Lipid availability influences ferroptosis sensitivity in cancer cells by regulating polyunsaturated fatty acid trafficking.

Ferroptosis is a form of cell death caused by lipid peroxidation that is emerging as a target for cancer therapy, highlighting the need to identify factors that govern ferroptosis susceptibility. Lipid peroxidation occurs primarily on phospholipids containing polyunsaturated fatty acids (PUFAs). Here, we show that even though extracellular lipid limitation reduces cellular PUFA levels, lipid-starved cancer cells are paradoxically more sensitive to ferroptosis. Using mass spectrometry-based lipidomics with stable isotope fatty acid labeling, we show that lipid limitation induces a fatty acid trafficking pathway in which PUFAs are liberated from triglycerides to synthesize highly unsaturated PUFAs such as arachidonic acid and adrenic acid. These PUFAs then accumulate in phospholipids, particularly ether phospholipids, to promote ferroptosis sensitivity. Therefore, PUFA levels within cancer cells do not necessarily correlate with ferroptosis susceptibility. Rather, how cancer cells respond to extracellular lipid levels by trafficking PUFAs into proper phospholipid pools dictates their sensitivity to ferroptosis.

Therapeutic Strategies to Ameliorate Neuronal Damage in Epilepsy by Regulating Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation.

Epilepsy is a central nervous system disorder involving spontaneous and recurring seizures that affects 50 million individuals globally. Because approximately one-third of patients with epilepsy do not respond to drug therapy, the development of new therapeutic strategies against epilepsy could be beneficial. Oxidative stress and mitochondrial dysfunction are frequently observed in epilepsy. Additionally, neuroinflammation is increasingly understood to contribute to the pathogenesis of epilepsy. Mitochondrial dysfunction is also recognized for its contributions to neuronal excitability and apoptosis, which can lead to neuronal loss in epilepsy. This review focuses on the roles of oxidative damage, mitochondrial dysfunction, NAPDH oxidase, the blood-brain barrier, excitotoxicity, and neuroinflammation in the development of epilepsy. We also review the therapies used to treat epilepsy and prevent seizures, including anti-seizure medications, anti-epileptic drugs, anti-inflammatory therapies, and antioxidant therapies. In addition, we review the use of neuromodulation and surgery in the treatment of epilepsy. Finally, we present the role of dietary and nutritional strategies in the management of epilepsy, including the ketogenic diet and the intake of vitamins, polyphenols, and flavonoids. By reviewing available interventions and research on the pathophysiology of epilepsy, this review points to areas of further development for therapies that can manage epilepsy.

Therapeutic Interventions to Mitigate Mitochondrial Dysfunction and Oxidative Stress-Induced Damage in Patients with Bipolar Disorder.

Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive-behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.

Most Effective Combination of Nutraceuticals for Improved Memory and Cognitive Performance in the House Cricket, Acheta domesticus.

BACKGROUND: Dietary intake of multivitamins, zinc, polyphenols, omega fatty acids, and probiotics have all shown benefits in learning, spatial memory, and cognitive function. It is important to determine the most effective combination of antioxidants and/or probiotics because regular ingestion of all nutraceuticals may not be practical. This study examined various combinations of nutrients to determine which may best enhance spatial memory and cognitive performance in the house cricket (Acheta domesticus (L.)). METHODS: Based on the 31 possible combinations of multivitamins, zinc, polyphenols, omega-3 polyunsaturated fatty acids (PUFAs), and probiotics, 128 house crickets were divided into one control group and 31 experimental groups with four house crickets in each group. Over eight weeks, crickets were fed their respective nutrients, and an Alternation Test and Recognition Memory Test were conducted every week using a Y-maze to test spatial working memory. RESULTS: The highest-scoring diets shared by both tests were the combination of multivitamins, zinc, and omega-3 fatty acids (VitZncPuf; Alternation: slope = 0.07226, Recognition Memory: slope = 0.07001), the combination of probiotics, polyphenols, multivitamins, zinc, and omega-3 PUFAs (ProPolVitZncPuf; Alternation: slope = 0.07182, Recognition Memory: slope = 0.07001), the combination of probiotics, multivitamins, zinc, and omega-3 PUFAs (ProVitZncPuf; Alternation: slope = 0.06999, Recognition Memory: slope = 0.07001), and the combination of polyphenols, multivitamins, zinc, and omega-3 PUFAs (PolVitZncPuf; Alternation: slope = 0.06873, Recognition Memory: slope = 0.06956). CONCLUSION: All of the nutrient combinations demonstrated a benefit over the control diet, but the most significant improvement compared to the control was found in the VitZncPuf, ProVitZncPuf, PolVitZncPuf, and ProPolVitZncPuf. Since this study found no significant difference between the performance and improvement of subjects within these four groups, the combination of multivitamins, zinc, and omega-3 fatty acids (VitZncPuf) was concluded to be the most effective option for improving memory and cognitive performance.

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia.

The biochemical integrity of the brain is paramount to the function of the central nervous system, and oxidative stress is a key contributor to cerebral biochemical impairment. Oxidative stress, which occurs when an imbalance arises between the production of reactive oxygen species (ROS) and the efficacy of the antioxidant defense mechanism, is believed to play a role in the pathophysiology of various brain disorders. One such disorder, schizophrenia, not only causes lifelong disability but also induces severe emotional distress; however, because of its onset in early adolescence or adulthood and its progressive development, consuming natural antioxidant products may help regulate the pathogenesis of schizophrenia. Therefore, elucidating the functions of ROS and dietary antioxidants in the pathogenesis of schizophrenia could help formulate improved therapeutic strategies for its prevention and treatment. This review focuses specifically on the roles of ROS and oxidative damage in the pathophysiology of schizophrenia, as well as the effects of nutrition, antipsychotic use, cognitive therapies, and quality of life on patients with schizophrenia. By improving our understanding of the effects of various nutrients on schizophrenia, it may become possible to develop nutritional strategies and supplements to treat the disorder, alleviate its symptoms, and facilitate long-term recovery.