Molecular mechanism of ferroptosis and its application in the treatment of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary tract, the incidence of which is continuously increasing and affects human health worldwide. Despite advances in existing treatments, treatment outcomes still need to be improved due to higher rates of postoperative recurrence, chemotherapy resistance, etc.; thus, there is an urgent need for innovative therapeutic approaches. Ferroptosis is a recently found type of regulated cell death that is characterized primarily by the buildup of lipid peroxidation products and fatal reactive oxygen species created by iron metabolism, which plays a crucial role in tumor progression and therapy.With the molecular mechanisms associated with ferroptosis being increasingly studied and refined, triggering ferroptosis by regulators that target ferroptosis and ccRCC may be the key to developing potential therapeutic strategies for ccRCC. Therefore, ferroptosis is expected to be a new breakthrough in treating ccRCC. This paper examines the mechanism of ferroptosis, the regulatory mechanism of ferroptosis in ccRCC, and the potential application of ferroptosis in combination with other therapies for the treatment of ccRCC. The goal is to offer novel perspectives for the research and clinical application of ferroptosis in the treatment of ccRCC.

Dietary L-carnitine supplementation changes lipid metabolism and glucose utilization of Rhynchocypris lagowskii fed diets with different lipid sources.

The widely available crop oil is an effective alternative to the increasingly scarce marine fish oil. However, simple alternative strategies have led to declining growth and the edible value of farmed fish. It is worthwhile to explore the effects of micro supplements in diets to improve the tolerance of fish to different dietary lipid sources, which finally optimizes the feeding strategies. This study aimed to investigate the regulation of L-carnitine and dietary oil conditions on nutrient composition, lipid metabolism, and glucose regulation of Rhynchocypris lagowskii. Four diets were prepared according to fish oil, fish oil supplemented with L-carnitine, corn oil, and corn oil supplemented with L-carnitine, and FO, LCFO, CO, and LCCO were labeled, respectively. R. lagowskii was fed experimental diets for 8 weeks, and the glucose tolerance test was performed. The CO diet significantly resulted in higher crude lipid content in muscle but a lower level of serum lipid parameters of R. lagowskii than the FO diet. However, dietary L-carnitine supplementation significantly reduced the crude lipid content in the hepatopancreas and muscle of the fish fed with the CO diet yet increased the serum lipid parameters. Additionally, the crude lipid content of muscle was reduced in the fish fed with an FO diet supplemented with L-carnitine. Compared with the FO diet, the CO diet significantly reduced the ratio of n3/n6 polyunsaturated fatty acid in the hepatopancreas and muscle of R.lagowskii. Dietary L-carnitine supplementation significantly reduced the contents of total saturated fatty acids and total monounsaturated fatty acids in hepatopancreas under both dietary lipid sources. The CO diet significantly up-regulated the expression of genes related to lipid uptake and adipogenesis in hepatopancreas, including lipoprotein lipase (lpl), acetyl-coenzyme A carboxylase alpha (accα), and sterol regulatory element binding protein-1 (srebp1), compared with the FO diet. While dietary L-carnitine supplementation significantly down-regulated the expressions of lpl, accα, srebp1, and fatty acid synthase in hepatopancreas and muscle of fish under both dietary lipid sources, along with up-regulated expression of carnitine palmitoyltransferase 1 in hepatopancreas. Moreover, the fish fed with a CO diet significantly increased the expression of glucose uptake and clearance and significantly down-regulated the expressions of glucose regulation-related genes, including glucose transporter 1, glycogen synthase 1, and phosphofructokinase in hepatopancreas and muscle, resulting in slower glucose uptake and clearance than fish fed with FO diet. Nevertheless, dietary L-carnitine supplementation up-regulated the expression of gluconeogenesis-related genes, including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the hepatopancreas of R. lagowskii under both dietary lipid sources. In conclusion, a higher dietary n6 PUFA resulted in lipid deposition, decreased serum lipid parameters, and limited serum glucose utilization of R. lagowskii. While the regulatory effect of L-carnitine on lipid metabolism and glucose utilization of R. lagowskii varies with dietary lipid sources and tissues.

Validation and application of the Chinese version of the Columbia-Suicide Severity Rating Scale: Suicidality and cognitive deficits in patients with major depressive disorder.

BACKGROUND: Depression is a significant risk factor for death by suicide. Additionally, patients with depression who have neurocognitive dysfunction are at a higher risk of exhibiting suicidal behaviors. We aimed to validate the Chinese version of the Columbia Suicide Severity Rating Scale (C-SSRS) and then employ it to examine the association between suicidality and cognitive deficits in patients with Major Depressive Disorder (MDD). METHODS: Data from 456 patients with MDD who underwent baseline assessment and 3-month follow-up were used for psychometric validation of the C-SSRS. 430 patients were divided into a mild cognitive impairment group (N = 390) and a severe cognitive impairment group (N = 40) using cluster analysis and compared with healthy controls. The relationship between C-SSRS scores and the degree of cognitive impairment was analyzed. RESULTS: 1) The Chinese version of C-SSRS demonstrated good internal consistency (Cronbach's alpha = 0.884/0.842), convergent and divergent validity. 2) The severity of suicidal ideation (SI), the intensity of SI, and the lifetime history of suicide attempts were significant independent predictors of short-term suicide attempts. 3) Higher worst-point lifetime SI severity and intensity scores in patients with MDD were significantly associated with severe cognitive impairment. LIMITATIONS: The analysis of cognition and suicide was based on cross-sectional studies. Hence, changes in SI and cognitive function over time could not be analyzed. CONCLUSIONS: The Chinese C-SSRS is a reliable and valid assessment tool for suicidal ideation and behavior in patients with depression. Suicidal ideation in patients with MDD is associated with cognitive dysfunction. These findings provide a reference for suicide prevention in patients with depression.