Frontiers in Endocrinology, Год журнала: 2024, Номер 15
Опубликована: Дек. 16, 2024
Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes that can potentially escalate into ulceration, amputation and other severe consequences. The aim this study was to construct validate predictive nomogram model for assessing the risk DPN development among diabetic patients, thereby facilitating early identification high-risk individuals mitigating incidence outcomes.
Язык: Английский
Nutrients, Год журнала: 2024, Номер 16(8), С. 1232 - 1232
Опубликована: Апрель 20, 2024
L-carnitine (LC), a vital nutritional supplement, plays crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application recovery treatment diverse cardiovascular cerebrovascular disorders. However, controversies persist regarding utilization LC nervous system diseases, with varying effects observed across numerous mental neurological This article primarily aims to gather analyze database information comprehensively summarize therapeutic potential patients suffering from diseases while providing valuable references for further research.
Язык: Английский
Процитировано
11
Advances in Medical Sciences, Год журнала: 2024, Номер 69(1), С. 36 - 50
Опубликована: Фев. 8, 2024
Glycation is a physiological process that determines the aging of organism, while in states metabolic disorders it significantly intensified. High concentrations compounds such as reducing sugars or reactive aldehydes derived from lipid oxidation, occurring for example diabetes, atherosclerosis, dyslipidemia, obesity syndrome, lead to increased glycation proteins, lipids and nucleic acids. The level advanced end-products (AGEs) body depends on rapidity their production rate removal by urinary system. AGEs, accumulated extracellular matrix blood vessels other organs, cause irreversible changes biochemical biomechanical properties tissues. As consequence, micro- macroangiopathies appear system, may contribute organ failure, like kidneys heart. Elevated levels AGEs also increase risk Alzheimer's disease various cancers. In this paper, we propose new classification due modified amino acid residues: arginyl-AGEs, monolysyl-AGEs lysyl-arginyl-AGEs dilysyl-AGEs. Furthermore, describe detail effect pathogenesis old age diseases, diabetic complications, atherosclerosis neurodegenerative diseases. We summarize currently available data diagnostic value present therapeutic goal wide range medical problems, including SARS-CoV-2 infection so-called long COVID.
Язык: Английский
Процитировано
10
Comprehensive physiology, Год журнала: 2025, Номер 15(1)
Опубликована: Фев. 1, 2025
ABSTRACT Humans are perhaps evolutionarily engineered to get deeply addicted sugar, as it not only provides energy but also helps in storing fats, which survival during starvation. Additionally, sugars (glucose and fructose) stimulate the feel‐good factor, they trigger secretion of serotonin dopamine brain, associated with reward sensation, uplifting mood general. However, when consumed excess, contributes imbalance, weight gain, obesity, leading onset a complex metabolic disorder, generally referred diabetes. Type 2 diabetes mellitus (T2DM) is one most prevalent forms diabetes, nearly affecting all age groups. T2DM clinically diagnosed cardinal sign chronic hyperglycemia (excessive sugar blood). Chronic hyperglycemia, coupled dysfunctions pancreatic β‐cells, insulin resistance, immune inflammation, further exacerbate pathology T2DM. Uncontrolled T2DM, major public health concern, significantly toward progression several micro‐ macrovascular diseases, such diabetic retinopathy, nephropathy, neuropathy, atherosclerosis, cardiovascular including cancer. The current review discusses epidemiology, causative factors, pathophysiology, comorbidities, existing emerging therapies related It future roadmap for alternative drug discovery management
Язык: Английский
Процитировано
1
Pharmacological Research, Год журнала: 2024, Номер 208, С. 107394 - 107394
Опубликована: Сен. 3, 2024
Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions diabetic neuropathy, it triggers cascade disruptions, including reduced energy production, increased oxidative stress, cell death, ultimately leading to various complications. Thus, targeting enhance may have emerged as promising therapeutic strategy for T2DM its Notably, plant-derived compounds with β-cell protective mitophagy-stimulating properties offer potential novel agents. This review highlights intricate mechanisms linking dysfunction complications, particularly elucidating interventions this debilitating disease.
Язык: Английский
Процитировано
5
Journal of Controlled Release, Год журнала: 2025, Номер 379, С. 409 - 420
Опубликована: Янв. 16, 2025
Язык: Английский
Процитировано
0
Journal of Global Health, Год журнала: 2025, Номер 15
Опубликована: Март 21, 2025
To comprehensively assess evidence from published systematic review and meta-analyses (SRMAs) on the genetics of vascular diabetes complications. A literature search conducted in Medline Embase identified 63 non-overlapping SRMAs. We re-conducted to compare with without complications using multiple genetic models; evaluated associations Venice criteria Bayesian false-discovery probability (BFDP); graded as highly credible, not credible. also contrasted credible recent genome-wide association studies (GWASs). Highly was discovered for single nucleotide polymorphisms (SNPs) rs1024611 at MCP-1 gene SNP rs3025039 VEGF diabetic retinopathy (DR) type 2 diabetes; rs2268388 ACACB gene, insertion/deletion (Ins/Del) variant ACE rs1801133 MTHFR rs7903146 TCF7L2 kidney disease (DKD) rs4880 SOD2 peripheral neuropathy (DPN) 1 diabetes. Combining diabetes, rs759853 AKR1B1 rs1044498 ENPP1 DKD, rs1617640 EPO combined endpoint DR DKD. None these directly replicated latest GWASs however, another SNP, rs55853916 had been detected a GWAS hit This umbrella rigorously assessed complications, complemented findings yielded insight into optimal selection models design Mechanistic or bioinformatic are warranted further role genes pathology their potential drug targets. PROSPERO: CRD42022384423.
Язык: Английский
Процитировано
0
Опубликована: Апрель 10, 2025
Aim: This study aimed to computationally identify and optimize 4-hydroxy isoleucine (4HILe) derivatives from fenugreek as multitarget antidiabetic agents against α-glucosidase, α-amylase, aldose reductase [PDB (protein data bank) IDs: 5NN8, 4GQR, 4QX4]. Methods: A multi-step computational workflow was employed 4HILe agents. Molecular docking using the Schrödinger Suite screened 23 ligands three enzyme targets evaluate binding affinities interactions. dynamic (MD) simulations conducted with GROMACS (Groningen machine chemical simulations) over 100 ns assessed conformational stability through RMSD (root mean square deviation) RMSF fluctuation) analysis. Binding free energy calculations [MM-GBSA (molecular mechanics-generalized Born surface area)] landscape (FEL) studies are performed validate thermodynamics of protein-ligand Additionally, generative AI modeling LigDream generated novel compounds derived 4HILe, subsequently validated promising inhibitors. Results: The identified 4HILe-4, 2R-3S-4R-4HILe, 4HILe-Amide-2 potent superior [ΔG (Gibbs energy): −49.3 −42.3 kcal/mol] compared co-crystal (−45.3 kcal/mol), determined by MM-GBSA calculations. MD revealed stable complexes, evidenced low values (0.2–0.4 nm) minimal residue fluctuations (RMSF), confirming their structural integrity. approach also derivatives, top candidates exhibiting strong scores key molecular interactions reductase. Notably, compound 10 (−9.424 4 (−8.167 28 (−13.760 kcal/mol) emerged inhibitors for further investigation. Conclusions: highlights diabetes-associated enzymes, demonstrating robust stability. Integrating dynamics, calculations, AI-driven provides a framework accelerating drug discovery. These findings pave way experimental validation development next-generation therapeutics targeting insulin resistance hyperglycemia.
Язык: Английский
Процитировано
0
Nutrients, Год журнала: 2023, Номер 15(11), С. 2597 - 2597
Опубликована: Июнь 1, 2023
Vitamin B12 (B12) is an essential cofactor of two important biochemical pathways, the degradation methylmalonic acid and synthesis methionine from homocysteine. Methionine donor methyl groups for numerous reactions, including DNA gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in may cause neurological symptoms, symptoms resembling diabetic neuropathy. Although extensively studied, underlining molecular mechanism development peripheral neuropathy (DPN) still unclear. Most studies have found contribution oxidative stress DPN. Detailed immunohistochemical investigations sural nerve biopsies obtained patients with DPN point to activation inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting increased stress. Similar results been deficiency, indicating that observed neural changes might be caused by cellular deficiency. Since novel show exerts intrinsic antioxidative activity vitro vivo, act as intracellular, particularly intramitochondrial, antioxidant, independent its classical, well-known function. These findings provide rationale use treatment DPN, subclinical early states.
Язык: Английский
Процитировано
12
Frontiers in Endocrinology, Год журнала: 2024, Номер 14
Опубликована: Янв. 19, 2024
Diabetes mellitus is a prevalent chronic disease characterized by hyperglycemia. Diabetic peripheral neuropathy (DPN) one of the complications diabetes and caused neuron injury induced hyperglycemic circumstances. The incidence DPN varies among different countries regions, ranging from nearly 20% to over 70%. Patients with may encounter symmetric pain or discomfort extremes, leading reduced quality life even amputation. pharmacological management for painful mainly includes antidepressants due their analgesic effects. Nevertheless, effective therapies impact pathogenesis progression are lacking. Glucagon-like peptide-1 receptor (GLP-1R) agonists show efficacy in controlling blood glucose serve as treatment modality mellitus. In recent years, evidence has been proposed that GLP-1R exert neuroprotective effects through modulating inflammation, oxidative stress, mitochondrial dysfunction. On other hand, clinical on potential treating still controversial limited. This narrative review summarizes preclinical studies investigating capacity therapeutic agents DPN.
Язык: Английский
Процитировано
2
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8881 - 8881
Опубликована: Авг. 15, 2024
Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying neurotrophic impact on peripheral nerve system (PNS) remains elusive. Our study delves into effects of DPP-4 including Diprotin A, linagliptin, sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), Stromal cell-derived factor (SDF)-1a-known substrates with properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth response to these agents. Remarkably, all inhibitors PACAP demonstrated significant elongation length DRG neurons (PACAP 0.1 μM: 2221 ± 466 μm, control: 1379 420,
Язык: Английский
Процитировано
2