Mitochondrial dysfunction in diabetic tubulopathy

Metabolism, Journal Year: 2022, Volume and Issue: 131, P. 155195 - 155195

Published: March 28, 2022

Diabetic kidney disease (DKD) is a devastating microvascular complication associated with diabetes mellitus. Recently, the major focus of glomerular lesions DKD has partly shifted to diabetic tubulopathy because renal insufficiency and prognosis patients closely related tubular atrophy interstitial fibrosis. Indeed, proximal tubule enriching in mitochondria for its high energy demand dependence on aerobic metabolism given us pause primarily mitochondria-centric view early tubulopathy. Multiple studies suggest that condition directly damages tubules, resulting dysfunction, including decreased bioenergetics, overproduction mitochondrial reactive oxygen species (mtROSs), defective mitophagy dynamics disturbances, which turn trigger series metabolic abnormalities. However, precise mechanism underlying dysfunction tubules still infancy. Understanding tubulointerstitial's pathobiology would facilitate search new biomarkers DKD. In this Review, we summarize current literature postulate potential effects may accelerate initiation early-stage tubulopathy, as well their therapeutic strategies.

Language: Английский

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Angiogenesis during diabetic wound repair: from mechanism to therapy opportunity

Burns & Trauma, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

Abstract Diabetes mellitus, a pervasive chronic metabolic disorder, is often associated with complications such as impaired wound healing. Various factors, most notably vascular deficiency, govern the repair process in diabetic patients, significantly impeding healing; therefore, angiogenesis and its role have emerged important areas of research. This review aims to delve into mechanisms angiogenesis, effects diabetes on association between repair. will ultimately offer valuable guidance regarding ideal timing treatment clinical setting.

Language: Английский

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Intracellular energy production and distribution in hypoxia

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(9), P. 105103 - 105103

Published: July 27, 2023

The hydrolysis of ATP is the primary source metabolic energy for eukaryotic cells. Under physiological conditions, cells generally produce more than sufficient levels to fuel active biological processes necessary maintain homeostasis. However, mechanisms underpinning distribution subcellular microenvironments with high local demand remain poorly understood. Intracellular in normal conditions has been proposed rely on passive diffusion across concentration gradients generated by producing systems such as mitochondria and glycolytic pathway. can develop deficiency due increases consumption. Alternatively, production be reduced during bioenergetic stress hypoxia. Mammalian therefore need have capacity alter their metabolism strategies compensate deficits while also controlling production. It highly likely that satisfying requirements cell involves regulated areas within cell. Recently, (both spatially temporally) ATP-producing become an area intense investigation. Here, we review what known (and unknown) about intracellular explore potential through which this targeted altered hypoxia, aim stimulating investigation important, yet understood field research.

Language: Английский

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Mechanism of damage of HIF-1 signaling in chronic diabetic foot ulcers and its related therapeutic perspectives

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e24656 - e24656

Published: Jan. 25, 2024

Diabetic foot ulcer (DFU) is a chronic complication of diabetes. Wound healing in patients with DFU generally very slow, high recurrence rate even after the healed. The remains major clinical challenge due to lack understanding its pathogenesis. Given significant impact on patient health and medical costs, enhancing our pathophysiological alterations wound critical. A growing body research has shown that impaired activation HIF-1 pathway diabetics, which weakens mediated responses hypoxia leads down-regulation downstream target genes, leading incurable diabetic ulcers. By analyzing summarizing literature recent years, this review summarizes mechanism signaling damage development DFU, analyzes compares application PHD inhibitors, VHL biomaterials stem cell therapy wounds diabetes, proposes new treatment scheme by participation pathway, provides ideas for DFU.

Language: Английский

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Mitochondria: An Emerging Unavoidable Link in the Pathogenesis of Periodontitis Caused by Porphyromonas gingivalis

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 737 - 737

Published: Jan. 6, 2024

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Non-Invasive Assessment of Vascular Circulation Based on Flow Mediated Skin Fluorescence (FMSF)

Biology, Journal Year: 2023, Volume and Issue: 12(3), P. 385 - 385

Published: Feb. 28, 2023

Flow Mediated Skin Fluorescence (FMSF) is a new non-invasive method for assessing vascular circulation and/or metabolic regulation. It enables assessment of both vasoconstriction and vasodilation. The measures stimulation the in response to post-occlusive reactive hyperemia (PORH). analyzes dynamical changes emission NADH fluorescence from skin tissue, providing information on mitochondrial status intracellular oxygen delivery through circulatory system. Assessment state using FMSF technique based three parameters: (RHR), hypoxia sensitivity (HS), normoxia oscillatory index (NOI). RHR HS parameters determine risk disorders are main diagnostic parameters. NOI parameter an auxiliary evaluating microcirculation under stress various origins (e.g., emotional stress, physical exhaustion, or post-infection stress). clinical data show that complications limited among people whose RHR, log(HS), not significantly below mean values determined by technique, especially if they simultaneously meet conditions > 30% log(HS) 1.5 (HS 30), 60%.

Language: Английский

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SKP alleviates the ferroptosis in diabetic kidney disease through suppression of HIF-1α/HO-1 pathway based on network pharmacology analysis and experimental validation

Chinese Medicine, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 25, 2024

Diabetic kidney disease (DKD) represents a microvascular complication of diabetes mellitus. Shenkang Pills (SKP), traditional Chinese medicine formula, has been widely used in the treatment DKD and obvious antioxidant effect. Ferroptosis, novel mode cell death due to iron overload, shown be associated with DKD. Nevertheless, precise effects underlying mechanisms SKP on ferroptosis diabetic remain unclear.

Language: Английский

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Advances in Smart-Response Hydrogels for Skin Wound Repair

Polymers, Journal Year: 2024, Volume and Issue: 16(19), P. 2818 - 2818

Published: Oct. 5, 2024

Hydrogels have emerged as promising candidates for biomedical applications, especially in the treatment of skin wounds, a result their unique structural properties, highly tunable physicochemical and excellent biocompatibility. The integration smart-response features into hydrogels allows dynamic responses to different external or internal stimuli. Therefore, this paper reviews design smart-responsive microenvironments field wound therapy. First, three typical chronic difficult-to-heal wounds key mechanisms affecting healing therapeutic measures are outlined. Strategies construction stimulus-responsive (e.g., pH, ROS, enzymes, glucose) temperature, light, electricity, magnetic fields) highlighted from perspective microenvironment vitro environment, constitutive relationships between material design, intelligent response, revealed. Finally, discusses severe challenges faced by during repair provides an outlook on combination artificial intelligence give scientific direction creating using hydrogel dressings that respond stimuli clinic.

Language: Английский

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Roles of β-Cell Hypoxia in the Progression of Type 2 Diabetes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4186 - 4186

Published: April 10, 2024

Type 2 diabetes is a chronic disease marked by hyperglycemia; impaired insulin secretion pancreatic β-cells hallmark of this disease. Recent studies have shown that hypoxia occurs in the patients with type and hypoxia, turn, contributes to defect β-cell loss through various mechanisms, including activation hypoxia-inducible factors, induction transcriptional repressors, AMP-activated protein kinase. This review focuses on advances our understanding contribution development dysfunction diabetes. A better might be useful new strategies for treating

Language: Английский

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Sensing the oxygen and temperature in the adipose tissues – who’s sensing what?

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(11), P. 2300 - 2307

Published: Nov. 1, 2023

Abstract Adipose tissues, composed of various cell types, including adipocytes, endothelial cells, neurons, and immune are organs that exposed to dynamic environmental challenges. During diet-induced obesity, white adipose tissues experience hypoxia due adipocyte hypertrophy dysfunctional vasculature. Under these conditions, cells in activate hypoxia-inducible factor (HIF), a transcription activates signaling pathways involved metabolism, angiogenesis, survival/apoptosis adapt such an environment. Exposure cold or activation the β-adrenergic receptor (through catecholamines chemicals) leads heat generation, mainly brown through activating uncoupling protein 1 (UCP1), proton uncoupler inner membrane mitochondria. White can undergo similar process under this condition, phenomenon known as ‘browning’ ‘beige adipocytes’. While UCP1 expression has largely been confined HIF be expressed many types cells. To dissect role specific during researchers have generated tissue-specific knockout (KO) mice targeting pathways, studies commonly revealed intact HIF-1 adipocytes tissue macrophages exacerbates inflammation insulin resistance. In review, we highlight some key findings obtained from transgenic mice, Ucp1 KO other models pathway macrophages, decipher their roles obesity.

Language: Английский

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