1.The role of polyunsaturated fatty acid lipid peroxidation in ferroptosis after intracerebral hemorrhage: a review of mecha-nisms and therapeutic implications.
Man GUO ; Guohui ZHAO ; Zhibiao CAI ; Zhenyu ZHANG ; Jie ZHOU
Journal of Zhejiang University. Medical sciences 2025;54(5):694-704
Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology*
;
Humans
;
Cerebral Hemorrhage/pathology*
;
Lipid Peroxidation
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Fatty Acids, Unsaturated/metabolism*
;
Reactive Oxygen Species/metabolism*
;
Iron/metabolism*
;
Animals
;
Mitochondria/metabolism*
3.Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns.
Lei QU ; Xinyu HE ; Qian TANG ; Xiao FAN ; Jian LIU ; Aifu LIN
Journal of Zhejiang University. Science. B 2022;23(10):844-862
Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation. As an essential trace element, iron is vital for many biological processes. Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation. Ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs), is a promising therapeutic target for therapy-resistant cancers. Previous studies have reported that long noncoding RNA (lncRNA) is a group of critical regulators involved in modulating cell metabolism, proliferation, apoptosis, and ferroptosis. In this review, we summarize the associations among iron metabolism, ferroptosis, and ferroptosis-related lncRNA in tumorigenesis. This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
Fatty Acids, Unsaturated
;
Ferroptosis
;
Humans
;
Iron/therapeutic use*
;
Neoplasms/metabolism*
;
RNA, Long Noncoding/genetics*
;
Trace Elements/therapeutic use*
4.Associations between plasma n-3 polyunsaturated fatty acids and gestational diabetes mellitus in the second trimester.
Yan LIU ; Yi Xiang YE ; Yi WANG ; Fan WANG ; Yi Chao HUANG ; Da CHEN ; Xiong Fei PAN ; An PAN
Chinese Journal of Preventive Medicine 2022;56(3):312-321
Objective: To examine the associations between plasma n-3 polyunsaturated fatty acids (PUFAs) in the second trimester and gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods: Based on data from the Tongji-Shuangliu Birth Cohort enrolled from 2017 to 2019 in the Shuangliu Maternal and Child Health Hospital, it conducted a case-control study among 269 GDM cases who were diagnosed by 75 g oral glucose tolerance test, and 538 non-GDM controls matched at a 1∶2 ratio on maternal age and gestational weeks. The age range of the 807 women was 18-40 years. Fasting plasma n-3 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester (24-28 weeks). Participants were categorized into quartiles (Q1-Q4) of plasma n-3 PUFAs based on distributions in the control group. Conditional logistic regression models were applied to estimate the associations between plasma n-3 PUFAs and GDM. Results: The median (interquartile) relative concentrations of plasma n-3 PUFA C22∶5n-3 was significantly lower in women with GDM 0.87 (0.72, 1.07) compared with women without GDM 0.94 (0.75, 1.19)(P=0.001). Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM, with an OR (95%CI) of 0.75 (0.62-0.90) for each SD increase of relative concentration. Compared with the Q1 group, the OR values and 95%CIs of Q2, Q3, and Q4 groups were 0.97 (0.62-1.51), 0.72 (0.45-1.15), and 0.54 (0.32-0.90), respectively (Ptrend<0.05). However, there were no significant associations of C18∶3n-3, C20∶5n-3, C22∶6n-3, and total n-3 PUFAs with GDM. Conclusion: Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM during the second trimester.
Case-Control Studies
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Child
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Diabetes, Gestational
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Fatty Acids, Unsaturated
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Female
;
Glucose Tolerance Test
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Humans
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Pregnancy
;
Pregnancy Trimester, Second
5.Research advances in the effect of long-chain polyunsaturated fatty acids on neonates.
Chinese Journal of Contemporary Pediatrics 2021;23(7):755-760
Adequate supply of long-chain polyunsaturated fatty acids (LCPUFAs) is of great importance for neonates, especially preterm infants. In particular,
Fatty Acids
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Fatty Acids, Omega-3
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Fatty Acids, Unsaturated
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Humans
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Infant
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Infant, Newborn
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Infant, Premature
6.2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages.
Wen Hua DUAN ; Li Ya JIN ; Zu Chao CAI ; David LIM ; Zhi Hui FENG
Biomedical and Environmental Sciences 2021;34(9):693-704
Objective:
The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.
Methods:
Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.
Results:
The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.
Conclusion
The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors
Animals
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Antineoplastic Agents/therapeutic use*
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Cell Proliferation/radiation effects*
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Combined Modality Therapy
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Cytokines/immunology*
;
Fatty Acids, Unsaturated/therapeutic use*
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Female
;
Mammary Neoplasms, Experimental/radiotherapy*
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Rats
;
Tumor-Associated Macrophages/radiation effects*
7.Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy
Murat CAKIR ; Sukran SENYUVA ; Sibel KUL ; Elif SAG ; Ali CANSU ; Fulya Balaban YUCESAN ; Serap Ozer YAMAN ; Asim OREM
Pediatric Gastroenterology, Hepatology & Nutrition 2019;22(2):171-180
PURPOSE: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. METHODS: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. RESULTS: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p < 0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p < 0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p < 0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p < 0.05, r=0.381). CONCLUSION: Calcium supplementation may improve neurocognitive development in malnourished infants.
Brain
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Calcium
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Cell Count
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Cell Movement
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Child
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Cognition
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Fatty Acids, Unsaturated
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Humans
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Infant
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Magnesium
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Magnetic Resonance Spectroscopy
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Malnutrition
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Mass Screening
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Micronutrients
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Spectrum Analysis
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Synaptic Transmission
8.Effect of Eicosapentaenoic Acid Supplementation on Paraoxonase 2 Gene Expression in Patients with Type 2 Diabetes Mellitus: a Randomized Double-blind Clinical Trial.
Mohammad Hassan GOLZARI ; Mohammad Hassan JAVANBAKHT ; Ehsan GHAEDI ; Hamed MOHAMMADI ; Mahmoud DJALALI
Clinical Nutrition Research 2019;8(1):17-27
Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03258840
Aryldialkylphosphatase*
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Atherosclerosis
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Blood Glucose
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Cardiovascular Diseases
;
Cholesterol
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Diabetes Mellitus, Type 2*
;
Dyslipidemias
;
Eicosapentaenoic Acid*
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Fasting
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Fatty Acids, Unsaturated
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Gene Expression*
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Humans
;
Lipoproteins
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Metabolic Diseases
;
Oxidative Stress
;
Up-Regulation
9.Identification of Soluble Epoxide Hydrolase Inhibitors from the Seeds of Passiflora edulis Cultivated in Vietnam
To Dao CUONG ; Hoang THI NGOC ANH ; Tran Thu HUONG ; Pham Ngoc KHANH ; Vu Thi HA ; Tran Manh HUNG ; Young Ho KIM ; Nguyen Manh CUONG
Natural Product Sciences 2019;25(4):348-353
Soluble epoxide hydrolases (sEH) are enzymes present in all living organisms, metabolize epoxy fatty acids to 1,2-diols. sEH in the metabolism of polyunsaturated fatty acids plays a key role in inflammation. In addition, the endogenous lipid mediators in cardiovascular disease are also broken down to diols by the action of sEH that enhanced cardiovascular protection. In this study, sEH inhibitory guided fractionation led to the isolation of five phenolic compounds trans-resveratrol (1), trans-piceatannol (2), sulfuretin (3), (+)-balanophonin (4), and cassigarol E (5) from the ethanol extract of the seeds of Passiflora edulis Sims cultivated in Vietnam. The chemical structures of isolated compounds were determined by the interpretation of NMR spectral data, mass spectra, and comparison with data from the literature. The soluble epoxide hydrolase (sEH) inhibitory activity of isolated compounds was evaluated. Among them, trans-piceatannol (2) showed the most potent inhibitory activity on sEH with an IC₅₀ value of 3.4 µM. This study marks the first time that sulfuretin (3) was isolated from Passiflora edulis as well as (+)-balanophonin (4), and cassigarol E (5) were isolated from Passiflora genus.
Cardiovascular Diseases
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Epoxide Hydrolases
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Ethanol
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Fatty Acids
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Fatty Acids, Unsaturated
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Inflammation
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Metabolism
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Passiflora
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Passifloraceae
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Phenol
;
Vietnam
10.Evaluation of Total Fat and Fatty Acids Intakes in the Korean Adult Population using Data from the 2016–2017 Korea National Health and Nutrition Examination Surveys
Korean Journal of Community Nutrition 2019;24(3):223-231
OBJECTIVES: This study evaluated dietary intakes of total fat and fatty acids among the Korean adult population. METHODS: This cross-sectional study used the 2016–2017 Korea National Health and Nutrition Examination Survey data. A total of 10,772 subjects aged ≥19 y for which dietary data were available were selected. Data pertaining to energy and nutrient intakes were obtained by a 24-h recall method. Total fat and fatty acids intakes were evaluated based on the Acceptable Macronutrient Distribution Ranges (AMDR) of 2015 Dietary Reference Intakes for Koreans by sex and age groups. All statistical analyses accounted for the complex sampling design effect and sampling weights. RESULTS: The mean intakes of energy and total fat were 1,952 kcal (95% CI: 1928–1977) and 46.1 g (45.2–47.1), respectively, and about 21% of the energy was obtained from fat in this study population (21.7% in men and 20.2% in women). The mean percentages of energy from saturated, monounsaturated, and polyunsaturated fatty acids were 6.4%, 6.7%, and 5.2%, respectively. About 18% of adults exceeded the AMDR for fat (30% of energy), whereas 37.6% exceeded the AMDR for saturated fatty acids (7% of energy). The proportions of subjects who consumed more than the AMDR for fat and saturated fatty acids decreased across age groups in both sexes. Among young adults (19–29 y), about 63% of the subjects obtained ≥7% of their energy from saturated fatty acids. About 61% of older adults obtained less than 15% of their energy from total fat. CONCLUSIONS: Increased intake of fat energy was prominent in saturated fatty acids. Our findings suggest current information on total fat and fatty acids intakes in Korean adults and can be used to provide dietary guidelines for the improvement of public health.
Adult
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Cross-Sectional Studies
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Dietary Fats
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Fatty Acids
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Fatty Acids, Unsaturated
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Humans
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Korea
;
Male
;
Methods
;
Nutrition Policy
;
Nutrition Surveys
;
Public Health
;
Recommended Dietary Allowances
;
Weights and Measures
;
Young Adult

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