Metabolic memory: mechanisms and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 28, 2024

Metabolic diseases and their complications impose health economic burdens worldwide. Evidence from past experimental studies clinical trials suggests our body may have the ability to remember metabolic environment, such as hyperglycemia or hyperlipidemia, thus leading chronic inflammatory disorders other even after elimination of these environments. The long-term effects that aberrant metabolism on been summarized memory are found assume a crucial role in states disease. Multiple molecular mechanisms collectively participate management, resulting different cellular alterations well tissue organ dysfunctions, culminating disease progression affecting offspring. elucidation expansion concept provides more comprehensive insight into pathogenic underlying promises be new target detection management. Here, we retrace history relevant research summarize its salient characteristics. We provide detailed discussion by which involved development at molecular, cellular, levels, with emphasis impact epigenetic modulations. Finally, present some pivotal findings arguing favor targeting develop therapeutic strategies for latest reflections consequences implications human diseases.

Language: Английский

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Correlation between lipoprotein-associated phospholipase A2 and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: A cross-sectional study

Journal of Diabetes and its Complications, Journal Year: 2025, Volume and Issue: 39(2), P. 108950 - 108950

Published: Jan. 14, 2025

Language: Английский

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Cytokine Signaling in Diabetic Neuropathy: A Key Player in Peripheral Nerve Damage

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 589 - 589

Published: Feb. 28, 2025

Diabetic peripheral neuropathy (DPN) is a debilitating complication of diabetes mellitus, characterized by progressive nerve damage driven chronic hyperglycemia and systemic inflammation. The pathophysiology DPN significantly influenced pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α. These cytokines promote oxidative stress, vascular dysfunction, neuronal degeneration activating important signaling pathways including NF-κB MAPK. While IL-6 promotes microenvironment, increasing neuropathic pain, TNF-α IL-1β worsen Schwann cell failure compromising axonal support causing demyelination. Immune infiltration TLR activation increase the inflammatory cascade in DPN, resulting persistent neuroinflammatory state that sustains injury. main characteristics are degeneration, decreased neurotrophic support, which weaken transmission susceptibility to damage. Advanced glycation end-products, TNF-α, CXCL10 examples biomarkers may be used for early diagnosis disease progression monitoring. Additionally, crucial molecular targets have been found using proteomic transcriptome techniques, enabling precision medicine treatment DPN. This review emphasizes importance cytokine pathogenesis how cytokine-targeted treatments might reduce inflammation, restore function, improve clinical outcomes diabetic patients.

Language: Английский

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Exploring shared therapeutic targets in diabetic cardiomyopathy and diabetic foot ulcers through bioinformatics analysis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 2, 2024

Abstract Advanced diabetic cardiomyopathy (DCM) patients are often accompanied by severe peripheral artery disease. For with DCM combined foot ulcer (DFU), there currently no good therapeutic targets and drugs. Here, we investigated the underlying network of molecular actions associated occurrence these two complications. The datasets were downloaded from Gene Expression Omnibus (GEO) database. We performed enrichment protein–protein interaction analyses, screened for hub genes. Construct transcription factors (TFs) microRNAs regulatory networks validated Finally, drug prediction docking verification performed. identified 299 common differentially expressed genes (DEGs), many which involved in inflammation lipid metabolism. 6 DEGs as (PPARG, JUN, SLC2A1, CD4, SCARB1 SERPINE1). These immune response. 31 TFs 2 key miRNAs closely related to Interestingly, our study suggested that fenofibrate, a lipid-lowering medication, holds promise potential treatment DFU due its stable binding revealed involves target DFU. Understanding is pivotal advancing comprehension multifaceted complications diabetes facilitating development future interventions.

Language: Английский

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Research progress of traditional Chinese medicine monomer in treating diabetic peripheral neuropathy: A review

Medicine, Journal Year: 2024, Volume and Issue: 103(13), P. e37767 - e37767

Published: March 29, 2024

Diabetes peripheral neuropathy is one of the most common complications diabetes. Early symptoms are insidious, while late mainly include numbness, pain, swelling, and loss sensation in limbs, which can lead to disability, foot ulcers, amputation, so on. At present, pathogenesis also complex diverse, it not yet clear. Western medicine treatment focuses on controlling blood sugar nourishing nerves, but effect ideal. In recent years, has been found that many drug monomers have shown good therapeutic prognostic effects prevention diabetes neuropathy, related research become a hot topic. To understand specific mechanism action traditional Chinese treatment, this article provides review their key roles. It includes flavonoids, phenols, terpenes, saponins, alkaloids, polysaccharides, etc. By nuclear factor-κB (NF-κB), signaling pathways adenosine monophosphate-activated protein kinase (AMPK), Nrf2/ARE, SIRT1/p53, etc, play role lowering sugar, antioxidant, anti-inflammatory, inhibiting cell apoptosis, autophagy, promoting sciatic nerve regeneration, great potential disease. A systematic summary its mechanisms was conducted, providing ideas for in-depth exploration richer components, relatively complete theoretical reference clinical treatment.

Language: Английский

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Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy

Pharmaceutical Biology, Journal Year: 2024, Volume and Issue: 62(1), P. 544 - 561

Published: June 30, 2024

Context Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug management DPN, traditional Chinese medicine (TCM) has increasingly drawn attention clinicians researchers around world due to its characteristics multiple targets, active components, exemplary safety.

Language: Английский

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Structure-based screening, optimization and biological evaluation of novel chrysin-based derivatives as selective PPARγ modulators for the treatment of T2DM and hepatic steatosis

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116728 - 116728

Published: July 30, 2024

Language: Английский

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Eugenol improves high-fat diet/streptomycin-induced type 2 diabetes mellitus (T2DM) mice muscle dysfunction by alleviating inflammation and increasing muscle glucose uptake

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Nov. 8, 2022

Eugenol has been used in dietary interventions for metabolic diseases such as diabetes and obesity. However, the protective effect of eugenol on muscle function is unclear. In this study, a high-fat diet (HFD) with streptozocin (STZ) injection induced type II mellitus mouse model. Oral lowered blood glucose insulin resistance HFD/STZ-treated mice. reduced HFD/STZ-induced inflammation prevented weakness atrophy. administration significantly increased GLUT4 translocation AMPK phosphorylation skeletal muscle, thereby enhancing uptake. By silencing transient receptor potential vanilloid channel 1 (TRPV1) gene C2C12 myotube cells, was found to increase intracellular Ca2+ levels through TRPV1, which then activated calmodulin-dependent protein kinase-2 (CaMKK2) affected phosphorylation. conclusion, nutraceutical preventing high-glucose-induced impairments, could be explained by its mediating effects absorption inflammatory responses muscle.

Language: Английский

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Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Journal of Pharmaceutical Analysis, Journal Year: 2023, Volume and Issue: 14(2), P. 225 - 243

Published: Sept. 22, 2023

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays crucial role in DPN pathogenesis. However, the integrated profile metabolism, especially central carbohydrate remains unclear DPN. Here, we developed metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry to illustrate integrative characteristics metabolism patients with streptozotocin-induced rats. Furthermore, JinMaiTong (JMT), traditional Chinese medicine (TCM) formula, was found be DPN, improving neurological function alleviating neuropathology rats even after demyelination axonal degeneration. JMT ameliorated regulating aberrant balance mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, increased adenosine triphosphate (ATP) generation. Bioenergetic cultured rat Schwann cells under high-glucose conditions, remarkably corrected treatment. In vivo vitro studies revealed that these effects were mainly attributed activation AMP-activated protein kinase downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha. Our results expand therapeutic framework suggest modulation TCMs, such as JMT, an strategy its

Language: Английский

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Network Pharmacology Combined With Metabolomics Reveals the Mechanism of Yangxuerongjin Pill Against Type 2 Diabetic Peripheral Neuropathy in Rats

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 325 - 347

Published: Jan. 1, 2025

This study aims to explore the mechanism of Yangxuerongjin pill (YXRJP) in treatment diabetic peripheral neuropathy (DPN) by network pharmacology and metabolomics technology combined with animal experiments, provide scientific basis for DPN. In this study, analysis was applied identify active compounds, core targets signal pathways, which might be responsible effect The DPN model established high-fat diet streptozotocin (STZ) injection, rats were given administration 12 weeks. body weight, thermal withdrawal latency (TWL), sciatic motor nerve conduction velocity (MNCV), biochemical indexes, pathological sections nerve, oxidative stress factors expression levels neuroprotection-related proteins detected. Metabolomics used analyze potential biomarkers metabolic pathways treated YXRJP. results showed that YXRJP could treat through baicalin, β-sitosterol, 7-methoxy-2-methylisoflavone, aloe-emodin luteolin on insulin resistance, Toll-like receptor (TLR), tumor necrosis factor (TNF) other signaling pathways. can prolong TWL, increase MNCV alleviate injury reduce triglyceride (TG), improve Insulin-like growth 1 (IGF-1) protein kinase B (AKT) protein. mainly involved amino acid metabolism such as arginine, alanine, aspartic acid, lipid nucleotide metabolism. effectively symptoms damage. effects are related reducing injury, promoting proteins, inflammation-related affecting metabolism, Our findings revealed has a good therapeutic DPN, provides reference further studies

Language: Английский

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