Diabetic microvascular disease in non-classical beds: the hidden impact beyond the retina, the kidney, and the peripheral nerves DOI Creative Commons
Dı́dac Mauricio, Mónica Gratacòs, Josep Franch‐Nadal

et al.

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 15, 2023

Abstract Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network microvessels beyond well-known documented target organs, i.e., retina, kidney, peripheral nerves. Indeed, an intact microvascular bed crucial for preserving each organ’s specific functions achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related dysfunction leads widespread multiorgan consequences in still-overlooked non-traditional organs such as brain, lung, bone tissue, skin, arterial wall, heart, or musculoskeletal system. All these are vulnerable physiopathological mechanisms that cause damage diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, endothelial dysfunction) collectively contribute microvessels’ structure function, compromising blood flow tissue perfusion. However, microcirculatory networks differ between due variations haemodynamic, vascular architecture, affected cells, resulting spectrum clinical presentations. The aim this review focus on multifaceted nature impairment through available evidence often overlooked organs. A better understanding microangiopathy non-target provides broader perspective systemic disease, underscoring importance recognising comprehensive range complications classic sites.

Language: Английский

Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression DOI
Thomas T. van Sloten, Sanaz Sedaghat, Mercedes R. Carnethon

et al.

The Lancet Diabetes & Endocrinology, Journal Year: 2020, Volume and Issue: 8(4), P. 325 - 336

Published: March 2, 2020

Language: Английский

Citations

481
Fluorescent small organic probes for biosensing DOI Creative Commons
Xue Tian, Lloyd C. Murfin, Luling Wu

et al.

Chemical Science, Journal Year: 2021, Volume and Issue: 12(10), P. 3406 - 3426

Published: Jan. 1, 2021

Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity sensitivity, whilst being non-invasive, suitable real-time analysis living systems. With this perspective we highlight sensing mechanisms including Förster resonance energy transfer (FRET), intramolecular charge (ICT), photoinduced electron (PeT), excited state proton (ESIPT), aggregation induced emission (AIE) multiple modality fluorescence approaches dual/triple (DSM or TSM). Throughout remaining challenges suggest potential directions development towards improved small-molecule biosensing.

Language: Английский

Citations

375
Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future DOI Creative Commons
Carla Iacobini, Martina Vitale, Carlo Pesce

et al.

Antioxidants, Journal Year: 2021, Volume and Issue: 10(5), P. 727 - 727

Published: May 5, 2021

Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as causal link between hyperglycemia four seemingly independent pathways that are involved pathogenesis diabetes-associated vascular disease. Before after milestone diabetes research, hundreds articles describe role ROS, but failure clinical trials to demonstrate antioxidant benefits some recent experimental studies showing ROS dispensable complications call time reflect. This twenty-year journey focuses on most relevant literature regarding main sources generation their cell dysfunction complications. To identify future research directions, review discusses evidence favor against oxidative stress an initial event cellular biochemical abnormalities induced by hyperglycemia. It also explores possible alternative mechanisms, including carbonyl Warburg effect, linking glucose lipid excess, mitochondrial dysfunction, activation metabolism leading injury inflammation.

Language: Английский

Citations

113
Toxicity of advanced glycation end products (Review) DOI Open Access
Aleksandra Kuzan

Biomedical Reports, Journal Year: 2021, Volume and Issue: 14(5)

Published: March 18, 2021

Advanced glycation end‑products (AGEs) are proteins or lipids glycated nonenzymatically by glucose, other reducing sugars and their derivatives, such as glyceraldehyde, glycolaldehyde, methyloglyoxal acetaldehyde. There three different means of AGE formation: i) Maillard reactions, the polyol pathway lipid peroxidation. AGEs participate in pathological mechanisms underlying development several diseases, diabetes its complications, retinopathy neuropathy, neurological disorders (for example, Parkinson's disease Alzheimer's disease), atherosclerosis, hypertension types cancer. levels increased patients with hyperglycaemia, is likely result high concentration substrates circulating blood. The present review summarises formation nomenclature advanced end‑products, an emphasis on role diabetes, disorders, well cancer pathologies. A particular focus placed functions toxic AGEs. Additionally, studies which have shown cytotoxicity albumin also discussed. Finally, diagnostic relevance for targeting therapeutic strategies highlighted.

Language: Английский

Citations

111
Honey: An Advanced Antimicrobial and Wound Healing Biomaterial for Tissue Engineering Applications DOI Creative Commons
Joel Yupanqui Mieles, Cian Vyas, Enes Aslan

et al.

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(8), P. 1663 - 1663

Published: Aug. 10, 2022

Honey was used in traditional medicine to treat wounds until the advent of modern medicine. The rising global antibiotic resistance has forced development novel therapies as alternatives combat infections. Consequently, honey is experiencing a resurgence evaluation for antimicrobial and wound healing applications. A range both Gram-positive Gram-negative bacteria, including antibiotic-resistant strains biofilms, are inhibited by honey. Furthermore, susceptibility antibiotics can be restored when synergistically with Honey’s activity also includes antifungal antiviral properties, most varieties honey, its attributed enzymatic generation hydrogen peroxide, reactive oxygen species. Non-peroxide factors include low water activity, acidity, phenolic content, defensin-1, methylglyoxal (Leptospermum honeys). been widely explored tissue-regenerative agent. It contribute all stages healing, thus direct application dressings. difficulty sustained delivery honey’s active ingredients site driven tissue engineering approaches (e.g., electrospinning hydrogels). This review presents in-depth up-to-date comprehensive overview commercial medical uses, growing experimental use tissue-engineered scaffolds.

Language: Английский

Citations

79
Methylglyoxal and Its Adducts: Induction, Repair, and Association with Disease DOI Creative Commons
Seigmund Wai Tsuen Lai, Edwin De Jesus Lopez Gonzalez,

Tala Zoukari

et al.

Chemical Research in Toxicology, Journal Year: 2022, Volume and Issue: 35(10), P. 1720 - 1746

Published: Oct. 5, 2022

Metabolism is an essential part of life that provides energy for cell growth. During metabolic flux, reactive electrophiles are produced covalently modify macromolecules, leading to detrimental cellular effects. Methylglyoxal (MG) abundant electrophile formed from lipid, protein, and glucose metabolism at intracellular levels 1-4 μM. MG modifies DNA, RNA, forming advanced glycation end products (MG-AGEs). MG-AGEs associated with the onset progression many pathologies including diabetes, cancer, liver kidney disease. Regulating a potential strategy prevent disease, they may also have utility as biomarkers predict disease risk, onset, progression. Here, we review recent advances knowledge surrounding MG, its production elimination, mechanisms formation, physiological impact in progression, latter context receptor RAGE. We discuss methods measuring their clinical application prognostic allow early detection intervention prior onset. Finally, consider relevant applications current therapeutic strategies aimed targeting MG-AGEs, RAGE ultimately improve patient outcomes.

Language: Английский

Citations

77
Advanced Glycation End Products in the Skin: Molecular Mechanisms, Methods of Measurement, and Inhibitory Pathways DOI Creative Commons
Chun‐Yu Chen, Jiaqi Zhang, Li Li

et al.

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

Published: May 11, 2022

Advanced glycation end products (AGEs) are a series of stable compounds produced under non-enzymatic conditions by the amino groups biomacromolecules and free carbonyl glucose or other reducing sugars commonly thermally processed foods. AGEs can cause various diseases, such as diabetes, atherosclerosis, neurodegeneration, chronic kidney disease, triggering receptors AGE (RAGEs) in human body. There is evidence that also affect different structures physiological functions skin. However, mechanism complicated cumbersome causes harms to This article aims identify summarise formation characteristics AGEs, focussing on molecular mechanisms which composition structure normal skin substances at layers induce issues. We discuss prevention inhibition pathways, provide systematic comprehensive method for measuring content skin, analyse their advantages disadvantages. work help researchers acquire deeper understanding relationship between provides basis development effective ingredients inhibit glycation.

Language: Английский

Citations

74
Paraoxonase 1 and atherosclerosis DOI Creative Commons
Paul N. Durrington, Bilal Bashir, Handrean Soran

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 16, 2023

Paraoxonase 1 (PON1), residing almost exclusively on HDL, was discovered because of its hydrolytic activity towards organophosphates. Subsequently, it also found to hydrolyse a wide range substrates, including lactones and lipid hydroperoxides. PON1 is critical for the capacity HDL protect LDL outer cell membranes against harmful oxidative modification, but this depends location within hydrophobic domains HDL. It does not prevent conjugated diene formation, directs peroxidation products derived from these become harmless carboxylic acids rather than aldehydes which might adduct apolipoprotein B. Serum inversely related incidence new atherosclerotic cardiovascular disease (ASCVD) events, particularly in diabetes established ASCVD. Its serum frequently discordant with that cholesterol. diminished dyslipidaemia, diabetes, inflammatory disease. Polymorphisms, most notably Q192R, can affect some phenyl acetate. Gene ablation or over-expression human rodent models associated increased decreased atherosclerosis susceptibility respectively. antioxidant enhanced by AI lecithin:cholesterol acyl transferase AII, amyloid A, myeloperoxidase. loses when separated environment. Information about structure has been obtained water soluble mutants created directed evolution. Such recombinant may, however, lose non-polar substrates. Whilst nutrition pre-existing modifying drugs influence there cogent need more specific PON1-raising medication be developed.

Language: Английский

Citations

46
The Glutathione System: A Journey from Cyanobacteria to Higher Eukaryotes DOI Creative Commons
Corinne Cassier‐Chauvat,

Fanny Marceau,

Sandrine Farci

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1199 - 1199

Published: May 31, 2023

From bacteria to plants and humans, the glutathione system plays a pleiotropic role in cell defense against metabolic, oxidative metal stresses. Glutathione (GSH), γ-L-glutamyl-L-cysteinyl-glycine nucleophile tri-peptide, is central player of this that acts redox homeostasis, detoxification iron metabolism most living organisms. GSH directly scavenges diverse reactive oxygen species (ROS), such as singlet oxygen, superoxide anion, hydrogen peroxide, hydroxyl radical, nitric oxide carbon radicals. It also serves cofactor for various enzymes, glutaredoxins (Grxs), peroxidases (Gpxs), reductase (GR) glutathione-S-transferases (GSTs), which play crucial roles detoxication. This review summarizes what known concerning GSH-system (GSH, GSH-derived metabolites GSH-dependent enzymes) selected model organisms (Escherichia coli, Saccharomyces cerevisiae, Arabidopsis thaliana human), emphasizing cyanobacteria following reasons. Cyanobacteria are environmentally biotechnologically important regarded having evolved photosynthesis protect themselves ROS produced by their active photoautotrophic metabolism. Furthermore, synthesize metabolites, ergothioneine phytochelatin, detoxication humans plants, respectively. thiol-less homologs ophthalmate norophthalmate serve biomarkers diseases humans. Hence, well-suited thoroughly analyze role/specificity/redundancy players using genetic approach (deletion/overproduction) hardly feasible with other (E. coli S. cerevisiae do not ergothioneine, while acquire it from soil diet, respectively).

Language: Английский

Citations

46
Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

Citations

39