ABSTRACT
Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium-which is a dynamic endocrine organ with autocrine and paracrine activity-regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.
ABSTRACT
Abundant experimental data suggest that hydrogen sulfide (H2S) is related to the pathophysiology of Diabetes Mellitus (DM). Multiple molecular mechanisms, including receptors, membrane ion channels, signalingmolecules, enzymes, and transcription factors, are known to be responsible for the H2S biological actions; however, H2S is not fully documented as a gaseous signaling molecule interfering with DM and vascular-linked pathology. In recent decades, multiple approaches regarding therapeutic exploitation of H2S have been identified, either based on H2S exogenous apport or on its modulated endogenous biosynthesis. This paper aims to synthesize and systematize, as comprehensively as possible, the recent literature-related data regarding the therapeutic/rehabilitative role of H2S in DM. This review was conducted following the "Preferred reporting items for systematic reviews and meta-analyses" (PRISMA) methodology, interrogating five international medically renowned databases by specific keyword combinations/"syntaxes" used contextually, over the last five years (2017-2021). The respective search/filtered and selection methodology we applied has identified, in the first step, 212 articles. After deploying the next specific quest steps, 51 unique published papers qualified for minute analysis resulted. To these bibliographic resources obtained through the PRISMA methodology, in order to have the best available information coverage, we added 86 papers that were freely found by a direct internet search. Finally, we selected for a connected meta-analysis eight relevant reports that included 1237 human subjects elicited from clinical trial registration platforms. Numerous H2S releasing/stimulating compounds have been produced, some being used in experimental models. However, very few of them were further advanced in clinical studies, indicating that the development of H2S as a therapeutic agent is still at the beginning.
Subject(s)
Diabetes Mellitus , Hydrogen Sulfide , Humans , Signal TransductionABSTRACT
Hypoxia represents the temporary or longer-term decrease or deprivation of oxygen in organs, tissues, and cells after oxygen supply drops or its excessive consumption. Hypoxia can be (para)-physiological-adaptive-or pathological. Thereby, the mechanisms of hypoxia have many implications, such as in adaptive processes of normal cells, but to the survival of neoplastic ones, too. Ischemia differs from hypoxia as it means a transient or permanent interruption or reduction of the blood supply in a given region or tissue and consequently a poor provision with oxygen and energetic substratum-inflammation and oxidative stress damages generating factors. Considering the implications of hypoxia on nerve tissue cells that go through different ischemic processes, in this paper, we will detail the molecular mechanisms by which such structures feel and adapt to hypoxia. We will present the hypoxic mechanisms and changes in the CNS. Also, we aimed to evaluate acute, subacute, and chronic central nervous hypoxic-ischemic changes, hoping to understand better and systematize some neuro-muscular recovery methods necessary to regain individual independence. To establish the link between CNS hypoxia, ischemic-lesional mechanisms, and neuro-motor and related recovery, we performed a systematic literature review following the" Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA") filtering method by interrogating five international medical renown databases, using, contextually, specific keywords combinations/"syntaxes", with supplementation of the afferent documentation through an amount of freely discovered, also contributive, bibliographic resources. As a result, 45 papers were eligible according to the PRISMA-inspired selection approach, thus covering information on both: intimate/molecular path-physiological specific mechanisms and, respectively, consequent clinical conditions. Such a systematic process is meant to help us construct an article structure skeleton giving a primary objective input about the assembly of the literature background to be approached, summarised, and synthesized. The afferent contextual search (by keywords combination/syntaxes) we have fulfilled considerably reduced the number of obtained articles. We consider this systematic literature review is warranted as hypoxia's mechanisms have opened new perspectives for understanding ischemic changes in the CNS neuraxis tissue/cells, starting at the intracellular level and continuing with experimental research to recover the consequent clinical-functional deficits better.
