linoleic-acid and Hypoxia

Recently, lactate has been considered as an alternative direct energy substance to glucose for tumor proliferation and metastasis. Meanwhile, mitochondria, as important energy-supplying organelles, are also closely related to tumor progression. Consequently, a new research direction for lactate comprises lactate deprivation coupled with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis. Herein, linoleic acid-conjugated hyaluronic acid (HL), disulfide bond-rich nanovehicle (mesoporous silica, MOS), mitochondria-targeted IR780 (M780) and lactate oxidase (LOD) are rationally designed as a specific-targeting metabolism nanomodulator (HL/MOS@M780&LOD NPs), fulfilling the task of simultaneous depriving cells of lactate and damaging mitochondria to prevent tumor metastasis. Interestingly, M780-mediated photodynamic therapy (PDT) and LOD-mediated starvation therapy can effectively exacerbate the hypoxia state of tumor cells, thereby increasing the free iron levels to activate ferroptosis. On one hand, pyruvic acid and H

Topics: Cell Line, Tumor; Humans; Hydrogen Peroxide; Hypoxia; Iron; Lactates; Linoleic Acid; Nanoparticles; Neoplasms; Photochemotherapy; Tumor Microenvironment

Hypoxia is a well-established feature of prostate cancer (PCa) and is associated with disease aggressiveness. The hypoxic microenvironment initiates multiple adaptive responses including epithelial-to-mesenchymal transition (EMT) and a remodeling of calcium homeostasis involved in cancer progression. In the present study, we identified a new hypoxia signaling pathway with a positive feedback loop between the EMT transcription factor Zeb1 and SK3, a Ca

Topics: Cell Line, Tumor; Cell Movement; Eicosapentaenoic Acid; Epithelial-Mesenchymal Transition; Glycolipids; Humans; Hypoxia; Linoleic Acid; Male; Prostatic Neoplasms; Small-Conductance Calcium-Activated Potassium Channels; Tumor Microenvironment; Zinc Finger E-box-Binding Homeobox 1

In the third part of this study a basic lipid model (regarding phospholipids, triglycerides, cholesterol esters and free fatty acids) for keloids (n=20), compared with normal skin of keloid prone and non-keloid prone patients (n=20 of each), was constructed according to standard methods, to serve as a sound foundation for essential fatty acid supplementation strategies in the prevention and treatment of keloid formations. Essential fatty acid deficiency (EFAD) of the omega-6 series (linoleic acid (LA), g-linolenic acid (GLA), and dihomo-g-linolenic acid (DGLA)) and the omega-3 series (a-linolenic acid (ALA) and eicosapentaenoic acid (EPA)), but enhanced arachidonic acid (AA) levels, were prevalent in keloid formations. Enhanced AA, but a deficiency of AA precursors (LA, GLA and DGLA) and inflammatory competitors (DGLA and EPA), are inevitably responsible for the overproduction of pro-inflammatory metabolites (prostaglandin E(2)(PGE(2))) participating in the pathogenesis of inflammation. Of particular interest was the extremely high free oleic acid (OA) levels present, apart from the high free AA levels, in the keloid formations. OA stimulates PKC activity which, in turn, activates PLA(2)activity for the release or further release of AA from membrane pools. Interactions between EFAs, eicosanoids, cytokines, growth factors and free radicals can modulate the immune response and the immune system in undoubtedly involved in keloid formation. The histopathology of keloids can be adequately explained by: persistence of inflammatory- and cytokine-mediated reactions in the keloid/dermal interface and peripheral areas, where fibroblast proliferation and continuous depletion of membrane linoleic acid occur; microvascular regeneration and circulation of sufficient EFAs in the interface and peripheral areas, where maintenance of metabolic active fibroblasts for collagen production occur; microvessel occlusion and hypoxia in the central areas, where deprivation of EFAs and oxygen with consequent fibroblast apoptosis occur, while excessive collagen remain. All these factors contribute to different fibroblast populations present in: the keloid / dermal interface and peripheral areas where increases in fibroblast proliferation and endogenous TGF-b occur, and these metabolic active fibroblast populations are responsible for enhanced collagen production: the central areas where fibroblast populations under hypoxic conditions occur, and these fibroblasts are responsible for

Topics: Apoptosis; Arachidonic Acid; Biopsy; Black People; Case-Control Studies; Cell Division; Cholesterol Esters; Chromatography, Gas; Chromatography, Thin Layer; Eicosapentaenoic Acid; Fatty Acids, Nonesterified; Fibroblasts; Groin; Humans; Hypoxia; Keloid; Linoleic Acid; Lipid Metabolism; Methylation; Models, Biological; Oleic Acid; Oxygen; Phospholipases A; Phospholipids; Protein Kinase C; Rural Population; South Africa; Transforming Growth Factor beta; Triglycerides

Free-radical activity was studied in patients on maintenance haemodialysis by measuring plasma octadeca-9, 11-dienoic acid (9,11-LA'), a diene-conjugated derivative of linoleic acid. Baseline values of 9,11-LA' (esterified as phospholipids and as free fatty acids) in 51 haemodialysis patients were similar to that of normal control subjects. However, during haemodialysis there was a highly significant (P less than 0.001) increase in 9,11-LA' in all 13 patients studied, which reached a peak 30 min after haemodialysis was started and then declined. The rise in plasma 9,11-LA' may be due to free radicals generated by activated neutrophils. Abnormal free-radical activity may be partly responsible for some haemodialysis-related complications, including pulmonary dysfunction in early haemodialysis.

Topics: Adult; Female; Free Radicals; Humans; Hypoxia; Kidney Failure, Chronic; Leukopenia; Linoleic Acid; Linoleic Acids; Male; Renal Dialysis

Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.

Topics: Adenosine Triphosphate; Animals; Chickens; Dose-Response Relationship, Drug; Electrocardiography; Electrolytes; Fatty Acids, Nonesterified; Hypoxia; Linoleic Acid; Linoleic Acids; Myocardial Contraction; Myocardium; Palmitic Acid; Palmitic Acids