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 ; Fatty Acids, Unsaturated/metabolism* ; Reactive Oxygen Species/metabolism* ; Iron/metabolism* ; Animals ; Mitochondria/metabolism*

Pregnancy ; Female ; Humans ; Milk, Human ; Overweight/genetics* ; Fatty Acids, Unsaturated ; Fatty Acids ; Adiponectin/genetics*

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 (P_trend<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 ; Child ; Diabetes, Gestational ; Fatty Acids, Unsaturated ; Female ; Glucose Tolerance Test ; Humans ; Pregnancy ; Pregnancy Trimester, Second

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*

Adequate supply of long-chain polyunsaturated fatty acids (LCPUFAs) is of great importance for neonates, especially preterm infants. In particular,
Fatty Acids ; Fatty Acids, Omega-3 ; Fatty Acids, Unsaturated ; Humans ; Infant ; Infant, Newborn ; Infant, Premature

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 ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation/radiation effects* ; Combined Modality Therapy ; Cytokines/immunology* ; Fatty Acids, Unsaturated/therapeutic use* ; Female ; Mammary Neoplasms, Experimental/radiotherapy* ; Rats ; Tumor-Associated Macrophages/radiation effects*

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 ; Epoxide Hydrolases ; Ethanol ; Fatty Acids ; Fatty Acids, Unsaturated ; Inflammation ; Metabolism ; Passiflora ; Passifloraceae ; Phenol ; Vietnam

Free fatty acid (FFA) intake regulates blood pressure and vascular reactivity but its direct effect on contractility of systemic arteries is not well understood. We investigated the effects of saturated fatty acid (SFA, palmitic acid), polyunsaturated fatty acid (PUFA, linoleic acid), and monounsaturated fatty acid (MUFA, oleic acid) on the contractility of isolated mesenteric (MA) and deep femoral arteries (DFA) of Sprague–Dawley rats. Isolated MA and DFA were mounted on a dual wire myograph and phenylephrine (PhE, 1–10 µM) concentration-dependent contraction was obtained with or without FFAs. Incubation with 100 µM of palmitic acid significantly increased PhE-induced contraction in both arteries. In MA, treatment with 100 µM of linoleic acid decreased 1 µM PhE-induced contraction while increasing the response to higher PhE concentrations. In DFA, linoleic acid slightly decreased PhE-induced contraction while 200 µM oleic acid significantly decreased it. In MA, oleic acid reduced contraction at low PhE concentration (1 and 2 µM) while increasing it at 10 µM PhE. Perplexingly, depolarization by 40 mM KCl-induced contraction of MA was commonly enhanced by the three fatty acids. The 40 mM KCl-contraction of DFA was also augmented by linoleic and oleic acids while not affected by palmitic acid. SFA persistently increased alpha-adrenergic contraction of systemic arteries whereas PUFA and MUFA attenuated PhE-induced contraction of skeletal arteries. PUFA and MUFA concentration-dependent dual effects on MA suggest differential mechanisms depending on the types of arteries. Further studies are needed to elucidate underlying mechanisms of the various effects of FFA on systemic arteries.
Animals ; Arteries ; Blood Pressure ; Fatty Acids ; Fatty Acids, Unsaturated ; Femoral Artery ; Linoleic Acid ; Mesenteric Arteries ; Oleic Acid ; Oleic Acids ; Palmitic Acid ; Phenylephrine ; Rats ; Receptors, Adrenergic, alpha ; Vasoconstriction

PURPOSE: Glucocorticoids (GCs) are implicated in secondary osteoporosis, and the resulting fractures cause significant morbidity. Polyunsaturated fatty acids (PUFAs) play a vital role in bone metabolism. However, few trials have studied the impact of omega-3 PUFA-containing oils against GC-induced osteoporosis. Therefore, the present study was undertaken to determine whether supplementation with omega-3 PUFA-containing dietary oils such as fish oil, flaxseed oil or soybean oil can impede the development of GC-induced osteoporosis. METHODS: The fatty acids (FAs) content of oils was determined using gas chromatography. Male rats were subdivided into 5 groups (8 rats each): normal control (balanced diet), prednisolone control (10 mg/kg prednisolone daily), soybean oil (prednisolone 10 mg/kg + soybean oil 7% w/w), flaxseed oil (prednisolone 10 mg/kg + flaxseed oil 7% w/w), and fish oil (from cod liver; prednisolone 10 mg/kg + fish oil 7% w/w). RESULTS: The study data exhibited a significant depletion in bone mineral density (BMD) and femur mass in the prednisolone control compared to the normal control, accompanied with a marked decrease in the levels of plasma calcium and 1,25-(OH)₂-vitamin D₃, and elevated levels of C-terminal telopeptide (CTX), tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA). Supplementation with fish oil, soybean oil or flaxseed oil helped to improve plasma calcium levels, and suppress oxidative stress and inflammatory markers. Additionally, bone resorption was suppressed as reflected by the decreased CTX levels. However, fish oil was more effective than the other two oils with a significant improvement in BMD and normal histological results compared to the normal control. CONCLUSION: This study demonstrated that supplementation with dietary oils containing omega-3 PUFAs such as fish oil, soybean oil or flaxseed oil can play a role in the prevention of bone loss and in the regulation of bone metabolism, especially fish oil which demonstrated a greater level of protection against GC-induced osteoporosis.
Animals ; Bone Density ; Bone Resorption ; Calcium ; Chromatography, Gas ; Dietary Fats, Unsaturated ; Fatty Acids ; Fatty Acids, Omega-3 ; Fatty Acids, Unsaturated ; Femur ; Fish Oils ; Glucocorticoids ; Humans ; Inflammation ; Linseed Oil ; Liver ; Male ; Malondialdehyde ; Metabolism ; Oils ; Osteoporosis ; Oxidative Stress ; Plasma ; Prednisolone ; Rats ; Soybean Oil ; Tumor Necrosis Factor-alpha

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 ; Cross-Sectional Studies ; Dietary Fats ; Fatty Acids ; Fatty Acids, Unsaturated ; Humans ; Korea ; Male ; Methods ; Nutrition Policy ; Nutrition Surveys ; Public Health ; Recommended Dietary Allowances ; Weights and Measures ; Young Adult