Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 10, 2023

Abstract Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on single vascular complication are no longer suitable for the long-term management patients with diabetes. Diabetic panvascular disease (DPD) is clinical syndrome in which vessels various sizes, including macrovessels microvessels cardiac, cerebral, renal, ophthalmic, peripheral systems diabetes, develop atherosclerosis as common pathology. Pathological manifestations DPDs usually manifest macrovascular atherosclerosis, well microvascular endothelial function impairment, basement membrane thickening, microthrombosis. Cardiac, microangiopathy coexist microangiopathy, while renal retinal predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, risk-predictive relationships diseases. Aggressive glycemic control combined early comprehensive intervention key prevention treatment. In addition widely recommended metformin, glucagon-like peptide-1 agonist, sodium-glucose cotransporter-2 inhibitors, latest aldose reductase peroxisome proliferator-activated receptor-γ agonizts, glucokinases mitochondrial energy modulators, etc. under active development. proposed obtain more systematic care requires center focusing This would leverage advantages cross-disciplinary approach achieve better integration pathogenesis therapeutic evidence. Such strategy confer benefits promote development DPD discipline.

Language: Английский

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Epigenetic modifications of inflammation in intervertebral disc degeneration

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101902 - 101902

Published: March 4, 2023

Intervertebral disc degeneration (IDD) is a common cause of joint-related chronic disability in elderly individuals worldwide. It seriously impacts the quality life and inflicts substantial social economic burden. The pathological mechanisms underlying IDD have not been fully revealed, leading to less satisfactory clinical treatment outcomes. More studies are urgently needed reveal its precise mechanisms. Numerous revealed that inflammation closely related various processes IDD, including continuous loss extracellular matrix, cell apoptosis, senescence, indicating important role mechanism IDD. Epigenetic modifications affect functions characteristics genes mainly through DNA methylation, histone modification, non-coding RNA regulation, other mechanisms, thus having major effect on survival state body. Recently, epigenetic during has attracting research interest. In this review, we summarize roles different types recent years, improve our understanding etiology transform basic strategy into clinically effective for individuals.

Language: Английский

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Cross Talks between Oxidative Stress, Inflammation and Epigenetics in Diabetic Retinopathy

Cells, Journal Year: 2023, Volume and Issue: 12(2), P. 300 - 300

Published: Jan. 12, 2023

Diabetic retinopathy, one of the most devastating complications diabetes, is a multifactorial progressing disease with very complex etiology. Although many metabolic, molecular, functional and structural changes have been identified in retina its vasculature, exact molecular mechanism pathogenesis still remains elusive. Sustained high-circulating glucose increases oxidative stress also activates inflammatory cascade. Free radicals increase mediators, inflammation can production free radicals, suggesting positive loop between them. In addition, diabetes facilitates epigenetic modifications that influence transcription gene without changing DNA sequence. Several genes associated diabetic retinopathy are influenced by modifications. This review discusses cross-talks stress, epigenetics retinopathy. Since external factors such as environment lifestyle, they be reversed, this opens up possibilities for new strategies to inhibit development/progression sight-threatening disease.

Language: Английский

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Epigenetics in Obesity and Diabetes Mellitus: New Insights

Nutrients, Journal Year: 2023, Volume and Issue: 15(4), P. 811 - 811

Published: Feb. 4, 2023

A long-term complication of obesity is the development type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics post-transcriptional modification DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications are methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at lysine residue amino terminus histones, affecting DNA, non-coding RNA. methylation has shown pancreatic islets, adipose tissue, skeletal muscle, liver. Furthermore, observed chronic complications T2D, such diabetic nephropathy, retinopathy, neuropathy. Recently, a new drug developed which acts on bromodomains extraterminal (BET) domain proteins, operate like readers communicate chromatin to make accessible for transcription by inhibiting them. This (apabetalone) being studied prevent major adverse cardiovascular events people low HDL cholesterol, kidney failure, recent coronary events. review aims describe relationship between obesity, their possible treatments.

Language: Английский

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Phytochemical profile and antioxidant capacity, α-amylase and α-glucosidase inhibitory activities of Oxalis pes-caprae extracts in alloxan-induced diabetic mice

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 160, P. 114393 - 114393

Published: Feb. 10, 2023

Diabetes and its complications are closely correlated with chronic hyperglycemia, causing severe oxidative stress leading to glycation reaction formation of advanced end products. However, medicinal plants still a source inspiration for the discovery new treatments several diseases, including diabetes. The present study was aimed evaluate antioxidant antidiabetic properties Oxalis pes-caprae flowers extract in alloxan-induced diabetic mice. phytochemical activities both aqueous methanolic extracts were assessed by in-vitro testing such as free radical scavenging assays (DPPH ABTS+), ferrous ions (Fe2+) chelating activity reducing power assay. Additionally, detection Amadori products used determine antiglycation potential. α-glucosidase α-amylase inhibitory assessment employed effect, while mice measure in-vivo antioxidants carbohydrates enzymes. effect on body weight blood glucose level extract-treated also investigated. Among tested extract, richest phenolic compounds which is directly related their remarkable antioxidant, enzyme activity. oral administration two doses (150 mg/kg 250 mg/kg) daily 3 weeks resulted hypoglycemic compared reference drug, glibenclamide (10 mg/kg). Furthermore, shown significantly increase glycolysis enzymes liver, kidney spleen mice, control group. Therefore, effectively exhibited effects indicated studies, confirming protective hyperglycemia damage.

Language: Английский

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Merged Red and NIR Light Sources for Photobiomodulation Therapy in Diabetic Wound Healing

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Photobiomodulation (PBM) is considered an effective and safe therapeutic modality in supporting the treatment of complications from a global pandemic-diabetes. In this study, PBM therapy investigated to accelerate wound healing diabetic mice (DM), under combined biological effects red light organic light-emitting diode (ROLED) near-infrared (NIR) NIR conversion film (NCF) with dispersed CuInS2/ZnS quantum dots (QDs). The QD concentration NCF structure were optimized maximize optical properties mechanical stability. A merged red/NIR device (MRND) was produced by integrating ROLED for therapy. As result irradiating DM MRND at dose 2 J/cm2, after 10 days, wounds recovered three times faster than without MRND. Additionally, not only restored epidermal thickness normal but also significantly reduced levels pro-inflammatory cytokines. experimental results show that proposed has potential improve quality life patients helping them rapid healing.

Language: Английский

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C/EBPα regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPARγ signalling pathway

Stem Cell Research & Therapy, Journal Year: 2022, Volume and Issue: 13(1)

Published: July 26, 2022

Abstract Background The imbalance of osteogenic/adipogenic differentiation bone marrow mesenchymal stem cells (BMSCs) is closely related to steroid-induced avascular necrosis the femoral head (SANFH). We aimed investigate epigenetic mechanism intramedullary fat accumulation and continuous osteonecrosis after glucocorticoid (GC) withdrawal in SANFH. Methods An SANFH model was established SD rats, which received an intermittent high GC dose for first 4 weeks followed by additional without GC. explored synergistic effects mechanisms C/EBPα PPARγ on BMSCs lentivirus-mediated gene knockdown overexpression assays. A chromatin immunoprecipitation assay performed identify modification sites vivo vitro. Results In model, significantly increased, transcription factors were upregulated simultaneously head. vitro, promoted adipogenic targeting signalling pathway, while impaired osteogenic differentiation. Further studies demonstrated that histone H3K27 acetylation played important role underlying upregulates level promoter region inhibiting HDAC1. Additionally, effectively prevented differentiation, thus slowing progression Conclusions Our results demonstrate molecular regulates expression acetylating histones revealed phenomenon time. Graphical abstract

Language: Английский

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Treatment and prevention of pathological mitochondrial dysfunction in retinal degeneration and in photoreceptor injury

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 203, P. 115168 - 115168

Published: July 12, 2022

Pathological deterioration of mitochondrial function is increasingly linked with multiple degenerative illnesses as a mediator wide range neurologic and age-related chronic diseases, including those genetic origin. Several these diseases are rare, typically defined in the United States an illness affecting fewer than 200,000 people U.S. population, or about one 1600 individuals. Vision impairment due to dysfunction eye prominent feature evident numerous primary common pathophysiology many familiar ophthalmic disorders, macular degeneration, diabetic retinopathy, glaucoma retinopathy prematurity — collection syndromes, disorders significant unmet medical needs. Focusing on metabolic pathway mechanisms, possible roles cuproptosis ferroptosis retinal dysfunction, we shed light potential α-lipoyl-L-carnitine treating diseases. α-Lipoyl-L-carnitine bioavailable mitochondria-targeting lipoic acid prodrug that has shown protecting against degeneration photoreceptor cell loss indications.

Language: Английский

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Physical exercise and persistent organic pollutants

Heliyon, Journal Year: 2023, Volume and Issue: 9(9), P. e19661 - e19661

Published: Sept. 1, 2023

Exposure to the legacy and emerging persistent organic pollutants (POPs) incessantly has become an important threat individual health, which is closely related neurodevelopment, endocrine cardiovascular homeostasis. Exercise, on other hand, been consistently shown improve physical fitness. Whereas associations between traditional air pollutants, exercise lung function have thoroughly reviewed, reviews are scarce. Hence, a literature review focused exercise, exposure POPs, health risk assessment was performed for studies published from 2004 2022. The purpose of this provide overview pathways levels POPs during as well impact concerns attributable redistribution, metabolism, excretion in vivo. Therein lies broader array benefits, including insulin sensitizing, mitochondrial DNA repair, lipid metabolism intestinal microecological balance. Physical conducive reduce body burden resistant hazards generally. Besides, condition critical factor evaluating potential link effects.

Language: Английский

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Expanding Role of Epigenetics in Human Health and Disease

Exploratory Research and Hypothesis in Medicine, Journal Year: 2024, Volume and Issue: 000(000), P. 000 - 000

Published: Jan. 11, 2024

The traditional definition of epigenetics encompasses all molecular pathways that affect how a genotype expresses itself on the way to particular phenotype, with serving as interface between and phenotype. Unlike genetic changes, which may have protracted, irreversible effects health emergence illnesses, epigenetic modifications are reversible do not change DNA sequence. However, they can our bodies interpret sequences. Gene expression regulated by has emerged major contributing element etiology many diseases over time crucial determinant human health. One strongest arguments in support gene controlled comes from startling discovery methylation causes X-chromosome inactivation, been connected several diseases. intrinsic uterine environment, where embryo fetus grow develop become neonates is vulnerable early settings throughout development, affecting offspring's long-term well their predisposition for different germ cell development influenced environmental factors, result transgenerational effects. Therefore, this article, we essentially provide summary present level understanding concerning function regarding critical facets health, including embryonic adulthood, emphasis explaining underlying diverse mechanisms regulate onset diseases, cutting-edge technological tools used study epigenome. Finally, talk about state therapies, might be put use treatment range

Language: Английский

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