OBJECTIVE: To explore the mechanism by which ω-3 polyunsaturated fatty acids (hereinafter referred to as "ω-3") exert antioxidant stress protection and promote osteogenic differentiation in MC3T3-E1 cells, and to reveal the relationship between ω-3 and the key antioxidant stress pathway involving nuclear factor E2-related factor 2 (Nrf2) and NAD (P) H quinone oxidoreductase 1 (NQO1) in MC3T3-E1 cells. METHODS: The optimal concentration of H ₂O ₂ (used to establish the oxidative stress model of MC3T3-E1 cells in vitro) and the optimal intervention concentrations of ω-3 were screened by cell counting kit 8. MC3T3-E1 cells were divided into blank control group, oxidative stress group (H ₂O ₂), low-dose ω-3 group (H ₂O ₂+low-dose ω-3), and high-dose ω-3 group (H ₂O ₂+high-dose ω-3). After osteoblastic differentiation for 7 or 14 days, the intracellular reactive oxygen species (ROS) level was measured by fluorescence staining and flow cytometry, and the mitochondrial morphological changes were observed by biological transmission electron microscope; the expression levels of Nrf2, NQO1, heme oxygenase 1 (HO-1), Mitofusin 1 (Mfn1), and Mfn2 were detected by Western blot to evaluate the cells' antioxidant stress capacity; the expression levels of Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were detected by immunofluorescence staining and Western blot; osteogenic potential of MC3T3-E1 cells was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining. RESULTS: Compared with the oxidative stress group, the content of ROS in the low and high dose ω-3 groups significantly decreased, and the protein expressions of Nrf2, NQO1, and HO-1 significantly increased ( P<0.05). At the same time, the mitochondrial morphology of MC3T3-E1 cells improved, and the expressions of mitochondrial morphology-related proteins Mfn1 and Mfn2 significantly increased ( P<0.05). ALP staining and alizarin red staining showed that the low-dose and high-dose ω-3 groups showed stronger osteogenic ability, and the expressions of osteogenesis-related proteins RUNX2 and OCN significantly increased ( P<0.05). And the above results showed a dose-dependence in the two ω-3 treatment groups ( P<0.05). CONCLUSION ω-3 can enhance the antioxidant capacity of MC3T3-E1 cells under oxidative stress conditions and upregulate their osteogenic activity, possibly through the Nrf2/NQO1 signaling pathway.
Oxidative Stress/drug effects* ; NF-E2-Related Factor 2/metabolism* ; NAD(P)H Dehydrogenase (Quinone)/metabolism* ; Animals ; Mice ; Osteogenesis/drug effects* ; Cell Differentiation/drug effects* ; Fatty Acids, Omega-3/pharmacology* ; Signal Transduction/drug effects* ; Osteoblasts/drug effects* ; Reactive Oxygen Species/metabolism* ; Cell Line ; Hydrogen Peroxide/pharmacology* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Antioxidants/pharmacology* ; Heme Oxygenase-1/metabolism*

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease that threatens the vision of premature infants. Various novel drugs have demonstrated therapeutic potential for ROP by targeting signaling pathways associated with vascular endothelial growth factor (VEGF) [such as PI3K/AKT, hypoxia-inducible factor (HIF)-1α/VEGF], oxidative stress, tumor necrosis factor (TNF)-α, and Notch pathways. Propranolol, insulin-like growth factor-1, and celecoxib attenuate pathological neovascularization via the PI3K/Akt signaling pathway. Tripterine and melatonin inhibit retinal neovascularization by modulating the HIF-1α/VEGF signaling axis. Adiponectin mitigates the damage caused by oxidative stress and preserves endothelial function by enhancing endothelial nitric oxide synthase activity. Omega-3 polyunsaturated fatty acids suppress TNF-α-mediated inflammatory responses, modulate retinal development and angiogenesis, and reduce retinal neovascular lesions. DAPT, a γ-secretase inhibitor, blocks Notch signaling to suppress abnormal vascular proliferation. These agents exhibit synergistic multi-pathway anti-angiogenic effects in preclinical models and early-phase clinical trials, offering critical insights for advancing drug development and clinical translation in ROP management.
Retinopathy of Prematurity/metabolism* ; Humans ; Signal Transduction/drug effects* ; Infant, Newborn ; Vascular Endothelial Growth Factor A/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Oxidative Stress/drug effects* ; Fatty Acids, Omega-3/therapeutic use* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Receptors, Notch/metabolism* ; Angiogenesis Inhibitors/therapeutic use* ; Insulin-Like Growth Factor I/therapeutic use*

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

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.
Apolipoprotein C-III ; Cardiovascular Diseases ; Diacylglycerol O-Acyltransferase ; Fatty Acids, Omega-3 ; Fibric Acids ; Hyperlipoproteinemia Type I ; Life Style ; Lipase ; Lipoprotein Lipase ; Lipoproteins ; Metabolism ; Mortality ; PPAR alpha ; Risk Factors ; Triglycerides

OBJECTIVETo investigate the effects of polyunsaturated fatty acids (PUFA) &omega;-3 and &omega;-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.

METHODSThe effects of &omega;-3, &omega;-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of &omega;-3, &omega;-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without &omega;-3, &omega;-6, PGE2 and PGE3 were designed as the control.

RESULTSWith the increased concentration of &omega;-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of &omega;-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by &omega;-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of &omega;-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by &omega;-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, &omega;-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, &omega;-6 could increase angiogenesis of gastric cancer cells(P<0.01), but &omega;-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, &omega;-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but &omega;-6 had no effect on angiogenesis.

CONCLUSIONSThe PUFA &omega;-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the &omega;-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.

Alprostadil ; analogs & derivatives ; pharmacology ; Angiogenesis Inducing Agents ; metabolism ; pharmacology ; Angiogenesis Inhibitors ; pharmacology ; Cell Count ; methods ; Cell Line, Tumor ; drug effects ; physiology ; Cell Migration Assays ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Coculture Techniques ; Cyclooxygenase 2 ; pharmacology ; Dinoprostone ; metabolism ; pharmacology ; Fatty Acids, Omega-3 ; pharmacology ; Fatty Acids, Omega-6 ; metabolism ; pharmacology ; Fatty Acids, Unsaturated ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; physiology ; Humans ; Lactones ; pharmacology ; Neovascularization, Pathologic ; physiopathology ; Stomach Neoplasms ; physiopathology ; Sulfones ; pharmacology

INTRODUCTIONThis study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus.

METHODSA total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured.

RESULTSArylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors.

CONCLUSIONVitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

Animals ; Aryldialkylphosphatase ; metabolism ; Ascorbic Acid ; pharmacology ; Carboxylic Ester Hydrolases ; metabolism ; Diabetes Mellitus, Experimental ; diet therapy ; metabolism ; Dietary Supplements ; Fatty Acids, Omega-3 ; pharmacology ; Liver ; enzymology ; Male ; Myocardium ; enzymology ; Rats ; Rats, Sprague-Dawley ; Vitamin A ; pharmacology ; Vitamins ; pharmacology

The aim of this study was to investigate whether the omega-3 fatty acids help to improve erectile function in an atherosclerosis-induced erectile dysfunction rat model. A total of 20 male Sprague-Dawley rats at age 8 weeks were divided into three groups: Control group (n = 6, untreated sham operated rats), Pathologic group (n = 7, untreated rats with chronic pelvic ischemia [CPI]), and Treatment group (n = 7, CPI rats treated with omega-3 fatty acids). For the in vivo study, electrical stimulation of the cavernosal nerve was performed and erectile function was measured in all groups. Immunohistochemical antibody staining was performed for transforming growth factor beta-1 (TGF-β1), endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor 1-alpha (HIF-1α). In vivo measurement of erectile function in the Pathologic group showed significantly lower values than those in the Control group, whereas the Treatment group showed significantly improved values in comparison with those in the Pathologic group. The results of western blot analysis revealed that systemically administered omega-3 fatty acids ameliorated the cavernosal molecular environment. Our study suggests that omega-3 fatty acids improve intracavernosal pressure and have a beneficial role against pathophysiological consequences such as fibrosis or hypoxic damage on a CPI rat model, which represents a structural erectile dysfunction model.
Animals ; Atherosclerosis/*complications ; Blotting, Western ; Carotid Arteries/physiology ; Chronic Disease ; Disease Models, Animal ; Electric Stimulation ; Fatty Acids, Omega-3/*pharmacology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Ischemia/etiology/*pathology ; Male ; Nitric Oxide Synthase Type III/metabolism ; Penile Erection/*drug effects ; Penis/metabolism/pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism

C-Reactive Protein ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; Dietary Supplements ; Fatty Acids, Omega-3 ; therapeutic use ; Female ; Humans ; Inflammation ; prevention & control ; Interleukin-2 ; blood ; Male ; Tumor Necrosis Factor-alpha ; blood

INTRODUCTIONConsumption of omega-3 fatty acids can alter the inflammatory response in diabetic patients. This study aimed to determine the effects of omega-3 fatty acid supplementation on the serum levels of C-reactive protein (CRP), interleukin (IL)-2 and tumour necrosis factor-alpha (TNF-α) in type 2 diabetes mellitus patients.

METHODSA randomised, double-blind, placebo-controlled clinical trial was conducted on 84 subjects aged 45-85 years with at least a two-year history of type 2 diabetes mellitus. Participants were randomly assigned to the treatment or control group. Each subject in the treatment group received three omega-3 capsules per day (eicosapentaenoic acid 1,548 mg; docosahexaenoic acid 828 mg; other omega-3 fatty acids 338 mg), while each subject in the control group received three placebo capsules (sunflower oil 2,100 mg) for a period of eight weeks. At the beginning of the study and post intervention, fasting blood samples were taken and serum concentrations of IL-2, TNF-α and CRP were assessed and compared.

RESULTSSerum IL-2 and TNF-α levels were significantly reduced in the treatment group compared to the controls (p < 0.01). There was no significant change in serum CRP levels.

CONCLUSIONShort-term omega-3 fatty acid supplementation (3 g/day for eight weeks) can decrease the serum levels of TNF-α and IL-2 in diabetic patients, with no change in CRP levels. Consumption of omega-3 fatty acid supplements is highly recommended to alleviate inflammation caused by type 2 diabetes mellitus.

Aged ; Aged, 80 and over ; Biomarkers ; blood ; C-Reactive Protein ; drug effects ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; immunology ; Dietary Supplements ; Double-Blind Method ; Fatty Acids, Omega-3 ; pharmacology ; therapeutic use ; Female ; Humans ; Inflammation ; blood ; prevention & control ; Interleukin-2 ; blood ; Male ; Middle Aged ; Tumor Necrosis Factor-alpha ; blood ; drug effects

OBJECTIVETo investigate the sheltering effects of &omega;-3 polyunsaturated fatty acid (&omega;-3PUFA) and lymphatic drainage on distant organs in intestinal ischemia-reperfusion injury in rats.

METHODSForty-eight healthy Sprague-Dawley (SD) male rats (SPF grade) were randomly divided into 3 groups (16 rats in each group): normal diet group (N), enteral nutrition group (EN), enteral nutrition and &omega;-3PUFA group(PUFA group). Each group was divided into lymphatic drainage (I/R + D) group and no-drainage (I/R) group (n = 8). Each rats received gastrostomy. After given different nutrition for five days, the rats subjected to 60 min ischemia and 120 min reperfusion injury of the superior mesenteric artery. When the rats subjected to ischemia-reperfusion injury, drained intestinal lymph for 180 min in the I/R + D group. The serum level of alanine aminotransferase (ALT) and level of myeloperoxidase (MPO), nitric oxide (NO), total of nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS) of lung were detected. The organ injury of lung and liver and the expression of high mobility group box 1(HMGB1, the endogenous ligand of TLR4) in these organs were investigated too.

RESULTSThe serum level of ALT in PUFA I/R + D and I/R group and EN I/R + D group were significantly lower than that in normal diet I/R group: (46 ± 20), (53 ± 15), (46 ± 21) and (100 ± 60) U/L (P < 0.05), respectively. The level of MPO, NO, tNOS, iNOS in lung in the I/R + D group were significantly lower than those in I/R group (P < 0.05): MPO (0.73 ± 0.15):(0.85 ± 0.10) unit/grams wet slice; NO (0.72 ± 0.51):(1.79 ± 1.32) µmol/gprot; tNOS (0.46 ± 0.15):(0.78 ± 0.27) U/mgprot; iNOS (0.06 ± 0.04):(0.11 ± 0.07) U/mgprot, respectively. The level of tNOS in PUFA I/R group was significantly lower than that in normal diet I/R group: (0.56 ± 0.13):(0.78 ± 0.27) U/mgprot (P < 0.05). MPO, NO, INOS levels in PUFA group were reduced compared with those in EN and normal diet group. HE stained sections and HMGB1 immunohistochemistry results showed that the organ injury in I/R group was severer than that in I/R + D group. The expression of HMGB1 increased in I/R group. The organ injury and the expression of HMGB1 in PUFA group were less than that in the other two main groups.

CONCLUSIONSLymphatic drainage can alleviate injury of distant organs after intestinal ischemia-reperfusion in rats. &omega;-3 polyunsaturated fatty acids can increase body resistance to injury and promote recovery.

Animals ; Disease Models, Animal ; Drainage ; Fatty Acids, Omega-3 ; pharmacology ; Intestines ; blood supply ; Liver ; metabolism ; pathology ; Lung ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; prevention & control