Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 9, 2024

Diabetic peripheral neuropathy (DPN) refers to the development of nerve dysfunction in patients with diabetes when other causes are excluded. distal symmetric polyneuropathy (DSPN) is most representative form DPN. As one common complications diabetes, its prevalence increases duration diabetes. 10-15% newly diagnosed T2DM have DSPN, and can exceed 50% for more than 10 years. Bilateral limb pain, numbness, paresthesia clinical manifestations DPN, severe cases, foot ulcers occur, even leading amputation. The etiology pathogenesis diabetic not yet completely clarified, but hyperglycemia, disorders lipid metabolism, abnormalities insulin signaling pathways currently considered be initiating factors a range pathophysiological changes In presence abnormal metabolic factors, normal structure function entire nervous system disrupted, including myelinated unmyelinated axons, perikaryon, neurovascular, glial cells. addition, pathway will inhibit neural axon repair promote apoptosis damaged Here, we discuss recent advances study DPN mechanisms, oxidative stress pathways, mechanisms microvascular damage, damage receptor potential associated neuroinflammation, mitochondrial dysfunction, cellular damage. Identifying contributions from each associations between them may help us further explore targeted screening treatment interventions.

Language: Английский

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Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12378 - 12378

Published: Aug. 3, 2023

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates increases in prevalence. Diabetic nephropathy (DN) is a specific kind kidney damage that occurs 40% patients DM and considered serious complication DM. Most modern methods for treatments aimed at slowing down progression DN have side effects do not produce unambiguous positive results long term. This fact has encouraged researchers search additional or alternative treatment methods. Hyperglycemia negative effect on renal structures due number factors, including activation polyol hexosamine glucose metabolism pathways, renin-angiotensin-aldosterone sympathetic nervous systems, accumulation advanced glycation end products insulin resistance endothelial dysfunction tissues. The above mechanisms cause development oxidative stress (OS) reactions mitochondrial dysfunction, which turn contribute DN. Modern antioxidant therapies involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), are widely used only diabetes but also other systemic diseases. It been suggested therapeutic approaches target source reactive oxygen species may certain advantages terms nephroprotection from OS. review describes significance studies OS biomarkers pathogenesis analyzes reducing intensity prevention

Language: Английский

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Recent advances of hydrogels as smart dressings for diabetic wounds

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(5), P. 1126 - 1148

Published: Jan. 1, 2024

This review highlights the latest progress of smart hydrogel dressings for bandaging, monitoring and therapy diabetic wounds.

Language: Английский

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Mitochondrial metabolic reprogramming in diabetic kidney disease

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(6)

Published: June 24, 2024

Abstract Diabetic kidney disease, known as a glomerular arises from metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo reprogramming compensatory mechanism fulfill energy needs for survival and growth, attracting scholarly attention recent years. Studies indicate that mitochondrial significantly influences the pathophysiological progression of DKD. Alterations lead abnormal expression signaling molecules activation pathways, inducing stress-related cellular damage, inflammatory responses, apoptosis, autophagy irregularities, culminating fibrosis insufficiency. This review delves into impact on DKD pathogenesis, emphasizing regulation regulators downstream pathways. Therapeutic interventions targeting can potentially delay progression. The findings underscore importance focusing develop safer more effective therapeutic approaches.

Language: Английский

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Role of oxidative stress in diabetes-induced complications and their management with antioxidants

Archives of Physiology and Biochemistry, Journal Year: 2023, Volume and Issue: 130(6), P. 616 - 641

Published: Aug. 11, 2023

Diabetes mellitus (DM) is a huge global health issue and one of the most studied diseases, with large prevalence. Oxidative stress cytotoxic consequence excessive development ROS suppression antioxidant defense system for elimination, which accelerates progression diabetes complications such as diabetic neuropathy, retinopathy, nephropathy. Hyperglycaemia induced oxidative causes activation seven major pathways implicated in pathogenesis complications. These increase production RNS, contributes to dysregulated autophagy, gene expression changes, numerous pro-inflammatory mediators may eventually lead This review will illustrate that plays vital role complications, use antioxidants help reduce thus alleviate

Language: Английский

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Kidney Fibrosis and Oxidative Stress: From Molecular Pathways to New Pharmacological Opportunities

Biomolecules, Journal Year: 2024, Volume and Issue: 14(1), P. 137 - 137

Published: Jan. 22, 2024

Kidney fibrosis, diffused into the interstitium, vessels, and glomerulus, is main pathologic feature associated with loss of renal function chronic kidney disease (CKD). Fibrosis may be triggered in diseases by different genetic molecular insults. However, several studies have shown that fibrosis can linked to oxidative stress mitochondrial dysfunction CKD. In this review, we will focus on three pathways link namely: (i) hyperglycemia energy imbalance, (ii) mineralocorticoid signaling pathway, (iii) hypoxia-inducible factor (HIF) pathway. We selected these because they are targeted available medications capable reducing such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, non-steroidal receptor antagonists (MRAs), HIF-1alpha-prolyl hydroxylase inhibitors. These drugs a reduction reduced collagen deposition across CKD subtypes. there still long winding road clear understanding anti-fibrotic effects compounds humans, due inherent practical ethical difficulties obtaining sequential biopsies lack specific biomarkers measurable easily accessible matrices like urine. narrative describe pathways, their interconnections, activity fibrosis.

Language: Английский

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Pharmacological functions of salidroside in renal diseases: facts and perspectives

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Rhodiola rosea is a valuable functional medicinal plant widely utilized in China and other Asian countries for its anti-fatigue, anti-aging, altitude sickness prevention properties. Salidroside, most active constituent derived from , exhibits potent antioxidative, hypoxia-resistant, anti-inflammatory, anticancer, anti-aging effects that have garnered significant attention. The appreciation of the pharmacological role salidroside has burgeoned over last decade, making it beneficial option treatment multiple diseases, including atherosclerosis, Alzheimer’s disease, Parkinson’s cardiovascular more. With renoprotective effects, parallel with inhibition oxidative stress inflammation, holds promise as potential therapeutic agent kidney damage. This article provides an overview microinflammatory state disease discuss current strategies, particular focus on highlighting recent advancements utilizing renal disease. mechanisms action are primarily associated regulation gene protein expression glomerular endothelial cells, podocytes, tubule mesangial cells cell carcinoma cell, TNF-α, TGF-β, IL-1β, IL-17A, IL-6, MCP-1, Bcl-2, VEGF, ECM protein, caspase-3, HIF-1α, BIM, well modulation AMPK/SIRT1, Nrf2/HO-1, Sirt1/PGC-1α, ROS/Src/Cav-1, Akt/GSK-3β, TXNIP-NLRP3, ERK1/2, TGF-β1/Smad2/3, PI3K/Akt, Wnt1/Wnt3a β-catenin, TLR4/NF-κB, MAPK, JAK2/STAT3, SIRT1/Nrf2 pathways. To best our knowledge, this review first to comprehensively cover protective diverse suggests great be developed drug metabolic syndrome, cerebrovascular diseases complications.

Language: Английский

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Perfluorooctane sulfonate causes pyroptosis and lipid metabolism disorders through ROS-mediated NLRP3 inflammasome activation in grass carp hepatocyte

Aquatic Toxicology, Journal Year: 2024, Volume and Issue: 267, P. 106839 - 106839

Published: Jan. 15, 2024

Language: Английский

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Endogenous/exogenous stimuli‐responsive smart hydrogels for diabetic wound healing

Aggregate, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Diabetes significantly impairs the body's wound‐healing capabilities, leading to chronic, infection‐prone wounds. These wounds are characterized by hyperglycemia, inflammation, hypoxia, variable pH levels, increased matrix metalloproteinase activity, oxidative stress, and bacterial colonization. complex conditions complicate effective wound management, prompting development of advanced diabetic care strategies that exploit specific characteristics such as acidic pH, high glucose stress trigger controlled drug release, thereby enhancing therapeutic effects dressings. Among solutions, hydrogels emerge promising due their stimuli‐responsive nature, making them highly for managing these The latest advancements in mono/multi‐stimuli‐responsive smart showcase superiority potential healthcare materials, highlighted relevant case studies. However, traditional dressings fall short meeting nuanced needs wounds, adjustable adhesion, easy removal, real‐time status monitoring, dynamic release adjustment according wound's conditions. Responsive represent a significant leap forward proficient sensing responding environment, offering more targeted approach treatment. This review highlights recent dressing, delivery, emphasizing role improving healing. It addresses ongoing challenges future directions, aiming guide clinical adoption.

Language: Английский

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FSTL1 aggravates high glucose-induced oxidative stress and transdifferentiation in HK-2 cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 2, 2025

Chronic hyperglycemia, a hallmark of diabetes, can trigger inflammatory responses in the kidney, leading to diabetic nephropathy (DN). Follistatin-like protein 1 (FSTL1) has emerged as potential therapeutic target various kidney diseases. This study investigated effect high glucose on FSTL1 expression and its role oxidative stress cellular transdifferentiation injury HK-2 human proximal tubule epithelial cells, model DN. We FSTL1's level cells exposed using Western blotting quantitative real-time polymerase chain reaction (qRT-PCR). was manipulated recombinant (rhFSTL1) or lentiviral shFSTL1. then analyzed proliferation, stress, transdifferentiation, cell migration, nuclear factor kappa-B (NF-κB) signaling pathway potentially involved effects. Finally, we blocked NF-κB see influence these processes. High exposure significantly increased with longer/higher further amplifying this effect. Silencing ameliorates damage by promoting enhancing superoxide dismutase (SOD) glutathione (GSH) activity, reducing malondialdehyde (MDA) production, inhibiting migration. Furthermore, it prevented harmful conversion from myofibroblast-like phenotypes, evidenced decreased fibronectin (FN) α-smooth muscle actin (α-SMA) preserved E-cadherin. Notably, silencing also inhibited pathway. Conversely, rhFSTL1 exhibited opposite Importantly, blocking reversed detrimental effects FSTL1. These findings suggest that contributes glucose-induced via Targeting may represent novel strategy for preventing mitigating DN progression.

Language: Английский

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