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An association between PPARα-L162V polymorphism and increased plasma LDL cholesterol levels after risperidone treatment PPARα-L162V 多态性与利培酮治疗后血浆低密度脂蛋白胆固醇水平升高之间的关系
IF 3 Pub Date : 2023-12-13 DOI: 10.1016/j.plefa.2023.102604
Sergej Nadalin , Lena Zatković , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Ante Silić , Sanja Dević Pavlić , Alena Buretić-Tomljanović

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %).

过氧化物酶体增殖激活受体α(PPARα)和抗精神病药物都会影响多不饱和脂肪酸(PUFA)的平衡,因此 PPARα 的多态性可能与抗精神病药物的治疗反应有关。在此,我们研究了PPARα的功能性亮氨酸162缬氨酸(L162V)多态性是否会影响一组精神病患者(N = 186)的抗精神病治疗,以及接受利培酮、帕利培酮或联合治疗的患者亚组(N = 65)的抗精神病治疗。通过聚合酶链式反应分析,对未服用抗精神病药的首发患者和未坚持治疗的慢性患者进行了基因分型。在基线和接受各种抗精神病药物治疗 8 周后,我们评估了患者的阳性和阴性综合征量表 (PANSS) 评分、PANSS 因素和代谢综合征相关参数,包括空腹血浆脂质和葡萄糖水平以及体重指数。在所有患者组中,PPARα多态性对PANSS精神病理学和代谢参数没有影响。然而,在接受利培酮、帕利培酮或联合治疗的亚组患者中,PPARα多态性影响了血浆低密度脂蛋白胆固醇的变化。具体而言,与PPARα-L162L同源患者相比,PPARα-L162V杂合患者在接受抗精神病药物治疗后,其低密度脂蛋白胆固醇水平的升高幅度明显更高。PPARα 多态性具有很强的效应大小,但对低密度脂蛋白胆固醇水平变化的贡献相对较弱(∼12.8%)。
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引用次数: 0
Corrigendum to “Hemodialysis and Biotransformation of Erythrocyte Epoxy Fatty Acids in Peripheral Tissue” 血液透析与外周组织中红细胞环氧脂肪酸的生物转化 "的更正
IF 3 Pub Date : 2023-12-01 DOI: 10.1016/j.plefa.2022.102521
Tong Liu , Inci Dogan , Michael Rothe , Julius V. Kunz , Felix Knauf , Maik Gollasch , Friedrich C. Luft , Benjamin Gollasch
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引用次数: 0
Response to Letter to Editor 对致编辑信的回应。
IF 3 Pub Date : 2023-12-01 DOI: 10.1016/j.plefa.2023.102594
KV. Giriraja , SK. Bhanagar , L. Tomlinson , F. Sancilio
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引用次数: 0
“Selection of statistical tests influences the interpretation of a study outcome” a comment on “Giriraja KV, Bhatnagar SK, Tomlinson L, Sancilio F. An open-label, multicenter, phase 2 study of a food enriched with docosahexaenoic acid in adults with sickle cell disease. Prostaglandins Leukot Essent Fatty Acids. 2023 Jun; 193:102574. Doi: 10.1016/j.plefa.2023.102574. Epub 2023 Apr 7. PMID: 37121179” “统计测试的选择影响对研究结果的解释”,Giriraja KV,Bhatnagar SK,Tomlinson L,Sancilio F.的评论。一项针对镰状细胞病成人富含二十二碳六烯酸的食品的开放标签、多中心、2期研究。前列腺素Leukot Essent Fatty Acids。2023 Jun;193:102574。Doi:10.1016/j.plefa.2023102574。Epub 2023 Apr 7。PMID:37121179“。
IF 3 Pub Date : 2023-12-01 DOI: 10.1016/j.plefa.2023.102591
Ashwin P Patel

Parametric tests such as t-tests require a normal distribution of data. However, the determination of normal distribution may not be conclusive while dealing with a small sample size. Non-parametric tests such as Wilcoxon tests may be used in this situation, as these tests do not require normal distribution.

诸如t检验之类的参数检验需要数据的正态分布。然而,在处理小样本量时,正态分布的确定可能不是决定性的。这种情况下可以使用非参数检验,如Wilcoxon检验,因为这些检验不需要正态分布。
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引用次数: 0
Subgroup analyses of a randomized trial of DHA supplementation for infants born preterm with assessments of cognitive development up to 7-years of age: What happens in infants born <29 weeks’ gestation? 一项针对7岁以下早产儿补充DHA的随机试验的亚组分析:妊娠<29周的婴儿会发生什么?
IF 3 Pub Date : 2023-11-03 DOI: 10.1016/j.plefa.2023.102593
JF Gould , JM Bednarz , TR Sullivan , AJ McPhee , RA Gibson , M Makrides

A recent trial showed that high-dose docosahexaenoic acid (high-DHA) supplementation of infants born <29 weeks’ gestation improves intelligence quotient (IQ) at five years’ corrected age. However, this finding has not been detected by other trials of DHA, which either did not measure IQ or included more mature infants. We analyzed the subgroup of 204 infants born <29 weeks’ from our earlier randomized trial of high-DHA (∼1 % total fatty acids) or standard-DHA (∼ 0.3 % total fatty acids). Participants were assessed for cognition at 18 months, and IQ and behavior at seven years’ corrected age. No group differences were detected for mean cognitive, IQ or behavior scores. At 18 months, 18.8 % of children in the high-DHA group had a cognitive score <85, compared with 31.1 % of children in the standard-DHA group, but at seven years there was no difference. Although an underpowered post-hoc subgroup analysis, this study provides limited support to recommendations that infants born <29 weeks’ gestation require supplemental DHA.

最近的一项试验表明,在妊娠29周出生的婴儿中补充高剂量二十二碳六烯酸(高dha)可提高其5岁修正年龄时的智商(IQ)。然而,这一发现并没有在DHA的其他试验中被发现,这些试验要么没有测量智商,要么包括更成熟的婴儿。我们分析了204名29周出生的婴儿亚组,这些婴儿来自我们早期的高dha(总脂肪酸约1%)或标准dha(总脂肪酸约0.3%)的随机试验。参与者在18个月大时接受认知评估,在7岁时接受智商和行为评估。在平均认知、智商或行为得分方面,没有发现组间差异。在18个月时,高dha组中18.8%的儿童的认知评分为85分,而标准dha组中31.1%的儿童的认知评分为85分,但在7岁时没有差异。尽管这项研究的亚组分析能力不足,但它对妊娠29周出生的婴儿需要补充DHA的建议提供了有限的支持。
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引用次数: 0
Phospholipase D1 activity is crucial for cytosolic phospholipase A2 –dependent prostaglandin E2 formation in murine osteoblastic MC3T3-E1 cells 在小鼠成骨细胞MC3T3-E1中,磷脂酶D1活性对于胞浆磷脂酶A2依赖性前列腺素E2的形成至关重要
IF 3 Pub Date : 2023-10-30 DOI: 10.1016/j.plefa.2023.102592
Hans Jörg Leis , Werner Windischhofer

In bone, prostaglandin E2 (PGE2) is highly osteogenic and formed by osteoblasts, a key modulatory event in the regulation of bone cell activity. MC3T3-E1 cells are widely used as an in vitro model of osteoblast function. It is still not clear which pathways contribute to the release of AA in these cells. In this study we have focussed on the contribution of phospholipase D (PLD) enzymes to osteoblastic PGE2 formation after stimulation with endothelin-1 (ET-1). Using specific inhibitors of PLD1 and PLD2 we could show that PGE2 formation was strictly dependent on PLD1 but not PLD2 activity and cytosolic phospholipase A2 (cPLA2) was activated by triggering through PLD1. We have identified diacyl glycerol (DAG) as a possible effector molecule which may serve as a triggering signal for PKC activation and subsequent cPLA2 phosphorylation.

在骨中,前列腺素E2 (PGE2)是高度成骨的,由成骨细胞形成,是骨细胞活性调节的关键调节事件。MC3T3-E1细胞被广泛用作成骨细胞功能的体外模型。目前尚不清楚哪些途径有助于这些细胞中AA的释放。在这项研究中,我们重点研究了磷脂酶D (PLD)酶在内皮素-1 (ET-1)刺激后对成骨细胞PGE2形成的贡献。使用特定的PLD1和PLD2抑制剂,我们可以发现PGE2的形成严格依赖于PLD1而不是PLD2的活性,细胞质磷脂酶A2 (cPLA2)通过PLD1触发激活。我们已经确定了二酰基甘油(DAG)作为可能的效应分子,它可能作为PKC激活和随后的cPLA2磷酸化的触发信号。
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引用次数: 0
Effect of maternal fish oil supplementation during lactation on socioemotional wellbeing and physical activity in 13-year-old children: A randomized clinical trial 母亲在哺乳期补充鱼油对13岁儿童社会情绪健康和体育活动的影响:一项随机临床试验。
IF 3 Pub Date : 2023-10-01 DOI: 10.1016/j.plefa.2023.102588
Lotte Lauritzen , Emilie R. Hegelund , Sara E. Eriksen , Janni Niclasen , Kim F. Michaelsen

Early dietary long-chain n-3PUFA (n-3LCPUFA) may affect brain development. We investigated if fish oil supplementation of lactating mothers affected socioemotional wellbeing in adolescents in a potentially gender-specific manner. At age 13, we invited 92 children of mothers who completed a randomized trial with 1.5 g/d n-3 LCPUFA or olive oil during the first 4 months of lactation and 48 children of mothers with a high habitual fish intake. Children and parents answered validated questionnaires regarding socioemotional wellbeing and physical activity was monitored by ActiGraph for 7 days. Participation rate was 71%. Univariate correlations between children's and parents’ ratings on the individual scales were moderate-strong, but correlations across questionnaires indicated that parents might base their ratings on proxy markers. We found no group differences in self-rated socioemotional outcomes or physical activity. Although the study was small, it was the first follow-up on effects of perinatal n-3LCPUFA supply on socioemotional wellbeing in adolescence.

早期饮食中的长链n-3PUFA(n-3LCPUFA)可能影响大脑发育。我们调查了哺乳期母亲补充鱼油是否以潜在的性别特异性方式影响青少年的社会情绪健康。在13岁时,我们邀请了92名母亲的孩子,他们在哺乳期的前4个月内完成了一项1.5 g/d n-3 LCPUFA或橄榄油的随机试验,以及48名习惯性鱼类摄入量高的母亲的孩子。儿童和家长回答了关于社会情绪健康和身体活动的经验证的问卷,并通过ActiGraph监测了7天。参与率为71%。儿童和父母在个人量表上的评分之间的单变量相关性中等偏强,但问卷之间的相关性表明,父母可能会根据代理标记进行评分。我们在自我评价的社会情绪结果或身体活动方面没有发现群体差异。尽管这项研究规模较小,但它是首次对围产期n-3LCPUFA供应对青春期社会情绪健康影响的随访。
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引用次数: 0
15-lipoxygenase and cyclooxygenase expression profile and their related modulators in COVID-19 infection 15-脂氧合酶和环氧合酶在新冠肺炎感染中的表达谱及其相关调节剂。
IF 3 Pub Date : 2023-10-01 DOI: 10.1016/j.plefa.2023.102587
Sara Kianfar , Vahid Salimi , Alireza Jahangirifard , Seyed Bashir Mirtajani , Mohammad Amin Vaezi , Jila Yavarian , Talat Mokhtari-Azad , Masoumeh Tavakoli-Yaraki

Background

The role of the lipoxygenase (LOX) and cyclooxygenase (COX) enzymes in maintaining cellular homeostasis and regulating immune responses promoted us in this study to analyze the pattern of changes in 15-lipoxygenase and cyclooxygenase isoforms and their related cytokines in SARS-CoV-2 infection.

Methods

15-LOX-1, 15-LOX-2, COX-1 and COX-2 gene expression levels were determined using qRT-PCR in nasopharynx specimens from patients with severe [N = 40] and non-severe [N = 40] confirmed SARS-CoV-2 infections and healthy controls. Circulating levels of lL-6, lL-10, PGE2, and IFN-γ were measured in patients and healthy controls using ELISA assay. The associations between the measured variables and the patient's clinic-pathological characteristics were assessed for all groups.

Results

The expression level of 15-LOX-1 was elevated significantly in male patients with severe infection; although female patients showed a different expression profile. 15-LOX-2 expression level was considerably increased in male patients with severe infection; while changes in its expression remained inconclusive in female patients. The relationship between 15-LOX expression and the male gender was prominent. Both COX isoforms expression showed elevation in male and female patients that were correlated with disease severity. The simultaneous increase in lL-6, PGE2 and IFN-γ levels also decrease in lL-10 in patients with severe infection indicating the possible regulatory network related to the COX and 15-LOX enzymes in the output of the SARS-CoV-2 infection.

Conclusion

The results of this study determined the pattern of possible changes in key enzymes of prostaglandin and eicosanoids synthesis pathway and their mediators, which can be helpful in mapping the SARS-CoV-2 pathogenicity and pharmaceutical approaches.

背景:脂氧合酶(LOX)和环氧合酶(COX)在维持细胞稳态和调节免疫反应中的作用促使我们在本研究中分析了严重急性呼吸系统综合征冠状病毒2型感染中15种脂氧合蛋白和环氧合蛋白亚型及其相关细胞因子的变化模式。方法:采用qRT-PCR方法测定严重和非严重确诊的严重急性呼吸系统综合征冠状病毒2型感染者和健康对照者鼻咽标本中15-LOX-1、15-LOX-2、COX-1和COX-2基因的表达水平。用ELISA法测定患者和健康对照组的循环中lL-6、lL-10、PGE2和IFN-γ的水平。对所有组的测量变量与患者临床病理特征之间的相关性进行了评估。结果:15-LOX-1在男性重症感染患者中的表达水平显著升高;尽管女性患者表现出不同的表达谱。15-LOX-2的表达水平在患有严重感染的男性患者中显著增加;而在女性患者中其表达的变化仍不确定。15-LOX的表达与男性的关系显著。两种COX亚型在男性和女性患者中的表达均升高,这与疾病的严重程度相关。严重感染患者的lL-6、PGE2和IFN-γ水平同时升高,lL-10水平也降低,这表明可能与严重急性呼吸系统综合征冠状病毒2型感染输出中的COX和15-LOX酶有关的调节网络。结论:本研究结果确定了前列腺素和类二十烷合成途径关键酶及其介质的可能变化模式,有助于绘制严重急性呼吸系统综合征冠状病毒2型的致病性和药物途径。
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引用次数: 0
Resolvin E1 heals injured cardiomyocytes: Therapeutic implications and H-FABP as a readout for cardiovascular disease & systemic inflammation Resolvin E1治愈受伤的心肌细胞:治疗意义和H-FABP作为心血管疾病和全身炎症的读数。
IF 3 Pub Date : 2023-10-01 DOI: 10.1016/j.plefa.2023.102586
A. Zheng , N. Huang , D. Bean , S. Rayapaneni , Jude Deeney , M. Sagar , James A. Hamilton

The purpose of this study is to investigate heart-fatty acid binding protein (H-FABP) leakage from cardiomyocytes as a quantitative measure of cell membrane damage and to test healing by Resolvin E1 (RVE1) as a potential therapeutic for patients with inflammatory diseases (cardiovascular disease and comorbidities) with high morbidity and mortality. Our quantitative ELISA assays demonstrated H-FABP as a sensitive and reliable biomarker for measuring cardiomyocyte damage induced by lipopolysaccharide (LPS) and healing by RvE1, a specialized pro-resolving mediator (SPM) derived from the Omega-3 fatty acid, eicosapentaenoic acid (EPA), a dietary nutrient that balances inflammation to restore homeostasis. RvE1 reduced leakage of H-FABP by up to 86%, which supports our hypothesis that inflammation as a mechanism of injury can be targeted for therapy. H-FABP as a blood biomarker was tested in 40 patients admitted to Boston Medical Center for respiratory distress, (20 patients with and 20 patients without COVID infection). High levels of H-FABP correlated with clinically diagnosed CVD, diabetes, and end-stage renal disease (ESRD) in both patient groups. The level of H-FABP indicates not only CVD damage but is a valuable measure for patients with increased inflammation disease comorbidities.

本研究的目的是研究心肌细胞的心脏脂肪酸结合蛋白(H-FABP)渗漏作为细胞膜损伤的定量测量,并测试Resolvin E1(RVE1)作为高发病率和高死亡率炎症性疾病(心血管疾病和合并症)患者的潜在治疗剂的愈合情况。我们的定量ELISA测定表明,H-FABP是一种敏感可靠的生物标志物,可用于测量脂多糖(LPS)诱导的心肌细胞损伤和RvE1的愈合,RvE1是一种专门的促分解介质(SPM),来源于Omega-3脂肪酸二十碳五烯酸(EPA),一种平衡炎症以恢复体内平衡的膳食营养素。RvE1将H-FABP的渗漏减少了86%,这支持了我们的假设,即炎症作为一种损伤机制可以作为治疗的靶点。H-FABP作为血液生物标志物在波士顿医疗中心因呼吸窘迫入院的40名患者中进行了测试(20名感染新冠肺炎的患者和20名未感染新冠病毒的患者)。在两个患者组中,高水平的H-FABP与临床诊断的CVD、糖尿病和终末期肾病(ESRD)相关。H-FABP水平不仅表明CVD损伤,而且对于炎症疾病合并症增加的患者来说是一个有价值的指标。
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引用次数: 0
Decreased plasma levels of sphingolipids and total cholesterol in adult cystic fibrosis patients 成年囊性纤维化患者血浆鞘脂和总胆固醇水平降低。
IF 3 Pub Date : 2023-10-01 DOI: 10.1016/j.plefa.2023.102590
Dilara Bal Topcu , Berrin Er , Filiz Ozcan , Mutay Aslan , Lutfi Coplu , Incilay Lay , Yesim Oztas

Background

Sphingolipid species in the lung epithelium have a critical role for continuity of membrane structure, vesicular transport, and cell survival. Sphingolipid species were reported to have a role in the inflammatory etiology of cystic fibrosis by previous work. The aim of the study was to investigate the levels of plasma sphingomyelin and ceramide in adult cystic fibrosis (CF) patients and compared with healthy controls.

Materials and methods

Blood samples were obtained from CF patients at exacerbation (n = 15), discharge (n = 13) and stable periods (n = 11). Healthy individuals (n = 15) of similar age served as control. Levels of C16–C24 sphingomyelin and C16–C24 ceramide were measured in the plasma by LC-MS/MS. Also, cholesterol and triglyceride levels were determined in plasma samples of the patients at stable period.

Results

All measured sphingomyelin and ceramide levels in all periods of CF patients were significantly lower than healthy controls except C16 sphingomyelin level in the stable period. However, plasma Cer and SM levels among exacerbation, discharge, and stable periods of CF were not different. CF patients had significantly lower cholesterol levels compared to healthy individuals. We found significant correlation of cholesterol with C16 sphingomyelin.

Conclusion

We observed lower plasma Cer and SM levels in adult CF patients at exacerbation, discharge, and stable periods compared to healthy controls. We didn't find any significant difference between patient Cer and SM levels among these three periods. Our limited number of patients might have resulted with this statistical insignificance. However, percentage of SM16 levels were increased at discharge compared to exacerbation levels, while percentage of Cer16 and Cer 20 decreased at stable compared to exacerbation. Inclusion of a larger number of CF patients in such a follow up study may better demonstrate any possible difference between exacerbation, discharge, and stable periods.

背景:肺上皮中的鞘氨醇脂质对膜结构的连续性、囊泡运输和细胞存活起着关键作用。先前的研究报道鞘氨醇脂质在囊性纤维化的炎症病因中起作用。本研究的目的是研究成年囊性纤维化(CF)患者血浆鞘磷脂和神经酰胺的水平,并与健康对照组进行比较。材料和方法:从CF患者急性发作期(n=15)、出院期(n=13)和稳定期(n=11)采集血样。年龄相近的健康个体(n=15)作为对照。通过LC-MS/MS测量血浆中C16-C24鞘磷脂和C16-C24-神经酰胺的水平。此外,还测定了稳定期患者血浆样本中的胆固醇和甘油三酯水平。结果:除稳定期C16鞘磷脂水平外,CF患者所有时期的鞘磷脂和神经酰胺水平均显著低于健康对照组。然而,CF发作期、出院期和稳定期的血浆Cer和SM水平没有差异。CF患者的胆固醇水平明显低于健康人。我们发现胆固醇与C16鞘磷脂显著相关。结论:与健康对照组相比,我们观察到成年CF患者在病情恶化、出院和稳定期的血浆Cer和SM水平较低。在这三个时期,我们没有发现患者的Cer和SM水平之间有任何显著差异。我们有限的患者数量可能导致了这种统计上的微不足道。然而,与病情恶化水平相比,出院时SM16水平的百分比增加,而与病情恶化相比,稳定时Cer16和Cer20的百分比下降。在这样的随访研究中纳入更多的CF患者可以更好地证明恶化期、出院期和稳定期之间的任何可能差异。
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引用次数: 0
期刊
Prostaglandins, leukotrienes, and essential fatty acids
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