The role of AMPK in macrophage metabolism, function and polarisation

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Дек. 8, 2023

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays key role regulating cellular homeostasis multiple aspects cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming macrophages, but also counter-regulates inflammatory function macrophages promotes their polarisation toward anti-inflammatory phenotype. located at intersection metabolism inflammation. The characteristics are closely related to immune-related diseases, infectious cancer progression immunotherapy. This review discusses structure its metabolism, macrophages. In addition, it summarises important pathway activators development macrophage-related diseases.

Язык: Английский

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Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease

Antioxidants, Год журнала: 2024, Номер 13(4), С. 455 - 455

Опубликована: Апрель 12, 2024

Diabetic kidney disease (DKD) is the principal culprit behind chronic (CKD), ultimately developing end-stage renal (ESRD) and necessitating costly dialysis or transplantation. The limited therapeutic efficiency among individuals with DKD a result of our finite understanding its pathogenesis. complex interactions between various factors. Oxidative stress fundamental factor that can establish link hyperglycemia vascular complications frequently encountered in diabetes, particularly DKD. It crucial to recognize essential integral role oxidative development diabetic complications, Hyperglycemia primary trigger an upsurge production reactive oxygen species (ROS), sparking stress. main endogenous sources ROS include mitochondrial production, NADPH oxidases (Nox), uncoupled endothelial nitric oxide synthase (eNOS), xanthine oxidase (XO), cytochrome P450 (CYP450), lipoxygenase. Under persistent high glucose levels, immune cells, complement system, advanced glycation end products (AGEs), protein kinase C (PKC), polyol pathway, hexosamine pathway are activated. Consequently, oxidant–antioxidant balance within body disrupted, which triggers series reactions downstream pathways, including phosphoinositide 3-kinase/protein B (PI3K/Akt), transforming growth beta/p38-mitogen-activated (TGF-β/p38-MAPK), nuclear kappa (NF-κB), adenosine monophosphate-activated (AMPK), Janus kinase/signal transducer activator transcription (JAK/STAT) signaling. might persist even if strict control achieved, be attributed epigenetic modifications. treatment remains unresolved issue. Therefore, reducing intriguing target. clinical trials have shown bardoxolone methyl, erythroid 2-related 2 (Nrf2) activator, blood glucose-lowering drugs, such as sodium-glucose cotransporter inhibitors, glucagon-like peptide-1 receptor agonists effectively slow down progression by Other antioxidants, vitamins, lipoic acid, Nox regulators, present promising option for In this review, we conduct thorough assessment both preclinical studies current findings from focus on targeted interventions aimed at manipulating these pathways. We aim provide comprehensive overview state research area identify key areas future exploration.

Язык: Английский

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Research progress on the mechanism of angiogenesis in wound repair and regeneration

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 27, 2023

Poor wound healing and pathological have been pressing issues in recent years, as they impact human quality of life pose risks long-term complications. The study neovascularization has emerged a prominent research focus to address these problems. During the process repair regeneration, establishment new vascular system is an indispensable stage for complete healing. It provides favorable conditions nutrient delivery, oxygen supply, creates inflammatory environment. Moreover, it key manifestation proliferative phase healing, bridging remodeling phases. These three stages are closely interconnected inseparable. This paper comprehensively integrates regulatory mechanisms blood vessel formation focusing on proliferation migration endothelial cells release angiogenesis-related factors under different outcomes. Additionally, hidden link between environment angiogenesis explored.

Язык: Английский

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The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Июль 3, 2024

Diabetic cardiomyopathy (DCM) is a myocardial-specific microvascular disease caused by diabetes that affects the structure and function of heart considered to be leading cause morbidity death in patients with diabetes. Currently, there no specific treatment or preventive drug for DCM, an urgent need develop new drugs treat DCM. Traditional Chinese medicine (TCM) has rich experience its characteristics multi-target, multi-pathway, multi-component, few side effects can effectively deal complexity long-term nature Growing evidence suggests myocardial fibrosis, inflammation, oxidative stress, apoptosis, cardiac hypertrophy, advanced glycation end product deposition were main pathologic mechanisms According pathological mechanism this study revealed potential metabolites prescriptions TCM against DCM from perspective signaling pathways. The results showed TGF-β/Smad, NF-κB, PI3K/AKT, Nrf2, AMPK, NLRP3, Wnt/β-catenin pathways key aim was summarize update screen targets candidates provide ideas more experimental clinical use

Язык: Английский

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Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications

APOPTOSIS, Год журнала: 2025, Номер unknown

Опубликована: Янв. 4, 2025

Язык: Английский

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FTO inhibition mitigates high-fat diet-induced metabolic disturbances and cognitive decline in SAMP8 mice

Molecular Medicine, Год журнала: 2025, Номер 31(1)

Опубликована: Фев. 21, 2025

Abstract This study investigated the effects of fat mass and obesity-associated (FTO) inhibition on cognitive function metabolic parameters senescence-accelerated mouse prone 8 (SAMP8) mice fed a high-fat diet (HFD). SAMP8 an HFD exhibited increased body weight, impaired glucose tolerance, elevated serum leptin levels. In epididymal white adipose tissue (eWAT), pharmacological treatment with FB23, well-established FTO inhibitor, production modulated genes involved in lipid metabolism (Cpt1a, Atgl , Hsl Fas) oxidative stress (OS) ( Bip Edem ), inflammation (Mcp1, Tnfα) . Expression hepatic related to Mgl, Dgat2, Srebp Plin2) OS (catalase, Edem) were by although steatosis remained unchanged. Remarkably, FB23 m6A RNA methylation brain, accompanied changes N6-methyladenosine (m6A)-regulatory enzymes modulation neuroinflammatory markers (Il6, Mcp1, iNOS) reduced activity matrix metalloproteases (Mmp2, Mmp9) altered IGF1 signaling (Igf1, Pten) Notably, enhanced was observed through expression immediate early (Arc, Fos) transcription factor Stat3 Improved synaptic plasticity evident, as shown levels neurotrophic factors (Bdnf Ngf) restored neurite length spine density. Consistent these findings, behavioral tests demonstrated that effectively rescued impairments mice. The novel object recognition test (NORT) location (OLT) revealed treated short- long-term memory spatial compared control group. Additionally, open field showed reduction anxiety-like behavior after FB23. conclusion, ameliorated HFD-induced disturbances decline These results suggest targeting may be promising therapeutic approach counteract obesity-induced impairment age-related neurodegeneration.

Язык: Английский

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Bioactive compounds from Polygonatum genus as anti-diabetic agents with future perspectives

Food Chemistry, Год журнала: 2022, Номер 408, С. 135183 - 135183

Опубликована: Дек. 12, 2022

Diabetes mellitus (DM) is one of the most serious health problems worldwide. Species in genus Polygonatum are traditional food and medicinal plants, which play an important role controlling blood glucose. In this reveiw, we systematically summarized modern applications DM, focused on material bases polysaccharides, flavonoids saponins. We highlighted their mechanisms action preventing obese diabetes, improving insulin resistance, promoting secretion, regulating intestinal microecology, inhibiting advanced glycation end products (AGEs) accumulation, suppressing carbohydrate digestion obsorption modulating gluconeogenesis. Based safety efficacy 'medicinal food' its utility prevention treatment proposed a research development program that includs diet design (supplementary food), medical nutrition therapy new drugs, could provide pathways for use natural plants DM.

Язык: Английский

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Targeting Nrf2 in ischemia-reperfusion alleviation: From signaling networks to therapeutic targeting

Life Sciences, Год журнала: 2022, Номер 300, С. 120561 - 120561

Опубликована: Апрель 20, 2022

Язык: Английский

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Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?

Medicina, Год журнала: 2022, Номер 58(4), С. 472 - 472

Опубликована: Март 25, 2022

Diabetes Mellitus (DM) is amongst the most notable causes of years life lost worldwide and its prevalence increases perpetually. The disease characterized as multisystemic dysfunctions attributed to hyperglycemia resulting directly from insulin resistance (IR), inadequate secretion, or enormous glucagon secretion. Insulin a highly anabolic peptide hormone that regulates blood glucose levels by hastening cellular uptake well controlling carbohydrate, protein, lipid metabolism. In course Type 2 (T2DM), which accounts for nearly 90% all cases diabetes, response inadequate, this condition defined Resistance. IR sequela include, but are not limited to, hyperglycemia, cardiovascular system impairment, chronic inflammation, disbalance in oxidative stress status, metabolic syndrome occurrence. Despite substantial progress understanding molecular pathways accounting injurious effects towards multiple body organs, still recognized ferocious enigma. number widely available therapeutic approaches growing, however, demand precise, safe, effective therapy also increasing. A literature search was carried out using MEDLINE/PubMed, Google Scholar, SCOPUS Clinical Trials Registry databases with combination keywords MeSH terms, papers published February 2021 March 2022 were selected recently papers. This review paper aims provide critical, concise, comprehensive insights into advances treatment achieved last months.

Язык: Английский

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Isorhamnetin Reduces Glucose Level, Inflammation, and Oxidative Stress in High-Fat Diet/Streptozotocin Diabetic Mice Model

Molecules, Год журнала: 2023, Номер 28(2), С. 502 - 502

Опубликована: Янв. 4, 2023

Background: Isorhamnetin is a flavonoid that found in medical plants. Several studies showed isorhamnetin has anti-inflammatory and anti-obesity effects. This study aims to investigate the anti-diabetic effects of high-fat diet Streptozotocin-(HFD/STZ)-induced mice model type 2 diabetes. Materials Methods: Mice were fed with HFD followed by two consecutive low doses STZ (40 mg/kg). HFD/STZ diabetic treated orally (10 mg/kg) or (200 metformin for 10 days before sacrificing collecting plasma soleus muscle further analysis. Results: reduced elevated levels serum glucose compared vehicle control group (p < 0.001). abrogated increase insulin The homeostasis assessment resistance (HOMA-IR) was decreased controls. Fasting level significantly lower during intraperitoneal tolerance test (IPGTT) skeletal protein contents GLUT4 p-AMPK-α upregulated following treatment > 0.01). LDL, triglyceride, cholesterol MDA, IL-6 0.001), increased GSH GSSG 0.05) control. Conclusions: ameliorates resistance, oxidative stress, inflammation. could represent promising therapeutic agent treat T2D.

Язык: Английский

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