialmente incrementados, volviendo a niveles normales tras el parto. Se han descrito asociaciones entre el aumento de la morbilidad durante el embarazo e incrementos excesivos de la concentración plasmática del colesterol y triglicéridos. Por dicho motivo hemos revisado la relación entre las alteraciones lipídicas, la preeclampsia, la diabetes gestacional y el parto pretérmino. El control metabólico global de la embarazada mejoraría los resultados obstétricos, y la detección de alteraciones suprafisiológicas del perfil lipídico debería clasificar el embarazo en un nivel de riesgo superior, lo que comportaría un control más estricto

Lipids play an important role during pregnancy, and in this period major changes occur in lipoprotein metabolism. During the third trimester plasma cholesterol and triglyceride levels are substantially increased, returning to normal after delivery. Described associations between increased morbidity during pregnancy and excessive increases in plasma cholesterol and triglycerides. For this reason we have reviewed the relationship between lipid alterations, preeclampsia, gestational diabetes and preterm birth. The overall metabolic control can improve pregnancy outcomes, and the assessment of supraphysiological changes in lipid profile will classify pregnancy risk at a higher level, which would entail a stricter control

Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes.

The human skin barrier has an important role in protection and defense, reflected not only in the ability to resist entry of harmful substances into the human body, but also in the ability to prevent loss of water and nutrients. Once the skin barrier is damaged, the skin may become dry, scaly, and wrinkled, and a series of skin problems may occur. In this article, we review the composition of lipids, such as ceramides, cholesterol, and free fatty acids, in the skin and examine the expression of enzymes related to lipid metabolism, such as kallikreins, elongase of elongation of very long-chain fatty acids, hydrolases, and lipid synthases. Additionally, we discuss the involvement of these proteins in skin barrier function and structure. The information presented in this review is expected to provide a theoretical basis for the development of skin care products facilitating the maintenance and repair of skin barrier function.

Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease.

Epidemiologic and clinical studies suggest that elevated triglyceride levels are a biomarker of cardiovascular (CV) risk. Consistent with these findings, recent genetic evidence from mutational analyses, genome-wide association studies, and Mendelian randomization studies provide robust evidence that triglycerides and triglyceride-rich lipoproteins are in the causal pathway for atherosclerotic CV disease, indicating that they may play a pathogenic role, much like low-density lipoprotein cholesterol (LDL-C). Although statins are the cornerstone of dyslipidemia management, high triglyceride levels may persist in some patients despite statin therapy. Several triglyceride-lowering agents are available, including fibrates, niacin, and omega-3 fatty acids, of which prescription omega-3 fatty acids have the best tolerability and safety profile. In clinical studies, omega-3 fatty acids have been shown to reduce triglyceride levels, but products containing both eicosapentaenoic acid and docosahexaenoic acid may increase LDL-C levels. Icosapent ethyl, a high-purity eicosapentaenoic acid-only product, does not raise LDL-C levels and also reduces triglyceride, non-high-density lipoprotein cholesterol, and triglyceride-rich lipoprotein levels. In conclusion, omega-3 fatty acids are currently being evaluated in large CV outcome studies in statin-treated patients; these studies should help to elucidate the causative role of triglycerides in atherosclerotic CV disease.

In silico modeling of the dynamics of low density lipoprotein composition via a single plasma sample.

Lipoproteins play a key role in the development of CVD, but the dynamics of lipoprotein metabolism are difficult to address experimentally. This article describes a novel two-step combined in vitro and in silico approach that enables the estimation of key reactions in lipoprotein metabolism using just one blood sample. Lipoproteins were isolated by ultracentrifugation from fasting plasma stored at 4°C. Plasma incubated at 37°C is no longer in a steady state, and changes in composition may be determined. From these changes, we estimated rates for reactions like LCAT (56.3 µM/h), ß-LCAT (15.62 µM/h), and cholesteryl ester (CE) transfer protein-mediated flux of CE from HDL to IDL/VLDL (21.5 µM/h) based on data from 15 healthy individuals. In a second step, we estimated LDL's HL activity (3.19 pools/day) and, for the very first time, selective CE efflux from LDL (8.39 µM/h) by relying on the previously derived reaction rates. The estimated metabolic rates were then confirmed in an independent group (n = 10). Although measurement uncertainties do not permit us to estimate parameters in individuals, the novel approach we describe here offers the unique possibility to investigate lipoprotein dynamics in various diseases like atherosclerosis or diabetes.