ABSTRACT
Ferroptosis represents a distinct form of programmed cell death triggered by excessive iron accumulation and lipid peroxidation-induced damage. This mode of cell death differentiates from classical programmed cell death in terms of morphology and biochemistry. Ferroptosis stands out for its exceptional biological characteristics and has garnered extensive research and conversations as a form of programmed cell death. Its dysfunctional activation is closely linked to the onset of diseases, particularly inflammation and cancer, making ferroptosis a promising avenue for combating these conditions. As such, exploring ferroptosis may offer innovative approaches to treating cancer and inflammatory diseases. Our review provides insights into the relevant regulatory mechanisms of ferroptosis, examining the impact of ferroptosis-related factors from both physiological and pathological perspectives. Describing the crosstalk between ferroptosis and tumor- and inflammation-associated signaling pathways and the potential of ferroptosis inducers in overcoming drug-resistant cancers are discussed, aiming to inform further novel therapeutic directions for ferroptosis in relation to inflammatory and cancer diseases.
ABSTRACT
PURPOSE: The mechanism underlying postprandial glucagon-like peptide-1 (GLP-1) changes after metabolic surgery remains mostly unclarified. This investigation aimed to address whether the vagus nerve-spleen anti-inflammatory axis is involved in the rise in postprandial GLP-1 levels in type 2 diabetes mellitus (T2DM) rats following metabolic surgery. MATERIALS AND METHODS: T2DM rat model was established with a high-fat diet and a low dose of streptozotocin and subjected to Roux-en-Y gastric bypass (RYGB) and splenic denervation. A mixed-meal tolerance test for postprandial GLP-1 response was performed. TNF-α in the plasma, spleen, and ileum was measured by ELISA, and alpha 7 nicotinic acetylcholine receptor (α7nAChR) expression in the spleen was analyzed by Western blot. RESULTS: Postprandial GLP-1 improvement by RYGB was accompanied by the reduction of TNF-α levels in spleen and ileum and up-regulation of splenic α7nAChR in T2DM rats. Splenic denervation abrogates a rise in postprandial GLP-1 levels in response to the mixed-meal challenge, along with higher TNF-α levels in spleen and ileum and down-regulation of splenicα7nAChR, compared with denervated sham rats. CONCLUSION: Our results reveal that the vagus nerve-spleen anti-inflammatory axis mediates the rise of postprandial GLP-1 response after RYGB through lowering TNF-α contents in the intestinal tissue in T2DM rats.
Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Gastric Bypass , Obesity, Morbid , Animals , Anti-Inflammatory Agents , Blood Glucose/metabolism , Diabetes Mellitus, Experimental/metabolism , Gastric Bypass/methods , Glucagon-Like Peptide 1 , Humans , Insulin , Obesity, Morbid/surgery , Rats , Spleen/chemistry , Spleen/metabolism , Spleen/surgery , Tumor Necrosis Factor-alpha/metabolism , Vagus Nerve/surgery , alpha7 Nicotinic Acetylcholine ReceptorABSTRACT
BACKGROUND: Type 2 diabetes mellitus patients complicated with infections experience severe vitamin D deficiency. High-dose vitamin D is applied to the treatment of corona virus disease 2019 (COVID-19) by some researchers, and good results have been achieved. However, the efficacy of vitamin D in the treatment of infections in COVID-19 patients with diabetes remains unclarified. This study aims to explore the effect of oral high-dose vitamin D in the treatment of diabetic patients with COVID-19. METHODS: Randomized controlled trials about the application of high-dose vitamin D in the treatment of diabetic patients with COVID-19 will be retrieved from such electronic databases as Embase, PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure database, Chinese Wanfang database and Chinese Biomedical Literature database. The retrieval time is from their inception to December 2020. According to the pre-designed inclusion/exclusion criteria, the data will be extracted independently by two researchers. The risk of bias of the included studies will be assessed by the Cochrane collaboration's tool. Meta-analysis will be conducted by using Revman 5.3 software. RESULTS: A high-quality and comprehensive evaluation of oral high-dose vitamin D for the treatment of diabetic patients with COVID-19 will be made. CONCLUSION: The article will provide more convincing evidence and evidence-based guidance for clinical practice. ETHICS AND DISSEMINATION: The private information of individuals will not be made public, and this systematic evaluation will also not infringe on the rights of participants. Ethical approval is not required. Research results may be published in a peer-reviewed journal or disseminated in relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020214284.
