Pub Date : 2025-02-24DOI: 10.1016/j.plefa.2025.102670
BN Yamaja Setty , Krishna Rao Maddipati , Scott W Keith , Ayako Shimada , Pari Sheerer , Robin E Miller
Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (n = 45) and control children (n = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.
{"title":"Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation","authors":"BN Yamaja Setty , Krishna Rao Maddipati , Scott W Keith , Ayako Shimada , Pari Sheerer , Robin E Miller","doi":"10.1016/j.plefa.2025.102670","DOIUrl":"10.1016/j.plefa.2025.102670","url":null,"abstract":"<div><div>Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (<em>n</em> = 45) and control children (<em>n</em> = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102670"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-24DOI: 10.1016/j.plefa.2025.102671
Nils Hoem , Stephen Harris , Grace Scott , Petter-Arnt Hals
To investigate the systemic kinetics of EPA and DHA across different lipid classes, male rats were administered [1–14C]-radiolabelled EPA and DHA as triglycerides (TAG), phosphatidylcholine (PC), or lyso-phosphatidylcholine (LPC) by gavage. LPC was also administered intravenously. Plasma and whole blood concentration-time profiles were recorded from 0 to 168 hours, while cumulative radioactivity in expired air, faeces, and urine was recorded for up to 336 hours.
Non-compartmental analysis and compartmental modelling demonstrated overall first-order radiotracer kinetics for both fatty acids, with comparable terminal half-lives. The primary difference was in maximum concentration (Cmax ((µg-eq/g)/(mg/kg)): DHA = 0.18± 0.089, EPA = 0.24± 0.103; P < 0.0001). Between TAG and PC, only time to maximum concentration (Tmax (h)) differed (PC = 3.23 ± 0.94, TAG = 2.55 ± 0.77; P = 0.0004). LPC showed significant differences from TAG and PC in area under the curve (AUC0-inf), Cmax, Tmax, and total clearance (CL/F (mL/(kg h))). Cumulative radioactivity levels in expired air and faeces were consistent with blood and plasma kinetics.
As suggested by early-phase (0 to 48 hours) radioactivity accumulation, which deviated from first-order behaviour, TAG and PC, but not LPC, exhibited some faecal loss without systemic absorption.
The compartmental models developed performed equally well for radiolabelled EPA and DHA, regardless of whether administered as TAG, PC, or LPC. The model can be adapted to handle non-zero endogenous baselines and was successfully applied to non-radiolabelled EPA, docosapentaenoic acid (DPA), and DHA, quantified via LC-MS/MS. These models can be applied to both radioactive and stable isotopes and adapted to include organ-specific kinetics, as well as those of EPA, DPA, and DHA in other species, including humans.
{"title":"The single-dose kinetics of [1–14C]-labelled EPA and DHA, administered to male rats as TAG, phosphatidylcholine (PC), and lyso-phosphatidylcholine (LPC), is structurally similar across lipid forms and can be described using the same compartmental models","authors":"Nils Hoem , Stephen Harris , Grace Scott , Petter-Arnt Hals","doi":"10.1016/j.plefa.2025.102671","DOIUrl":"10.1016/j.plefa.2025.102671","url":null,"abstract":"<div><div>To investigate the systemic kinetics of EPA and DHA across different lipid classes, male rats were administered [1–<sup>14</sup>C]-radiolabelled EPA and DHA as triglycerides (TAG), phosphatidylcholine (PC), or lyso-phosphatidylcholine (LPC) by gavage. LPC was also administered intravenously. Plasma and whole blood concentration-time profiles were recorded from 0 to 168 hours, while cumulative radioactivity in expired air, faeces, and urine was recorded for up to 336 hours.</div><div>Non-compartmental analysis and compartmental modelling demonstrated overall first-order radiotracer kinetics for both fatty acids, with comparable terminal half-lives. The primary difference was in maximum concentration (Cmax ((µg-eq/g)/(mg/kg)): DHA = 0.18± 0.089, EPA = 0.24± 0.103; P < 0.0001). Between TAG and PC, only time to maximum concentration (Tmax (h)) differed (PC = 3.23 ± 0.94, TAG = 2.55 ± 0.77; P = 0.0004). LPC showed significant differences from TAG and PC in area under the curve (AUC0-inf), Cmax, Tmax, and total clearance (CL/F (mL/(kg h))). Cumulative radioactivity levels in expired air and faeces were consistent with blood and plasma kinetics.</div><div>As suggested by early-phase (0 to 48 hours) radioactivity accumulation, which deviated from first-order behaviour, TAG and PC, but not LPC, exhibited some faecal loss without systemic absorption.</div><div>The compartmental models developed performed equally well for radiolabelled EPA and DHA, regardless of whether administered as TAG, PC, or LPC. The model can be adapted to handle non-zero endogenous baselines and was successfully applied to non-radiolabelled EPA, docosapentaenoic acid (DPA), and DHA, quantified via LC-MS/MS. These models can be applied to both radioactive and stable isotopes and adapted to include organ-specific kinetics, as well as those of EPA, DPA, and DHA in other species, including humans.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102671"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Controlling food intake and improving fat distribution are crucial for preventing and treating cardiovascular disease. Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) can inhibit fat deposition and facilitate bodyweight reduction, suggesting its potential to safeguard against cardiovascular disease. The transgenic (tg) mice, which inserted Pai expression cassette into the Rosa26 locus, can produce endogenous t10c12-CLA. In the present study, we used tg mice to evaluate whether the long-term existence of t10c12-CLA has a protective effect on the vascular fibrosis phenotype. The male wild-type (wt) and tg mice were marked as wt+chow, tg+chow, wt+HFD and tg+HFD groups with 24 weeks feeding the chow diet or high-fat diet (HFD). Compared with wt+chow and tg+chow mice, wt+HFD mice showed a significant (P < 0.05) increase in bodyweight and circulating lipid levels. The arterial blood vessels of wt+HFD mice displayed obvious lipid streaks and disorganization of collagen fibers. While compared with wt+HFD mice, tg+HFD mice showed a significant (P < 0.05) decrease in body weight and circulating lipid levels. The arterial blood vessels of tg+HFD mice displayed slight foam cells, predicting that t10c12-CLA can alleviates vascular fibrosis degree caused by HFD. The RNA and protein expression of proinflammatory factors in arterial blood vessels of tg+HFD mice were significantly (P < 0.05) decreased than those of wt+HFD mice. In conclusion, long-term existence of t10c12-CLA can improve lipid metabolism and circulating lipid levels and inhibit vascular inflammation and vascular fibrosis degree in obese mice, thereby preventing the further development of cardiovascular disease.
{"title":"Trans 10, cis 12-conjugated linoleic acid alleviates vascular fibrosis in obese mice","authors":"Shuai Yu , Yu Rao , Jiaqi Lu, Jiarun Li, Baozhu Wang, Kemian Gou","doi":"10.1016/j.plefa.2025.102669","DOIUrl":"10.1016/j.plefa.2025.102669","url":null,"abstract":"<div><div>Controlling food intake and improving fat distribution are crucial for preventing and treating cardiovascular disease. Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) can inhibit fat deposition and facilitate bodyweight reduction, suggesting its potential to safeguard against cardiovascular disease. The transgenic (tg) mice, which inserted Pai expression cassette into the Rosa26 locus, can produce endogenous t10c12-CLA. In the present study, we used tg mice to evaluate whether the long-term existence of t10c12-CLA has a protective effect on the vascular fibrosis phenotype. The male wild-type (wt) and tg mice were marked as wt+chow, tg+chow, wt+HFD and tg+HFD groups with 24 weeks feeding the chow diet or high-fat diet (HFD). Compared with wt+chow and tg+chow mice, wt+HFD mice showed a significant (<em>P</em> < 0.05) increase in bodyweight and circulating lipid levels. The arterial blood vessels of wt+HFD mice displayed obvious lipid streaks and disorganization of collagen fibers. While compared with wt+HFD mice, tg+HFD mice showed a significant (<em>P</em> < 0.05) decrease in body weight and circulating lipid levels. The arterial blood vessels of tg+HFD mice displayed slight foam cells, predicting that t10c12-CLA can alleviates vascular fibrosis degree caused by HFD. The RNA and protein expression of proinflammatory factors in arterial blood vessels of tg+HFD mice were significantly (<em>P</em> < 0.05) decreased than those of wt+HFD mice. In conclusion, long-term existence of t10c12-CLA can improve lipid metabolism and circulating lipid levels and inhibit vascular inflammation and vascular fibrosis degree in obese mice, thereby preventing the further development of cardiovascular disease.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102669"},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-30DOI: 10.1016/j.plefa.2025.102667
Heitor O. Santos, Rafaela Nehme, Larissa S. Limirio, Maria Eduarda de F. Mendonça, Flávia M.S. de Branco, Erick P. de Oliveira
Background & aims
Several studies have suggested that increased intake of saturated fatty acids (SFAs) may have a pro-inflammatory effect, potentially impacting muscle mass and strength. However, the relationship of plasma SFAs and their subtypes (which reflect dietary SFA intake) with muscle mass and strength remains poorly understood. This study aimed to evaluate the association of plasma SFAs with lean mass and handgrip strength in adults.
Methods
A cross-sectional study was conducted with 896 participants aged 20-59 years, selected from a subsample of the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Total plasma SFAs and their subtypes were detected using gas chromatography-mass spectrometry. Lean mass was assessed using dual-energy X-ray absorptiometry, with evaluations of both total lean mass and appendicular lean mass. Muscle strength was measured using a handgrip dynamometer, with combined grip strength calculated by summing the highest values from each hand. Linear regression analysis was conducted to examine the association between plasma SFAs, lean mass, and handgrip strength, adjusting for potential confounders.
Results
Total lean mass was negatively associated with total plasma SFAs and several of their subtypes such as plasma levels of stearic acid, palmitic acid, arachidic acid, tricosanoic acid, lignoceric acid, and docosanoic acid. Similarly, appendicular lean mass was negatively associated with total plasma SFAs, as well as with several specific subtypes, including palmitic acid, stearic acid, margaric acid, pentadecanoic acid, and myristic acid. Handgrip strength also demonstrated a negative association with total plasma SFAs, including specific subtypes such as lauric acid, palmitic acid, capric acid, margaric acid, pentadecanoic acid, and myristic acid.
Conclusion
Total plasma SFAs and several of their subtypes are inversely associated with lean mass and muscle strength in adults.
{"title":"Plasma saturated fatty acids are inversely associated with lean mass and strength in adults: NHANES 2011–2012","authors":"Heitor O. Santos, Rafaela Nehme, Larissa S. Limirio, Maria Eduarda de F. Mendonça, Flávia M.S. de Branco, Erick P. de Oliveira","doi":"10.1016/j.plefa.2025.102667","DOIUrl":"10.1016/j.plefa.2025.102667","url":null,"abstract":"<div><h3>Background & aims</h3><div>Several studies have suggested that increased intake of saturated fatty acids (SFAs) may have a pro-inflammatory effect, potentially impacting muscle mass and strength. However, the relationship of plasma SFAs and their subtypes (which reflect dietary SFA intake) with muscle mass and strength remains poorly understood. This study aimed to evaluate the association of plasma SFAs with lean mass and handgrip strength in adults.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted with 896 participants aged 20-59 years, selected from a subsample of the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Total plasma SFAs and their subtypes were detected using gas chromatography-mass spectrometry. Lean mass was assessed using dual-energy X-ray absorptiometry, with evaluations of both total lean mass and appendicular lean mass. Muscle strength was measured using a handgrip dynamometer, with combined grip strength calculated by summing the highest values from each hand. Linear regression analysis was conducted to examine the association between plasma SFAs, lean mass, and handgrip strength, adjusting for potential confounders.</div></div><div><h3>Results</h3><div>Total lean mass was negatively associated with total plasma SFAs and several of their subtypes such as plasma levels of stearic acid, palmitic acid, arachidic acid, tricosanoic acid, lignoceric acid, and docosanoic acid. Similarly, appendicular lean mass was negatively associated with total plasma SFAs, as well as with several specific subtypes, including palmitic acid, stearic acid, margaric acid, pentadecanoic acid, and myristic acid. Handgrip strength also demonstrated a negative association with total plasma SFAs, including specific subtypes such as lauric acid, palmitic acid, capric acid, margaric acid, pentadecanoic acid, and myristic acid.</div></div><div><h3>Conclusion</h3><div>Total plasma SFAs and several of their subtypes are inversely associated with lean mass and muscle strength in adults.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102667"},"PeriodicalIF":3.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-29DOI: 10.1016/j.plefa.2025.102665
Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović
Several studies have shown antipsychotic effects of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib as an add-on treatment to antipsychotic treatment. The functional rs689466 (A/G) polymorphism in the gene encoding COX-2 (also known as the prostaglandin-endoperoxide synthase 2 gene) has been correlated with schizophrenia risk and the niacin skin flush response among chronic patients under antipsychotic treatment. Here, we investigated whether this polymorphism was associated with antipsychotic treatment in a group of total psychosis patients (N = 186), as well as a subgroup of patients treated with clozapine (N = 74). Antipsychotic-naïve first-episode patients and non-adherent chronic psychosis patients were genotyped by polymerase chain reaction/restriction fragment length polymorphism analysis. At baseline and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores, factors, and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels and body mass index. In the total patient group, the COX-2 polymorphism was not associated with PANSS psychopathology scores or metabolic parameters. However, in the subgroup of patients treated with clozapine, the COX-2 polymorphism was associated with changes in plasma HDL cholesterol. Specifically, compared to patients homozygous for the A allele, the subgroup of patients treated with clozapine and positive for the G allele (i.e., GG or AG genotype) exhibited significantly higher increases in HDL cholesterol levels. The COX-2 polymorphism had a moderate effect size but made a relatively weak contribution to variations in the HDL cholesterol level (∼9.6 %).
{"title":"Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients","authors":"Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović","doi":"10.1016/j.plefa.2025.102665","DOIUrl":"10.1016/j.plefa.2025.102665","url":null,"abstract":"<div><div>Several studies have shown antipsychotic effects of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib as an add-on treatment to antipsychotic treatment. The functional rs689466 (A/G) polymorphism in the gene encoding COX-2 (also known as the prostaglandin-endoperoxide synthase 2 gene) has been correlated with schizophrenia risk and the niacin skin flush response among chronic patients under antipsychotic treatment. Here, we investigated whether this polymorphism was associated with antipsychotic treatment in a group of total psychosis patients (<em>N</em> = 186), as well as a subgroup of patients treated with clozapine (<em>N</em> = 74). Antipsychotic-naïve first-episode patients and non-adherent chronic psychosis patients were genotyped by polymerase chain reaction/restriction fragment length polymorphism analysis. At baseline and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores, factors, and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels and body mass index. In the total patient group, the COX-2 polymorphism was not associated with PANSS psychopathology scores or metabolic parameters. However, in the subgroup of patients treated with clozapine, the COX-2 polymorphism was associated with changes in plasma HDL cholesterol. Specifically, compared to patients homozygous for the A allele, the subgroup of patients treated with clozapine and positive for the G allele (i.e., GG or AG genotype) exhibited significantly higher increases in HDL cholesterol levels. The COX-2 polymorphism had a moderate effect size but made a relatively weak contribution to variations in the HDL cholesterol level (∼9.6 %).</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102665"},"PeriodicalIF":3.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-29DOI: 10.1016/j.plefa.2025.102666
Mariano Gallo Ruelas , Ivo Queiroz , Túlio Pimentel , Arthur Henrique Tavares , Maria L.R. Defante , Lucas M. Barbosa , Igor Eckert
Background
Seal oil (SO) supplementation has been purported to have cardiovascular health benefits due to its content of omega-3 fatty acids; however, the clinical evidence base for this intervention has yet to be comprehensively assessed.
Objective
We aimed to evaluate the effects of oral SO supplementation on lipid profile biomarkers.
Methods
A systematic search was performed on Pubmed, Embase, Web of Science and Cochrane Library, from inception to August 2024. Only randomized controlled trials (RCTs) assessing the effect of SO on lipid profile biomarkers were included. A random-effects meta-analysis was applied to determine the overall effect estimate. The certainty of evidence (CoE) was evaluated using the GRADE approach.
Results
Nine RCTs were included in the review after the screening of 242 studies, comprising a total of 626 patients. Supplementation of SO resulted in no statistically significant effects on LDL-C (MD -0.07 mmol/L; 95 % CI [-0.19, 0.05]; CoE: Low) and total cholesterol (MD -0.12 mmol/L; 95 % CI [-0.30, 0.06]; CoE: Very low). There were statistically significant results of modest-to-trivial clinical importance on triglycerides (MD -0.19 mmol/L, 95 % CI [-0.30, -0.08]; CoE: Low) and trivial importance on HDL-C (MD 0.07 mmol/L, 95 % CI [0.003, 0.13]; CoE: Very low).
Conclusion
There is no sufficiently certain evidence to determine the effects of SO on cardiovascular lipid biomarkers. Our analyses may suggest a modest-to-trivial, clinically uncertain beneficial effect on triglyceride levels; and little to no effect on LDL-C. Effect estimates for HDL-C and total cholesterol levels were highly uncertain. Further evidence is required to conclusively determine the effects of oral SO on lipid biomarkers.
Protocol registration number
CRD42024583739
海豹油（SO）补充剂被认为对心血管健康有益，因为它含有omega-3脂肪酸；然而，这种干预的临床证据基础尚未得到全面评估。目的评价口服SO补充剂对血脂生物标志物的影响。方法系统检索Pubmed、Embase、Web of Science和Cochrane Library，检索时间为建站至2024年8月。仅纳入了评估SO对血脂生物标志物影响的随机对照试验（rct）。采用随机效应荟萃分析确定总体效应估计。使用GRADE方法评估证据的确定性（CoE）。结果在242项研究筛选后，纳入9项rct，共纳入626例患者。补充SO对LDL-C的影响无统计学意义(MD -0.07 mmol/L；95% ci [-0.19, 0.05]；CoE：低)和总胆固醇(MD -0.12 mmol/L；95% ci [-0.30, 0.06]；CoE：非常低)。甘油三酯的临床重要性有统计学意义（MD -0.19 mmol/L, 95% CI [-0.30, -0.08]）；CoE：低)，对HDL-C不重要(MD 0.07 mmol/L, 95% CI [0.003, 0.13]；CoE：非常低)。结论目前尚没有足够的证据表明大豆油对心血管脂质生物标志物的影响。我们的分析可能表明对甘油三酯水平有轻微到微不足道的、临床不确定的有益影响；对LDL-C几乎没有影响对HDL-C和总胆固醇水平的影响估计高度不确定。需要进一步的证据来确定口服SO对脂质生物标志物的影响。协议注册号crd42024583739
{"title":"Effects of seal oil supplementation on lipid profile biomarkers: A systematic review and meta-analysis of randomized controlled trials","authors":"Mariano Gallo Ruelas , Ivo Queiroz , Túlio Pimentel , Arthur Henrique Tavares , Maria L.R. Defante , Lucas M. Barbosa , Igor Eckert","doi":"10.1016/j.plefa.2025.102666","DOIUrl":"10.1016/j.plefa.2025.102666","url":null,"abstract":"<div><h3>Background</h3><div>Seal oil (SO) supplementation has been purported to have cardiovascular health benefits due to its content of omega-3 fatty acids; however, the clinical evidence base for this intervention has yet to be comprehensively assessed.</div></div><div><h3>Objective</h3><div>We aimed to evaluate the effects of oral SO supplementation on lipid profile biomarkers.</div></div><div><h3>Methods</h3><div>A systematic search was performed on Pubmed, Embase, Web of Science and Cochrane Library, from inception to August 2024. Only randomized controlled trials (RCTs) assessing the effect of SO on lipid profile biomarkers were included. A random-effects meta-analysis was applied to determine the overall effect estimate. The certainty of evidence (CoE) was evaluated using the GRADE approach.</div></div><div><h3>Results</h3><div>Nine RCTs were included in the review after the screening of 242 studies, comprising a total of 626 patients. Supplementation of SO resulted in no statistically significant effects on LDL-C (MD -0.07 mmol/L; 95 % CI [-0.19, 0.05]; CoE: Low) and total cholesterol (MD -0.12 mmol/L; 95 % CI [-0.30, 0.06]; CoE: Very low). There were statistically significant results of modest-to-trivial clinical importance on triglycerides (MD -0.19 mmol/L, 95 % CI [-0.30, -0.08]; CoE: Low) and trivial importance on HDL-C (MD 0.07 mmol/L, 95 % CI [0.003, 0.13]; CoE: Very low).</div></div><div><h3>Conclusion</h3><div>There is no sufficiently certain evidence to determine the effects of SO on cardiovascular lipid biomarkers. Our analyses may suggest a modest-to-trivial, clinically uncertain beneficial effect on triglyceride levels; and little to no effect on LDL-C. Effect estimates for HDL-C and total cholesterol levels were highly uncertain. Further evidence is required to conclusively determine the effects of oral SO on lipid biomarkers.</div></div><div><h3>Protocol registration number</h3><div>CRD42024583739</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102666"},"PeriodicalIF":3.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143217649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-28DOI: 10.1016/j.plefa.2025.102668
Mohammed Al Sinani , Mark Johnson , Michael Crawford , Mohammed Al Maqbali , Samir Al-Adawi
Introduction
Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.
Methodology
In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8–12 and 24–28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al.
Results
Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (p = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (p = 0.01), total omega 6 FAs, (p = 0.03), docosahexaenoic acid (22:6 n-3) (p = 0.03), docosapentaenoic acid (22:5 n-3) (p = 0.04), eicosapentaenoic acid (20:5 n-3) (p = 0.005), total omega 3 FAs (p = 0.005), omega-3 index (p = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.
Conclusions
Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.
{"title":"Depression and anxiety in the pregnant Omani population in relation to their fatty acid intake and levels","authors":"Mohammed Al Sinani , Mark Johnson , Michael Crawford , Mohammed Al Maqbali , Samir Al-Adawi","doi":"10.1016/j.plefa.2025.102668","DOIUrl":"10.1016/j.plefa.2025.102668","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.</div></div><div><h3>Methodology</h3><div>In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8–12 and 24–28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al.</div></div><div><h3>Results</h3><div>Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (<em>p</em> = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (<em>p</em> = 0.01), total omega 6 FAs, (<em>p</em> = 0.03), docosahexaenoic acid (22:6 n-3) (<em>p</em> = 0.03), docosapentaenoic acid (22:5 n-3) (<em>p</em> = 0.04), eicosapentaenoic acid (20:5 n-3) (<em>p</em> = 0.005), total omega 3 FAs (<em>p</em> = 0.005), omega-3 index (<em>p</em> = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.</div></div><div><h3>Conclusions</h3><div>Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102668"},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-16DOI: 10.1016/j.plefa.2025.102664
Paul Faulkner , E.Leigh Gibson , Simon C. Dyall
Background
The long-chain omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects in depression, and these effects may be mediated via changes in functional brain connectivity. However, little is known about these effects in those with subthreshold depression.
Methods
15 Participants aged 18–29 years with Patient Health Questionnaire-8 (PHQ-8) scores ≥ 4 and Generalised Anxiety Disorder Assessment-7 (GAD-7) scores ≥ 5, underwent resting-state functional magnetic resonance imaging. Whole-brain, seed-based connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala seeds. Omega-3 and -6 PUFA status was assessed from dried bloodspot analysis of %DHA, %EPA, Omega-3 Index (calculated as the sum of DHA plus EPA expressed as a percentage of the total measured fatty acids and a correction applied as dried blood spot samples were used instead of erythrocytes) and ratio of the omega-6 PUFA arachidonic acid (ARA) to EPA (ARA/EPA).
Results
PHQ-8 scores indicated subthreshold depression (mean = 10.0; SD = 4.2) and were negatively associated with DHA levels and Omega-3 Index. Significant negative associations were also identified between connectivity of the OFC with the angular gyrus and DHA and Omega-3 Index, while weaker connectivity of these regions was associated with lower PHQ-8 and GAD-7 scores. DHA and Omega-3 Index values were significantly associated with greater connectivity of the amygdala with the posterior cingulate cortex, which was also associated with lower PHQ-8 scores.
Conclusions
Higher omega-3 PUFA status in young adults with moderate, but mean subthreshold depression was associated with lower depression rating scores and altered functional connectivity of brain regions shown to play a role in the neurobiology of depression.
{"title":"Long-chain omega-3 polyunsaturated fatty acids are associated with brain connectivity and mood in young adults with subthreshold depression: A preliminary study","authors":"Paul Faulkner , E.Leigh Gibson , Simon C. Dyall","doi":"10.1016/j.plefa.2025.102664","DOIUrl":"10.1016/j.plefa.2025.102664","url":null,"abstract":"<div><h3>Background</h3><div>The long-chain omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects in depression, and these effects may be mediated via changes in functional brain connectivity. However, little is known about these effects in those with subthreshold depression.</div></div><div><h3>Methods</h3><div>15 Participants aged 18–29 years with Patient Health Questionnaire-8 (PHQ-8) scores ≥ 4 and Generalised Anxiety Disorder Assessment-7 (GAD-7) scores ≥ 5, underwent resting-state functional magnetic resonance imaging. Whole-brain, seed-based connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala seeds. Omega-3 and -6 PUFA status was assessed from dried bloodspot analysis of %DHA, %EPA, Omega-3 Index (calculated as the sum of DHA plus EPA expressed as a percentage of the total measured fatty acids and a correction applied as dried blood spot samples were used instead of erythrocytes) and ratio of the omega-6 PUFA arachidonic acid (ARA) to EPA (ARA/EPA).</div></div><div><h3>Results</h3><div>PHQ-8 scores indicated subthreshold depression (mean = 10.0; SD = 4.2) and were negatively associated with DHA levels and Omega-3 Index. Significant negative associations were also identified between connectivity of the OFC with the angular gyrus and DHA and Omega-3 Index, while weaker connectivity of these regions was associated with lower PHQ-8 and GAD-7 scores. DHA and Omega-3 Index values were significantly associated with greater connectivity of the amygdala with the posterior cingulate cortex, which was also associated with lower PHQ-8 scores.</div></div><div><h3>Conclusions</h3><div>Higher omega-3 PUFA status in young adults with moderate, but mean subthreshold depression was associated with lower depression rating scores and altered functional connectivity of brain regions shown to play a role in the neurobiology of depression.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102664"},"PeriodicalIF":3.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-16DOI: 10.1016/j.plefa.2024.102662
J. Geertsema , M.A. Franßen , F. Barban , L. Šarauskytė , M. Giera , G. Kooij , A Korosi
Lipid dyshomeostasis and neuroinflammation are key hallmarks of neuropsychiatric and neurodegenerative disorders, including major depressive disorder and Alzheimer's disease. In particular, polyunsaturated fatty acids (PUFAs) and their derivatives called oxylipins gained specific interest in this context, especially considering their capacity to orchestrate neuroinflammatory responses via direct modulation of microglia. The hippocampus and hypothalamus are crucial brain regions for regulating mood and cognition that are implicated in a variety of neuropsychiatric and neurodegenerative disorders and there is ample evidence for the sex-bias in risks for the development as well as sex-bias in the presentation of such psychiatric diseases, including the neuroinflammatory response. To better understand the local PUFA/oxylipin profiles and microglia responses in disease, we here assessed their brain region and sex-dependent profiles in homeostatic brains. In 2-month-old male and female mice, we measured non-esterified (free) PUFA/oxylipin profiles using liquid chromatography-tandem mass spectrometry and characterized microglia morphology via immunohistochemistry. The hypothalamus and hippocampus exhibit a different free PUFA/oxylipin profile, independent of sex. The hippocampus was characterized by a higher density of complex Iba1+ microglial cells than the hypothalamus, without sex effects. Hypothalamic microglial morphology correlated more strongly with free PUFA- and oxylipin species than hippocampal microglia, correlating with species from both the N-3 and N-6 PUFA metabolization pathways, while hippocampal microglial parameters correlated only with N-6 pathway-related species. Our findings provide a basis for future studies to investigate the relationship between PUFAs, their derivatives and neuroinflammation in the context of diseases.
{"title":"Brain region and sex-dependent heterogeneity of PUFA/oxylipin profile, microglia morphology and their relationship","authors":"J. Geertsema , M.A. Franßen , F. Barban , L. Šarauskytė , M. Giera , G. Kooij , A Korosi","doi":"10.1016/j.plefa.2024.102662","DOIUrl":"10.1016/j.plefa.2024.102662","url":null,"abstract":"<div><div>Lipid dyshomeostasis and neuroinflammation are key hallmarks of neuropsychiatric and neurodegenerative disorders, including major depressive disorder and Alzheimer's disease. In particular, polyunsaturated fatty acids (PUFAs) and their derivatives called oxylipins gained specific interest in this context, especially considering their capacity to orchestrate neuroinflammatory responses via direct modulation of microglia. The hippocampus and hypothalamus are crucial brain regions for regulating mood and cognition that are implicated in a variety of neuropsychiatric and neurodegenerative disorders and there is ample evidence for the sex-bias in risks for the development as well as sex-bias in the presentation of such psychiatric diseases, including the neuroinflammatory response. To better understand the local PUFA/oxylipin profiles and microglia responses in disease, we here assessed their brain region and sex-dependent profiles in homeostatic brains. In 2-month-old male and female mice, we measured non-esterified (free) PUFA/oxylipin profiles using liquid chromatography-tandem mass spectrometry and characterized microglia morphology via immunohistochemistry. The hypothalamus and hippocampus exhibit a different free PUFA/oxylipin profile, independent of sex. The hippocampus was characterized by a higher density of complex Iba1<sup>+</sup> microglial cells than the hypothalamus, without sex effects. Hypothalamic microglial morphology correlated more strongly with free PUFA- and oxylipin species than hippocampal microglia, correlating with species from both the N-3 and N-6 PUFA metabolization pathways, while hippocampal microglial parameters correlated only with N-6 pathway-related species. Our findings provide a basis for future studies to investigate the relationship between PUFAs, their derivatives and neuroinflammation in the context of diseases.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102662"},"PeriodicalIF":3.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-12DOI: 10.1016/j.plefa.2024.102663
Rebeka Joerg , Bianca K. Itariu , Melina Amor , Martin Bilban , Felix Langer , Gerhard Prager , Florian Joerg , Thomas M. Stulnig
Background and aims
Obesity is associated with a higher risk of severe diseases such as atherosclerotic cardiovascular disease, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). Polyunsaturated fatty acids, of the omega-3 family (n-3 PUFA), have been shown to reduce adipose tissue inflammation in obesity, as well as to have lipid-lowering effects and improve insulin sensitivity. However, direct effects on liver transcriptome in humans have not been described. Our aim was to understand the impact of n-3 PUFA on gene expression in obese human liver.
Approach and Results
Patients with obesity (BMI 40 kg/m2) were treated for eight weeks with 3.36 g n-3 PUFAs (1.84 g eicosapentaenoic acid (EPA) and 1.53 g docosahexaenoic acid (DHA)), or with 5 g of butter as a control (n = 15 per group) before undergoing bariatric surgery where liver biopsies were taken. Liver samples were used for mRNA microarray analyses and subsequently Gene Set Enrichment Analysis (GSEA) was performed. This bioinformatic approach led us to identify 80 significantly dysregulated pathways that were divided into 9 different clusters including insulin and lipid metabolism, and immunity. N-3 PUFA treatment significantly affected pathways related to immunity, metabolism, and inflammation. Specifically, it upregulated pathways involved in T-cell and B-cell functions and lipid metabolism, while downregulating glucagon signalling. These findings highlight the impact of n-3 PUFAs on key metabolic and immune processes in the liver of patients with obesity.
Conclusion
This study provides further insights into the impact on n-3 PUFA on human liver gene expression, particularly in pathways associated with immunity, lipid metabolism, and inflammation, setting basis for further clinical research.
Summary
Obesity increases the risk of diseases like atherosclerotic- cardiovascular disease, type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD). Omega-3 polyunsaturated fatty acids (n-3 PUFA) are known for their anti-inflammatory and metabolic benefits, but their direct impact on liver gene expression in people with obesity, remains unclear. In this study, patients with obesity (BMI ≥ 40 kg/m2) were administered either n-3 PUFAs or butter before bariatric surgery. Liver biopsies were analysed for gene expression via Gene Set Enrichment Analysis (GSEA). The results revealed 80 dysregulated pathways across 9 clusters, including those related to insulin and lipid metabolism, and immunity. This sheds light on how n-3 PUFAs influence gene expression in the liver of patients with obesity, setting the groundwork for further clinical exploration.
{"title":"The effect of long-chain n-3 PUFA on liver transcriptome in human obesity","authors":"Rebeka Joerg , Bianca K. Itariu , Melina Amor , Martin Bilban , Felix Langer , Gerhard Prager , Florian Joerg , Thomas M. Stulnig","doi":"10.1016/j.plefa.2024.102663","DOIUrl":"10.1016/j.plefa.2024.102663","url":null,"abstract":"<div><h3>Background and aims</h3><div>Obesity is associated with a higher risk of severe diseases such as atherosclerotic cardiovascular disease, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). Polyunsaturated fatty acids, of the omega-3 family (n-3 PUFA), have been shown to reduce adipose tissue inflammation in obesity, as well as to have lipid-lowering effects and improve insulin sensitivity. However, direct effects on liver transcriptome in humans have not been described. Our aim was to understand the impact of n-3 PUFA on gene expression in obese human liver.</div></div><div><h3>Approach and Results</h3><div>Patients with obesity (BMI <span><math><mo>≥</mo></math></span> 40 kg/m<sup>2</sup>) were treated for eight weeks with 3.36 g n-3 PUFAs (1.84 g eicosapentaenoic acid (EPA) and 1.53 g docosahexaenoic acid (DHA)), or with 5 g of butter as a control (<em>n</em> = 15 per group) before undergoing bariatric surgery where liver biopsies were taken. Liver samples were used for mRNA microarray analyses and subsequently Gene Set Enrichment Analysis (GSEA) was performed. This bioinformatic approach led us to identify 80 significantly dysregulated pathways that were divided into 9 different clusters including insulin and lipid metabolism, and immunity. N-3 PUFA treatment significantly affected pathways related to immunity, metabolism, and inflammation. Specifically, it upregulated pathways involved in T-cell and B-cell functions and lipid metabolism, while downregulating glucagon signalling. These findings highlight the impact of n-3 PUFAs on key metabolic and immune processes in the liver of patients with obesity.</div></div><div><h3>Conclusion</h3><div>This study provides further insights into the impact on n-3 PUFA on human liver gene expression, particularly in pathways associated with immunity, lipid metabolism, and inflammation, setting basis for further clinical research.</div></div><div><h3>Summary</h3><div>Obesity increases the risk of diseases like atherosclerotic- cardiovascular disease, type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD). Omega-3 polyunsaturated fatty acids (n-3 PUFA) are known for their anti-inflammatory and metabolic benefits, but their direct impact on liver gene expression in people with obesity, remains unclear. In this study, patients with obesity (BMI ≥ 40 kg/m2) were administered either n-3 PUFAs or butter before bariatric surgery. Liver biopsies were analysed for gene expression via Gene Set Enrichment Analysis (GSEA). The results revealed 80 dysregulated pathways across 9 clusters, including those related to insulin and lipid metabolism, and immunity. This sheds light on how n-3 PUFAs influence gene expression in the liver of patients with obesity, setting the groundwork for further clinical exploration.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102663"},"PeriodicalIF":3.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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